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.
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.
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.
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.
Luke Timmerman, founder & editor, Timmerman Report
Biotech has always depended on the ideas and energy of young people.
But it’s time to think more broadly about how biotech and young people relate.
Let’s start with young people.
Recall the column from two weeks ago, which cited a 2017 Pentagon study. That study found that a full 71 percent of Americans between the ages of 18-24 aren’t eligible to serve in the US military. Three main reasons stand out as disqualifiers – obesity, criminal records, and lack of a high school diploma.
Let that sink in for a minute.
Think about how many millions of young people whose lives were going off the rails in the 2010s, because of long-simmering societal ills.
That was clear before the pandemic.
Now, consider how many young people are struggling, especially with mental health issues exacerbated by the pandemic.
All of us need hope. This is a hard time. But young adults need to be especially optimistic when making some of the big choices in life — what career to pursue, where to live, who to marry, how to maybe someday buy a home. Maybe some young people would make different life choices, and be more attractive to employers, if they had more hope.
What does any of this have to do with biopharma?
Consider manufacturing.
We are in the early phase of a cell and gene therapy revolution.
About 900 Investigational New Drug (IND) applications for cell and gene therapies were on file with the FDA as of February 2020. More are coming. Every week, more capital flows into startups aspiring to churn out more of these valuable next-generation medicines.
The opportunity for growth is obvious. There are more than 1,000 clinical trials for cell and gene therapies that could enroll as many as 60,000 patients worldwide, according to the Alliance for Regenerative Medicine. The FDA says it anticipates approving 10-20 such cell and gene therapies per year by 2025.
Whatever the numbers are, some of these specialized therapies will pan out. Some will get FDA approved. Some will need to scale up to meet global demand.
Jobs will have to be created in specialized, customized manufacturing plants to make these cell and gene therapies. Advanced biologics aren’t going away, either. The making of these medicines can’t be completely automated, and shouldn’t be entirely shipped offshore. There are national security reasons, national competitive advantage reasons, logistical shipping reasons, and workforce development reasons to keep most of this work on US soil.
There are large swaths of the map outside of San Francisco, New York and Boston where this work can be done inexpensively.
Biotech can choose to invest in people, equipment, and places to get ready for this manufacturing boom.
Actually getting this done will require a shift in employer mindset. Not everyone needs a 4-year degree to work in a cell therapy manufacturing plant. Some of these jobs are better suited to people with 2-year community college training.
These can be high-salary/good-benefits/steady paycheck blue collar jobs. As biotech matures as an industry, it will depend on more of these jobs. When the industry invests in people to do this skilled work, it makes good long-term economic sense to pay high wages to keep people motivated and productive and loyal.
I grew up in the industrial and agricultural economy of the Upper Midwest. The high salaries and good benefits offered by companies like John Deere were considered the ticket to middle-class life. There was pride and dignity in this work for people like my Dad. He got a community college certificate to become a welder. He got a job with that skill at John Deere in Dubuque, Iowa. He thought he had it made.
He lost that job in a round of layoffs when I was in preschool.
Jobs like that today are scarce. My Dad had to reinvent himself a couple times to provide for our family.
Now I live in Seattle. It’s a tech metropolis. But before the tech boom, it was put on the map by Boeing. Tens of thousands of blue-collar, union workers built Seattle. They earned good wages and solid benefits. They took pride in work assembling “the best airplanes in the world.” That’s what Boeing commercial airplanes chief Alan Mulally, a boy from Kansas, used to say.
Like any for-profit industry, of course, biotech isn’t in the business of creating jobs just for the sake of creating jobs. But it is an industry on the upswing. It needs to think long-term about people to meet long-term business needs.
Young people seeking purpose could step up for this line of work, whether they aspire to be scientists or blue-collar machine operators.
What if biotech were to open up to more people without 4-year or advanced college degrees? What kinds of manufacturing jobs, in particular, might be doable for people with community college training? Would it make sense to invest in apprenticeship programs, and then continue to invest in training people to keep skills updated over an entire career?
Might some of these people become longtime, loyal, productive employees? Might some rise through the ranks to make even greater contributions to their companies? Might the kids of manufacturing workers grow up to be scientists and executives of tomorrow?
Biotech can be the new Boeing, the new John Deere. It will require extending a hand to young people. It will require taking chances on people who might not otherwise get one.
It will take some imagination. But the potential is clear. Biotech, as I wrote here a few weeks ago, is radiant at a dark time.
Let’s make biotech into a beacon of hope for young people.
Cambridge, Mass.-based Bluebird Bio, the cell and gene therapy company, is experiencing a nightmare. The company said it halted clinical trials of its Lentiglobin gene therapy for sickle cell disease after seeing a report of a patient dosed five years ago now coming down with acute myeloid leukemia. Around the same time, the company said it learned of another case of a patient getting myelodysplastic syndrome (MDS), a pre-leukemia syndrome. The company hasn’t been able to confirm whether the cancerous conditions are related to its lentiviral vector. But because that possibility can’t be ruled out, and because its only marketed therapy uses the same vector, it shut down sales and marketing of that other treatment for beta-thalassemia in Europe and the UK.
Shares in Bluebird crashed, down 41 percent in value from $45.76 last Friday to $26.95 at yesterday’s close. Many investors have to be wondering about the decision Bluebird recently announced to split into two companies – one focused on genetic diseases, and the other focused on cancer. The future for genetic diseases will hinge on what investigators uncover in days and weeks ahead about what might have caused the severe adverse events.
Analyst Raju Prasad of William Blair downgraded the stock immediately, as many investors surely aren’t going to hang around long to find out. At best, the situation means Bluebird will suffer from a significant delay. At worst, if the vector ends up looking like the culprit, it could be devastating to the company and send a chill through investor sentiment in other gene therapy companies. It’s too early to say yet what the answer will be. “While there is precedent of [sickle cell disease] patients to have an increased risk of leukemia compared with the general population, we believe the complexity of the issue is likely to lead to a thorough investigation and potentially a significant delay to trial timelines and/or change to trial design,” Prasad wrote in a note to clients.
Bluebird shares this week.
Moderna said it expects to deliver 100 million doses of its mRNA COVID-19 vaccine to the US government by the end of March, another 100 million by the end of May, and another 100 million by the end of July. Those are faster timelines than the company had agreed to previously, and enough for this company alone to fully vaccinate almost half of the US population with a two-shot regimen. The company also agreed to provide an additional 150 million doses to the European Union, bringing the total doses ordered there to 310 million in 2021. The European Commission also secured an option for another 150 million doses in 2022. It’s all pretty breathtaking to consider, knowing the pressure to move this fast with global-scale manufacturing of a novel mRNA vaccine technology with lipid nanoparticle delivery.
Pfizer and BioNTech said they will supply 200 million extra doses of its mRNA COVID-19 vaccine to the European Union, bringing its total supply agreement there to 500 million doses. The plan is to deliver by the end of 2021. The European Commission obtained an option to request another 100 million doses. Last week, the companies said they upped their commitment to the US government by 100 million doses, bringing its total commitment to the US government to 300 million doses.
Novavax reached an agreement with GAVI to provide 1.1 billion cumulative doses of its protein-adjuvant vaccine for COVID-19 through the COVAX facility, to provide vaccine access to people in low-income, middle-income, and high-income countries. Gaithersburg, Maryland-based Novavax is working in partnership with Serum Institute of India to boost manufacturing output.
Johnson & Johnson, the developer of a single-shot vaccine for COVID-19 that’s due to go before an FDA advisory committee for review Feb. 26, is still planning to supply 100 million doses to the US government in the first half of 2021. But it’s unclear how many doses will be available in March and April, assuming it wins Emergency Use Authorization from the FDA. Tony Fauci told CNN he’s “a little disappointed” in the expected number of doses available from J&J this spring.
While the race is on to vaccinate in wealthy countries, Science magazine reporter Kai Kupferschmidt notes that not a single healthcare worker in Africa has been vaccinated, until South Africa started this week.
Reduced Neutralization of SARS-CoV-2 B.1.1.7 Variant by Convalescent and Vaccine Sera. This study isn’t quite as bad as the headline suggests. The authors write, “widespread escape from monoclonal antibodies or antibody responses generated by natural infection or vaccination was not observed.” Cell. Feb. 18. (Piyada Supasa et al Oxford University)
Transmission of COVID-19 in 282 clusters in Catalonia, Spain. This study shows that people with high viral loads of SARS-CoV-2 are main drivers of transmission. The Lancet. Feb. 2. (Michael Marks et al).
Densely sampled viral trajectories suggest longer duration of acute infection with B.1.1.7 variant relative to non-B.1.1.7 SARS-CoV-2. Why does the new variant seem so concerning? One reason, according to this Harvard study, is that it appears to last longer, naturally creating more opportunities for transmission. Digital Access to Scholarship at Harvard. Feb. 10 preprint. (Stephen Kissler et al)
Inhibitory CD161 receptor identified in glioma-infiltrating T cells by single-cell analysis. Cell. Feb. 15. (Kai Wucherpfennig et al Broad Institute). Researchers at the Broad Institute analyzed tumor-infiltrating T-cells with single-cell analysis, and identified the gene that encodes for CD161 which appears on NK cells and T cells. It’s the basis for cell therapy work being done at Waltham, Mass.-based Immunitas, which raised a $39 million Series A financing in 2019. (Company statement).
Neutralizing Activity of BNT162b2-Elicited Serum — Preliminary Report. NEJM. Feb. 17. (Pfizer / BioNTech research teams). The mRNA vaccine showed in vitro that it can neutralize the SARS-CoV-2 virus with the B.1.351 variant to the spike protein (more widely known as the South Africa variant). (Pfizer statement).
Brazil is trying to answer one of the key outstanding questions about the COVID-19 vaccines. Do they help reduce transmission of the virus? It’s difficult to run such a study, but the Brazilians are trying a pilot project – vaccinate an entire town of 45,000 people to see what happens. (WSJ coverage).
The myth of ‘good’ and ‘bad’ Covid vaccines. This article discusses how false perceptions about the next batch of vaccines could complicate the vaccine hesitancy story, especially in communities of color. STAT. Feb. 17. (Helen Branswell)
UK-based Synairgen said it started enrolling in a Phase II/III study with an inhalable interferon beta treatment for mild-to-moderate COVID-19 patients who aren’t hospitalized.
South Plainfield, NJ-based PTC Therapeutics said it started the second stage of a Phase II/III trial of an oral therapy it developed against a cellular enzyme, dihydroorotate dehydrogenase (DHODH). By targeting this enzyme instead of a protein on SARS-CoV-2, PTC hopes to inhibit viral replication and calm down the excessive inflammatory responses that result from infection. CEO Stu Peltz noted in a statement that the drug could be taken at home, as well as in the hospital, and that if it’s effective, it ought to work against wildtype virus as well as the variants.
Thermo Fisher Scientific said it secured FDA Emergency Use Authorization for the TaqPath RT-PCR diagnostic test, which can tell the difference between COVID-19, Flu A and Flu B in a single sample. It’s for CLIA lab use.
New York and San Francisco-based Adjuvant Capital, founded in 2019 but quiet until this week, announced its initial $300 million fund to invest in public health needs that deliver social and financial returns. Merck, Novartis, IFC, the Bill & Melinda Gates Foundation, Children’s Investment Fund Foundation, and Dalio Philanthropies are among the LPs supporting the team led by Glenn Rockman and Jenny Yip. (TR coverage by Anika Gupta).
Cambridge, Mass.-based Centessa Pharmaceuticals raised $250 million in a Series A, to roll up 10 Medicxi Ventures-backed asset-centric virtual biotech companies into an umbrella organization. Saurabh Saha, formerly of Bristol-Myers Squibb, is the CEO, while Moncef Slaoui, the former chief scientific advisor of Operation Warp Speed, is the CSO. (Timmerman Report coverage).
Durham, NC-based Humacyte went public through a SPAC deal that brought in $255 million in cash proceeds to advance its work in making universally implantable, off-the-shelf human tissues for transplant at large commercial scale. Fresenius Medical Care, OrbiMed, Monashee Investment Management, and Alexandria Venture Investments were among the participants in the related PIPE deal.
