Please subscribe and tell your friends why it’s worthwhile. Quality journalism costs money. When you subscribe to Timmerman Report at $169 per year, you reward quality independent biotech reporting, and encourage more.
Dr. Larry Corey is an internationally renowned expert in virology, immunology, and vaccine development and a leader of the COVID-19 Prevention Network (CoVPN), which was formed by the National Institute of Allergy and Infectious Diseases at the U.S. National Institutes of Health to respond to the global pandemic. He is a Professor in the Vaccine and Infectious Disease Division at the Fred Hutchinson Cancer Research Center, past President and Director of Fred Hutch, and a Professor of Medicine and Virology at University of Washington.
On Dec. 2, the New England Journal of Medicine published an article coauthored by many prominent medical scientists, including physicians, who advocated for extending the time in which volunteers in the placebo group enrolled in the Pfizer and Moderna COVID-19 clinical trials should be followed.
Essentially, they are arguing that the study volunteers – people who sacrificed for the greater good to join the trials in the first place – should be prohibited from getting the actual vaccines, even after the vaccines become widely available under an EUA (Emergency Use Authorization), because there is “additional scientific information that can be learned.”
Of course, there are always new things we can learn from a clinical trial. But at some point, we know enough that the risk to persons not being given these markedly effective vaccines is greater than benefit that can be learned from withholding vaccination to these persons.
As a physician and a scientist, I recognize no one clinical trial ever solves all the issues needing to be addressed for public health. However, in making decisions when to offer vaccine to placebo participants in a trial in which high efficacy has been demonstrated, one needs to carefully balance scientific interests with withholding the benefits of vaccination to clinical trial participants themselves.
We must consider the real issue of fairness, and perceptions of fairness, at both the individual and community level.
So, let’s discuss these issues.
First, let’s look at what’s to be learned from keeping people on placebo while the EUA is being evaluated and the early days of market authorization, when supplies will be scarce.
Both the Moderna and Pfizer studies, which enrolled 30,000 and 43,000 volunteers, respectively, have reached their goal. Enough information on the number of pre-defined cases of COVID-19 required to define the vaccines’ effectiveness has been reached. More than 150 cases of COVID-19 were found among participants in each trial, and the vast majority of those cases were in people who were on placebo.
The analysis which compared the vaccine to the placebo occurred nearly two months earlier than projected. We got the answer quickly because people at high risk of infection enrolled swiftly in trials, and the widespread epidemic of COVID-19 across our country meant we didn’t have to wait long for cases to appear among volunteers.
The endpoints were well defined. Scientists asked, first and foremost, whether the vaccine reduced the chance of people getting symptomatic disease. The most important secondary endpoint looked at whether the vaccine reduced severe disease (hospitalization).
The results were simply spectacular—approximately 95% efficacy in the primary endpoint; 100% in the secondary for the Moderna vaccine. Even more compelling is that the results were remarkably similar between both the Pfizer and Moderna clinical trials, which both are testing messenger RNA based vaccines.
That’s a key validation for this emerging type of vaccine technology.
To date, the only reported death related to COVID-19 in the trials was in the Moderna trial and that was in the placebo group.
These data are clear and compelling. It’s hard to believe any more data are needed to show that the vaccines reduce the likelihood of developing moderate-to-severe COVID-19. By keeping people on placebo, we are only subjecting them to a higher risk of contracting severe COVID-19 disease. Are we trying to show that hospitalization and/or mortality is only 90% rather than 100%? I doubt that.
Everyone wants to know how long the vaccine can protect people. More time is required to answer that question. But by the time January rolls around and more vaccine doses become available, we will have close to six months of data from the start of the clinical trials in late July.
As I’ll explain below, there is a very good way to assess vaccine durability. One way to assess continued vaccine effectiveness against COVID-19 would be by vaccinating the placebo recipients in a crossover design.
This literally allows people who were on the placebo to “cross over” to get the real vaccine in a second phase of an ongoing study. The participants, and researchers, would still remain blinded as to what they are getting.
By continuing in this way, we could ensure that everyone in the study is getting vaccinated, while we’ll also get the chance to learn something new what the difference is between early versus late effects of vaccination. These data can be obtained by vaccinating the placebo recipients in early 2021, rather than simply waiting and watching them as more and more of them acquire COVID-19 disease in the trial.
Understandably, people want more safety data, and longer-term follow-up.
However, to assess the infrequent side effects of vaccination, it is not the vaccine cohort in the Phase III trials (about 21,500 for Pfizer and 15,000 for Moderna) that will discern this. Instead, this information will be gathered from the cohort of millions of people who receive the vaccine under the EUA and are then closely followed post-vaccination.
Respecting the thoughtfulness of the guidance documents from the FDA, regulators still want to know whether vaccination can result in enhanced disease. They also want to compare the background rate of severe pulmonary infection in placebo recipients. So far, there is no evidence in either trial of severe pulmonary disease from vaccination. In fact, it is quite the converse.
Between the two trials, there are between 40 to 50 cases of severe disease, and while the details of these cases are not known to me or the public (and such data are critical to unpack), it all says these pneumonias and hypoxemias are in placebo recipients.
Should we be more worried about a chance of enhanced disease from the vaccine – even though there’s no evidence to say that’s a real concern – or should we be more worried about exposing unvaccinated placebo recipients who self-identified as at-risk of COVID-19 infection?
In the Moderna trial, 30 (16%) of the 187 reported cases of COVID-19 were classified as severe over the four-month review period. Do we really want to see another 30 people get severe disease by watching them for four more months?
The question in my mind is what scientific justification is there to not vaccinate placebo recipients who had participated in the trial in which there was 95% efficacy and 100% effectiveness from hospitalization?
One can mitigate these numbers by saying only the healthy, so to speak, should be left alone. The tactic of differential handling of placebo recipients is, however, problematic. To take placebo recipients who fall under the category of EUA eligibility—in other words, medical care or first-line workers, nursing home personnel, those who are elderly or essential workers—and provide the vaccine because they are in group 1 of the EUA in their state, or nationally, is logical. But to deny their companions who joined them in being a clinical trial participant is quite problematic both from a social justice, fairness, and public perception point of view.
First, trial participants are essentially a community bonded together in a clinical trial. Thirty to forty thousand people were grouped together and placed under common scrutiny and rules.
We in clinical trials authenticate this bonding by calling them a study cohort. In this medical vernacular all are equal and each benefits from the other. The goal of the cohort is to achieve the study goal, which is not asking participants to get sick, but recognizing that in the course of human life some people will develop this disease.
Within the common community of trial participants, did the endpoints on the trial come from the medical workers or the non-medical workers? Was severe disease only in the elderly or in one group or the other? Does it matter? Does a medical worker who participated in the trial deserve vaccination more than the group of essential workers or someone who lived in the household of an essential worker who developed COVID-19 on the trial? Does either group feel good that the other is excluded when they entered the trial as equals in their own community? Differential access inserts nonequity among this “Band of Brothers and Sisters.” Are they being asked what they want? If so, would they say that they deserve the vaccine more than someone else in the trial? Did the medical worker who did not get infected sacrifice more than the bus driver who did or his friend who did not get infected?
Need I say more?
There are many dispassionate people who say we need and have a societal obligation to learn about the durability of the vaccine’s effectiveness. My colleagues at the CoVPN (COVID-19 Prevention Network) have, in fact, developed a proposal that would answer this quite effectively by vaccinating the placebo recipients, keeping the trial blinded, and following participants for signs of COVID-19 disease for the subsequent 18 months.
In this scenario, the people who got vaccine in the first place would get their blood drawn and be randomized to placebo injection. And those who initially got placebo would get their blood drawn and be injected with vaccine.
Let’s say we start in early January with the first dose, by the end of January after the second dose has been administered, everyone on the trial(s) would be vaccinated. Some could have been vaccinated last July 2020 at the start of the trials; some in January 2021.
By running the trial this way, we will be able to see the changes in durability in that six-month time difference, but everyone in the trials would then be vaccinated and therefore protected.
My colleagues and I feel this is best done blinded, but that is perhaps a lesser issue. The key point is that receipt of the vaccine is intended for all who originally signed up for the trials. Hopefully, most participants will want to continue with the study, and help answer this longer-term issue and continue to go to the clinic for COVID-19 testing and follow-up when they are ill.
With this proposed way forward, we can continue to learn about the efficacy and durability of the vaccine with the placebo group being vaccinated. It is medically difficult to justify keeping people on placebo when we don’t have absolute markers of risk — when we see that even some people ages 15 to 55 have been shown to experience severe disease, when we see increased hospitalization and death but have no clear marker of risk that can guide us as to who is at risk and who is not.
Keeping the vaccine from the very people who got us this far by participating in the trial, and who could benefit from it, is in my view, untenable. I, and almost all of my colleagues I surveyed who conducted these trials, honestly feel it is just not right.
Lastly, some people might argue that by vaccinating those in the placebo group, we would be taking vaccine away from others who are more deserving or who might have a higher risk. This is not the case. Vaccine vials labeled for research purposes are permanently labeled as such and are not those allocated to the general population.
If we’re going to adhere to the determinants of social justice; if we’re going to advocate for the underserved; if we’re going to declare the importance of altruism and act with principles of fairness, then we must treat all of the placebo recipients equally.
They themselves have become their own Band of Brothers…and Sisters, and we must honor their service to us all.
Dr. Larry Corey is an internationally renowned expert in virology, immunology, and vaccine development and a leader of the COVID-19 Prevention Network (CoVPN), which was formed by the National Institute of Allergy and Infectious Diseases at the U.S. National Institutes of Health to respond to the global pandemic. He is a Professor in the Vaccine and Infectious Disease Division at the Fred Hutchinson Cancer Research Center, past President and Director of Fred Hutch, and a Professor of Medicine and Virology at University of Washington.
E. Blair Clark-Schoeb, SVP of communications, Aruvant Sciences (Photo credit: Fisk Foto)
Our daughter celebrated her 14th birthday on Mar. 14. It’s an event none of us will forget.
Our family invited a few of her friends to join us for dinner in New York City to celebrate.
Scary headlines about the COVID-19 outbreak in New York were everywhere in the days leading up to her birthday. We had to stop and think. We debated whether to cancel this gathering. But we decided to move forward since we were just going to be with a small group.
Five days later, we came down with the Coronavirus. My husband Scott felt exhausted. I had a headache. When I felt a weird sensation of shortness of breath, like I had never felt before, I knew we needed to be tested.
Scott got tested on a Monday. A day later, we all knew. My mother and father, 77 and 84, respectively, were staying with us at our home in Summit, NJ. They immediately jumped in a car to go back to their house in Delaware. Thankfully, neither of them developed any symptoms.
For the next two weeks, my husband and I essentially stayed in bed. It was a struggle to stand up and walk to the bathroom. Our kids, staying downstairs or somewhere at arm’s length in the house, brought us food and plenty of liquids. They would leave food for us and walk back downstairs.
We felt terrible. The symptoms were typical — headache, fever, body aches, sore throat, GI issues. Although we had shortness of breath, we never needed to go on supplemental oxygen or felt so sick we needed to go to the hospital. We had what doctors call a “mild” case.
After two weeks, we started to feel a bit better. Around three weeks out, Scott was on the road back to normal. (Although he says he is not the same as before, he now is able to run over five miles these days).
By mid-April, I felt like I was recovering as well. Then, by Week 5, I started going backwards. I got tested again. Sure enough, it was positive.
Over the next month or so, I continued to feel OK. Not terrible, not great. Looking on the bright side, we decided to get out of the house. In May, we wanted to go see my parents in Delaware. The stay-at-home orders had lifted by then, and the first wave of cases in the pandemic appeared to be subsiding. We all got tested, and — good news! — we all tested negative.
We were ready to put our COVID-19 experience behind us.
The summer months were a roller coaster. One day I took my daughter to an outdoor lacrosse event. A fever came over me. At the event check-in table, they checked my temperature, and asked me the standard questions designed to prevent spread of the virus. I told the young lady that I still had occasional fevers even though I recently tested negative.
I managed to sit in the shade to cool down from the original 101 degrees Fahrenheit I had shown at check-in. (That, by the way, was the highest fever I have ever recorded, even when I was actively shedding detectable levels of the virus). They allowed me to stay to watch, from a distance. It was a hot day, and somewhat miserable.
Word got around at the event that I had a fever. A particularly pushy mom called the head of the lacrosse club to complain. Next thing I knew, I was getting chased out of the event.
The confusion about this virus makes people nutty. I sat in the parking lot, with tears rolling down my face. The proverbial scarlet letter, in my case a “C” on my chest, was humiliating. It was also upsetting that I still felt like crap months after I was first infected.
Like every other long hauler, I can paint the picture of what I was like before I got this lovely virus. I was a working mother of four who exercised almost every day. I alternated cardio and yoga days. You can check my Peloton app and see that I was active. I was a college athlete, playing squash at Harvard University. Staying fit and healthy is an important part of who I am.
Since being infected, I have attempted to exercise a few times. Most days, I feel like an elephant is sitting on me.
What I find particularly frustrating is the lack of understanding. One day, about four months into our COVID experience, my husband and I were out for a walk. (Essentially, he was dragging me outside to try and get me some exercise.) I remember it was a beautiful day that normally I would have relished being outside, but I really just wanted to go back to bed. We ran into a family practice doc in our neighborhood. Scott was telling her how I still have symptoms.
“It’s probably something else,” she said dismissively.
Other people, who aren’t physicians, freely offer their own speculative diagnoses. “Oh, maybe you have Lyme disease,” — I’ve heard that more than once.
The worst of these baseless conjectures came during a recent trip to an urgent care facility. I was there having my son tested after he had been exposed. I overheard the nurse telling the doctor that I am one of those “long haulers.”
The doctor replied, “This is today’s version of fibromyalgia.”
The condescending tone, and the implication that this illness was all just my overactive imagination, was beyond annoying. The inherent sexism and insensitivity that provider showed still burns me today.
I now feel like I can relate to what it must feel like for individuals who suffer from a rare disease with no cure. Everyone has an opinion and people aren’t sure how to interact with you.
I do not want pity from anyone. I hate being asked how I am feeling. Because it never changes, and my answer is always the same. At this point, I do not want to talk about it. But if we do talk about it, I certainly do not want to hear people’s uninformed theories on how maybe I have Lyme disease or something else.
I want to find something to help me recover, and I’d be happy, as a member of the biopharma community, to participate in some way to help advance scientific understanding of what’s going on with COVID-19 long haulers.
Recently, I had a visit with the University Pennsylvania Post-COVID-19 Care Center. We tried a round of steroids. That did nothing. They had me wear a cardiac halter for two weeks. I am waiting on the results. The one thing the team at Penn says appears to make a difference is physical therapy. So I’m giving that a try. At the same time, I am exploring Eastern medicine. I have done acupuncture. They prescribed me some herbs that made my heart race. I am open to anything.
The latest vaccine developments from Pfizer and Moderna thrill me. Some people see those results and imagine a return to normal, which in their mind means eating out once again.
I am just hopeful that the vaccine will help me feel even a little bit more like my former self. I do not want to feel like an old lady whose hips hurt, who can’t sleep through the night because of leg pain, who has shortness of breath.
I want to feel young again — like the 46-year-old that I was just nine months ago. A day without a headache would be nice, especially a day without the kinds of headaches that make me jump at loud noises or that knock me out in pain.
