Luke Timmerman, founder & editor, Timmerman Report

My first real journalism job flashed to mind this week.

It was 1998-1999. I was a kid reporter fresh out of the University of Wisconsin. My job was to cover Dane County government for The Capital Times, the progressive newspaper in Madison.

Dane County had about 400,000 people. Half lived in the beating liberal heart of the City of Madison – home to one of America’s great state universities and many government workers.

The other half of the county’s residents lived in suburban villages and rural farmland. Former Wisconsin Gov. Lee Dreyfus once famously needled Madison as “30 square miles surrounded by reality.” Think dairy farms, feed mills, rolling hills, and the occasional small-town Main Street.

The Dane County executive, who I was supposed to watch like a hawk and report on daily, was a former environmental activist. The editors of my newspaper were supportive of her political positions.

I loved that job. What an education this was for 23-year-old me.

Kathleen Falk struck me as a bright and dedicated public servant. But she had her work cut out. This was a tense, pressure cooker of a job.

After years of being a legal activist on the outside, advocating fiercely and intelligently for clean water and clean air and all kinds of good environmental causes, she had weighty responsibility.

As County Executive, she had to manage the classic urban-versus-rural land use battles. Wisconsin was losing an average of 2-3 family farms per day in those years (my Mom and Dad’s family farm in Grant County included). Corporate agriculture was ascendant. Family farmers, left with no economic legs to stand on and not enough in the younger generation willing to carry on with that way of life, felt compelled to sell their land to housing developers in order to retire.

Farmland was disappearing under suburban cul de sacs. Wildlife – deer, squirrels, rabbits, pheasants, ruffed grouse, Canada geese – were being left with less habitat.

Falk had a North Star. She wanted to protect the land. But she also governed at a time when Money magazine ranked Madison as one of America’s Best Places to Live. Newcomers were coming, like it or not.

Falk had to balance competing interests — do we allow more housing subdivisions on the periphery of the City of Madison? What about rebuilding some run-down neighborhoods? Would people want to live there? Where exactly were all these new people supposed to live, anyway? How were they supposed to get to and from work, without spewing too much CO2, or jamming up the roads and disrupting the wonderful quality of life which drew people to Madison in the first place?

County Executive Falk, to my mind, never abandoned her principles. But she realized that there is another side to the story, she needed to listen, and needed to take it into account. Representing her tribe in Madison, and ignoring the rest of Dane County, wasn’t going to fly. It was her job to mediate, to carve out pragmatic solutions that both sides could live with.

This was not easy. These issues were emotionally heated with partisan rhetoric, even then.

To get anything of substance done, Falk had to work with a 39-member legislative branch, the Dane County Board. I covered their meetings that ran late into the night. Firebrand 1960s-style liberals from Madison (picture Vermont Senator Bernie Sanders) would step to the microphone and let it rip. When they were done, their counterparts from the rural parts of Dane County (picture Iowa Senator Chuck Grassley) would dish out their counterarguments, sometimes dripping with contempt about the liberals and their lack of “common sense.”

Some of these people really didn’t like each other. They’d come by the press gallery off to the side of the main chamber, and fill this reporter’s ear with gossip about how such-and-such supervisor was full of baloney, or how he or she was in the pocket of special interests.

Yet, these people had to find ways to work together to do basic things, like build and maintain roads, preserve the environment, take care of the most vulnerable citizens, and keep taxes in line with what people could stomach. Falk liked to describe her approach as “progressive policies with fiscal restraint.”

There was always the tension between individual rights and the common good. When you have a retiring farmer who’s worked hard his whole life and struggled to make a living with weak commodity crop prices, how do you tell him that he can’t sell his land to a housing developer?

What else is the farmer supposed to do?

Lord knows, our world needs activists to focus on injustice and demand change. But we’re all citizens in a democracy. We need to recognize this is a fractious country, and we have to balance competing interests. None of us is 100 percent right 100 percent of the time. None of us can win every battle. We need to seek common ground with people we strongly disagree with on some things if we want to accomplish anything.

Falk did her best. She clearly disappointed friends on the left at times. She never won over her skeptics on the right. But when she announced her retirement in 2010, as the longest-running Dane County Executive ever, a local newspaper wrote:

Part of what played into her decision to step down is the fact she fulfilled the two promises she made when re-elected in April 2009: building the nation’s first community manure digester and launching real cultural change around the big costs and wholesale suffering from the community’s abuse of alcohol.

“Getting this manure digester and changing the paradigm of how we clean up our lakes was very important, and I am really proud that we have broken ground on that and will be flipping the switch in a few months,” Falk said.

That’s no punch line. Building a manure digester means dealing with waste from farm livestock in a way that allows farmers to continue making a living, while keeping Dane County’s beloved lakes clean.

That’s smart problem-solving, smart balancing of competing interests. This is what we want, and what we should demand, from our more competent public representatives.

We are in a very dark chapter in our country’s history, worse even than the Red Scare of the 1950s McCarthy era. We can’t go on like this.

I grew up in Wisconsin and still have friends and family there. Some are staunch conservatives. There are things on which I will not yield, and which they won’t either. But we do have things in common.

This might take the rest of our lives to dig ourselves out of this ditch, and get our society back on a stable footing. Our society isn’t structured this way in the social media era, but if we talk less, listen more, and assume good faith from others, we can work together again and start solving some of our biggest problems.

Financings

Boston-based Atea Pharmaceuticals, a developer of antiviral therapies, raised $300 million in an IPO at $24 a share.

Seattle-based Icosavax secured $16.5 million in financing, including a $10 million grant from the Bill & Melinda Gates Foundation, to advance work on a virus-like particle approach to a COVID-19 vaccine.

Treatments

• An Ultrapotent Synthetic Nanobody Neutralizes SARS-CoV-2 by Stabilizing Inactive Spike. Science. Nov. 4. (Michael Schoof et al, UCSF)
• Versatile and Multivalent Nanobodies Efficiently Neutralize SARS-CoV-2. Science. Nov. 4. (Yufei Xiang et al, University of Pittsburgh)
• Regeneron Data Safety Monitoring Board Recommends Clinical Trial for Antibody Cocktail be Modified to Exclude Patients on Ventilation, or High-Flow Oxygen. Oct. 30. (Regeneron statement)

Science

• De Novo Design of Potent and Resilient hACE2 Decoys to Neutralize SARS-CoV-2. Science. Nov. 5. (Thomas Linsky et al)
• Multi-omics Resolves a Sharp Disease-State Shift Between Mild and Moderate COVID-19. Cell. Oct. 28. (Yapeng Su et al)
• Viral genome sequencing places White House COVID-19 outbreak into phylogenetic context. MedRxiv. Nov. 1. (Trevor Bedford et al)

Deals

Merck agreed to acquire San Diego-based VelosBio for $2.75 billion in cash. The private company is developing and antibody-drug conjugate aimed at ROR1. It’s a Phase 1 trial for hematologic malignancies, and a Phase 2 clinical trial for solid tumors. Merck cited some encouraging preliminary data that’s set to be presented at the American Society of Hematology meeting next month. VelosBio was founded in 2017, and raised $202 million in its history, including a $137 million Series B in July. Investors who are cashing in on the Merck deal include: Matrix Capital Management, Surveyor Capital, Adage Capital Management, Cormorant Asset Management, Farallon, Foresite Capital, Janus Henderson Investors, Logos Capital, OrbiMed, T. Rowe Price Associates, Venrock Healthcare Capital Partners, Viking Global Investors, Wellington Management, Arix Bioscience, Decheng Capital, Pappas Capital, Sofinnova Investments, and Takeda Ventures.

Sanofi agreed to acquire Netherlands-based Kiadis Pharma for 308 million EUR. The company is developing an off the shelf’ K-NK cell technology platform.

Seattle-based Sana Biotechnology agreed to acquire Oscine Corp., a company developing cell therapies for the brain and central nervous system. Terms weren’t disclosed. (See my October interview with Sana Biotechnology CEO Steve Harr, for Geekwire.)

PerkinElmer agreed to acquire UK-based Horizon Discovery for $383 million. Horizon provides CRISPR and RNAi reagents, cell models, cell engineering and base editing offerings.

Science Features

• Will a Small Long Shot US Company End Up Producing the Best Coronavirus Vaccine? Science. Nov. 3. (Meredith Wadman)
• Down to the Atoms. In the Pipeline. Oct. 30. (Derek Lowe)
• The Science of Superspreading. Science. Oct. 30. (Martin Enserink, Kai Kupferschmidt, Nirja Desai)
• How Can Public Health Recover From the Rebuke at the Polls? STAT. Nov. 4. (Nicholas Florko)
• Why the US Doesn’t Have At-Home Coronavirus Tests Yet. Politico. Oct. 21. (David Lim)
• Denmark to Cull 17 Million Mink After Coronavirus Mutation Found. WSJ. Nov. 5. (Sune Engel Rasmussen)
• A Rapid Virus Test Falters in People Without Symptoms, Study Finds. NYT. Nov. 2. (Katherine Wu)
• Courage in a Climate of Fear. Science Editorial. Nov. 4. (Abraham Verghese and Eric Topol)

Regulatory Action

FDA staff issued briefing documents for an advisory committee hearing on Biogen’s aducanumab treatment for Alzheimer’s disease. The staff review was surprisingly positive of the application, especially since FDA reviewers tend to raise pointed questions and (appropriately) probe for weaknesses in sponsor presentation. The FDA advisory committee will review the data presented on Friday Nov. 6, and the staff deadline to review the application is in March. Biogen shares surged (chart below) on what looks like a surprisingly easy pass from the FDA.

