Your Edge In Biotech.
1
Mar
2021

Investing in Manufacturing, Mental Health & More: Bob Nelsen on The Long Run

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01 Mar 2021

Today’s guest on The Long Run is Bob Nelsen.

Bob is the co-founder and managing director of ARCH Venture Partners. He’s one of the most prolific, and successful, venture capitalists in biotech history.

Bob Nelsen, co-founder and managing director, ARCH Venture Partners

Bob likes to get involved in startups in the earliest days. He is willing to stick his neck out, and generally do things that might seem weird or premature to most people at the time.

He was an early investor in gene sequencing technology with Illumina, RNA interference with Alnylam, cell therapy with Juno, and infectious disease with VIR.  

He dreams big, thinks ahead of the pack, and isn’t afraid to take big risks.

Bob was one of the first people I met when starting out covering biotech 20 years ago. I’ve interviewed him too many times to count. In 2016 when he made the Forbes Midas List, I wrote that Bob is “whip-smart, quirky, funny, profane, audacious and quotable.”

Still true. He’s always been a character, love him or hate him for whatever reason.

For this conversation, I focused mainly on what Bob and the ARCH investing team are doing with the latest fund, Fund XI. It’s a $1.85 billion colossus.

He talked some about priority indications for investment, including some new higher priorities coming out of the pandemic – especially mental health and bio-manufacturing. I didn’t ask Bob about his personal story, as others have covered it before. (Matt Herper wrote a nice profile of Bob for Forbes in 2016).

Now, before we get dive in…a word from the sponsor of The Long Run.

Synthego is a genome engineering company that enables the acceleration of life science research and development in the pursuit of improved human health.

The company leverages gene editing, machine learning, and automation to build platforms for science at scale. By enabling unprecedented access to cutting-edge genome engineering, Synthego is at the forefront of innovation, accelerating the development of truly engineered biology.

Synthego’s expertise in CRISPR, combined with their proprietary software and technology, means you have a trusted partner whether you are at early stages of basic research or ready to take your therapy to the clinic.

Visit Synthego.com/timmerman to learn more.

Now, please join me and Bob Nelsen on The Long Run.

27
Feb
2021

Digital Tools Helped Enable COVID-19 Vaccine Trials. What are the Lessons Learned?

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27 Feb 2021

David Shaywitz

Digital tools played a critical role in accelerating the development and evaluation of COVID-19 vaccines, according to leaders at the companies driving this effort. 

Speaking at a recent virtual panel discussion organized by the Galien Foundation (and available here), leaders from Pfizer, AstraZeneca, Janssen, Moderna, and the CRO IQVIA shared their experiences leveraging digital tools for vaccine development.

Data Deluge

The first striking observation was simply the staggering scale and raw intensity of the undertaking.  Pfizer’s phase 2/3 study, for example, involved around 44,000 subjects, 156 research sites in six countries – and was executed in four months. Janssen shared similar data – a 45,000 person study, which managed to recruited 3,000 subjects on a single day.

These are eye-popping figures.

The volume and velocity of trial data – far outside the norm for conventional clinical studies – presented urgent challenges to vaccine developers, who responded by leaning into existing data management platforms, and supplementing them with fit-for-purpose tools such as highly customized dashboards.  This enabled study sponsors to monitor a range of vital study parameters — including site start-up, participant diversity, data entry, and data cleaning — and where necessary, make adjustments on the fly. 

A particular challenge for COVID-19 studies was anticipating where the virus was likely to be most prevalent – regions where the impact of the candidate vaccine would be most readily ascertained.  All the companies claimed to use a range of analytic techniques and diverse data sources (such as mobility data) to identify the most promising study locations.

The “Last Mile Touch”

Another important challenge highlighted by several speakers involved the implementation of technology, the “learning curve that we had to bring our sites and investigators and staff on board,” as one leader put it. 

Some companies took to deploying “virtual study coordinators” who were “trained up on the tech” and could “bring folks up to speed with the new mobile devices, and help with the back office.” Help desks were staffed up to manage the increased call volume, and tech coordinators were also assigned to research sites. 

Takeway: Technology may be powerful, but people are required to make it effective. 

As one speaker said:

“Technology works, but actually technology had to be complemented with humans….you do need that last mile touch…one of the things we realized in the scale up is how do you bring the human and technologies together, complementing each other so that we can make sure this delivers the promise, what it’s designed for.”

Moreover, study sponsors discovered that technology wasn’t equally embraced by all participants, “some of whom will find it easier to use a tool than others.”  

Consider the question of using an electronic diary versus a paper diary.

“Sure,” a speaker suggested, “the electronic is easier for us, for many people around the world, actually putting X’s on a piece of paper is easier than finding the app on their iPhone.” 

Another speaker noted many participants “would not necessarily respond to super techie reminders,” and thus sponsors recognized the need to add “at times the human touch to really complement the technology when we need it.”

The New Normal?

The speed of COVID-19 vaccine development inevitably raises the question of whether the approaches used to accelerate the process will become standard, and represent the new normal. 

On the one hand, there was clearly the ambition to leverage the tools and learnings from the vaccine experience, as suggested by one company’s mantra, “no going back.” 

At the same time, speakers acknowledged just how exceptional these circumstances truly were – from the worldwide prevalence of disease to continuous (versus episodic) engagement with regulators, cited by all sponsors as critical to study acceleration. COVID-19 vaccine studies also operated under economics, and in the presence of resources that were far from typical.

The toll on all the people involved in executing these studies was also palpable – speakers described teams working “flat out” for months, to the point of utter exhaustion. It felt like the sort of superhuman effort that could be mustered and sustained only for a cause as cataclysmic as a global pandemic.

The ability of data platforms to support (apparently effectively) large volume COVID vaccine studies may also not speak to their ability to support the more usual trials companies sponsor, where the numbers are significantly lower, cost is a more pressing factor, and identifying and recruiting difficult-to-find subjects a recurring challenge. It will also be important to pressure-check the triumphalist story shared by these digital champions and stakeholders against reality, to the extent such an independent after-action report is possible.

Fix vs Reinvent?

Perhaps the most intriguing observation emerging from the discussion was a point made by several speakers, and elegantly summarized and extended upon by the moderator, Jessica Federer (former Chief Digital Officer of Bayer, and currently Managing Director of Huma Health):

“Something that we hear from so many pharmaceutical companies and manufacturers [is] that we’re using new technology, but we’re retrofitting our old processes and we’re trying to do the same things we’ve always done using new tech. And that clash is creating a complexity and it’s not shortening the timelines and it’s causing barriers. And the challenge for us as an industry is to  try to do new things with new tech instead of the same old ways we’ve always done it.”

This perfectly captures the challenge of technology implementation in medicine, as I’ve discussed here.  One prominent example: electronic medical records, which hew closely to traditional physician notes, in a deliberate effort to ease adoption. 

The “fix vs reinvent” tension turns out to pervade the history of technological innovation (see here), including the classic example of electrification of factories. Data suggest that electrifying legacy factories – historically built in a dense three-dimensional configuration to leverage the single source of steam power – by swapping in an electrical generator didn’t do much to goose productivity. It wasn’t until innovators completely rethought the design of the factory and developed an entirely new layout and workflow that huge productivity gains were finally achieved.

In the case of factories, innovation was spurred by the economic gains associated with improved efficiency. In medicine, the economic incentives, as Todd Park recently discussed, can be far less intuitive – perhaps the most substantial barrier faced by aspiring healthcare innovators. (Harvard’s Zak Kohane makes a similar point here).

Bottom Line

Vaccine developers leveraged digital platforms to manage the staggering data requirements and clinical trial needs. Successful implementation of new technologies required people to assist with the last mile. The exceptional global circumstances associated with vaccine development suggest we ought to exercise caution before generalizing from the experience, even as we’re inspired by the results. Coming up with novel ways to leverage technology for evidence generation, rather than adapting new technologies to established procedures, represents a future frontier; aligning economic incentives will be critical.

27
Feb
2021

AI in Healthcare: Harvard’s Zak Kohane on What Innovators Are Missing

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27 Feb 2021

David Shaywitz

Despite, or perhaps because, of the incessant hype, it can be difficult to assess the impact AI is actually having in medicine. 

Enter Harvard’s Zak Kohane, who in a remarkably astute recent seminar, available on YouTube, highlighted the opportunities for AI in healthcare while revealing some of the ways AI is falling short – generally by being deployed in a rote fashion that neglects the dynamics of patient care.

Kohane views medicine as “the great frontier,” with “boundless opportunity” – though he emphasizes that “the complexity and breadth of medicine require a multidisciplinary approach.”

Many data scientists, Kohane observes, are enamored of the promise of electronic health data, yet lack an intuitive understanding of the context in which these data were developed. The context is critical, Kohane emphasizes, adding that it’s essential to tease apart at least two very different dynamics captured in medical records data: the physiology of patients and the behavior of doctors.

Zak Kohane, Chair of the Department of Biomedical Informatics, Harvard Medical School

Consider the observation that a patient with a normal white blood count at 3 am has a far worse prognosis than a patient with an abnormal white blood count at 3 pm.

A tech guru to whom Kohane presented these data suggested that perhaps this reflected a circadian pattern. 

But ask any physician, and the answer is obvious: the only reason anyone would have a blood draw at 3 am would be if something was desperately wrong. In contrast, labs in the afternoon are drawn routinely, and it’s fairly common, incidentally, to see values outside the standard reference range.

Kohane cites a celebrated paper by Google demonstrating the potential of AI to predict hospital readmission rates from EHR data. But hold on for a second, he says. He then shares additional research revealing that nearly all the power from this comes from the AI learning not from the medical values in the EHR records, but rather from the pattern of tests and procedures that were performed. 

In other words, the AI is learning from the behavior of physicians as the doctors pursue diagnoses.  Kohane shares data demonstrating that when the AI is fed purely procedural information – the “chargemaster” data used for hospital billing – and has no idea what any of these tests and procedures showed, it does nearly as well as the algorithm running off all the actual EHR data, including test results.

Kohane also describes an EHR company’s proprietary algorithm that was developed during the early days of COVID-19, to predict patient deterioration. When it was subsequently tested by an independent investigator on data from a different hospital, the algorithm didn’t perform as well.

The most likely explanation, Kohane says, is also surprisingly common: the algorithm was trained on patients with different characteristics, and involved doctors who might have a different approach to treatment. 