Often, I have heard people talk about just wanting to have the virus so they can get it out of the way and build up their immunity.
I have also heard how this is like the flu. I have never had a flu that has lasted for nine months. I suggest trying to avoid it and get vaccinated as soon as possible. My husband has antibodies and has even donated plasma. I can’t do that, because I don’t appear to have any antibodies. I am hopeful the vaccine will help me produce antibodies so I can feel better.
I have asked if I qualify for any of the current available treatments, and the answer is always no. We joke that we are going to do our own experiment and my husband will donate his plasma to me.
It would be so nice to get some clarity — a clear and confident bill of health that would allow me to plan for the future with confidence.
So much of this experience is about dealing with endless uncertainty and surprise.
Remember my daughter’s fateful 14th birthday dinner on Mar. 14? Turns out that wasn’t the exposure event we all thought it was. After a recent visit to a local furniture store, I discovered that in all likelihood, I did not even contract the virus at a restaurant in New York after all. The furniture store owner shared that she had been infected five days prior to when we had seen her in early March.
“It’s fine,” I told her, trying to coolly absorb what she had just said. “It’s been a mild case…”
E. Blair Clark-Schoeb is the senior vice president of communications at Aruvant Sciences a company developing gene therapies for rare diseases. She is a founding member of the Society of Healthcare Innovation. Twitter: @EBCS22
Luke Timmerman, founder & editor, Timmerman Report
Take two weeks between Frontpoints columns, and a lot of stuff happens.
On Monday Nov. 23, AstraZeneca presented a muddy picture from its Phase III clinical trial with a COVID-19 vaccine developed on adenovirus technology with Oxford University. It’s either delivering 90 percent efficacy or 62 percent efficacy, depending on the dose. So it’s either great or good, but we’re not entirely sure.
Importantly, it costs less than $3 per dose and it easy to manufacture at global scale. So there’s that. AZ might have to run a new trial to get a clear answer on safety and efficacy, and that will take time, and maybe be hard to conduct with actual approved vaccines on the market.
Even though AstraZeneca has done many things this year to undermine public trust in itself (no more private CEO calls to JPMorgan clients, and more transparency on adverse events, please), this generally effective third vaccine in line is still a positive development.
One week after AstraZeneca’s muddy but directionally positive announcement, Moderna released its extraordinary full results from its 30,000-volunteer Phase III trial with its COVID-19 vaccine candidate. A vaccine that’s 95 percent effective at preventing COVID-19, and that protected everyone from severe disease. Hot damn. That’s a home run.
Then there’s Pfizer. Like Moderna, they have lightning in a bottle — an awesomely 95 percent efficacious vaccine in their hands, thanks to years of innovative work by BioNtech. But it turns out Pfizer can only ship half of the 100 million doses they expected to be able to ship by the end of the year, according to the Wall Street Journal.
Messenger RNA, amazing technology that it is, has quite obviously never been manufactured at global scale before. We knew this, and should expect more hiccups in manufacturing and supply. When this happens, it’s not the end of the world.
Pfizer, I’m sure, will get this fixed and deliver the goods. The whole world is watching and counting on it. A manufacturing supply issue, even with intricate lipid nanoparticles at global scale, is challenging, but solvable. The hard part is figuring out whether you have a good vaccine at all. We do know that for Pfizer and Moderna.
The Emergency Use Authorization applications are on file with the FDA. The FDA vaccine advisory committee will consider Pfizer’s application on Dec. 10 and Moderna’s on Dec. 17.
Priorities are being set on who should get the vaccines first, and who will have to wait until supply can meet demand. See Larry Corey’s excellent summary of the vaccine scarcity challenge to come.
We have struggled with clear scientific communication about the pandemic this year — but this distribution plan is an opportunity to make that right. The stakes are as high as it gets now, when people are getting ready to get in line.
The story now is about doing everything possible to save lives through the next few months.
Most public health officials expect another surge of cases in weeks ahead, after a Thanksgiving weekend in which many Americans ignored advice and traveled to visit family.
The vaccines are on the way. Therapies that make a difference are here (Gilead, Regeneron, Lilly). Biotech has undoubtedly risen to the occasion.
But dark, dark days lay ahead. The death toll could exceed 450,000 by the end of February, according to the CDC director. We’ll all be wearing masks and physical distancing for many months into 2021, until we can get a critical mass of people vaccinated. Our country, suffering from a breakdown of trust in our fellow countrymen, is going to struggle to overcome the vaccine hesitancy that’s sadly become so common.
This weekend, I’m going to keep fingers crossed for Johnson & Johnson to nail its Phase III with a single-shot adenoviral vaccine. This one has been flying below the radar, but could provide a cheap, easy to manufacture, easy to distribute, effective vaccine option.
We need all the help we can get.
Biopharma, this is the time to show what it’s all about.
It’s one thing to be wrong. Happens to everyone. But then there’s dead wrong. John Ioannidis of Stanford University, in my view, is one of the people who fell into that unfortunate latter camp, in a very public way. He argued on Mar. 17 in STAT that public health authorities didn’t have enough data on COVID-19 to order the drastic non-pharmaceutical interventions of that time. Apparently, he missed a lot of the memos on how to respond to deadly pandemic viruses that spread at exponential speed (act fast, act bold, don’t wait for perfect data). Now, along comes Scientific American with a retrospective about the controversy. It only made things messier. See this doozy of an Editor’s Note.
Biogen agreed to pay Cambridge, Mass.-based Sage Therapeutics $1.525 billion upfront as part of a deal to co-develop and co-commercialize zuranolone for major depressive disorder and postpartum depression, as well as SAGE-324 for essential tremor. The companies will split expenses and profits / losses 50-50 in the US. Biogen bought shares in Sage at $104.14 a share – a 40 percent premium over the company’s prior 30-day trading average.
Merck & Co. divested its equity stake in Moderna, after seeing the stock surge 7-fold this year. Merck purchased a $50 million equity stake in the mRNA vaccine and therapeutics developer in January 2015.
Merck agreed to acquire Oncoimmune for $425 million upfront in cash. OncoImmune recently announced an interim analysis of a Phase 3 study with its CD24Fc directed treatment for patients with severe and critical COVID-19. Merck said that patients in the study had a 60 percent higher probability of improvement in clinical status. Details to come in a peer-reviewed medical journal.
Penn Medicine, home of gene therapy pioneer James Wilson, agreed to collaborate with Regeneron Pharmaceuticals on an AAV viral-vector based approach to prevention of COVID-19. The gene therapy approach quite obviously doesn’t scale like a dirt-cheap vaccine, but scientists suspect it will provide rapid onset of antibody production, and lasting protection – features that might be useful for immunocompromised groups of patients and healthcare workers.
Janssen Pharmaceuticals acquired the rights to an experimental gene therapy for severe age-related macular degeneration from Hemera Biosciences. Terms weren’t disclosed.
AbbVie agreed to pay $100 million upfront to South San Francisco-based Frontier Medicines as part of a collaboration to make small molecules against E3 ligases and other difficult targets for cancer and autoimmune disease.
Germany-based Merck KGaA agreed to pay $30 million upfront to New York-based Artios Pharma through a deal to work on precision cancer drugs focused on DNA damage repair mechanisms.
Palo Alto, Calif.-based Eiger Biopharmaceuticals sold a Priority Review Voucher to AbbVie for a $95 million lump sum payment. Eiger will split the proceeds 50-50 with The Progeria Research Foundation.
Rockville, MD-based Macrogenics collected a $25 million milestone payment from Incyte for its continuing collaborative work on an anti-PD-1 antibody. Separately, Macrogenics said it formed a partnership with Eversana to commercialize margetuximab, its Fc-optimized HER-2 directed antibody for cancer. The FDA deadline to complete its review of the drug candidate is coming up on Dec. 18.
South San Francisco-based Sunesis Pharmaceuticals agreed to merge with San Diego-based Viracta Therapeutics. The merged company will have $120 million in cash to work on viral-based cancers, including its lead program for Epstein-Barr virus-positive lymphomas.
Cambridge, Mass.-based Agios Pharmaceuticals introduced a program called Anemia ID, in which people suspected of having hereditary anemias can get genetic testing at no cost. This sort of program makes sense, because this is America, where most people live in fear of being gouged by the healthcare system. As a result, many people are thought to be suffering from undiagnosed hereditary anemias. Agios has reason to do rigorous outreach to this patient community (see below).
New York-based Schrodinger, the computational drug discovery company, struck a multi-target partnership with Bristol-Myers Squibb. Schrodinger is getting $55 million upfront. (See my in-depth interview with Schrodinger CEO Ramy Farid, Jan. 2019.)
Cambridge, Mass.-based Agios Pharmaceuticals met the primary endpoint in a pivotal study of mitapivat in adults with pyruvate kinase deficiency, a rare form of hereditary anemia, who are not regularly transfused. Regulatory filings are on deck for the US and EU in 2021.
New York-based Ovid Therapeutics failed in a Phase III clinical trial of its drug candidate for Angelman Syndrome. CEO Jeremy Levin didn’t try to sugarcoat or spin the results, and demonstrated some class on a hard day for the company. I have no doubt his team will learn and move on in a productive way.
San Diego and Boston-based Resilience, a company aiming to create an more advanced biologics manufacturing ecosystem in North America, came out of stealth mode with $800 million in committed capital. ARCH Venture Partners managing director Bob Nelsen is the founder and chairman, and ARCH co-led the $750 million Series B investment round with 8VC. GV and NEA also participated.
Medfield, Mass.-based Kinaset Therapeutics raised $40 million in a Series A financing to develop an inhalable pan-JAK inhibitor for severe asthma. 5AM Ventures and Atlas Venture co-led. (Timmerman Report coverage)
Burlingame, Calif.-based Genesis Therapeutics raised $52 million in a Series A financing to further develop its AI platform for predicting the potency and bioavailability of drug candidates. Rock Springs Capital led. (Timmerman Report coverage).
Burlingame, Calif.-based Tallac Therapeutics, a company leveraging the innate and adaptive immune system against cancer, raised $62 million in a Series A. VenBio, Morningside Venture, Lightstone Ventures, Matrix Partners China, and MRL Ventures Fund participated.
San Francisco-based Spotlight Therapeutics, a company developing non-viral gene editing therapeutics for direct in vivo editing of target genes, raised $30 million in a Series A financing. GV led.
Seattle and Vancouver, BC-based Achieve Life Sciences raised $15 million in an IPO to develop cytisinicline for smoking cessation and nicotine addiction.
Boston-based Karuna Therapeutics named David Wheadon to its board of directors, replacing Ed Harrigan. Wheadon, a psychiatrist and former AstraZeneca executive, also serves on Karuna’s scientific advisory board.
France-based Transgene, a viral immunotherapy cancer drug developer, named Hedi Ben Brahim as chairman and CEO. He replaces Philippe Archinard.
Chrissy Farr, health-tech reporter for CNBC in the San Francisco Bay Area, left to join OMERS Ventures as a principal, focused on health-tech investments. (See her Personal News column).
Arvin Yang joined Cambridge, Mass.-based Mersana Therapeutics as chief medical officer.
Shanghai-based Gannex, a unit of Ascletis Pharma dedicated to developing drugs for NASH, hired Melissa Palmer as chief medical officer. A hepatologist by training, Palmer was previously head of liver disease clinical development at Takeda Pharmaceuticals.
ASCO named a new chief medical officer. It’s Julie Gralow, professor of medical oncology and director of breast medical oncology at the University of Washington, Fred Hutchinson Cancer Research Center, and the Seattle Cancer Care Alliance.
Cambridge, Mass.-based Vedanta Biosciences, the developer of microbiome-based therapies, named Troy Ignelzi to its board of directors. He’s the chief financial officer of Karuna Therapeutics.
Ann Arbor, Mich.-based Penrose Therapeutics, a cancer drug developer, named Mark de Souza as CEO.
Scott Atlas resigned from his role advising the White House on coronavirus response.
Regeneron Pharmaceuticals won an Emergency Use Authorization from the FDA for its double-antibody cocktail, casirivimab and imdevimab, for mild to moderate COVID-19 in patients ages 12 and up (weighing at least 88 pounds). It’s not for patients who are hospitalized or on oxygen. Now the pressure is on to see how far and wide Regeneron can manufacture and distribute this important medicine, which in all likelihood will save a lot of lives. See Meg Tirrell’s Tweet on the supply timelines.
New York-based yMabs won FDA clearance to start selling naxitamab-gqgk (Danyelza) for neuroblastoma in kids age 1 and older. It’s given in combo with GM-CSF. The new drug, first developed at Memorial Sloan Kettering Cancer Center, is an antibody that targets ganglioside GD2.
Tarrytown, NY-based Regeneron Pharmaceuticals won EU clearance for dupilumab (Dupixent), as a treatment for eczema (atopic dermatitis) in children ages 6-11. Nearly three-fourths of kids with this condition saw a 75 percent or greater improvement in their disease extent and severity, compared with 26 percent who did that well on placebo in a pivotal study. As a coincidence, a friend asked me recently about new treatments for two kids with this condition. I was happy to be the bearer of good news, encouraging him to look into the data, and ask his kids’ doctor about it.
Palo Alto, Calif.-based Eiger Biopharmaceuticals won FDA approval for lonafarnib (Zokinvy) as a treatment for Hutchinson-Gilford Progeria Syndrome (HGPS or Progeria) and processing-deficient Progeroid Laminopathies (PL). These are ultra-rare diseases in which young kids are struck with premature aging.
Boston-based Rhythm Pharmaceuticals won FDA approval for setmelanotide (Imcivree) to treat chronic weight management in patients with certain genetic abnormalities confirmed by genetic testing.
Genentech won FDA approval for baloxavir marboxil (Xofluza) as a one-time treatment for influenza in people who have been exposed to an infected person. The approval is for patients ages 12 and up.
New York-based Kantaro Biosciences won FDA Emergency Use Authorization for an antibody test for COVID-19 that provides a quantitative readout on SARS-CoV-2 IgG antibodies.
This was a big deal for AI in drug discovery. Read some solid summaries of the results below.
Nobel laureate Frances Arnold of Caltech was impressed with the AlphaFold achievement, using AI to predict protein folding. But yes, there’s more.
Please subscribe and tell your friends why it’s worthwhile. Quality journalism costs money. When you subscribe to Timmerman Report at $169 per year, you reward quality independent biotech reporting, and encourage more.
Larry Corey, MD
The Pfizer and Moderna vaccines are likely to secure Emergency Use Authorizations (EUAs) from the FDA by Christmas.
These are amazing gifts of science. They also arrive with high expectations from a weary public, especially since the clinical trials of these mRNA vaccines indicate near-complete protection from severe disease.
These first two vaccines arrive at the most tumultuous time yet in the pandemic. We are seeing a surge of people being newly diagnosed with COVID-19 across the country. More than 90,000 people are now hospitalized, and our healthcare capacity is being stretched to the limits. The death rate, after months of decline, is now heading back up. The upheaval in our daily lives has been with us for nine solid months. This terrible set of circumstances should help push back against the vaccine hesitancy we have heard about from public opinion polls.
The desire for protection from this sinister virus ought to prevail, and lead to a successful national vaccination campaign in the months ahead.