Cambridge, Mass.-based Elicio Therapeutics, an immunotherapy company targeting the lymph nodes, raised $73 million in a Series B financing. It didn’t name the investors, but said there were “multiple strategic and international investors.”
San Francisco-based Excision Biotherapeutics said it raised $60 million to develop CRISPR-based antiviral therapies. Greatpoint Ventures led.
Cambridge, Mass.-based Immune ID raised a $17 million seed financing led by Longwood Fund, and which included Arch Venture Partners, Pitango HealthTech, In-Q-Tel and Xfund. The company is working to identify therapeutic targets based on antibody interactions that drive immune diseases.
New York and Guilford, Conn.-based Quantum Si, a proteomics company founded by Jonathan Rothberg, went public through a SPAC transaction with HighCape Capital. The deal involves $540 million of gross proceeds to the company, including a $425 million private investment in a public equity (PIPE) that included Foresite Capital Management and Redmile Group, among others.
Boston-based Gamida Cell, a cell therapy company, raised $75 million in a convertible debt offering with Highbridge Capital Management. The cash is supposed to keep the company going into the second half of 2022.
Seattle-based Ozette raised $6 million in a seed financing to advance AI for immune system monitoring. Madrona Venture Group led, and was joined by the Allen Institute for Artificial Intelligence (AI2) and Vulcan Capital.
Houston-based Iterion Therapeutics pulled in $17 million in a Series B financing led by Lumira Ventures to develop a potent and selective nuclear beta-catenin inhibitor for desmoid tumors.
Charles River Labs agreed to acquire Cognate Bioservices, a cell and gene therapy contract manufacturing organization, for $875 million in cash.
Novartis and the Bill & Melinda Gates Foundation agreed to work on a more affordable, globally accessible in vivo gene therapy for sickle cell disease. The Gates Foundation has agreed to fund “a research team within NIBR wholly dedicated to developing an approach to delivering this potential treatment.” Terms weren’t disclosed.
Cambridge, Mass.-based Cytovia Therapeutics agreed to work with Cellectis on TALEN-engineered iPSC-derived Natural Killer cell therapies. Cellectis will get either $15 million in equity in Cytovia, or $15 million in cash, by the end of 2021.
GSK and San Francisco-based VIR Biotechnology agreed to expand the collaboration that started in April 2020 to work on neutralizing antibody therapies for COVID-19. The expanded deal now includes other viral infectious diseases, including influenza. GSK will partner on development of an intramuscular injection that’s supposed to work as a universal prophylactic for influenza A, and that has completed a Phase 1 trial. Next-generation antibodies to prevent or treat flu are also part of a three-year research collaboration. GSK is agreeing to pay $225 million upfront, plus make an additional $120 million equity investment.
Eli Lilly agreed to pay $125 million upfront to South San Francisco-based Rigel Pharmaceuticals to co-develop Rigel’s receptor-interacting serine/threonine-protein kinase 1 (RIPK1) inhibitor. The deal is global, exclusive, and covers all therapeutic indications.
San Francisco-based Nektar Therapeutics said it will receive as much as $150 million from SFJ Pharmaceuticals, a company backed by Abingworth and Blackstone Life Sciences, to develop bempegaldesleukin (BEMPEG), an IL-2 agonist in combo with Merck’s pembrolizumab (Keytruda) for head and neck cancer. Nektar will serve as the sponsor of the Phase II/III study. It has agreed to pay milestones over 7-8 years to SFJ, if it wins regulatory clearance.
Merck and AstraZeneca said they were planning to halt a Phase III trial early, at an interim analysis, because a data monitoring committee reported the drug has demonstrated superiority over placebo. The drug, olaparib, (Lyparza), is a PARP inhibitor being tested in the adjuvant setting for germline BRCA mutated, high-risk HER2 negative breast cancer after local treatment and neoadjuvant or adjuvant chemotherapy. Data will be presented at a medical meeting.
Sara Nayeem joined New York-based Avoro Ventures as a partner. She was previously with NEA for 12 years. She will source and manage biotech investments from early-stage to late-stage to crossover, the firm said in a statement.
Kizzmekia Corbett, the mRNA vaccine scientist at the NIH, was named to the TIME100. Read about her contribution in this essay by Tony Fauci.
Salt Lake City-based Recursion, the company using AI and other tech tools for drug discovery, hired Louisa Daniels as chief legal officer and general counsel. She was a vice president at Pfizer. (TR coverage of Recursion, Sept. 2020).
BIO hired Shaye Mandle as chief operating officer. He comes to the biotech trade association with experience in restructuring and rebranding Minnesota’s Medical Alley Association.
Westlake Village Biopartners hired Peter Calveley as chief operating officer.
South San Francisco-based Day One Biopharmaceuticals, the developer of treatments for kids with cancer, hired Charles York as chief operating and chief financial officer. (TR coverage of Day One’s $130m Series B round, Feb. 2021).
Boston-based Dewpoint Therapeutics added Regina Barzilay, Distinguished Professor for AI and Health at MIT, to its board of directors. (TR coverage of Dewpoint, Apr. 2019)
Cambridge, Mass.-based Evelo Biosciences, a microbiome-based therapeutics company, named John Hohneker to its board of directors. (The Long Run podcast with Evelo CEO Simba Gill, Nov. 2020).
Amgen said the FDA has granted Priority Review status to its application to market sotorasib, the KRAS G12C-directed small molecule drug for non-small cell lung cancer. The PDUFA review deadline is Aug. 16, but it wouldn’t be a surprise if the FDA acted sooner to approve this potentially pathbreaking medicine against one of the classic hard targets of oncology.
South San Francisco-based Cortexyme said its atuzaginstat Phase II/III trial for Alzheimer’s disease is on partial clinical hold, following an FDA review of “hepatic adverse events” – aka liver toxicity. The events were reversible and didn’t appear to cause long-term damage, the company said.
Novartis secured an expanded label from the FDA for sacubitril/valsartan (Entresto). The drug’s prescribing information is now thought to cover about 5 million of the estimated 6 million people in the US with forms of chronic heart failure.
The CDC, newly empowered to lead in the pandemic, pledged a $200 million “down payment” on improved genomic surveillance of SARS-CoV-2 and its increasingly troubling variants. For the world leader in genomics, this is an embarrassing late date to get moving in a nationally coordinated way to help us adapt our behavior as the virus evolves. We are sequencing fewer than 1 percent of samples, and expert say we need to get to 5 percent, and do it with samples from around the country, if we’re going to have an adequate surveillance system.
See below this Twitter exchange with a genomic surveillance expert, explaining why so little sequencing of viral samples was being done as recently as December. We late to the game, and have some serious catching up to do.
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.
Michele Andrasik, PhD. Director, Social & Behavioral Sciences and Community Engagement
HIV Vaccine Trials Network; Affiliate Assistant Professor, Global Health, University of Washington
By Michele Andrasik, Sally Bock, Stephaun Wallace and Michael Ferguson
This month, when the news was full of stories of vaccine scarcity and images of long lines of people hoping to get immunized, the COVID-19 Prevention Network and Fred Hutch ran TV ads during the Super Bowl for people still hesitant about the vaccine in Washington state.
When given this rare opportunity to reach so many people, we were careful about what to say and not to say.
There was no scolding or chiding or pleading.
The narrator of the ad invites people to engage, and empowers them to come to their own conclusion. “You may still be doubtful. That’s OK. We can work together to get answers to your questions,” the narrator says.
In one word: equity.
COVID-19 vaccinations in Washington state began on Dec. 14. As of Feb. 8 — 56 days later — a little over 10% of Washington state residents received their 1st dose and slightly less than 3% were fully vaccinated.
The large majority of those who have gotten their first shot (66.6%) and who have gotten fully vaccinated (65.8%) are White.
Only 18% of individuals initiating vaccinations are from BIPOC communities. The people who are suffering disproportionately from the pandemic are also less likely to get the vaccine.
For BIPOC communities hardest hit by COVID-19, vaccination rates are disturbingly low, particularly among Native Hawaiian/Pacific Islander (0.5% of the vaccinated population), American Indian/Alaska Native (2.2%), Black/African American (2.2%), Hispanic/Latino/a (4.7%) and Asian Americans (8.3%).
Although Black, Indigenous and People of Color (BIPOC) represent 34.6% of the total population of Washington state, as is the case nationally, these groups carry the greatest COVID-19 burden, representing 52% of all COVID-19 cases, 47% of COVID-19 hospitalizations and 29% of COVID-19 deaths.
Among BIPOC communities, the Hispanic/Latino/a community is most disparately impacted by COVID-19, representing 32% of all COVID-19 cases, 24% of hospitalizations and 12% of deaths.
The rates are also disproportionately high among Asian, Black, Native Hawaiian, Pacific Islander, American Indian and Alaska Native communities. These rates are likely higher as testing is limited across the state and a significant number of confirmed cases, hospitalizations and deaths are missing racial and ethnic information.
The creative strategy behind the vaccine confidence campaign is to validate the questions and concerns of the hesitant, and to empower people to get back to the things COVID-19 has taken away—gathering with family and friends, freedom from masks and worry about the virus, and reopening businesses.
But ads alone won’t build confidence. It takes open and transparent dialogue, hearing from trusted messengers, and assurance that the research behind the vaccines is thorough and that people that look like them have been part of it.
The campaign is supported by a website — PreventCovidWA.org — to continue the dialogue. It uses an integrated media strategy with animated videos breaking down the science behind the vaccines, “Ask An Expert” videos featuring the diverse physicians and researchers who led the Phase III vaccine trials, and testimonials from people who volunteered for studies and people who have been vaccinated.
With deep listening through digital channels and on-the-ground community engagement, the content is dynamic. It’s responsive to community conversation as the scientific narrative unfolds and changes and new and novel misinformation and myths arise.
These aren’t just strategies suggested by audience research. These are the strategies the COVID-19 Prevention Network (CoVPN) has been developing and refining since spring 2020 when it began preparing for Phase III COVID-19 vaccine trials. Those studies were conducted at unprecedented speed and scale and with some of the highest representation of BIPOC people ever.
The CoVPN was formed in April 2020. Tony Fauci turned to the clinical trial networks the NIH had established for HIV/AIDS and charged them with conducting large scale Phase III trials for COVID-19 vaccines being developed under what came to be called Operation Warp Speed.
One of those leaders was Larry Corey, renowned virologist, head of the HIV Vaccine Trial Network and past president and director of Fred Hutch. We were well-positioned for this work based on years of experience in HIV vaccine trial work.
Immediately, the HIV Vaccine Trials Network (HVTN) Community Engagement and External Relations teams began reaching out to longstanding community partners to learn more about the impact of COVID-19 in their respective communities, to better understand COVID-19 fears and uncertainty, and to identify what information was needed to ensure that communities had the resources they needed to make informed decisions about participation in the vaccine trials in the short term and vaccine acceptability and uptake in the long term.
Priority populations — older adults (65+), Black, Latino/a/Hispanic, Indigenous and People of Color — have been the focus of these efforts for months. Strong community partnerships — rooted in bidirectional communication, trust and reciprocity — were the cornerstones of the plan.
A few weeks into the new CoVPN efforts, a strategic communications and marketing effort was launched to extend out from the community-based work. A creative partnership was formed among CoVPN leadership and the agencies Socialisssima and Sam Bonds Creative, who brought their deep expertise in BIPOC consumer mindsets to develop a mass media campaign that was both national and localized.
The community engagement plan focused on increasing awareness and knowledge. We sought to build trust by lifting up the voices of people with lived experiences. Our community-based researchers listened carefully to the concerns being raised. The campaign sought to address the common fears, uncertainty, isolation, mistrust and misinformation by offering hope, a way to end the uncertainty and a call to action.
The Super Bowl ad reflects this emphasis — it features real people who might look like you and have questions and concerns. Those questions and concerns are dealt with respectfully.