RIP

Philip Lee, a former chancellor of UCSF and an assistant secretary of health during the critical early days of Medicare, died at 96. Reading obituaries like this, of people who you’ve never heard of but who lived meaningful lives, is the kind of thing that can restore one’s faith in humanity. These people exist in our country, even if they tend not to attract the lion’s share of attention.

Personnel File

BeiGene CFO and chief strategy officer Howard Liang announced he’s retiring in the first quarter of 2021.

Deep Genomics, an AI for therapeutics company, hired Amanda Kay as chief business officer. Tom Hughes, the CEO of Navitor Pharmaceuticals, joined the board.

Novavax added Gregg Alton, the veteran biotech executive formerly of Gilead Sciences, to its board of directors.

Data That Mattered

South San Francisco-based Allogene Therapeutics reported on some preliminary Phase I dose-escalation data from its anti-BCMA cell therapy. Four out of 17 patients (24 percent) had Grade 3 or 4 (severe) infections.

The company then went on to describe another adverse event in what could only be described as so-clinical-as-to-be-obfuscatory language. Quote below:

“The fourth was a Grade 5 event of suspected fungal pneumonia that occurred on day eight post-ALLO-715 infusion. The suspected fungal pneumonia was diagnosed on the day after cell infusion in this patient with advanced and rapidly progressing disease who had failed multiple lines of therapy. This event occurred in the CA cohort, and it was assessed by the investigator as related to progressive disease and the CA conditioning.”

Translation: The fourth patient died. The patient was pretty sick already when he or she entered the trial. When the patient died, the doctor figured it was probably because of a combination of the patient’s illness, and the chemotherapy conditioning agent. Nobody, nobody, nobody is saying here in black and white ink that our experimental cell therapy might have something to do with sad result.

Come on, guys. I suppose it’s possible that Allogene is correct in this innocuous interpretation of events. It may be true that no one really knows at this point what really happened. But the standard clinical language here serves to confuse people, deflect blame, or perhaps lull people to sleep so they just move on.

This isn’t the kind of communication that builds trust. This industry, like so many parts of our modern world, needs to think harder about how to build trust, not further erode it.    

Luke Timmerman, founder & editor, Timmerman Report

America, my old conservative friend from a Mountain West state told me on the phone in April, can’t handle the pandemic.

We’re soft, he said.

Like the characters in the 2008 Pixar film “Wall-E,” he said, we’re sucking on our Slurpees and so drunk on cheap 24/7 entertainment that we can’t even stand on our own two feet anymore.

Forget about lockdowns, social distancing, or masks to flatten the curve. Won’t happen, he said. We ought to let individuals do what they want, using their best judgment, like in Sweden, as Rand Paul was arguing at the time.

Wrong, I replied. People in pandemics of the past found a way to curb the spread with disciplined social distancing, hand-washing, and masks. Look at the gutsy healthcare workers and tireless essential workers getting us through these hard times. They were sacrificing so much. We only had to sacrifice a little to wrestle the virus to the ground, breaking the chain of community transmission.

While all of us are stuck at home doing our part, I told my friend, look at the biomedical enterprise running on its toes at Olympic pace. We’ve seen nothing comparable since World War II. Government, academia and industry were setting aside their usual differences, and coming together in common cause in an inspiring way. The cavalry was here, I said, to develop mRNA vaccines, therapeutic neutralizing antibodies, more sensitive and rapid tests for SARS-CoV-2.

To go from a raw DNA sequence of a brand new virus to a vaccine candidate injected in a human arm in two months? My head still spins just thinking about it. Within 12 months of that most basic scientific step, we are likely to have at least one vaccine that can be rolled out at scale. Writing that sentence would have been unthinkable one year ago.

Thinking back on this phone conversation with my old friend in April 2020 – between a couple guys who grew up in the same small town in southwestern Wisconsin and grew far apart ideologically as adults – both of us were about half-right.

We have made some terrible choices as a country. We are living with the consequences. The most salient facts are ones that shouldn’t have to be written this far into the pandemic – 80,000 new cases a day, 1,000 new deaths a day, 40+ states with uncontained community spread, no national plan.

The beauty of our democratic system is that we get a chance every so often to correct our mistakes. We do that with our votes. It won’t bring an immediate end to this nightmare. It will take time to halt the spread, and to mend our tattered social fabric.

This has been the hardest year many of us have ever lived through. But people have encountered more difficult hardships before, on vast scales. We will get back on own two feet. We will come out of this with more resilience, more toughness, and more empathy for our fellow human beings.

Plenty of you in biotech are already thriving in this new environment. I look forward to seeing the biotech industry lead the way, showing the rest of the country what a brighter future can look like.

Vaccines

We started the week with good news on the vaccine front. Both AstraZeneca and Johnson & Johnson, developers of viral vector-based vaccines for COVID-19, were able to resume enrollment of their pivotal trials. AZ’s candidate had been on hold in the US since September, while J&J did a voluntary pause to suss out an adverse event in a trial participant. In both cases, the events were not deemed to be caused by the experimental vaccine – so we can all exhale that these serious big-company contenders are still in the mix.

Treatments

Eli Lilly’s neutralizing antibody for COVID-19 didn’t help hospitalized patients, according to the NIH-sponsored ACTIV-3 trial. As Lilly pointed out in a statement, there are other trials running that look at mild to moderate COVID-19 patients. Many experts expect the drug to be more likely to work in this population.

Regeneron’s antibody cocktail produced another slice of encouraging data. Scientifically, the neutralizing antibodies are hammering down the viral loads within the first 7 days, as you’d want to see. That biological phenomenon matched up nicely with the key clinical observation – a 57 percent reduction in hospital visits through Day 29. The difference between drug and placebo was even more meaningful for patient groups with underlying chronic conditions — cardiovascular, metabolic, lung, liver or kidney disease; or immunocompromised. This is good news, especially because efficacy was seen at the low dose – 2.4 grams – meaning that more patients can be served with existing manufacturing capacity. But Regeneron is still saying it has capacity for about 50,000 doses – obviously not enough to fulfill the fanciful promises of antibodies for everyone that are being issued on the campaign trail.

Financings

Boston-based Scorpion Therapeutics raised a $108 million Series A financing to develop precision cancer drugs. Atlas Venture, Omega Funds and Vida Ventures participated, and serial entrepreneur Gary Glick is the founding CEO. (See TR coverage of Glick’s past ventures at IFM Therapeutics, in December 2019, and April 2019).

Novato, Calif.-based Ultragenyx Pharmaceutical, the developer of drugs for rare diseases, raised $400 million in a stock offering at $90 a share.

Shanghai-based LianBio raised $310 million in a crossover financing to develop new medicines for China and other Asian markets. RA Capital, Venrock Healthcare Capital Partners and Chinese investor CMG-SDIC Capital co-led.

Irving, Tex.-based Caris Life Sciences raised $310 million in a financing composed of $235 million in equity and $75 million in debt. Caris said it plans to apply AI to its database of 215,000 patients with molecular and clinical outcome data to advance its precision medicine programs.

Boston-based Puretech Health filed a 20-F listing which would allow it to be publicly traded both in London, and on the NASDAQ.

Madison, Wis.-based Exact Sciences, the maker of molecular diagnostics for cancer, raised $869 million in a stock offering at $101 a share.

Cambridge, Mass.-based Foghorn Therapeutics, the developer of genetic medicines based on emerging science around the chromatin regulatory system, raised $120 million in an IPO priced at $16 a share.

Boston and Copenhagen-based Galecto, a fibrosis drug developer, raised $85 million in an IPO at $15 a share.

Watertown, Mass.-based SQZ Biotech raised $70.6 million in an IPO priced at $16 a share. The company is developing cell therapies.

Boulder, Colo.-based Biodesix raised $72 million in an IPO priced at $18 a share. The company is working on diagnostics for lung diseases.

San Diego-based Arena Pharmaceuticals spun out a startup, Longboard Pharmaceuticals, with a $56 million Series A financing led by Farallon Capital Management. The new company will focus on developing drugs for CNS disorders that can be targeted via G-protein coupled receptors.

Boston-based Cerevel Therapeutics became a public company through a merger with a Special Purpose Acquisition Company (SPAC) sponsored by Perceptive Advisors. The deal is putting $440 million to work at Cerevel. The neuroscience drug developer is led by Tony Coles.

Deals

Exact Sciences agreed to acquire Cambridge, Mass.-based Thrive Earlier Detection for as much as $2.1 billion in cash and stock. About $1.7 billion is upfront, with the rest in milestones. Thrive Earlier Detection is attempting to develop blood-based tests that can catch multiple types of cancer at an earlier stage, when it’s most treatable with standard oncology treatments. (Read in-depth TR coverage of Thrive Earlier Detection’s $110 million Series A round, led by Third Rock Ventures, from May 2019.)