The demand for a vaccine is clear. Unfortunately, however, the demand for these vaccines will markedly outstrip their supply, at least for the next four to five months. That seems like an eternity, especially with the rate of community spread we are now seeing. Vaccine scarcity will be in the news for the next several months until one or two other types of vaccines — beyond the initial batch of mRNA vaccines — can meet the safety and efficacy requirements for an EUA distribution and become widely available.
How did we get into this predicament — where science came up with a couple of exceptional vaccines, but we can’t deliver them to everyone?
The pace of vaccine development has been unbelievably quick; quicker than anyone ever expected. This remarkable scientific accomplishment has outstripped the existing manufacturing supply chain. The conceptual framework of a victory against the virus exists, but in order to proclaim victory, we need mass vaccine manufacturing distribution and uptake.
Making and distributing vaccines is a complex process. There are many steps, and each step requires detailed quality control measures to ensure that each and every vial contains the right dose and right substance. To think of it in a more personalized way, what goes into every arm — including yours and mine — needs to meet manufacturing standards. That is not an easy task and one that takes specialized facilities and highly trained personnel, more than currently exist.
It’s especially difficult when you recognize that mRNA vaccines are an altogether new type of platform for vaccine development. Never before have they been manufactured at the scale of millions — even billions — of doses.
When we look at the number of doses being made versus what we need, it’s a daunting thought. Between Pfizer and Moderna, we expect only 20 million doses to be available in December; 30 to 40 million in January and February; and 60 million per month in March and April. Even if we reach 200 million doses, that’s only 100 million people vaccinated at best — less than half the U.S. adult population.
As I’ll describe below, these doses may not even cover the populations we feel most need the vaccine.
So, who’s in line for this scarce resource and who decides who gets vaccinated first? We knew that vaccine scarcity would be inevitable since the beginning of the Operation Warp Speed (OWS) program. Independent groups and other experts have been evaluating all along how to define and develop an equitable national vaccine access strategy.
The National Academy of Medicine, or NAM, the country’s premier independent group of scientists and medical policy makers, was commissioned by the National Institutes of Health (NIH) and OWS to evaluate this issue.
NAM divided access to effective vaccines into four categories and estimated the number of people in each of these categories. As shown in the first phase (1A and 1B), they prioritized health care workers and the elderly in high-density communities, such as nursing homes, followed by the elderly that have comorbidities like autoimmune disease or diabetes, which raise their risk of severe COVID-19. The NAM panel classified essential workers as the second group.
In both phases of distribution, the panel emphasized that economically disadvantaged communities must be given equal access in all situations.
The second group of experts enlisted was the Advisory Committee on Immunization Practices (ACIP). That’s the CDC’s arm that makes recommendations for public health authorities around the country. The ACIP is the committee that has defined populations recommended for vaccination for over 50 years. Its advice is linked to public health–funded programs and defines insurance coverage for vaccines.
This group has been discussing who ought to get the COVID-19 vaccines first for many weeks in open meetings. It has, in its first rendition noted below, suggested that essential workers and first responders and medical personnel be in the first group.
Essential workers comprise group 1B, for example grocery store workers and meat packers. The third priority group (1C) is the elderly and those people with comorbidities. These 3 groups of people alone comprise well over 150 million people.
That all adds up to a lot of vulnerable people – more than we can vaccinate right away. Estimates are we’ll have enough vaccine supply for about 90 million people by April 2021.
How does one handle this scarcity when a case for vaccination exists for a very large segment of our adult population?
How does one choose between a healthy frontline essential worker with no comorbidities — someone with a lower risk of death but a higher chance of becoming exposed and infecting others — than an elderly person with comorbidities who has a much higher risk of death but could perhaps self-protect more by limiting exposure?
Is there a right answer to who gets vaccinated first or do we have to understand and practice principles of equity and patience until we have enough vaccine for everyone?
Both groups — the National Academy of Medicine and the ACIP — are advisory. They make recommendations to the public and executive branches of state governments. We have national-guidelines, but we don’t have a nationally controlled distribution plan.
Each state will make its own choice about allocation. We will see differences in distribution by locale. Understanding and communicating these differences to the public will be challenging. Some will call it confusing.
I’m sure there will be some disagreement, some of it loud and angry, about who should get the vaccine when.
One principle should be upheld; we should use every available vial. Nothing should get wasted.
The only real solution to overcome vaccine scarcity is, of course, to remove scarcity, which means that the remaining vaccines need to be made available. So, the AstraZeneca vaccine that you’ve heard about, which reports about 70% effectiveness; the single-shot Johnson & Johnson vaccine still being tested in a blinded pivotal clinical trial and others, will need to pass scientific muster and then be made widely available as well.
We are hopeful that answers on how these vaccines perform in the U.S. will be known by late January 2021 — less than two months from today.
For the time being, we’re going to have to get used to this issue of vaccine scarcity. However difficult it may be, we will have to be patient, and conscientious of broader societal needs, at least until more manufacturing capacity for the mRNA vaccines exists, or more likely, other types of vaccines become available for all of us.
Dr. Larry Corey is an internationally renowned expert in virology, immunology, and vaccine development and a leader of the COVID-19 Prevention Network (CoVPN), which was formed by the National Institute of Allergy and Infectious Diseases at the U.S. National Institutes of Health to respond to the global pandemic. He is a Professor of Medicine and Virology at University of Washington and a Professor in the Vaccine and Infectious Disease Division and past President and Director of Fred Hutchinson Cancer Research Center.
Frank Vinluan, correspondent, Timmerman Report
Though polymerase chain reaction, PCR, is regarded as the gold standard in molecular diagnostics, the COVID-19 pandemic has taken off some of the shine.
Under normal circumstances, samples processed in commercial diagnostic labs that run standard PCR machines can take hours to yield results. In a pandemic, with a surge in demand for tests, turnaround times are creeping upward and creating a shortage of PCR supplies.
Sometimes the results can take so long to come back that the test is rendered effectively meaningless.
CRISPR is among the technologies increasingly seen as a viable diagnostic alternative.
Better known for research underway in experimental gene-editing therapies, CRISPR’s ability to target and cut nucleic acids can also be used to precisely detect disease in biological samples.
Cambridge, Mass.-based Sherlock Biosciences was awarded the first emergency use authorization (EUA) for a CRISPR-based COVID-19 lab test. CEO Rahul Dhanda says the technology produces results that are as accurate as PCR, but that arrive far more quickly – sometimes in minutes.
Now Sherlock and other companies are trying to take CRISPR’s diagnostic capabilities beyond the controlled environment of commercial labs, and into the place where many people are stuck.
Rahul Dhanda, co-founder and CEO, Sherlock Biosciences
“I think of this as an evolution toward a molecular diagnostic that can be done at home,” Dhanda said.
Both PCR and CRISPR diagnostics seek out a tiny amount of genetic material and make it detectable for disease diagnosis, but they accomplish that in different ways. PCR, a decades-old technique, works only on DNA. In order to detect SARS-CoV-2, the virus’s RNA must be reverse transcribed to DNA. That DNA is then amplified – turned into millions of detectable copies. In addition to taking time, some steps of the process must be done at precise temperatures, a task that’s automated by an instrument.
In both therapeutic and diagnostic applications, CRISPR molecules find nucleic acids under the guidance of RNA that have been programmed to match a target genetic sequence. The CRISPR molecule includes a Cas enzyme that cuts nucleic acids. The most commonly used enzyme in therapeutic applications is Cas9. In recent years, scientists have discovered other Cas enzymes that are thought to be better suited for diagnostics. Cas12 cuts DNA while Cas13 cuts RNA, for instance.
Like PCR, a CRISPR diagnostic needs to reverse transcribe viral RNA to DNA, which is then amplified. But a CRISPR diagnostic does its work in fewer steps and at room temperature, Dhanda said. When a CRISPR molecule encounters its target, the Cas enzyme is activated to start cutting the nucleic acid.
But the cutting doesn’t stop there. Once activated, these enzymes also cut loose a reporting molecule that’s added to the sample. The signal from this reporter molecule is what lab equipment can read as a positive sign of the disease. Sherlock’s CRISPR diagnostic yields results in about an hour, compared with six hours for standard PCR, Dhanda says. The new technology is adaptable, and can be used to develop assays for any disease with a DNA or RNA signature, he adds.
The market appetite for new types of diagnostic tests has never been greater. Since the World Health Organization’s pandemic declaration in March, the FDA has granted emergency authorizations to nearly 200 molecular diagnostic products.
Diagnostic development typically surges in response to disease outbreaks, said Gerald Kost, emeritus professor of pathology and laboratory medicine at the University of California, Davis. The Ebola outbreak six years ago sparked a similar, but smaller wave of research. Though the disease’s spread in West Africa showed the need for more point-of-care diagnostics, the number of U.S cases was small. Consequently, companies did not see enough of a market to develop tests in anticipation of a future pandemic, Kost said.
That’s not to say there haven’t been advances spurred by the 2014 Ebola outbreak.
PCR testing has already moved beyond labs to patient settings. As an example, Kost points to the cobas Liat, a Roche Diagnostics instrument that was granted FDA clearance in 2014 for diagnosing streptococcus A. Roche has since added other diseases to the instrument’s testing menu, including an EUA in September for COVID-19 and influenza. Hospitals that had previously purchased the devices can also run COVID-19 tests on them.
Consumers clearly aren’t going to spend $16,000 to buy a Liat, Kost said. That creates an opening in the market for a high-accuracy / high-speed / low-cost alternative.
Kost added that while CRISPR’s potential for diagnostics has been discussed for years, the challenge for the technology in point-of-care applications is designing a device that can conduct these tests outside of a lab.
The goal for developers of home-based CRISPR diagnostics is a test that is as affordable and accessible as pregnancy tests available in pharmacies. Many of these tests show their results on a paper strip whose color change indicates the presence of a protein.
San Francisco and Buenos Aires-based Caspr Biotech is taking a similar approach. It’s developing a small, portable CRISPR test for use in places were PCR testing is unavailable. In a March preprint, scientists from Caspr and the University of Buenos Aires described how the technology detected a genetic signal on a paper strip, which the authors said demonstrates that this system could be made into a portable test.
However, developing a CRISPR diagnostic is not as simple as overlaying CRISPR technology on a pregnancy test platform, said Janice Chen, co-founder and chief technology officer of South San Francisco-based Mammoth Biosciences. Such consumer tests aren’t molecular diagnostics, which require more complicated preparation of samples for analysis. The challenge for a CRISPR-based home testing kit is miniaturizing the capabilities of a molecular lab into a handheld device.
Janice Chen, co-founder and chief technology officer, Mammoth Biosciences
“It has to be simple enough for any user to run the test, but the accuracy has to match what one would expect in a lab molecular test, Chen said.
Mammoth, co-founded by UC Berkeley CRISPR pioneer Jennifer Doudna, is developing a handheld COVID diagnostic through a partnership with GlaxoSmithKline Consumer Healthcare. The companies aim to offer a disposable test capable of identifying viral RNA from a nasal swab sample in about 20 minutes.
In parallel, the startup is also developing a lab-based CRISPR test for the SARS-CoV-2 virus. That research is supported by the National Institutes of Health’s RADx initiative, which aims to speed up the development and commercialization of new COVID-19 diagnostics. Chen said it’s too soon to say when the Mammoth/GSK home test could be ready for EUA consideration. In August, the FDA awarded Mammoth’s reagent kit emergency authorization for lab use.
Ann DeWitt, partner at The Engine, a venture capital firm spun out of MIT that invests in “tough tech,” said at-home molecular diagnostics fit that definition. She said The Engine defines “tough tech” as transformative technology addressing the world’s biggest problems. A point-of-care CRISPR diagnostic would ease the testing burden of the current pandemic and give hospitals and labs another tool to prepare for the next one, said DeWitt, whose firm has invested in diagnostics startups but has no connections to any CRISPR companies.
She said that startups aiming to develop a CRISPR diagnostic for home use must design a product that doesn’t require expertise to perform the test and read the results.
“If you’re using equipment that isn’t readily available in a home, a centrifuge for example, a lot of that product development is going to have to be rethought,” DeWitt said.
So far, one at-home molecular diagnostic has received an EUA for COVID, and it’s not based on either PCR or CRISPR. The Lucira Health product tests for the genetic signs of the novel coronavirus by analyzing a sample from a nasal swab. The swab is swirled in a vial, which is then placed in the Lucira device. The instrument reverse transcribes viral RNA to DNA and employs a technique called loop-mediated isothermal amplification (LAMP) to amplify the genetic material from the virus. (The lab kits of Sherlock and Mammoth also use LAMP for amplification.)
Lucira’s diagnostic produces test results in about 30 minutes. Results are shown as a color change on an LED display. The test requires a prescription from a healthcare provider, which some critics have said will limit the sort of widespread adoption necessary to make at-home testing most useful.
Whether a CRISPR test can be engineered into an at-home test that can be self-ordered and self-administered is an open question. CRISPR’s next move closer to patients is more likely to be a product for health care settings.
Sherlock’s research includes a diagnostic that pairs its CRISPR technology with an FDA-cleared testing platform from Boston-based binx health. That COVID test would process a sample on a single-use cartridge that’s analyzed by a benchtop instrument. Dhanda said that this cartridge test could yield results in about 20 minutes. It does not yet have emergency authorization from the FDA.
Sherlock still aims to address the home market, but not with CRISPR — at least not yet. The company is developing yet another test that programs a synthetic gene to generate a signal in the presence of its target. Dhanda says this technology, dubbed INSPECTR, doesn’t require lab equipment, can be done at room temperature, and yields results just as sensitive as PCR. Those results would show up on a detection strip, similar to a home pregnancy test.
Sherlock, which has yet to publish data about its CRISPR or synthetic biology diagnostics, aims to have a COVID INSPECTR test ready to submit to the FDA for a potential EUA decision in the first half of 2021.
Kost, the UC Davis professor, said the most promising COVID diagnostics will be useful in a post-pandemic world. The 1918 flu pandemic petered out after four years but vaccinations could end COVID-19 in half that time, he said.
Gerald Kost
If vaccination campaigns succeed and demand for COVID-19 testing dries up, companies will have to find new markets for the technologies they’ve developed in this pressure-cooker of a year.
Kost suggested that a diagnostic company could strike up a contract with an airline that wants to test passengers before departures, or perhaps with businesses that require regular employee screening.
Even better would be further work to convert a single test into something that screens for multiple pathogens. Kost points to Sunnyvale, Calif.-based Cepheid, whose benchtop PCR system, GeneXpert, has been used for rapid diagnosis of infectious diseases such as tuberculosis and Ebola.
In October, GeneXpert was awarded FDA emergency authorization for a test that diagnoses COVID, influenza A and B, and respiratory syncytial virus from a single patient sample. Results for all four pathogens are ready in less than 40 minutes.
That test is particularly useful because people with those diseases often display similar symptoms, and it’s cumbersome, time-consuming and more expensive for healthcare providers or individuals to provide multiple samples to run through multiple tests.
“That’s the kind of change we need to see in technology – tech that is adaptable to multiplexing, that allows us to look not just at one disease but several,” Kost said.
Lisa Suennen
I really miss waiters.
I was recently talking, via the mixed blessing of Zoom, with the very awesome members of a women’s group to which I belong.
Our full group of about 35 meets once a year. Normally, we do so in person, at a spa, where food is brought to us by actual waiters.
Remember waiters? Man, I miss waiters.