People working to build vaccine confidence in Washington state. From left to right: Sally Bock, senior director, marketing, CoVPN; Stephaun Wallace, director of external relations, CoVPN; Michael Ferguson, director of marketing, CoVPN; Norberto Zylberberg, founder, Socialisssima; Sam Bonds, principal, Sam Bonds Creative
All of these efforts to engage community built a strong foundation for the Washington state effort.
Then we got a bit lucky.
When our CBS affiliate reached out on short notice with available Super Bowl commercial space, we were able to produce a strategic and emotionally on-target 30-second Public Service Announcement in just days.
Of course, a Super Bowl ad is just one opportunity to spread the word. We also partnered with the Washington State Department of Health to develop a user-friendly vaccination website specific to Washington state – PreventCovidWA.org – where people from across the state can obtain information about available vaccines, hear testimonials from people who participated in the vaccine trials and from people who have been vaccinated, and schedule a vaccination appointment.
Partnering with community and working together, with all members providing direction and guidance, is what ensured equity and inclusion in the COVID-19 vaccine clinical trials.
This approach worked before – it is what made the vaccine trials as diverse as they were.
It IS the same approach that will help us achieve equity and inclusion in this vaccination campaign.
For more information on the PreventCovidWA campaign, check Instagram and Facebook.
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.
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.
Luke Timmerman, founder & editor, Timmerman Report
Our culture tells us to fear death.
Every day, we hear updates on the COVID-19 death toll. Deaths are broken down by age, race, ethnicity. By state and nationality.
The US numbers – 473,000 and increasing by more than 3,000 a day – are tragic and numbing.
But while we fixate on death, we are devoting scant attention to the insidious, cumulative toll of morbidity from COVID-19. The ‘Long COVID’ story is one of those gradual ones that sneaks up on us over time.
The types of symptoms, the number of people struggling, the severity of chronic disease, how long the symptoms might last – these are all important questions are only beginning to come into focus.
The Mt. Sinai Center for Post-COVID Care in New York estimates that 10 to 30 percent of all COVID patients will suffer from long-term symptoms. As of this writing, we have had 27.3 million confirmed cases of COVID-19. That’s an undercount, but if you use that number for the sake of argument, we could be looking at 2.7 million-8.2 million people in the US alone who are struggling with some sort of chronic disease stemming from COVID-19.
Doctors who see COVID patients are telling me that Long COVID is the real thing, not just a few anecdotes here or there, and not some minor bellyaching from hypochondriacs as was sometimes implied by some stressed-out clinicians early in the pandemic.
“The Long Haul story is not one that has been fully told,” said Peter Hotez, a virologist at Baylor College of Medicine in Houston, and director of vaccine development at Texas Children’s Hospital Center, in a recent appearance on CNBC. “Literally millions of people could have some lingering symptoms.”
Deaths are “the tip of the iceberg,” Hotez said.
What are common Long COVID symptoms?
Data are just beginning to surface to tell the story. A 6-month follow-up study from Wuhan, China, published last month in The Lancet, found that 63 percent of COVID-19 survivors complained of fatigue and muscle weakness, and 26 percent reported sleep difficulties. About one out of every four people discharged from the hospital reported depression or anxiety. One-fourth of patients were unable to reach the lower limit of normal distance on the 6-minute walk test.
Tony Fauci has described some of the symptoms as similar to myalgic encephalomyelitis (aka chronic fatigue syndrome). While lingering inflammation may be a common thread in the two conditions, the set of symptoms don’t exactly overlap. To collect more data from Long COVID patients, Johns Hopkins Bloomberg School of Public Health is conducting an online survey. It hopes to recruit 25,000 participants. (Survey Here).
My hope is that in the coming weeks, as our country continues to ramp up the biggest vaccination campaign in history, that we keep these devastating long-term consequences in mind.
I’ve heard stories in my extended family. There’s a distant cousin, a 20-something college undergraduate. She dropped out of college because of brain fog from Long COVID. She can’t concentrate. She’s unsure if or when she’ll be able to go back.
What must that be like, to be 21 and get a bug that doesn’t seem too terrible at first, but that ends up altering the trajectory of your life?
Often, the Long COVID effects show up in middle-aged, healthy people. Recall the Dec. 7 TR article by Blair Clark-Schoeb. She’s in her mid-40s, a parent, an athlete, and a successful biotech professional.
E. Blair Clark-Schoeb, SVP of communications, Aruvant Sciences
Her struggle with Long COVID began in March. It continues. She described it on a recent podcast.
Entire biotech funds will probably be raised in the months ahead to deal with the whole new set of chronic diseases that our healthcare system will have to confront. There will be ideas for treating chronic inflammation, for the clotting disorders, the depression, the anxiety, the diabetes-like symptoms.
The demand for biopharma to step up and deliver will be clear.
That’s a good thing. It will give purpose and drive to many in this industry. If biotech can rise to the occasion with vaccines, therapies and diagnostics, it can find a way forward here.
The main thing to remember in the urgent here and now is the importance of hunkering down for another couple of months, with masking and distancing, until the vaccines have a chance to crush the curve.
I’m much more optimistic than I was at the start of the year, because we have not just two outstanding vaccines, but two more excellent and practical options on the way from J&J and Novavax.
Let’s do everything we can to help everyone see why getting vaccinated is so vital, and so urgent. It’s not only about saving lives. It’s about helping us all live long and healthy lives.
The CDC – still the world’s premier epidemiology and public health agency – screwed up big-time with testing at the start of the biggest pandemic in a century. Things got worse when it was muzzled and marginalized. But now that CDC has a capable leader in Rochelle Walensky with support from the White House, the CDC is in a stronger position to bring down community transmission. To that end, the CDC urged the public to consider “double-masking” as a more rugged defense against the more troubling B117 and B.1.351 variants now in circulation. For more, see this Feb. 10 JAMA article on “Effectiveness of Mask Wearing to Control Community Spread” by a couple of CDC scientists.
The CDC reported on vaccine hesitancy in its Morbidity and Mortality Weekly Report (MMWR), and the numbers are moving in the right direction. If you group together respondents who said they were “absolutely certain,” or “very likely,” or “somewhat likely” to be vaccinated, the intent to get vaccinated increased overall from September (61.9%) to December (68.0%). Those household surveys, it should be noted were taken during the intense emotions of election season, news reports of astounding efficacy for Pfizer and Moderna, and FDA Emergency Use Authorizations in December.
People age 65 and older, the ones at highest risk of COVID-19, showed increasing willingness to get the shot.
And yet, the pockets of resistance are high, and stubborn. See this recent snapshot from the Kaiser Family Foundation Vaccine Tracker. The percentages below are people who say they will “Definitely Not” get a COVID-19 vaccine. That’s 13 percent of the country, including 25 percent of Republicans and 21 percent of Rural people. (Survey data: Jan. 11-18, 2021)
Some people, on the extreme left and right, are going to be unreachable in their anti-vaccine attitudes. Maybe the biggest area of concern are the people who are in the middle, suffering from the breakdown of trust, the epistemic crisis at the bottom of the barrel of cynicism. Millions of people don’t know who or what to believe. As David Shaywitz wrote here last week, this is the result of “manufactured nihilism.”
The results are plain to see. Weeks after news about 95 percent effective vaccines becoming authorized by the FDA – one of the greatest achievements in the history of science – we still see huge swaths of the US public struggling along, saying they’ll “Wait and See.” (See the demographic breakdown from the Kaiser Family Foundation survey, Jan. 11-18.)
Will these numbers trend in ever-more positive directions in coming weeks and months? I hope so. The NYT ran an editorial co-signed by 60 Black members of the National Academy of Medicine urging African Americans to get vaccinated. The Kaiser Family Foundation notes that openness to vaccination tends to increase when people know someone else who has been vaccinated.
Repurposed Antiviral Drugs for Covid-19. NEJM. Feb. 11. (WHO Solidarity Trial Group)
Tocilizumab IL-6 inhibiting therapy in COVID-19 patients admitted to the hospital. Overall, 596 (29%) of the 2022 patients on tocilizumab and 694 (33%) of the 2094 44 patients on usual care died within 28 days. MedRxiv. Feb. 11. (RECOVERY trial group)
Researchers reported that once-weekly subcutaneous injections of semaglutide (Ozempic), a GLP-1 peptide analog drug for diabetes from Novo Nordisk, significantly increased weight loss when boosted up to a 2.4 milligram dose (the drug is usually given in a 0.5 to 1 mg subcutaneous once weekly shot for diabetes).
The mean change in body weight from baseline to week 68 was −14.9% in the semaglutide group compared with −2.4% with placebo, according to investigators from the STEP1 trial, writing in the New England Journal of Medicine. Nausea and diarrhea were the most common side effects; but were typically mild to moderate and went away over time. See comment from Sek Kathiresan, a cardiovascular genetics expert, and CEO of Verve Therapeutics.
Given the huge and rising prevalence of obesity in the US, this is maybe the most clinically relevant result I’ve seen on a population level in a long time. See the CDC state-by-state graphic below that shows rates of obesity, defined as people with Body Mass Index of 30 or higher. Obesity, by the way, is an added risk factor for COVID-19 complications.
The US government agreed to order 100 million more doses of the mRNA vaccine from Moderna. That means that US government has agreements to get 300 million doses out of the 631 million doses Moderna has lined up in supply agreements with governments around the world.
Merck is reportedly in negotiations with governments, public health agencies, and other companies to fire up its considerable capabilities for manufacturing COVID-19 vaccines. The Kenilworth, NJ-based company, one of the world’s major vaccine producers, scrapped its novel vaccine programs after they failed to generate an adequate immune response.
Pharmacies around the country were due to get 1 million doses of COVID-19 vaccines from the federal government as of yesterday, Feb. 11. The companies, including national chains like CVS and Walmart, have confirmed they don’t want to let any doses go to waste. That raises the question of who will get leftover doses. Their employees, or the public?
A Houston doctor had 10 doses of vaccines that were due to expire, and had to be used. He gave them to people with medical conditions. He got fired and publicly humiliated for trying to do the right thing, trying to avoid a travesty. This is one of those zeitgeist stories about a society suffering from a breakdown of trust. (NYT, Feb. 10, 2021)
Vaccinated People Are Going to Hug Each Other. Julia Marcus writes: “The vaccines are phenomenal. Belaboring their imperfections—and telling people who receive them never to let down their guard—carries its own risks.” The Atlantic. Jan. 27. (Julia Marcus of Harvard Medical School)
South San Francisco-based Day One Biopharmaceuticals, the developer of pediatric cancer drugs, raised $130 million in a Series B deal led by RA Capital Management. (Timmerman Report coverage).
Boston-based Ensoma raised $70 million in a Series A financing to develop adenoviral vectors for cell therapies that can be made more accessible around the world. 5AM Ventures led. Ensoma also announced a partnership with Takeda Pharmaceuticals to work on in vivo gene therapies for up to five rare disease programs. (Timmerman Report coverage).
Menlo Park, Calif.-based PacBio, the developer of long-read DNA sequencing instruments and technology, raised $900 million in convertible debt from an affiliate of Softbank Group.
London-based Quell Therapeutics, a developer of T-regulatory cell therapies, expanded its Series A to $84 million.
New York and Stamford, Conn.-based Sema4 went public by combining with a Special Purpose Acquisition Company (SPAC) sponsored by Casdin Capital and Corvex Management. Sema4 describes itself as an “AI- and machine learning-driven patient-centered genomic and clinical data intelligence company.” The deal is expected to bring $793 million in total cash.
Seattle-based Nautilus Biotechnology, a proteomics company, merged into a SPAC sponsored by Perceptive Advisors, going public in a deal that’s fetching about $350 million. (TR coverage of Nautilus, June 2020).
New York-based Nuvation Bio went public via a merger with a SPAC sponsored by EcoR1 Capital. Nuvation, led by former Medivation CEO David Hung, is working on novel cancer drugs. It secured $646 million through the SPAC and related transactions, bringing its cash balance to $830 million.
