Top Stories for Week of December 7, 2020

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COVID-19 vaccines raise hopes for eventual end to pandemic, but cruel months lie ahead.

US leaders and scientific advisers urgently called on Americans to wear masks immediately and threatened even more drastic stay-at-home orders after deaths from the coronavirus set a single-day record last week, with two people dying every minute. After the first cases of COVID-19 were confirmed in the US on January 20, it took almost 100 days to reach one million infections.

On Sunday, CNN reported that the country added more than one million cases to its appalling total–in just five days. From last Tuesday to Saturday, 1,000,882 new coronavirus cases were registered in the US, according to data from Johns Hopkins University, bringing the totals to more than 14.5 million confirmed cases and 281,199 deaths from the virus. The US figures comprise 21.8% and 18.7% respectively of the global totals. November registered startling peaks in the daily number of coronavirus cases–reaching 100,000 for the first time. On December 2, more than 200,000 new cases were reported for the previous 24 hours. As the impacts of Thanksgiving travel and gatherings begin to reveal themselves, and hospitals fill to capacity, experts say it is only going to get worse.

President-elect Joe Biden promised a new national strategy that will impose mask mandates where he will have authority, such as federal buildings and for interstate travel, once he takes over for departing President Donald Trump on Jan. 20. Beyond the mandate, he urged people to voluntarily wear masks, seeking to counter lax public discipline to date and Trump’s own timid endorsement of mask-wearing. Coronavirus vaccines are poised to be approved and distributed in the coming weeks in the US, but that promising news comes amid record levels of infections and hospitalizations, with experts warning that the most brutal period of the pandemic lies ahead.

The message is clearly that the pandemic is far from over.

“The vaccine has not come in time to do much about the winter wave,” said Christopher Murray, director of the University of Washington’s Institute for Health Metrics and Evaluation. “Vaccination is coming too late even if we do a really great job of scale-up. It’s coming too late to do much by March 1, or really by April 1.”

Only at that point, he added, will the widespread distribution of vaccines begin to crush the virus. In the meantime, the country faces what could turn out to be the most challenging few months in the public health history of the nation, Robert Redfield, director of the Centers for Disease Control and Prevention, warned in a speech last Wednesday. That kind of dire language is increasingly coming from the top experts in the field and from the highest levels of the federal medical establishment.

A new aggregation of 37 models sent to the Centers for Disease Control and Prevention–projected that 9,500 to 19,500 people would die of COVID-19 in the week encompassing Christmas. Murray’s institute, meanwhile, has been putting the final touches on a new forecast that he said would show an increase from its Nov. 19 projection of 470,000 deaths by March 1.

Two vaccines are being reviewed by the Food and Drug Administration and expected to receive clearance in the coming weeks. One of them, from Pfizer Inc. (NYC) and BioNTech SE (Mainz DEU), was approved last week in the United Kingdom. Four more vaccine candidates are in late-stage trials. Later this year or early next year, there could be more than a million doses of vaccines going into arms every day in the US. But experts say it will take time to change the trajectory of the epidemic which is now thundering across much of the country.

COVID-19 Addenda: Pfizer Inc. (NYC) and BioNTech SE (Mainz DEU) expect to ship only half of the 100 million doses of COVID-19 vaccine they had originally targeted for worldwide delivery this year because of hurdles encountered with the supply chain, according to a report in the Wall Street Journal on Thursday. A person directly involved in the development of the mRNA-based BNT162b2 candidate said “some early batches of the raw materials failed to meet the standards. We fixed it, but ran out of time to meet this year’s projected shipments.”

However, Pfizer and BioNTech maintain that they are on track to roll out 1.3 billion vaccines in 2021, while the 50-million dose shortfall this year will be covered as production ramps up, the WSJ said. UK regulators granted the first emergency-use authorization for BNT162b2 earlier last week. The two-dose vaccine is also under review for emergency use in the US, with an FDA advisory panel scheduled to meet to discuss the filing on December 10. Results from a recent analysis demonstrated that BNT162b2 has an efficacy rate of 95% based on 170 cases of COVID-19 seen in a Phase 3 study of 44,000 participants.

