Your Edge in Biotech.
29
Mar
2020

As COVID19 Comes to India, Expect Drug Supplies to Run Short

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29 Mar 2020

Bruce Carter

Generic medicines aren’t glamorous. But they are a linchpin of healthcare in the United States, representing nearly 90% of all prescriptions filled.

Where do these vital medicines come from? The vast majority of the active pharmaceutical ingredients (APIs) for those drugs are manufactured in China and India. Indeed, about 90% of the manufacturing plants making API’s are outside the United States; China and India each have approximately 40% market share, according to the National Review of Economic Research.

You can see where I’m going. We live in an interconnected world. The coronavirus pandemic has done more than anything in recent history to remind us of that.

Clearly the pandemic disrupted the supply of raw materials and intermediates from China, when the attempts to contain and suppress the SARS-CoV-2 virus got serious in January. Now we see that India — the second-most populous country in the world with almost 1.4 billion people — is experiencing the ravages of the virus.

What will the outbreak in India mean to supplies of crucial generic medicines to the US and rest of the world?

The Times of India newspaper has reported that the lockdown across the country, put in place to curb the spread of COVID-19, is cutting off supplies of drugs and medical devices to Indian hospitals. This has happened already, despite the fact these manufacturers have been exempted from government restrictions.

Inevitably, restrictions on the movement of goods will not only disrupt domestic supply but also the supply to overseas markets like the United States. The situation is further complicated by the fact that many Indian manufacturers source raw materials and intermediates from China and those supplies are potentially compromised. In mid-February, the Indian Pharmaceutical Alliance said access to pharmaceutical raw materials from China was “grim.”

Most countries look after their own first. India is no exception. In early March, the government of India restricted the export of nearly 30 specified APIs and formulations made from those APIs “with immediate effect.” Currently, most of the drugs being retained strictly for India’s domestic use are antibiotics.

If this situation were to continue for an extended period, it could turn into a serious drug shortage. The United States shut down its last domestic antibiotic manufacturing plant in 2004. There aren’t a lot of other places to turn, besides China and India, for those who need to import antibiotics.

Hydroxychloroquine has been widely publicized as a possible treatment of COVID-19, although it has not passed randomized studies and is not FDA-approved for that use. Still, as governments from around the world seek to place orders for this medicine, the Indian Directorate General of Foreign Trade responded by swiftly placing restrictions on the export of hydroxychloroquine from India.

Clearly, there will be shortages in the supply of certain generic drugs to the United States. Inventory in both Indian supply chains, and in the United States, plus the Strategic National Stockpile in the US, should cushion this situation, at least for a while.

Even if India can escape the worst of the outbreak, its manufacturers will struggle to keep up with worldwide demand for medicines. Not only will they encounter shortages of raw materials for making medicines, but there could also be shortages of coal, fuel and solvents. Productivity will drop in the manufacturing plants because of the necessity to maintain social distancing. That translates into sub-optimal staffing configurations, as well as an inherent drop in worker productivity caused by anxiety from the pandemic. A certain percentage of the workforce is also likely to be out sick, perhaps for weeks.

At the same time, Indian drug manufacturers face rising costs of doing business. Marine shipment rates have gone up. Not as much as air freight, which has doubled or more.

Many of the Indian generic manufacturers have been improving their manufacturing plants, processes and people in recent years, but some companies cannot export to the United States until they comply with Food and Drug Administration standards. Last year, FDA inspectors conducted over 3,000 overseas inspections. The FDA has now stopped routine inspections of food, drugs and medical devices overseas at least through April and likely beyond.

In such a fluid and complex situation, it is hard to predict the degree and duration of drug shortages. But shortages there will be.

Bruce Carter is the former CEO of ZymoGenetics and former chief scientific officer of Novo Nordisk. He’s also a member of the board of directors at Dr. Reddy’s Laboratories.

29
Mar
2020

COVID-19 Teaches Us the Real Definition of a ‘Novel’ Drug

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29 Mar 2020

Peter Kolchinsky, managing partner, RA Capital

Will the world care how we beat COVID-19 – whether with a drug we make from scratch or an older one that turns out to get the job done? As people concerned for our families, we all know the answer. Just get it done!

But as drug developers, let’s be honest that it doesn’t feel quite as heroic unless it’s really novel.

I think we may have developed an unhealthy, facile relationship with the word “novel,” looking to it for security against the attacks on our industry that, while deserved by some companies, seem indiscriminate at this point. As if experiencing Stockholm Syndrome, we are on the brink of accepting the public’s notion of novelty at the expense of the novelty that really matters.

After years of being ridiculed by Congress, the media, and the public as highly profitable, greedy, and not innovative — merely retweaking old drugs — it’s no surprise that the drug industry would want to emphasize all of the incontrovertibly novel breakthroughs of late. Gene therapy is hardly a modest tweak. Neither are RNAi, antibody-drug conjugates, and protein folding correctors. Those who are working with technologies like these can rightfully claim the term “novel” in the most straightforward way most people mean it, which is to say “never before seen” or “had to be developed from scratch.”

Many of our industry leaders believe that pursuing such novelty should be the industry’s sole purpose. Recall the letter signed by over 200 biotech CEOs in January that promised:

“We will invest only in novel therapies that address unmet patient needs.”

If indeed we did that, presumably the public would have a harder time claiming that high drug prices are unjustified because the drugs weren’t innovative-looking enough, so I can understand the merits of this imperative.

The reality is that the public doesn’t actually care about novelty. The public only claims to care, or maybe only thinks that it cares. Consider the urgency with which the public has looked to innovators to come up with treatments for COVID-19. Companies are running new discovery programs and screening for novel inhibitors of various viral components. I have no doubt some of these programs could eventually succeed, but they are far from the market and each faces long odds.

Meanwhile there are already dozens of older drugs, including many generics, being tested individually or in combination for the treatment of COVID-19. Dozens more older but unapproved compounds, like Gilead’s remdesivir, that failed in their original indications, are being reheated. If we’re lucky enough that any of those programs really can reduce the severity of the disease, keep patients out of hospital, and/or save lives, then the world will have been saved by… drug repurposing.

Yes, we could end up saving lives with an old drug that most people wouldn’t consider “novel.”

Does that mean developing those drugs for COVID-19 will have been easy? No. Without risk? No. Inexpensive? No.

Will it matter to the people whose lives are saved and to everyone who will be able to come back to work once the pandemic is resolved that their salvation wasn’t “novel”? It absolutely shouldn’t, though some of the harshest critics will never be satisfied, but the vast majority of people would be grateful. And certainly all of us in the drug industry should know better than to denigrate a COVID-19 treatment simply because it didn’t require inventing a new drug from scratch. We should be so lucky.

COVID-19 might just leave us with a novel definition of the word “novel” that we’ve long needed. Specifically, all anyone should care about is whether we’ve addressed an unmet need. That’s what society should reward, and that’s what our industry should commit to doing.

Whatever therapy or intervention solves a previously unmet need is inherently novel. Any treatments for COVID-19, that turn out to work will be “novel” in every way that matters.

For many in our industry, swearing by novelty is a means of, let’s say, #socialdistancing themselves from notorious drug companies that the public reviled for charging high prices without engaging in almost any actual drug development. Here I’m thinking of the Marathons and Belchers of the world, which, seeing no competition from altruists, stepped up to earn high rewards for doing low-risk paperwork the FDA needed someone to do.

Though they make for bad press, we mustn’t overreact to these fringe cases. If we feel that the few outliers like this are a stain on our names, we should push for reforms that empower the FDA to contract with a nonprofit to, for example, get a foreign generic drug licensed, labeled, and marketed in the US at a low price so patients don’t have to illegally import it. Turning our noses up at Marathon and Belcher just because their work didn’t seem novel enough to merit a high price is not only unproductive, the unintended consequences could be counter-productive.

Here’s the harm of committing to “novelty” at all costs. Imagine if a company suspected it could repurpose a low dose of an old generic HIV drug combined with an old generic epilepsy drug to treat a different neurological disorder. They know the combination would likely be safe because the drugs, as single agents, have already been in millions of patients. Yet studies would still need to demonstrate efficacy in the new indication and determine proper dosing limits. But the company would worry that payers, enjoying the support of a jeering public conditioned to denigrate anything that isn’t clearly novel, will refuse to pay for this combination drug. The company might fear that insurers would tacitly nudge physicians to prescribe the old generic drug components together, failing to reward the company that invested significant time and money in teaching the world about the medical value of this new drug combination. Would it risk the ridicule and financial uncertainty of repurposing these generics?

Or would it instead develop an entirely new molecule that does the same thing? That would take longer and be riskier. The final product would have a high price, and payers might resent having to pay, but at least no one could say that the product wasn’t “novel” in the conventional sense.

What would patients want? A safe and effective treatment they can afford. In other words, for insurance to pay for whatever works. So what should society want? The same.

To the extent that the public, the media, and Congress are concerned about novelty, it’s because it’s a litmus test for whether they think an innovation deserves to be rewarded with a high drug price. The corollary is if it’s not novel, then calls for price controls are fair.

The public, the media, and Congress are outraged over drug prices because many patients can’t afford the treatments they need. Unfortunately, society has collectively misdiagnosed the reasons drugs are unaffordable. It isn’t systematic price gouging by drug companies (the industry’s profit margins are too modest to tolerate even a 20% cut in US drug prices); it is, has always been, and continues to be America’s terrible insurance coverage. While many Americans do have good insurance and can afford their copays, some are crushed by their out-of-pocket costs, and ~15% of Americans have no insurance at all. Nothing about healthcare is affordable without insurance.

If there were ever an illustration of how stupidly counter-productive America’s health insurance designs are, recall the people who dutifully reported for COVID-19 testing and were sent home with massive bills, deterring others from seeking testing at all. They went home, or back to work, and unwittingly started spreading the new coronavirus. And even when ordered to cover COVID-19 testing, some payers interpreted that narrowly, sticking patients with bills for necessary but ancillary tests, such as those for flu, that doctors would order to help them interpret COVID-19 testing results. We all see the absurdity of that because we know that testing is essential for our collective public health. We’re outraged that payers, as our chosen agents for making appropriately-prescribed care affordable, are deterring healthcare that is essential for the public health.

But what’s true for COVID-19 and for testing is also true for all diseases and all treatments. And while it’s not as obvious as with COVID-19 coverage, affordable healthcare for all diseases for any individual is also a public health issue for all.  When payers don’t cover insulin well enough for patients to afford it, then some will ration it and suffer. Later, when they go blind because they couldn’t afford to manage their diabetes, the added cost of that care is unavoidable. Yet so much individual suffering and societal cost could have been avoided had the insulin been covered properly by the insurer in the first place. It’s an example of being penny wise, pound foolish.

So let’s recognize that the pressure that we as drug developers feel to only develop and charge for what society agrees is “novel” is really an outcry over two things.

First, we need proper insurance to make all appropriately-prescribed drugs affordable for everyone. Second, the pharmaceutical industry should only develop and charge America high prices for products that solve problems that are still unmet by all the known uses of our existing armamentarium of generic drugs (which, with few exceptions, it already does – just consider how impossible it would be to even run a trial for a new drug that aspired to be no better than a statin).

Society doesn’t want anyone playing games with REMS programs to price-jack an old, off-patent drug for the same old use, as Turing notoriously did with Daraprim. But the public does want biosimilars. By design, those aren’t novel, but they will bring down drug prices. The public doesn’t want companies exploiting ASP+ loopholes in Medicare Part B reimbursement to enjoy high revenues from branded drugs that are undifferentiated from generics. But it does want fast-followers (aka me-too drugs) in new classes that offer a greater variety of treatment options and drive price competition, as has happened with PCSK9s, SGLT2s, GLP-1s, CGRPs, and and many of the other acronyms we’ve ever drugged. Consider that America would have enjoyed greater negotiating power and discounts from Humira had there been a comparable me-too; developing competitors to branded drugs should be encouraged, not shunned by a commitment to “only invest in novel therapies.”

So what should we as an industry commit to so that it shows that we are aligned with what society really wants and deserves from us?

I propose this:

We will invest in drug development to address healthcare needs that are not yet met by the known uses of generic drugs.

Some might not find this satisfying because it doesn’t include the word “novel,” which the public likes to hear. Yet this statement captures everything we are doing to solve COVID-19 as quickly as possible, including new drug discovery and old drug repurposing.

And this statement applies to all of drug development for all our remaining unmet needs. Whether that means we will repurpose an old drug for a new use, reformulate an old drug to make it safer or more effective, invent an entirely new drug, or launch a similar competitor to another branded drug, it’s all in the public’s interest.

As long as all Americans are properly insured with affordable (or no) out of pocket costs, they will all be able to get the care they need. And as long as all those drugs go generic without undue delay — which means patents expire when they should, and aren’t extended through patent gamesmanship — then America and the world will be getting value for its money. I’ve written elsewhere, including a book, proposing specific reforms to shore up genericization for all drugs that would spur innovation.

So let’s either retire the word “novel” or at least resist the urge to cave to the public’s old notions of what it means. The COVID-19 crisis has primed the public to appreciate both the value of having an armamentarium of approved drugs and the benefits of searching for new uses for them. Let’s therefore learn together to see all solutions of important unsolved problems as “novel, in every way that matters.”

Peter Kolchinsky, a biotechnology investor and virologist, is Managing Partner of RA Capital Management, L.P., and author of The Great American Drug Deal.

28
Mar
2020

Knowledge is Power: Don’t Give Up on Diagnostic Tests for COVID19

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28 Mar 2020

Mike Pellini, managing partner, Section32

Let’s not mince words.

We are in the midst of the worst health care emergency since the flu pandemic of 1918-19 that killed 650,000 Americans and 50 million people worldwide. And, we are told that on the horizon may be the worst economic and unemployment crisis since the Great Depression.

These challenges are coming in biblical proportions, and yet the main strategies proposed thus far to combat the SARS-CoV-2 (COVID-19) virus have been non-pharmaceutical interventions. We are told to wash hands, and to do “social distancing” to “flatten the curve.” The US is struggling to provide even the most basic commodity gear for frontline healthcare workers. Personal Protective Equipment (PPE) is getting scarce. We have people using 3-D printers from home to make improvised face masks. The federal government, and state governments, are struggling to secure enough ventilators for  patients in intensive care, and the many more surely to come.

Incredibly, this is the case even after a decade of breathtaking progress in our biology, drug development, and the science and technology underpinning diagnostic tests.

But, here’s the really bad news, which we all need to understand: even if the non-pharmaceutical interventions we’re using now are successful and equipment shortages are solved in a consistent fashion across the nation, that’s not enough. If successful, those interventions will have some effect on easing the immediate challenge of reducing a spike in illness and lowering the death rate. They will also have a drastic effect on our economy. Because we know so little about this novel coronavirus, including the basics like how it is spreading and how it can and should be treated, we have to bring the full power of US academic and industrial science to bear.

It starts with diagnostic testing. Without fast, accurate and widespread testing across the country, the measures currently in place may well prove woefully inadequate.

Even as the virus rips across the country with exponential speed, pushing hospitals to the brink, we have seemingly given up on widespread implementation of diagnostic testing to identify individuals who have contracted COVID-19. Some hospital leaders, under wartime triage pressure, have argued that diagnostic testing is almost irrelevant, because this bug is so contagious and has been uncontained for so long, that’s it’s virtually impossible to run all the necessary diagnostic tests. They say we should prioritize resources toward protecting frontline healthcare workers from the coming surge of infected patients.

This is a mistake.

We have the technology and means to rapidly implement testing at a national level.

We must demand that our government apply urgent focus to the deployment of a national COVID-19 diagnostic testing program. Our scientists know how to do this. We have seen rapid progress in other areas of medicine. Our pharmaceutical, biotechnology and academic colleagues, coupled with the U.S. Food and Drug Administration (FDA), promptly committed to the timely development of antivirals to combat COVID-19, like Gilead Sciences’ remdesivir, a polymerase inhibitor. The National Institute of Allergy and Infectious Disease, in collaboration with mRNA vaccine developer Moderna, went from the discovery of the novel coronavirus to a vaccine candidate ready for first-in-human injections in just two months.

Now, our policymakers must learn that diagnostic testing and appropriate treatment and prevention go hand in hand. There’s no other path.

Imagine what’s possible with an all-out, national effort around diagnostic testing. We’ll be able to identify all the sick people — and the asymptomatic people — who are unwittingly spreading the disease. Once identified, the infected can be isolated until they are no longer  infectious. Once the cases are properly identified at large scale, local public health officials can do the tracing of those peoples’ contacts, and urge those contacts — even those without symptoms — to self-quarantine while they await test results to see if they, too, are positive.

This is the essential blocking-and-tackling of public health that must come simultaneously with national “social distancing” efforts to mitigate the spread of SARS-CoV-2. The testing and tracing program is absolutely central to a national suppression strategy.

Just yesterday, we saw a positive sign. Abbott Laboratories won emergency FDA clearance for a molecular point-of-care testing device that can deliver positive COVID19 test results in 5 minutes, and a negative result in 13 minutes. Abbott, a big company with the necessary people and resources to scale up to a national challenge, said it will make the device available this week and that it plans to ramp up capacity to 50,000 tests per day. This approval comes after recent advancements were announced by Roche and Thermo Fisher Scientific as well.