Vancouver, BC-based Notch Therapeutics raised $85 million in a Series A financing to develop induced pluripotent stem cell-derived therapies for cancer. Allogene Therapeutics, Lumira Ventures, and CCRM Enterprises Holdings, EcoR1 Capital, Casdin Capital, Samsara BioCapital, and Amplitude Ventures participated.
Cambridge, Mass.-based KalVista Pharmaceuticals raised $193 million in a stock offering at $36 a share. It’s developing small molecules against hereditary angioedema and diabetic macular edema.
San Mateo, Calif.-based Sagimet Biosciences raised $80 million in a crossover financing. Its lead program is for NASH.
San Diego-based Pipeline Therapeutics said it raised $80 million in a Series C financing to advance its work on small molecules for neurodegeneration. New investors include Perceptive Advisors, Franklin Templeton, Casdin Capital, Samsara BioCapital, and Suvretta Capital.
Menlo Park, Calif. and Boston-based Adicet Bio raised $120 million in a stock offering. It’s working on allogeneic T cell therapies.
Lexington, Mass.-based Cyteir Therapeutics, the developer of synthetic lethal cancer drugs, raised an $80 million Series C financing. RA Capital Management led.
Baltimore, Maryland-based Personal Genome Diagnostics, a cancer genomic profiling company, raised $103 million in a Series C deal led by Cowen Healthcare Investments.
San Francisco-based Adagene, the developer of antibody drugs for cancer, raised $140 million in an IPO at $19 a share for American Depositary Shares.
San Carlos, Calif.-based BigHat Biosciences raised $19 million in a Series A financing to advance its AI-guided antibody design platform. A16Z led.
London-based Autolus, a T-cell therapy developer, raised $100 million in a stock offering.
Charlottesville, Virginia-based Hemoshear Therapeutics, the developer of treatments for rare metabolic disorders, raised $40 million in a Series A financing led by Suvretta Capital.
Indianapolis-based Apria Health, a home healthcare equipment and sleep apnea equipment provider, raised $150 million in an IPO at $20 a share.
Durham, NC-based Bioventus, the developer of orthobiologics for musculoskeletal conditions, to avoid elective surgeries, raised $104 million in an IPO at $13 a share.
New York-based Kadmon Holdings took on $200 million in debt.
Eli Lilly won FDA Emergency Use Authorization for the neutralizing antibody combination of bamlanivimab (LY-CoV555) and etesevimab (LY-CoV016) for COVID-19. It’s for mild-to-moderate COVID-19 patients at high risk of progression to severe disease. The FDA is also allowing a shorter infusion time of 16 or 21 minutes, compared with the previous 60 minutes, which ought to make the infusion more practical in a pressure-packed hospital environment where minutes count.
Regeneron said it won FDA clearance to market evinacumab-dgnb (Evkeeza), a monoclonal antibody directed at ANGPTL3, as a treatment for homozygous familial hypercholesterolemia – a rare genetic disease that results in elevated cholesterol levels and raises the risk of heart attack, stroke and death. A couple days earlier, Regeneron won FDA clearance for cemiplimab-rwlc (Libtayo), a PD-1 inhibitor for advanced basal cell carcinoma for patients who have previously gotten a hedgehog pathway inhibitor, or for whom that kind of medicine isn’t appropriate.
The FDA’s Oncologic Drugs Advisory Committee voted against approval of Merck’s PD-1 inhibitor pembrolizumab (Keytruda) as a neoadjuvant treatment for high-risk, early-stage triple-negative breast cancer in combination with chemotherapy after surgery. The data were premature, leaving the door open to a future reconsideration.
Cambridge, Mass.-based Surface Oncology promoted Robert Ross to president and CEO. He was previously chief medical officer. Current CEO Jeff Goater will remain chairman of the board.
South San Francisco-based Cortexyme, the developer of a treatment for Alzheimer’s disease, promoted Chris Lowe to chief operating officer and chief financial officer.
Cambridge, Mass.-based Synlogic named Lisa Kelly Croswell to its board of directors. She is senior vice president and chief human resources officer for Boston Medical Center Health System.
Cambridge, Mass.-based Dewpoint Therapeutics named Joel Sendek as its chief financial officer. He was previously CFO at Sema4.
San Francisco-based Lyell Immunopharma, a developer of T cell therapies for solid tumors, hired Charlie Newton as chief financial officer. He was previously with BofA Securities as a healthcare investment banker.
Vancouver, BC-based AbCellera, the antibody discovery company, promoted Ester Falconer to chief technology officer. She was previously head of R&D.
Eli Lilly said Anat Ashenazi has been promoted to chief financial officer, replacing Josh Smiley, after learning of “an inappropriate personal relationship between Mr. Smiley and an employee.”
Los Altos, Calif.-based Retrotope, a company working on degenerative diseases, said Rick Winningham has been named its new chairman of the board. He’s the chairman and CEO of Theravance Biopharma.
Gilead’s Kite Pharma cell therapy unit said Frank Neumann has joined as senior vice president and worldwide head of clinical development. He replaces Ken Takeshia, who is leaving the company at the end of February.
Cambridge, Mass.-based Gemini Therapeutics hired Brian Piekos as chief financial officer. The company is working on precision medicines for age-related macular degeneration.
Berkeley, Calif.-based Caribou Biosciences, a CRISPR genome editing company focused on CAR-T and CAR-NK cell engineering, hired Jason O’Byrne as chief financial officer. He was previously SVP of finance at Audentes Therapeutics.
UK-based Exscientia, an AI pharmatech company, named Elizabeth Crain to its board, along with Ben Taylor, the company’s chief financial officer.
Gilead Sciences and its partner, Belgium-based Galapagos NV, said they are shutting down the Phase III trials of ziritaxestat in patients with idiopathic pulmonary fibrosis. A Data Safety Monitoring Board recommended the trials be halted. The latest failure comes after another Gilead / Galapagos partnered program, filgotinib for rheumatoid arthritis, was rejected by the FDA. The partnership was originally valued at $5 billion in 2019.
Dallas-based Taysha Gene Therapies announced a pair of research collaborations with the Cleveland Clinic and University of Texas-Southwestern to further develop AAV vectors to carry mini-gene payloads for epilepsy and other CNS diseases. Terms weren’t disclosed.
AbbVie agreed to work with Berkeley, Calif.-based Caribou Biosciences on CRISPR-based genome editing programs for CAR-T cell therapies. Caribou is pocketing $40 million upfront.
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.
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.
Today’s guest on The Long Run is Sek Kathiresan.
Sek is the co-founder and CEO of Cambridge, Mass.-based Verve Therapeutics.
Sekar Kathiresan, co-founder and CEO, Verve Therapeutics
Verve is using genome editing technology in a bold fashion. Its idea is to develop a one-and-done shot that essentially would prevent cardiovascular disease in adults. Its plan is to start out with a group of patients at very high risk of cardiovascular disease, and potentially broaden the availability of the treatment later.
The treatment, which uses a newer-generation editing technique known as base editing, takes aim at a gene called PCSK9. Scientists have long for a long time that if you knock out the activity of this gene out, you can dramatically reduce LDL cholesterol and reduce the risk of heart attack, stroke and death from cardiovascular disease. Verve’s technology aspires to do this with a single shot.
The company has shown some pretty compelling data that this approach works in monkeys, and the effects are holding up after 6 months of follow-up.
Sek is a native of India, and immigrated to Pittsburgh in elementary school. He got a broad-based education there, including a bachelor’s degree in history, that he says served him well before he became a physician and scientist and entrepreneur. I think you’ll enjoy Sek’s story.
Now, before we get dive in…a word from the sponsor of The Long Run.
Synthego is a genome engineering company that enables the acceleration of life science research and development in the pursuit of improved human health. The company leverages machine learning, automation, and gene editing to build platforms for science at scale. With its foundations in engineering disciplines, the company’s platforms vertically integrate proprietary hardware, software, bioinformatics, chemistries, and molecular biology to advance life sciences from basic research through therapeutic development programs. By providing commercial and academic researchers, and therapeutic developers with unprecedented access to cutting-edge genome engineering products and services, Synthego is at the forefront of innovation in engineered biology.
If you click there, you’ll learn about Synthego and help Timmerman Report along the way, so what’s not to like?
Now, please join me and Sek Kathiresan on The Long Run.
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.
Mara Aspinall, managing director, BlueStone Venture Partners; professor of the practice, biomedical diagnostics, Arizona State University
The biggest questions at this moment in the pandemic concern emerging variants.
Over the past two weeks in preprint publications, we have learned:
A word on biology: all viruses evolve new point mutations (aka variants) all the time, and the vast majority of these reduce strain fitness. Fitness means that a particular strain outcompetes all others to become the dominant source of infection in a region. A particular strain’s fitness may be based on spreading faster or more easily and/or because it is better at escaping the immune system.
Both of these aspects are concerning, but as we get better at countermeasures (antibody treatments and vaccines), it is immune escape that most threatens to derail our hopes for beating the epidemic. Fitness results from the net benefit of all the underlying positive, neutral and beneficial mutations that have evolved and are packaged with a “headline” mutation.
We tend to focus on single point differences within a strain. Currently, the greatest concern stems from the E484K mutation, (found in COVID-19 samples from South Africa and Brazil). The next most concerning mutation is known as N501Y (first identified in the UK, but present in South African, Brazilian and US strains also). In distant 3rd place, we there’s the Y453F mutation (the Danish mink strain). These new mutations have now all combined with the D614G mutation, which became the globally dominant form of SARS-CoV-2 in February 2020.
It can be misleading to focus on single headline mutations only. For example, see a small study in the UK that found that the Pfizer/BioNTech vaccine, originally developed based on the genetic code of SARS-CoV-2 from Wuhan in January 2020, was equally effective in neutralizing a modified strain containing only the 3 key UK mutations (N501Y; A570D; del69/70).
That sounded good at first glance. But when faced with all 23 mutations present in the wild type UK B.1.1.7 variant, the Pfizer / BioNTech vaccine was 3.9x less neutralizing. Of course, we know that even a reduction of this magnitude is still highly effective in mitigating or protecting from the disease for most cases, but we do not know how much of an immune response is enough to protect individuals, or whole populations, from illness.
Carefully controlled lab tests of new viral variants against the vaccines are essential, but can be only directional guides to what might happen in the real clinical world. Unfortunately, the strains that embed the variants of most concern, are now spreading around the world and appear to be fueling recent growth waves of COVID-19, especially in the UK.
We are in a scramble to figure out what they mean against a background of limited but growing scientific data. There is evidence that N501Y accelerates transmission by 50-70% (10x greater affinity to the ACE2 receptor on human cells reduces the viral load necessary for successful infection). Plus, early data on N501Y indicates that it also contributes to more serious disease and immune escape. E484K appears to drive immune escape more strongly than N501Y, making the combination present in the South African strain of great concern.
If we have a circulating variant that is more transmissible, causes more severe illness, and is more able to escape vaccine-induced immune responses – then we are truly up against a much more formidable virus.
Until the E484K variant was identified, the answer was no.Now that we see E484K containing strains in both South Africa and Brazil, the early answer appears to be yes. Before the emergence of the E484K variant, there was a consensus that for all but the immune-compromised, natural infection protected against reinfection for at least 6 months or longer. Reinfection cases had been documented, but at very low rates (e.g. 0.16% of previously COVID positive UK health workers).
Most concerning is the emergence of a second — more lethal — wave of infection in Manaus, Brazil. The experience from Manaus implies novel spike variants can re-infect those who have recovered from the strains circulating in early 2020. Manaus is an isolated community of 2 million in the Amazon rain forest, where effective control had been achieved by May 2020. By mid-December, an estimated 76% of the population had been previously infected and was presumably COVID-immune.
But that turned out to be an illusion. In January, a more transmissible and virulent strain (P.1, a derivative of the B.1.1.28 Brazil strain) was identified, supported by a case investigation of a patient who had recovered in late March but became reinfected in December. Data are preliminary and limited, but highly suggestive that the new strain in Brazil can overcome immunity gained from previous SARS-CoV-2 infection.