It would have been foolish, Kohane says, to rely on such an algorithm, given how rapidly our understanding of the virus changed during the year, including both our approach to treatment and the characteristics of the patients infected. An algorithm developed in the context of one dataset could fail badly if the dataset shifts, especially if the algorithm was used reflexively, and not updated to keep up with the fast-changing circumstances.

Kohane tries more generally to moderate our expectations for AI; for example, he points out that algorithms like the one used to master chess and Go are likely to have only modest applicability to medicine. He quotes a leader in the field, Andrej Karpathy, now at Tesla, who has pointed out that these types of algorithms only work under certain conditions: when the system is deterministic and fully-observed, the action space is discrete, and we have access to a perfect simulator (e.g. the game itself) so that the effects of any action are known. 

“Unfortunately,” Kohane observers, “none of this is true of the physiology of disease course, of drug responsiveness, of surgery.”

In fact, Kohane adds ruefully, the only area of medicine where these conditions seem to hold involves reimbursement. He said he expects we will see extensive application of these sorts of algorithms — for the purpose of maximizing billing.

Nevertheless, Kohane is optimistic about the ability of AI to profoundly impact medicine and patient care. One promising application he sees is as an automated note-taker for physicians. That would free doctors up to focus on the patient, while the AI distilled and summarized the doctor’s observations, assessment, and treatment plan.

Identifying relevant disease subtypes is another potential application of AI. One particularly poignant example Kohane noted was the identification of a previously underappreciated subtype of autism with a prominent inflammatory bowel disease (IBD) component. 

Savvy analytics helped spot this pattern (which could also help form a hypothesis for further study of what the relation between these two conditions might be). Recognition of the autism/IBD association was especially meaningful to these patients and their families, Kohane explained, because it’s something a physician might otherwise miss – or misdiagnose. Many of these patients are non-verbal, he says, and when they experience gastrointestinal discomfort, their only way to respond is to act out, which is then often treated with tranquilizers – hardly the right therapy for IBD.

Yet now, thanks to data science-enabled research, Kohane says, IBD is more likely to be considered in autistic patients, leading to more appropriate diagnosis and treatment.

Moving forward, Kohane argues, requires us to explicitly recognize and separate health system dynamics and disease physiology; he adds that a third critical component will be patient-gathered data.

Perhaps the most powerful part of the talk occurs after Kohane cites several apparent examples of AI-driven successes. One approach was shown to be helpful in more rapidly weaning premature infants from ventilators. Another algorithm was used to integrate disparate info in a patient’s medical history to suggest a higher probability of domestic abuse. 

Yet, Kohane emphasizes, these are not true success stories. Yes, these results were published and shared, but the approaches were never broadly implemented – which he attributes to a failure of leadership, starting with his own.

“We need to recognize our own agency, our own ability to actually change the practice of medicine,” he urges. 

Kohane’s other advice for students and young innovators seeking to drive AI through to implementation: “Get an MBA, because business can drive this, and learn about health care policy, because what drives it in the end is money. Having business models and policy models and regulatory models is the way this is going to happen.”

Bottom Line:

The ability of AI-driven approaches to impact the care of patients will depend upon the ability of data scientists to meaningfully incorporate clinical experience and expertise. Determination, leadership — and perhaps a reasonable business plan — are required to ensure that successful AI approaches are not just published in journals but implemented, and find routine expression in the care and treatment of patients.

25
Feb
2021

Pfizer/BioNTech Ace Real-World Test, J&J Faces FDA Scrutiny, & Merck Pays Up

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25 Feb 2021

Luke Timmerman, founder & editor, Timmerman Report

Vaccine news keeps getting better by the day. The number of new people being diagnosed with COVID-19 has been plummeting for weeks.

That’s the good news. Read on and synthesize the most important financings, deals, and scientific developments of the week in biotech.

Vaccines

Let’s start with the best news of the week. Researchers from Israel reported on the Pfizer / BioNtech vaccination campaign in the real world – a potentially chaotic and messy situation under the best of circumstances. Even so, they found that the vaccine’s performance delivered more than 90 percent protection against severe disease after two doses. That’s no small feat, as it’s on par with what was seen in well-controlled clinical trials. New England Journal of Medicine. Feb. 24. (Ran Balicer, Ben Reis, Marc Lipsitch and colleagues).

The second-best news of the week was for the Pfizer / BioNTech vaccine among 23,000 healthcare workers in the UK. See The Lancet Preprint, Feb. 22, by Victoria Jane Hall. Sek Kathiresan, a recent guest on The Long Run podcast, succinctly summarized a key finding about the vaccine’s ability to curtail asymptomatic spread of the virus.

Some of the most vulnerable people to COVID-19 are elderly people in nursing homes. They were among the first to get vaccinated, and now we can start to see the results. Deaths in this group are coming way down. (See NYT graphic).

Cambridge, Mass.-based Moderna said in its quarterly and year-end financial report that it has advance purchase agreements worth $18.4 billion in sales for its COVID-19 vaccine in 2021.

That windfall will surely cue up critics howling about profiteering. It is a lot of money, and it’s legitimate to ask questions in good faith about what the fair price ought to be. The companies, if they are smart and thinking about the long-term, will exercise restraint on this point, as advised by John LaMattina in Forbes. Some of the insider stock sales from executives at the companies last year were ham-fisted and regrettable, and some of the corporate communications were premature and undermined public confidence.

Then again, they — Moderna and Pfizer/BioNTech — are moving heaven and Earth to scale up production (140 million extra doses for the US in 5 weeks) beyond anything previously conceivable with the new mRNA and lipid nanoparticle delivery vehicles. They have done, and are doing, herculean work everyone thought impossible a year ago. The value to the world from this vaccine vastly exceeds what we’re paying. The total, cumulative cost of COVID-19 is estimated at $16 trillion in the US by Harvard University economists David Cutler and Larry Summers. We should remember to reward and incentivize achievements of this magnitude. Our willingness to pay today supports capital investments and further incentivizes future work against SARS-CoV-2 variants and other threats like flu.

Today (Feb. 26) is the long-awaited day when the FDA advisory committee reviews the safety and efficacy profile of J&J’s adenoviral vaccine candidate for COVID-19. Reasonable people can debate the merits of the evidence, but the full protection against severe disease and death, conducted in more than 40,000 subjects around the world under fast-changing conditions against tough new viral variants – I think J&J has a compelling new tool to offer the world. Add up the practicalities of a single-shot, refrigeration-only, low-cost, scalable-to-manufacture vaccine, and you have an essential new intervention to help vaccinate a world with more than 7 billion people. (FDA briefing document). See also Derek Lowe’s positive review at In The Pipeline.

Speaking of what it will take to crush COVID-19, let’s not forget about Novavax. The little company from Gaithersburg, Maryland, left for dead not long ago, has risen from the ashes in the most spectacular “only in biotech” way. Its protein-and-adjuvant vaccine has shown 90 percent efficacy in a study of 15,000 subjects in the UK, and its 30,000-subject study has now completed enrollment in the US and Mexico. While we wait for those results with bated breath, partnerships are in place for Novavax to scale up and deliver more than 1 billion doses of its vaccine to the world. Read this inspiring WSJ story about a remarkable comeback.

Diagnostics

Seattle-based Adaptive Biotechnologies, the company that sequences B and T cells of the adaptive immune system to develop diagnostics and treatments, said this week it has started offering the first T-cell based test to tell people if they’ve had COVID-19 recently or in the further past. Adaptive is offering the test with its partner, LabCorp, which has 2,000 sites where it can take the necessary blood draw. Adaptive is seeking an Emergency Use Authorization from the FDA for the test, but is able to market its test in the meantime as a CLIA-certified lab, a company spokeswoman said.

Treatments

The WHO Solidarity Trial, a massive study of 11,000 randomized participants conducted in the frenzied early days of the pandemic, looked at a lot of different repurposed antiviral therapies. The outcomes were not good. The latest NEJM paper is withering. “These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay,” the authors wrote.

Science of SARS-CoV-2

The new tools of biology allow for incredible precision and speed. See this paper based on single-cell sorting technology used to identify the most potent neutralizing antibodies from COVID-19 survivors. “Extremely potent human monoclonal antibodies from COVID-19 convalescent patients.” Cell. Feb. 23. (Emanuele Andreano et al colleagues in Italy and London)

A couple of new variants are circulating. This time they are not being associated with some faraway place – it’s a place like many others in the US with long-festering, uncontained community transmission. “A Novel SARS-CoV-2 Variant of Concern, B.1.526, Identified in New York.” MedRxiv. Feb. 23. (Medini Annavajhala et al Columbia University). See also the latest on the CAL.20C variant, now known as B.1.427/B.1.429 and described by Carl Zimmer in the NYT.

How does the B.1.351 variant – aka the South Africa variant – appear to escape from neutralizing antibodies? An Oxford University team that did structure-function analysis on antibodies from convalescent sera and vaccine-induced antibodies found that receptor binding domain mutations provide tighter binding to ACE2. Cell. Feb. 17. (Daming Zhou et al Oxford University).

From China, researchers looked at the 501.Y.V2 variant and found no higher rate of infectivity, but they also saw a higher rate of escape from neutralizing antibodies. Again, they pointed to mutations affecting the receptor binding domain. Cell. Feb. 18. (Qianqian Li et al)

What is AI good for in the pandemic? Apparently, it’s being put to work hoovering up adverse event reports from people getting the COVID-19 vaccine to help researchers understand the real-world/real-time safety profile and put things in context. MedRxiv. Feb. 23. (Reid McMurry et al nFerence Labs)

The National Institutes of Health announced a call for scientific applications to tear into the many unknowns around Long COVID. In December, Congress allocated $1.15 billion over four years to help scientists explore what’s going on with the brain fog, fatigue, shortness of breath and other symptoms that so many people are suffering from. The scope and severity of this condition are only beginning to come into focus. Researchers at the University of Washington led by Helen Chu – who were remarkably well-positioned to respond to COVID-19 because of pre-existing infrastructure from the Gates Foundation-funded Seattle Flu Study – reported this week in JAMA on what they’ve learned about Long COVID since they pivoted in that direction in early 2020. According to 234 COVID-19 survivors who answered a research questionnaire, a full one-third (32.4 percent) reported at least one persistent symptom of COVID between 3 and 9 months after the original infection. If those numbers are a close approximation of the national incidence of Long COVID, then we are looking at an enormous toll of long-term chronic disease with perhaps 30 million cases of Long COVID (using a conservative estimate of 100 million infections).