It’s a start.

But the overall picture remains discouraging. It’s late in the game. That approval came after we already have more than 100,000 confirmed cases in the US.

To date, there has been a failure of technology deployment and leadership because our society has not properly prioritized diagnostics to track the spread of this particularly virulent enemy, to understand its characteristics, and to reveal how different people respond to it. In fact, our national focus appears to have recently shifted from rapidly identifying patients through diagnostic testing to skipping the testing on the presumption that everyone with a COVID-19 exposure or flu-like symptoms is positive for the SARS-CoV-2 virus.

To forgo diagnostic testing in this context borders on malpractice at a national level.

We must instead immediately work to understand everything about this virus, from its geographical spread to how it manifests itself differently in individual patients. We need a national program where tests are made available in areas of critical need, like New York City, Seattle, San Francisco, New Orleans, Atlanta, Chicago, and Detroit. Only then can we truly understand how Americans might be treated appropriately and, where possible, prevented from contracting the virus.

As we deploy 100-year-old strategies to deal with this global pandemic, we must also supplement them with our best available digital technology. We need to collect the data generated by diagnostic testing to figure out how and where COVID-19 manifests if we are to slow its spread. These national data from broadly available tests could inform both the intelligent distribution of clinical care and the aggressive development of antivirals and vaccines.

Thankfully, the diagnostic industry has stepped up. Tests, including ones at the point of care like Abbott’s, that don’t require samples to be shipped by cargo planes to faraway labs, have been developed, approved, and manufactured in record time. But supply chains must also be fixed, and diagnostic tests need to be aggressively and broadly deployed to every local hospital in the country. Then the data need to be swiftly reported in a systematic way, so they can analyzed and integrated quickly into clinical care.

Without these diagnostic data, we are flying blind.

But here’s the good news: right now, we have the ability to put millions of tests into operation.

Here’s what it will take:

First, we must broaden the distribution network to allow our national, regional, and local labs to continue the work they are already doing in scaling up their testing capacity. We can’t rely only on large national labs like LabCorp, Quest, and the CDC lab in Atlanta, or academic centers like the University of Washington Virology Lab, which stepped in to fill a void in the Seattle area’s diagnostic testing capacity. We should also enable local clinical labs, which routinely work together to validate one another’s results, to go online withCOVID-19 testing.

Second, we need to get creative, while continuing to put patient safety first. Nasopharyngeal swabs are cheap, easy-to-use commodity supplies, as evidence by a recent Gates Foundation clinical study. They should be made available for in-home use immediately. Telemedicine approaches can allow the tests to be ordered, while individuals can sample themselves or family members and send the swabs overnight to the appropriate lab. Complete home diagnostic tests, while still new, can be deployed in a safe and effective fashion once they are validated. The Bill & Melinda Gates Foundation recognized this opportunity and has been supporting work along these lines.

Third, the FDA and Centers for Disease Control and Prevention (CDC), in conjunction with the national, state, and local governments, must work together to promote the process and cooperation. This means speaking clearly, calmly, and forcefully on the national stage about why we need to do a better job of diagnostic testing, and what real success would look like. A National Diagnostic Testing Czar for COVID-19 should be appointed immediately to oversee these efforts.

Fourth, testing priority must be given to health care providers, the elderly, and populations with co-morbid conditions, and anyone expressing symptoms. Of course, as we ramp up and reduce the bottlenecks, we can broaden testing criteria to include the general population rapidly.  

Fifth, the results from all COVID-19 tests should be uploaded to a central database, allowing epidemiologists to make intelligent decisions about quarantines and the allocation of care, instead of guessing where and whom the virus is going to strike and imposing blunt “shelter-in-place” mandates across ever-wider geographic expanses. Individuals who test positive could be quarantined without closing down the entire economies of states and the nation, as is the case today.

A coherent diagnostic testing approach will yield data that will inform our ability to combat COVID-19’s spread strategically and over the months to come. In the immediate term, it will help to target isolation approaches where they are needed and allow COVID-19 negative patients, to return to work. These tests will also alleviate patient angst while at home. They will help us stratify COVID19 patients, so they can stay in hospital areas away from other patients.

In the medium-term outlook, the next 2 to 4 months, the data will teach us more about the clinical manifestations of the virus, yielding information on individuals who have been exposed in the past, perhaps without symptoms, those who are at greater risk for aggressive forms of the disease (smokers, diabetics, etc.), and even those who have developed immunity. And, in the longer term (6 -18 months), the information will assist with the development of essential therapeutics and vaccines.

We must not give up on broad-based diagnostic testing. It is the foundation to overcoming this pandemic in every country.  The playbook is already in hand if we choose to engage.

Once upon a time, Americans understood that knowledge was power. It still is. And, in this case, knowledge comes from utilizing diagnostic testing, not ignoring it.

Michael Pellini, M.D., is managing partner of Section 32, a venture capital firm. He’s also a board member of the Personalized Medicine Coalition.

27
Mar
2020

The Seattle Scientific Community, Mobilized

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27 Mar 2020

Kristin Anderson, postdoctoral fellow, Fred Hutch

“When I was a boy and I would see scary things in the news, my mother would say to me, ‘Look for the helpers. You will always find people who are helping.’” – Fred Rogers

The Seattle scientific community has always been tight-knit and collaborative, but we have mobilized like never before to respond to the threat of COVID-19. My friend and fellow Climb to Fight teammate, Bob More (@Bobmorevc), recently wrote an excellent piece recognizing a number of Unsung Heroes in this battle.

My hope is to share just a few stories of people working behind the scenes which you may not have heard yet. From the scientists who led the charge to make testing widely available, to the community members who have stepped up to support all of their efforts – we see you. And we are grateful.

Here are just a few stories to highlight how our Seattle community has come together to support each other.

Dr. Helen Chu (@HelenChuMD) is an infectious disease expert and the lead scientist for the Seattle Flu Study (@seattleflustudy). In short, the project asks volunteers in the community with flu-like symptoms to send in nasal swabs. Her team of scientists studies those samples to learn more about the flu.

Dr. Helen Chu, assistant professor, allergy and infectious diseases, University of Washington

In January, when the outbreak in Wuhan, China was in the news, Dr. Chu hypothesized that the coronavirus was already in the United States and being transmitted through the community, not just by people who had recently traveled to the US from China. She asked Washington state, the Centers for Disease Control and Prevention, and the Food and Drug Administration for permission to test the Flu Study samples for the novel coronavirus. The samples and all the infrastructure to study them were already in place. The study was up and running, collecting samples. It wouldn’t take much to shift gears to look at those same samples for the new virus. But Dr. Chu was firmly denied. That wasn’t part of what participants had signed up for. A new consent form, potentially taking weeks or months, would normally be required to move ahead on such a major amendment to study protocol.

Dr. Chu considered the ethics of the situation. This was a fast-moving and deadly pathogen. She discussed it with colleagues. Ultimately, she decided to test for the novel coronavirus anyway. They couldn’t wait any longer. Her results, from samples tested Feb. 25, are the reason we know the virus was spreading undetected through the community in Washington state. Her results are the reason that public health experts began sounding the alarm about the virus in the United States. Her results are also the reason we now have the Seattle Coronavirus Assessment Network (SCAN) program, the first coronavirus surveillance program in the country, which can begin to assess the basics of how many asymptomatic spreaders we have in the community, and where they are, so they can be isolated. Like the Seattle Flu Study, SCAN utilizes simple nasal swabs that community members can perform at home. Dr. Chu’s decision to persevere has been instrumental in our fight against this virus.

Keith Jerome, head of UW Virology division

Equally important in the early stages was the work of Dr. Keith Jerome and Dr. Alex Greninger, experts in virology at the University of Washington (@UWVirology) and Fred Hutchinson Cancer Research Center (@FredHutch). Shortly after the new coronavirus was being discussed in the news, they realized the country needed a diagnostic test for the virus and decided to divert some of their lab resources to develop one. When the Centers for Disease Control and Prevention’s tests did not work, these UW / Fred Hutch scientists applied to have their lab, and the test they developed there, certified by the Food and Drug Administration. That way, they could perform diagnostic tests for healthcare providers across the country. Their decision to develop a test using their own resources, even if it had not ever been needed, is saving lives every day.

This is not the norm for a research lab to turn itself, virtually overnight, into an industrial-scale high-volume diagnostic testing facility. Normally, they’d focus entirely on research questions, such as incubation times for a new virus, viral shedding rates, or various modes of transmissibility. They put their horsepower into doing an industrial task for patients in need in our community because somebody had to do it.

Once their clinical lab was approved to run patient samples, their small team started running diagnostic tests as fast as humanly possible. But even at peak speed they could only run about 200 samples per day. Knowing they needed to ramp up their throughput, they purchased machines to automate some of the process, but there were some steps that still needed to be done by hand. UW Virology put out a call for help. The Seattle science community answered. Volunteers from a variety of scientific disciplines, many of whom are young graduate students and post-doctoral fellows, set aside their own research to learn molecular virology techniques so they could process patient samples and open up the bottleneck. These volunteers are currently working in shifts around the clock and have helped increased the lab’s throughput to a maximum of more than 3,000 patient samples per day.

Processing thousands of samples is a massive undertaking. Administrators from multiple departments at the University of Washington quickly began volunteering their time providing logistical support. Almost immediately, the lab realized they were short on a critical lab supply: pipette tips. They again sent out a blast for help, this time on social media. Within 24 hours, local research labs and Roche (@Roche) delivered thousands of tips.

In response to the request, members of the community also reached out asking what they could contribute. One generous volunteer made hundreds of bags of healthy snacks for the researchers to “grab and go” between processing samples. Portage Bay Café (@portagebaycafe) donated breakfast, Starbucks (@Starbucks) donated coffee, and Pagliacci Pizza and Taste of India donated dinner for all the volunteers. Ellen Kuwana (@EllenKuwana) organized a Facebook Fundraiser and to date has raised over $15,000 to provide meals for the lab volunteers and healthcare workers while simultaneously supporting local restaurants.


Pavitra Roychoudhury

Once the clinical lab received the first sample containing coronavirus, bioinformatician Dr. Pavitra Roychoudhury (@pavitrarc) led UW Virology’s effort to analyze the complete viral genome in each of the local samples. Their goal is to develop a better understanding of transmission dynamics and viral genetic diversity. To do that, they plan to sequence every positive sample run in the clinical UW Virology lab. So far, they have deposited over 230 sequences to the Global Initiative on Sharing All Influenza Data (@GISAID) database. With sequences from this database, Dr. Trevor Bedford (@trvrb) and the team at Nextstrain (@nextstrain) construct a map of global transmission dynamics and viral evolution. These sequences are now open to the international scientific community to study, and to help other locations get a jump on the virus that’s likely headed their way.

Importantly, sequencing, assembling, annotating, and depositing sequences in these databases is no small feat. To speed up this data sharing, UW Virology again put out a call for support. Within 24 hours, they had dozens of offers from people with computational expertise volunteering their time. This collaborative effort to make data available as quickly as possible is a sea change in how scientific findings and data are often shared. Science and knowledge are being made freely available, and in real-time. There’s no waiting around for six months to get your manuscript published. It is inspiring.

The timing of this massive open science movement seems particularly appropriate. In an age when misinformation is so widely available on the internet, many people have been turning to scientists for answers. Community members are offering appreciation and virtual support through social media to scientists who they might otherwise not meet, or might not understand well in normal times. Parents are sharing that their kids want to be scientists. People are raiding their homes for supplies to donate, like masks, hand sanitizer and disinfectant wipes, which are desperately needed by caregivers in local clinics and hospitals. For people in the lab or the clinic, working long days and putting their own health at risk, gestures like this provide an immeasurable morale boost.

We are all contributing to something monumental that will likely be the defining events of our lifetimes. I could not be prouder of my friends, colleagues, and community. #WeGotThisSeattle #WeGotThisWA

27
Mar
2020

Do’s and Don’ts of Staying Connected in the Time of Physical Distancing

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27 Mar 2020

Nina Kjellson, general partner, Canaan Partners

“There are some things you learn best in calm, and some in storm.” –Willa Cather

Faced with the harsh realities of COVID-19 and mandatory isolation, we are increasingly challenged to learn new ways of reaching out and connecting with each other. Effective videoconferencing is becoming a critical skill for weathering these times.

For better or worse, videoconferencing has long been a part of my work and personal life. As a partner in a bi-coastal firm with investments and colleagues across the country and globe, it’s been essential for weekly partner meetings and board meetings, company pitches and even speaking engagements. And with beloved family scattered from Vermont to Helsinki, I’ve logged countless hours of virtual hugs via FaceTime and WhatsApp. I’m very glad to share a few practical videoconferencing dos and don’ts.

Don’t Wing It

A little preparation goes a long way for making virtual meetings smooth and successful. Whether you’re the host or a participant, take time before your virtual meeting to make sure you have all of the information and technology you need. If it’s your first time on the meeting platform (Zoom, RingCentral, BlueJeans, Skype, etc), download the app to at least one device and create an app-specific account, if necessary, and log on and test it out. Familiarize yourself with different views, how to share content and how to use the chat function if there is one. (Mid-call is not the time to discover virtual backgrounds or to upload your vacation shot and fiddle with orientation). Check out your lighting. It is nice when people can see you well. (There are gadgets for enhancing your video “look.” I’ll let you search for those yourself on Amazon).

If you’re the host or meeting sponsor, it’s now more important than ever to create an agenda and distribute it to participants before your meeting. If you’re a participant, familiarize yourself with the agenda and do the pre-meeting homework. Plan to log-on two to three minutes early. Be ready to roll when the meeting starts. Note on calendaring: Most apps have a calendaring feature that enables easy one-click log on for participants. If you are using Outlook or Google Calendar or other to schedule, try to make logging on as simple as humanly possible for participants: a link and a simple thread with meeting ID and password as back-up.

Do Embrace Your Role

In a virtual setting, leaders must lead. As the host, your job is to be on in video, introduce yourself, outline the agenda, and establish expectations for participation. You might say: Please use the chat window to send me your questions. Kindly mute yourself when you are not speaking. If you need to move around during the call, please turn off your camera to minimize distractions. If you’re a participant, be a good follower. Lean into the conversation (literally) so your attention can be felt by others. Follow the format provided by the call host and mind your airtime. In the Videocon, body language can be harder to read so the louder voice often stands out above the softer voice. Help include each other and follow up with the quieter participants to make sure folks are heard. If you have real-time feedback about the virtual experience, save it for after the call but do share.

Don’t Go it Alone

If you’re the host, assign someone on your team ahead of time to be the technology or content troubleshooter if people have issues during the call. Assign someone else to take notes or alert you if you’ve accidentally muted yourself. Ask a participant to help manage the time.

Do Expect Hiccups and Assume Best Intentions

Embrace the real life in WFH circumstances. Interruptions (kid with a question, barking dog, grocery delivery) are to be expected. Be patient. These things usually resolve quickly and provide a window into our whole selves as we cope as best we can. Technical glitches also happen. Videoconferencing platforms are experiencing a deluge of traffic. The videoconferencing learning curve can be steep, even for the brightest minds. Many people are functioning at 50-75% of their normal capacity due to stress and life/work situations. Bad news is coming in unpredictable waves. All of these things can impact your virtual meeting experience. Be ready to gracefully reschedule if needed.

Do Stay Positive and Reach Out

This relates to good videoconferencing and everything else we are so desperately trying to accomplish right now. In a virtual meeting space, your tone matters. Your kindness echoes. Reach out to other participants after your videoconference to appreciate their contributions and make an added connection. Make new, impromptu, and informal opportunities to meet virtually with colleagues, friends, and family just because you can.

From my past week, I can attest that videoconferencing lends itself to happy hours, workouts, shared meals, community organizing, tutoring, and various group reunions, including an alumni reunion of “Luke Timmerman Drags 27 Biotechies up Mt. Kilimanjaro 2019.”

Wherever you are, I’m sending you virtual hugs and a thousand wishes for safe passage through the storm, plus this small reminder of beautiful things that I captured a few days ago.

 

 

27
Mar
2020

Singapore: Braving the Second Wave of COVID19

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27 Mar 2020

Carolyn Ng, managing director, Vertex Ventures HC

A week ago, I wrote an article for Timmerman Report on Singapore’s COVID19 response, and how the country has kept its cases low with no COVID19-related deaths.

In that article on Mar. 19, I elaborated on how Singapore had not ordered any businesses to shut down. Instead, the country had kept the number of cases low over the last few months through early and aggressive targeted containment policies, which were reinforced and implemented with high efficiency before cases surged.

That’s all changed in one week.

Literally a day after my article was published, it was announced that two patients (a 75-year-old female, and a 64-year-old male) died in Singapore from COVID19-related complications. Not unexpectedly, the country is now facing a second and larger wave of case spikes. The main reason for the surge in cases is coming from Singaporeans and long-term residents returning home from the UK and US, where uncontained outbreaks have clearly been raging for weeks, largely undetected. At this point in writing, Singapore has reported a total of 732 confirmed cases in the country – more than double from 313 a week ago.