But despite talking via Zoom and definitely not in the company of waiters, the plan for this year was still the same as always: each of us in virtual attendance would get 15-20 minutes to talk about whatever we want. It’s wonderful.
You can solicit advice. You can ask for silence. You can open up about your deepest moments of loss and sadness or your small and large victories. You can brag about your family or complain about them. You can share your work challenges or talk about your excitement about opportunities ahead. And you can whine, bitch, moan and lament to your heart’s content and get unqualified and loving support from the best pit crew ever.
When it was my turn to pour my guts out, I tried to describe the silver linings of the current world order (or at least my slice of it). There are many, and I reminded myself of them this past Thanksgiving weekend. I have much for which to be thankful.
But I also ended up unloading on my friends about all of the things that Just. Totally. Suck.
Normally, I’m not one to unload a double-barreled shotgun of crap on other people. But I was struck by the tidal wave of positive reinforcement I received while wallowing in suckage, and particularly the sense that this suckativity is shared at a visceral level by so many who look like they have their acts totally together. It was kind of cathartic for me, and apparently for others in the group, too.
I left that Zoom call encouraged to write about it, because I realized these are shared experiences, not my own personal hell.
So lucky you, welcome to my “Life Sucks the Big One” blog post.
We all know the toll this pandemic has taken on our families, friends and selves. The number of deaths or terrible illnesses experienced is beyond words.
And yet, for those of us fortunate enough to have avoided the virus, there is tremendous guilt. Complaining too much about how we are feeling, mentally and emotionally, during this shitstorm of a year feels petty and wrong.
You don’t have to look around long to see extreme suffering of others.
And yet, the seemingly small miseries of those of us with COVID survivor’s guilt do exist. They are real (if not spectacular — congrats if you get that joke).
The mental health of many is taking a toll and I’ll admit to being one of those doling out quarters at this particular toll bridge. I have definitely been down-beat more than usual. I can cry at the slightest thing. Sentimental toilet paper commercial? Here come the tears. I run out of ice cream, here come the water works. God help me if I read a story in the newspaper that reminds me how much crap is going on in the real world – it makes me try to burrow under the couch (so THAT’s where all the dog toys are).
The only upside is that I gave up makeup sometime in April and thus I am saving money on all the mascara that would otherwise now be streaming down my cheeks.
I have a constant sense of fear and paranoia about getting sick. I’m annoyed that a few of my friends have exerted some peer pressure about getting together in ways that just don’t seem optimal under the COVID circumstances.
I feel bad saying No, but would feel stupid saying Yes. Few would mistake me for an introvert, yet I am doing my best impression of one and it is getting more and more natural. Sometimes I wonder if I’m turning into a hermit. That also sucks.
I miss traveling and seeing people. It is scary to think that the huge network I have built over a lifetime is somehow moving ahead without me. When I’m being sane, which occurs every other Thursday from 7:32 am to 7:36 am (now the best time to reach me) I realize that there is so little going on out there that my fear of being left behind is unlikely to translate in reality. Even so, it gnaws at me, driving me at moments into of a crazy kind of FOMO. For those who don’t use this acronym several times a day, Fear of Missing Out is an occupational hazard for venture capitalists and entrepreneurs in the best of times.
Turns out, I’m not the only one feeling the FOMO dialed up to 11. I was fascinated to learn that this is also at the top of the list of worries for so many of my women’s group friends. COVID stress and anxiety is apparently triggering an epidemic level of insecurity and low self-esteem that would be wholly unexpected among this crew of accomplished over-achievers.
One of the things I worry about (and worry about how I’m worrying about it) is how I have lost, at least for now, some of the silly but real ways I used to define myself in the world.
Those who know me even a little bit know how much I love shoes. Yet I haven’t bought a pair of shoes in about 8 months. This has to be some kind of personal record. I suspect that any economic woes being experienced by Manolo Blahnik and the Nordstrom shoe department are directly traceable to me and my absence.
Furthermore, I always ran around in the world with elaborately painted toenails. Again, hardly a life crisis to have naked toenails when so many people I know are truly suffering, but it was a mode of accessorizing that kicked off a lot of fun conversations and a means of self-expression that I have really enjoyed for well over a decade.
That’s actually the crux of this – the lack of access to things that “bring me joy,” as Marie Kondo would say. If a person is the sum total of their triumphs and tribulations (and toes), and there are few triumphs (because they are hard to achieve when locked up like Rapunzel after a big haircut), and too many tribulations – then you start to feel like a pale version of your former self. Certainly, it’s hard to feel like you’re at the top of your game.
And, speaking of games, up until March I also played squash 2-3 times a week for most of the last 16+ years; that is, alas, also gone for now. Not only does squash make for good aerobic exercise, it used to be the primary way I removed stress from my system. Smashing things repeatedly while swearing, it turns out, is excellent therapy.
My gym in Northern California is remarkably still open. They keep calling me to come back. Part of me wants to go back. But given that what I would do there is lock myself into a small, fully enclosed room with little circulating air and with another sweaty person expelling spit through aggressive swearing, I’m thinking…probably not such a great idea.
Alas, leisurely walks through the park just don’t cut it for my fitness routine. It turns out that if you stomp aggressively down the street while swearing, people stare and dial 911.
My coping skills, as a result of my sloth-like fitness routine, are less than stellar. On the plus side, my over-reaction time is dropping so fast I could win some sort of panic contest. Everything that goes wrong feels like a disaster. Spilling water from a glass could trigger an international incident.
Like everyone else in America trying to soothe rattled nerves, we got a puppy. The little critter is cute as can be and needs a ton of attention; so, naturally, any extra time available is time I spend feeling guilty about how little time I am spending with the cat. Look, I’m Jewish, so anxiety comes with the bloodline, but this is getting ridiculous.
So why am I telling you all this? It is not for sympathy. It is for connection and so we can all share a little self-validation.
The feelings of guilt, insecurity, isolation, anxiety, loss of self-expression – they seem to be universal constants right now. Most of us are feeling stressed, anxious, a little lonely, a little lost and very stir-crazy. The idea that we may have months or even another year of this to go is daunting. We have gone from talking about testing 103% of the time to talking about vaccination timelines morning, noon and night. Yes, there was a momentary election conversation interlude (thank God that’s over with), but otherwise it’s all COVID all the time.
For many people it’s really tough to share feelings, no matter what the circumstances. It is especially tough when those feelings seem shallow as compared to the true depths of despair that so many families have faced. But as one of my friends pointed out, misery doesn’t have to be a zero-sum game – we are all entitled to our feelings and fears and to having those validated. In fact, if we don’t let the feelings out, we are going to start seeing people spontaneously combust in the grocery store.
Some of us are self-medicating in ways that we normally never would. By the way, if you’re at the grocery store buying chocolate and can’t find any, it’s because I ate it all.
But seriously, alcohol and drug consumption is booming (Nielsen reported a 54 percent year over year increase in alcohol sales during the initial pandemic surge in mid-March). That is terrifying considering how that alcohol consumption had been steadily rising for 25 years, even before the pandemic. We really don’t know what damage we will all be left with psychologically, physically, and culturally after the pandemic passes.
So, again, it’s essential to find ways to express your feelings, to feel validated for having them and to know you are not alone. We may have a country that is quite divided, but bottom line, we are actually all in this together. Never has it been clearer that we are as connected as the bones in that old song – our knee bones are connected to our leg bones and so on. There is no getting around it.
So, here’s my request: ask a friend or acquaintance how they are doing and really hear them out. Listen to their litany of woe and do not judge. Validate. One person’s little problems are another person’s crisis. Your job is to empathize and support. Acknowledge. Be there. Be attentive. Err on the side of loving kindness. And when that is done, be kind to yourself and seek the reciprocity you deserve. We will get past this if we help each other through.
Please subscribe and tell your friends why it’s worthwhile. Quality journalism costs money. When you subscribe to Timmerman Report at $169 per year, you reward quality independent biotech reporting, and encourage more.
Mike Huckman
I am not brave.
Once, I passed out after a routine blood draw for a diagnostic test. Ever since that first scary and embarrassing episode at a LabCorp location in Manhattan several years ago, the act of giving a blood sample, no matter how small, has been a source of anxiety.
Will I break out in a cold sweat? Feel lightheaded? Collapse on the floor?
Fearing a repeat performance, I get myself tied up in knots. It also should be evident by now that I’m not fond of needles. I’m 58 years old, but I still look away like a squeamish kid whenever I get a flu shot or some other routine vaccination. Just make it quick and tell me when it’s over.
All of the above makes me an unlikely candidate for a COVID-19 vaccine clinical trial. But a few months ago, when I read in my local newspaper that vaccine developers Pfizer and Moderna needed more volunteers, I decided to participate—or at least see if I could enroll in one of the studies.
My first call happened to be to a Wilmington, North Carolina clinic working on the Pfizer test. It is here that I want to make a disclosure. Pfizer is a client of W2O Group, the communications agency where I work. One has nothing to do with the other. I volunteered like the tens of thousands of others who want to support the global vaccine research and development effort.
The coordinator at the local study site called me back pretty quickly. How about 7 am the very next day? I was in.
First shot.
There was some trepidation. More than once, I considered backing out.
But I kept the appointment. I walked in the door at the clinic, and signed the required consent agreement. I sat down, took a deep breath, and looked away when the nurse swabbed my arm with antiseptic before taking a routine blood draw.
Everything was OK, so far. Next, they stuck the swab up my nose to collect a sample to look for signs of the SARS-CoV-2 virus.
Then, I waited. About 45 minutes later — time for the experimental vaccine to thaw out from deep freeze — I got either the experimental vaccine or the saltwater dummy vaccine. A nurse came in to give the mystery injection.
After 30 minutes of observation by a staffer, seeing no serious adverse effects, I was sent home.
Three weeks later, I returned on schedule for the second injection. Same deal as before. One week after that, they asked that I return for a follow-up blood draw.
Second shot.
Participants in this clinical trial are not told about the blood sample test results, in keeping with the stringent study protocol. I have not gotten an antibody test on my own since receiving the second shot, and still don’t know if I have developed neutralizing antibodies to SARS-CoV-2.
Here’s what I do know. Several hours after receiving each injection, I experienced what I would refer to as a hot flash lasting a few minutes or so. There was a touch of nausea, too—but only after the first shot.
Both sensations passed and never came back. As Pfizer seeks an Emergency Use Authorization from the FDA, who got what remains a secret to those of us in this more than 43,000-person study. All we know is that half of the participants received the real vaccine and half were given the placebo.
Did I experience a so-called placebo effect where people who receive the dummy version of a treatment or vaccine trick themselves into thinking they’re on the real thing or did I have a reaction to the genuine vaccine, one that might even suggest my immune system was being effectively primed against the virus?
I am not a doctor or a vaccine expert, and I will not hazard a guess. I have to wait for Pfizer to “unblind” the study to find out for sure.
Every Friday since receiving the first shot, I also have to go into a clinical trial app and input whether I have or had any COVID-19 symptoms. Thankfully my answer, so far, has been no.
After each clinic visit, I get $119 loaded onto a special debit card the office provides. I am not doing this for the pocket money. I am doing it because I have trust and faith in science and in the scientists—the people—who prove or disprove that science.
For nearly 10 years, I covered the biopharmaceutical industry as an on-air reporter at the business cable network, CNBC. I regularly interviewed scientists, researchers, therapeutics developers, and corporate executives.
For the past 10 years, since transitioning to become a communications consultant, I have worked alongside dozens of biopharmaceutical company scientists, academic researchers and clinicians, helping them talk about their passion, ingenuity, and data.
They are the most intelligent, disciplined, rigorous, uncompromising, fact-driven people I have ever met.
If I received the vaccine, I’ll have some peace of mind. But I will continue to wear a mask, wash my hands, and maintain physical distance at least until the public health experts say we can get back to normal.
If I was injected with the saline solution, I will wait my turn to receive a vaccine, if or when it’s approved by the FDA. Since I’m not in a high-risk group, an essential worker or on the front lines, that could be a while.
People tell me on social media that I am brave and courageous for volunteering to be in a COVID-19 vaccine study. I am neither. I’m just a needle-phobic guy who wants to play a very small role in getting us out of this hell. Each of us has a role to play, large or small.
From 2000-2010, Mike Huckman was CNBC’s pharmaceuticals reporter. He is currently the Global Practice Leader, Executive Communications at W2O Group.
Carolyn Ng, managing director, Vertex Ventures HC
So there it was, hanging in the closet.
My carefully chosen bridal gown, with its lace in a delicate shade of ivory. Beside it was my bridal veil, featherlight, translucent, and freshly purchased just the day before the wedding.
When Anna, my girlfriend, gingerly pinned it on my head, I heard the words of my mother sounding in my head. She had once told me, sweet and soft, “Don’t forget your veil. There is nothing more bridal and more beautiful than a bridal veil.”
My heart sank for a moment. Because I know my mother would have given anything to see me walk down the aisle as a bride, veil and all.
Yet I had to tell her, no, mum, Matt and I are getting married, but you will not be able to attend in person. We won’t allow you, or other family members to attend.
It was a difficult conversation, and 2020 was full of all the most difficult conversations, for us as individuals, as a family, as a country.
As the years pass, and as Matt and I grow old together, what would we want our wedding day to be remembered for? I want it to be centered on us and our love. But for it to be about us and our love, it has to, by my definition, naturally include all the important people around us in our lives. Friends and family who have shaped us, challenged us, cared for us, and molded Matt and I to be who we are today, choosing each other as life partners.
There is no celebration of “us,” if it does not include “them.”
And that is why this COVID-19 pandemic has taken such a toll on us all. It is not only the headlines-grabbing devastation that has robbed the US of more than 250,000 lives and over 20 million jobs. What is also draining and painful is the multitude of mundane daily decisions we have all been deliberating over and over in the past nine months, calculating the risks of a deadly virus exposure against the very human need for togetherness.
After all, it is this need for social interactions and physical closeness that define us all as human beings.
Weddings present a special conundrum in the pandemic. We got engaged in November 2019, and were originally planning to be married in July of 2020.
How did we change plans? Well, one thing for sure, we certainly did NOT want our parents and aunts and uncles and any of our lovely guests catching the SARS-CoV-2 virus from our wedding. Given our professions — we are both healthcare venture capitalists — we have front row access to scientific and clinical knowledge pertaining to the SARS-CoV-2 virus and what it is doing to public health and the economy.
They say with knowledge comes power. And I would add, the power to act responsibly.
So, some tears were shed. Some hearts broken.
But eventually all of our parents and family members agreed to stay in the safety of their respective homes and not fly to attend our wedding in person. Instead of the original 150-person guest list, we had a couple of our dearest local friends witness (and operate the Zoom for) our wedding, which they did with aplomb. Our wedding was held outdoors in a beautiful private garden, and we also made sure that all of us involved had a negative COVID-19 test within that week of our wedding. Face masks were given to our in-person guests as wedding favors.
It was not completely risk-free. We recognized that. But we could conscientiously say that utmost effort was taken to reduce COVID-19 risk to as low as possible, while allowing for a figment of magic to still be conjured for our special day.
I would like to think there was still magic in the air, and that all of our Zoom wedding guests could feel it. It was as magical as a video technology like Zoom could allow you to feel. We had a couple of technical glitches of course, as any respectable wedding would have. But save for a few hangovers, we were immensely fortunate that our beautiful wedding concluded with no real sequelae. I mean the COVID-19 types.