Individual test effectiveness will have to be continuously monitored for evasion, but none of the known variants have yet had a significant impact on test accuracy since most (all of the rapid antigen tests) detect the abundant nucleocapsid protein and its mRNA. Almost none target the mutated spike regions, and very, very few focus on the spike region alone.
Variants do threaten the highly specific monoclonal antibody-based therapies. The antibodies most effective at neutralizing the virus are those directed at very specific epitopes within the receptor binding domain of the spike protein. This is a small region, and is where the variants of most concern reside. There is evidence that the SARS-CoV-2 virus is able to generate variants to escape focused antibody therapies, but since very few of these have been used clinically to date, emerging strains must have been able to develop current immune mitigation strategies (e.g. E484K) even under the much wider pressure of the immune response to natural infection.
Current vaccines are all designed to focus on the most effective aspects of response to natural infection i.e. to the spike protein, and so there is a parallel threat that the virus will be able to evolve further escape variants as vaccination is rolled out, and puts greater pressure on the virus to adapt or die.
Notably, Israel is providing early data that vaccines will retain substantial effectiveness – the dominant strain in Israel is becoming the UK B.1.1.7 strain, and vaccine effectiveness is already apparent, but at lower levels than in clinical trials.
The faster we vaccinate, the less opportunity there is for escape adaptation to occur and spread.
We need to proactively adapt our vaccine portfolio to the strain mutations that are rapidly emerging and becoming dominant, while remaining vigilant that testing targets do not mutate away from current probes and primers.
For now, it appears that current vaccines still have adequate, albeit reduced, efficacy in the face of emerging variants. However, time is not on our side – in the year it has taken for science to deploy vaccines against the original Wuhan sequence, the virus has evolved 4 novel mutations. Taken together, these mutations substantially enhance transmissibility and virulence.
We have the ability to keep up, but only if we adopt a flu-vaccine-like timetable. In early 2020 Moderna, among others, developed their first vaccine candidate 4 days after publication of the SARS-CoV-2 genome on Jan. 12; two months later an improved candidate was beginning Phase I/II trials. The FDA granted an Emergency Use Authorization on Dec. 18.
This is light speed by the standards of prior novel vaccine approvals – a 10-year timeframe reduced to 10 months. Shortening traditional approval timelines, for new mRNA vaccine variations designed against the new variants, will be absolutely essential. A further reduction to 10 weeks or less is required to counter emerging mutations.
Safety is less concerning since vaccines will utilize unchanged packaging – this is akin to a slight modification like we see with flu vaccines each year. No major 30,000-volunteer study will be needed to demonstrate safety and efficacy. Variants require minimal changes to vaccine payloads, and testing targets. Efficacy can be monitored post-launch in a Phase IV manner since it will be reasonable to expect only improved efficacy from including novel point mutations in payload design.
The FDA sees the need for urgency. On Feb. 4, the FDA issued a statement on accelerated timetables for confronting the emerging variants – “We do not believe that there will be the need to start at square one with any of these products” (i.e. tests, therapies and vaccines). Few specifics were included, but keeping up with the variants means not only quickly adapting our vaccines, but also enhancing variant surveillance, evaluation and communication.
We should not underestimate the degree of culture change required of both regulators and risk managers at vaccine companies if an adequately speedy response is to be successful. It’s a serious challenge. There’s no time to waste.
David Shaywitz
The goal of “alternative facts,” is “to flood the zone with sh*t,” as former Trump advisor Steve Bannon notoriously explained to the author Michael Lewis. The idea is to persuade us it’s just too difficult to know what to believe about anything.
This “manufactured nihilism,” as Vox’s Sean Illing memorably described it, enables us to default to our own instincts and inclinations. If you’re inclined to believe that COVID is a hoax, say, the consequences can be lethal.
Manufacturing nihilism isn’t a heavy lift: as economist Tim Harford reviews in his new book, The Data Detective, lots of behavioral research suggests we’re easily persuaded to doubt information we don’t want to believe.
For instance, when the tobacco industry was initially attacked after robust clinical data demonstrated their product was deadly, for instance, it launched a deliberate public relations campaign to muddy the water. The facts were uncertain, the companies argued.
Many dedicated smokers, sadly, were all too eager to believe this fundamentally bogus message.
*****
As if facts weren’t in enough trouble already, new research, published in January in Proceedings of the National Academy of Sciences (PNAS), demonstrates that when it comes to moral or political issues, we are more likely to respect an argument based on personal experience than one rooted in data.
“In moral disagreements,” the authors report, “experiences seem truer than facts.”
They continue,
“Across many studies, basing one’s stance on personal experiences (versus facts) seems to make people appear more rational to opponents. We suggest that this effect is because personal experiences are unimpugnable; first-hand suffering may be relatively immune to doubt.”
Especially as a scientist, it’s hard not to feel demoralized by these results. A cornerstone of science is the importance of not confusing anecdotes with data – you can actually buy a “scientist shirt” on Amazon bearing the motto, “The plural of anecdote is not data.”
Yet now scientists have data demonstrating that anecdotes tend to be more persuasive.
Adding insult to injury, the final experiment reported by the researchers compared a subject’s reactions to:
The result?
“[P]articipants saw the personal experiences of the layperson as the ‘truest,’ followed by the scientific research, and then facts provided by a layperson. That people see one person’s anecdotal experience as truer than the conclusion of scientific research is striking.”
Striking, and also scary, because it means truth is effectively defined by the most compelling personal story.
*****
In The Black Swan, Nassim Taleb introduces us to “narrative fallacy,” a cognitive deception “associated with our vulnerability to overinterpretation and our predilection for compact stories over raw truths.”
It’s hardly news that we are drawn to stories, of course. But motivated by behavioral researchers such as Daniel Kahneman, we’ve started to quantify the remarkable strength of this attraction, and to reach for a more productive response than casual despair.
The power and relatability of anecdote might be used to bridge divergent perspectives, the authors of the January PNAS paper write, noting their results can be read as offering guidance for engaging those who are on the opposite side of fraught issues.
Rather than trying to lead with facts, the authors suggest, “personal experiences might be deployed early in conversations to first build a foundation of mutual respect, and then facts could be introduced as the conversation moves to policy specifics.”
A similar strategy was used in the 2020 election by Republican Voters Against Trump (RVAT), which sought to encourage GOP defections not by presenting data on, say, the deficit under Trump or the number of lives lost to COVID, but rather, by letting people tell their own stories. RVAT encouraged disaffected Republicans to upload raw video selfies – relatable and compelling personal stories about why they opposed Trump. RVAT would then curate and promote the best videos, in hopes that these personal anecdotes would resonate with other disaffected Republicans.
*****
It’s hard – especially as a scientist – to escape the sense that persuasion should be based on a common set of facts and shared standards for evaluation – the premise of the scientific method – rather than accessible anecdotes. Yet at a time when a quarter of unvaccinated adults say they don’t want to get immunized, and most Republican voters continue to insist the election was stolen – it’s clear that facts alone aren’t cutting it.
Purists may need to take a page from the RVAT playbook, and lean into personal narratives to convey the vital lessons suggested by the data.
Perhaps some Republicans would be moved by the raw, personal stories of Trump-leaning state election workers — ordinary people — who describe their own, meticulous efforts to ensure the vote was free and fair, even if they were disappointed by the outcome.
Similarly, efforts to encourage vaccination will need to go beyond the recitation of the (extraordinarily reassuring) safety and efficacy data, especially given the tendency of any rare adverse event to be widely publicized by the media and amplified by critics.
To counter this, a marketing expert advised in a recent New England Journal of Medicine,
“[V]accine communications teams should proactively spread their own ‘cases’ in addition to statistics. News briefings or websites could include real individual success stories — a Georgia family going out for ice cream after being vaccinated, perhaps, or Indiana retirees joyfully visiting neighbors 10 days after receiving the vaccine. Such stories, however banal, can help counteract the shock value of a few bad-effect stories.”
At best, these approaches are likely to change only a few minds. It’s notoriously difficult to move people off the comfort of their prior assumptions.
But even a few percentage points can make a big difference, both in deciding a close election and in blunting the spread of a deadly contagious virus.
If leaning on stories feels unseemly or unscientific, remember that if you want to persuade skeptics, the data are clear: in a world of alternative facts, the personal narrative is king.
Luke Timmerman, founder & editor, Timmerman Report
One photograph captured our contradictions on Jan. 6.
There was the man carrying the Confederate flag where it had never flown before – inside the US Capitol.
A violent mob, carrying symbols like that and worse, sought to assassinate elected officials and overthrow our democracy. They were sent there by other elected leaders who were telling lies.
It was horrific.
But look closer at the photo. There’s a portrait on the wall of a true American visionary — Justin Smith Morrill.
Kevin Seefried holds a Confederate flag outside the Senate Chamber during a riot in the U.S. Capitol on Jan. 6. (Associated Press)
Who?
US Rep. Morrill, from Vermont, was a founding member of the Republican Party. His signature achievement was the Land Grant College Act of 1862, also known as the Morrill Act. The law allowed proceeds from federal land sales to benefit states. The states, the ones still in the Union at the time, could use the bounty to start up technical and agricultural colleges. The law contained a community outreach component, and Reserve Officer Training Corps (ROTC) programs for decentralized military training across the states.
The bill had stalled for years in Congress, but was finally passed at the height of the Civil War. It was signed into law by President Abraham Lincoln.
This turned into one of the best investments in American history. MIT, Cornell University, the University of Wisconsin-Madison, University of California-Berkeley, and Michigan State University are a few of the outstanding education and research centers that owe their existence to this act (see map). Years after the war, former Confederate states were able to participate, as were the Historically Black Colleges and Universities.
Institutions established under the Morrill Act of 1862, and its subsequent expansions in 1890 and 1994.
These institutions, more than 150 years later, are integral parts of the country we inherited. The land grant universities are engines of research, teaching, education, community outreach, and economic development in all 50 states. They created — and continue to create — a national talent pool for science, engineering, and agricultural disciplines.
This investment, more than any single initiative, set the stage for the US to build the world’s leading network of research universities. When the NIH and NSF and Defense Department research agencies hit their stride after World War II, they were positioned to send grant dollars flowing through this pre-existing network.
It was like running semi-trucks full of equipment down an Interstate highway that someone had already thought to build.
The knowledge-based industries the US dominates today – tech and biotech – can trace their origins to this series of investments.
Yes, it’s hard to be a determined optimist these days. It’s hard to think about investing big for the future in a country this divided. We have 450,000 dead in the pandemic, and more than 3,000 deaths a day. Millions more are suffering mentally, physically, economically, and spiritually. We must vaccinate about 80-90 percent of a nation of 330 million people, jump start the world’s largest economy, and get serious about creating a more fair, decent and humane society. Then we have to confront the threat of future pandemics, and get serious about climate change.
But look at what Justin Smith Morrill and his contemporaries were up against. They had to win a brutal war that left 700,000 dead, while holding the Union together, ending slavery, rewriting the Constitution with the 13th, 14th and 15th amendments, and sending in federal troops to enforce the rule of law in the former Confederate states.
Even with so many fires to put out at once, the leaders in that generation thought in expansive terms.
We are at our best when thinking along these lines. We have reason to believe it can be done, even under the hardest of circumstances.
For Republicans who may be skeptical of those agencies above, take a look at our national security apparatus.
For instance, in October 2013, the Defense Advanced Research Projects Agency (DARPA) made a $25 million grant to a little startup called Cambridge, Mass.-based Moderna Therapeutics. The objective was to support mRNA vaccine development for pandemic preparedness.
I interviewed CEO Stephane Bancel. At the time, I wrote:
“By making this grant, [DARPA] is betting on what could become a superfast, cheap, and unusually adaptable method for fighting today’s known pandemic threats, and the unknown threats of the future.”
The US government was prescient. Moderna wouldn’t be where it is today without DARPA and the NIH supporting it every step of the way.
So what can we do now, besides the obvious things the President and leaders in Congress are working on?
Our failure to invest in young people is mind-boggling.
Consider a 2017 report from the Pentagon. It says that 71 percent of Americans ages 18-24 are ineligible to serve in the US military primarily because of three reasons: obesity, failure to graduate from high school, or a criminal record.