Deals

Cambridge, Mass.-based Beam Therapeutics, the company developing base-edited gene therapies, used the leverage from its sky-high market capitalization (more than $5 billion) to acquire a little company to help with delivery. Beam agreed to pay $120 million upfront with its stock, plus another $320 million in milestones to acquire Guide Therapeutics. Guide is focused on nonviral delivery mechanisms of gene therapy, specifically with screening technology to identify lipid nanoparticles that can be delivered in vivo with “novel biodistribution and high selectivity for target cells,” the company said in a statement. Biomatics Capital, GreatPoint Ventures, and GV were the early backers of GuideTx.

Merck agreed to pay up to acquire another small company with a sky-high valuation – Watertown, Mass.-based Pandion Therapeutics. The price was $1.85 billion, or $60 a share. That’s more than double the previous day’s closing share price of $25.63. Pandion secured a $58 million Series A financing in January 2018 co-led by Polaris Partners, Versant Ventures and Roche Venture Fund. SR One and BioInnovation Capital also participated. See Timmerman Report coverage of the Series A about its approach to flip some of the learnings from immuno-oncology toward the treatment of autoimmune disease. Three years later, the company’s named lead candidate is an engineered IL-2 mutein fused to a protein backbone that’s supposed to selectively activate and expand regulatory T cells (Tregs) to tamp down overactive immune responses. Ulcerative colitis is the lead indication. Pandion also has PD-1 agonists in development for autoimmunity – obviously an area of interest at Merck, the maker of the market-leading PD-1 inhibitor for cancer.

South San Francisco-based Day One Biopharmaceuticals has told me on two occasions (the Series A financing and its recent $130 million Series B financing) that it planned to in-license another program to develop as a cancer drug specifically for kids. This week, it followed through. Day One worked with Merck KGaA to in-license pimasertib and another oral, highly-selective small molecule allosteric inhibitor of MEK 1/2, a key enzyme in the MAPK signaling pathway. Pimasertib has been through 10 clinical trials in about 900 patients with different tumor types. Day One said it believes there’s a scientific rationale to combine the MEK inhibitors with its existing pan-RAF inhibitor.

Somerset, NJ-based Catalent agreed to acquire Belgium-based Delphi Genetics, a plasmid DNA cell and gene therapy contract development and manufacturing organization. Financial terms weren’t disclosed.

Menlo Park, Calif.-based Grail agreed to work with Quest Diagnostics to collect the blood samples necessary for its Galleri product for blood-based early detection of cancer. Grail plans to start marketing in the second quarter. Quest has a network of 2,200 blood collection sites.

Financings

Waltham, Mass.-based Xilio Therapeutics, the developer of tumor-selective cancer therapies, raised $95 million in a Series C financing. Rock Springs Capital led. A tumor-selective version of IL-2, and a tumor-selective anti-CTLA-4, are being teed up to enter clinical trials in 2021.

San Diego-based Truvian Sciences raised $105 million in a Series C financing to push through to FDA approval for its benchtop blood diagnostic instrument that’s supposed to rival the capabilities central labs have for routine blood work. (TR coverage).

Cambridge, Mass.-based Orna Therapeutics raised $80 million in a Series A financing to advance work on circular RNA therapies, as opposed to the traditional linear kind. It’s based on research from the MIT lab of Dan Anderson, and was seeded and incubated by MPM Capital. (TR coverage).

Cambridge, Mass.-based Cellarity said it raised $123 million in a Series B financing to advance work on computational modeling of cell behavior for drug discovery. Flagship Pioneering founded the company, and was joined in the new round by BlackRock, The Baupost Group, Banque Pictet among others.

San Diego-based Vividion Therapeutics, the developer of precision medicines against previously undruggable targets for cancer and immune disorders, raised $135 million in a Series C financing. Logos Capital and Boxer Capital of Tavistock Group co-led.

San Francisco-based Miroculus completed a $45 million Series B round to develop lab automation tools. Cota Capital and Section32 joined the round.

San Diego-based Halozyme, the company that turns IV biologics into subcutaneous formulations, said it agreed to borrow $700 million in a convertible note offering due in 2027. The debt converts to equity if Halozyme stock reaches $77.17 a share. It’s at $47.17 now.

Beijing-based YishengBio, the developer of cancer and infectious disease therapies, raised $130 million in a Series B financing. Oceanpine and OrbiMed co-led.

Shanghai-based WuXi Diagnostics secured a $150 million Series B financing. Thermo Fisher joined the round. WuXi Diagnostics said in a statement that it is “the first platform company in China focusing on integrated diagnostics.”

FDA Leadership

Who will be the next FDA commissioner, and what will it mean for industry? The former president of R&D at Pfizer and a board member at Puretech Health looks at the contrasts between candidates Janet Woodcock and Joshua Sharfstein. Forbes. Feb. 24. (John LaMattina)

Our Shared Humanity

Too many Americans don’t learn our country’s history, and don’t want to grapple with the long-term consequences. It’s important for people to know that things like the infamous Tuskegee experiment happened. It harmed African Americans. It left an understandable legacy of mistrust.

Even those who are aware sometimes take home the wrong lesson. Tuskegee can sometimes unwittingly be used for blame-shifting onto African Americans. We would do better by acknowledging there are reasons why so many people are mistrustful of the healthcare system in the urgent now, and that racism in healthcare isn’t a thing of the past.

We would do better by asking ourselves: Are there things our healthcare systems can do to foster more trust in vaccines?

As USC social work professor Karen Lincoln put it in an interview with San Francisco public radio KQED:

If you continue to use it as a way of explaining why many African Americans are hesitant, it almost absolves you of having to learn more, do more, involve other people – admit that racism is actually a thing today.

Why might some people still be mistrustful of those urging use of the vaccine? Sadly, we have to listen to reports like this from NPR about San Francisco-based One Medical, which has allowed its well-to-do concierge medicine clients to skip ahead in the vaccine line. It’s more healthcare inequity in real-time.

Racial inequity is not a thing of the past. It’s not someone else’s problem. It will not resolve itself with time. We all pay a price for failing to fix this. Biopharma has a part to play, and some companies are busy doing the work. It will require vigilance.

Science

“Muscarinic Cholinergic Receptor Agonist and Peripheral Antagonist for Schizophrenia.” NEJM. Feb. 25. (Stephen K. Brannan, Sharon Sawchak, Andrew C. Miller, Jeffrey A. Lieberman, Steven M. Paul, and Alan Breier) For the backstory on xanomeline-trospium, being developed as KarXT by Boston-based Karuna Therapeutics, listen to Karuna CEO Steve Paul on The Long Run podcast.

“Phage-assisted evolution of botulinum neurotoxin proteases with reprogrammed specificity.” Science. Feb. 19. (David Liu et al Broad Institute and Harvard University). (See TR coverage of the latest spinout from Liu’s lab, Exo Therapeutics, December 2020).

“Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma.” This is the paper describing the BMS-Bluebird cell therapy directed at the BCMA antigen. The companies are seeking FDA approval. NEJM. Feb. 25. (Nikhil Munshi et al)

“Risdiplam in Type 1 Spinal Muscular Atrophy.” Genentech’s risdiplam (Evrysdi) helped 19 of 21 infants with spinal muscular atrophy Type 1 survive without permanent ventilation. One-third of the infants, 7 out of 21, were able to sit without support for at least five seconds – not normal in the natural course of disease. NEJM. Feb. 24. (Giovanni Baranello et al FIREFISH Working Group)

Book Review

The Genome Odyssey. From Code to Clinic. WSJ. Feb. 24. (David Shaywitz)

Personnel File

Cynthia Pussinen joined Philadelphia-based Spark Therapeutics, the Roche gene therapy unit, as chief technical officer.

Heidi Hagen was named interim CEO of Boston-based Ziopharm Oncology, a cancer immunotherapy company. She replaces Laurence Cooper effective immediately. James Huang was named executive chairman. Hagen, a cell therapy expert and co-founder of Vineti, was the lead independent director at Ziopharm.

Jerry Cacia joined South San Francisco-based Graphite Bio, a gene editing company, as chief technical officer. (TR coverage, Sept. 2020)

New York-based Intercept Pharma, the NASH drug developer, said Jason Campagna, the chief medical officer is resigning effective Mar. 5.

Waltham, Mass.-based Tscan Therapeutics hired Brian Silver as chief financial officer. He will step down from the board of directors to take the operating job. He’s a former investment banker, so you can probably set you can set the over/under date for when this company goes public.

Regulatory Action

The FDA placed two Bluebird Bio clinical trials for sickle cell disease on clinical hold. It was a formality, after the Cambridge, Mass.-based company already voluntarily paused the studies after learning of two cases of patients on its treatment who developed cancer. The investigation is ongoing into what caused the cases of cancer, and whether it’s related at all to the treatment. The world of gene therapy is watching.

AbbVie won another FDA label expansion for the aging franchise of adalimumab (Humira). This one is for pediatric patients with moderate to severe ulcerative colitis.

Restoring Honest Public Discourse

While we are busy trying to crush the pandemic, we have to stitch back together the fabric of a society ripped apart by 24/7 information war.

There is such a thing as honest inquiry and debate that doesn’t devolve into ad hominem attacks and bottomless nihilism for fun and profit.

Carl Bergstrom, a University of Washington professor and co-author of “Calling Bullshit” offers a glimpse of how to dig ourselves out of this ditch. It’s OK for people to disagree. It’s OK to change one’s mind based on new data. There isn’t *always* some sinister hidden agenda or dishonest subterfuge going on with people we disagree with on one issue or another.

That’s true for COVID-19, for drug pricing, and for a thousand other issues we need to be able to think about and discuss like intelligent adults.

There has to be a way forward to discuss issues without constant thermonuclear infowarfare. I’ve seen some encouraging signs. I hope to see more. Otherwise, the infowar will never end, and no one will win.

24
Feb
2021

Comprehensive Policy for Infection: There Has Never Been a Better Time

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24 Feb 2021

Ankit Mahadevia, CEO, Spero Therapeutics

The suffering from COVID-19 can be measured in multiple, sobering ways:

Life expectancy in the US has fallen by a full year, according to the CDC.

The economic cost – measured in reduced gross domestic product, premature death, and long-term disability – has been estimated at $16 trillion by economists David Cutler and Larry Summers at Harvard University.

This week, the US passed the grim milestone of half a million deaths from COVID-19.