Something Else You Need to Know About Singapore — Not Shown in “Crazy Rich Asians”

A little blurb on Singapore, this small, densely populated city state: we gained independence from our British colonial masters in 1946 after WWII and Singapore joined the Federation of Malaysia in 1963. In 1965, Singapore was expelled from the Federation of Malaysia as a standalone country with absolutely no natural resources, not even a clean water supply of its own. Every Singaporean grows up being intimately familiar with the famous historic scene of our former Prime Minister Lee Kuan Yew shedding tears into a piece of tissue when he announced the separation of Singapore from Malaysia as he had grave concerns for the survival of the island state.

I often hear my tourist friends complain that Singapore is “boring,” that there is nothing else to do in the country other than walking down Orchard Road, the shopping mecca of the country lined with gigantic shopping malls, one after another.

To them I calmly say: as you look around these ridiculously clean surroundings, which some criticize as “overly sterile,” please bear in mind that you are in fact standing on the ground of a miracle of an economy. Within a few mere decades, Singapore transformed itself from third world to first world. It is now one of the highest-ranking countries in the world in terms of GDP per capita. All that with zero natural resources.

That also means one thing: the country’s service and trade-dependent economy is all it has to ensure its survival and prosperity. The economy is its bloodline. Officials there think very carefully about how to best balance public health and the country’s economy.

Singapore’s Hybrid Model: Not (Yet) a Full Lockdown, But “Don’t Play Play”

In view of the second wave of case spikes in late March, Singapore took tough new steps to curb coronavirus spread. There are two specific objectives. One is to isolate and reduce imported cases. The second is to slow down community transmission.

1. Stemming Imported Cases: Borders Closed and Stringent Isolation of All Returnees

Singapore is an important transportation hub, with a significant fraction of its GDP generated from its airport and shipping ports. Last week, the government took the painful step of shutting its borders to all short-term visitors. Only long-term work pass holders working in essential sectors such as healthcare and transportation are allowed re-entry into the country.

As for Singaporeans and Singaporean Permanent Residents returning home from abroad, every single returnee is made to serve a 14-day isolation notice – with no exception. In particular, Singapore residents returning from the UK and the US are taken from the airport to designated hotels directly with special transportation arranged by the authorities to minimize their human contact during the commute. Accommodation and all meals are to be provided for by the government.

There is a common Singlish lingo used by us Singaporeans, known as “don’t play play,” which literally means “don’t mess around with me.” Consistent with that spirit, the Singaporean government means it when they serve you a 14-day stay home (or hotel) notice. Spot checks are done via text messages, video calls and surprise visits. People can choose to wait for two weeks before heading out to their favorite chicken rice stall, or face jail time of up to six months and/or up to a $10,000 fine in Singapore dollars. In just a few days, 89 work passes have already been revoked by the government for flouting stay-at-home notices.

2. Curbing Community Transmission: Stepwise Approach in Social Distancing

Singapore’s multi-ministry COVID19 task force has announced mandatory closures of bars, cinemas and all other entertainment outlets from Mar. 26 to Apr. 30. These are the island state’s most draconian measures yet. The order also include suspension of tuition centers, religious services, and gatherings of more than 10 people.

Is the country now considered to be in “lockdown” or even a partial lockdown? No. Schools have thus far remained open. Restaurants have been required to create more space between patrons, but they do remain open. Working-from-home is not mandatory, but has become the norm. Except for those served stay-at-home notices, other residents are not required by law to stay at home.

In a typical Singaporean fashion, even in the absence of a lockdown, the government is unmistakably serious about its social distancing measures. One just need to look at the headline splashed across Singapore’s Straits Times (the country’s most dominant media channel) yesterday:

 

Lockdown or Not?

Not surprisingly, given the various forms of lockdown/shelter-in-place in various cities around the world, people are questioning if Singapore should be more strict, and start enforcing a full lockdown immediately.

When asked that question at a press conference on Mar. 24, co-chair of Singapore’s COVID task force Lawrence Wong explained that Singapore’s measures have been designed, right from the beginning of the COVID19 crisis, to be meted out in tiers and in response to close monitoring of fast evolving risks.

The intent of the Singaporean government has always been, from the beginning, to introduce targeted containment measures early, swiftly and decisively so that the country will be able to nip the spread in its bud without triggering an emergency lockdown that will bring the country’s economy to a halt.

BUT, before I go any further, let me emphasize that this decision was taken by Singapore in January when the world first heard of COVID19. Most parts of the world ignored it at that time.

To put things in perspective, Singapore currently has, since the first reported case in January, a total of only 732 confirmed COVID19 cases, and two COVID19 related deaths. The magnitude of the COVID19 crisis in Singapore, even with the second surge (and adjusting for population), does not come close to the crisis that’s unfortunately occurring in the United States. Since the world first heard about COVID19 in January, the US has largely responded with delays and inaction. As of this writing, the US now has the most confirmed cases in the world — more than 87,000 — exceeding both Italy and China. More than 1,300 Americans have died, and the numbers are increasingly rapidly every day.

So, please, my dear American friends, please do not point to my beloved country Singapore as an exemplar of how to best balance public health and economic prosperity.

Yes, Singapore has managed to keep its schools and businesses open, economy running AND cases low. Some people argue that the US can do the same. But that’s impossible. The reason is that, simply, for many parts in the US, such as New York, it is too late: we have lost the window of opportunity for less drastic measures. A virus that spreads with exponential speed, and which has been spreading nationwide without containment for weeks can no longer be contained. It can only be mitigated with the kinds of extraordinary physical distancing and shutdown measures that are currently being employed in a number of states and localities. However, some of the other strategies deployed in Singapore may still be applicable and useful in the US, which the following sections will describe.

Saving Lives with the 3Ts: Test, Track and Treat

While the world awaits a prophylactic vaccine, the “3Ts” approach of test, track and treat remains the gold standard. Singapore is throwing its weight aggressively behind these efforts.

  1. Test: Singapore has one of the highest COVID19 test rates in the world. So far, at least 39,000 tests have been conducted to date, which translates to 6,800 tests per million people in Singapore. This compares favorably to around 6,500 in South Korea, another country lauded for high test rates. To that end, it is also very encouraging to see the United States ramping up its effort on that front, with New York leading with the most tests per million people (about 5,300).
  2. Contact Tracing and Tracking: Singapore has done a particularly impressive job of contact tracing to identify target hot spots for isolation. In fact, Singapore is making its contact tracing technology freely available to developers globally. The app, called TraceTogether, allows Singapore’s health ministry to access users mobile app data to identify people who had close contact with the infected individual. (Readers may cringe at the thought of alleged state surveillance with such a technology, this is a topic for another day — perhaps after we overcome this COVID19 crisis. For now, infected patients in Singapore are required by law to assist the health ministry in mapping out their location timelines for contact tracing.)
  3. Treat: The nation city has started its preparation to substantially expand its healthcare infrastructure and capacity. Unlike China and Italy, where healthcare workers may be deployed from other states or provinces, Singapore has no hinterland to draw resources from. Instead, the country has devised creative solutions for the private and public hospitals to work together. For example, stable COVID19 patients will be transferred to selected private hospitals to free up bed spaces for the public sector.

Last But Not Least, Saving Livelihoods

Returning to my earlier introduction of Singapore, with no hinterland and no natural resources, Singapore’s trade-dependent economy is the country’s lifeline. Deputy Prime Minister Heng Swee Keat announced an unprecedented COVID19 Resilience Budget of $48B Singapore Dollars package to carry the country through this difficult time. Another $17B Singapore dollars in stimulus will also be drawn from Singapore’s past reserves, increasing this budget to 11% of the country’s GDP.

I am not an economist, so most of the finer technical details were lost on me as I watched the parliament session in which this budget was worked out. What did catch my attention was:

  1. A Training Support scheme was included for self-employed individuals to improve their skills during the downtime. How thoughtful!
  2. On the next parliamentary session’s agenda, the Ministry of Law is set to address the issue of upfront deposits paid for large gatherings such as weddings, which are now cancelled/postponed. (As an anxious bride-to-be who has literally just paid an arm and a leg to our wedding venue and vendors in California, we are now struggling to find the right — legal and non-legal — recourse to our situation, which admittedly is very minor relative to everything else that the world is going through. To see Singapore’s government going to this level of extreme detail to address their citizens’ day-to-day issues is nothing short of impressive and reassuring.)
  3. Lastly, all political office holders in Singapore are taking a three-month pay cut in salary. To demonstrate solidarity with our home country and with our portfolio companies, the senior management at Vertex HC, Vertex Southeast Asia, Vertex Growth and Vertex Holdings, have also taken a voluntary salary cut, with proceeds being donated to not-for-profit organizations which aid families in need in Singapore.

The Worst is Not Over

I said it last week, and unfortunately I will have to say it again: the worst is not over – not for Singapore, and certainly not for the US or the rest of the world.

May the strong carry the weak, may the wise lead the way for the masses, and may the masses stay on their couches, for now.

Disclaimer:

This article expresses the personal views and perspectives of the author. The views and perspectives expressed here do not necessarily represent the views or perspectives of Vertex Ventures HC, or any officer, director, partner, member, manager or employee of Vertex Ventures HC, or any of its affiliated entities. 

26
Mar
2020

Adjusting to Telemedicine: A First-Hand Account

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26 Mar 2020

David Shaywitz

One consequence of the present crisis is the urgent embrace of telemedicine, as I recently discussed. Whether the adoption is sustained beyond the crisis period remains to be determined, although use seemed to be increasing overall even before the pandemic hit. 

As more physicians and patients find themselves pressed to adopt telemedicine, I thought it might be helpful to better understand what this transition and experience is like, first-hand. So I asked my brother Jonathan, a psychiatrist in Los Angeles and a relatively early adopter of telemedicine, about his experience.   

Jonathan is an adult psychiatrist, with a focus on anxiety and affective disorders (depression, bipolar, mood disorders), and a particular expertise in psychopharmacology.

Here is what he had to say.

Jonathan Shaywitz, psychiatrist, Los Angeles

Timmerman Report (TR): For starters, help us understand what you typically cover with patients in a (pre-COVID) in-person visit?

Jonathan Shaywitz (JS): Most visits are follow-ups, tend to be extremely targeted, about 15-20 minutes long, and focus on medication management, following up on side-effects, for example.  There’s no physical exam; the questions are generally subjective.

TR: How did you first get involved in telemedicine?

JS: About six years ago, I was medical director at a Southern California hospital system with two large hospitals, half an hour from each other. At the time I joined, the hospital had already installed a telemedicine capability to enable staff at one location to see emergency room (ER) patients and floor [in-patient] consults from the other hospital – you could provide care from one site while physically being in the other. Most importantly, this allowed the ER staff to get in touch with a psychiatrist right away, so it wouldn’t delay the care of patients, and interrupt the flow of ER patients waiting to be seen. In many ER settings, a common hold-up can be waiting for a psychiatrist to come and evaluate a patient.

TR: When you first heard about this set up, were you skeptical? Interested?

JS: I was both interested and skeptical. I was especially skeptical about the technology, because you are really relying on it. I am at my desk at one site, and on the other end, they are wheeling a robot with a video screen with you projected on it. You are counting on the fact that the robot is available and functioning – plus you need someone to appropriately set up the machine. In my experience, this tended to work very well in the ER – basically because there was a single person responsible, and they were very familiar with the technology. Floor consults tended to be more challenging – depending on the floor, you might not have someone around who really knew how to set up the technology.

TR: Do you feel you were able to do as good an exam remotely as if you had seen the patient in person?

JS: I do. There were no procedures involved. Emergency room patients tended to be especially accepting because they were so happy to see a psychiatrist and not have to wait – there was a real sense of time being an issue. The typical evaluation would be for acute depression, often focused on the question of whether the patient was at risk for self-injury.

TR:  Seems like a high stakes evaluation to do remotely – did you feel comfortable, and was it a difficult adjustment?

JS: I did feel comfortable, and it didn’t seem like a difficult adjustment, at least not in this setting, because the exam is so targeted and focused, and the patient is in a well-controlled environment. Floor consults were a little more challenging, both because of the technology issues I mentioned earlier, and also because the consults could be more vague, and less focused.

TR: Did you feel that on these floor consults, you were able to be as effective when you used the robot?

JS: It can be a little more difficult; when you consult in person, you often are dependent on collateral information, such at what you might learn from a family member who’s nearby or waiting outside. It’s harder to get some of that information when you’re using the robot.

TR: You went on to use telemedicine extensively in out-patient psychiatry; what was that experience like?

JS: In the outpatient setting, you can’t control the environment, in contrast to the hospital ER and floor consults. You’re at the whim of the patients, and often they take it a little less seriously. When patients come to the doctor’s office, they tend to be more focused, and in the moment. The big advantage of telemedicine, of course, is the convenience, but this can also mean a patient is multitasking, or not speaking from a conducive location. Many telemedicine doctors talk about this challenge. I’ve had patients who would be talking with their friends, watching television, or just in a crowded place. This is a problem not only in terms of security and privacy, of course, but also, at least as importantly, because the patients tend to be distracted by the environment. Telemedicine doctors try to manage this by setting limits and having boundaries.

TR: So given all this, what’s your view of telemedicine? 

JS: I encourage it. Even with all the challenges, it is still better than people not being able to make it to appointments. The overall quality of care you can deliver because of the continuity more than makes up for the occasional challenges of a session.

The overall quality of care you can deliver because of the continuity more than makes up for the occasional challenges of a session

TR: How do you have to adjust your style for telemedicine?

JS:  You need to be more structured with patients. You also have to set limits.

TR: For your outpatient interactions, was technology an issue? 

JS: No, not at all – we used a HIPAA-compliant app, which worked extremely well.

TR: What about reimbursement – it sounds like that can be a problem for many?

JS: When I first started, some insurance companies would only reimburse for face to face encounters – but that’s really improved now. 

TR: And is there a requirement for an initial meeting face to face? 

JS: Initially that was true, but it seems to have gotten relaxed over time for many payors.  Often, it’s the physician that wants the initial meeting in person.

TR: Finally, what do you see as the future of telemedicine?

JS: Even before COVID-19, telemedicine was skyrocketing. It is the future, especially in areas like psychiatry. Because it’s not procedural, the major factor is convenience – time and geography – and telemedicine allows patients to fit in appointments much more easily. The key needs are checking in and continuity, and telemedicine affords this.

26
Mar
2020

The Coronavirus Tsunami, Lyell’s $492M Megaround & Some Deals You Missed

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26 Mar 2020

Luke Timmerman, founder & editor, Timmerman Report

When a story moves with exponential speed and deadly force, it’s hard for a human being to keep up.

Hard for you, and hard for me.

My approach these past few weeks has been to work with purpose and passion on this story that touches all of humanity. The plan has been to seek out diverse voices with fresh perspectives on the pandemic, recruit them to write for TR, and aggressively edit and publish their work in addition to mine. All of the pandemic coverage is being made completely free (no ads, no subscription required), so you can share this quality coverage with family, friends, and colleagues. I am grateful to see so many of you appreciate it.

Human life is on the line. People need quality information to make the best decisions in their daily lives. Journalism always has a public service duty, but it’s never more important than times like now. That’s why everything on Timmerman Report related to the pandemic is being made free, so you can share it with your loved ones, friends, and colleagues who need quality news and information, as opposed to the propaganda and entertainment that tends to drive too much public discourse.

My hope is that in the weeks ahead, you can count on TR to keep things in perspective, while you do what you have to do to keep your families safe and your companies operating under stress. Expect a mix of informative, data-rich voices, and fresh perspectives that can help guide us all through the crisis. Knowing the emotional strain the pandemic puts on people, expect these pages to also shine a light on writers who tap into the human dimension which is too often overlooked in the business world. You may even get a dose of humor once in a while, like yesterday’s piece by Lisa Suennen.

As a Timmerman Report subscriber, I want you know my inbox is open to you. I’m listening.

If you have suggestions of people and ideas that I should consider, let me know. luke@timmermanreport.com.

Now on to your regularly weekly Frontpoints.

The Table That Has Me Most Worried

The US healthcare system apparently relies on threadbare-thin just-in-time inventory stocking for essentials, like personal protective equipment, to a far greater extent than most of us imagined. The shortages of PPE this early in the pandemic response, along with woefully inadequate diagnostic testing in too many parts of the country, are deeply troubling at this late date of Mar. 26. Why in the world didn’t we scale up manufacturing starting Feb. 1, when the alarm bells were clear from China. Or how about Mar. 1, when it was abundantly clear we had uncontained community transmission in the Seattle area for the preceding six weeks? The federal government’s denial, incompetence, short-term thinking, and outright dangerous lies  — it’s a nightmare beyond even my darkest fears from the past few years.

I’ve spoken with doctors and nurses. The fear in their voices is palpable. They know this virus is highly contagious. They know it sends about 15-20 percent of people who get it to the hospital. Many patients need ventilators which we don’t have. Where in the world are all these patients going to go to get the adequate first-world care they need to survive?

How far do we have to go to catch up? Forgive the crude table below, which includes data compiled by OECD on hospital beds per 1000 people, through 2017. You have to scroll a long way down to find the United States.

The United States ranks No. 32 in the world, with fewer than 3 hospital beds per 1,000 people (below countries like Italy and Spain, which have been overwhelmed).