Bayer agreed to acquire AskBio, a leading AAV-vector based gene therapy company, for $2 billion upfront and another $2 billion in milestones.

South San Francisco-based insitro, the developer of a machine learning platform for drug discovery, secured a five-year collaboration with Bristol-Myers Squibb to work on neurological diseases like amyotrophic lateral sclerosis and frontotemporal dementia. Insitro is getting $50 million upfront. (Listen to CEO Daphne Koller on The Long Run podcast, recorded before this deal was announced.)

Novato, Calif.-based Ultragenyx Pharmaceutical struck a deal with Cambridge, Mass.-based Solid Biosciences to co-develop gene therapies for Duchenne Muscular Dystrophy. Solid is pocketing $40 million cash upfront.

Hayward, Calif.-based Arcus Biosciences formed a partnership with AstraZeneca. The smaller company is bringing its anti-TIGIT antibody to the table, and will pair it with the anti-PD-L1 antibody durvalumab (Imfinzi), for a Phase III trial for non-small cell lung cancer.

Novartis agreed to acquire Cambridge, Mass.-based Vedere Bio for $150 million upfront and $130 million in milestones. Vedere is developing optogenetic therapies that are delivered to the retina intravitreally to restore functional vision

San Diego-based Retrophin agreed to pay $90 million upfront to acquire Orphan Technologies, the developer of a treatment for classical homocystinuria.

Manufacturing and Access

Cambridge, Mass.-based Moderna formed an agreement with Takeda Pharmaceutical and the government of Japan to supply 50 million doses of its mRNA COVID-19 vaccine that’s currently in Phase III development. The mRNA vaccine and therapy company reported it had about $4 billion of cash in the bank on Sept. 30. That’s up from about $1.26 billion on Dec. 31, 2019.

Personnel File

Veteran biotech leaders George Golumbeski and Faheem Hasnain joined Vertex Ventures HC as executive advisors.

Boulder, Colo.-based Inscripta, the genome engineering company, said it hired Sri Kosaraju as its new CEO. He replaces Kevin Ness.

Boston-based Monte Rosa Therapeutics, the developer of targeted protein degrading drugs, hired Min Wang as chief operating officer, Ajim Tamboli as chief financial officer and Jullian Jones as senior vice president, head of business development.

Watertown, Mass.-based SQZ Biotech, a cell therapy company, hired Micah Zajic as chief business officer. Marc Schegerin and Sapna Srivastava also were named to the board of directors.

Houston-based Bellicum Pharmaceuticals cut its staff from 68 to 14 – a 79 percent reduction – after a clinical trial of a CAR-T therapy failed in the first four patients.

Public Health

• Winter is Coming: Time for a Mask Mandate. WSJ Editorial. Oct. 25. (Scott Gottlieb)
• Preventing the Spread of SARS-CoV-2 With Masks and Other ‘Low Tech’ Interventions. JAMA. Oct. 26. (Andrea Lerner et al)
• Effectiveness of Face Masks in Preventing Airborne Transmission of SARS-CoV-2. Msphere. Oct. 29. (Hiroshi Ueki et al)
• COVID-19 Mitigation Behaviors by Age Group – US April-June 2020. CDC Morbidity and Mortality Weekly Report. Oct. 27. (Helena Hutchins et al)
• Hospitals Are Reeling Under a 46 Percent Spike in COVID-19 Patients. NYT. Oct. 27. (Giulia McDonnell Nieto del Rio, Simon Romero and Mike Baker)
• President Trump Issues Executive Order, Setting the Stage for Loyalty Tests for Thousands of Federal Civil Servants. Government Executive. Oct. 22. (Donald Kettl)

Science

• Identification of Required Host Factors for SARS-CoV-2 Infection in Human Cells. Cell. Oct. 24. (Zharko Daniloski et al)
• SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with COVID-19. NEJM. Oct. 28. (Peter Chen et al)
• SARS-CoV-2 Orf6 Hijacks Nup98 to Block STAT Nuclear Import and Antagonize Interferon Signaling. PNAS. Oct. 23. (Lisa Miorin et al)

Science Features

• America Is About to Choose How Bad the Pandemic Will Get. The Atlantic. Oct. 28. (Ed Yong)
• There’s Only One Chance to Do This Right. FDA Panel Wrestles With COVID-19 Vaccine Issues. Science. Oct. 23. (Jon Cohen)
• The Very, Very Bad Look of Remdesivir, the First FDA Approved COVID-19 Drug. Science. Oct. 28. (Jon Cohen and Kai Kupferschmidt)
• CRISPR Gene Editing Can Lead to Big Mistakes in Human Embryos. WSJ. Oct. 29. (Amy Dockser Marcus)

Our Shared Humanity

• I’m a Black Psychiatrist. I’m Never Prepared for the Emptiness and Grief I Feel When Police Shoot a Black Person. STAT. Oct. 23. (Chase Anderson)

Regulatory Action

Cambridge, Mass.-based Foundation Medicine received FDA approval for a companion diagnostic for larotrectinib (Vitrakvi), the cancer treatment designed for solid tumors with NTRK fusions.

Catch up on the main events of the week in biotech with Frontpoints.

Luke Timmerman, founder & editor, Timmerman Report

The FDA issued a surprising approval – not another watered-down Emergency Use Authorization – to Gilead Sciences for remdesivir (Veklury) its antiviral against COVID-19. The antiviral, designed to stop the SARS-CoV-2 virus from copying itself, is now the first treatment fully approved by the FDA against this particularly nefarious virus. Gilead’s approval is for hospitalized patients. The company added that it can manufacture enough of the drug to make it widely available at US hospitals.

The main piece of evidence in favor of approval is the ACTT-1 trial, conducted with the National Institute of Allergy and Infectious Disease, which showed that remdesivir could reduce hospitalization time by a median of five days in the overall patient population, and by seven days in patients who were given supplemental oxygen at baseline.

No rigorous randomized study has yet shown that remdesivir can increase the chances that patients with survive.

With that rather large caveat, I’ll call this a piece of good news.

Not everyone agrees.

Immediately, skeptics pointed to the Solidarity study results from the WHO, which came out last week. That trial didn’t show a survival benefit for remdesivir. But for those who look closely at the protocol and conduct of the study, it looks like a hot mess. Patient subgroups weren’t adequately characterized. WHO researchers weren’t able to answer basic questions, like whether remdesivir worked better for patients with mild disease on low-flow oxygen than for more severely ill patients with overactive immune reactions. Local protocols were all over the place, creating inconsistent data collection across 30 countries. There’s also a curious decision to use 99 percent Confidence Intervals in the meta-analysis (Fig. 4), when it would be standard practice to use 95 percent Confidence Intervals.

Why move to that high of a bar? It’s odd – and to me – a largely inconclusive study that represents frantic, panicked efforts by doctors to do their best in an emergency, but ultimately arriving at a sloppy result at best.

You can see some of the Twitter chatter below, from Eric Topol and Peter Bach, who are expressing skepticism, but really come down in the “inconclusive” camp on remdesivir. It is curious to see the FDA give the green light without more evidence. But under the circumstances, I think there’s good reason to prescribe remdesivir. I know I’d demand it right now if I had a family member hospitalized (while also fighting to get into a clinical trial of a neutralizing antibody from Regeneron, Lilly or VIR).

A Word on Trust

Yesterday, I listened to most of the FDA advisory committee evaluating COVID19 vaccines. The most striking moment of the day came during a presentation by representatives from the Reagan-Udall Foundation for the FDA. They surveyed public opinion on the COVID19 vaccine race. Their findings were sad. So sad, for all of us who care about science as a method for seeking the truth.  

Take a look at their key slides below.

Now let that sink in for a second. And as a card-carrying member of the scientific enterprise, ask yourself:

What am I doing today, this month, and this year, to build strong relationships outside my immediate professional circles? What am I doing to foster more confidence in science in my community? What am I doing to push back against the tidal wave of cynicism and apathy in our country?

This isn’t someone else’s problem. This is something we all have to work on.

Vaccines

Moderna said it completed enrollment in the Phase III trial of its COVID19 mRNA vaccine candidate. The company pointed out that minority populations represent 37 percent of those enrolled. CEO Stephane Bancel said the company could receive Emergency Use Authorization as soon as December. The minority enrollment, and demographic breakout on safety and efficacy, will surely factor in the public mind as people think about whether to take any COVID19 vaccine. Especially at a time of rising skepticism, and hesitancy to take vaccines.

Pfizer CEO Albert Bourla, who previously has said it could possibly have a positive readout on its COVID19 vaccine candidate in late October, backed away from that aggressive position this week, posting a letter on the company website saying that the company could apply for an Emergency Use Authorization after a key safety milestone is achieved in the third week of November.

Brief Note on the Pandemic

We are heading now to a horrible third peak. More than 70,000 new cases a day are piling up in the US. We are back to seeing 1,000 deaths a day. More than 223,000 are officially dead from COVID19, and the excess death toll now exceeds 300,000. The trendlines look ominous this fall and winter, even though we have seen some tremendous progress has been made with therapeutics and vaccines.