The pandemic has shaken the foundations of our society. It has forced people to question assumptions about scientific priorities to better prepare for pandemics an interconnected world.  Further, multi-drug resistant bacterial infections pose one of the major threats to global health and prosperity, and these troublesome bugs haven’t gone away.

Even so, there is reason for optimism: there has never been a better time to muster the will, resources and expertise to reduce the threat from infectious disease.   

New Opportunities in Washington

We applaud the work underway at the World Health Organization and international governments. The US, under a new Administration, is well positioned to extend its global leadership in science with short-term and long-term investments.

Scientists with knowledge of the infectious threats are in a better position to help shape policy than ever before. President Biden, in his letter to his new science advisor Eric Lander, asked him to think broadly about pandemic preparedness. That call specifically included antibiotic resistance. Lander’s work in this area will not be marginalized – he is the first science advisor to be elevated to the Cabinet.

Within Congress, a change in party leadership and a focus on broad solutions for everything from COVID-19 to immigration creates an opportunity.  Well thought-out solutions are being crafted. The PASTEUR Act, with bipartisan co-sponsorship, is one. 

PASTEUR would commit transformational, multi-hundred-million-dollar investments to support drug development against key microbial threats that are not prevalent today, but would be deadly without effective medicines. The bill changes the incentives for antibiotic developers — allowing for investment returns that aren’t based on maximizing prescribing volumes. This would be a powerful incentive for industry to develop these critical defenses, while avoiding overprescribing that undermines effectiveness over time.

Expanded Support for Innovators

New and existing organizations have stepped up to provide support for new weapons against infection. The government-supported efforts are being supplemented by the Bill & Melinda Gates Foundation, the NOVO Repair Fund, and CARB-X – as well as traditional biotech investors.

The Biomedical Advanced Research and Development Authority (BARDA) continues to support R&D for diagnostics and therapeutics for existing and emerging threats. We applaud the agency’s timely response to the COVID-19 challenge; along with continued support for defense against drug-resistant bacteria.

The AMR Action Fund is the latest player on the scene. It’s a global organization established in 2020 by more than 20 pharmaceutical companies to fund development of innovative medicines against infectious threats.

The fund recently added Henry Skinner, a former Novartis Ventures investor, as CEO. The stated plan is to begin investing this year. The pharma companies and nonprofit groups backing the AMR Action Fund agreed last week to contribute another $140 million to the more than $1 billion it had already raised for R&D against multi-drug resistant bacteria. 

Bold Strategies Are Needed…and They Already Exist     

As Operation Warp Speed has taught us, we need bold, wide-ranging strategies against fast-moving and far-reaching pathogens. Incremental policy incentives, such as targeted changes to reimbursement for therapeutics, are necessary but not sufficient.

Fortunately, more ambitious plans do exist. The PASTEUR Act is one such example. Another is the Bipartisan Commission on Biodefense’s Apollo Program.

Founded in 2014 and co-chaired by former US Sen. Joe Lieberman and former Secretary of Homeland Security Tom Ridge, the Bipartisan Commission has proposed ~$10 billion a year for a comprehensive approach to testing, tracing, and treating future pathogenic threats. Former BIO president Jim Greenwood serves on the commission, so this group at least has some industry input.

What Next?

It has been some time since the conditions were so favorable for infectious disease. The time is now to work together.

Drug developers in infectious disease continue to have a duty to choose sustainable programs that marry clinical need with commercial benefit. This creates a stable base of R&D and expertise that can respond to future threats. 

The biotech industry at large can make its priorities clear.

  1. Bold, transformative solutions that give our industry what it needs for pandemic defense.
  2. Advocate for policies that prioritize treatments against infection. We can do this through our representative organizations such as BIO.

As private citizens, we can make clear to our elected officials that we want bold solutions to make sure we don’t have another COVID-19. 

We have the technology, talented drug developers, clinicians, and public health professionals. What we need is leadership, long-term focus, and coordinated efforts against a problem that’s bigger than any one company, or any one country. If we act together behind a comprehensive plan, we’ll be in position to prevent future pandemics.

Special thanks to Aleks Engel of the NOVO Repair Fund, Tim Hunt, and the Spero team for their contributions

18
Feb
2021

Biotech as a Beacon for Youth

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18 Feb 2021

Luke Timmerman, founder & editor, Timmerman Report

Biotech has always depended on the ideas and energy of young people.

But it’s time to think more broadly about how biotech and young people relate.

Let’s start with young people.

Recall the column from two weeks ago, which cited a 2017 Pentagon study. That study found that a full 71 percent of Americans between the ages of 18-24 aren’t eligible to serve in the US military. Three main reasons stand out as disqualifiers – obesity, criminal records, and lack of a high school diploma.

Let that sink in for a minute.

Think about how many millions of young people whose lives were going off the rails in the 2010s, because of long-simmering societal ills.

That was clear before the pandemic.

Now, consider how many young people are struggling, especially with mental health issues exacerbated by the pandemic.

All of us need hope. This is a hard time. But young adults need to be especially optimistic when making some of the big choices in life — what career to pursue, where to live, who to marry, how to maybe someday buy a home. Maybe some young people would make different life choices, and be more attractive to employers, if they had more hope.

What does any of this have to do with biopharma?

Consider manufacturing.

We are in the early phase of a cell and gene therapy revolution.

About 900 Investigational New Drug (IND) applications for cell and gene therapies were on file with the FDA as of February 2020. More are coming. Every week, more capital flows into startups aspiring to churn out more of these valuable next-generation medicines.

The opportunity for growth is obvious. There are more than 1,000 clinical trials for cell and gene therapies that could enroll as many as 60,000 patients worldwide, according to the Alliance for Regenerative Medicine. The FDA says it anticipates approving 10-20 such cell and gene therapies per year by 2025.

Whatever the numbers are, some of these specialized therapies will pan out. Some will get FDA approved. Some will need to scale up to meet global demand.

Jobs will have to be created in specialized, customized manufacturing plants to make these cell and gene therapies. Advanced biologics aren’t going away, either. The making of these medicines can’t be completely automated, and shouldn’t be entirely shipped offshore. There are national security reasons, national competitive advantage reasons, logistical shipping reasons, and workforce development reasons to keep most of this work on US soil.

There are large swaths of the map outside of San Francisco, New York and Boston where this work can be done inexpensively.

Biotech can choose to invest in people, equipment, and places to get ready for this manufacturing boom.

Actually getting this done will require a shift in employer mindset. Not everyone needs a 4-year degree to work in a cell therapy manufacturing plant. Some of these jobs are better suited to people with 2-year community college training.

These can be high-salary/good-benefits/steady paycheck blue collar jobs. As biotech matures as an industry, it will depend on more of these jobs. When the industry invests in people to do this skilled work, it makes good long-term economic sense to pay high wages to keep people motivated and productive and loyal.

I grew up in the industrial and agricultural economy of the Upper Midwest. The high salaries and good benefits offered by companies like John Deere were considered the ticket to middle-class life. There was pride and dignity in this work for people like my Dad. He got a community college certificate to become a welder. He got a job with that skill at John Deere in Dubuque, Iowa. He thought he had it made.

He lost that job in a round of layoffs when I was in preschool.

Jobs like that today are scarce. My Dad had to reinvent himself a couple times to provide for our family.

Now I live in Seattle. It’s a tech metropolis. But before the tech boom, it was put on the map by Boeing. Tens of thousands of blue-collar, union workers built Seattle. They earned good wages and solid benefits. They took pride in work assembling “the best airplanes in the world.” That’s what Boeing commercial airplanes chief Alan Mulally, a boy from Kansas, used to say.

Like any for-profit industry, of course, biotech isn’t in the business of creating jobs just for the sake of creating jobs. But it is an industry on the upswing. It needs to think long-term about people to meet long-term business needs.

Young people seeking purpose could step up for this line of work, whether they aspire to be scientists or blue-collar machine operators.

What if biotech were to open up to more people without 4-year or advanced college degrees? What kinds of manufacturing jobs, in particular, might be doable for people with community college training? Would it make sense to invest in apprenticeship programs, and then continue to invest in training people to keep skills updated over an entire career?

Might some of these people become longtime, loyal, productive employees? Might some rise through the ranks to make even greater contributions to their companies? Might the kids of manufacturing workers grow up to be scientists and executives of tomorrow?

Biotech can be the new Boeing, the new John Deere. It will require extending a hand to young people. It will require taking chances on people who might not otherwise get one.

It will take some imagination. But the potential is clear. Biotech, as I wrote here a few weeks ago, is radiant at a dark time.

Let’s make biotech into a beacon of hope for young people.

An Ominous Development at Bluebird

Cambridge, Mass.-based Bluebird Bio, the cell and gene therapy company, is experiencing a nightmare. The company said it halted clinical trials of its Lentiglobin gene therapy for sickle cell disease after seeing a report of a patient dosed five years ago now coming down with acute myeloid leukemia. Around the same time, the company said it learned of another case of a patient getting myelodysplastic syndrome (MDS), a pre-leukemia syndrome. The company hasn’t been able to confirm whether the cancerous conditions are related to its lentiviral vector. But because that possibility can’t be ruled out, and because its only marketed therapy uses the same vector, it shut down sales and marketing of that other treatment for beta-thalassemia in Europe and the UK.

Shares in Bluebird crashed, down 41 percent in value from $45.76 last Friday to $26.95 at yesterday’s close. Many investors have to be wondering about the decision Bluebird recently announced to split into two companies – one focused on genetic diseases, and the other focused on cancer. The future for genetic diseases will hinge on what investigators uncover in days and weeks ahead about what might have caused the severe adverse events.

Analyst Raju Prasad of William Blair downgraded the stock immediately, as many investors surely aren’t going to hang around long to find out. At best, the situation means Bluebird will suffer from a significant delay. At worst, if the vector ends up looking like the culprit, it could be devastating to the company and send a chill through investor sentiment in other gene therapy companies. It’s too early to say yet what the answer will be. “While there is precedent of [sickle cell disease] patients to have an increased risk of leukemia compared with the general population, we believe the complexity of the issue is likely to lead to a thorough investigation and potentially a significant delay to trial timelines and/or change to trial design,” Prasad wrote in a note to clients.

Bluebird shares this week.