“This is a very real risk to our national security,” said Steve Doster, Pennsylvania State director of Military Readiness for Council for a Strong America, told the York Daily Record in 2019.
It’s also a sign of a country struggling with apathy. Our young people are yearning for purpose and hope. We’ve seen in other countries what happens when young people are hopeless. They turn to violent extremism, or surrender, living in fear of authoritarian leaders.
Biotech, as I wrote here last month, is shining with possibility amid the darkness. It’s one of the bright spots in the US. It’s why I think this industry needs to shine that light as far and wide as possible.
Those of you in industry can share the wonder and joy of discovery, especially with underserved communities that are full of untapped human potential. If kids in middle school and high school knew a fraction of what’s happening in biomedicine today, and they could pursue advanced study without taking on a mountain of debt, they’d tune in. (Life Science Cares is a terrific organization that connects biotech companies with nonprofit partners that advance education, and anti-poverty work.)
Too many people have given up on the American dream. We need to shake off the malaise. We should know our history, and never forget where our amazing scientific enterprise comes from.
Science of SARS-CoV-2
Vaccines
Access and Distribution
Genomic Surveillance
Features
Personnel File
Merck CEO Ken Frazier announced he plans to retire June 30, 2021 after a decade in the job. He will continue as executive chairman. Robert Davis, the current CFO, will become president in April and CEO on July 1 as part of the transition process. (See Matt Herper’s STAT article on Frazier’s career).
Merck said Stephen Mayo, a professor of biology and chemistry at Caltech, is joining the board of directors Mar. 15.
Ramona Sequeira, president of Takeda Pharmaceuticals USA, is the new chair-elect of PhRMA. She will be the first woman to serve as chair of PhRMA. She will replace Eli Lilly CEO Dave Ricks in that role next year. Novartis CEO Vas Narasimhan was elected to serve as PhRMA board treasurer.
Germany-based Merck KGaA said Rehan Verjee, the president of EMD Serono and head of innovative medicines, is leaving the company for a new job to be announced. He’s being replaced by Andrew Paterson.
South San Francisco-based Twist Bioscience, the DNA synthesis company, announced a series of promotions. Siyuan Chen was promoted to chief technology officer and Aaron Sato was promoted to chief scientific officer. Paula Green was promoted to senior vice president of human resources, and Angela Bitting joined the company as senior vice president of corporate affairs.
Cambridge, Mass.-based Scholar Rock announced a string of promotions, including Gregory Carven’s promotion to chief scientific officer.
Cambridge, Mass.-based Revitope Oncology, a cancer immunotherapy company, added Louis Lange to its board of directors. He’s a general partner at Asset Management.
Cambridge, Mass.-based TCR2 Therapeutics named Shawn Tomasello to its board. She has a 35-year track record in commercial operations and medical affairs, including time at Pharmacyclics, Celgene and Genentech.
Cambridge, Mass.-based Moma Therapeutics named Asit Parikh as its new CEO. It’s a precision medicine company backed by Third Rock Ventures.
Burlingame, Calif.-based Lyra Health, the provider of mental health care benefits for employers, added Danielle Gray to its board of directors. She is senior vice president, chief legal and administrative officer for Blue Cross and Blue Shield of North Carolina.
Katie Porter’s Swing-and-a-Miss
Rep. Katie Porter of California is a smart progressive and a formidable prosecutor. I cheered when she grilled former Celgene CEO Mark Alles about that company’s unjustifiable price increases for Revlimid. He deserved a public dressing down after getting wealthy while running the company into the ground. Rep. Porter is channeling much of the frustration people have with our current form of capitalism, which punishes people who follow the rules and rewards the lying, cheating and stealing.
But Rep. Porter issued a 16-page report on mergers and acquisitions in biopharma late last week that was an oversimplified rant that won’t do anyone any good. She called it a “bombshell” report on how M&A stifles innovation.
This report is actually a swing-and-a-miss.
Porter used the Amgen-Immunex acquisition of 2002 as a case study. I covered the Amgen-Immunex deal day-by-day for The Seattle Times. It was a fascinating, nuanced story. Porter’s team interviewed a number of former Immunex employees. They rightly complained about how the vibrant scientific culture at Immunex got smothered. But Porter missed some crucial context to understand the situation. She failed to mention that Immunex screwed up manufacturing. It couldn’t make enough etanercept (Enbrel) to meet the demand from rheumatoid arthritis patients. They left tens of thousands of patients in the lurch, struggling in pain. That fiasco depressed its stock, making it vulnerable to takeover.
Amgen, arrogant and stifling as it was in many ways under CEO Kevin Sharer, was able to fix the manufacturing supply problem in short order. Patients were better served by having Enbrel in its hands. And Amgen, over time, was able to combine some IP with Immunex that led to the development of denosumab (Prolia) for osteoporosis and (Xgeva) for bone metastases.
In the big picture, is M&A good for innovation? I’m no fan of megamergers like BMS-Celgene, because they create organizations so big it’s hard for anyone to do nimble, innovative work. But most deals aren’t like that. Often, but not always, a new product is better off in the hands of a big company. Small companies and their investors also need to know there’s a strong incentive, a pot of gold at the end of the rainbow, if they’re going to invest and do the risky, innovative work in the first place. As John LaMattina rightly pointed out in Forbes, the Pfizer / BioNTech partnership in mRNA vaccines is a great example of different kinds of players playing to their respective strengths. Neither the big company or the small company could have made the vaccine alone. It took both entities, working together, to pull off that historic feat.
The Federal Trade Commission needs to have clear and consistent criteria for when to bring antitrust cases, like when a merger is really about snuffing out competition or depressing innovation to protect an existing franchise. FTC prosecutors need to exercise good judgment on when to take action. Members of Congress should provide oversight and accountability.
Rep. Porter, instead of painting in broad brushstrokes about the ills of M&A, would be wise to leave this work to the FTC. We don’t need more complex issues like this reduced into dumbed-down left-right food fights. That sort of thinking has done a lot of damage already.
Deals
Jazz Pharmaceuticals agreed to pay $7.2 billion to acquire London-based GW Pharmaceuticals, the marketer of cannabidiol oral solution (Epidiolex) for epileptic seizures. The deal includes $200 a share in cash and $20 in Jazz ordinary shares.
Gilead Sciences agreed to work with Gritstone Oncology to use the smaller company’s vaccine technology to work on an HIV cure. The plan is to develop a prime-boost product “comprised of self-amplifying mRNA (SAM) and adenoviral vectors, with antigens developed by Gilead.” Gritstone is getting $30 million in cash and $30 million in an equity investment from Gilead.
South San Francisco-based Veracyte agreed to acquire San Diego-based Deciphera Biosciences for $600 million — $250 million in cash and up to $350 million in stock. The deal strengthens Veracyte’s position in genomic diagnostics for cancer, and provides a foothold in another biotech talent pool.
GSK and Germany-based CureVac agreed to work together on multi-valent mRNA vaccines for COVID-19, which hopefully will be able to address multiple variants in a single vaccine. The deal is worth 150 million Euros, and GSK said it will support manufacturing of 100 million doses in 2021.
Horizon Therapeutics agreed to acquire Gaithersburg, Maryland-based Viela Bio for $3.05 billion or $53 a share.
Bristol-Myers Squibb agreed to in-license a COVID-19 treatment composed of two monoclonal antibodies from Rockefeller University. The dual antibody treatment is designed as a longer-lasting subcutaneous formulation, that is supposed to be more suitable to give to non-hospitalized patients than earlier antibodies that are given intravenously.
Redwood City, Calif.-based Coherus Biosciences paid $150 million upfront to Shanghai Junshi Biosciences to obtain US and Canada rights to a late-stage PD-1 inhibitor, toripalimab. Coherus also obtained an option to Junshi’s TIGIT and IL-2 drug candidates that could be used in combination.
A group of more than a dozen pharma R&D leaders have formed a new COVID-19 R&D alliance.
Financings
ARCH Venture Partners raised a new fund with $1.85 billion to create and finance new biotech startups. ARCH listed a long list of interests for this new fund — infectious disease, mental health, immunology, oncology, neurology, manufacturing, clinical trials, anti-aging medicines, genomic and biological tools, data sciences, and ways of reimagining diagnostics and therapies.
Abingworth raised its 13th biotech fund, Abingworth Bioventures 8, with $465 million to invest. It has already made three investments in the new fund, including one in gene therapy company Atsena (profiled in TR, December 2020)
Seattle-based Sana Biotechnology raised $588 million in an IPO of 23.5 million shares at $25 a share. Initial valuation: $4.9 billion. The cell therapy company is still in preclinical development. It’s the largest preclinical stage IPO ever. Shares climbed another 40 percent in first-day trading to close at $35.10.
Boston and Rockville, Maryland-based Sensei Biotherapeutics, a cancer drug developer, raised $133 million in an IPO at $19 a share.
Watertown, Mass.-based EyePoint Pharmaceuticals raised $100 million in an IPO at $11 a share. The company is developing a treatment for the wet form of age-related macular degeneration.
23andMe, the consumer genetics company, went public through a SPAC sponsored by Richard Branson’s Virgin Group. The deal comes with $759 million of proceeds ($509 million in cash, plus a $250 million private placement), and pegs the company’s enterprise value at $3.5 billion.
Blacksburg, Virginia-based Landos Biopharma raised $100 million in an IPO priced at $16 a share. It’s working on treatments that work on novel mechanisms for autoimmune diseases. The lead candidate is for ulcerative colitis and Crohn’s disease, and targets the LANCL2 pathway.
Biogen said it’s issuing $1.75 billion in debt.
Billerica, Mass.-based Quanterix, which does digital biomarker analysis for precision health, raised $200 million in a stock offering.
Redwood City, Calif.-based Revolution Medicines raised $261 million in a stock offering at $45 a share.
Lexington, Mass.-based Kaleido Biosciences raised $60 million in a stock offering at $11.50 a share.
Regulatory Action
Biogen and Eisai said the FDA has extended its review of the Alzheimer’s drug aducanumab by another three months, to a review deadline of June 7.
The FDA cleared tepotinib (Tepmetko) from Merck KGaA as a new treatment for metastatic non-small cell lung cancer (NSCLC) harboring mesenchymal-epithelial transition (MET) exon 14 skipping alterations.
RIP
Dr. Emil Freireich, a pioneer of treatments for children with leukemia, died at age 93. (USA Today obituary)
Andrew Brooks, the Rutgers scientist who developed a quick saliva-based test for COVID-19 in the early days of the pandemic, died of a heart attack at 51.
Otello Stampacchia, founder, Omega Funds (illustration by Praveen Tipirneni)
This column will have a “glass half full / glass half empty” feeling for many readers, I fear.
Before diving deep into the troubling emergence of highly transmissible and virulent SARS-CoV-2 variants, a couple of brief reminders:
Science is moving very fast indeed, and it must continue at this relentless pace because we still have much to learn.
To drive this point home, allow me to relay a personal anecdote. I was asked to opine if it was safe for a pregnant woman (friend of a friend) to receive one of the mRNA vaccines currently being distributed in the US (she is in her third trimester). After many obvious and obligatory caveats (I am not an MD, and *definitely* not an ob/gyn, nobody should listen to me for medical prescriptions, etc etc), I mentioned that, yes, mRNA vaccines do elicit a strong immune response (the main goal with any vaccine), but that I suspect the potential risk of harm to the fetus was indeed very low (though not zero).
Two days later, WHO issued guidance “recommending generally against the use of the vaccine during pregnancy except for those at high risk of exposure or having a severe case”… Indeed, neither the ModeRNA nor the Pfizer/BioNTech mRNA vaccines have been tested so far in this population (there are plans to do so shortly). If I could print here the faceplant emoji, I would.
The WHO guidance isn’t based on any data from vaccine trials, as far as I can tell, but more out of an abundance of caution. That said, this is not straightforward, since pregnant women appear to be at higher risk of contracting severe cases of COVID-19 as well as (possibly) having a higher risk of preterm delivery (incidentally, the CDC has maintained that pregnant women should get vaccinated).