Our president chooses to blame Tony Fauci “and these idiots” who people are tired of listening to.

If we as a country were willing to follow the science, and course-correct when presented with new data on what works and what doesn’t — like Tony Fauci and “those idiots” — we’d be in a far better position than we are today. (See Timmerman Report July 9 editorial on Standing With Fauci)

Science

• COVID-19: All the Wrong Moves, in All the Wrong Places. Science. Sept. 15. (Christopher Barrett and Michael Yaffe)
• COVID-19 Can Affect the Heart. Science. Oct. 23. (Eric Topol)
• Understanding COVID-19 Vaccine Efficacy. Science. Oct. 21. (Marc Lipsitch and Natalie Dean)
• The Engines of SARS-CoV-2 Spread. Science. Oct. 23. (Elizabeth Lee et al)
• Will COVID19 Vaccines Save Lives? Current Trials Aren’t Designed to Tell Us. BMJ. Oct. 21. (Peter Doshi)
• Therapeutic Activity of an Inhaled Potent SARS-CoV-2 Neutralizing Human Monoclonal Antibody in Hamsters. BioRxiv. Oct. 14. (Michael Piepenbrink et al)
• A Structural Model of the Endogenous Human BAF Complex Informs Disease Mechanisms. Cell. Oct. 13. (Nazar Mashtalir et al)
• Structural Analysis of Full-Length SARS-CoV-2 Spike Protein from an Advanced Vaccine Candidate. Science. Oct. 20. (Sandhya Bangaru et al)
• Unbiased Screens Show CD8+ T cells of COVID19 Patients Recognize Shared Epitopes in SARS-CoV-2, Most of Which Are Not Located in the Spike Protein. Immunity. Oct. 20. (Andrew Ferretti et al)
• Outcomes of Neonates Born to Mothers With SARS-CoV-2 Infections at a Large Medical Center in New York City. JAMA Pediatrics. Oct. 12. (Dani Dumitriu et al)

Science Features

• Should COVID Be Left to Spread Among the Young and Healthy? Two Clashing Petitions. The Economist. Oct. 21.
• Studies Point to a Big Drop in COVID19 Death Rates. NPR Shots. Oct. 20. (Geoff Brumfiel)
• Cryo-Electron Microscopy Breaks the Atomic Resolution Barrier at Last. Science. Oct. 21. (Robert Service)

Public Health

• The Pandemic Has Caused Nearly 300,000 More Deaths Than Expected in a Typical Year. Washington Post. Oct. 20. (Lenny Bernstein)
• Excess Deaths Associated With COVID19 by Age, Race and Ethnicity, United States, Jan. 26-Oct. 3, 2020. CDC Morbidity and Mortality Report. Oct. 20. (Lauren Rossen et al)

Manufacturing and Patient Access

• Where Do I Go to Get My COVID Antibody Cocktail? WSJ. Oct. 18. (Scott Gottlieb and Mark McClellan)

Trust, or Lack Thereof

• Supporting US Public Health Experts. Nature Bioengineering. Oct. 22. (Jeremy Levin et al)
• Eight Persistent COVID19 Myths and Why People Believe Them. Scientific American. Oct. 12. (Tanya Lewis)

RIP

Michael Lane, who the New York Times called “a general in the rout of smallpox,” died at the age of 84. His name isn’t one that kids learn in school, but he was one of the American heroes, along with Bill Foege, who oversaw the Herculean task of wiping that scourge from the face of the Earth. Maybe when we emerge from this terrible pandemic, we’ll get better at recognizing some of these unsung heroes of the scientific enterprise.

Financings

RA Capital Management raised $461 million for a second venture fund to invest in biotech startups.

Menlo Ventures raised its 15^th fund. This one has $500 million. Part of the focus will be on “therapeutics, particularly companies built around platform technologies and massive datasets that can produce multiple new treatments, and transformative health technologies, including applications of genomics and synthetic biology,” the firm said.

Cambridge, Mass.-based Be Biopharma raised a $52 million Series A financing led by Atlas Venture and RA Capital Management. It’s developing B-cell medicines, based on research from David Rawlings and Richard James at Seattle Children’s Research Institute. Aleks Radovic-Moreno is the founding president.

UK-based Abcam, a biological reagents and tool marketer, raised $157 million in an IPO at $17.50 a share.

Australia-based Opthea raised $128 million in an IPO at $13.50 a share. The company is developing a VEGF inhibitor for the wet form of age-related macular degeneration.

South San Francisco-based Aligos Therapeutics raised $150 million in an IPO at $15 a share. The company is working on antiviral therapies for chronic hepatitis B and coronaviruses.

Boston-based Replimune, the developer of oncolytic virus treatments, raised $250 million in a stock offering at $40 a share.

Evanston, Ill.-based Aptinyx raised $42 million in a stock offering at $3 a share after releasing some encouraging data for

Houston-based Kiromic Biopharma raised $15 million in an IPO to advance an AI platform for immuno-oncology therapy development.

Cambridge, Mass.-based Praxis Precision Medicines raised $219 million in an IPO at $19 a share. The company is working on CNS drugs.

Irvine, Calif.-based Tarsus Pharmaceuticals raised $88 million in an IPO at $16 a share. It’s working on ophthalmic drugs.

San Francisco-based InCarda Therapeutics raised $30 million in the first close of a Series C financing to develop inhalable treatments for cardiovascular disease. Innoviva led the deal, and existing investors Deerfield Management, HealthCap and Morningside Venture also joined the financing.

Boston-based Allonia, a spinout from Ginkgo Bioworks, raised $40 million in a Series A financing to make enzymes to clean up environmental contaminants.

Sarissa Capital Management raised $175 million in an IPO at $10 per unit. It’s a blank check company.

Israel-based Azura Ophthalmics raised $20 million to develop a treatment for dry eye.

Paris-based SparingVision raised 44 million EUR to develop genomic medicines for ocular diseases.

Cambridge, Mass.-based Compass Therapeutics, a cancer immunotherapy company, filed a prospectus with the SEC to raise up to $50 million in an IPO.

This Week in the Opioid Crisis

Purdue Pharma agreed to plead guilty to three criminal charges for its role in fostering the opioid painkiller addiction crisis. Purdue will reportedly make a $225 million direct payment to the federal government, but it will likely not have to cough up the full $8 billion extent of the settlement, because it is now in bankruptcy. While a guilty plea on three federal counts is pretty straightforward, David Sackler told Vanity Fair “we didn’t cause the crisis.”

Personnel File

Cambridge, Mass.-based Seres Therapeutics, the microbiome-based therapy developer, hired David Ege as chief technology officer and Jayne Gansler as chief people officer.

BD hired Patrick Kaltenbach as chief technology officer. Dave Hickey was promoted to president of the life sciences segment of the company.

Cambridge, Mass-based Nimbus Therapeutics hired Erin Cowhig as chief people officer. She was previously VP of HR at Vertex Pharmaceuticals.

Gaithersburg, MD-based Sensei Biotherapeutics, a developer of off-the-shelf cell therapies for cancer, hired Anu Hoey as chief business officer.

Cambridge, Mass.-based Sage Therapeutics said CEO Jeff Jonas was scheduled to undergo surgery yesterday (Oct. 22), and will essentially be on a medical leave until December. “While Dr. Jonas is recuperating, he will be available as needed, and during this time, the Sage leadership team will direct business operations,” the company said in a statement.

Democrats in the nation’s capital, according to STAT, apparently want to fire Moncef Slaoui from Operation Warp Speed because of his pharmaceutical industry track record and network. Bad idea.

Cambridge, Mass.-based AVROBio added Gail Farfel to its board.

UK-based Vaccitech hired Margaret (Meg) Marshall as chief medical officer.

Flagship Pioneering said Tuyen Ong has joined the venture firm as a CEO-partner. He’ll lead Ring Therapeutics, a gene therapy company.

Kudos

The National Academy of Medicine named 100 new members. Wendy Chung, a geneticist at Columbia University, Levi Garraway, now at Genentech, and David Liu of Harvard University, Marc Lipsitch of Harvard University, Aviv Regev of Genentech, Antoni Ribas of UCLA, Pardis Sabeti of the Broad Institute, and Bob Wachter of UCSF are members of this year’s stellar cast that are well-known in the biopharma community. (Full list).

Peter Byers of the University of Washington won the 2020 Victor McKusick Leadership award from the American Society of Human Genetics.

Data That Mattered

Switzerland and Cambridge, Mass.-based CRISPR Therapeutics provided an update on a Phase I trial of CTX110, as a treatment for CD19-positive B-cell malignancies. The company reported that 2 out of 4 patients on Dose Level 3 achieved Complete Responses at 3 months. A patient on Dose Level 4 developed cytokine release syndrome, appeared to have a Complete Response at Day 25, but then took turn a for the worse and died at day 52.

Cambridge, Mass.-based Alnylam Pharmaceuticals reported on Phase III results from the Illuminate-B study of pediatric patients who got lumasiran for Primary Hyperoxaluria Type 1. The drug showed a 72 percent mean reduction in urinary oxalate. The product is a subcutaneously administered RNAi drug.