 

Beds are something of a proxy for hospital capacity. Now, you might say, beds can be obtained and rolled out in surge hospitals like the Javits Center in New York. Sure. But even if beds are installed, who will tend to the patients? Anyone familiar with unionization drives for nurses over the past 10 years knows that they are being run ragged and overscheduled,  even in normal times. We don’t have a deep bench of reserves to call up. If these frontline workers start getting sick, we simply won’t have enough skilled people to provide care. (See table below from Kaiser Family Foundation, based on OECD data).

 

Dashboards to Help You Keep Up (Which You Probably Already Have)

The New York Times has a nice visualization of the US map, along with new cases, and deaths, reported on a daily basis. (NYT Latest Map and Case Count). The NYT, given its resources, should lead the US media. It has been simply superb in its overall team coverage.  

Johns Hopkins University is a go-to source for worldwide case counts, and deaths, updated in real-time. Sadly, you can see the US moving up to the top of the list, surpassing China as of Mar. 26, in terms of total number of confirmed cases. (Johns Hopkins dashboard).

Covidactnow.org is an excellent resource that provides colorful state-by-state projections of what various scenarios look like, with aggressive community mitigation and without. (H/t to TR subscriber Steve Dickman of CBT Advisors for sharing).

Covidly.com. A simple display. US is now No. 1 in the world in terms of confirmed cases.

Sad, but Predictable Fallout

Eli Lilly announced something that should have been pretty easy to anticipate a couple weeks ago. Clinical trial activity is being curtailed during the COVID19 pandemic. New trials in the queue aren’t being started. Enrollment of new patients in existing trials, are being paused. Existing patients in trials who need to stay on protocol as part of their care plan, will maintain continuity on study. I’d watch for more shoes like this to drop in coming weeks.

Silver-lining Department

Scientists, doctors and nurses will be the new heroes in our society in the 2020s and beyond.

A few highlights from the world of science:

Seattle is a few weeks ahead of the rest of country in the coronavirus outbreak. The Seattle Flu Study, which was set up as a $20 million project to gather samples from people suffering flu-like symptoms in the community to better understand that virus, has been nimbly, and heroically, repurposed to evaluate the community spread of SARS-CoV-2. These scientists from the University of Washington and Fred Hutch have not only provided a crucial set of data-driven warnings to scientists around the US, they’ve turned virology labs into a high-volume testing center when the federal government failed to keep up with a virus that spreads with exponential speed. Read about the Seattle team’s new research plan here.

A brute force team of scientists led by the famous drug hunter Kevan Shokat at UCSF published what you’d have to call a tour de force of a preprint on BioRxiv. They described their work probing for an Achilles heel in SARS-CoV-2. They found “332 high confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 existing FDA-approved drugs, drugs in clinical trials and/or preclinical compounds, that we are currently evaluating for efficacy in live SARS-CoV-2 infection assays.” Talk about working with purpose and passion. Who knows where this will lead, but holy mackerel. Read the preprint yourself here.

Scientists in China, alongside US peers, are looking at lightning speed for broadly neutralizing antibodies against SARS-CoV-2. Chinese scientists reported Mar. 25 on an almost incredible 206 broadly neutralizing antibodies against the receptor-binding domain on the virus. Antibodies can provide exquisite specificity to a target. The Chinese team reported surprisingly little cross-reactivity with SARS and MERS. But one challenge with antibodies is they are difficult to scale up for all-out mass production quickly. If these go anywhere, antibodies in beginning small batches could be an especially important tool for treatment of patients in severe distress, and potentially for prophylaxis of healthcare workers on the front line. That would be an interim step before we get a cheap, effective vaccine that can be given worldwide.

Disease modelers at Imperial College London rocked the world with their original report on Mar. 16 that as many as 2.2 million people in the US could die from COVID19 in a worst-case scenario. Some skeptics wondered if this was alarmism, given the thin gruel of actual hard testing data that the modelers had to work with in order to make their projections, including the crucially-important Case Fatality Rate. Data on hospitalization rates, similarly, is hard to pin down with sweeping, and accurate, testing data. Even so, a lot more data has come in worldwide in the last 10 days. Now the Imperial College London team is out with a new report on Mar. 26. The updated report expects 7 billion infections and 40 million deaths worldwide this year with no interventions. Mitigation strategies could cut the death toll in half, but would still result in overwhelmed healthcare systems. (Full Mar. 26 report here).

COVID-19 Reading from Around the Web

 

TR Coverage of the Pandemic (Free & shareable with friends, family & colleagues)

Tweetworthy

Craig Spencer is a physician in New York City. Healthcare workers there are in serious trouble. The wave of COVID19 patients is coming to parts of the US, too.

Read this tweet, which sums up this disastrous state of affairs, and boils with frustration.

In Other News…

Deals

Redwood City, Calif.-based Codexis formed a partnership with Takeda to make novel enzyme sequences for use in gene therapy preclinical development. Terms not disclosed.

South San Francisco-based CytomX Therapeutics pocketed an $80 million upfront payment from Astellas to co-develop bispecific antibody treatments for cancer. 

Pfizer partnered with Germany-based BioNTech to work on an mRNA-based Covid-19 vaccine. Plans to work out financing terms will get worked out later, given the urgent need. Cambridge, Mass.-based Moderna staked out a lead in the category, dosing the first patient in a healthy volunteers trial in Seattle, the epicenter of outbreak in the US.

Data That Mattered

Genentech and AbbVie reported that venetoclax (Venclexta) improved overall survival time, in combo with azacitadine, compared with the standard chemo, in a Phase III trial of patients with acute myeloid leukemia. Details coming at a future medical meeting (whenever they might be held again).

Financings

South San Francisco-based Lyell Immunopharma raised $492 million in a Series C equity financing that included 10 investors, according to a regulatory filing with the SEC. The company didn’t issue a press release on the financing, but Bob Nelsen of Arch Venture Partners confirmed to me that Arch participated, and has plans to continue with three large financings in coming weeks, despite the pandemic. Lyell is led by CEO Rick Klausner, a former director of the National Cancer Institute and a co-founder of Juno Therapeutics.

South San Francisco-based CERo Therapeutics raised $40 million in a Series A financing. The company is working on engineered T cells for solid tumors. Arch Venture Partners participated. (See TR coverage on T cells for solid tumors, March 2020). CERo also said it struck a partnership with Lyell Immunopharma.

San Diego-based Design Therapeutics raised $45 million in a Series A financing led by SR One. The plan is to work on nucleotide repeat disorders, starting with Friedreich’s ataxia.

Menlo Park, Calif.-based ReCode Therapeutics secured an $80 million Series A financing, co-led by OrbiMed Advisors and Colt Ventures. The company pools some assets for mRNA and tRNA therapeutic development for lung diseases, starting with primary ciliary dyskinesia and cystic fibrosis.

Emeryville, Calif.-based Eureka Therapeutics raised a $45 million Series E financing to advance its cancer treatment programs. Lyell Immunopharma led.

26
Mar
2020

Pharmacy as the Biomarker of Biopharma’s Strategic Change, After Coronavirus

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26 Mar 2020

Jeff Berkowitz, CEO, Real Endpoints

Maybe it was my jarring transition from a decade and a half inside the gilded halls of large pharma to the rough-and-tumble world of retail pharmacy 10 years ago, but I’m a wee bit cautious of the current self-congratulatory tone of the biopharma industry’s response to the pandemic. 

I’ll certainly be delighted if Regeneron and Sanofi’s IL-6 receptor inhibitor sarilumab (Kevzara), Genentech / Roche’s IL-6 inhibitor tocilizumab (Actemra) or Gilead’s antiviral remdesivir work against COVID-19. A vaccine would be the ultimate victory. But biopharmas will likely get well paid for this work.

Not so with most of the folks Robert More listed in his piece yesterday on the uncrowned (uncorona’d?) heroes of the COVID-19 wars. 

I’d like to focus on a group More doesn’t mention — also on the front lines of this crisis and usually — even now — ignored, when not actively disdained, by the flashier, high-science, high-equity end of the pharmaceutical supply chain. I’m referring to pharmacy workers — pharmacists and pharmacy technicians. 

First off: they’re at the front lines with patients handing out drugs, now. Some part-time pharmacy techs get by with just-above-poverty-line average salaries and no benefits. Some of them work for the largest of employers working on 2% net profit margins (despite their highly paid executives), not the 25% net profit margins Big Pharma collects each year. These unsung heroes are tasked, in their 30-second interactions with patients, with checking for drug/drug interactions, making sure the product is dispensed correctly, and address complex reimbursement issues. They are trained to communicate, clearly, so that the patient understands the potential side-effects, etc. … all while being asked to ring up someone’s beef jerky and People magazine. 

Look, I recognize that these people aren’t doing their jobs to be heroic – they need the salary. And right now, those jobs look pretty secure, albeit hardly lucrative.

But I don’t mean merely to deliver a panegyric to dispensing pharmacists. The broader strategic point is that the novel coronavirus is going to make these unsung warhorses more, not less, important to the pharmaceutical industry.

Consider, first, that retail pharmacies have dramatically lowered the cost of healthcare in the US by making vaccines — particularly the flu vaccine — widely available at virtually no cost.  The same distribution model — at consumer-friendly outlets that don’t require appointments and are located within a 5-mile drive for about 80 percent of Americans — is being applied to higher-margin vaccines. Look at the recombinant, adjuvanted shingles vaccine (Shingrix), a $2 billion a year blockbuster marketed by GlaxoSmithKline. Like the humble, cheap, generic flu vaccine, this higher-margin product is largely dispensed at pharmacies – sans doctor visit, sans office copay. 

Now imagine what happens when millions more go for a COVID-19 vaccine jab — not to doctors’ offices, but to Walgreens or CVS or even better their mom-and-pop pharmacy.

It’s not a giant intellectual leap from there to the Minute Clinic vision of CVS/Aetna – or perhaps less ambitious, the permitting of all pharmacies to administer medical-benefit drugs, at vastly lower cost than the current buy-and-bill model allows. Already, pharmas are arguing that, with millions sheltering in place and avoiding medical offices, the Center for Medicare and Medicaid Services, CMS, should pay for home infusion of virtually all non-hospital Part B drugs. How far from there to administration of these infusion medicines in retail pharmacies? 

Given the potential disruption to all those lucrative, doctor-owned infusion centers, drug companies may have to reconsider just who they’re marketing to. They might find that price competition – true market forces to undercut rivals on price – may come to the heretofore largely price-protected, comfortable buy-and-bill world of today. 

More broadly, however, what we predict as pharmacy’s ever more prominent role in what might be called true population medicine could also change pharma. Even in the midst of this pandemic, pharmacies address on a daily basis the most common ailments that plague our nation – cardiovascular disease, diabetes, COPD, and asthma (and maybe soon, NASH). Any one of those diseases kills more people each year than COVID-19 is likely to. 

What pharmacies have lacked are the same tools the pharmaceutical industry has chosen to, and will, develop to solve COVID-19. Instead of working collaboratively throughout the healthcare ecosystem to solve the largest, most vexing problems, the biopharma industry has chosen to focus its attention on the narrowest of problems, rare and orphan diseases which they perceive as being immune from price pressures. (See “We’ve Been Neglecting Common Diseases.” By Alex Harding, Timmerman Report, Jan. 2020).

We recognize the reimbursement challenges of primary care: but COVID-19 represents an alternative view – what can happen when an industry mobilizes to solve the biggest problems in human health.  

Until very recently, senior pharma management rarely spoke to payers, let alone the rest of the supply chain.  Indeed, pharma has historically operated in its own ecosystem – a kind of prehistoric Australia, linguistically and culturally independent (Alexis Borisy – whose new company EQRx aims to disrupt pharma with a strategy enabling radically reduced, payer-friendly pricing, made the same point on the most recent Long Run podcast with Luke Timmerman). 

Indeed, one of the dirty little secrets of our success at Real Endpoints is that we speak to payers and distributors all the time, in their language – translating their concerns and the implications of them back to pharma C-suite executives. We expect that there will be a BC and an AC in pharmaceutical history – before COVID-19 and after. And that pharmacies will be one of the biomarkers of that change.

Next week I plan to write about COVID-19’s impact on payers – and how that will affect pharmaceutical strategy.

Jeff Berkowitz is CEO of Real Endpoints, a health-care advisory/analytics firm delivering solutions that enhance appropriate access to innovation

26
Mar
2020

We Interrupt This Nightmare to Bring You a Few Giggles

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26 Mar 2020

Lisa Suennen

Here we are, all of us, stuck in our houses, scared, stressed and exhausted. Some of the people we love are very sick or worse. People are justifiably worried.

Reading the news is enough to raise your blood pressure so high, it becomes a risk factor for COVID19 all by itself. Which is particularly problematic, because you can’t get a regular doctor’s appointment now unless you have Ebola (thankfully under control now in Africa).

As a break from the non-stop misery feed, I have been trying to laugh. You have to laugh during times like this if you can. There is not enough Xanax in the world to be as solemn as the situation demands. I don’t mean to minimize the horrible challenges facing many people. I’m just saying, if you are one of the lucky ones who is safe while under modern-day house arrest, laughter is a good way to stay sane.

There’s a reason we have a technical term called “gallows humor.” If New Yorkers were allowed to leave their homes, I would already have asked someone to swim out to the Statue of Liberty and change her plaque to say:

“Give me your anxious, your stressed out, your huddled masses yearning to go anywhere, even the Comcast store, The wretched refuse of your unshowered, LuLuLemon hordes. Send these, the shut-ins, tempest-tost to their PC. I lift my lamp from inside your Zoom background!”

For those with small kids, the brazen screaming and swearing that colors so many senior management meetings gives a whole new meaning to NSFW (“not safe for work” for you are not up to date on your hipster acronyms). The challenge is keeping your kids from hearing the stuff you say at work without their demanding that you put $1 in the swear jar. I know a few people who would go broke in about two weeks if they enforced that one. I’d be one of them if my kid weren’t grown up already.

NSFW may also apply to that moment on the Zoom meeting where you get up to refill your coffee and everyone else gets to see you’re working in boxers or briefs, the new  business casual. I have been on at least 11,947 Zoom calls in the last week and a half. It has been hilarious seeing people’s cats, kids, funny hair styles, burgeoning beards, breakfast foods. Suddenly every day is casual Friday. I have been alternating between the same two pairs of leggings and T-shirts pretty much every other day. They are all black, like my mood. I have also decided “to hell with makeup.” Sorry, MAC and Bobbi Brown. Messed up times call for un-dolled-up faces, though Zoom has an app for that.   

(If you are not aware of the Zoom feature called “Make Me Look Better,” you haven’t lived. If only they had a feature called “Make Me Look Taller,” I’d be enjoying this working from home thing a whole lot more).

Speaking of NSFW…for every company that is teetering toward bankruptcy, there is also one that is able to capitalize on the situation in some way. My favorite opportunistic marketing gimmick so far is from CamSoda, an adult entertainment site.

Their press release states:

“Coronavirus has left much of the U.S. stuck inside. This has not only taken a toll on people’s sanity, but it’s had – and will continue to have – a terrible impact on businesses, especially those in the entertainment space, who have been forced to shut their doors,” said Daryn Parker, VP, CamSoda. “In an effort to provide consumers with some top-of-line entertainment remotely, and to enable businesses to earn money, we’re leveraging our technology that allows adult entertainers to broadcast to millions annually and launching CamSodaLive.”

CamSodaLive, you see, is working with StandUp NY to broadcast comedy for when the porn just isn’t working for you anymore. Comedians get to make some money, consumers get a diversion, and when they’re done, they’ll probably be ready to come back for some more porn. Genius.  

I love the idea of bringing more comedy to the masses (even if they are naked masses).  I have been using Twitter largely to broadcast amusement. I call it “Comedy as a Service” (CAAS for the venture capitalists out there looking for new business models with cool new acronyms). My favorite example so far is this:

The best line in that song is how bad this would all be without the Internet. Can you imagine? True, we couldn’t see things on endless repeat that make us worry the end is nigh, like Tony Fauci hitting his forehead with the palm of his hand. But without the Internet, we would be forced to speak with our family members ALL DAY LONG. I love my family members, ages 64 and 24 (plus those that are 5 months old and 13 years old if you count the puppy and the cat), but all I can say right now is: Thank God for Doors.

Among the many things that people are doing more of (besides sighing deeply about the general fuckitivity of it all) is cooking.  Food delivery companies are working overtime, but many consumers are nervous about them, reasonable or not.  I have decided that one of the 7 signs that this is an actual apocalypse is that Burger King is now doing home delivery. 

We are venturing out to go grocery shopping occasionally. We have started a shopping list to inform the efforts of the unlucky one among the three of us who loses at rock, paper scissors and has to venture out among the germs.  We have dubbed our shopping list “The Apocalyst.” 

Given all of the sitting around we do planning for the next meal, I can only imagine how our collective national weight gain is going to look in a few months when we get released from sorta solitary.  You know how when you go to college, you gain the Freshman 15?  We are all going to gain that COVID 19 before this is over. That is likely an understatement if you are already in “make mine with extra cheese” mode.  Yes, there are on-line exercise classes to help you burn off some of the extra comfort foods being ingested, but I would like to know the relative utilization of those vs. utilization of CamSoda’s core business. 

From talks with friends, a few common themes have emerged.   