So, we still have a lot to learn. And we need to remain humble about how much we still do not (yet) know.
In the US, after the rise in cases and fatalities derived from Thanksgiving and Christmas mingling, we seem to be turning the corner (all the graphs below from @COVID19Tracking). It’s yet another reminder that strict Non-Pharmaceutical Interventions (NPIs) — that we knew worked 100 years ago — are still effective in preventing viral spreading via the respiratory route (see, for example, how flu transmission has basically been wiped out this season).
As you can see, cases / hospitalizations are coming down (though from what is an exceedingly high level): cases are definitely trending down and are ~40% below the recent peak in early-to-mid January; hospitalizations are also ~30% down from peak. Tragically, deaths remain extremely elevated at >3,000/day, and will continue to be for several (2-3) more weeks: yet another reminder that deaths are a lagging indicator resulting from infections that occurred ~4-6 weeks prior. The country will soon surpass the sober milestone of >500,000 overall fatalities.
That said, we should expect COVID-19 deaths to begin trending down soon-ish (never soon enough), assuming we continue to behave responsibly (more on this later). Encouragingly, the US administration communication policy has taken a U-turn versus the previous one (even the CDC, under new leadership, has *finally* issued a mask mandate for people using planes, trains and other public transportation).
Another, unabashedly positive piece of news: we now have positive results from two more vaccines, J&J’s and Novavax’s. This is in addition to a slew of data showing several antibodies (from Lilly and Regeneron: alone and in combination) are also extremely effective at preventing deaths and reducing hospitalizations, or in reducing overall infections within the first week, with 100% prevention of symptomatic infections.
At least one study (Regeneron’s) shows markedly decreased levels / duration of viral shedding in the asymptomatic infections that occurred in the treatment group. Of course, these antibodies need to be given at the right time, prior to hospitalization, and that’s a tricky thing for an intravenous medication (though subcutaneous formulations are in the works). But still, these are important medicines.
In case it needed to be said (again), the biotech / pharma industry is rallying at unprecedented scale and speed to provide a solution to this pandemic. What are GameStop or AMC doing in comparison??
For how I see future treatment regimens (vaccines vs antibodies vs antivirals etc), I will direct you to the “Forecasts” section of this column (at the end).
Back to the (new) vaccine data: I would like to make several (non-mutually exclusive) observations (starting with the inevitable request to compare the different vaccine results):
The table below (source: https://cov-lineages.org/global_report.html) shows some information about the currently-known viral variants that are spreading in different geographies: for the non-geeks/amateur virologists amongst you, B.1.1.7 is the “UK variant”, B.1.351 is the “South African variant”, and P.1 is the “Brazilian variant”.
You have likely been hearing about those variants quite a bit, so will spare you a lengthy and geeky discussion. If you really want to go deep into the rabbit hole, this thread from eminent virologist Florian Krammer (@florian_krammer) does a pretty amazing job.
Here are some broader thoughts that should worry you, hopefully arranged in some sort of logical order:
I leave you with a mixed message: it is stunning what human ingenuity has achieved in such a short period against this pandemic. Vaccines (and other pharmaceutical interventions) are a necessary, but not sufficient component of the effort to overcome it. Public health measures, improvements in logistics / vaccine distribution, broad / fast genome surveillance, and many other measures are also necessary.
That’s because — and it pains me to say this — this pandemic really is but a dress rehearsal. Viruses and other infectious diseases are humanity’s oldest and strongest enemy.
We need to win this battle and prepare for the inevitable, bloodier wars that are surely coming.
[Added: 9 am ET Feb. 2] Within hours after this column went to “print,” there is now evidence that the UK variant B.1.1.7 has picked up the E484K mutation (linked to some degree of ability to evade the immune system in the South African and Brazilian variants): and for a more thoughtful / full thread, please check out this from @kakape. This is pure speculation at this stage, but it feels sensible to infer that this viral mutation confers an evolutionary advantage in populations with some degree of existing immunity (UK, South Africa and Brazil were hit extremely hard in the first wave of infections in the Spring of 2020).
I will leave you (again) with this quote from Kai Kupferschmidt: “this virus is telling us again and again, that it will gladly take any opportunity we allow it of spreading and replicating to evolve and make our lives even harder.”
In retrospect, I now wish that the entire planet would have gotten into a synchronized and strictly enforced lockdown for 3 weeks or so in early March…
Larry Corey, MD
For about a month, we were lulled into thinking we had turned the corner and were winning the battle against the virus.
With 95% effectiveness in preventing COVID-19 illness and nearly 100% efficacy in preventing severe disease, we just needed to mass produce these wonderful mRNA vaccines developed by Pfizer / BioNTech and Moderna. Then we could bring an end to this nightmare in a few months.
This illusion can now be called a delusion. We are in a new phase.
Our South African brethren have pointed the way. They had the foresight to set up a genomic surveillance system in a systematic, regionalized way to see how the virus was mutating day by day. This is the way molecular epidemiology and pandemic control should be undertaken.
What they’ve learned has been disturbing. They detected incredibly sudden changes in the virus’s mutational pattern. These were not single nucleotide changes of little consequence. These were multiple sudden changes to the viral RNA code that caused significant structural alterations to several areas of the spike protein on SARS-CoV-2. This has set off alarms in the scientific community. The spike protein is the structure that makes the vaccines work.
The changes we’ve witnessed were in regions of SARS-CoV-2 that were stable over the past year. The mutations were particularly concerning because they affect the Receptor Binding Domain (RBD), which defines the part of the spike protein where the virus attaches to the ACE2 receptor in human cells.
The current vaccines elicit neutralizing antibodies to the Receptor Binding Domain. Some of these mutations look so unusual, that scientists began to wonder whether the antibodies induced by the original vaccines can still bind and neutralize as intended. Might this new Receptor Binding Domain structure resist all neutralizing antibodies, from either natural infection or from vaccine-induced immunity? We’ve had to ask and answer that question. There are also changes to the viral RNA that encodes for another area we call N-terminal domain (NTD) that we don’t really understand.
The South Africans reported these changes first to the United Kingdom (UK), because the predominant strains circulating in South Africa in the early parts of the epidemic were similar to the most common one in the UK. It’s no surprise the two countries have similar viral strains, as there is considerable international travel between the two countries.
Once informed of the new strain from South Africa, now known as B.1.351, UK molecular biologists started to look harder at strains circulating in their own country. They found a new variant that was starting to sweep over the country, called B.1.1.7. That new variant has driven a second wave of infection.
The second wave is worse than the first, as seen by increased rates of transmission and increased rates of hospitalization in the UK. This variant had one of the mutations in the RBD part of the genome, the one that appears associated with increased replication in the nose and transmission to other people, but fortunately not the changes that alter the neutralizing antibodies.
Very quickly, scientists put two and two together. The virus was evolving more rapidly than previously detected. Changes were occurring across two behavioral characteristics. And, the changes to these two characteristics were being detected in the same virus.
We have seen variations pop up over the past year. In June, we had a variation in the US where the original strain from Wuhan was overtaken by what we call the D to G614 strain; that’s what is mainly circulating here now. This strain also increased attachment to the ACE2 receptor, but the newer F105Y mutation enhances these characteristics even more and facilitates an even greater rate of spread.
This B.1.1.7 variant, commonly referred to as the UK variant, has now spread throughout Europe, and is being increasingly recognized in the US. The CDC predicts that this strain, with its evolved advantages, will become the predominant form of the virus circulating in the US over the next few months.
The B.1.351 variant, widely known as the South African variant, also has the increased transmissibility stemming from the mutation in the F105Y gene. But that’s not all. The South African variant has a couple more nasty mutations, one called E484K, that is associated with escape from an important neutralizing epitope that most people have after contracting COVID-19. That neutralizing epitope is also found on antibodies induced by vaccination. This escape mutation on the part of the virus has been seen in other unrelated strains, so it seems to be a frequent way the virus tries to use to escape from people who have acquired immunity. So, people who have been infected with prior strains and developed immunity to those prior strains appear to be at an increased risk of re-infection with the B.1.351 variant.
We call this escape from neutralization or adaptive immune escape from the virus’s point of view.
This is what RNA viruses do. Influenza does this; HIV does it too.
In retrospect, we were a bit naïve about SARS-CoV-2, thinking that because this subgroup of coronaviruses edits its mutations more efficiently, we might escape from having lots of different strains. But natural selection is very powerful, as Darwin taught us. We have had more than 100 million confirmed cases of COVID-19 worldwide thus far, and the real number is certainly much, much bigger. When a virus spreads to this many hosts, this fast, it creates a lot of opportunity for the virus to adapt against the natural selection pressure placed on it by the human immune system.
The bad news is that we continue to give the virus opportunity to adapt. We’re tired of social distancing. Not everyone wears masks. We have limited supplies of vaccine at the moment. So, we find ourselves in a situation where mathematically, this pandemic is not going to stop anytime soon.
What do we do about it? This week brought us data that says we don’t have to panic. We do really have evidence that our current tools are going to be OK. Moderna reported that its vaccine, in lab tests, continued to produce robust neutralizing antibodies against the B.1.1.7 variant. The Moderna vaccine produced 6-fold lower titers of antibodies against B.1.351, but those antibody levels that are still higher than what are typically seen in cases of natural infection. Importantly, the nature of the mRNA technology makes it possible for Moderna to make a new mRNA construct very quickly to educate the immune system against this new B.1.351 variant, and that new “updated” vaccine can be tested in a small, fast clinical trial to validate its use as a “booster.”
Scientifically, this is the good news. But it’s only a piece of the puzzle. We have to create strategies to get us back up to the optimal state. This means vaccinating everyone globally as fast as possible. What impacts one of us impacts all of us, including here in the US. Ongoing community spread anywhere with this virus means it can spread everywhere in our interconnected world.
Besides findings from lab tests, we now have hard clinical evidence that our current vaccines will work as well against the UK variant as they have for the variants circulating in the US. The best evidence of this is a 14,500-person clinical trial of the Novavax vaccine which showed a 90% efficacy rate in a UK study where the UK variant constituted 30% to 40% of the strains circulating at the time of the trial. The antibody concentration from this two-dose vaccine is pretty similar to what we saw in the Moderna and Pfizer vaccines. Several scientific teams have now shown that sera from people vaccinated with either of these vaccines also neutralize the B.1.1.7 isolate as well as the isolate from Wuhan. That’s good news.
More importantly, we got data from the Johnson & Johnson (J&J) vaccine trial out of South Africa on Friday. We were lucky. We didn’t know when we conducted the J&J trial that there would be marked viral strain differences between South Africa and the US. In fact, when I worked with the company to design the trial, the reason we went to South America and South Africa for an international trial was because J&J is a global company and they wanted a globally developed vaccine. Their vaccine is also tailor-made for global vaccination efforts, since it can be given in a single shot, and shipped to remote parts of the world with standard refrigeration – no need for deep freeze.
My network was already working with J&J on their experimental HIV vaccines and we had great investigators in both South Africa and South America who were tackling the COVID-19 epidemic and wanted to help. We were conducting so many vaccine trials in the US, we felt we could distribute some of the work internationally and everyone would benefit. At the time these decisions were made last summer, we didn’t realize how fortuitous this decision would be. A month ago, after the South Africans noted that the B.1.351 variant was the main circulating strain in the country, we got nervous about whether the vaccine would be effective against this tough new variant.
Fortunately, this anxiety was alleviated when the data arrived from the 43,000-volunteer global trial. The J&J vaccine protected against hospitalization and death in 88% of the enrollees in South Africa! There were zero deaths in the vaccine group; six in the placebo group in South Africa. Overall, the vaccine was 57% effective against moderate and severe disease in South Africa.
The efficacy number in the US was 72%; in Brazil, 71%. Worldwide, the numbers worked out to 66 percent protection against moderate and severe disease.
Yes, we do have an 18% to 20% difference in the effectiveness in the J&J vaccine by region, and this is some source of concern. And I will add that the Novavax vaccine, which was shown to be 90% effective in the UK, showed 55% protection in South Africa. So, here too we saw a reduction in efficacy.