Cambridge, Mass.-based Biogen said it has discontinued development of opicinumab, the anti-LINGO antibody for multiple sclerosis.

San Francisco-based VIR Biotechnology presented data on a broadly neutralizing antibody against influenza A which showed it could bind with and potentially neutralize all major strains of the virus from the past 100 years. That was a preclinical finding. A separate Phase I study found the antibody, VIR-2482, could last long enough to be given once per flu season. Findings were presented at IDWeek.

Evanston, Ill.-based Aptinyx reported top-line data from a Phase II study in post-traumatic stress disorder (PTSD). More detail will be presented at a scientific meeting.

Merck reported positive Phase III results from two more studies of its 15-valent pneumococcal vaccine candidate. Merck also reported 3-year follow-up survival data for pembrolizumab (Keytruda) in first-line treatment of non-small cell lung cancer.

Regulatory Action

Roche won full FDA approval for venetoclax (Venclexta) for newly diagnosed acute myeloid leukemia in adults 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy. The drug had gotten an accelerated approval in November 2018.

Deals

New York-based Nuvation Bio, a cancer drug developer, and Panacea Acqusition (a SPAC backed by EcoR1 Capital) merged in a deal that will bring $500 million in concurrent equity financings.

San Francisco-based Invitae and Menlo Park, Calif.-based PacBio agreed to a research collaboration to use whole genome sequencing to find clinically relevant molecular targets to develop diagnostic tests for kids with epilepsy.

South San Francisco-based insitro, a company using machine learning to advance drug discovery, agreed to acquire Haystack Sciences. Haystack is working on “large, diverse combinatorial chemical libraries encoded by unique DNA sequences called DNA-encoded libraries, or DELs.” Terms weren’t disclosed.

Genentech agreed to work on an AI for drug discovery partnership with Genesis Therapeutics, a spinout from the Pande Lab at Stanford University.

Roche agreed to work with Boston-based Atea Pharmaceuticals on a direct-acting antiviral treatment against COVID-19. Atea’s AT-527 is being developed as an oral nucleotide prodrug, with potential for hospitalized and non-hospitalized patients. It has shown broad potential against human flaviviruses and coronaviruses. Roche agreed to pay $350 million.

Vifor Pharma secured US commercial rights from Cara Therapeutics to IV Korsuva as a treatment for kidney dialysis patients with pruritis (itching). Cara is getting $100 million upfront.

Luke Timmerman, founder & editor, Timmerman Report

It’s hard to tell yet whether the J&J vaccine and Eli Lilly antibody trials are suffering from momentary blips, or something more serious on the safety front.

The AstraZeneca vaccine trial has been stuck on pause in the US since September, which seems like a rather lengthy delay in pandemic terms. Let’s hope they all get back in the saddle shortly.

Catch up on the main happenings of the week in biotech, and try not to get blinded by the distortions of election season.

Save yourself some time and keep things in perspective with Frontpoints.

Vaccines

Johnson & Johnson said it put a temporary pause on all dosing with its adenoviral vector-based, single-shot vaccine candidate for COVID-19 after observing an “unexplained illness in a study participant.” The halt of all clinical trials with this vaccine candidate includes the ongoing Phase III Ensemble trial, was done in accordance with company policies, and isn’t a clinical hold imposed by the FDA, the company said. I’ll be interviewing J&J chief scientific officer Paul Stoffels on a panel at BIO-Europe Oct. 26, and will be sure to ask him about the latest on this program (which hopefully will be back enrolling participants by then).

Sanofi and Lexington, Mass.-based Translate Bio said their mRNA vaccine candidate passed preclinical studies in mice and monkeys, and is being readied to enter clinical trials in the fourth quarter of 2020. The mRNA vaccine candidate generated dose-dependent levels of binding antibodies and neutralizing antibodies to the SARS-CoV-2 spike protein. Scientists at the companies also saw a Th1-biased T cell responses against virus in mice and monkeys. The vaccine is being developed in a two-shot regimen, given three weeks apart. (Preprint article here.)

Treatments

Remdesivir, the antiviral developed by Gilead Sciences, didn’t offer a survival benefit to hospitalized patients in the long-awaited Solidarity trial of 11,000 patients, according to a copy of the World Health Organization study first reported by the Financial Times. The drug also had little effect on hospitalization time. The preprint summary came out later in the day on MedRxiv.

AstraZeneca said it has advanced its long-acting antibody therapy combination, AZD7442, for COVID-19 into a pair of Phase III trials that will enroll 6,000 patients. The LAABs were optimised with half-life extension and reduced Fc receptor binding, and they should provide six to 12 months of protection from COVID-19, the company said. The US government is set to spend $486 million to get access to 100,000 doses, and it can acquire another 1 million doses, the company said.

Eli Lilly and Incyte said baricitinib (Olumiant), a JAK1/JAK2 inhibitor for rheumatoid arthritis, was found to shorten the time to recovery from COVID-19 when given in tandem with remdesivir, compared with remdesivir alone. Patients on the combo got out of the hospital in a median time of 7 days, compared with 8 days for those in the control group. The combo appeared marginally better on survival rates than remdesivir alone, but the difference wasn’t statistically significant, Lilly said. The data came from the Adaptive COVID-19 Treatment Trial, sponsored by the National Institute of Allergy and Infectious Disease.

The NIH said it paused a clinical trial of Eli Lilly’s monoclonal antibody for COVID-19, LY-CoV555, after a Data Safety Monitoring Board reported that study had reached a “predefined boundary for safety” after five days of treatment.

Regulatory Action

The FDA cleared Regeneron Pharmaceuticals to market atoltivimab, maftivimab, and odesivimab-ebgn (Inmazeb), a three-antibody mixture, as the first treatment for Ebola virus in adults and children. This landmark therapeutic approval comes 10 months after the agency approved the first Ebola vaccine, designed to prevent infections. The Ebola work at Regeneron in recent years set the stage for it to move with clarity and speed on its double-antibody cocktail for SARS-CoV-2.

Waltham, Mass. and Dublin-based Alkermes won a 16-1 positive recommendation from an FDA advisory committee that evaluated ALKS3831 – its combo of olanzapine/samidorphan – as a once-daily, oral atypical antipsychotic drug candidate for adults with schizophrenia and for bipolar I disorder. The advisory committee also voted 13-3 that the company had adequately characterized the safety profile.

Beckman Coulter received an Emergency Use Authorization from the FDA for an IgM antibody test that that the company said demonstrates 99.9% specificity and 98.3% sensitivity for the spike protein of the SARS-CoV-2 virus. It’s part of a suite of serology tests, including an IgG assay cleared in June.

Dallas-based Livmor won FDA 510k clearance for a wearable device that provides continuous monitoring of pulse rhythms to detect atrial fibrillation.

Cambridge, Mass.-based Voyager Therapeutics said its IND to begin clinical trials of a gene therapy for Huntington’s disease was placed on hold by the FDA because of questions about chemistry, manufacturing and controls (CMC).

Deals

Eli Lilly agreed to acquire Cambridge, Mass.-based Disarm Therapeutics for $135 million upfront, plus $1.2 billion in potential milestone payments. Disarm is in preclinical development with SARM1 inhibitors  for axonal degeneration diseases such as peripheral neuropathy, amyotrophic lateral sclerosis, and multiple sclerosis.

Japan-based Astellas Pharma agreed to acquire Berkeley, Calif.-based iota Biosciences for $127 million to get the rest of the company that it doesn’t already own, plus another $176 million to iota shareholders if certain milestones are met. Iota is developing ultra-small implantable medical devices to advance the field of bioelectronics.

Cambridge, Mass.-based Dyno Therapeutics, the developer of AAV-based vectors for gene therapies, struck a partnership with Roche. Dyno is getting an undisclosed upfront payment, and total deal value with milestones worth $1.8 billion.

Data That Mattered

Pfizer’s CDK4/6 inhibitor for HER2-negative breast cancer, palbociclib (Ibrance) failed in a Phase III clinical trial of patients with early breast cancer who have residual invasive disease after completing neoadjuvant chemotherapy.

Boston-based Vertex Pharmaceuticals shut down a Phase II clinical trial of VX-814 for alpha-1 antitrypsin deficiency after seeing elevated liver enzymes in several patients. Vertex stock plunged 20 percent on the news of the new safety signal. The company has another compound, VX-864, that’s structurally distinct and also in Phase II development for AATD.

Cambridge, Mass.-based Sage Therapeutics reported positive interim results from the Phase III Shoreline study that looked at zuranalone, an oral GABA_A receptor-positive allosteric modulator for major depressive disorder. The drug is designed to be given in a two-week course of treatment, and therapy can be resumed on an as-needed basis. About 70 percent of patients in the study only needed one or two treatment courses, the company said. Sage said it expects more data in the first half of 2021.

Tarrytown, NY-based Regeneron Pharmaceuticals and Sanofi said dupilumab (Dupixent) passed a Phase III clinical trial for children ages 6-11 with uncontrolled moderate-to-severe asthma. The antibody, which inhibits the inflammatory cytokines IL-4 and IL-13, reduced severe asthma attacks by 65 percent compared with placebo after one year. Researchers also saw improved lung function within two weeks, which continued through the 52-week study.