  • Among women, the greatest source of panic is lack of access to hair colorists. Our roots are growing out. We are going to look like a nation of skunks before long.  Thank God for enterprising hair-dressers who are finding ways to ship us the goods so we don’t need a Zoom setting called “cover my white roots.”
  • It is five o’clock EVERYWHERE AT ALL TIMES. This would be a great time to buy stock in Diageo or Constellation Brands. Both companies sell a lot of hard liquors. And now they have a supersized Total Addressable Market. But poor Constellation is also home of Corona beer. There are actually people who are afraid to drink Corona beer right now, and it’s not because they lack the sliced limes. Um, really? I have dubbed these people “Covidiots.” Note that liquor stores are considered “essential workplaces” by numerous states that have implemented lock down rules, proving that politicians are smarter than they look.  I have not heard whether cannabis dispensaries are being treated similarly, but I can only imagine the delivery ones are doing a booming business. 
  • People who have dogs have “license to walk” and are out and about as if their dogs have never had to pee so badly. I took my dog for a walk and encountered so many others doing the same, that some of their butts had to go un-sniffed. So many dog butts, so little time outside.
  • Families with teenage kids are totally set because they have built in IT support in their homes. Families without teenage kids are constantly getting kicked out of their Zoom accounts and struggling with Comcast. I would offer a king’s ransom for anyone who can help me set up my new printer, as my old one took this opportunity to commit suicide. Clearly, electronics can have a sense of humor too.
  • There are fierce, if unspoken, competitions to have the most compellingly ironic or entertaining Zoom background. Personally, I am a fan of the aurora borealis background, but I’ve seen some good stuff as people import their personal photos and display them to all their work connections in a way they would never do in real life. Nothing like having a conference call about economic crises while looking at a glittery photo of Las Vegas at night.
  • Companies of all types are trying desperately to keep their employees and keep them connected and socializing. People are playing games, sharing recipes, providing group counseling, you name it. Some are hosting happy hours for their teams because…why the hell not?  

To amuse myself in the 11 seconds per day between Zoom calls, I started a contest (on Twitter, of course). The challenge was for someone out there to write the best COVID19-related lyrics sung to the tune of “Hey Nineteen” by Steely Dan. This seems to me the perfect parody song opportunity and I hadn’t seen anyone do it yet. I got but one response, but it was a great one.

In closing, I offer you the best stanzas from the tour de force by David J Whelan of Bespoke Business Strategy (just get the tune in your mind first by going here:

 

COVID Nineteen,

We got six feet between us

(we can’t dance together)

No, we can’t talk at all

Please take me along when you Zoom on by

 

COVID Nineteen

That’s a lethal virus

We don’t remember the Spanish Flu

It’s hard times repeated

The sole survivors

Trump thinks we’re crazy

But we’re just safe at home

 

A Corona bold

That fine N95

Make tonight a Netflix and chill

(Tweet it again)

A Corona bold

That fine N95

Make tonight a Netflix and chill

 

Here’s to hoping all of you are safe, healthy, and chilling as best you can. 

 

Lisa Suennen is the leader of Manatt Phelps & Phillips digital and technology businesses, and the firm’s venture capital fund. Her role spans technology across sectors, although she works very closely with Manatt Health, engaging with payers, health systems and companies to provide strategic advice on innovation, digital strategy and growth.

25
Mar
2020

Unsung Heroes Who Give Me Hope

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25 Mar 2020

Bob More, managing director, Alta Partners

The spread of COVID-19 is likely to be one of the defining issues of our time. Just like those that lived through the Great Depression, World War II, and perhaps even 9/11, it will live with us for the rest of our lives and leave its imprint for decades.

Our children, and grandchildren, will remember this — and be influenced by — our collective actions against this dangerous virus. 

My son, Jake, is an EMT in Salt Lake City. He is on the front lines. I worry. But I have not heard a word out of him about his risks. He is doing his job. I am sure he, like everyone else, simply wants to do whatever is possible to be part of the solution. To be part of the community. To be part of our collective humanity.

And as with all defining moments, we are vividly living our common humanity. Almost anything we do – an ordinary trip to the grocery store, a lonely walk in the park for a moment of respite — takes on new meaning and depth. We are all faced with daily decisions that may have consequences. And those consequences could mean life or death.

For all but a few of us, this is not normal.

Physicians and particularly surgeons come to mind. But also military, police, fire, and emergency workers. And these people are professionally trained to be decisive and clinical, and they understand that it is part of the job.

How about the rest of us? Most of us aren’t on the front lines, and shouldn’t be. The best thing we can do is to stay at home, keep our physical distance from other people when we go outside  for a breath of fresh air, and hold our loved ones close to us emotionally (even if it’s by phone or Zoom).

Never have I been more hopeful. I have never smiled at so many strangers. And I have never thanked so many people who, perhaps, I did not even notice before.

People are stepping up. It seems everyone is willing to put personal risk aside, and find a way to make a meaningful contribution to the world in this moment. There are certainly exceptions, largely born of ignorance. But for people that understand what we are facing, the almost universal response I hear is “how can I help?”

From the first days when scientists began discussing the novel coronavirus we now call SARS-CoV-2, even when we had no idea what we were dealing with, physicians and healthcare workers on the front lines in China were knowingly putting themselves in harm’s way. It was for the patients they served, but also to try to gain an understanding of what we were dealing with to warn the world.

Li Wenliang was on the front lines. He sounded the alarm early in December. For that service to  the world, he was imprisoned by Chinese authorities, who accused him of spreading rumors. (He died in early February, and was recently exonerated by the authorities). Li, understandably, is front page news. But almost no one else will be. Everyone in the medical profession knows the risks they face when they work with patients, and yet it is hard to keep them away from the hospitals. They want to be there.

People are making adjustments on the fly. Retired healthcare workers are back volunteering. Restaurants are delivering healthy, delicious meals to healthcare workers to support them and keep them focused on critical patient needs. Medical school students are screening patients via telemedicine with systems that simply did not exist 10 days ago. They are making it work.

What impresses me most of all are the people who are stepping up, even when they have no duty, no sworn professional oath and no real rewards for running toward the fire.

Think of the people working the cash registers in grocery stores and pharmacies. The people who keep the water supplies, the energy grid, the TV and the WiFi information pipelines working. The janitors, garbage workers and maids handling our refuse and stepping in to clean what is surely biohazard material without the appropriate personal protection equipment. How about the home healthcare workers who assist elderly people, who change bedpans? Not only do they do that, they are doing it while extending some needed compassion with elderly folks during what’s surely a stressful time.

We need to keep the supply chains and society running, at least for what are considered essential services. It is perhaps humbling that so many of us in so-called “high-level jobs” do not fit into the definition of “essential services.”

It is in times like these where we see so much of better angels of humanity. And some of the beautiful and selfless things people do to help one another. Younger people are checking on older neighbors and volunteering to get them their groceries or medicines. Stores have altered their schedules to accommodate shopping for seniors-only during the early morning hours. Teachers are finding ways to teach their students online and keep them busy and learning.

I serve on the board of San Francisco-based VIR Biotechnology. It’s a company that was purposely built up over the past few years to go after infectious diseases. Those capabilities are now springing into action against this virus that was unknown to the international scientific community until Jan. 11. People there now are working in the labs, if they need to be there to keep their experiments going. Some early, preliminary work on neutralizing antibodies has shown promise.

But this is truly a worldwide collaboration of scientists working with passion and purpose. Lab workers at our subsidiary company Humabs BioMed are working in Switzerland near the Italian border in what amounts to a war zone. These scientists never take their eyes off the ball in their search for antibodies to fight COVID-19. And they never asked for anything special in return.

A pandemic like this has heroes. For the most part, I think of the professional healthcare workers and scientists that are working with patients and searching for cures. That is amazing.

But what is even more amazing to me are the people who have never trained, and perhaps do not even fully understand the risks, but know that they are a critical part of keeping society moving forward. They will not be recognized for what they are doing. We rely on them every single day. We simply expect that their work will be done. We rarely thank them. We rarely take the time to ask how they are weathering this storm.

I recently moved to Jackson Hole, Wyoming. We are far from New York City, Seattle and San Francisco. Yet the virus is here as well. And many people live paycheck to paycheck in Jackson. In a tourist town like this, I would imagine the unemployment rate just went over 30%. The ski resort is closed. People are still out in nature, but at a distance. The folks that plow the streets are up every day at 6 am, plowing and shoveling snow. Everyone is worried. But they seem more worried for their neighbors. There is a community here. We are all reliant on many of the invisible jobs to keep things from falling apart. What is most impressive is that nothing is falling apart.

We all know we are in this together.

So thank the folks that are bagging your groceries. Appreciate the flight attendants and pilots who are traveling despite the risks. Be kind and empathetic to those who are going about their days to make life work for the rest of us. They are human. They are at great health risk, great financial risk, and facing all of the same fears as the rest of us.

That is heroic.

25
Mar
2020

A Surge of Gratitude, From a Doctor on the Front Lines of COVID-19 in Boston

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25 Mar 2020

Alex Harding, MD, associate, Atlas Venture

Eleven days ago I wrote an article for Timmerman Report on my initial emotions as a doctor on the front lines of the COVID-19 pandemic: fear, frustration, and confusion.

Today, I’d like to add another emotion to that list. Gratitude.

Above all, I am grateful that I can do something to help. My impact is small—miniscule in fact. I’m working about 4 evenings per week at MGH as I balance with my job at Atlas Venture, and usually can’t see more than 8 or 10 patients per shift. But it’s enough to keep me busy and give me some direction in a world that otherwise could feel adrift. What I did not expect, though, was to see how other people have found disparate ways to help.

Over the past week and a half, I have witnessed more impossibilities become reality than I can list here.

At Mass General Hospital, people have united behind the common goal of confronting this pandemic and protecting our patients. Outpatient practices have cut back to skeleton staff as routine appointments have moved online or been canceled. Normally bustling surgical suites are deserted. Instead, it’s all hands at our front-line clinics receiving patients with respiratory illnesses and testing (when appropriate) for COVID-19.

Orthopedic surgeons are working alongside psychiatrists, neurologists teamed with endocrinologists and anesthesiologists. In the medical community, large cultural and stylistic differences have historically separated the specialties. Normally, we don’t talk much. In this crisis, whatever differences we have between our specialties no longer matter. We’re all doctors. We’re all doing everything we can to bring this outbreak under control.

Since my last article on Mar. 14, my clinic has been converted from the Medical Walk-In Unit—a quiet clinic intended to help patients with issues like urinary tract infections and sprained ankles—to the Respiratory Illness Clinic. It’s a highly controlled, carefully sanitized environment intended to exclusively manage patients at high risk for COVID-19.

Everything about our clinical workflow has changed. The tests we can order, how we counsel patients, and how we manage them. The waiting room has been transformed by sealed plastic walls that isolate the patients, who are potentially infectious, from the patient services coordinator who registers them. Seats in the waiting room are spaced six feet apart. Everyone—patients, nurses, doctors, medical assistants, security guards—wears a surgical mask.

Everyone’s job has also completely transformed over the past week. People have been thrust into unfamiliar—and sometimes hazardous—environments all over the hospital. Remarkably, people have adapted without complaint.

I’m grateful to work with people who are doing whatever it takes to fight this virus off. It’s the only way we’re going to win.

Outside of the hospital, I have been surprised over and over by the support and appreciation people express for me and my colleagues working to take care of patients with COVID-19. As healthcare workers, we see ourselves as just doing our jobs, even if we never expected a situation quite like this. But under these circumstances, the community support is uplifting. It helps with morale. I’m grateful for it.

One of the great things I’m seeing is the creativity in how non-healthcare workers are finding myriad ways they can help. A relative, who is currently recovering from COVID-19 and doing well, actually offered to help screen patients since she may be immune to the virus once her infection is cleared. (Given the need for specialized training in the proper use of PPE and patient management, I told her ‘thanks, but no thanks.’)

In the biotechnology industry, the desire to take action seems universal. Companies have donated masks and gloves from their facilities to help replenish depleted stores of PPE in hospitals. Companies are starting up compassionate use programs for their medications that hold promise for treating COVID-19. Other companies are crafting entirely new programs against COVID-19 – whether their expertise is in diagnostics, treatments, or vaccines. Despite knowing the odds are not in their favor to create an effective treatment for this disease, companies are pouring their limited resources into these risky programs.

I have friends and acquaintances asking me how they can set up their home 3D printers to help make face masks to protect healthcare workers. Others are writing me notes to see how they can donate spare masks they have at home, researching the best evidence for potential COVID-19 treatments, organizing webinars, and tweeting words of encouragement. Even the simple act of staying at home to avoid spreading the disease is an act of solidarity for which I’m grateful.

I don’t intend to sugarcoat the dire situation we’re in. Hospitals in New York are overrun as you read this; workers there are haphazardly reusing protective equipment and wondering when they will run out of ventilators. Even in Boston, cases are rising exponentially and our inpatient units are starting to fill up. The uncoordinated response at the state and national levels is baffling. But I’m still grateful to be surrounded by so many people on the front lines, united in the singular goal of defeating this virus.

The other day I had a young patient with a viral infection and asthma. To use some medical jargon, she was “pretty sick.” She had a wheeze and shortness of breath, as well as the telltale fever and cough typical for COVID-19. She was wearing a navy blue cloth mask. She told me she had bought it a few months ago on a trip to Indonesia to protect against pollution. I wore a paper gown, rubber gloves, a mask, and goggles. I prescribed her an inhaler, adjusted her other medications, and sent her to be tested for COVID-19. On her way out, she turned around, looked me in the eye through my flimsy plastic goggles, and thanked me for being there.

I could honestly tell her, without any exaggeration, that there was no other place I would rather be.

24
Mar
2020

What Not To Do: Lessons From Spain’s Cavalier Response to COVID-19

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24 Mar 2020

Bernat Olle, CEO, Vedanta Biosciences

I grew up in Catalonia, in the north-east of Spain, and came to Boston in my late 20s for a PhD at MIT. Today, I am the CEO of Vedanta Biosciences, a Boston-based biotech I co-founded.

As I write this, the coronavirus epidemic is extending across Spain faster and more broadly than it has anywhere else in the world (see figure below).

On Mar. 23 alone, 462 people died in Spain from COVID-19. The death toll now exceeds 2,300.

The total number of deaths doubled in three days.

The worst scenes are coming from Madrid, the capital and largest city in Spain with 3.3 million people. The hospital system in Madrid has already collapsed. Over the next two days, the hospital systems in other regions will collapse, too. I am seeing videos of doctors in tears explaining how they have to remove respirators from people over 65 to give them to the younger patients, and then sedating seniors to minimize their suffering.

The failure of the Spanish government to respond to this crisis has been perhaps the most spectacular of any country in the world, so far.

COVID-19’s emergence took China’s government by surprise. Elected officials there first silenced scientists, but soon realized their mistake and acted with determination to fix it.

Italy was caught off guard, perhaps too comfortable with its geographical separation from China, and the virus ravaged its northern regions.

Spain’s elected officials saw the tragedy in nearby Italy unfold. They had the benefit of a several-week advance notice from a close neighbor and had absolutely no excuse for inaction.

Denial Can Be Fatal

“Spain will have, at most, a few isolated cases of coronavirus.”

“There is no coronavirus in Spain.”

These were the words of the government officials in charge of coordinating Spain’s response only a few weeks ago. These statements were coming out at about the same time that here in the US, President Trump was saying “we have it totally under control.”

Neither country was doing any meaningful testing at the time.

These are words that will go down in infamy.

As COVID-19 was ravaging northern Italy, Spanish government officials took a criminally cavalier approach. In early March, with already over 130 cases and several deaths in Madrid, the prime minister allowed mass gatherings including the 120,000 people-strong march in downtown to celebrate International Women’s Day on Mar. 8. Soccer games with tens of thousands of fans packed in stadiums. Around that time, a political rally of 9,000 people gathered in a bullring.

All of these things should have been cancelled, given what was known about the virus at the time.

Despite being hit several weeks before Spain, Italy acted faster in reducing mobility in the initial cluster of cases in its northern region of Lombardy. Spain, instead, allowed people to move freely in and out of Madrid early on, and these people dispersed across the country. Officials also allowed mobility inside Madrid, with 50% of people still going to work as recently as last Friday, Mar. 20. Lombardy and Wuhan were in lockdown well before they hit that same point in the epidemic curve. Now Spain has the fastest spreading contagion in the world.

The lesson here is that the government’s blasé approach and its failure to take strict mitigation steps sooner caused thousands of unnecessary deaths, and it cannot be allowed to happen elsewhere. It was a mistake to allow mass gatherings well into the epidemic. It was a mistake to allow geographical dispersion of the cluster of cases from Madrid. It was a mistake to allow so much mobility within Madrid and clusters that sprouted up in other parts of the country.

Don’t Silence the Scientists. Events Will Force You To Do What They Say

In China, when now deceased Dr. Lu Wenliang tried to warn the elected officials about the coronavirus outbreak, he was threatened by the police to “stop spreading false rumors.” In Spain, this type of restriction on freedom of speech is frowned upon as unsophisticated. Instead, the government has relied on its friends in the press to defame scientists that sounded the alarm. 