Vaccine Access and Distribution

Moderna said it expects to deliver 100 million doses of its mRNA COVID-19 vaccine to the US government by the end of March, another 100 million by the end of May, and another 100 million by the end of July. Those are faster timelines than the company had agreed to previously, and enough for this company alone to fully vaccinate almost half of the US population with a two-shot regimen. The company also agreed to provide an additional 150 million doses to the European Union, bringing the total doses ordered there to 310 million in 2021. The European Commission also secured an option for another 150 million doses in 2022. It’s all pretty breathtaking to consider, knowing the pressure to move this fast with global-scale manufacturing of a novel mRNA vaccine technology with lipid nanoparticle delivery.

Pfizer and BioNTech said they will supply 200 million extra doses of its mRNA COVID-19 vaccine to the European Union, bringing its total supply agreement there to 500 million doses. The plan is to deliver by the end of 2021. The European Commission obtained an option to request another 100 million doses. Last week, the companies said they upped their commitment to the US government by 100 million doses, bringing its total commitment to the US government to 300 million doses.

Novavax reached an agreement with GAVI to provide 1.1 billion cumulative doses of its protein-adjuvant vaccine for COVID-19 through the COVAX facility, to provide vaccine access to people in low-income, middle-income, and high-income countries. Gaithersburg, Maryland-based Novavax is working in partnership with Serum Institute of India to boost manufacturing output.

Johnson & Johnson, the developer of a single-shot vaccine for COVID-19 that’s due to go before an FDA advisory committee for review Feb. 26, is still planning to supply 100 million doses to the US government in the first half of 2021. But it’s unclear how many doses will be available in March and April, assuming it wins Emergency Use Authorization from the FDA. Tony Fauci told CNN he’s “a little disappointed” in the expected number of doses available from J&J this spring.

While the race is on to vaccinate in wealthy countries, Science magazine reporter Kai Kupferschmidt notes that not a single healthcare worker in Africa has been vaccinated, until South Africa started this week.

Science of SARS-CoV-2

Reduced Neutralization of SARS-CoV-2 B.1.1.7 Variant by Convalescent and Vaccine Sera. This study isn’t quite as bad as the headline suggests. The authors write, “widespread escape from monoclonal antibodies or antibody responses generated by natural infection or vaccination was not observed.” Cell. Feb. 18. (Piyada Supasa et al Oxford University)

Transmission of COVID-19 in 282 clusters in Catalonia, Spain. This study shows that people with high viral loads of SARS-CoV-2 are main drivers of transmission. The Lancet. Feb. 2. (Michael Marks et al).

Densely sampled viral trajectories suggest longer duration of acute infection with B.1.1.7 variant relative to non-B.1.1.7 SARS-CoV-2. Why does the new variant seem so concerning? One reason, according to this Harvard study, is that it appears to last longer, naturally creating more opportunities for transmission. Digital Access to Scholarship at Harvard. Feb. 10 preprint. (Stephen Kissler et al)

Science

Inhibitory CD161 receptor identified in glioma-infiltrating T cells by single-cell analysis. Cell. Feb. 15. (Kai Wucherpfennig et al Broad Institute). Researchers at the Broad Institute analyzed tumor-infiltrating T-cells with single-cell analysis, and identified the gene that encodes for CD161 which appears on NK cells and T cells. It’s the basis for cell therapy work being done at Waltham, Mass.-based Immunitas, which raised a $39 million Series A financing in 2019. (Company statement).

Vaccines

Neutralizing Activity of BNT162b2-Elicited Serum — Preliminary Report. NEJM. Feb. 17. (Pfizer / BioNTech research teams). The mRNA vaccine showed in vitro that it can neutralize the SARS-CoV-2 virus with the B.1.351 variant to the spike protein (more widely known as the South Africa variant). (Pfizer statement).

Brazil is trying to answer one of the key outstanding questions about the COVID-19 vaccines. Do they help reduce transmission of the virus? It’s difficult to run such a study, but the Brazilians are trying a pilot project – vaccinate an entire town of 45,000 people to see what happens. (WSJ coverage).

Vaccine Hesitancy

The myth of ‘good’ and ‘bad’ Covid vaccines. This article discusses how false perceptions about the next batch of vaccines could complicate the vaccine hesitancy story, especially in communities of color. STAT. Feb. 17. (Helen Branswell)

Therapeutics

UK-based Synairgen said it started enrolling in a Phase II/III study with an inhalable interferon beta treatment for mild-to-moderate COVID-19 patients who aren’t hospitalized.

South Plainfield, NJ-based PTC Therapeutics said it started the second stage of a Phase II/III trial of an oral therapy it developed against a cellular enzyme, dihydroorotate dehydrogenase (DHODH). By targeting this enzyme instead of a protein on SARS-CoV-2, PTC hopes to inhibit viral replication and calm down the excessive inflammatory responses that result from infection. CEO Stu Peltz noted in a statement that the drug could be taken at home, as well as in the hospital, and that if it’s effective, it ought to work against wildtype virus as well as the variants.

Diagnostics

Thermo Fisher Scientific said it secured FDA Emergency Use Authorization for the TaqPath RT-PCR diagnostic test, which can tell the difference between COVID-19, Flu A and Flu B in a single sample. It’s for CLIA lab use.

Financings

New York and San Francisco-based Adjuvant Capital, founded in 2019 but quiet until this week, announced its initial $300 million fund to invest in public health needs that deliver social and financial returns. Merck, Novartis, IFC, the Bill & Melinda Gates Foundation, Children’s Investment Fund Foundation, and Dalio Philanthropies are among the LPs supporting the team led by Glenn Rockman and Jenny Yip. (TR coverage by Anika Gupta).

Cambridge, Mass.-based Centessa Pharmaceuticals raised $250 million in a Series A, to roll up 10 Medicxi Ventures-backed asset-centric virtual biotech companies into an umbrella organization. Saurabh Saha, formerly of Bristol-Myers Squibb, is the CEO, while Moncef Slaoui, the former chief scientific advisor of Operation Warp Speed, is the CSO. (Timmerman Report coverage).

Durham, NC-based Humacyte went public through a SPAC deal that brought in $255 million in cash proceeds to advance its work in making universally implantable, off-the-shelf human tissues for transplant at large commercial scale. Fresenius Medical Care, OrbiMed, Monashee Investment Management, and Alexandria Venture Investments were among the participants in the related PIPE deal.

Cambridge, Mass.-based Elicio Therapeutics, an immunotherapy company targeting the lymph nodes, raised $73 million in a Series B financing. It didn’t name the investors, but said there were “multiple strategic and international investors.”

San Francisco-based Excision Biotherapeutics said it raised $60 million to develop CRISPR-based antiviral therapies. Greatpoint Ventures led.

Cambridge, Mass.-based Immune ID raised a $17 million seed financing led by Longwood Fund, and which included Arch Venture Partners, Pitango HealthTech, In-Q-Tel and Xfund. The company is working to identify therapeutic targets based on antibody interactions that drive immune diseases.

New York and Guilford, Conn.-based Quantum Si, a proteomics company founded by Jonathan Rothberg, went public through a SPAC transaction with HighCape Capital. The deal involves $540 million of gross proceeds to the company, including a $425 million private investment in a public equity (PIPE) that included Foresite Capital Management and Redmile Group, among others.

Boston-based Gamida Cell, a cell therapy company, raised $75 million in a convertible debt offering with Highbridge Capital Management. The cash is supposed to keep the company going into the second half of 2022.

Seattle-based Ozette raised $6 million in a seed financing to advance AI for immune system monitoring. Madrona Venture Group led, and was joined by the Allen Institute for Artificial Intelligence (AI2) and Vulcan Capital.

Houston-based Iterion Therapeutics pulled in $17 million in a Series B financing led by Lumira Ventures to develop a potent and selective nuclear beta-catenin inhibitor for desmoid tumors.

Deals

Charles River Labs agreed to acquire Cognate Bioservices, a cell and gene therapy contract manufacturing organization, for $875 million in cash.

Novartis and the Bill & Melinda Gates Foundation agreed to work on a more affordable, globally accessible in vivo gene therapy for sickle cell disease. The Gates Foundation has agreed to fund “a research team within NIBR wholly dedicated to developing an approach to delivering this potential treatment.” Terms weren’t disclosed.

Cambridge, Mass.-based Cytovia Therapeutics agreed to work with Cellectis on TALEN-engineered iPSC-derived Natural Killer cell therapies. Cellectis will get either $15 million in equity in Cytovia, or $15 million in cash, by the end of 2021.

GSK and San Francisco-based VIR Biotechnology agreed to expand the collaboration that started in April 2020 to work on neutralizing antibody therapies for COVID-19. The expanded deal now includes other viral infectious diseases, including influenza. GSK will partner on development of an intramuscular injection that’s supposed to work as a universal prophylactic for influenza A, and that has completed a Phase 1 trial. Next-generation antibodies to prevent or treat flu are also part of a three-year research collaboration. GSK is agreeing to pay $225 million upfront, plus make an additional $120 million equity investment.

Eli Lilly agreed to pay $125 million upfront to South San Francisco-based Rigel Pharmaceuticals to co-develop Rigel’s receptor-interacting serine/threonine-protein kinase 1 (RIPK1) inhibitor. The deal is global, exclusive, and covers all therapeutic indications.

San Francisco-based Nektar Therapeutics said it will receive as much as $150 million from SFJ Pharmaceuticals, a company backed by Abingworth and Blackstone Life Sciences, to develop bempegaldesleukin (BEMPEG), an IL-2 agonist in combo with Merck’s pembrolizumab (Keytruda) for head and neck cancer. Nektar will serve as the sponsor of the Phase II/III study. It has agreed to pay milestones over 7-8 years to SFJ, if it wins regulatory clearance.

Data That Mattered

Merck and AstraZeneca said they were planning to halt a Phase III trial early, at an interim analysis, because a data monitoring committee reported the drug has demonstrated superiority over placebo. The drug, olaparib, (Lyparza), is a PARP inhibitor being tested in the adjuvant setting for germline BRCA mutated, high-risk HER2 negative breast cancer after local treatment and neoadjuvant or adjuvant chemotherapy. Data will be presented at a medical meeting.

Personnel File

Sara Nayeem joined New York-based Avoro Ventures as a partner. She was previously with NEA for 12 years. She will source and manage biotech investments from early-stage to late-stage to crossover, the firm said in a statement.

Kizzmekia Corbett, the mRNA vaccine scientist at the NIH, was named to the TIME100. Read about her contribution in this essay by Tony Fauci.

Salt Lake City-based Recursion, the company using AI and other tech tools for drug discovery, hired Louisa Daniels as chief legal officer and general counsel. She was a vice president at Pfizer. (TR coverage of Recursion, Sept. 2020).