Belgium-based Galapagos NV and its partner, Servier, reported that an experimental drug for knee osteoarthritis failed in a 52-week Phase II study of 932 patients.

San Diego-based Gossamer Bio said it missed the primary endpoint in a pair of Phase II studies, with its drug candidate for moderate-to-severe eosinophilic asthma, and for chronic rhinosinusitis.

Science

• Immunogenicity of Novel mRNA COVID19 Vaccine MRT5500 in Mice and Non-Human Primates. BioRxiv. Oct. 14. (Kirill Kalnan et al)
• Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms. Science. Oct. 15. (QBI COVID-19 Research Group (QCRG), San Francisco)
• Genomic Evidence for Reinfection With SARS-CoV-2: A Case Study. The Lancet Infectious Diseases. Oct. 12. (Richard Tillett et al)
• Heterogeneity in Transmissability and Shedding of SARS-CoV-2 Via Droplets and Aerosols. MedRxiv. Oct. 15. (Paul Chen et al)
• REGN-COV2 Antibodies Prevent and Treat SARS-CoV-2 Infection in Rhesus Macaques and Hamsters. Science. Oct. 9. (Regeneron team)
• Repurposed Antiviral Drugs for COVID-19, interim WHO Solidarity Trial Results. MedRxiv. Oct. 15. (WHO Solidarity Trial Consortium)

Science Features

• Immunity and Re-Infection. In the Pipeline. Oct. 14. (Derek Lowe)
• First, a Vaccine Approval. Then Chaos and Confusion. NYT. Oct. 12. (Carl Zimmer)
• The Coronavirus Unveiled. NYT. Oct. 9. (Carl Zimmer)

The Infodemic

• She Hunts Viral Rumors About Real Viruses. Profile of Heidi Larson, director of the Vaccine Confidence Project. NYT. Oct. 15. (Jenny Anderson)
• Another Unfounded Study on Origins of Virus Spread Online. NYT. Oct. 13. (Katherine Wu)

Strategy

• It’s Raining Biotech SPACs. LifeSciVC. Oct. 15. (Bruce Booth)

Building Trust, or Eroding Trust?

• Selling Stock Like Clockwork, Moderna’s Top Doctor Gets $1M Richer Every Week. STAT. Oct. 13. (Damian Garde and Adam Feuerstein)
• Pfizer Trying to Defuse Critics Amid Push for Vaccine Before Election Day. Politico. Oct. 15. (Adam Cancryn and Sarah Owermohle)

Manufacturing

• Merck, after facing years of pressure from urologists to address the shortage of its live BCG therapy for bladder cancer, said it will build a new facility in North Carolina to increase capacity to meet the increased demand. The company said it will 5-6 years to get the new facility up and running, in part because “each batch takes more than 3 months to make, 30 days of which is waiting for the growth of bacteria used to make the medicine.”

Our Shared Humanity

• Kids Have Suffered Enough. Let Them Have Halloween. NYT. Oct. 15. (Aaron Carroll)
• What Strength Really Means When You’re Sick. The Atlantic. Oct. 9. (Ed Yong)
• An Especially Inspiring Nobel Prize. Timmerman Report. Oct. 13. (Jennifer E. Adair)

Investigative Reporting

• Inside the Fall of the CDC. How the world’s greatest public health organization was brought to its knees by a virus, the president and the capitulation of its own leaders, causing damage that could last much longer than the coronavirus ProPublica. Oct. 15. (James Bandler, Patricia Callahan, Sebastian Rotella and Kirsten Berg)
• The Inside Story of How the Coronavirus Task Force Coordinator Undermined the World’s Top Health Agency. Science. Oct. 14. (Charles Piller)

Public Health

• Scientific Consensus on the COVID-19 Pandemic: We Need to Act Now. The Lancet. Oct. 15. (Nireen Alwan and 30 leading epidemiologist co-authors.)
• Herd Immunity Strategy Endorsed by White House a ‘Ridiculous’ Way to Stop COVID. It Will Just Kill People, Scientists Say. USA Today. Oct. 14. (Elizabeth Weise)
• White House Blocked CDC From Requiring Masks on Public Transportation. NYT. Oct. 9. (Sheila Kaplan)
• Federal Official Threatens Nevada for Halting Rapid Testing in Nursing Homes. Nevada Said Tests Had High False Positive Rate. NYT. Oct. 9. (Katherine Wu)
• FDA Chief Defends Vaccine Trial Halts as Vital to Public Safety. Bloomberg News. Oct. 14. (Drew Armstrong)
• An Outbreak of COVID-19 Associated With a Recreational Hockey Game in Florida. CDC Weekly Morbidity and Mortality Report. Oct. 16. (David Atrubin, Michael Wiese, Becky Bohinc)

Politics

• Why Nature Supports Joe Biden for President. Nature. Oct. 14. (The Editors)
• On Nov. 3, Vote to End Attacks on Science. Scientific American. Oct. 9. (The Editors)
• Fauci: I’m Not Going Anywhere. Says He’ll Serve Next 4-Year Term, No Matter Who Wins. NBC News. Oct. 12. (Dareh Gregorian)
• The White House Embraces Herd Immunity Strategy From Great Barrington Declaration. NYT. Oct. 15. (Coronavirus coverage) (Great Barrington Declaration)

Perspective

• Before Virus, After Virus. A Reckoning. Cell. Oct. 15. (Siddharta Mukherjee)

This Week in Drug Pricing

• Biden Hints At What Could Be a Model for Drug Pricing Compromise: The Germany Model. Inside Health Policy. Oct. 15. (John Wilkerson)

This Week in the Opioid Crisis

Johnson & Johnson reported in its third quarter earnings statement that it will pony up another $1 billion as part of the settlement with state Attorneys General for its role in the opioid epidemic. The company’s total liability now stands at $5 billion.

Financings

Canaan Partners raised its 12^th fund. This one is worth $800 million, and will be put to work in healthcare and technology companies.

Cambridge, Mass.-based Codiak Biosciences, the exosome therapeutics developer, raised $82.5 million in an IPO priced at $15 a share. (See TR coverage of Codiak’s partnership with Sarepta, June 2020).

Cambridge, Mass.-based Nimbus Therapeutics, the small molecule drug discovery operation that leans heavily on structural biology and computational chemistry, secured a $60 million private financing from RA Capital Management and BVF Partners to continue advancing its Tyk2 inhibitor into Phase II, an HPK1 inhibitor into the clinic, and more preclinical candidates. (See TR coverage of Nimbus / Celgene partnership, Oct. 2017).

San Francisco-based Vineti, the developer of a digital platform to manage distribution of personalized gene and cell therapies, expanded its Series C financing by an additional $33 million, bringing the total to $68 million. Cardinal Health led the deal, and Marc Benioff joined the syndicate. (See TR coverage of Vineti’s initial Series C close, Feb. 2020).

San Diego-based RayzeBio raised $45 million in a Series A financing to develop a new platform for radiopharmaceuticals for cancer. Versant Ventures and venBio co-led, and were joined by Samsara BioCapital. (See TR coverage).

Seattle-based NanoString Technologies, the maker of life sciences tools, raised $230 million in a public offering at $40 a share. (See recent TR article by Nanostring’s Sarah Warren and Jason Reeves about spatial biology research into COVID-19).

San Francisco-based Spruce Biosciences raised $103 million in an IPO priced at $15 a share. The company is working on rare endocrine disorders.

Switzerland-based VectivBio raised $110 million to advance Phase III development and commercialization of apraglutide, a GLP-2 analogue to treat short bowel syndrome.

Dublin-based Priothera raised 30 million EUR to develop oral sphingosine 1 phosphate (S1P) receptor modulators for hematological malignancies. Fountain Healthcare Partners and HealthCap co-led.

UK-based Oxford Nanopore raised $100 million to advance its commercial work, and further R&D, of its nanopore-based DNA/RNA sequencing technology.

Beijing and Cambridge, Mass.-based EdiGene raised about $67 million in a Series B financing to advance its gene editing programs into clinical trials.

Watertown, Mass.-based SQZ Biotechnologies, the developer of cell therapies for cancer and infectious disease, filed an S-1 prospectus with the SEC to raise up to $75 million in an IPO.

San Diego-based Evofem Biosciences, a women’s health company, raised $25 million in convertible debt from Adjuvant Capital.

Branford, CT-based Azitra raised $17 million in a Series B financing to advance a microbiome-based therapy for dermatology indications. Leaps by Bayer led.

Personnel File

Cambridge, Mass.-based Dewpoint Therapeutics hired Ameet Nathwani as CEO. (See TR coverage of Dewpoint and its membraneless organelles for drug discovery, Apr. 2019).

Joe Anderson joined France-based Sofinnova Partners a partner in its crossover fund. He comes from Abingworth.

Tom Graney, formerly of Vertex, joined Belgium and Boston-based Oxurion as CFO. The company is working on treating diabetic macular edema.

Germany-based Merck KGaA said Luciano Rossetti is retiring as global head of R&D for healthcare. He’ll be replaced by Danny Bar-Zohar, who joins the company Nov. 1, and Joern-Peter Halle. Bar-Zohar takes on the development work, while Halle will oversee research.