Elsewhere, Anthony Fauci, the leader of the National Institute of Allergy and Infectious Diseases (NIAID) and newly-appointed chief medical adviser for President-elect Joe Biden, has apologized for suggesting that the UK “rushed” through the authorization process to clear Pfizer and BioNTech’s vaccine. It had been the first country in the world to do so. Appearing on the BBC, Fauci said there has been a misunderstanding and asserted “great faith” in British scientists and regulators. His comments on Fox and CBS News, he added, were meant to contextualize the decision for the US, where regulators need to take into account widespread vaccine skepticism and any potential pushback from the society.

“Our process is one that takes more time than it takes in the UK. And that’s just the reality,” he said, adding: “I did not mean to imply any sloppiness even though it came out that way.”

The emphasis on trust echoes comments made by FDA commissioner Stephen Hahn, who said a team of 150 is working around the clock to ensure the vaccine meets the gold standard.

States drafted plans Thursday for who will go to the front of the line when the first doses of COVID-19 vaccine become available later this month, as US deaths from the outbreak eclipsed 3,100 in a single day, obliterating the record set last spring. With initial supplies of the vaccine certain to be limited, governors and other state officials are weighing both health and economic concerns in deciding the order in which the shots will be dispensed, according to the Associated Press.

States faced a Friday deadline to submit requests for doses of the Pfizer vaccine and specify where they should be shipped, and many appear to be heeding nonbinding guidelines adopted this week by the Centers for Disease Control and Prevention to put healthcare workers and nursing home patients first. But they’re also facing a multitude of decisions about other categories of residents–some specific to their states; some vital to their economies. Colorado’s draft plan, which is being revised, puts ski resort workers who share close quarters in the second phase of vaccine distribution, in recognition of the $6 billion industry’s linchpin role in the state’s economy.

And updated National Institutes of Health guidelines narrowed the scope of recommended use for remdesivir (Veklury) in hospitalized COVID-19 patients, and the quality of evidence backing the drug’s use also took a hit. In a revision to its therapeutic management guidelines released on Thursday, the NIH no longer recommends remdesivir with dexamethasone as an option for hospitalized COVID-19 patients who require mechanical ventilation or ECMO, recommending only dexamethasone instead. For patients who are hospitalized and require supplemental oxygen, remdesivir is recommended for patients who require “minimal supplemental oxygen,” with dexamethasone and remdesivir recommended for patients who require “increasing amounts” of supplemental oxygen.

The rating of recommendations for remdesivir also dropped from A (strong) to B (moderate). Previously, remdesivir was recommended for hospitalized patients requiring supplemental oxygen, with dexamethasone only recommended in this population if remdesivir could not be used. Gilead Sciences Inc. (Foster City CA) developed remdesivir.(Ref: MedPage Today)

UK approves Pfizer COVID-19 vaccine ahead of US endorsement.

The United Kingdom last week became the first country to approve a COVID-19 vaccine developed by Pfizer Inc. (NYC) and its partner BioNTech SE (Mainz DEU), a decision that will likely put pressure on the Food and Drug Administration to move swiftly to do the same. The vaccine is also the first to run the gauntlet of clinical studies normally required for approval, according to STAT News. Russia and China have authorized vaccines without Phase 3 clinical trial data.

The fact that the UK approved a vaccine developed by an American company–in partnership with a German one–before the US could pour fuel on the already tense relationship between President Trump and the FDA, which has taken a more deliberative process in reviewing vaccine data. Over the course of the pandemic, Trump has often used his bully pulpit–and Twitter account–to pressure the agency, and the FDA has taken several steps that critics worried were politically motivated, including granting emergency use authorizations to hydroxychloroquine, an old malaria drug, and convalescent plasma, a blood product, as treatments for COVID-19 despite a lack of evidence that either is effective. The authorization for hydroxychloroquine was later rescinded.