BIO hired Shaye Mandle as chief operating officer. He comes to the biotech trade association with experience in restructuring and rebranding Minnesota’s Medical Alley Association.

Westlake Village Biopartners hired Peter Calveley as chief operating officer.

South San Francisco-based Day One Biopharmaceuticals, the developer of treatments for kids with cancer, hired Charles York as chief operating and chief financial officer. (TR coverage of Day One’s $130m Series B round, Feb. 2021).

Boston-based Dewpoint Therapeutics added Regina Barzilay, Distinguished Professor for AI and Health at MIT, to its board of directors. (TR coverage of Dewpoint, Apr. 2019)

Cambridge, Mass.-based Evelo Biosciences, a microbiome-based therapeutics company, named John Hohneker to its board of directors. (The Long Run podcast with Evelo CEO Simba Gill, Nov. 2020).

Regulatory Action

Amgen said the FDA has granted Priority Review status to its application to market sotorasib, the KRAS G12C-directed small molecule drug for non-small cell lung cancer. The PDUFA review deadline is Aug. 16, but it wouldn’t be a surprise if the FDA acted sooner to approve this potentially pathbreaking medicine against one of the classic hard targets of oncology.

South San Francisco-based Cortexyme said its atuzaginstat Phase II/III trial for Alzheimer’s disease is on partial clinical hold, following an FDA review of “hepatic adverse events” – aka liver toxicity. The events were reversible and didn’t appear to cause long-term damage, the company said.

Novartis secured an expanded label from the FDA for sacubitril/valsartan (Entresto). The drug’s prescribing information is now thought to cover about 5 million of the estimated 6 million people in the US with forms of chronic heart failure.

Genomic Surveillance

The CDC, newly empowered to lead in the pandemic, pledged a $200 million “down payment” on improved genomic surveillance of SARS-CoV-2 and its increasingly troubling variants. For the world leader in genomics, this is an embarrassing late date to get moving in a nationally coordinated way to help us adapt our behavior as the virus evolves. We are sequencing fewer than 1 percent of samples, and expert say we need to get to 5 percent, and do it with samples from around the country, if we’re going to have an adequate surveillance system.

See below this Twitter exchange with a genomic surveillance expert, explaining why so little sequencing of viral samples was being done as recently as December. We late to the game, and have some serious catching up to do.

 

16
Feb
2021

Increasing Vaccine Confidence With the Tools That Got Us This Far

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16 Feb 2021

Michele Andrasik, PhD. Director, Social & Behavioral Sciences and Community Engagement
HIV Vaccine Trials Network; Affiliate Assistant Professor, Global Health, University of Washington

By Michele Andrasik, Sally Bock, Stephaun Wallace and Michael Ferguson

This month, when the news was full of stories of vaccine scarcity and images of long lines of people hoping to get immunized, the COVID-19 Prevention Network and Fred Hutch ran TV ads during the Super Bowl for people still hesitant about the vaccine in Washington state.

When given this rare opportunity to reach so many people, we were careful about what to say and not to say.

There was no scolding or chiding or pleading.

The narrator of the ad invites people to engage, and empowers them to come to their own conclusion. “You may still be doubtful. That’s OK. We can work together to get answers to your questions,” the narrator says.

Why seek to build more demand during a vaccine shortage?

In one word: equity.

COVID-19 vaccinations in Washington state began on Dec. 14. As of Feb. 8 — 56 days later — a little over 10% of Washington state residents received their 1st dose and slightly less than 3% were fully vaccinated.

The large majority of those who have gotten their first shot (66.6%) and who have gotten fully vaccinated (65.8%) are White.

Only 18% of individuals initiating vaccinations are from BIPOC communities. The people who are suffering disproportionately from the pandemic are also less likely to get the vaccine.

For BIPOC communities hardest hit by COVID-19, vaccination rates are disturbingly low, particularly among Native Hawaiian/Pacific Islander (0.5% of the vaccinated population), American Indian/Alaska Native (2.2%), Black/African American (2.2%), Hispanic/Latino/a (4.7%) and Asian Americans (8.3%).

Although Black, Indigenous and People of Color (BIPOC) represent 34.6% of the total population of Washington state, as is the case nationally, these groups carry the greatest COVID-19 burden, representing 52% of all COVID-19 cases, 47% of COVID-19 hospitalizations and 29% of COVID-19 deaths.

Among BIPOC communities, the Hispanic/Latino/a community is most disparately impacted by COVID-19, representing 32% of all COVID-19 cases, 24% of hospitalizations and 12% of deaths. 

The rates are also disproportionately high among Asian, Black, Native Hawaiian, Pacific Islander, American Indian and Alaska Native communities. These rates are likely higher as testing is limited across the state and a significant number of confirmed cases, hospitalizations and deaths are missing racial and ethnic information. 

What does it take to build trust and confidence in vaccines?

The creative strategy behind the vaccine confidence campaign is to validate the questions and concerns of the hesitant, and to empower people to get back to the things COVID-19 has taken away—gathering with family and friends, freedom from masks and worry about the virus, and reopening businesses.

But ads alone won’t build confidence. It takes open and transparent dialogue, hearing from trusted messengers, and assurance that the research behind the vaccines is thorough and that people that look like them have been part of it.

The campaign is supported by a website — PreventCovidWA.org — to continue the dialogue. It uses an integrated media strategy with animated videos breaking down the science behind the vaccines, “Ask An Expert” videos featuring the diverse physicians and researchers who led the Phase III vaccine trials, and testimonials from people who volunteered for studies and people who have been vaccinated.

With deep listening through digital channels and on-the-ground community engagement, the content is dynamic. It’s responsive to community conversation as the scientific narrative unfolds and changes and new and novel misinformation and myths arise.

These aren’t just strategies suggested by audience research. These are the strategies the COVID-19 Prevention Network (CoVPN) has been developing and refining since spring 2020 when it began preparing for Phase III COVID-19 vaccine trials. Those studies were conducted at unprecedented speed and scale and with some of the highest representation of BIPOC people ever.

Pivoting to the pandemic

The CoVPN was formed in April 2020. Tony Fauci turned to the clinical trial networks the NIH had established for HIV/AIDS and charged them with conducting large scale Phase III trials for COVID-19 vaccines being developed under what came to be called Operation Warp Speed.

One of those leaders was Larry Corey, renowned virologist, head of the HIV Vaccine Trial Network and past president and director of Fred Hutch. We were well-positioned for this work based on years of experience in HIV vaccine trial work.

Immediately, the HIV Vaccine Trials Network (HVTN) Community Engagement and External Relations teams began reaching out to longstanding community partners to learn more about the impact of COVID-19 in their respective communities, to better understand COVID-19 fears and uncertainty, and to identify what information was needed to ensure that communities had the resources they needed to make informed decisions about participation in the vaccine trials in the short term and vaccine acceptability and uptake in the long term. 

Priority populations — older adults (65+), Black, Latino/a/Hispanic, Indigenous and People of Color — have been the focus of these efforts for months. Strong community partnerships — rooted in bidirectional communication, trust and reciprocity — were the cornerstones of the plan.  

A few weeks into the new CoVPN efforts, a strategic communications and marketing effort was launched to extend out from the community-based work. A creative partnership was formed among CoVPN leadership and the agencies Socialisssima and Sam Bonds Creative, who brought their deep expertise in BIPOC consumer mindsets to develop a mass media campaign that was both national and localized.  

The community engagement plan focused on increasing awareness and knowledge. We sought to build trust by lifting up the voices of people with lived experiences. Our community-based researchers listened carefully to the concerns being raised. The campaign sought to address the common fears, uncertainty, isolation, mistrust and misinformation by offering hope, a way to end the uncertainty and a call to action.

The Super Bowl ad reflects this emphasis — it features real people who might look like you and have questions and concerns. Those questions and concerns are dealt with respectfully.

People working to build vaccine confidence in Washington state. From left to right: Sally Bock, senior director, marketing, CoVPN; Stephaun Wallace, director of external relations, CoVPN; Michael Ferguson, director of marketing, CoVPN; Norberto Zylberberg, founder, Socialisssima; Sam Bonds, principal, Sam Bonds Creative

Lessons from clinical study recruitment

All of these efforts to engage community built a strong foundation for the Washington state effort.

Then we got a bit lucky.

When our CBS affiliate reached out on short notice with available Super Bowl commercial space, we were able to produce a strategic and emotionally on-target 30-second Public Service Announcement in just days.

Of course, a Super Bowl ad is just one opportunity to spread the word. We also partnered with the Washington State Department of Health to develop a user-friendly vaccination website specific to Washington state – PreventCovidWA.org – where people from across the state can obtain information about available vaccines, hear testimonials from people who participated in the vaccine trials and from people who have been vaccinated, and schedule a vaccination appointment. 

Partnering with community and working together, with all members providing direction and guidance, is what ensured equity and inclusion in the COVID-19 vaccine clinical trials.

This approach worked before – it is what made the vaccine trials as diverse as they were.

It IS the same approach that will help us achieve equity and inclusion in this vaccination campaign.

For more information on the PreventCovidWA campaign, check Instagram and Facebook.

11
Feb
2021

Long COVID’s Insidious Toll, Novo’s Victory Against Obesity, & Gilead’s Stumble in IPF

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11 Feb 2021

Luke Timmerman, founder & editor, Timmerman Report

Our culture tells us to fear death.

Every day, we hear updates on the COVID-19 death toll. Deaths are broken down by age, race, ethnicity. By state and nationality.

The US numbers – 473,000 and increasing by more than 3,000 a day – are tragic and numbing.

But while we fixate on death, we are devoting scant attention to the insidious, cumulative toll of morbidity from COVID-19. The ‘Long COVID’ story is one of those gradual ones that sneaks up on us over time.

The types of symptoms, the number of people struggling, the severity of chronic disease, how long the symptoms might last – these are all important questions are only beginning to come into focus.

The Mt. Sinai Center for Post-COVID Care in New York estimates that 10 to 30 percent of all COVID patients will suffer from long-term symptoms. As of this writing, we have had 27.3 million confirmed cases of COVID-19. That’s an undercount, but if you use that number for the sake of argument, we could be looking at 2.7 million-8.2 million people in the US alone who are struggling with some sort of chronic disease stemming from COVID-19.

Doctors who see COVID patients are telling me that Long COVID is the real thing, not just a few anecdotes here or there, and not some minor bellyaching from hypochondriacs as was sometimes implied by some stressed-out clinicians early in the pandemic.