Not every wedding couple has been as lucky as we were. Some took bigger risks and faced dire and deadly consequences. Barely two weeks after our nuptials, I read with a heavy heart an article authored by the CDC on the wedding in August which turned into a nightmarish super-spreader event.
In that case, the couple from California held a 55-person indoor wedding in rural Maine. It was reported that almost none of the guests wore masks indoors, nor did they maintain physical distancing of at least 6 feet apart. At least 177 infection cases were linked to this single event, including outbreaks at a long-term care facility and a correctional facility, which were 100 and 200 miles away from the wedding venue!
Tragically, seven people died from COVID-19 as a result of this wedding.
And even more tragically, perhaps, none of those who died were even in attendance. They were all secondary and tertiary infection cases. The virus has won the R0 game.
To have your wedding be the cause of seven innocent people’s deaths? I cannot imagine the pain and anguish of the newlywed couple. That burden of guilt and despair that will forever lace the memory of the day they tied the knot. An event of negligence, a lifetime of regrets.
Regrets. We desperately try to avoid them. Every critical decision, step, action that we make in our lives, we are propelled to take the ones that will render the highest probability of “no regrets”.
In a pandemic, these decisions that would give us “no regrets” become way more difficult to make.
Pre-COVID-19, we had been talking fondly, for the longest time, of a visit to Kentucky. There, we would visit Matt’s grandmother. He calls her “Mommom” in the most endearing way, and I hear lovely stories of how he grew up spending the most wonderful time with her when she was still living in Philadelphia.
And then the pandemic hit and turned the world upside down, killing people and infecting many more. We put our Kentucky trip plans on ice. We could visit her in 2021, we said. Vaccines would be coming and we would be visiting her safely, we said. We would also do a bourbon tasting tour, we said.
Mommom will love you so much when she meets you, Matt said.
Mommom, 91, passed away this past weekend.
We never made it out to Kentucky. Matt did not get to say his good-bye to his closest grandmother. I never got to meet this incredible woman who was part of what made Matt who he is today.
Regrets and also sorrow. How desperately we avoid them. Our scientist/doctor selves keep reminding us that it was a prudent decision we made not flying over this year and introducing additional virus risk to Mommom who was obviously in a high-risk age group. But nothing can stop our human hearts from bleeding.
We can’t help but ask ourselves, “Could we have done this?” or “Could we have done that?” to see her one last time?
We felt the tug again to see family this Thanksgiving. But seeing the surge to more than 180,000 cases a day in the US, we decided to cancel our flights from San Francisco to Philadelphia. It is cold this time of the year in Philly, rendering outdoor dining impractical and social distancing difficult. Flying also introduces additional risks to our parents and we are not confident how we can mitigate them without quarantines and testing. In short, we will not be tasting Matt’s mum’s famous 25-pound turkey this year.
So with Thanksgiving and Christmas around the corner, how would you like this year’s special family holidays to be remembered?
There are trade-offs in every arrangement we make in the midst of a global pandemic. But may we choose actions that we may live with for years to come even post-pandemic, conscientiously, responsibly and lovingly. And without regrets, if we are so blessed.
Carolyn Ng and Matt McAviney at their wedding. (Credit: iPhone photography by Kevin Dai, Vivo Capital)
Written, in loving tribute, to my husband Matt McAviney’s grandmother “Mommom”, who left us this past weekend peacefully. I wish I have had the chance to get to know you.
Today’s guest on The Long Run is Andrew Farnum.
Andrew is the CEO of Seattle-based Variant Bio.
Andrew Farnum, CEO, Variant Bio
Variant Bio is a startup seeking to discover new drugs, by finding gene variants in rare ethnic groups. It’s especially interested in what can be learned by sequencing exceptional groups of people in countries where there hasn’t been much sequencing.
This is a company seeking to bring the benefits of an exciting new technology to a wider group of traditionally underserved people. If Variant is successful, it could help improve health and wellbeing in these rare ethnic groups, as well as wider groups of people all around the world.
Andrew comes to this challenge after spending 9 years working on the $2 billion strategic investment fund at the Bill & Melinda Gates Foundation. That gave him an up-close look at some of the most exciting technologies, the best biomedical entrepreneurs, and the classic challenges of how to broadly improve health outcomes in poor countries.
He has thought long and hard about how to build trust with many different players to execute on a vision like the one at Variant Bio.
Please join me and Andrew Farnum on The Long Run.
Mike Kuczkowski, founder and CEO, Orangefiery
With COVID-19 cases, hospitalizations and deaths surging, the impressive vaccine results from Pfizer/BioNTech, Moderna and now AstraZeneca arrive just in time to provide some needed hope.
But for these vaccines to bring the pandemic to an end, enough people need to be willing to take them. That’s not a given.
Various polls have told a story this year about a rising tide of hesitancy. Polls in September showed a slim majority of Americans – 51 percent in one survey – are willing to take COVID-19 vaccines. More recent surveys show a slight uptick in confidence.
About 65 to 70 percent of people will need to either survive COVID-19 infections or get vaccinated in order for us to achieve herd immunity, according to the World Health Organization. In the U.S., that’s 182 million adults. (Based on 70 percent of 260 million US adults, according to US Census Bureau.)
While vaccines for infectious diseases such as measles, polio, tetanus and smallpox are widely regarded as the greatest public health interventions in history after clean drinking water, global vaccination rates have been flattening or declining in many parts of the world for the past two decades.
Vaccine hesitancy is a complex phenomenon. It is rooted in social and cultural issues like parental authority, historical experiences, religious views and confidence in various information sources. Anyone can be vaccine hesitant — there’s not a clear correlation between levels of education, wealth or access to information and vaccine hesitancy.
The traditional public health communications response in the face of these trends has been to speak louder and more emphatically about the importance of vaccination and to highlight the risks of vaccine refusal on communities. It hasn’t worked.
Heidi Larson, director, Vaccine Confidence Project
That’s because the conversation about vaccines isn’t really about vaccines. Writing about cases where communities have refused vaccination, Heidi J. Larson, Ph.D., director of the Vaccine Confidence Project in London and author of Stuck: How Vaccine Rumors Start—and Why They Don’t Go Away says:
“Vaccine revolts unleash underlying sentiments about personal and collective histories, relationships with government, big business and international bodies.”
Vaccine hesitancy, it seems, is about power, fear and trust. Overlay these trends on our pandemic moment – with declining trust in our public health institutions, rising misinformation, a polarized media and social media environment –and it’s a recipe for resistance.
So how do we respond? I’ve seen people ask who this generation’s Elvis Presley is, suggesting that a well-lit photo of the right celebrity will turn the tide of public opinion. There’s certainly a role for celebrity influencers, but if vaccine hesitancy is rooted in issues of power and control, something more will be needed. COVID-19 presents an opportunity to do something dramatically different in vaccine communications, an approach that abandons a paternalistic tone in favor of a shared decision-making model and potentially reframes the problem of vaccine hesitancy.
There are some efforts like this underway. In July, an interdisciplinary working group convened by the Johns Hopkins Center for Health Security produced a report urging the groups involved in vaccine development to take a ‘design thinking’ approach that put the public at the center of the effort. The recommendations emphasized the need to understand public expectations, earn public confidence in the fairness and even-handedness of vaccine allotment and availability, make vaccines available in familiar settings and communicate in meaningful, relevant and personal terms.
We can do this. But it means rethinking how we talk about vaccines and how we engage people around them. From a positioning standpoint, vaccination messaging has to be grounded in the science, but it has to focus on things that are more personal and meaningful than efficacy and safety information. Think about common everyday concerns — jobs, schools, restaurant dining, travel — that will be enabled by a successful vaccination program.
It also requires a dynamic set of outreach and communications strategies that will be rooted not in selling but in education and engagement.
Here are a few examples of things various stakeholders should consider doing:
In short, it will take a team effort. A big one. One that is less reliant on authority and more invested in transparency, authenticity and two-way communications. An effort that treats people like they’re smart, have agency and can make their own decisions. Which, after all, is true.
We all have a stake in ending this pandemic. We appear to have worked out crucial aspects of the science. That, in turn, gives us the opportunity to talk about the science in transparent, accessible ways, and engage people in the decision about getting a vaccine with dignity. In so doing, we can achieve the goal of herd immunity that would end the pandemic.
Over the long term, this new model for communication about COVID-19 vaccines could set the stage for more successful vaccination campaigns. That’s worth our valuable time and energy.
Mike Kuczkowski is the founder and CEO of Orangefiery, a consulting and communications firm that serves biotech, pharmaceutical and nonprofit clients in healthcare. With more than 25 years of experience in consulting, communications, politics and journalism, he and his team help organizations navigate complex issues of public interest and create growth and change through a combination of insights, messaging, engagement and organizational learning. He is a trustee of the Institute for Public Relations.
Dr. Larry Corey is an internationally renowned expert in virology, immunology, and vaccine development and a leader of the COVID-19 Prevention Network (CoVPN), which was formed by the National Institute of Allergy and Infectious Diseases at the U.S. National Institutes of Health to respond to the global pandemic. He is a Professor of Medicine and Virology at University of Washington and a Professor in the Vaccine and Infectious Disease Division and past President and Director of Fred Hutchinson Cancer Research Center.
[Editor’s Note: a version of this article was first published on Nov. 13 on the Johns Hopkins University Coronavirus Resource Center. —LT ]
The COVID-19 Operation Warp Speed (OWS) trials have taken some criticism in the medical press, and lay press, for evaluating what some consider to be “trivial” characteristics of mild COVID-19 disease.
Some are arguing that it would make more sense to evaluate vaccine efficacy entirely on ability to prevent severe COVID-19 disease, hospitalizations and deaths.
There’s a reason why the trials weren’t focused entirely on those narrow parameters. Allow me a few minutes to explain.
The trial protocols for four major vaccine developers – Pfizer, Moderna, AstraZeneca and Janssen (Johnson & Johnson) — show that the primary endpoint of the OWS vaccine trials is a reduction of coronavirus disease.
The disease is defined broadly in this case, and includes reducing the signs and symptoms of mild COVID-19 illness (e.g., headache, cough, fever, myalgias, signs of loss of taste and smell).
By including mild COVID-19 disease within a primary endpoint, the trials can capture the wide range of symptoms, including sometimes surprising symptoms, observed in patients with COVID-19.
This approach will ultimately allow for vaccines, if successful, to be given to the widest group of people possible – not just a couple important subpopulations. The trials should provide the kind of evidence necessary for efficient real-world rapid assessment of the vaccines’ effect on COVID-19.
For companies developing vaccines, inclusion of mild COVID-19 disease within a primary endpoint for the OWS trials makes sense; these companies recognize the wide range of COVID-19 disease, from mild to severe, and want to produce an effective vaccine with widespread benefit.
Reading further into the vaccine trial protocols shows that a wealth of information is being collected for analysis. Within each trial, there is a deeper evaluation of disease severity: the trials have an endpoint that includes measurement of disease severity at diagnosis and over three weeks of follow-up for every participant who develops COVID-19.
If one looks in the tables at the end of the protocols, (Table 17 in the Moderna protocol, Table 4 in the AstraZeneca protocol, and Appendices 2, 6-8 in the Janssen protocol), one sees that every person in the trials with COVID-19 infection is intensively followed from the time of diagnosis over the next three weeks with standardized assessments of their signs and symptoms. The assessment includes hard objective measurements, such as the use of medical facilities, hospitalizations, and what as investigators we all hope is rare – death.
At the time the vaccine trials were designed in the spring and summer, there was no consensus about the frequency with which those who volunteered to enroll would actually get COVID-19. More importantly, it was unknown what the spectrum of COVID-19 disease among trial participants would be.
In fact, we were pretty certain we would not see what, at that point, had been the norm in the pandemic (i.e., large numbers of people presenting to hospital emergency rooms with full-blown end-stage pneumonia). We suspected that as testing became more widely available in the summer and fall, the vaccine trials would begin to reflect some of this change. We expected participants would report to their investigators earlier, with milder COVID-19 symptoms than what was, at that time, being seen in medical practice or in any published literature.
Healthy volunteers who enroll in clinical trials, especially ones with the complexity and follow-up required in the COVID-19 vaccine efficacy trials, generally have to be interested and concerned about the disease.
The design of the OWS trials involves active disease surveillance. There is essentially no barrier to COVID-19 testing for the 30,000 participants per study. Moreover, these 30,000 participants are knowledgeable about COVID-19, likely anxious about getting the disease, and the experience of serving as a trial participant makes them attuned to any aspect of the disease, all the time. Participants in the trials receive weekly calls/texts about coming to the clinic at the first signs of any respiratory illness or fever. Importantly, trial participants have essentially unlimited access to COVID-19 testing.
Thus, we felt that a clinical classification of COVID-19 disease severity at the time of diagnosis would not really provide an accurate reflection of a participant’s COVID-19 illness. We expected that most trial participants would get worse after an initial diagnosis. As such, the real endpoint evaluation of disease severity – and hence the ultimate “primary endpoint” – would be the constellation of signs and symptoms that were collected over the two to three weeks post-diagnosis. The section outlining the detailed follow-up of COVID-19 cases within each study had its own schematic diagrams/tables and was “costed out” for site funding separately.
One of the harmonizing aspects across all the vaccine trials is that participants with COVID-19 are queried daily with a standardized questionnaire evaluating their signs and symptoms on a mild-to-moderate-to-severe scale. Samples for viral shedding in saliva or the nose are taken every second to fourth day, depending on the protocol, to evaluate the duration for which the virus is shed. Duration of fever and pulse oximetry data are also recorded.
These data allow one to grade the rate of progression, duration of symptoms, duration of signs, duration and severity of systemic effects, and need for any follow-up medical interventions (e.g., physician visits, telemedicine visits, ER visits, hospitalizations, and any complications of hospitalizations). Evaluations of these data are blinded and will be analyzed between the vaccinated and placebo recipients to determine whether disease duration and severity are reduced.
Data outlined in the prior paragraph are listed as secondary endpoints in the trials. While “relegated” to this section, it does not mean their importance is secondary. This was highlighted in a recent paper on using burden of disease as the primary endpoint in COVID-19 vaccine studies by Mehrotra and colleagues, as well as recent analyses of data from the monoclonal antibody studies conducted by Lilly and Regeneron.
The monoclonal antibody studies do a nice job of aggregating medically complicated disease to show the benefits of early use of the antibodies. They also show one approach to compiling recorded signs and symptoms of COVID-19 to show clinical benefit to patients over time. This offers a model to structure analyses both within and between individual and collated vaccine studies. In addition, the prospective close follow-up that will occur in the vaccine studies lays the groundwork for future studies and maximizes what we learn from the 150 expected COVID-19 cases in each vaccine trial of 30,000 participants.
It is unlikely that, in any individual trial, we will see enough hospitalization and death to evaluate efficacy of a vaccine versus placebo for severe COVID-19 disease. Obtaining this information within a trial would require lengthening the time to determine whether a vaccine works by 18 months.
That is simply too long to wait in a fast-moving pandemic.
Vaccines for other diseases offer a useful perspective about the inclusion of mild illness as a primary endpoint within a trial: data from other vaccines show that those capable of modifying outpatient/modest illnesses have almost universally been capable of modifying more severe illness. With most vaccines, efficacy in reducing the severe spectrum of a disease is actually somewhat higher than for mild aspects of a disease.