San Carlos, Calif.-based Nautilus Biotechnology, a proteomics company, hired Nick Nelson as chief business officer.

San Diego-based Effector Therapeutics, the developer of selective translation regulator inhibitors (STRIs) for the treatment of cancer, hired Premal Patel as chief medical officer.

Menlo Park, Calif. and Dallas-based ReCode Therapeutics, working on respiratory diseases, hired Julie Eastland as chief operating and chief financial officer.

Luke Timmerman, founder & editor, Timmerman Report

What a time to be alive in biomedicine. Catch up on the main events in Frontpoints.

The Babe Ruth of Public Health Speaks Out

William Foege is in his mid-80s. There’s a genome sciences building at the University of Washington named after him because Bill Gates gave money to build it, and he wanted it named after a scientific hero. Foege has nothing to prove to anyone, and doesn’t seek attention. He’s belongs on the Mount Rushmore of global health for his strategically brilliant and relentless campaign to eradicate smallpox from Earth.

So I snapped straight up and read every word Foege wrote when USA Today discovered and published a private letter Foege wrote to current CDC director Robert Redfield, dated Sept. 23.

Foege empathizes with the embattled CDC director in the opening, but like an angry and baffled father, he chastised Redfield for this monumental failing of American leadership in public health. The only real alternative at this point, Foege wrote, is for Redfield to document the horrifying cascade of White House incompetence and mendacity, and resign to save the CDC, a once-proud and now humiliated agency.

Read the full, scathing letter here.

CDC, Finally, Updates Airborne Guidance

We’ve known since January that SARS-CoV-2 is transmitted through the air. There have been debates over the relative extent of droplets versus aerosols, and how far is far enough for social distancing, but still, but the science on tiny aerosol transmission has been clear for some time. And yet, the CDC, has been unable to effectively communicate this to the public. Remember when Dr. Redfield told a Congressional committee that a mask was an even more effective defense tool than a vaccine, and when the President slapped him down for that act of fact-based insubordination? The latest shameful episode in CDC history came when the agency briefly took down guidance from its website in September that emphasized the risk from airborne transmission of the virus. It took until Oct. 5 – yet another day with more than 40,000 new cases – before the CDC was able to update its guidance on its website about airborne transmission. Look at the terrible case of confusing whiplash this gives the public, neatly captured in WSJ editor Jonathan Rockoff’s tweets.

If citizens had been given the straight scoop, straight from the podium of the CDC starting in January and continuously updated from that point forward, I firmly believe this country would have looked more like Germany today. We would have been able to save tens of thousands of lives. But now, as things are, many thousands more are going to die – still 1,000 a day! This horse should never have gotten so far out of the barn. The body politic should never have been so thoroughly poisoned that we’d up in a cynical abyss where large numbers of citizens refuse to wear masks and engage in common sense social distancing.

All of the elected officials who are responsible, and those who continue to enable this daily rolling national train wreck, must be voted out of office.

Kudos

The Nobel Prizes came out, and were quite illustrative of the golden age of biomedicine. On Monday, the Nobel Prize in Physiology or Medicine went to Harvey Alter at the National Institutes of Health; Michael Houghton, now at the University of Alberta; and Charles Rice, now at Rockefeller University. Their work on the hepatitis C virus laid the groundwork for one of the biggest success stories in biotech history – cures for this chronic, liver-damaging infection. Houghton, by the way, did his pioneering work on HCV while at Chiron, one of the early biotech companies (now part of Novartis).  

Then, on Wednesday, came an even bigger award – the Nobel Prize for Chemistry went to Jennifer Doudna and Emmanuelle Charpentier for their discovery of CRISPR-Cas9 gene editing. This discovery of precise editing tools was revolutionary, and is now setting the stage for a new crop of gene-edited medicines with potential to cure diseases like sickle-cell disease, a new generation of drug discovery platforms to speed up precision medicine development, clever agricultural applications, cheap and fast diagnostics and so much more. The cheap, fast, easy nature of CRISPR editing makes it an accessible lab tool widely distributed in labs around the world. Doudna and Charpentier’s contribution not only changed biomedicine, but this dynamic duo is especially inspiring to women scientists and young girls. That was the bigger story than the long-running patent dispute between the University of California-Berkeley and the Broad Institute. George Church and Eric Lander, a couple of leading lions of science with competing claims to novelty in the early work on CRISPR, both made gracious public comments, rather than resort to the kind of occasionally ugly professional jealousy that often swirls around the Nobels. Church, when asked about Doudna and Charpentier’s prize, told STAT “they made the key discovery.”

Isaac Kohane, a professor of biomedical informatics at Harvard Medical School, was awarded the 2020 Morris F. Collen Award of Excellence from the American College of Medical Informatics.

Regulatory Action

The FDA released guidance for COVID-19 vaccine development, and what the standards are for an Emergency Use Authorization, in advance of the upcoming Oct. 22 advisory committee to review the latest safety and efficacy data on this historic effort. The big news in the document (full version here) was that the FDA is calling for at least two months of safety data (see Appendix II) from participants in trials after getting their second and final dose. That means there’s no way an EUA can be issued before the general election on Nov. 3. The White House had reportedly balked at the guidance document, and held it up with questions for FDA. The White House has done considerable damage to the FDA’s reputation for scientific independence this year, but as the President was ill with COVID-19, the White House ultimately backed off, dropping its objections to the balance the agency has been trying to strike between the need for speed, as well as the need for adequate safety data. Given the state of vaccine hesitancy in the public, which perceives a corner-cutting job in the works for electoral purposes, we can be thankful that cooler heads have prevailed.

Albert Bourla, the CEO of Pfizer, may have had a hand in the White House backing off from its aggressive stance, as he said unequivocally that his company wouldn’t try to undercut the independence of the FDA (even if it’s presumably financially advantageous for the company to get a jump on rivals and start selling its COVID vaccine as fast as possible). See his Tweet below.

One final point about COVID-19 vaccine timelines that has gotten less attention: waiting just a few weeks longer for the trials to play out could be the difference between making a momentous decision on a rather skimpy data set, or making it based on a fully mature dataset rich with information on key subgroups like the elderly, and racial and ethnic groups that have been reluctant to enroll in trials (and who especially need vaccines because of the higher-than-average risk minority groups face.) See this comment I tweeted in the moment from Larry Corey of Fred Hutch, one of the leaders of the Operation Warp Speed effort, who spoke at a Johns Hopkins University and University of Washington symposium on Oct. 6.

Tarrytown, NY-based Regeneron Pharmaceuticals submitted a request Oct. 7 to the FDA for Emergency Use Authorization for its REGN-COV2 two-antibody cocktail that’s designed to neutralize the SARS-CoV-2 virus. This comes after the company issued a press release Sept. 29 with the first meaningful slice of clinical data, showing the antibody could significantly reduce viral loads, especially among patients with high amounts of circulating virus. Data from that rolling clinical program haven’t yet been published in a peer-reviewed journal. The move to seek an EUA for wide distribution to patients came the same day the President extolled the virtues of the therapeutic neutralizing antibody from Regeneron, which he received on a Compassionate Use basis, and which he publicly credited with helping him recover from COVID-19. Whether that’s true, of course, we don’t know.

New York-based Mesoblast received a dreaded Complete Response Letter from the FDA, explaining why it wasn’t willing to approve the company’s application to market a new treatment for pediatric steroid-refractory graft-versus-host-disease in children. This was a surprise, given that the FDA’s Oncologic Drugs Advisory Committee voted 9-1 in favor, saying the available data support the drug’s efficacy. The FDA disagreed, saying the company should run at least one additional randomized study in adults or children.

New York-based Y-mAbs Therapeutics received a Refusal to File letter – meaning the FDA declined to review its application to start marketing omburtamab as a treatment of pediatric patients with CNS/leptomeningeal metastasis from neuroblastoma. The agency said the company needs to provide more detail in its Chemistry Manufacturing and Control (CMC) section, and the Clinical section of the Biologics License Application.

San Carlos, Calif.-based Iovance Biotherapeutics reported that its plans to file a Biologics License Application to the FDA have been delayed, based on a disagreement with the agency over “the required potency assays to fully define its TIL therapy.” The company is developing lifileucel as a Tumor-Infiltrating Lymphocyte therapy for metastatic melanoma.

Deals

Bristol-Myers Squibb agreed to pay $13.1 billion in cash, or $225 a share, to acquire Brisbane, Calif.-based Myokardia, the developer of targeted therapies for cardiovascular diseases. Through the deal, BMS obtains mavacamten, a first-in-class treatment for obstructive hypertrophic cardiomyopathy which has gone through Phase III development, and which is expected to go before the FDA with a New Drug Application in the first quarter of 2021. Third Rock Ventures bet $38 million on this company in a Series A financing in September 2012 (see my coverage at the time on Xconomy.)

Pleasanton, Calif.-based 10X Genomics acquired Boston-based ReadCoor for $350 million, a few weeks after its acquisition of Stockholm-based CartaNA. The two acquisitions represent a strategic move into In Situ analysis. (See TR coverage of ReadCoor in this June 2020 feature on “Complexity in Motion.”)