But to put it in perspective: What’s more important, do we develop these vaccines to reduce the frequency and severity of sore throats and cough? Or do we develop vaccines to prevent us from getting hospitalized, being put on supplemental oxygen, put on a ventilator, or dying?
I think all of us would take a vaccine that prevents us from dying, even though it might still mean a case of COVID-19 with a sore throat and a headache and body aches for a couple days. I’d take that deal.
In my next blog, I’ll talk more about the J&J vaccine and where it fits in the vaccine response in the US and globally. We need a bit more data to become public before we tackle this task. There are lots of opinions here and there’s nothing wrong with that. But it’s been a very good week. We now have two new safe and effective vaccines—Novavax and J&J. That can be nothing but great news.
As in all science, all good clinical trial outcomes lead to more good questions that we’ll need to answer to bring an end to this pandemic.
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.
Luke Timmerman, founder & editor, Timmerman Report
The FDA needs to get healthy, and fast.
Its credibility as the world’s No. 1 science-based regulator of food and drugs has been tarnished.
From the start, it had to play catch-up on RT-PCR diagnostic tests in the wake of CDC’s epic screwup. Partly to make up lost ground, it swung open the floodgates for antibody tests. A Wild West debacle ensued. Then came hydroxychloroquine (caving in with a premature Emergency Use Authorization, followed by the embarrassing withdrawal when failure was obvious). Then came the convalescent plasma fiasco.
It’s painful to write those words.
Throughout, there was a failure of leadership to level with citizens and clearly communicate the rationale for its decisions in real-time.
Even when FDA staff were inspired to burn the midnight oil to make sure we got vaccines without delay, and the news was good, the agency was tainted. It wasn’t able to speak with the gravitas needed to shore up confidence in therapies and vaccines. Too many people came away thinking FDA was a bunch of bureaucrats or political hacks, cutting corners, probably engaged in skullduggery.
Anyone who gives a damn about healthcare, and about biopharmaceutical innovation, ought to care about restoring the FDA as the world’s leading scientific regulator. We all ought to focus our prying, skeptical eyes on the agency to hold it accountable and keep it on its toes. But we shouldn’t go overboard into bottomless cynicism.
So, today I’d like to propose a few bold ideas to help the FDA get back on its feet.
By moving out of the Washington, DC metro area, the federal government could reap a real estate windfall. The FDA has valuable land that could be redeveloped by private developers of mixed-use business and residential properties. FDA could take the windfall proceeds and build a reimagined, tightly integrated campus in the middle of the country on cheaper land.
I’m thinking of a place like Wichita, Kansas (pop. 390,000) or Tulsa, Oklahoma (pop. 402,000). These cities offer low cost of living and high quality of life. They have diverse demographics with White, Black, Hispanic and Native American populations that closely reflect the population of the country as a whole. The FDA, operating down the street from healthcare providers in a place like this, could test out lots of cool new initiatives in a “real world” healthcare setting. Done right, the FDA could gain valuable insights into how to operationalize things like telemedicine for clinical trials, remote patient monitoring and more.
A move could also refresh the agency’s staff, by clearing out some people ready for early retirement, and providing an opportunity for an influx of new talent attracted to work on hard challenges. These people could be good scientific citizens in their communities. They would be parents of kids in local schools, and neighbors to ordinary people. FDA staff could weave themselves in with local schools that don’t get enough exposure to the wonders of 21st century medical science.
For almost 30 years, the agency has long been kept on a tight leash with Congressional appropriations, and has been forced to rely increasingly on industry user fees. That’s one way to be penny-wise. But it also creates a financial dependence on industry, and a closeness that can sometimes get a little too close in ways that are subtle and hard to quantify. I think there’s a place for user fees in the FDA budget, but the lion’s share ought to come from us, the taxpayers. Either we as taxpayers think this work is important, or we don’t. If the COVID-19 pandemic has taught us a few lessons, one is the importance of an independent, nimble, science-based FDA.
With more pandemic threats looming and so many groundbreaking biopharma products coming down the pike, we need to double the budget just to keep with the anticipated demands on this stretched agency. Pay raises should go to agency veterans who have gone above and beyond.
But at a moment when the agency needs to restore public trust, and break out of some of limited thinking of the past, it needs a commissioner with excellent communication skills and a vision for a 21st century FDA. The next FDA commissioner needs to communicate to the public and advocate passionately with leaders on Capitol Hill and the executive branch. Scott Gottlieb was skilled at this part of the job, and understood how to strike the balance of protecting public health while facilitating quality development of new products. Margaret Hamburg, who made a great impact as commissioner, wasn’t the kind of public spokesperson the agency needs now.
I’m thinking of someone to lead the FDA who has public health experience, who believes in the FDA mission to the bone, who can communicate scientific risk / benefit equations to a Nobel laureate or your grandma, and who doesn’t have too many industry conflicts. I could imagine a few excellent candidates.
Amy Abernethy, deputy commissioner, FDA
How about Bob Wachter of UCSF, one of the most trenchant observers of the pandemic response? Or Julie Gerberding, a former CDC director and now an EVP at Merck with tons of experience in communications? Or Anna Barker, a National Cancer Institute veteran and now the chief strategy officer at the Ellison Institute for Transformative Medicine at USC? Or FDA deputy commissioner Amy Abernethy, who’s spearheading a futuristic data science initiative, and who has credentials from academia (Duke) and industry (Flatiron Health).
Or maybe bring Gottlieb into the Biden Administration, even though he’s a Republican? He’d have to quit his board activities, and work for a Democratic administration, but that would be one way to show that the FDA isn’t a partisan institution.
The FDA is staring at a mountain work ahead on cell and gene therapies. About 900 gene therapy INDs were in the pipeline as of February 2020. Former FDA commissioner Gottlieb and Peter Marks, head of the Center for Biologics Evaluation and Research, forecasted in 2019 that if current trends continue, the FDA will have to be in position to approve 10-20 cell and gene therapies a year by 2025.
The FDA has to staff up with people in CBER to keep up with the anticipated workload. This unit of FDA, remember, has been running at full tilt all year.
Besides the obvious need for more staff, there’s always a need to stay current with information technology, and lab technology tools, to keep up with an industry that is well-funded and moving faster than ever. The agency also needs resources for staffing up far-flung field offices so it can adequately do facility inspections, especially with the vast array of generic drug facilities around the world, and the boom in biologic manufacturing here and abroad. If we don’t make this investment, we can expect a slowdown in approvals — an abundance of innovations that can’t get all the way to people. It would be an “innovation pile-up” reminiscent of a Third World country.
If we’re smart, we’ll invest now to get ahead of the curve of the needs for CBER, while also preparing for healthcare and biopharma changes. Consider the FDA’s data science initiatives led by deputy commissioner Amy Abernethy. Or, consider master protocol study designs that could cut down on some of the waste that bogs down clinical trials today.
Neglecting the basics of how we gather medical evidence comes with a cost. There were too many small, single-site, investigator-sponsored studies in this pandemic – small and crappy trials. The FDA is the one agency that can take the lead on demanding new standards, but it needs strong leadership and adequate funding.
It’s easy to overlook the FDA. It’s easy to criticize. Often, we’re right when we do.
But the FDA also needs our support. It deserves our most creative, constructive ideas on how to fulfill its mission. We shouldn’t take it for granted. The pharmaceutical industry wouldn’t be worth much if it were to wither on the vine.
We can’t allow that to happen. I don’t think it will. Let’s revitalize the FDA, and put it in position to be great at what it does for the next 100 years.
The GameStop retail shareholder attack against hedge funds of Wall Street has prompted a lot of bewildered hot takes. As someone who formerly covered biotech stocks for Bloomberg News, I have some sympathy for the little guy who always gets screwed by the big guys. It’s been going on far too long (for just one example in biotech, see my “Selling Drug Secrets” investigation for The Seattle Times in 2005). At the simplest level, this retail shareholder rebellion makes some sense in a world that’s come unglued and where it appears there are no consequences for people who incite society-wide lawbreaking and mayhem. But when you open a Pandora’s Box of lawlessness and bottomless cynicism and too many people don’t know what’s true and don’t care, terrible damage gets done to innocent victims.
Look at Vir Biotechnology. The San Francisco-based developer of infectious disease therapies scored a fundamental win this week with its hepatitis B treatment. The stock skyrocketed to a high of $135 this week, before falling to as low as $51. There’s no fundamental reason for this much volatility. It had good news for hepatitis B, and some more good news for its combo therapy partnership on COVID-19 with Lilly and GSK. Apparently, part of the volatility can be explained because there’s a large percentage of shareholders who have a short position in the company based on a belief that it’s overvalued for its COVID-19 therapeutic antibody work. It’s fine for people to argue about valuations in the market – that’s what the market is supposed to do. But I think most people would also agree that we don’t want to have a system where it’s fun and profitable to launch manipulative attacks – bearish or bullish – to settle scores against Hedge Fund Bad Guys, if it means companies tackling the world’s biggest health challenges become collateral damage.
Our Shared Humanity
Worth a Listen
RIP
Kirk Raab, the former CEO of Genentech, died from complications of COVID-19. He was 85.
Deals
San Francisco-based Verana Health struck an agreement with Janssen Pharmaceuticals to curate real-world evidence for data analysis to inform R&D in ophthalmology and urology. Terms weren’t disclosed. (TR coverage of Verana, July 2018)
Data That Mattered
Takeda Pharmaceuticals said that its experimental drug mobocertinib, an oral tyrosine kinase inhibitor, showed positive results in a Phase I/II trial of non-small cell lung cancer patients with EGFR Exon20 insertions. Researchers reported a 35 percent overall response rate, in patients who had previously worsened after platinum-based chemotherapy. Data were presented at the World Conference on Lung Cancer.
Amgen’s sotorasib, the oral KRAS G12C inhibitor, generated an overall response rate in 37 percent of patients with advanced lung cancer, according to data presented at the World Conference on Lung Cancer.
Genentech’s faricimab met the primary endpoint of in a pair of Phase III studies of patents with the wet form of age-related macular degeneration. The Genentech medicine is a bispecific antibody aimed at angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-A). The drug, administered every 16 weeks, was found non-inferior compared with Regeneron’s aflibercept (Eylea).
Personnel File
San Diego-based Cidara Therapeutics, the developer of antifungal and antiviral therapies, named molecular biologist Bonnie Bassler of Princeton University and Carin Canale-Theakston, founder and CEO of Canale Communications, to its board of directors.
Seattle-based Umoja Biopharma, an in vivo immunotherapy company, added Rob Glassman to its board of directors. He has been a vice chair at Credit Suisse since 2015.
Philadelphia-based Tmunity Therapeutics, the developer of T-cell therapies for solid tumors, said Jeff Leiden has become its new chairman of the board. Leiden is executive chairman of Vertex Pharmaceuticals.
San Diego-based ViaCyte, a regenerative medicine company, named Michael Yang as President and CEO. Brittany Bradrick was promoted to COO and CFO, and Steve White was named chief technology officer.
Financings
Waltham, Mass.-based Tscan Therapeutics raised $100 million to advance T-cell receptor engineered T-cell therapies for cancer. BlackRock and RA Capital Management participated.
Cambridge, Mass.-based Nuvalent raised $50 million in a Series A financing from Deerfield Management to work on kinase inhibitors for treatment-resistant cancers.
Seattle-based Lumen Bioscience received funding from CARB-X worth up to $14.5 million to develop orally available monoclonal antibody cocktails for serious diarrheal diseases.
Redwood City, Calif.-based Seer, a proteomics company, said it’s raising $251 million in a stock offering at $67 a share.
Germany-based CureVac, a mRNA therapeutics and vaccine developer, raised $450 million in a follow-on stock offering.
Israel and Palo Alto, Calif.-based Ukko raised $40 million to combat food allergies. Leaps by Bayer led.
Regulatory Action
Alameda, Calif.-based Exelixis won FDA clearance for cabozantinib (Cabometyx) in combo with nivolumab (Opdivo) as a first-line treatment for patients with advanced renal cell carcinoma.