Renowned epidemiologist Oriol Mitja, who was involved in leading research to eradicate yaws from endemic countries, has been one of the most vocal scientists asking for stricter measures. A month ago, he advocated common sense measures including cancelling gatherings, getting ICUs ready, or isolation of symptomatic cases, and asked for transparent communication of the imminent risks by the government.  A week ago, with deaths already skyrocketing, he asked for a strict shelter-in-place and called for the resignation of the government official coordinating the COVID-19 response.

Not only were his warnings ignored, he was bullied for speaking out. Some of the country’s newspapers with close ties to the government accused him of being politically motivated. Gradually, the government has been forced to enact the exact set of measures that he proposed early in the outbreak, when the measures would have been more effective. A large group of Spanish scientists is now saying that the government actions are still not sufficient to control the exponential phase of the epidemic, and are asking for stricter measures. This time, the government should listen.

“If Your Government Won’t Help You, Do It Yourself”

This pandemic has put on display the complete failure of leadership by the elected leaders in Spain. The same is happening in the US with Trump. There really are tremendous social costs to electing inept leaders to office. But the pandemic has also exposed the ability of other groups of individuals — usually at the state or local level — to make change happen.

In Spain, several regional governments have asked their people to follow more strict social distancing measures than those recommended by the central government, and in Catalonia, a consortium of automobile and tech companies have banded together to develop an industrially scalable respirator prototype of which they plan to produce 100 units daily by next week. In the US, we have seen some state governments take decisive action where the federal government came up short. We have seen private industry and academic institutions step up, and create work-arounds, to help address the tremendous deficiencies in testing and availability of personal protective equipment and respirators.

And each of us can individually also do things to protect ourselves and others.

Bill Hanage, a Harvard University infectious disease epidemiologist and acquaintance, recently wrote to his UK fellow countrymen, in criticism of the UK government’s maligned ‘herd immunity’ plan:

“The most fundamental function of a government is to keep its people safe. It is from this that it derives its authority, the confidence of the people and its legitimacy,” he wrote. “If your government won’t help you, do it yourself.”

That’s what I told my 70-year-old parents in Spain. They are now secluded in a house in the mountains. My brother is temporarily not living under the same roof, to limit the risk of contagion. Elderly people all over the country are being isolated from their loved ones for their protection.

Right now, I’m very angry. I wrote a first draft of this piece last night. As I get ready to hit send on revisions this morning, just a few hours later, the toll has gone up by 500 new deaths and 7,000 contagions. The hospital in Reus, my hometown, has 23 COVID-19 patients, eight in the ICU. The average stay is 25 days.

They are 3 respirators short.

They expect to be collapsed by this weekend.

Leadership matters.

24
Mar
2020

Doctor, Mother, CEO: Balancing Competing Needs, and Opting for the Front Lines

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24 Mar 2020

Amanda Banks Christini, MD; CEO, Blackfynn

Yesterday I woke up on an island.

I am temporarily – but purposefully — isolating myself and my two children, ages 10 and 12, in a familiar place that carries with it a slower rhythm from a different time. It’s our second home.

It also happens that, on the first day of spring, there are still no cases of suspected or confirmed COVID-19 on this island. Talk about isolation.  

A week ago, I left Philadelphia to come here for the safety of my family.

But I didn’t leave our communities, or our world, behind. I’ve decided to come back, and put my medical training to work on the front lines during this time of urgent need.

We are all struggling with, distracted by, this new reality that has been thrust upon us by the completely predictable intersection of a rapidly transmissible, emerging infectious disease and a fatally neglected public health infrastructure.

Our current administration is adding fuel to this fire through characteristic and striking ignorance. The administration’s actions — and inaction — will have profound long-term effects on our fragile healthcare system and on our economy. But while the temptation to place all the blame at the feet of elected officials is strong, we are in this situation because of many decades of broken policies and misplaced investment.

I am angry and frustrated. But I don’t have time for this now, because I am consumed by the balance between being a CEO of a company with 36 employees, a mother, a daughter, a sister, a friend, and, a practicing internal medicine physician who also works as a hospitalist in Philadelphia to care for acutely ill inpatients.

I am profoundly wrestling with the obligations of these roles, which, in this new reality, can be both fully aligned and simultaneously in stark conflict.

I have a fiduciary duty, as CEO, to not take undue risks as a “key person” at my company. But the healthcare system will collapse under the weight of this pandemic if healthcare workers don’t step up. And they are stepping up in droves, despite the lack of supplies. My employees need decisive leadership. They also seek my medical advice at a time when the mixed messages of state and federal officials, combined with certain media outlets with irresponsible tendencies and partisan biases, is deafening. It’s hard to know what to believe. I am balancing my passionate dedication to patients with a fierce instinct to protect my children.

I jumped on the front lines in 2014 as a first responder against Ebola and was a (pregnant) medical resident taking care of patients with H1N1 flu in 2009. I will not sit on the sidelines and watch my colleagues fight this battle.

In the end, despite the risk I know it will pose to me and possibly my kids, I will have to leave the temporary isolation of my island retreat. I will have to make arrangements for child care, and then go to the front lines. I need to help care for not just patients with COVID-19 infection, but also for the many patients with heart failure exacerbations, complications of uncontrolled diabetes and hypertension, renal disease, heart attacks and strokes who are admitted in greater numbers because their routine clinic visits have been cancelled to make way for the surge of pandemic victims in dire need. We are going to see a chain reaction of more sickness in these patients, because they won’t get adequate telemedicine consults. That’s because this country has never prioritized, nor authorized reimbursement for, telemedicine services.

As CEO I made the decision, like many others, to make working remotely mandatory. I am trying to keep a company of now fully remote workers engaged, productive, motivated and safe – a company that I co-founded, that I lead, to which I am passionately dedicated. The employees are people to whom I am deeply connected and feel a tremendous responsibility. In a world where the financial markets went from soaring to reactive, trepidatious and emotional, I am also trying to steer our company through an unprecedented time, at a moment when we were, and are, poised to do great things to impact patients.

We all have our version of this struggle. We are all some combination of parents, kids, friends, leaders, colleagues. We will redefine what social engagement means. We will find new ways to fulfill our need for community. We will get sick, and help others get well. Realistically, some of us will die.

But, as a community, a nation, and a world, we will get through this. I can only hope that when we do, we indeed come through to the other side stronger.

I implore everyone to learn from this unprecedented moment in history; in a nation so fundamentally short-sighted and focused on the value of the individual, can we become a country with a longer view? One informed by science, epidemiology and the value of basic principles of public health? The decision is ours: as a world, as a nation, as a community, but also as individuals.

I do not have the answers. I can – we all can – ask questions. Today, I am back in Philadelphia preparing to go on service on nights and weekends to treat patients. This is my contribution.

We must all contribute in our own way: Don’t hide. Don’t let fear paralyze you: find facts and resist the noise. Be kind to each other. Find empathy. Resist hoarding food and supplies — especially masks that medical workers and people on the front lines desperately need and are in dangerously short supply. Build virtual communities. Support a friend or coworker or family member who is alone and at risk.

And vote. Especially, vote.

Together we can use this remarkable moment to catalyze the change our nation and our world so desperately needs. The time is now.

What will you do?

24
Mar
2020

Digital Tools in Clinical Trials Find Opportunity During Pandemic

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24 Mar 2020

David Shaywitz

The current crisis represents a potentially defining moment for at least some health technologies and technology-enabled services. 

Telehealth, as discussed in my last column, is one conspicuous example, and the jury is still out. The potential benefit seems especially striking at a time when so many Americans are being told to stay at home, yet there are also serious concerns, both short-term (can existing telehealth capabilities adapt to exploding demand?), and longer-term (including not only a thicket of regulatory and reimbursement hurdles, but also challenges around data governance and trust).

Nevertheless, as Dr. Joseph Kvedar, VP of Connected Health at Partners HealthCare puts it, “telehealth is clearly making the case for how technology should be used to imagine how care and services are delivered.  I believe that there will be no turning back.”

The corresponding example from the pharma world might be the use of technology to enable remote trials. It’s an urgent consideration in light of the pandemic, which is having a predictably negative impact on clinical trials. In the last 24 hours, Lilly announced it would “delay most new study starts and pause enrollment in most ongoing studies,” while “continuing ongoing clinical trials for patients who are already enrolled.”  Meanwhile, the New York Times reports BMS has told researchers “it will put off beginning new clinical trials for at least three weeks,” “will not initiate any new sites for clinical trials until April 13” (or later), and said “studies involving healthy volunteers should be paused if they are at a natural break point until at least April 13.”

Clinical trials, like much of clinical medicine, have historically focused around global networks of brick-and-mortar centers. These centers can be stand-alone facilities, which are typical for early phase, highly monitored studies. They can also exist in large medical centers with physicians who have agreed to participate in the study. That model is quite common for larger, mid- and late-phase studies.

While operating in a site-focused fashion enables a relatively high degree of process control, it also means that studies are generally limited to subjects who can show up to a single location, often repeatedly over days, weeks, and typically months. The convenience challenge is often cited as a major reason why participation in clinical trials is so abysmally low.

This matters for many reasons: a key hurdle for clinical studies is it often really difficult to find enough patients to study, a persistent challenge which adds significantly to the length and cost of trials.It also means that many potential subjects never have the opportunity to participate because they are not located near a trial site and/or the time and travel commitments are prohibitive.

Estimates vary for just how small the percentage of eligible patients who participate in trials is. Some suggest the figure is as low as 2%; a recent study led by Joseph Unger of the Fred Hutchinson Cancer Research Center and focused on cancer patients puts the number at 8%. Foremost among the factors cited for low participation by Unger and his co-authors is that “a trial may not be available where the patient is being treated.” As they point out, “Having to travel to participate in a trial can be an overwhelming burden to patients.” 

Driven by these widely recognized needs, there has been profound interest in finding ways to increase the reach of clinical trials, which often involve the idea of the trial going to the patient, rather than the patient going to the trial. This was the driving force for Novartis to ink a high-profile deal with the remote trial company Science37 in 2018, a pact aiming to deliver 10 studies in three years (our TechTonics episode with Science37 co-founder and former-CEO Noah Craft, who stepped down in 2019, is here).

As the Novartis press release put it, “Decentralized, or virtual, trials harness digital technology to allow some or all aspects of a clinical trial to be carried out at a participant’s home or local physician’s office, rather than at a central trial site such as a large hospital…”

Improving the diversity of participants is another attraction of virtual approaches. As a Novartis executive says in the same statement, “Remote participation in research has the benefit of improving the breadth of participation from wider community and socio-economic backgrounds, while also allowing us to gather more meaningful real-world evidence in our clinical trials.”

In theory, a company that had an established, decentralized trial capability might be more robust to site-focused challenges like those associated with the pandemic. Certainly, the FDA’s recent guidance makes clear it is receptive, under the conditions of the pandemic, to remote approaches as supportive of participant safety. 

The guidance document specifically encourages sponsors to consider “alternative methods for safety assessments” such as “phone contact, virtual visit, alternative location for assessment,” and presses sponsors to “determine if in-person visits are necessary to fully assure the safety of trial participants.” 

The Agency goes on to note that depending on the circumstances, some “investigational products that are normally administered in a health care setting” might be given some other way (“e.g. home nursing or alternative sites by trained by non-study personnel”). The Agency even suggested the possibility of “the use of virtual assessments” for efficacy evaluations. Collectively, the document at a minimum highlights the potential of a remote clinical trial capability, which would seem useful in the context of this crisis. 

My best guess, however, is that remote trial monitoring is still such an emerging capability that few, if any, pharmas have it available as a ready substitute for in-person visits; this may not even be appropriate for many study protocols. Some experts such as Andrew Matzkin, a partner at the consultancy Health Advances, believe that decentralized clinical trials may be a promising concept that could work technologically, but still need to provide more evidence, demonstrate real world usability, establish credibility, and  describe a reliable path to commercial scale before they’re likely to gain general acceptance.

Perhaps for a few very high priority trials that are already underway, pharmas are likely to do every possible thing they can to keep these studies advancing. Pharma companies will try to use remote capabilities and deployed specialists to perform the necessary evaluations, assessments, and (where required) dosing. Especially at a time when health systems and healthcare workers are already so overwhelmed, any success from this approach is likely to be extremely limited.

At times of crisis, it’s often said that the startups that benefit the most aren’t those that are formed in the heat of the moment to address the emergent needs, but rather those that were created years back, and are poised, for lack of a more tasteful term, to take advantage of the moment. 

Two startups in this space are Evidation Health and Koneksa Health, which both offer flavors of what might be called “digital tool enablement as a service.” While neither seem positioned to save pharma from the trial continuity crisis, the value of their capabilities is likely to be evaluated and recognized at this moment.

Evidation Health, led by Deb Kilpatrick (her TechTonics episode here), is perhaps best known in recent days for its partnership in the “Heartline” 150,000 person study – “a big deal of digital health” according to CNBC’s Chrissy Farr – recently launched by J&J and Apple. Heartline’s website says Evidation “provides the technology and study operations that enable the Heartline app and study experience for participants.” Their role, Kilpatrick says, is as the “software-based virtual site,” explaining that Evidation’s research platform enables a contemporary, decentralized research experience for older adults mediated entirely through the iPhone while collecting and processing their (explicitly consented) research data.

Evidation believes its secret sauce is gleaning insight from the data generated by these digital tools – information the company refers to as “person-generated health data, or PGHD), a distinctly non-trivial task accomplished by the data science team build by co-founder Luca Foschini. Evidation’s approach has been used in studies of the flu, as well in a recently-launched longitudinal program seeking to better understand the perceptions, experience, and health of Americans in response to the pandemic; using its already-deployed patient engagement app called Achievement, the company hopes to integrate surveys and digital measurements from users who opt-in; as of March 18, over 100,000 people apparently had.

If Evidation’s focus is obtaining meaningful clinical insights by analyzing what it would describe as high-quality, person-generated health data from consumer devices and engagement apps, Koneksa Health is especially focused on the validation of remote measures for use in traditional clinical trials, and supporting pharma stakeholders who make go/no-go decisions, as well as the regulatory authorities who must accept digital measures in place of, or in addition to, the current gold standard. (My simple-minded dichotomy sees Koneksa focused on pre-approval trials, and Evidation capturing value from post-approval studies and other research; in reality, the capabilities of these two companies presumably overlap).

Koneksa’s focus, says founder and CEO Chris Benko (his TechTonics episode here) is the use of patient-focused digital biomarkers (e.g. remote, device and app based measures of pulmonary function, activity, sleep, vital and hefty signals) to support development of novel therapeutics.”

Benko’s view is that the current crisis, and the FDA’s response, “will require technology tools already designed as fit-for-purpose clinical trial tools,” adding “Koneksa has been deploying tools like this into clinical trials since we launched in 2015.”

Bottom Line: While no company seems poised to save pharma from the clinical trial interruption the pandemic has necessitated, the urgent search for partners with digital capabilities may accelerate the growth of startups like Koneksa and Evidation who are progressively establishing themselves in this nascent and promising space.

23
Mar
2020

New Drugs at Low Prices: Alexis Borisy and Melanie Nallicheri of EQRx on The Long Run

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23 Mar 2020

Today’s guests on The Long Run are Alexis Borisy and Melanie Nallicheri.

Alexis Borisy, chairman and CEO, EQRx

Alexis is the chairman and CEO of EQRx, and Melanie is the president and chief operating officer.

EQRx is a startup in Cambridge, Massachusetts. It aspires to develop new medicines for serious diseases like cancer. That’s nothing unusual.

What is unusual is that EQRx is seeking to create a company that makes a profit, but does so by churning out many new drugs so it can get by without resorting to the unjustifiable price increases, or outright price-gouging, that has poisoned the reservoir of public trust in the biopharmaceutical industry.

Essentially, it wants to develop and sell lots of innovative drugs at low prices.

EQRx is seeking to mitigate technical risk somewhat by pursuing a “fast-follower” strategy in which the underlying target biology is relatively well-known, and it can learn and quickly adapt to development plans laid out by trailblazers in a new therapeutic category.

By reducing technical risk as a fast-follower, EQRx believes it can run faster, cheaper, lean and mean clinical trials with a higher probability of success. That would reduce its R&D spending and opportunity cost. If it can pull this off several times in a row, the diversified portfolio should give it the flexibility to price its ultimate products a lot cheaper. That’s the thinking.

Melanie Nallicheri, president and COO, EQRx

You might be skeptical. Plenty of people are. Drug pricing has been so dysfunctional for so long. So many vulnerable people in our society have felt exploited and gouged and ripped off for so long. They flat-out don’t trust the biopharmaceutical industry. The public has good reason to be skeptical.

There’s a lot here to think about, in terms of how pharma can and should operate, whether you agree or disagree with what Alexis and Melanie have in mind. It’s worth re-thinking especially in this new moment of crisis and collective spirit during the global pandemic.

I hope you enjoy this conversation.

Please join me and Alexis Borisy and Melanie Nallicheri on The Long Run.

23
Mar
2020

Let it Rip or Shelter at Home? Choosing Between Two Bad Options on Coronavirus

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23 Mar 2020

Otello Stampacchia, founder, Omega Funds

Like most of you, I have been obsessively following “the virus.”

It is having a devastating impact on human life, hospital systems, governments and economies. The worst is still to come, based on what we know about this new coronavirus and its ability to spread with exponential force.

Here are some thoughts on the difficult choices laying ahead.