Let us hope that vaccination will easily produce discernible, measurable, medically important differences in COVID-19 disease in the populations enrolled in the trials. The current surge in activity in the U.S. reminds us of the urgent need for vaccines.
Dr. Larry Corey is an internationally renowned expert in virology, immunology, and vaccine development and a leader of the COVID-19 Prevention Network (CoVPN), which was formed by the National Institute of Allergy and Infectious Diseases at the U.S. National Institutes of Health to respond to the global pandemic. He is a Professor of Medicine and Virology at University of Washington and a Professor in the Vaccine and Infectious Disease Division and past President and Director of Fred Hutchinson Cancer Research Center.
1 Pfizer. PF-07302048 (BNT162 RNA-Based COVID-19 Vaccines) Protocol C4591001. 2020. https://pfe-pfizercom-d8-prod.s3.amazonaws.com/2020-09/C4591001_Clinical_Protocol.pdf.
2 Moderna TX. Protocol mRNA-1273-P301, Amendment 3. 2020. https://www.modernatx.com/sites/default/files/mRNA-1273-P301-Protocol.pdf.
3 AstraZeneca. Clinical Study Protocol – Amendment 2 AZD1222- D8110C00001. 2020. https://s3.amazonaws.com/ctr-med-7111/D8110C00001/52bec400-80f6-4c1b-8791-0483923d0867/c8070a4e-6a9d-46f9-8c32-cece903592b9/D8110C00001_CSP-v2.pdf.
4 Janssen Vaccines & Prevention BV. VAC31518 (JNJ-78436735) clinical protocol VAC31518COV3001 amendment 1. 2020. https://www.jnj.com/coronavirus/covid-19-phase-3-study-clinical-protocol.
5 Moderna TX. Protocol mRNA-1273-P301, Amendment 3. 2020. https://www.modernatx.com/sites/default/files/mRNA-1273-P301-Protocol.pdf.
6 AstraZeneca. Clinical Study Protocol – Amendment 2 AZD1222- D8110C00001. 2020. https://s3.amazonaws.com/ctr-med-7111/D8110C00001/52bec400-80f6-4c1b-8791-0483923d0867/c8070a4e-6a9d-46f9-8c32-cece903592b9/D8110C00001_CSP-v2.pdf.
7 Janssen Vaccines & Prevention BV. VAC31518 (JNJ-78436735) clinical protocol VAC31518COV3001 amendment 1. 2020. https://www.jnj.com/coronavirus/covid-19-phase-3-study-clinical-protocol.
8 Mehrotra, DV, et al. “Clinical Endpoints for Evaluating Efficacy in COVID-19 Vaccine Trials.” Annals of Internal Medicine. https://doi.org/10.7326/M20-6169. Published: 22 October 2020(https://doi.org/10.7326/M20-6169. Published: 22 October 2020).
9 Chen, Peter, et al. “SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19.” The New England Journal of Medicine. https://www.nejm.org/doi/full/10.1056/NEJMoa2029849. Published: 28 October 2020(https://www.nejm.org/doi/full/10.1056/NEJMoa2029849. Published: 28 October 2020).
Luke Timmerman, founder & editor, Timmerman Report
It wasn’t the dominant headline it should have been, and few are in the mood to celebrate with the pandemic out of control, but this was a week to celebrate a monumental scientific victory that provides hope for 2021.
Moderna dazzled everyone on Monday by reporting its mRNA vaccine candidate for COVID-19, developed in partnership with the National Institute for Allergy and Infectious Disease, was 94.5 percent effective at preventing people from getting sick. The data were strong. Of the 30,000 volunteers who enrolled in this study, 90 in the placebo group came down with COVID-19 compared with 5 in the vaccine group.
Importantly, of the 11 cases of severe disease spotted in the study, all were among people in the placebo group. Most of the reported adverse events were mild to moderate, with injection site reactions and fatigue showing up in small numbers.
Science showed it can light the way out of the pandemic.
A couple days later, we got further evidence.
Pfizer and BioNTech showed that a competing mRNA vaccine technology is also the real deal for COVID-19. The companies provided a detailed update from its 43,000-participant study of its COVID-19 vaccine. Pfizer/BioNTech showed theirs was 95 percent effective, with 162 cases of disease showing up in the placebo group compared with 8 in the vaccine group. That same level of protection extended to people over 65 – a key subgroup of vulnerable people.
We can expect more vaccines to come down the pike from other companies using different platforms.
That’s the good news. The biopharma community came together with partners in academia and government and worked like no other time since World War II. The global scientific enterprise, when focused and mobilized by a threat of this magnitude, is a marvel.
It’s been heartening to see people in industry set aside the usual competitive rivalries to cheer for the success of others.
Some of the conversation will rightly focus on supply constraints with mRNA vaccines, cold-chain shipping and storage logistics, and equitable distribution plans. The commitment ought to be there to work through those challenges all the way to the last mile, because the products are that good and fighting the disease is that important. These are solvable problems.
Now for the bad news.
What worries me the most is that this vaccine is arriving at a time when the US is ailing from a social disease. The infodemic – a supernova of misinformation and conspiracy theorizing and denial of reality – poses a threat to the vaccine relief effort that will hang over our heads for months.
The polls, if you can trust them anymore, are showing high levels of “vaccine hesitancy”. During September and October, between 50-60 percent of American adults expressed willingness to get vaccinated, according to Gallup.
Those numbers may go up now that the Moderna and Pfizer news has been so positive in November.
But we can’t just take that for granted and assume everyone will line up when the shots are available. Anti-vaccine activists used to be written off as fringe actors. But you can see that show coming to the main stage now in an extreme, fractured world.
Some people on the extreme left will refuse the vaccine, and shout loudly, about a Big Pharma greedfest or a perceived plot to give kids autism. Some people on the extreme right will refuse the vaccine, and shout loudly, about a Deep State plot (or a Big Pharma moneymaking plot).
Some will say it’s just the flu, and the harsh non-pharmaceutical interventions we’ve had to endure this year are worse than the disease itself. Who needs a vaccine if it’s just a hoax to begin with?
Even reasonable people without an axe to grind will ask questions such as: Do we have enough long-term safety data to know it’s safe?
Reasonable questions, of course, aren’t really at the center of debate anymore. Bill Gates was asked about pandemic conspiracy mongering at the New York Times Dealbook conference this week. He’s now the target of a widely-shared conspiracy theory that says he’s either trying to make money off the vaccines, or use the vaccine campaign as a false front to implant microchips into people to achieve global mind control, or some combination of that and worse.
He looked a bit flummoxed by this question. He didn’t have a good answer on how he deals with this, or how to put this infodemic back into Pandora’s Box.
A vaccine that’s 95 percent effective at preventing illness is remarkably good. But, obviously, it’s only good if you can get a couple hundred million people in a nation of 330 million people to take it over a period of months. And the way you get 200 million people to take a vaccine is if people believe it’s good for them, and their community, to protect against a pernicious virus.
This ought to be an easy sell. But the vaccination campaign to come will have to fight an uphill battle against a rip-roaring, many-sided misinformation enemy. It’s really a battle for science itself, and the scientific way of thinking, as opposed to other kinds of evidence-free assertions, and conspiratorial thinking that are thriving in the online engagement platforms.
As scientific citizens, we can’t fix the infodemic alone. But we have roles to play. We have non-scientific friends, family, and neighbors who look to us for trusted views on the fast-moving, constantly changing state of the science. We can serve as trusted brokers of information in these conversations. We can try to listen more, and keep the eye-rolling to a minimum (I have to work on that).
These conversations will surely be frustrating for some over the holidays. But let’s be as clear as we can about the science, as honest as we can about what’s known and what isn’t. Hard as it may be to stomach, we have to be patient with people who are stressed, and might need a little more time to come around and get themselves vaccinated in 2021.
As Pfizer CEO Albert Bourla said at the Dealbook conference: “Trust is lost in buckets, and gained back in drips.”
Financings
San Francisco and London-based SR One announced it has closed on its first $500 million, following the completion of its transition from a GSK corporate venture firm into an independent venture firm. Simeon George, a veteran of SR One since 2007, is the CEO of the new independent SR One.
Bedford, Mass.-based Stoke Therapeutics, a developer of drugs that upregulate protein expression, raised $97.5 million in an IPO at $39 a share.
South San Francisco-based Imago BioSciences raised $80 million in a Series C financing led by Farallon Capital Management. The company is developing treatments for myeloproliferative neoplasms.
Palo Alto, Calif.-based Medable, a tech company that enables digital and decentralized clinical trials, raised $91 million in a Series C financing round led by Sapphire Ventures. PPD participated.
Shanghai-based D3 Bio, a cancer and immunology-based drug developer, raised $200 million in a Series A financing that included Boyu Capital, Matrix Partners China, Sequoia Capital China, Temasek, and WuXi AppTec’s Corporate Venture Fund.
Sotera Health, a lab testing company, raised $1.1 billion in an IPO at $23 a share.
Santa Clara, Calif.-based Rebus Biosystems raised a $20 million B financing to continue “building innovative tools to enable spatial omics without compromise.” Illumina Ventures led.
Seattle-based Umoja Biopharma raised $53 million in a Series A financing led by MPM Capital and Qiming Venture Partners USA. The company is working on an in vivo immunotherapy platform.
Palo Alto, Calif.-based Jiya Acquisition, a SPAC sponsored by Samsara Biocapital, raised $100 million in an IPO at $10 a share.
South San Francisco-based InterVenn Biosciences raised $34 million in a Series B financing led by Anzu Partners. The company plans to start sales and marketing of its high-throughput-glycoproteomic diagnostic for ovarian cancer.
Data That Mattered
South San Francisco-based Day One Biopharmaceuticals reported on preliminary results from nine children and young adult patients with relapsed low-grade gliomas. The patients got Day One’s oral, once-weekly, pan-RAF kinase inhibitor that’s designed to get into the brain. Two of 8 patients with RAF gene fusions had Complete Responses, while three had Partial Responses, and three more had Stable Disease. Dana-Farber and the Pacific Pediatric Neuro-Oncology Consortium (PNOC) conducted the study. Day One said it plans to move next to a registration study in children and young adults with recurrent or progressive BRAF-altered low-grade gliomas. (See TR’s in-depth coverage of Day One’s Series A financing and clinical strategy, May 2020).
GSK and Medicines for Malaria Venture (MMV), announced that tafenoquine, an 8-aminoquinoline, passed a clinical trial that looked at relapse rates for of Plasmodium vivax (P. vivax) malaria in children and adolescents. Researchers found that 95 percent of the study’s 60 participants had no recurrence of P. vivax malaria during four months of follow-up. That was with a weight-based dosing regimen. Results are consistent with prior findings in adults.
Gilead Sciences, a week after facing a tough competitive challenge from ViiV Healthcare in HIV prophylaxis for women, announced that its own long-acting HIV-1 capsid inhibitor passed a Phase 2/3 study in heavily pre-treated patients. The drug, lenacapavir, is designed to be given subcutaneously every six months, as part of an anti-retroviral regimen. Gilead said 21 of 24 patients (88 percent) saw at least a 0.5 log reduction in HIV-1 after 14 days on this treatment, as a functional monotherapy.
New York-based Brainstorm Cell Therapeutics failed in a Phase III study of a cell therapy for ALS.
Science
Science Features
Policy
Science Communications
Deals
South San Francisco-based Twist Bioscience, the DNA synthesis company, partnered with New York-based Biotia on a nucleic acid hybridization capture-based research assay to detect, characterize, and monitor the SARS-CoV-2 virus for environmental surveillance. Biotia presented data on the test at Infectious Disease Week.
Twist had another interesting deal this week. The DNA synthesis company partnered with Illumina and Western Digital and Microsoft on a DNA data storage alliance. The alliance’s goal is to “help establish the foundations for a cost-effective commercial archival storage ecosystem for the explosive growth of digital data.” DNA, of course, is a compact molecule that can store information for a long time in many different environments. That might be useful for future historians to extract some meaning from the explosion of data – a supernova of information and misinformation – that has been the defining feature of the 21st century.
Pfizer and China-based LianBio, founded by Perceptive Advisors, agreed to collaborate on innovative new therapies for the China market. Pfizer will contribute $70 million of non-dilutive capital for in-licensing and co-development.
San Rafael, Calif.-based BioMarin Pharmaceutical formed a deal with Toronto-based Deep Genomics, an AI for drug discovery company. BioMarin will work with Deep Genomics to discover oligonucleotide drug candidates for four rare disease indications.
Our Shared Humanity
Johnson & Johnson committed $100 million over 5 years in a program to “eliminate health inequities for people of color.” That’s a strong word, eliminate. It needs to be met with tenacious long-term commitment. (Read Karl Simpson’s detailed Nov. 10 roundup of biopharma social and racial justice initiatives).
Life Science Cares, the nonprofit that organizes biotech companies to give to local charities focused on poverty, gave $755,000 of grants to 27 social service organizations in the Boston area. (TR is a proud supporter of Life Science Cares. See how you can give HERE).
The Mayo Clinic, the renowned institution in Rochester, Minnesota, reported that it has 900 staff who have contracted COVID-19. It is now reportedly “very worried” about whether it has the capacity to treat all the patients coming down with the novel coronavirus in its neighboring Midwestern states.
Regulatory Action
Alnylam Pharmaceuticals won EU approval for lumasiran (Oxlumo) for Primary Hyperoxaluria Type 1. It’s a rare kidney disease driven by a toxic metabolite (oxalate), which the Alnylam medicine is designed to stop. It’s the third marketed medicine from the RNA interference drug developer.
The FDA gave an Emergency Use Authorization to the first at-home COVID-19 test. The Lucira COVID-19 All-In-One Test Kit takes self-collected nasal swab samples in people age 14 and up who are suspected of having the novel coronavirus infection by their health care provider. Critics complained that it still requires a prescription, and therefore won’t achieve the wide adoption necessary to make an impact.
Eli Lilly and Incyte received an FDA Emergency Use Authorization for baricitinib, the oral JAK inhibitor, to be used in combo with remdesivir for COVID-19 patients in bad shape – those who require supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).
Bristol-Myers Squibb said its application to market the cell therapy lisocabtagene maraleucel (liso-cel) has been held up because the FDA couldn’t inspect a manufacturing plant in Texas. This is the CD-19 directed cell therapy for relapsed/refractory large B-cell lymphoma that was originally developed by Juno Therapeutics, and acquired by BMS through its acquisition of Celgene. Shareholders with Contingent Value Rights (CVRs) from the Celgene deal suffered another disappointment in this long-delayed program.
Personnel File
Waltham, Mass.-based Arrakis Therapeutics, the developer of small molecule drugs against RNA targets, hired Patrizio Renzetti as VP of human resources.
South San Francisco-based Veracyte, a molecular diagnostics company, created a new general manager structure. John Hanna, currently chief commercial officer, will become GM of endocrinology, breast cancer and lymphoma. Morton Frost, a new hire, will be GM of pulmonology. They both start the new roles Jan. 1.
Kudos
Merck CEO Ken Frazier won the Courage Against Hate award from the Anti-Defamation League. The award goes to “a visionary leader from the business community who uses their platform to promote understanding and unity in a complex world and to encourage others to actively make the world a better place.” Congratulations, Mr. Frazier. I salute you, and everyone in the biopharma community who lives those values every day.