“The Long Haul story is not one that has been fully told,” said Peter Hotez, a virologist at Baylor College of Medicine in Houston, and director of vaccine development at Texas Children’s Hospital Center, in a recent appearance on CNBC. “Literally millions of people could have some lingering symptoms.”

Deaths are “the tip of the iceberg,” Hotez said.

What are common Long COVID symptoms?

  • Lung fibrosis / shortness of breath
  • An inability to concentrate, or “brain fog”
  • Blood clotting
  • Heart arrythmias
  • Kidney damage
  • Metabolic dysregulation that looks like Type 1 diabetes
  • Long-term fatigue
  • Depression and anxiety that stems from any of the above chronic conditions

Data are just beginning to surface to tell the story. A 6-month follow-up study from Wuhan, China, published last month in The Lancet, found that 63 percent of COVID-19 survivors complained of fatigue and muscle weakness, and 26 percent reported sleep difficulties. About one out of every four people discharged from the hospital reported depression or anxiety. One-fourth of patients were unable to reach the lower limit of normal distance on the 6-minute walk test.

Tony Fauci has described some of the symptoms as similar to myalgic encephalomyelitis (aka chronic fatigue syndrome). While lingering inflammation may be a common thread in the two conditions, the set of symptoms don’t exactly overlap. To collect more data from Long COVID patients, Johns Hopkins Bloomberg School of Public Health is conducting an online survey. It hopes to recruit 25,000 participants. (Survey Here).

My hope is that in the coming weeks, as our country continues to ramp up the biggest vaccination campaign in history, that we keep these devastating long-term consequences in mind.

I’ve heard stories in my extended family. There’s a distant cousin, a 20-something college undergraduate. She dropped out of college because of brain fog from Long COVID. She can’t concentrate. She’s unsure if or when she’ll be able to go back.

What must that be like, to be 21 and get a bug that doesn’t seem too terrible at first, but that ends up altering the trajectory of your life?

Often, the Long COVID effects show up in middle-aged, healthy people. Recall the Dec. 7 TR article by Blair Clark-Schoeb. She’s in her mid-40s, a parent, an athlete, and a successful biotech professional.

E. Blair Clark-Schoeb, SVP of communications, Aruvant Sciences

Her struggle with Long COVID began in March. It continues. She described it on a recent podcast.

Entire biotech funds will probably be raised in the months ahead to deal with the whole new set of chronic diseases that our healthcare system will have to confront. There will be ideas for treating chronic inflammation, for the clotting disorders, the depression, the anxiety, the diabetes-like symptoms.

The demand for biopharma to step up and deliver will be clear.

That’s a good thing. It will give purpose and drive to many in this industry. If biotech can rise to the occasion with vaccines, therapies and diagnostics, it can find a way forward here.

The main thing to remember in the urgent here and now is the importance of hunkering down for another couple of months, with masking and distancing, until the vaccines have a chance to crush the curve.

I’m much more optimistic than I was at the start of the year, because we have not just two outstanding vaccines, but two more excellent and practical options on the way from J&J and Novavax.

Let’s do everything we can to help everyone see why getting vaccinated is so vital, and so urgent. It’s not only about saving lives. It’s about helping us all live long and healthy lives.

 

Public Health

The CDC – still the world’s premier epidemiology and public health agency – screwed up big-time with testing at the start of the biggest pandemic in a century. Things got worse when it was muzzled and marginalized. But now that CDC has a capable leader in Rochelle Walensky with support from the White House, the CDC is in a stronger position to bring down community transmission. To that end, the CDC urged the public to consider “double-masking” as a more rugged defense against the more troubling B117 and B.1.351 variants now in circulation. For more, see this Feb. 10 JAMA article on “Effectiveness of Mask Wearing to Control Community Spread” by a couple of CDC scientists.

Vaccine Hesitancy

The CDC reported on vaccine hesitancy in its Morbidity and Mortality Weekly Report (MMWR), and the numbers are moving in the right direction. If you group together respondents who said they were “absolutely certain,” or “very likely,” or “somewhat likely” to be vaccinated, the intent to get vaccinated increased overall from September (61.9%) to December (68.0%). Those household surveys, it should be noted were taken during the intense emotions of election season, news reports of astounding efficacy for Pfizer and Moderna, and FDA Emergency Use Authorizations in December.

People age 65 and older, the ones at highest risk of COVID-19, showed increasing willingness to get the shot.

And yet, the pockets of resistance are high, and stubborn. See this recent snapshot from the Kaiser Family Foundation Vaccine Tracker. The percentages below are people who say they will “Definitely Not” get a COVID-19 vaccine. That’s 13 percent of the country, including 25 percent of Republicans and 21 percent of Rural people. (Survey data: Jan. 11-18, 2021)

Some people, on the extreme left and right, are going to be unreachable in their anti-vaccine attitudes. Maybe the biggest area of concern are the people who are in the middle, suffering from the breakdown of trust, the epistemic crisis at the bottom of the barrel of cynicism. Millions of people don’t know who or what to believe. As David Shaywitz wrote here last week, this is the result of “manufactured nihilism.”

The results are plain to see. Weeks after news about 95 percent effective vaccines becoming authorized by the FDA – one of the greatest achievements in the history of science – we still see huge swaths of the US public struggling along, saying they’ll “Wait and See.” (See the demographic breakdown from the Kaiser Family Foundation survey, Jan. 11-18.)

 

Will these numbers trend in ever-more positive directions in coming weeks and months? I hope so. The NYT ran an editorial co-signed by 60 Black members of the National Academy of Medicine urging African Americans to get vaccinated. The Kaiser Family Foundation notes that openness to vaccination tends to increase when people know someone else who has been vaccinated.

Treatments for COVID-19

Repurposed Antiviral Drugs for Covid-19. NEJM. Feb. 11. (WHO Solidarity Trial Group)

Tocilizumab IL-6 inhibiting therapy in COVID-19 patients admitted to the hospital. Overall, 596 (29%) of the 2022 patients on tocilizumab and 694 (33%) of the 2094 44 patients on usual care died within 28 days. MedRxiv. Feb. 11. (RECOVERY trial group)

Good News for Obesity

Researchers reported that once-weekly subcutaneous injections of semaglutide (Ozempic), a GLP-1 peptide analog drug for diabetes from Novo Nordisk, significantly increased weight loss when boosted up to a 2.4 milligram dose (the drug is usually given in a 0.5 to 1 mg subcutaneous once weekly shot for diabetes).

The mean change in body weight from baseline to week 68 was −14.9% in the semaglutide group compared with −2.4% with placebo, according to investigators from the STEP1 trial, writing in the New England Journal of Medicine. Nausea and diarrhea were the most common side effects; but were typically mild to moderate and went away over time. See comment from Sek Kathiresan, a cardiovascular genetics expert, and CEO of Verve Therapeutics.

Given the huge and rising prevalence of obesity in the US, this is maybe the most clinically relevant result I’ve seen on a population level in a long time. See the CDC state-by-state graphic below that shows rates of obesity, defined as people with Body Mass Index of 30 or higher. Obesity, by the way, is an added risk factor for COVID-19 complications.

Variants vs. Vaccines
  • mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants. Feb. 10. (Michel Nussenzweig et al Rockefeller University)
  • Coronavirus Variants and Mutations. An Excellent Graphic. Feb. 11. (Jonathan Corum and Carl Zimmer)
  • Variants mean the coronavirus is here to stay — but perhaps as a lesser threat. Washington Post. Feb. 9. (Carolyn Johnson)
  • Could a Single Vaccine Work Against All Coronaviruses? NYT. Feb. 9. (Carl Zimmer)
  • Herd Immunity Might be Unattainable. But Vaccines Can Still Help End the Pandemic. The Atlantic. Feb. 9. (Sarah Zhang)
  • Mapping Which Coronavirus Variants Will Resist Antibody Treatments. NIH Director’s Blog. Feb. 9. (Francis Collins)
  • S. rushes to fill void in viral sequencing as worrisome coronavirus variants spread. Science. Feb. 9. (Meredith Wadman)
Epidemiology
  • Quantifying asymptomatic infection and transmission of COVID-19 in New York City using observed cases, serology, and testing capacity. PNAS. (Rahul Subramanian et al)
  • The effects of school closures on SARS-CoV-2 among parents and teachers. PNAS. (Jonas Vlachos et al Stockholm University)
  • The role of children in the spread of COVID-19: Using household data from Bnei Brak, Israel, to estimate the relative susceptibility and infectivity of children. PLoS Computational Biology. Feb. 11. (Itai Dattner et al)
Science of SARS-CoV-2
  • Exhaled aerosol increases with COVID-19 infection, age, and obesity. PNAS. (David Edwards et al Harvard University)
  • Rapid Coronavirus Tests: A Guide for the Perplexed. Nature. Feb. 9. (Georgia Guglielmi)
  • COVID-19 immune signatures reveal stable antiviral T cell function despite declining humoral responses. Cell Immunity. Feb. 9. (Agnes Bonifacius et al Hannover Medical School, Germany)
  • Seasonal human coronavirus antibodies are boosted upon SARS-CoV-2 infection but not associated with protection. Cell. Feb. 9. (Scott Hensley et al Penn Medicine)
Access and Distribution

The US government agreed to order 100 million more doses of the mRNA vaccine from Moderna. That means that US government has agreements to get 300 million doses out of the 631 million doses Moderna has lined up in supply agreements with governments around the world.

Merck is reportedly in negotiations with governments, public health agencies, and other companies to fire up its considerable capabilities for manufacturing COVID-19 vaccines. The Kenilworth, NJ-based company, one of the world’s major vaccine producers, scrapped its novel vaccine programs after they failed to generate an adequate immune response.

Pharmacies around the country were due to get 1 million doses of COVID-19 vaccines from the federal government as of yesterday, Feb. 11. The companies, including national chains like CVS and Walmart, have confirmed they don’t want to let any doses go to waste. That raises the question of who will get leftover doses. Their employees, or the public?