Before I start, here’s a little on where I’m coming from. I have the dubious advantages of being at the same time Italian-born and a US-based venture capitalist active in healthcare. This gives me a lens into the government, healthcare and culture of a country that has been decimated, and an insider’s view into the scientific community and its prospects for counterattack (mainly therapeutics in my case). As an investor in public and private markets, math is part of the job, and I have a somehow intuitive feeling about exponential growth rates. Please refer to two previous articles on Timmerman Report, warning of the upcoming disaster on Mar. 10, and then on Mar. 18.  

As with most (all?) of you, I am watching the daily avalanche of terrible news and the public / policy responses trying to catch up to the inexorable progression of the virus. Note the use of the words “catch up” here, they will come in handy later.

In the US, we went from 89 confirmed cases on March 1 to ~41,000 as I write on the afternoon of March 23 (source: www.worldometers.info/coronavirus). The US, so far, has lagged far behind other countries’ in testing capacity and administrations, so it is catching up there as well. A patchwork of local, state and federal measures are being implemented across the country to try to limit the spread of the disease and preserve hospital capacity (and healthcare workers’ safety).

The economic fallout (at least the initial one) is also becoming starkly evident. Starting in late February, US stock market indices have to date lost ~$12 Trillion (herein shortened to “T”) in market value, or roughly 25-30% from their pre-crisis peak (I will strive to be roughly accurate versus precisely wrong throughout this article).

More importantly, entire sectors of the economy (employing a huge portion of the US workforce) are veering rapidly towards bankruptcy: the lethal combination of lack of demand and restrictions on movement has made their business no longer viable (in these circumstances). Hotels, restaurants, airlines, gyms, physical therapists, etc etc are making millions of people redundant across the board.

The US lacks (for the time being) social safety nets that are much more prevalent in other countries. That increases the severity and amplitude of these kind of shocks. The US economy generates about~$40T per year in gross domestic product. Of that, ~70% is composed of services and consumers’ consumption. It is painfully obvious to see how broadening, enforcing and / or continuing “shelter at home” policies in the US for a much longer period will cause incalculable economic damage. The chief of the St Louis Fed was quoted recently saying unemployment in the US could reach 30% in Q2 2020, and GDP could go down by ~50%. This is equivalent to what happened to the US economy during the Great Depression of late 1929 and through the 1930s, and it is happening at a much faster pace – a matter of weeks.

In this context, I see / hear / read a number of voices arguing for a “let it rip” strategy: i.e., continue “life as normal,” spreading the contagion without any radical social distancing measures, accepting that there will be a (slight?) increase in the number of casualties but preserving the broad health of the economy. This virus has a mortality rate of close to, and quite possibly, lower than 1%. On Mar. 16, disease modelers at Imperial College London, factoring in the best available estimates at the time, estimated that the novel coronavirus would kill about 2.2 million people in the US alone under what you could call a “let it rip” strategy – one that doesn’t utilize the disruptive social distancing interventions currently being imposed. A day later, Mar. 17, Stanford University epidemiologist John Ioannidis argued that “we are making decisions without reliable data.”

One of the basic arguments underlying the “let it rip” strategy appears to be the Precautionary Principle: “The precautionary principle (or precautionary approach) is a strategy for approaching issues of potential harm when extensive scientific knowledge on the matter is lacking. It emphasizes caution, pausing and review before leaping into new innovations that may prove disastrous.” (Wikipedia).

Spoiler alert: this discussion is based on fundamental flawed assumptions, at many levels. The (strongly worded, high conviction, HIGHLY evidence-supported) response to this “argument” should be: “(expletive removed) no!” If you carefully, cautiously wait for all the data to come in, your actions will come way too late. Also, interestingly enough, I will end up using the same Principle to argue exactly the opposite of the proponents of “let it rip.”

Now please bear with me as I try to discuss in some tedious detail why this is the case.

The Importance of R0 and Some Exponential Growth Rate Basics:

R0 (or R “naught”) is a measure of how many people one person infects. R0 = 0 (if you are by yourself on a desert island) means you will not infect anybody during the course of your infection; R0 = 1, means you will only infect one person. R0 = 3 means (ah, ok, I see that you got it by now).

For the sake of comparison, “normal” seasonal flu is considered to have an R0 of ~1.3-1.4. Coronavirus is considered to have an R0 of ~2.5-3.0. You REALLY want R0 to go below 1 to contain a pandemic. Importantly, in addition to depending on the virus’ infectivity, incubation period etc etc, R0 is ALSO LARGELY DEPENDENT ON PHYSICAL PROXIMITY. Simply put, if you have a highly contagious (possibly asymptomatic) Italian carrier in an Italian bar in Milan, every bar customer (and almost every surface) will be covered with virus by the time it takes to finish an aperitivo (kind of kidding, but kind of not kidding).

Now, let’s assume the coronavirus average infection cycle is ~4 days (meaning one person infects an R0 nr of people every 4 days). This is where problems start with exponential growth rates. What happens with 10 cycles following the initial infection(s) caused by that person: 10 incremental infection cycles (~1.5 months): normal seasonal flu (R0: 1.4): ~29 people infected. Coronavirus (R0: 3.0): ~59,000 people infected. That means one asymptomatic person, in this coronavirus season, leads to the infection of another FIFTY NINE THOUSAND (I thought that deserved all caps).

Professor Hugh Montgomery, Director of the University College London Center Institute for Human Health and Performance explains this really well (and with a better British accent that I could ever muster) in an interview with Channel 4 here.

The Problem is Hospital Capacity:

Again, please read the previous articles published on this topic on Timmerman Report from Mar. 10 and Mar. 18.

Basically, the important argument behind the “let it rip” approach is that a 1% fatality rate is a price (steep, but worth paying I guess?) for maintaining a functioning economy and not lose ~$1T / month in US GDP. We also do not know enough about the virus mortality rate, natural immunity etc etc so we should not “rush to judgment.”

I am not going to dignify the “natural / herd immunity” argument (there is no natural / herd immunity against the virus: it is a NEW VIRUS that no human on this planet has been exposed to before). What we know today about it is dwarfed by what we still need to learn.

First fallacy: consumption / economic activity will continue as “normal” should we lift restrictions on movements. I am really not sure how to address that one, unless it relies on the assumption that people are completely ignorant of the fact that there is a pandemic going on, and they’ll instantly snap back to life as normal once social distancing restrictions are lifted. Are you really going to take that trip to Milan for Easter now? Scheduling your wedding with all grandparents attending (knowing 1 in 4 of them will likely die if they get infected)? Assuming you could even board a plane, that is. (Full disclosure: my wife and I HAD a wonderful holiday trip planned to Milan to see my family there for Easter. Obviously, we cancelled).

Second, MASSIVE fallacy: the assumptions behind the 1% mortality rate. This might possibly end up being the “undisturbed” mortality rate, when it is all said and done: meaning, this SHOULD be the mortality rate IF you can obtain proper medical care (hospital bed, sufficient supply of oxygen / drugs if needed, caring and competent nurses and doctors).

Now is probably a good time to make the obvious argument that lean, efficient hospital systems (we are in a capitalist society after all) are not structured to be resilient and provide, additional capacity in a pinch.It is actually extremely expensive for a hospital to have spare capacity in terms of critical care beds, ventilators, nurses, doctors, drugs etc. So, they do not do it. Even countries perceived to be more like “social democracies” than the US do not have nearly enough spare capacity to tackle such a surge in cases. Italy has a very good hospital system. China, notwithstanding popular perception, has an excellent healthcare system, no lack of critical care equipment, and they moved 40,000 doctors into Wuhan’s hospitals to make sure they could cope. They also shut down the city when they had 500 officially diagnosed cases. Still, Italy and Wuhan had mortality rates skyrocket as soon as hospitals were saturated. Any incremental patient who needs oxygen (and cannot be properly tended to) will die. Mortality also greatly increases as hospital infrastructure degrades: you cannot fast track the training and education of new doctors and nurses in a few days. Healthcare workers are toiling under wartime conditions, getting infected themselves and dying. Which further compounds the lack of hospital capacity.

In addition, if hospitals get saturated / overwhelmed: every heart attack can become fatal if ambulances cannot reach you / hospitals cannot administer proper care. The US has ~1.5M heart attacks a year, causing ~500,000 deaths when proper care can be administered. The US has roughly 1.9M new cancer cases per year (source: https://www.cdc.gov/cancer/dcpc/research/articles/cancer_2020.htm). These patients are usually immunocompromised after getting chemotherapy or radiation treatment, which makes them very much at risk from opportunistic infections like this coronavirus. In addition they need urgent, critical treatment to achieve remission. In 2018, 34.2 million Americans (10.5% of the population), had diabetes (source: www.diabetes.org/resources/statistics/statistics-about-diabetes). Apparently, diabetics coronavirus patients have a much higher mortality rate. We don’t really understand why that is yet. The list goes on.

One (scary, but I believe accurate) way to look at this in the US is to check out the website www.covidactnow.org: it simulates by when different US states’ hospitals will be overwhelmed by the number of confirmed  cases of infection, depending on how we slow down the virus by using different types of social distancing measures to reduce R0 as much as possible.

As you can see, for a number of places, in particular NY, it is too late already. The number of cases will continue to mount over the next two – three weeks. This is why New York Gov. Andrew Cuomo (I cannot help but appreciate another fellow Italian’s decisive response) has asked for federal assistance, and is trying his best to increase hospital capacity in the city. May the fates be always in his favor as well.

Finally, please read Tomas Pueyo’s insightful blog post on this as well. Conclusions are similar to what you will find herein and in my Timmerman Report from Mar. 10.

Bottom line: “let it rip” is not sustainable. The economic and (more importantly) social cost of the disease is going to be even higher than if we undergo a 3-4 weeks shut down. Assuming even modest degradation of the US healthcare infrastructure, the death toll could rise to much more than 1% of US population (about 329 million people currently, according to the US Census Bureau).

But: We Cannot Have Radical Social Distancing for 18 Months!

True, it is not sustainable to have the global economy on lockdown for 18 months. Most important, people cannot comply with such isolation measures (especially those pesky, frolicking fools celebrating Spring Break in Palm Beach). Absolutely agree on that.

OK, here then are some thoughts (feel free to pass them along your favorite policymakers): in temporal sequence from now:  

1. We (the US) need NOW a nationwide, ideally even globally-coordinated, “pause” of 3-4 weeks at a minimum, with as little movement of people as possible, across the entire US. I mean a shut down like Italy, enforced by police etc to make sure these frolicking teen fools in Palm Beach (see above) do not continue spreading the virus; no travel unless absolutely necessary. Note: from the moment you impose and enforce such a lock down, then it takes ~2 weeks for cases and deaths to reach a peak. They will continue going up in the meantime. New York City now is like Milan and could become very soon like Bergamo otherwise. ALSO NOTE: two weeks after you impose such a lockdown, things improve. Italy has now turned the corner: in the last two days, the number of new confirmed cases and most importantly, number of fatalities, is decreasing. The lockdown in Italy started on Mar. 9, exactly two weeks ago.  

2. There needs to be absolutely clear and effective communication from the federal government. They need to enlist any traditional media sources and social media (Twitter, Facebook) with a simple, clearly communicated message: Social distancing / stay at home will work to reduce the infection rate; BUT it needs 2-3 weeks to show some results and it NEEDS TO BE ENFORCED. Our social structure and citizen relationship to authority is very different from Asian countries: but this means even more clear communication is absolutely necessary. We need to enroll every citizen in the effort. Make sure supply chains / logistics distribution / food and essential medical equipment manufacturing / energy production / broadband infrastructure can take the strain. All these activities can enroll people otherwise made redundant by the industries most affected.

3. In the meantime, during that pause period:

  • Increase massively testing capacity and manufacturing (I mean, massively: the only way to resume some semblance of normal economic activity after the lock down, and only IF we have put R0 below 1 by then, is by having RAPID tests available on a massive scale). Including providing serological tests to make sure immune people can roam around freely (and ideally be enlisted in the healthcare / manufacturing effort).So, drive-thru tests, at home easy-to-use tests, phone booth tests, all within a few minutes ideally; and not administered in hospitals where infections can otherwise cluster.
  • Increase hospital capacity and resilience: identify and staff separate physical hospital structures and caregivers for cancer patients; increase ICU and critical care capacity (ventilator manufacturing, etc ). Every city with an international airport needs to be prepared for surges in cases; train more nurses, doctors, to prepare for the onslaught; use / adapt hotel structures in big cities for isolating people tested positive (including asymptomatics); divert car manufacturing to more ambulances; increase manufacturing for oxygen, painkillers for intubated patients, etc.
  • Have separate structures (hotels? island resorts?) for at-risk demographics: elderly, people with co-morbidities (diabetes).They need to be completely isolated for ~10-12 weeks, at least until prophylactic treatments are available (Japan has been using this strategy very successfully).This will reduce death rates and preserve hospital capacity; these structures can be staffed by (for example) airline staff who has recovered from the virus already.
  • Massive increase in R&D spending: vaccine / antibody manufacturing capacity. We must start GMP manufacturing of all drugs that potentially look likely to work in pre-clinical models so we do not lose time for scaling up manufacturing. Diagnostics need R&D support, as well (Korea and China have portable CT scans, for example). There’s no time to lose. Every month of a lockdown the US loses >$1 trillion of GDP.

4. The other stuff (how to make sure workers maintain healthcare insurance), can still survive if tens of millions of people are unemployed starting next week etc. This is way above my pay grade but also super important to make sure we can come out the other side.   

We will come out of this. But, the next 6-8 weeks are critical in preserving our hospital infrastructure. The virus spreads way faster than you think. If we delay implementing these measures even a couple days more, the consequences are disastrous. The math is inescapable.

To leave you on a lighter note, and a perhaps more entertaining take on how efficient technocracies should make decisions (versus the dilemmas facing politicians), this video clip from the old British show “Yes, Minister” is priceless. Moral: I hope we can stop listening to other “opinions” and start listening to the science.

Follow Otello Stampacchia on Twitter: @OtelloVC

This article expresses the personal views and perspectives of the author. The views and perspectives expressed here do not necessarily represent the views or perspectives of Omega Fund Management, LLC or any officer, director, partner, member, manager or employee of Omega Fund Management, LLC or any of its affiliated entities.

23
Mar
2020

Staying Mentally Healthy to Weather the COVID19 Crisis

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23 Mar 2020

Jeffrey Lieberman, MD, chairman of Psychiatry at Columbia University Vagelos College of Physicians and Surgeons

The Mind Set

The message to people on the front lines of the healthcare system — and citizens alike — has been: “This is going to be a marathon, not a sprint.”

We have heard that phrase many times in the past weeks to help healthcare workers prepare for what’s coming next in the COVID crisis.

It sounds inspired, thinking of our healthcare colleagues as elite runners:  The comparison suggests dedication, strength and stamina.

However, the COVID-19 reality is far more grim: The route to the finish line will be changing as we run. There won’t be water at all the mile markers and to the extent there is water, we won’t know when it’s coming. It’s possible the finish line will also be moved. There won’t be any fans on the sidelines cheering us on and holding homemade signs of encouragement, because they’ll be “sheltering in place.” And we’ll have to keep running. But because of who we are, we will want to keep running. It’s how we’ve been trained and who we are.

The Reality

COVID-19 is a novel virus to which humans have no immunity. It is highly contagious. While the medical severity, complications and mortality are serious threats to be sure, the larger consequences to our society are due to its prevalence and the consequences that threaten to overwhelm our health care system, deplete our workforce, and disrupt our economy.

Based on currently available statistics:

  • 40% of patients develop a mild illness
  • 40% develop a moderate illness
  • 15% develop a severe illness
  • 5% develop a critical illness
  • The risk of mortality increases with age:
    • 15% for patients >80 yo.
    • 3% for patients >60 yo. 
    • 1% for patients <60 yo, the risk is 1%
    • With concurrent comorbid illness (e.g., hypertension, diabetes, cardiovascular disease) the mortality rate rises to about 15%
    • Although the true mortality risk is likely lower, given that the rate of infection in asymptomatic patients is not known.

The guidance for containment and personal protection recommends:

  • Physical or Social Distancing:
    • Avoid close contact, stay 6-10 ft. away from people.
    • This virus is transmitted by droplets and not airborne, so we don’t need to worry about the air we breathe unless we are in close contact
  • Hand washing
  • Use of disinfectant on surfaces.
  • Avoid touching your face
  • Wear gloves outside
  • Do not travel
  • Avoid crowds
  • Isolate as feasible
  • If exposed to someone, or symptomatic don’t go to the hospital unless severely ill, call your physician or one of the hotlines
  • Testing limited: 2 forms Diagnostic and Serologic
  • High risk groups include elderly, immune compromised or medically comorbid patients
  • Young people may be transmitters but less prone to serious illness

The Psychological Effects

For everyone and particularly healthcare workers, living in the time of COVID-19 is complex and stressful. In many ways the uncertainty of what lies ahead causes anxiety and worry. The limited availability of testing (although this is improving), the lack of effective therapies, the process for developing new treatments and an effective vaccine, although in the works, will take time to develop and the waiting can contribute to hopelessness and despair. In addition, the prolonged isolation and interruption of normal activities adds to the dejection people are feeling.