Dr. Larry Corey is an internationally renowned expert in virology, immunology, and vaccine development and a leader of the COVID-19 Prevention Network (CoVPN), which was formed by the National Institute of Allergy and Infectious Diseases at the U.S. National Institutes of Health to respond to the global pandemic. He is a Professor of Medicine and Virology at University of Washington and a Professor in the Vaccine and Infectious Disease Division and past President and Director of Fred Hutchinson Cancer Research Center.
[Editor’s Note: a version of this article was first published on the Johns Hopkins University Coronavirus Resource Center. —LT ]
Clinical trials are usually designed to answer one or two specific questions.
For the pivotal COVID-19 trials evaluating messenger RNA vaccines from Pfizer and Moderna, researchers are looking at whether these vaccines prevent a person from getting sick, keep them from suffering a severe, prolonged illness, or keep them from having to be hospitalized.
These are important questions. And the initial trial results are an ironclad demonstration of the power of science. But there are still many more questions we’d like to answer, and more studies will need to be done to allow us to return to a more normal life.
Importantly, these clinical trials are not focused on whether a vaccine boosts immunity to the point that it prevents someone from getting infected with the SARS-CoV-2 virus at all.
It’s possible that a COVID-19 vaccine may benefit the individual who gets vaccinated by protecting them from getting sick. But we know that many people who get infected with the virus can spread it for several days without displaying symptoms, without even knowing they are ill. That means it’s theoretically possible – if not likely – that the virus could invade the body of a vaccinated person, and that vaccinated person might still unwittingly be able to spread the virus to others.
This is a critical distinction that has received little attention.
If you think about it, infecting someone without them knowing it is a great strategy for a virus whose evolutionary goal is to “replicate and survive.”
HIV is a master of this approach. The HIV virus infects most people while causing minimal symptoms. It persists for years before an individual develops the symptoms of AIDS. While the virus is hiding out, unnoticed, the HIV can spread through sexual contact.
SARS-CoV-2 differs from HIV in several ways. For starters, the new coronavirus is most infectious in the first few days after a person has gotten infected. For those first few days, the virus has explosive infectivity — until the body’s immune defense start to kick in against this novel virus it has never seen before.
And, SARS-CoV-2 isn’t transmitted through sex. This virus spreads through much less intimate interactions such as breathing, talking and sneezing around people in your immediate vicinity. This ability to spread through the air makes SARS-CoV-2 way more infectious than HIV. Get close – inches – to someone who’s infected and SARS-CoV-2 is highly contagious. Step a few feet away, and the risk goes down considerably. Wear a mask and it’s a heck of a lot less risky.
So, enter a vaccine. What does it do to this dynamic? Answer… we don’t know yet.
Some of these open questions are quite personal.
People will ask:
If I get vaccinated, do I lessen my risk of actually getting infected? Will I walk around with the virus and not know it?
Do I still shed the virus from my nose, and therefore pose a risk to others if I sneeze? Is my risk of spreading the virus to others reduced by the vaccine, or is it at the same level as if I were not vaccinated at all? How long might the vaccine protect me from getting sick? How long might it keep me from infecting others? Could I be one of those super-spreaders without me knowing that I am sick?
Scientists want to know those answers, because they will be informative for how we adjust our public health response.
If, for example, we have vaccines that are protective against illness, but ineffective against the spread, then we could have a new public health – and communications – challenge.
Imagine if we have hundreds of vaccinated people walking around with the virus unknowingly, behaving with a false sense of security, and yet putting unvaccinated people at an even higher risk of contracting COVID-19?
In medical terms: will vaccinated persons be asymptomatic carriers who can still transmit throughout their household, their community, their school? Will the virus still end up preying on clusters of vulnerable people, like in nursing homes, as it has this year? This is what we call onward transmission.
These questions are of obvious importance. If vaccinated individuals are capable of transmitting infection, then anybody who is not vaccinated faces the same risks of infection as they did before the arrival of the COVID-19 vaccine.
With vaccine hesitancy resulting in fewer people agreeing to be vaccinated, we do not yet know whether and when we will be able to markedly reduce the public health implications of COVID-19 and reduce its circulation in the workplace, in close communities, and stop super-spreading events.
With the promise of a vaccine, many continue to ask: will I still have to wear a mask?
The answer is yes, for now. At least until we know more about infectiousness among the vaccinated.
The way we generally look at a vaccine preventing infection is whether a vaccinated person makes a neutralizing antibody. We want to see increasing levels of those neutralizing antibodies, and for those biological markers to line up with clinical measurements that look at whether people get infected throughout an entire trial. We look at antibodies pre- and post-vaccination to gain this crucial insight into whether the vaccines are doing what they are supposed to do.
We also have tests that determine whether the placebo groups get asymptomatically infected more than the vaccine groups. For example, the most common respiratory virus vaccine – influenza vaccine – sometimes prevents someone from getting a severe case of flu but doesn’t often prevent people from getting infected.
Put differently, one can still acquire the infection even after getting vaccinated. The main goal of most vaccines is to prevent people from getting sick. Preventing a person from getting infected, and therefore preventing them from potentially transmitting the disease, is usually considered to be a higher hurdle to clear.
So, at this point on Nov. 18, we do not know – even with the high efficacy reported in reducing symptomatic disease – whether after vaccination individuals are still infectious. Once a vaccine is widely available, do we still need to be careful about whom we invite to our home for dinner? Do we need to continue to wear masks with other people around, especially casual acquaintances or strangers?
At the moment, the answer is still yes until we unravel these issues.
Mathematicians have modeled and made predictions about COVID-19, and they have envisioned all sorts of scenarios. And, one scenario they have created imagines that if we have a vaccine that makes everybody asymptomatic, but individuals remain infectious, then whoa! We may actually end up with more people who get infected!
Scenarios like these raise the concern that a lot of people will shrug their shoulders, not get vaccinated, and they will get infected. We will still see a lot of hospitalizations because of COVID-19. There will be more waves of death.
This realization helps explain why we must maximize the number of people in the population who get vaccinated. This requires a concentrated push to overcome vaccine hesitancy, especially in persons who are at high risk. Because we certainly are going to see behavioral changes once people get vaccinated. They’ll think, “I got vaccinated, why do I need to wear a mask?”
So, those modelers, they’ve forewarned us that we do need to learn about infectivity after vaccination.
In the end, to answer the “mask or no mask” question, we need to do a study. That’s where I am today. I’m discussing the issue with colleagues and advocating for a study. Households and college campuses, I think, are a good place to consider for this. These are places where we can vaccinate and sample people every other day and see if they acquire COVID-19. And if they do get vaccinated and give periodic samples, what’s the amount of virus showing up in their noses, their airways, or their bloodstreams?
With that kind of information in hand, we can do some contact tracing to see if people spread it to their roommates and classmates. Colleges are starting to do this anyway. Let’s piggyback on their efforts.
We should do studies that answer the question once and for all: mask or no mask?
Dr. Larry Corey is an internationally renowned expert in virology, immunology, and vaccine development and a leader of the COVID-19 Prevention Network (CoVPN), which was formed by the National Institute of Allergy and Infectious Diseases at the U.S. National Institutes of Health to respond to the global pandemic. He is a Professor of Medicine and Virology at University of Washington and a Professor in the Vaccine and Infectious Disease Division and past President and Director of Fred Hutchinson Cancer Research Center.
Luke Timmerman, founder & editor, Timmerman Report
First thing Monday, we all woke up to the brightest ray of light in this dark year.
Pfizer and Germany-based BioNTech reported that their vaccine candidate was found to be more than 90 percent effective at preventing COVID-19. The report was via press release, not peer-reviewed journal, but this was still a moment to celebrate.
The interim analysis wasn’t based on a thin-gruel data set of 30 events. The companies enrolled 43,538 people in the pivotal study, and derived the efficacy calculation off of 94 confirmed cases of COVID-19. This is a more solid persuasive set of data than I expected, based on reading the Phase III clinical trial protocol in September. The protection number might dip when the full analysis is run on 164 confirmed cases, but still, this is meaningful.
What’s more, the study wasn’t just a bunch of white people. It had diverse participants. Pfizer expanded the enrollment population to make sure this trial didn’t suffer from that Achilles heel.
The sheer magnitude of benefit, and the fact it was distributed across diverse populations, ought to go a long way toward allaying the fears of so many people – which we now have a popular name for (vaccine hesitancy). My worst nightmare for months has been that the scientific enterprise would deliver something important – a safe vaccine with 60-65 percent protection – but that it would be pointless because people would be afraid to take it, out of fear that it wasn’t proven safe.
I don’t believe that will happen now. People will likely line up to take a vaccine if they know it’s 90 percent effective, that’s been shown safe in more than 40,000 people, and that will — along with mask-wearing and some more social distancing — help bring this global nightmare to an end in 2021.
What’s more, this is the kind of scientific validation we all needed to see for mRNA vaccines as a platform, and for our efforts at targeting the SARS-CoV-2 spike protein. The Pfizer / BioNTech news bodes especially well for Moderna, and for other vaccine candidates in the pipeline. With multiple companies going all-out on manufacturing and distribution, and with some having different refrigeration requirements, we have a good chance to achieve the vaccination coverage across the population that we need to break the chain of transmission once and for all.
Between now and that day, a lot is up to us. It’s hard for people to see how seemingly innocuous individual actions, from people with no apparent symptoms, can add up to so much compound harm. But if you have family members or relatives that have any doubt, please steer them to this chilling CDC report about the ripple effect from a wedding in rural Maine in August, when people weren’t wearing masks.
You can read the full CDC report for yourself.
This ought to make everyone stop and think about family plans for the holidays.
It’s a sad thing to miss family gatherings this year. But there is hope, and good reason for us to stick it out a few months longer.
Everyone reading this publication probably doesn’t need to be reminded of what works. The virus spreads through the air. Cloth masks, physical distancing, crowd avoidance, and hand-washing are still the best non-pharmaceutical interventions we have until the vaccine cavalry arrives. We have good reason to have confidence in the neutralizing antibody therapies for patients who get mild to moderate illness.
Our country has been deeply damaged by pernicious efforts to undermine science and truth itself. Millions of people have been told repeatedly, that COVID-19 was a hoax, that it was magically going away, and it was cooked up by the media and Democrats to undermine the President in an election year.
That’s, of course, a lie. We had 150,000 new cases reported yesterday, and 66,000 people hospitalized. This is uncontained national spread, not just a cluster here or there. More than 1,000 people are dying every day, and estimates are 100,000-150,000 will die before Inauguration Day.
A huge amount of suffering and death could have been avoided, if the pernicious lies hadn’t been told over and over and over.
The result is that we now have to sift through the ashes to build a new society where people can talk to each other again like rational adults. If we can start there, maybe we can begin to listen to each other, find toeholds of common ground, and begin to cobble together some more of the social glue we call trust.
The election of Nov. 3 was a clear and convincing start down that path toward a better world. Now, if people of good faith are willing to do the work, with eyes on the North Star of creating a better world for ourselves and for future generations, then we have a chance to wake up to some more bright mornings like we did when Pfizer and BioNTech surprised us on Nov. 9.
Therapeutics
Eli Lilly got an Emergency Use Authorization for bamlanivimab as a therapeutic neutralizing antibody for newly diagnosed patients with mild-to-moderate COVID-19. Now we’ll see if Lilly can make enough of the antibody to help patients who are rapidly filling up hospitals.
Regulatory Action
AstraZeneca won FDA clearance for ticagrelor (Brilinta) to reduce the risk of stroke. The twice-daily medication also comes with a slightly elevated risk of bleeding.
An FDA advisory committee voted against approval of Biogen’s aducanumab for Alzheimer’s disease. The agency’s advisors were clearly unimpressed with the application, despite a rather unusually rosy appraisal of the drug by the FDA staff. The agency has a Mar. 7, 2021 deadline to complete its review and make a decision.
Foundation Medicine won FDA clearance for its FoundationOne Liquid CDx as a companion diagnostic for olaparib (Lynparza), a treatment for BRCA1/2 mutated prostate cancer.
Science
Epidemiology
Long COVID
Public Health
Strategy
Features
Our Shared Humanity
Trust
Policy Responses
Financings
Boston-based Decibel Therapeutics, the developer of gene therapies for hearing loss, raised $82.2 million in a Series D financing. OrbiMed led.
Cambridge, Mass. and Suzhou, China-based Kira Pharmaceuticals said it raised $46 million to advance work on complement-targeted therapies to treat immune-mediated diseases. Quan Capital led. Frederick Beddingfield was named CEO.
Emeryville, Calif. and Germany-based Metagenomi raised $65 million in a Series A financing to do CRISPR-based gene editing of microorganisms. Leaps by Bayer and Humboldt Fund co-led.
Bedford, Mass.-based Homology Medicines, a genetic medicines company, raised $60 million in an equity investment from Pfizer. The big drugmaker bought 5 million shares at $12.
Shanghai-based Immagene Biopharmaceuticals, an immunology-based drug developer, closed a $21 million Series B financing led by Vertex Ventures China.
Personnel File
South San Francisco-based Graphite Bio hired Katherine Vega Stultz as chief operating officer and Philip P. Gutry as chief business officer and head of finance & investor relations. (See TR coverage of Graphite Bio’s $45 million Series A, September 2020).
Vancouver, BC and Seattle-based Chinook Therapeutics, the developer of precision kidney medicines, hired Eric Bjerkholt as Chief Financial Officer.
Cambridge, Mass.-based Foghorn Therapeutics hired Michael LaCascia as chief legal officer.
Seattle-based Qiming Venture Partners USA said it promoted Anna French and Colin Walsh from principals to partners. French is in the Boston office and Walsh is in the San Francisco office.
Cambridge, Mass.-based Magenta Therapeutics hired Steve Mahoney as chief financial and chief operating officer.
Data That Mattered
San Diego-based Arena Pharmaceuticals failed to hit the primary endpoint in a Phase II trial with its once-daily, oral sphingosine 1-phosphate (S1P) receptor modulator, etrasimod, for moderate to severe atopic dermatitis. The primary endpoint was Eczema Area and Severity Index (EASI), evaluated for the drug and placebo groups at 12 weeks. The company, however, slapped a positive headline on its press release, saying the drug did better on the validated Investigator Global Assessment (vIGA). Despite missing the primary endpoint in Phase II, the company said it will advance the drug into Phase III anyway. Shares fell.
South San Francisco-based Five Prime Therapeutics showed in a randomized, placebo-controlled Phase II trial that bemarituzumab in combination with mFOLFOX6 chemotherapy was able to improve progression-free survival, and overall survival time, for patients with front-line advanced gastric and gastroesophageal cancer. The drug is designed to block activation of fibroblast growth factor receptor 2b. Five Prime stock boomed from $5.34 a share before the news to $22.43 in the two days after. It announced plans to strike while the iron is hot, doing a new offering of 5 million shares to raise cash.
AstraZeneca and Amgen reported positive results from a Phase III trial of patients with severe asthma. The drug, Tezepelumab, is designed to inhibit TSLP, a cytokine in epithelial cells that is thought to play a key role in multiple inflammatory cascades that cause airways to inflame. The drug showed an ability to reduce asthma exacerbations over 52 weeks. Data will be presented at a medical meeting.
ViiV Healthcare, the HIV drug developer established by GSK and Pfizer, said its every-other-month injectable treatment for HIV, cabotegravir, beat Gilead’s emtricitabine/tenofovir disoproxil fumarate (Truvada) in a head-to-head study. Researchers with the HIV Prevention Trials Network found the injectable medicine was 89 percent more effective than the once-daily oral regimen at prevention women from getting HIV.