The controversy over the earlier decisions and the pressure from the White House led to fears that the FDA would be forced to authorize COVID-19 vaccines without a proper review. As a result, the agency has taken pains to be transparent about its review processes and insisted decisions would be made by career staff. But the result has been impatience at the White House. Last Tuesday, the news site Axios reported that White House chief of staff Mark Meadows summoned Stephen Hahn, the FDA commissioner, to explain why the agency hadn’t already moved to authorize the Pfizer/BioNTech vaccine, or another vaccine developed by the biotechnology firm Moderna Inc (Cambridge MA). Both the Pfizer/BioNTech and Moderna vaccines have been shown in large trials to reduce the risk of developing symptomatic COVID-19 infection by more than 90%. But full details on both trials have been made available only by press releases, not in medical journals.

The FDA normally conducts the most rigorous reviews of medical products in the world, re-analyzing the databases from clinical trials and conducting its own reviews of the safety and efficacy of products, as well as independent statistical reviews of their clinical trials. A key part of that process is scheduled for Dec. 10, for the Pfizer/BioNTech vaccine, and Dec. 17, for the Moderna vaccine. That is when an FDA advisory panel of outside experts is scheduled to go over the data in meticulous detail in a public meeting. These advisory panels are not necessary for an emergency use authorization, as opposed to a full approval, but it is extremely unlikely that the FDA would issue a decision without waiting for the meetings to occur.

Moderna offers glance at its COVID vaccine’s endurance data.

Antibody responses to Moderna Inc.’s (Cambridge MA) COVID-19 vaccine candidate, mRNA-1273, remained robust for nearly four months following vaccination, data from a Phase 1 trial indicated. Serum neutralizing antibodies were detected in 34 healthy adult volunteers at day 119 following the first dose, and 90 days following the second dose, reported Alicia Widge, MD, of the National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, MD, and colleagues. Moreover, both binding and neutralizing geometric mean titers exceeded those in 41 healthy controls who were recovering from COVID-19, the authors wrote in a Correspondence piece in the New England Journal of Medicine. “Although correlates of protection against SARS-CoV-2 infection in humans are not yet established, these results show […] mRNA-1273 has the potential to provide durable humoral immunity,” the researchers wrote. Importantly, they also found no new adverse events considered to be related to the vaccine after day 57.

Moderna recently made news with the interim results of Phase 3 data that found 94.5% efficacy for its COVID-19 vaccine candidate, which NIAID co-developed, versus placebo. The company has applied for emergency use authorization, and an FDA advisory committee meeting to discuss this application is slated for Dec. 17, MedPage Today reports. While researchers reported immunogenic results covering 57 days after the first vaccination, they noted “longitudinal vaccine responses are critically important.” Here, 34 participants, ages 18 and older, who received the 100-μg vaccine dose, were assessed at day 119. They were stratified by age: 18-55, 56-70, and 71 and older.

Binding and neutralizing antibodies remained “elevated” in all participants 3 months following the booster vaccination, the authors said, with the highest geometric mean titers in the youngest group. Declines over time were more pronounced in the two older cohorts, which were expected and remained well above baseline. The authors added that the vaccine also elicited primary CD4 type 1 helper T responses 43 days after vaccination, with studies of vaccine-induced B cells ongoing.

An ongoing follow-up analysis plans to assess safety and immunogenicity in these participants for 13 months. The Phase 3 trial is also ongoing.