Laurel Mayer, MD, Associate Professor of Psychiatry at Columbia University Vagelos College of Physicians and Surgeons and Director, New York Presbyterian Hospital Housestaff Mental Health Service

It is important to understand these reactions, so they can be acknowledged and addressed. Rather than serve as a barrier that interferes, responding and validating these emotions can facilitate collaboration and cooperation in the communal response to the crisis. Anxiety is a normal emotion and it is to be expected during this unprecedented crisis. It increases when we experience uncertainty, are in unpredictable situations and feel unable to control our circumstances.

Mental health first aid strategies including the following can reduce and help to manage untoward emotional reactions to the crisis.

  • Distract yourself or avoid focusing on the situation
    • Recreational activities
    • Tasks you usually don’t have time for
    • If you have nothing else to do try this mindfulness exercise
      • Hold an ice cube in your hand and let it melt.
    • Don’t catastrophize
    • Don’t watch news media 24/7
    • Reach out virtually and communicate with family, friends, and health care providers as needed
    • Try to reframe and take some control of your situation.
      • Reframe the situation
        • This will pass, it already has in China and Korea
        • There are anti-retroviral treatments that are currently being tested around the world — about 200 studies currently underway.  Based on the prior SARS epidemic, there has been considerable knowledge gained about coronaviruses.  
      • Diagnose yourself and understand your needs
        • Stress indicators include disturbances in sleep, appetite, concentration, mood
        • If you have a primary psychiatric condition,
          • Monitor symptoms
          • Adjust meds accordingly
          • Increase contact with your doctor or provider as needed
  • Think about protecting yourself, then others. Start with family, then society. Like instructions for oxygen masks when on an airplane. First put mask on yourself, then your child, then others.

Differential Effects on People

People will be differentially affected, have different needs and require different treatment. Relevant subgroups include:

  1. The worried well – should be able to manage their stress and mental state with Mental Health First Aid as described above.
  2. People with mild/moderate severity mental disorders including Anxiety, Mood, Stress, Obsessive-Compulsive Disorders – will likely need increased treatment in form of adjustment in meds and/or increased contact with doctor or therapist through Telepsychiatry
  3. People with substance use disorders will have – temptation to use substances will increase. Increased virtual support and monitoring will be critical.
  4. People with serious mental disorders – meaning affective and non-affective psychotic disorders interestingly are less reactive to such crises but will need attention to their medical needs
  5. Medical high risk group patients need – guidance on protection from exposure, mitigate effects of isolation
  6. Health Care Providers are on the front lines are under the greatest pressure and stress and performing heroically at great risk to themselves.

Final Thoughts

Coming together as a community and strengthening our resilience will help. Strong bonds at the community level foster cohesion and facilitate hope.

While this may be a novel situation, we have the skills to adapt and others are here for support. Cooperation, adaptation and resourcefulness combat isolation, helplessness and hopelessness.  Resilience depends on maintaining an objective assessment of the current situation coupled with an unyielding optimism that we will successfully navigate the challenges ahead.

Referring back to the marathon metaphor, we may not know the route to the finish line until we run it, there may not be water when we need it, but we have the skills we need, we just need to use them. If we do this and offer support to others along the way, together we will finish the race. 

In closing, we share a quote by Albert Camus from The Plague. It’s told from a courageous doctor’s point of view who was caring for people during an epidemic:

“He knew that the tale he had to tell could not be one of final victory. It could be only the record of what had had to be done … and despite their personal afflictions, by all who, while unable to be saints but refusing to bow down to pestilences, strive their utmost to be healers.”

Stay Strong, Stay Safe.

Jeffrey A. Lieberman, M.D., is Chairman of Psychiatry at Columbia University Vagelos College of Physicians and Surgeons, Past President of the American Psychiatric Association and the author of “Shrinks: The Untold Story of Psychiatry.”

Laurel Mayer, M.D. is Associate Professor of Psychiatry at Columbia University Vagelos College of Physicians and Surgeons and Director, New York Presbyterian Hospital House staff Mental Health Service.

22
Mar
2020

Why Telehealth Champions Are Worried About Trust

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22 Mar 2020

David Shaywitz

Crises can serve as catalysts. History has shown they increase the recognition that change is needed, and lower the activation energy required for it to occur.

The COVID-19 crisis has already been widely recognized as potential catalyst for telemedicine, and more generally for the accelerated adoption of digital tools in both clinical medicine and clinical trials. In just the last week, the FDA released urgent new guidance (here, here) seeking to smooth the way for both.

The surprise is: some of the most ardent champions of digital health are thinking critically about the current moment, warning that if we abandon vitally important safeguards in our rush to embrace technologies, the adverse impact on patient trust will poison the field for decades to come. Moreover, they argue, even in a crisis, you don’t need to choose between rapid execution and good data privacy rights – indeed, they suggest, especially in a crisis, we can, should, and must push for both.

***

Telemedicine has long seemed like an application of technology particularly well suited to pragmatic incorporation into care, enabling patients and providers to engage remotely, without the time and aggravation of traveling to a medical office.   

In concept, it embodies at least some aspects of the house call, albeit without the laying on of the hands.

Yet, telemedicine long struggled for real traction. Some, like Eric Topol, a thought leader in this area, believe that “[the] past decade saw telemedicine finally cross [the] chasm,” described by Geoffrey Moore, where the adoption of emerging technology moves from a few visionaries to the “early majority of pragmatists,” as Topol and E. Ray Dorsey recently wrote in The Lancet. 

Others would surely argue that even if telemedicine hasn’t quite crossed the chasm in most areas, it is at least getting close. But almost everyone agrees that the adoption over the past two decades has been much slower than many had expected.

Why has telemedicine been such a hard sell, especially in an age where consumers routinely use their phones for everything else?

To oversimplify only a bit, a big part of the answer is: incentives. Providers have struggled to get paid for telemedicine, at least at levels comparable with in-person visits. As venture capitalist and health systems expert Bob Kocher says, Medicare requires an in-person visit before a patient can access care virtually, and even then, the reimbursement for a telemedicine visit tends to be relatively low. 

My Tech Tonics co-host and digital health guru and investor Lisa Suennen agrees reimbursement is an important issue –“telehealth-provided services needed to be reimbursed the same as the equivalent service provided in person,” she says. As Peter Antall, chief medical officer of telehealth company American Well recently told STAT’s Erin Brodwin, “The reimbursement challenge still exists for telehealth,” a lament echoing the complaints of genetic testing companies a few years back.

Suennen also highlights another challenge: the need for in-state medical licensure adds another wrinkle: a licensed California physician can’t provide telecare in New York — or Nevada, or any other state — unless she is also licensed in each of those states. The burden is therefore on the practitioner – who’s already loaded with responsibilities — to jump through a series of hoops to get licensed in multiple states if they want to create a thriving telemedicine practice. By design, this makes it more difficult for less busy physicians in one state to ease the burden of overwhelmed doctors somewhere else.

An additional hurdle, physician-entrepreneur and telemedicine guru Dr. Seth Feuerstein points out, is “general inertia in a system filled with risk averse folks who have little or no incentive to do things in a better way.”

Add to this the problem of what Kocher calls “clunky technology.” As Suennen points out “some technologies are really good and some aren’t – you need to choose wisely.”  (Providers generally need to use technology that is compliant with HIPAA regulations, meaning you can’t just use whatever consumer videochat app you have available.)

Yet another often appreciated challenge is cultural: as one expert pointed out, “some doctors don’t like the loss of control” that might be associated with telemedicine. Suennen says there’s a lot of “provider discomfort” with the idea, and many don’t like being on screen.   

Many patients are equally reluctant to change; Kocher cites as another barrier “the lack of demand by patients who are happy with the status quo.” Or as Suennen bluntly puts it, “people still want healthcare mostly from people” rather than videoscreens.

* * *

Enter the COVID-19 crisis, which has changed, at least for the moment a few key factors.  Today, both patients and physicians are highly motivated to minimize clinical visits, which intrinsically introduce an increased risk of infection for both physicians and patients – hospitals and clinics are good places to avoid these days, if at all possible. 

In addition, some reimbursement and HIPAA barriers have been waived to make it easier for seniors to access telecare, and for physicians to get reimbursed for this – changes that actually unleashed a tidal wave of demand that overwhelmed telehealth providers, according a recent STAT article. (STAT’s coverage of the pandemic in general, and this aspect in particular, has been superb.) 

Of course, many of these COVID-19-motivated changes may revert after the pandemic subsides.

On the face of it, the crisis would seem like a transformative opportunity for telehealth (at least once the initial crush of interest is managed). Yet, as I spoke with a number of savvy stakeholders who have been champions of digital health, I was struck by their caution, which seems almost more prominent than their enthusiasm. 

The key issue for many, including Andy Coravos, CEO of Elektra Labs, and Eric Perakslis, a Rubenstein fellow at Duke, is precisely the potential of a crisis to drive – and justify – significant change. Both Coravos and Perakslis advocate for the importance of privacy (Coravos prefers the term data governance). They both emphasize that even in a crisis, we must not be lulled into a perceived false choice between speed and privacy (or speed and good governance).

Coravos and Perakslis contend that there are plenty of opportunities to have speed and privacy, and argue we should push citizens and governments to renegotiate for those opportunities. Privacy policies, terms of services, and end-user-license agreements can be re-written during public health emergencies, they suggest, to protect those who are vulnerable. Hospital systems, governments and others purchasing on behalf of those who cannot make these decisions, Coravos and Perakslis emphasize, can and should factor these considerations into their procurement negotiations. (For more on the risks of data governance in telehealth, see this recent opinion piece in STAT by Kirsten Ostherr). 

The core issue, Coravos suggests, is trust; for telemedicine and other digital tools to truly gain traction, users need to be able to engage these tools with trust – trust in the fidelity of the measurement, and trust that the data won’t wind up being used, without their permission, to sell them ads (best case), or deny them insurance, a worrisome concern.

For Coravos, the key opportunity of a crisis isn’t to accept the necessity of a false, bad choice — such as supporting public health at the cost of personal privacy — but rather, to use this moment to push for strong governance, so that the tools and approaches developed at this moment of need will earn the trust needed to support their use once the emergency has passed.

A particular concern raised by Perakslis is that, in the context of the crisis, many “people are running in with dubious products and solutions,” adding “lots of dodgy stuff is going on.” Echoing the flavor of concern raised by Coravos, Perakslis adds he’s very worried that “Silicon Valley and the VC world are pushing for relaxation of every basis of regulation and ethics.  The harms will be significant, and this could set things back.” In other words, if people don’t trust the system, they won’t willingly participate in the system, especially after the pandemic is over, and perhaps even during the current crisis.

Adds Coravos: “Good regulation is a necessary precondition for innovation because it creates trust in a system.”

Bottom line: The COVID-19 crisis has created a potential breakthrough moment for telemedicine and other digital technologies.  But if these aren’t implemented with care, security and good data rights, any short-term benefit is likely to be offset by the corrosion of trust critically required for enthusiastic patient engagement and long-term success.

21
Mar
2020

Love in the Time of Coronavirus

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21 Mar 2020

Julie Sunderland, managing director, Biomatics Capital

The Seattle community is about two weeks ahead of the rest of the US in adapting to our new coronavirus-driven reality.

My three kids have been out of school for two weeks now.

Although incomparable with the challenges facing our health system, as all parents of young children know, having them at home all day, every day without the structure of school can be something of an unmitigated disaster (my husband just asked me at 2 pm “is it too early to start drinking?”)

Our last restaurant meal seems a distant and lovely memory: a 20th anniversary dinner at our gem of a favorite local restaurant — How to Cook a Wolf on Seattle’s Queen Anne hill.

We are now worried that this wonderful small business might permanently shut.

More seriously, the epidemic is becoming personal as people in Seattle have started to sicken and die, including a beloved professor in the UW community (Steve Schwartz) and, today, the father of a friend of a friend. 

At risk of being maudlin (Luke has assured me that “biotech people are people too”) I thought I would share the cycle of emotions that I have experienced over the last few weeks:

  1. Skepticism. In my previous job at the Bill & Melinda Gates Foundation, we lived through crisis response to H1N1 in 2009 and Ebola in 2014. When this new coronavirus first emerged, I viewed it as another case of an infectious diseases that creates hysteria in a country pampered by developed world healthcare. My friends in Africa have to deal with their families getting sick with and dying of malaria and other infectious diseases every day. I even wrote on Feb. 7 about how ill-prepared we are for pandemics.
  2. Frustration. As we started getting calls from serious people who are not prone to hysteria, I started to take it very seriously. Modeling work at the Institute for Disease Modeling suggested worrisome community spread in Seattle. Direct reports from doctors in the overwhelmed health system in Italy indicated that this was — in technical terms — a “very gnarly virus.” Having worked with the most skilled people in the world at managing epidemics at the CDC and WHO, I assumed that we would have our best people on it. Yet, as any board member knows, leadership matters. The US national leadership response was delusional and narcissistic, with direct and dire consequences to Seattle because of limited and faulty testing.
  3. Fear. To be effective in the world of biotech startups you have to have an optimistic belief that science, when well-executed, can solve problems. But as schools and non-essential services began to shut down, I realized viscerally how little control we actually have over our biological world. My brain, and that of my friends and neighbors, became infected by the most basic of fears: of sickness of children, of death of parents, of social unrest, of unknown outcomes. These fears were exacerbated by the lack of data about the scope and scale of the spread in Seattle. 
  4. Guilt. Many of my friends at the Gates Foundation, including our own venture partner Mike Poole, galvanized to coordinate local and global responses and to fast track therapeutic and vaccine development. Meanwhile, I am making Annie’s Mac & Cheese for my kids. I wish I could do more. But as my former boss Sue Desmond-Hellmann often said: you have to know when to be a leader and when to be a follower. I am not an expert in epidemiology or vaccine development or even intubation. The best thing I can do right now is to support the people who are.    

Which brings me to the final emotion, which is my predominant one these days. I have four objects of love in this time of coronavirus:

  1. For science, and for scientists. For the first time, I logged on to Twitter and it is extraordinary to see how quickly scientists are learning and adapting. My favorite pandemic crush is our hometown hero Trevor Bedford whom, with his team at the Seattle Flu Study, is tracking the genomic epidemiology of the virus. On Feb. 29, he provided the first coherent explanation of the uncontained community spread in King County and more recently a recommendation for the steps we would need to take as a society to actually contain the pandemic. I still have faith that we will eventually find a way out of this mess because of scientists and the leaders who listen to scientists. Our own Governor, Jay Inslee, has been a steady hand and is clearly listening to scientists. And will somebody please let former FDA commissioner Scott Gottlieb run the country?
  2. For caretakers. The doctors and health workers on the frontline in Seattle and elsewhere are the soldiers of this pandemic, putting their lives on the line without access to adequate personal protective equipment (PPE) or other essential life-saving equipment. This hits as close to home as it gets. Our kid’s favorite babysitter who works in a health clinic just got exposed to the virus from a patient. My second pandemic crush is the CEO of one of our portfolio companies, Farzad Mostashari. He was the national coordinator of health IT in the Obama Administration. Now with his team at Aledade, he has been fighting to get PPE and telehealth options to his network of Primary Care Physicians while also sharing his knowledge of data and epidemiology. More personally, my kid’s teachers have seamlessly shifted to patiently teaching via remote learning five hours a day, and are the only thing preventing complete havoc in our household.  
  3. For innovators. I am so proud of the biotech community’s response, and how companies that I have worked with — Vir Biotechnology, Moderna, CureVac — have quickly initiated development of therapeutics and vaccines. My third pandemic crush is Moderna CEO Stephane Bancel. Despite being regularly sniffed at by critics who see Moderna as being overhyped and overvalued, he has sustained his unassailable belief in Moderna’s mRNA platform and its ability to save lives. Moderna has the first COVID-19 vaccine in trials, right here in Seattle. I am so hopeful that despite the challenges of an as yet unproven technology — and the impossibly fast timelines being demanded — that this one will work. More personally, Seattle’s fanciest fine dining restaurant Canlis has come up with a surprising innovation of its own — a new business model as a drive-thru burger joint and bagel shop (Fast Company article here) which is saving people’s mental lives through pure happiness.   
  4. For my people. A strange thing has happened in the last two weeks. I have group text strings with colleagues and friends checking on each other. I get calls and texts from people that I normally only talk to about work just to make each other laugh. We are normally so busy and caught up with work that we don’t interact with each other personally. It has taken a pandemic to realize how much I love my people, in the biotech community and beyond, and how glad I am that they are in my life. 

I believe that this ethic of love and community support for each other will spread faster than the virus. The biotech community has already mobilized and so many people in the Seattle community are doing their best to help each other under the hash tag #wegotthisseattle (see the Seattle Mayor’s Resource Center and You Are Here for ways to donate to Seattle community organizations).

The scientists and innovators will eventually get us out of this mess, and the caretakers will keep us alive, but in the meantime, it is love and connectedness within our communities that will sustain us. 

 

Julie Sunderland is co-founder and managing director of Biomatics Capital Partners. Prior to co-founding Biomatics Capital Partners in 2016, Ms. Sunderland was director of Program Related Investments for the Bill & Melinda Gates Foundation. Ms. Sunderland sits on the Board of Directors for several of Biomatics’ portfolio companies including Aledade, BlackThorn, eGenesis and Verana.

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