Deals
Vifor Pharma agreed to pay $30 million upfront, another $30 million equity investment, and $20 million in clinical study milestone payments to Angion Biomedica. The deal is part of a collaboration to deveop a small-molecule hepatocyte growth factor (HGF) mimetic to treat acute kidney injuries.
Today’s guest on The Long Run is Simba Gill.
Simba is the CEO of Cambridge, Mass.-based Evelo Biosciences.
Simba Gill, CEO, Evelo Biosciences
Evelo is part of a new generation of biotech companies seeking to make medicines based on new understanding of the microbiome. The science here is fascinating. Evelo’s drug candidates are biologics designed to be taken orally, to act directly in the gut, and to have therapeutic effects throughout the body.
In this conversation, Simba describes what the key scientific discoveries were that inspired the founding of Evelo, and how the company created a strategy for therapeutic interventions (which is no obvious thing). Evelo is in the clinical development stages with drug candidates for chronic inflammatory diseases like psoriasis and for cancer. Based on some of its clinical observations, there’s even a rationale for testing one of its candidates for COVID-19 – clinical studies are ongoing.
Simba grew up in the UK, and got his scientific training as an immunologist. He is a global citizen, and has consistently gravitated to big new ideas when the biology risk was high, and entrepreneurs have to be a little extra comfortable entering the unknown.
Simba also thinks a lot about the intersection between science and society. Much of his drive is about creating therapies that can help the largest number of people possible around the world.
As you’ll hear from the start, Simba was part of the 27-member Kilimanjaro Climb to Fight Cancer team in 2019. He and I got to know each other, and discovered our shared interest in science and society, while on that trip to climb the highest mountain in Africa. He’s someone with a big heart.
Now, please join me and Simba Gill on The Long Run.
Please subscribe and tell your friends why it’s worthwhile. Quality journalism costs money. When you subscribe to Timmerman Report at $169 per year, you reward quality independent biotech reporting, and encourage more.
Karl Simpson, CEO, Liftstream
First came the pandemic. Then the economic slump. Then the push for racial justice. Taken together, you have three major challenges for business leaders to tackle all at once.
Because the pandemic has illuminated many racial inequalities, these issues have become intertwined.
In the biopharma sector, many company leaders stepped up. Decisive moves were made to reorganize working patterns to protect their staff, while continuing important work. In some cases, work that is vital to meet the need for new therapies to treat COVID-19 patients, and find a possible vaccine at “warp speed”.
Many leaders have also made statements, and created action plans, to address racial inequality in their companies. While the individual motives may differ, it has provided the industry with an opportunity to re-establish its bonds of trust with citizens; a chance CEOs appear keen to take.
Most employees in biotech and pharma are motivated by the mission to help patients, regardless of their race, gender or socioeconomic circumstance. This north star has burned brightly throughout the pandemic. As the industry has risen to the COVID-19 challenge, it has done so while paying attention to the need for conducting diverse clinical trials.
Pfizer/BioNTech reported Nov. 9 that 42% of their 43,538 trial participants who enrolled in their COVID-19 vaccine pivotal trial have racially or ethnically diverse backgrounds. Moderna, another front runner in the race for a COVID-19 vaccine, said that 37 percent of the people enrolled in its pivotal study are from diverse communities — 11,000 out of the 30,000 total. Specifically, the trial included 6,000 Hispanic or Latinx participants, and more than 3,000 African American participants.
Diversity in clinical trials is one area where the industry can take direct, immediate, and positive action. It’s a crucial step toward, delivering better patient outcomes and reducing inequities in healthcare. The industry must also address health equity more broadly, including the issue of access to new treatments, especially for people with no health insurance, or inadequate health insurance.
Many of the large companies in biopharma have already been focused for some time on improving access to medicines for low-income and underserved populations.
That’s one place to start. But for biopharma to restore trust with patients and minority communities it will require some internal changes too. These factors rely on the range of perspectives contributing to the process of innovation and the management of companies. For this reason, diversity is becoming imperative in all aspects of the life sciences sector.
What are companies doing? How have they been responding to the intersecting challenges of the racial justice issue and a pandemic? – Here, we look at a sample of companies, large and small, and explore what action they have taken.
The converging opportunities of more diverse clinical trials, improved health equity, and a more diverse and equal workforce has led BMS to announce a $300 million, 5-year investment. BMS aims to double executive roles for Black and Latinx employees by 2022 and to level up on pay.
Like many other companies, BMS will look to impact the supply chain too, through a pledge to spend $1 billion globally by 2025 with black and diverse-owned suppliers. Plus, BMS said it will double-match donations its employees make to non-profits dedicated to fighting discrimination or inequities in the health system.
This ambitious initiative came about six weeks after BMS added Paula Price and Derica Rice, both black candidates, to its board of directors. BMS, along with other biopharma companies, has also committed to the NYC Comptroller, Scott Stringer, to disclose its consolidated EEO-1 data, which details some useful standardized data on its employment of racial and ethnic workplace minorities.
Biogen has a long been committed toward diversity, equity and inclusion. This June, Biogen built on its foundational Diversity, Equity & Inclusion (DE&I) program to increase its breadth and depth, both internally in areas like hiring and development, and externally in things like clinical trial engagement strategy.
Minita Shah-Mara, head of organization effectiveness & diversity and inclusion
“Our equity and inclusivity journey is ongoing,” said Minita Shah-Mara, Head of Diversity, Equity & Inclusion at Biogen, “but we should also be excited about where we are on this journey. It requires collaboration, learning, vulnerability and holding ourselves accountable to meet our goals.”
Biogen is aiming for a 30% increase in Black, African American and Latinx people employed in its leadership ranks by the end of next year. Biogen’s plan also focuses on Asian employees where underrepresented, and women too, until parity or population demographics is achieved by level and function. Biogen is also looking to increase the representation of veterans, people of disability, and LGBTQ individuals. The plan doesn’t stop with hiring. It includes tailored development programming for underrepresented employees who may be ready to move into first-time supervisor roles. Research shows this is a pivotal career stage where the opportunity gap widens, and Biogen should be commended for designing a targeted intervention.
Biogen’s plan contains specific data-driven goals, and a framework for measuring progress against the goals. By collecting richer sets of data, companies can create dashboards to measure progress. This new analytical approach allows leaders to see how the company is performing by geography, by job function and seniority level. Gathering and analyzing this data also paves the way for a better understanding of employee advancement and promotion, hiring, and team composition. Periodic updates will be communicated within the entire organization.
The DE&I strategy, encompassing extensive staff training on inclusive hiring, promotion and retention, extends beyond the walls of the company’s offices. For one thing, Biogen recognizes its ability to boost financial empowerment for minorities. Biogen is increasing its spending with minority-owned businesses. This financial empowerment strategy has already resulted in Biogen depositing $10 million with OneUnited Bank, the largest Black-owned bank in the United States.
Biogen recognizes that serving patients is the priority, and that is embedded in its DE&I strategy. There are multiple components to the external side of Biogen’s strategy. It is seeking to boost minority participation in its clinical trials, to conduct more studies of underrepresented groups in disease areas relevant to the company, and to invest more in patient engagement, education, and access to medicines in underserved communities. As with BMS, Biogen is willing to submit to external scrutiny on how it’s doing on these goals. Biogen is one of the companies that has agreed to disclose its consolidated EEO-1 data. Taken together, with the internal and external components, this is a serious plan.
Smaller companies are getting involved as well. South San Francisco-based Sutro Biopharma, a developer of drugs for cancer and autoimmune disease, has been following through on the CEO’s open letter to employees and stakeholders in the aftermath of George Floyd’s killing. CEO William Newell has committed company resources to improve the company’s connections with underrepresented and lower socioeconomic communities, having linked in with local organizations like Students Rising Above and Peninsula Bridge. Sutro opened its doors this past summer to nine interns from diverse backgrounds, offering these students real work experience, despite the operational challenges of COVID-19.
Bill Newell, CEO, Sutro Biopharma
Newell says Sutro is just beginning. Sutro is becoming more intentional about addressing racial diversity at all levels of the company, from the board of directors down. The company has created a diversity section on its website with curated content, and all the employees have T-shirts emblazoned with the word SAWUBONA, a Zulu word meaning ‘I see you, you are important to me and I value you’. Newell said several factors have compelled him to become more active. He’s been feeling the call of the broader movement for racial equity. He’s been working to learn more about the subject. And Sutro has grown to a point where it has resources to take meaningful action.
Newell, a member of the BIO board, is serving on the trade group’s Workforce Development, Diversity and Inclusion committee. He is also on the board at the California Life Sciences Association, which is also adopting a strategy for DE&I. He is very engaged in the topic, and his early efforts are commendable. There is still a lot for Sutro to do, but Newell is showing what can happen at a development-stage biotech company when the CEO is personally committed.
Waltham, Mass.-based Xilio Therapeutics is a venture-backed cancer immunotherapy startup, at an early phase of development, like many companies in the Timmerman Report readership. The CEO, Rene Russo, is an advocate for diversity. She signed MassBio’s Open Letter 2.0, which asked leaders to commit to several commitments on racial and ethnic diversity.
Rene Russo, CEO, Xilio Therapeutics
Russo’s public pledge coincided with the company concentrating its DE&I efforts in the past few months. Xilio hired a chief human resources officer, Jason Robart, to help formulate a human capital strategy, of which DE&I is an integral part, rather than somehow being separate. The view at Xilio is that it has to be part of the corporate planning process.
As a relatively young company with good intentions, Xilio has an opportunity to turn DE&I into an integral part of how it grows up. This is a good time to act intentionally. In Xilio, as with many small and early-stage ventures, the reliance on networks for hiring is high. This network dependence has the potential to seed homogeny. People tend to hire other people who look like them. To counteract this well-known unconscious bias, Xilio is being very intentional about reviewing and assessing the job profiles for which it is recruiting, thereby widening the aperture through which to view prospective employees. More diligence about the relevant experience of candidates too, will support this more expansive hiring approach.
“Xilio’s success in developing therapeutics that serve the needs of a diverse patient population will be enhanced by having a diverse workforce,” Russo noted. About one-third of the company’s current workforce identifies as racial or ethnic minorities, while about half are women.
Xilio has experienced a groundswell of interest in DE&I by employees since the racial injustice protests swept the country in June. The company has conducted some initial survey work to understand better the composition and needs and preferences of the workforce. As a science-based organization, data will be a key component of measuring the effectiveness of its DE&I efforts, but the company will also monitor some of the less quantifiable indicators. “Successful DE&I efforts will show up in the numbers, but perhaps equally important, they will also show up in how we do business,” Russo said. “When we see a material and consistent change in the nature of conversations and in the behaviors of employees, we’ll know that we’re making progress.”
To help develop a comprehensive DE&I program, Xilio has formed a DE&I council made up of employees, including senior leaders. This council will also have members from outside the company too, to introduce external accountability as well as infuse different ideas.
The company has been working with Project OnRamp, an initiative started by Life Science Cares, which gives interns from underrepresented communities opportunities to work in life sciences companies.
One challenge for Xilio is to reduce its reliance on existing networks, and to be open to hiring more diverse candidates from unfamiliar sources. The company is in a building phase, and diversity often gives way to just-in-time hiring. Xilio has been busily hiring in recent months, adding an independent Chairman, two independent directors, a Chief Medical Officer and a Chief Human Resources Officer. While only one of these individuals is a racial minority, Xilio deserves credit for having three women on the board.
When COVID-19 forced everyone to change how their organizations work, Genocea CEO Chip Clark had employees working from home like everyone else. But this dislocation has meant that Clark has had to place extra emphasis on internal communication to keep everyone on the team engaged and connected. Clark has been sending daily notes to staff, in addition to inviting employees to attend the usual company happy hour, if they choose.
Chip Clark, CEO, Genocea Biosciences
In the immediate aftermath of George Floyd’s death, Clark, a black man, had to search for the right response. The Monday morning note-to-all had to strike the right balance in terms of what the event meant to him, the employees, the company and the other stakeholders, not least the patients they’re all trying to help.
The company made a statement on its website, decrying racism and claiming that it cannot be neutral in the face of such events. Clark’s note to staff, and the public statement, would begin an internal dialogue about the issue and what to do about it. This conversation needed pragmatism and balance, and could not be casual or overly political, although keeping these separate isn’t easy. Clark was keen to remind his team that they were privileged to do what they do, get paid for it, and to be part of a vibrant and dynamic local bioscience economy in Massachusetts.
This dialogue led to the first of the company’s deliberate actions. People needed an outlet for their anger, frustration, and desire to improve the situation. Genocea agreed to provide a company match when employees donate to non-profits dedicated to tackling racial and social justice. While donations are a demonstration of this, the company is also encouraging employees to invest their time and talent, through taking time off for community service days.
The company formed a D&I committee. Clark believes that the company is performing well on workforce composition, relative to peers, but acknowledges there is also more the company can, and must, do. One way he is zeroing in on this is to apply a renewed focus on hiring practices, including widening the scope of recruiting efforts, accessing more diverse candidate populations, and monitoring measurable benchmarks; all supported by a documented process.
Clark says the social context of the current environment has increased his recent drive for change, but that the company’s stronger financial position today and the accountability of external groups driving for progress have all made it possible to set positive changes in motion. He admits much of this DE&I work is hard, but he is committed on continuing to build a company where a range of views is welcome. These include political views, which can be a source of tension on such issues as DE&I, but creating an environment where people can live their values and feel connected to the culture of the company is crucial.
Management teams always have many competing priorities to juggle, but it’s clear that racial equity and diversity is now a top-of-mind priority at many companies. Each company was already making efforts and progress on diversity and inclusion, but the events of this summer have provided new impetus.
Every company has its starting place, with different end goals in mind, and they’ll approach it in their way, mainly using tools, processes, systems and strategies that have been proven to work, yet need tailoring to their needs. No doubt, each will have ways they can improve on their scorecards too.
All of the companies reviewed are aware of the social context their respective firms operate within. They are working for all their stakeholders, including their employees of today, and tomorrow. Every one of these companies understands that by bringing equity, diversity and inclusion to their firms, they reduce risks which jeopardize their long-term success and sustainability.
Leaders are making a risk/benefit calculus on DE&I, and the scales seem to be tilting ever increasingly towards the considerable benefits that being more inclusive offers. Most leaders recognize they are reliant on the developing generation of talents currently making the bioscience community the force that it is. Future generations of biotech workers will be increasingly diverse. To be an attractive employer, companies will need to be fully inclusive of the workforce, and in their interactions with society.
The slow increase in the representation of Black, Latinx and other racial workplace minorities in the industry is still a problem; no one can pretend otherwise. These companies know it. It should not take the tragic racial events of 2020 to cause momentum to shift, but it appears the wheels are in motion to bring about the change we need to see.
Karl Simpson is CEO of Liftstream, an executive search and leadership consulting practice that exclusively serves clients in the life sciences industry by supporting board and executive appointments, and consulting on diversity and governance. Karl is co-founder of BioDirector, a diverse international network of board director which is improving corporate governance and diversity in the boardrooms of innovative healthcare companies. He is also the founder of the Bioscience & Investor Inclusion Group, an industry coalition developing DE&I solutions for VCs and innovator companies.