A Houston doctor had 10 doses of vaccines that were due to expire, and had to be used. He gave them to people with medical conditions. He got fired and publicly humiliated for trying to do the right thing, trying to avoid a travesty. This is one of those zeitgeist stories about a society suffering from a breakdown of trust. (NYT, Feb. 10, 2021)

Our Shared Humanity

Vaccinated People Are Going to Hug Each Other. Julia Marcus writes: “The vaccines are phenomenal. Belaboring their imperfections—and telling people who receive them never to let down their guard—carries its own risks.” The Atlantic. Jan. 27. (Julia Marcus of Harvard Medical School)

Pandemic Effect on Cancer R&D
  • Dramatic drop in new cancer drug trials during the COVID-19 pandemic. The Lancet. Feb. 4. (Emma Wilkinson)
  • Cancer groups aim to broaden clinical trial participant pool. Bloomberg Law. Feb. 9. (Jeannie Baumann)
Financings

South San Francisco-based Day One Biopharmaceuticals, the developer of pediatric cancer drugs, raised $130 million in a Series B deal led by RA Capital Management. (Timmerman Report coverage).

Boston-based Ensoma raised $70 million in a Series A financing to develop adenoviral vectors for cell therapies that can be made more accessible around the world. 5AM Ventures led. Ensoma also announced a partnership with Takeda Pharmaceuticals to work on in vivo gene therapies for up to five rare disease programs. (Timmerman Report coverage).

Menlo Park, Calif.-based PacBio, the developer of long-read DNA sequencing instruments and technology, raised $900 million in convertible debt from an affiliate of Softbank Group.

London-based Quell Therapeutics, a developer of T-regulatory cell therapies, expanded its Series A to $84 million.

New York and Stamford, Conn.-based Sema4 went public by combining with a Special Purpose Acquisition Company (SPAC) sponsored by Casdin Capital and Corvex Management. Sema4 describes itself as an “AI- and machine learning-driven patient-centered genomic and clinical data intelligence company.” The deal is expected to bring $793 million in total cash.

Seattle-based Nautilus Biotechnology, a proteomics company, merged into a SPAC sponsored by Perceptive Advisors, going public in a deal that’s fetching about $350 million. (TR coverage of Nautilus, June 2020).

New York-based Nuvation Bio went public via a merger with a SPAC sponsored by EcoR1 Capital. Nuvation, led by former Medivation CEO David Hung, is working on novel cancer drugs. It secured $646 million through the SPAC and related transactions, bringing its cash balance to $830 million.

Vancouver, BC-based Notch Therapeutics raised $85 million in a Series A financing to develop induced pluripotent stem cell-derived therapies for cancer. Allogene Therapeutics, Lumira Ventures, and CCRM Enterprises Holdings, EcoR1 Capital, Casdin Capital, Samsara BioCapital, and Amplitude Ventures participated.

Cambridge, Mass.-based KalVista Pharmaceuticals raised $193 million in a stock offering at $36 a share. It’s developing small molecules against hereditary angioedema and diabetic macular edema.

San Mateo, Calif.-based Sagimet Biosciences raised $80 million in a crossover financing. Its lead program is for NASH.

San Diego-based Pipeline Therapeutics said it raised $80 million in a Series C financing to advance its work on small molecules for neurodegeneration. New investors include Perceptive Advisors, Franklin Templeton, Casdin Capital, Samsara BioCapital, and Suvretta Capital.

Menlo Park, Calif. and Boston-based Adicet Bio raised $120 million in a stock offering. It’s working on allogeneic T cell therapies.

Lexington, Mass.-based Cyteir Therapeutics, the developer of synthetic lethal cancer drugs, raised an $80 million Series C financing. RA Capital Management led.

Baltimore, Maryland-based Personal Genome Diagnostics, a cancer genomic profiling company, raised $103 million in a Series C deal led by Cowen Healthcare Investments.

San Francisco-based Adagene, the developer of antibody drugs for cancer, raised $140 million in an IPO at $19 a share for American Depositary Shares.

San Carlos, Calif.-based BigHat Biosciences raised $19 million in a Series A financing to advance its AI-guided antibody design platform. A16Z led.

London-based Autolus, a T-cell therapy developer, raised $100 million in a stock offering.

Charlottesville, Virginia-based Hemoshear Therapeutics, the developer of treatments for rare metabolic disorders, raised $40 million in a Series A financing led by Suvretta Capital.

Indianapolis-based Apria Health, a home healthcare equipment and sleep apnea equipment provider, raised $150 million in an IPO at $20 a share.

Durham, NC-based Bioventus, the developer of orthobiologics for musculoskeletal conditions, to avoid elective surgeries, raised $104 million in an IPO at $13 a share.

New York-based Kadmon Holdings took on $200 million in debt.

Regulatory Action

Eli Lilly won FDA Emergency Use Authorization for the neutralizing antibody combination of bamlanivimab (LY-CoV555) and etesevimab (LY-CoV016) for COVID-19. It’s for mild-to-moderate COVID-19 patients at high risk of progression to severe disease. The FDA is also allowing a shorter infusion time of 16 or 21 minutes, compared with the previous 60 minutes, which ought to make the infusion more practical in a pressure-packed hospital environment where minutes count.

Regeneron said it won FDA clearance to market evinacumab-dgnb (Evkeeza), a monoclonal antibody directed at ANGPTL3, as a treatment for homozygous familial hypercholesterolemia – a rare genetic disease that results in elevated cholesterol levels and raises the risk of heart attack, stroke and death. A couple days earlier, Regeneron won FDA clearance for cemiplimab-rwlc (Libtayo), a PD-1 inhibitor for advanced basal cell carcinoma for patients who have previously gotten a hedgehog pathway inhibitor, or for whom that kind of medicine isn’t appropriate.

The FDA’s Oncologic Drugs Advisory Committee voted against approval of Merck’s PD-1 inhibitor pembrolizumab (Keytruda) as a neoadjuvant treatment for high-risk, early-stage triple-negative breast cancer in combination with chemotherapy after surgery. The data were premature, leaving the door open to a future reconsideration.

Personnel File

Cambridge, Mass.-based Surface Oncology promoted Robert Ross to president and CEO. He was previously chief medical officer. Current CEO Jeff Goater will remain chairman of the board.

South San Francisco-based Cortexyme, the developer of a treatment for Alzheimer’s disease, promoted Chris Lowe to chief operating officer and chief financial officer.

Cambridge, Mass.-based Synlogic named Lisa Kelly Croswell to its board of directors. She is senior vice president and chief human resources officer for Boston Medical Center Health System.

Cambridge, Mass.-based Dewpoint Therapeutics named Joel Sendek as its chief financial officer. He was previously CFO at Sema4.

San Francisco-based Lyell Immunopharma, a developer of T cell therapies for solid tumors, hired Charlie Newton as chief financial officer. He was previously with BofA Securities as a healthcare investment banker.

Vancouver, BC-based AbCellera, the antibody discovery company, promoted Ester Falconer to chief technology officer. She was previously head of R&D.

Eli Lilly said Anat Ashenazi has been promoted to chief financial officer, replacing Josh Smiley, after learning of “an inappropriate personal relationship between Mr. Smiley and an employee.”

Los Altos, Calif.-based Retrotope, a company working on degenerative diseases, said Rick Winningham has been named its new chairman of the board. He’s the chairman and CEO of Theravance Biopharma.

Gilead’s Kite Pharma cell therapy unit said Frank Neumann has joined as senior vice president and worldwide head of clinical development. He replaces Ken Takeshia, who is leaving the company at the end of February.

Cambridge, Mass.-based Gemini Therapeutics hired Brian Piekos as chief financial officer. The company is working on precision medicines for age-related macular degeneration.

Berkeley, Calif.-based Caribou Biosciences, a CRISPR genome editing company focused on CAR-T and CAR-NK cell engineering, hired Jason O’Byrne as chief financial officer. He was previously SVP of finance at Audentes Therapeutics.

UK-based Exscientia, an AI pharmatech company, named Elizabeth Crain to its board, along with Ben Taylor, the company’s chief financial officer.

Deals

Gilead Sciences and its partner, Belgium-based Galapagos NV, said they are shutting down the Phase III trials of ziritaxestat in patients with idiopathic pulmonary fibrosis. A Data Safety Monitoring Board recommended the trials be halted. The latest failure comes after another Gilead / Galapagos partnered program, filgotinib for rheumatoid arthritis, was rejected by the FDA. The partnership was originally valued at $5 billion in 2019.

Dallas-based Taysha Gene Therapies announced a pair of research collaborations with the Cleveland Clinic and University of Texas-Southwestern to further develop AAV vectors to carry mini-gene payloads for epilepsy and other CNS diseases. Terms weren’t disclosed.

AbbVie agreed to work with Berkeley, Calif.-based Caribou Biosciences on CRISPR-based genome editing programs for CAR-T cell therapies. Caribou is pocketing $40 million upfront.

8
Feb
2021

A Single Shot for Heart Disease: Sekar Kathiresan on The Long Run

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08 Feb 2021

Today’s guest on The Long Run is Sek Kathiresan.

Sek is the co-founder and CEO of Cambridge, Mass.-based Verve Therapeutics.

Sekar Kathiresan, co-founder and CEO, Verve Therapeutics

Verve is using genome editing technology in a bold fashion. Its idea is to develop a one-and-done shot that essentially would prevent cardiovascular disease in adults. Its plan is to start out with a group of patients at very high risk of cardiovascular disease, and potentially broaden the availability of the treatment later.

The treatment, which uses a newer-generation editing technique known as base editing, takes aim at a gene called PCSK9. Scientists have long for a long time that if you knock out the activity of this gene out, you can dramatically reduce LDL cholesterol and reduce the risk of heart attack, stroke and death from cardiovascular disease. Verve’s technology aspires to do this with a single shot.

The company has shown some pretty compelling data that this approach works in monkeys, and the effects are holding up after 6 months of follow-up.

Sek is a native of India, and immigrated to Pittsburgh in elementary school. He got a broad-based education there, including a bachelor’s degree in history, that he says served him well before he became a physician and scientist and entrepreneur. I think you’ll enjoy Sek’s story.

Now, before we get dive in…a word from the sponsor of The Long Run.

Synthego is a genome engineering company that enables the acceleration of life science research and development in the pursuit of improved human health. The company leverages machine learning, automation, and gene editing to build platforms for science at scale. With its foundations in engineering disciplines, the company’s platforms vertically integrate proprietary hardware, software, bioinformatics, chemistries, and molecular biology to advance life sciences from basic research through therapeutic development programs. By providing commercial and academic researchers, and therapeutic developers with unprecedented access to cutting-edge genome engineering products and services, Synthego is at the forefront of innovation in engineered biology.

To learn more, visit Synthego.com/timmerman

If you click there, you’ll learn about Synthego and help Timmerman Report along the way, so what’s not to like?

Now, please join me and Sek Kathiresan on The Long Run.

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