IPO Sector: Kinnate Biopharma Inc., a preclinical biotech developing targeted kinase inhibitors for difficult-to-treat cancers, raised $240 million by offering 12 million shares at $20, above the range of $18 to $19. The company offered 0.5 million more shares than anticipated. It originally planned to offer 10 million shares at a range of $16 to $18, before revising its terms last Tuesday. The San Diego, CA-based company is focused on the discovery and development of small molecule kinase inhibitors for difficult-to-treat, genomically defined cancers. Its lead candidate, KIN002787, is a Rapidly Accelerated Fibrosarcoma (RAF) inhibitor for the treatment of patients with lung cancer, melanoma, and other solid tumors. The company expects to file an IND for KIN002787 in the 1H21. Kinnate Biopharma was founded in 2018 and lists on the Nasdaq under the symbol “KNTE.” Goldman Sachs, SVB Leerink and Piper Sandler are the joint bookrunners on the deal. Shares more than doubled over the week (+217%) to $43.46.

Elsewhere, Sigilon Therapeutics Inc., a Phase 1/2 biotech developing allogeneic therapies for hemophilia A and diabetes, raised $126 million by offering 7 million shares at $18, within the range of $17 to $19. The company offered 1.4 million more shares than anticipated. At pricing, Sigilon Therapeutics commands a fully diluted market value of $598 million. The Cambridge, MA-based company is pioneering a new class of therapeutics for patients with chronic diseases by providing stable and durable levels of therapeutic molecules. The Shielded Living Therapeutics platform combines advanced cell engineering with innovations in biocompatible materials and enables product candidates to produce a wide range of therapeutic molecules that may be missing or deficient. Sigilon’s lead candidate, SIG-001, is designed to prevent bleeding episodes in patients with Hemophilia A and recently began a Phase 1/2 trial. Sigilon Therapeutics was founded in 2015 and lists on the Nasdaq under the symbol “SGTX.” Morgan Stanley, Jefferies, Barclays and Canaccord Genuity acted as lead managers on the deal. Shares nearly doubled over the week (+193%) to $34.78.

Seer Inc., which is developing next-generation proteome analysis tests for biomedical research, raised $175 million by offering 9.2 million shares at $19, above the range of $16 to $18. At pricing, Seer commands a fully diluted market value of $1.3 billion. The Redwood City, CA-based company aims to commercialize proteome research products starting with its initial product, the Proteograph Product Suite. Seer will leverage its proprietary engineered nanoparticle (NP) technology to provide rapid large-scale access across the proteome. The Proteograph Product Suite is an integrated solution that is comprised of consumables, an automation instrument, and software, and will be sold and marketed for research use only (RUO). Its first Proteograph was delivered to one of its first collaborators in October 2020, and the company expects to place another Proteograph with a second collaborator before the end of 2020, pending any COVID-19-related delays. Seer was founded in 2017 and lists on the Nasdaq under the symbol “SEER.” J.P. Morgan, Morgan Stanley, BofA Securities and Cowen acted as lead managers on the deal. Shares nearly tripled over the week (+297%) to $56.46.

And Silverback Therapeutics Inc., a Phase 1 biotech developing TLR8 agonist-antibodies for HER2/3 solid tumors, raised $242 million by offering 11.5 million shares at $21, above the range of $19 to $20. At pricing, Silverback commands a fully diluted market value of $758 million. The Seattle-based company uses its proprietary ImmunoTAC technology platform to develop tissue targeted therapeutics for the treatment of cancer, chronic viral infections, and other serious diseases. Initially, the platform is being used to create a new class of targeted immuno-oncology agents that direct a myeloid cell activator to the tumor microenvironment (TME) in solid tumors to promote cancer cell killing. Lead candidate SBT6050 is currently in a Phase 1/1b clinical trial for advanced or metastatic HER2-expressing solid tumors, with an update on interim data from the Phase 1 dose-escalation cohorts expected in the 2H21. Silverback was founded in 2016 and lists on the Nasdaq under the symbol “SBTX.” Goldman Sachs, SVB Leerink and Stifel acted as lead managers on the deal. Shares closed the week up 19% at $25.

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