Vancouver, BC-and Seattle-based Chinook Therapeutics closed its merger with Aduro Biotech and completed a $115 million private placement that leaves it with $275 million in cash to develop precision medicine therapies for kidney diseases.

Palo Alto, Calif.-based BridgeBio Pharma agreed to pay $175 million to acquire the remainder of Eidos Therapeutics which it didn’t already own. Eidos is developing acoramidis, a TTR stabilizer for patients with ATTR cardiomyopathy and polyneuropathy.

Cambridge, Mass.-based AVROBio in-licensed a lentiviral gene therapy program from the University of Manchester, to treat patients with Hunter Syndrome. (See TR coverage of AVROBio, September 2020)

The Netherlands and Belgium-based argenx announced a series of partnerships with Chugai Pharmaceuticals, The Clayton Foundation, and Halozyme Therapeutics to expand its antibody engineering capabilities.

Takeda Pharmaceuticals and Arrowhead Pharmaceuticals agreed to work together on further developing ARO-AAT for Alpha-1 Antitrypsin-Associated Liver Disease. Arrowhead is getting $300 million upfront.

Data That Mattered

Eli Lilly had the best clinical data of the week, hands down. The Indianapolis-based pharma company reported that its neutralizing antibody program for COVID-19, developed in collaboration with AbCellera against the spike protein of SARS-CoV-2, nailed an interim analysis of the BLAZE-1 clinical trial that looked at mild-to-moderate COVID-19 patients. The combo therapy of two antibodies did especially well at taking down viral loads at Day 3, Day 7 and Day 11, and reduced COVID-related hospitalization and ER visits. The company said it will seek Emergency Use Authorization from the FDA based on the result. This is the kind of biological and clinical data alignment that we all want to see. Key slide below.

Amgen had a mixed bag of recent results. The company reported positive top-line results for its KRAS G12C directed small molecule drug candidate, sotorasib, in a Phase II study of 126 patients with KRAS G12C mutated forms of advanced non-small cell lung cancer. A few days later, Amgen reported on a failed Phase III result for omecamtiv mecarbil in patients with heart failure with reduced ejection fraction (HFrEF). Technically, the trial hit the primary composite endpoint, but the benefit on that score was miniscule, and the drug failed to demonstrate an improvement in cardiovascular death, a key secondary endpoint. Results from the GALACTIC-HF study, which enrolled, 8,256 patients in 35 countries, will be presented at the American Heart Association’s Scientific Sessions on Nov. 13.

Gilead Sciences and collaborators from the National Institute of Allergy and Infectious Disease published final results for remdesivir in the New England Journal of Medicine. The full analysis confirms the earlier reports that the antiviral can help patients recover more quickly, and get out of the hospital faster. The drug didn’t show a statistically significant benefit on mortality at Day 29, but a post-hoc analysis showed there was a 72 percent mortality benefit in a subgroup of patients who got low-flow oxygen upon hospital admission.

Science

• Airborne Transmission of SARS-CoV-2. Science. Oct. 5. (Kimberly Prather et al)
• Cross Reactive Memory T-cells and Herd Immunity to SARS-CoV-2. Nature Reviews Immunology. Oct. 6. (Marc Lipsitch et al)
• Antigen-based Testing, But Not Real-Time PCR, Correlates With SARS-CoV-2 Virus Culture. MedRxiv. Oct. 5. (Andrew Pekosz et al)
• Remdesivir for the Treatment of COVID-19. Final Report. New England Journal of Medicine. Oct. 8. (John Biegel et al)
• Effect of Hydroxychloroquine in Hospitalized Patients With COVID-19. New England Journal of Medicine. Oct. 8. (The RECOVERY Collaborative Group)
• Remdesivir Targets a Structurally Analogous Region of the Ebola and SARS-CoV-2 Polymerases. Proceedings of the National Academy of Sciences. Oct. 7. (Michael Lo et al)

Science Features

• Charting a COVID19 Immune Response. NYT. Oct. 5. (Katherine Wu and Jonathan Corum)
• LongCovid: Let Patients Help Define Long-Lasting Symptoms. Nature Editorial. Oct. 7. (The Editors)
• How Superspreading Events Drive Most COVID-19 Spread. Scientific American. June 23. (Christie Aschwanden)
• How the White House Flouted Basic Coronavirus Rules. NYT. Oct. 8. (Lauren Leatherby et al)

Public Health

• Get Serious About the People Putting All of Us at Risk. Let’s Enforce Mask Wearing. NYT. Sept. 29. (Elisabeth Rosenthal)
• Against COVID-19, Imperfect Measures Do the Most Good. NYT. Oct. 4. (Joshua Schiffer)

Strategy

• Playing to Win: Scenario Planning for a Binary Readout in Biotech. LifeSciVC. Oct. 8. (Ankit Mahadevia)

Politics

• Why Nature Needs to Cover Politics More Than Ever Now. Nature Editorial. Oct. 6. (The Editors)
• Dying in a Leadership Vacuum. New England Journal of Medicine Editorial. Oct. 8. (The Editors)
• Coronavirus Advisor Scott Atlas Hits Back at Fauci and Others Who Doubt His Advice. “I’m Here Because the Country’s Off the Rails.” Business Insider. Oct. 6. (Ashley Collman)

Worth a Listen

• Moncef Slaoui, The Man Behind America’s Race for a Coronavirus Vaccine. Sway podcast. Oct. 5. (Kara Swisher)

Personnel File

Merck said that Roger Perlmutter, president of Merck Research Laboratories since 2013, is retiring on Jan. 1, 2021. He will be replaced by Dean Li, the company’s senior vice president of discovery sciences and translational medicine. Li is a former professor of medicine and cardiology at the University of Utah. Perlmutter, an immunologist by training, presided over the breakout success of the cancer immunotherapy pembrolizumab (Keytruda).

Brett Zbar joined General Atlantic as global head of life sciences, as the growth equity firm formally established life sciences as its fifth core investment sector. Zbar was previously a managing director with Foresite Capital. (I wrote about Zbar in 2018 as one of “Nine VCs Who Matter, But You Never Read About.”)

Paul Medeiros joined Cambridge, Mass.-based Q-State Biosciences as president and CEO. The company is developing drugs for diseases associated with electrically excitable cells.

San Rafael, Calif.-based BioMarin Pharmaceutical hired Kevin Eggan as Group Vice President, Head of Research and Early Development. He was formerly a tenured professor in the Department of Stem Cell and Regenerative Biology at Harvard University, the Director of Stem Cell Biology for the Stanley Center for Psychiatric Research at the Broad Institute, and an Institute Member of the Broad Institute of MIT and Harvard.

San Diego-based Expansion Therapeutics named Renato Skerlj as its new CEO. The company is developing small molecule drugs against RNA targets.

Sarah Noonberg was hired as chief medical officer of San Francisco-based Maze Therapeutics. (See TR coverage of the $191 million Series A in this company in February 2019, led by Third Rock Ventures and Arch Venture Partners.)

Rick Bright, the former head of the Biomedical Advanced Research and Development Authority who became a whistleblower on the political interference in the COVID-19 response effort, including the unwarranted push for hydroxychloroquine, resigned. In his amended whistleblower complaint, he said he had only been given one assignment since being transferred to the NIH.

Norwood, Mass.-based Corbus Pharmaceuticals cut its workforce by 54 percent.

Name Change

Seattle Genetics officially changed its name to SeaGen Inc. – which has been its informal name for years. The company is actually based in suburban Bothell, Wash. and isn’t exactly a genetics company, it’s a cancer drug developer. It’s never made a lot of buzz for itself, but it has long been the unquestioned bellwether of the Seattle biotech hub with a $35 billion market valuation.

Financings

San Mateo, Calif. and Cambridge, Mass.-based Kronos Bio, a cancer drug developer led by former Gilead CSO Norbert Bischofberger, raised $250 million in an IPO at $19 a share.

Watertown, Mass.-based C4 Therapeutics, the developer of targeted protein degrading drugs, raised $210 million in an IPO at $19 a share.

Silver Spring, Maryland-based Aziyo Biologics raised $50 million in an IPO at $17 a share.

Durham, NC and Austin, Tex.-based Shattuck Labs, a cancer drug developer, raised $202 million in an IPO at $17 a share.

Exton, Penn.-based Immunome, a company working on memory B-cells to develop antibody therapies, raised $39 million in an IPO at $12 a share.

Cambridge, Mass.-based Oncorus, a viral immunotherapy developer for cancer, raised $87 million in an IPO at $15 a share.

Alameda, Calif.-based Scribe Therapeutics raised $20 million in a Series A financing to develop in vivo CRISPR gene editing medicines. Andreesen Horowitz led. It spun out of the Doudna Lab, Oakes Lab, and the Innovative Genomics Institute. Scribe also announced a Biogen partnership to work on neurodegeneration.

South San Francisco-based Federation Bio got started with a $50 million Series A to develop microbiome therapies. Horizons Ventures led, and was joined by existing investors Venrock and Altitude. Emily Drabant Conley, formerly of 23andMe, was named CEO.

Stamford, Conn.-based Springworks Therapeutics, a cancer drug developer, raised $250 million in a stock offering at $51 a share.