Top Stories for Week of April 13, 2020

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Trump Administration sets coronavirus conditions to reviving US economy.

Vice President Mike Pence and one of the top US health officials said regenerating the country’s economy hinges on the government seeing major communities at the end of their coronavirus outbreaks and developing treatments for the disease, among other outcomes.

“Let’s be clear: Reopening the country, as the President is very anxious to do at the earliest responsible moment, will be through a combination of facts,” Pence said Thursday evening at a White House briefing.

Most major communities must be “at the end” of their outbreaks, said Pence, who leads the White House’s coronavirus task force. The country also should have widespread testing available, therapeutics for Americans who contract the disease, and guidance from the Centers for Disease Control and Prevention on how large and small businesses can operate safely.

The comments were the most detailed yet from the administration about its parameters for urging citizens back to work. The US continues to lead the world in cases, Bloomberg News reports, but has begun to see caseloads level off in the worst hotspots, while other communities are just at the start of their outbreaks.

CDC Director Robert Redfield outlined similar criteria on Thursday during an interview with CNN. Officials, he said, need to understand the spread of the virus, strengthen public health infrastructure, prepare hospitals and other medical facilities, and foster a belief among Americans that it’s the right time to do this.

“Those are really the four most critical elements that we’re working and planning on now, with the anticipation of beginning to reopen our nation one region at a time and get us all back to work and get prepared for next year, which will be another challenging time,” he said.

Redfield expects next year to be more bearable, if the outbreak can be beaten back to a scale that can be handed by case identification, isolation and contact tracing.

“So we don’t have to go through the serious mitigation steps that we’re taking to get this under control today,” he said.

Pence said he expects the US to have so-called surveillance testing, which can identify people who may have already had coronavirus and may be immune, in place as soon as the summer.

The US was on track on Saturday to surpass Italy in the total number of confirmed deaths from the coronavirus, reaching its deadliest day on Friday with 2,057 deaths, according to The New York Times. Already the pandemic has killed more than 20,000 Americans and put more than 16 million out of work, forcing President Trump into the difficult choice of reopening the country as it reels economically from the coronavirus pandemic.

Trump is eager to jump start the US economy, which has been hobbled by the pandemic as he ramps up his re-election campaign. Another 6.61 million people applied for unemployment benefits last week, bringing the three-week total to about 16.8 million during the economic shutdown.

COVID-19 Addenda: 1) California to spend nearly $1 billion for 200 million masks per month; 2) Chloroquine trials underway for COVID19 prophylaxis; and 3) Vigilance urged as New York sees signs of coronavirus progress.

Saying “enough is enough” with states competing for critical medical equipment in the coronavirus crisis, California Gov. Gavin Newsom announced that he has inked deals with a consortium of nonprofits and acquired technology that will provide 200 million medical masks a month for his state and possibly others in the US.

“We’ve been competing against other states, against other nations, against our own federal government for PPE–coveralls, masks, shields, N95 masks–and we’re not waiting around any longer,” Newsom told MSNBC host Rachel Maddow. “We decided enough is enough: let’s use the purchasing power of the state of California as a nation-state,” he added.

The state plans to spend $990 million in state funds on protective gear, according to a letter Newsom’s Department of Finance sent to lawmakers. California must make a down payment of half that amount–$495 million–within the next 48 hours. California is cobbling together the initial payment with $188 million in coronavirus funding approved by state lawmakers before they left Sacramento last month, plus $307 million in funds from a state disaster account. It is not clear yet where the additional $495 million will come from. (Ref: Politico)

In the US and Europe, a handful of clinical trials have begun to test ways to keep healthcare workers and other vulnerable people safe from COVID-19. Most are testing drugs called chloroquine or hydroxychloroquine that have long been used to prevent and treat malaria, and also as a therapy against rheumatoid arthritis and lupus. The hope is that, given before infection or early in the course of the disease, the drugs will protect someone against infection and illness from the virus, or, if they do, will ensure that their case is mild.

But whether these drugs will help, as President Trump has touted, or harm or do nothing remains an open question. Scientists strongly support these trials, but are equally vehement that these drugs should only be used in the context of a clinical trial–to carefully test effectiveness, be on the lookout for any negative effects, and to ensure that there is an adequate supply of the drugs if they prove useful. “This is a virus that targets healthcare workers,” because they are in close proximity to very contagious people, says Warner Greene, a senior virologist with the Gladstone Institutes, an independent, nonprofit research organization based in San Francisco.

And, Americans must resist the impulse to ease social-separation measures at the first glimpse of progress now being seen in the coronavirus battle, state government and public health leaders warned, as the US death toll surpassed 18,000 as of Saturday. Calls for heightened vigilance, countering talk from the Trump administration of reopening the economy next month, came as new evidence emerged that stay-at-home restrictions were working to flatten the arc of infections in New York state, the US epicenter of the pandemic.

The number of newly hospitalized patients in New York dropped for a second day Thursday, to 200. Governor Andrew Cuomo said it was a sign that social distancing was succeeding, even though the number of coronavirus-related deaths in the state rose by 799 on Wednesday, a record high for a third day.

“You can’t relax. The flattening of the curve last night happened because of what we did yesterday,” Cuomo said.

IPO Sector: There are no US IPOs scheduled for this week. But with recent, successful public introductions from Keros Therapeutics Inc. and Zentalis Pharmaceuticals Inc., the most likely April IPO launches in the healthcare sector include several biotechs, such as oncology-focused Ayala Pharmaceuticals (AYLA) and ORIC Pharmaceuticals (ORIC), ENT biotech Lyra Therapeutics (LYRA), and CNS drug developer NLS Pharmaceuticals (NLSP). Massive capital raises by biotech VCs also indicate investor optimism in the space.

But let’s zero in on last week’s action where Keros Therapeutics Inc., a Phase 1 biotech developing therapies for blood and musculoskeletal disorders, raised $96 million by offering 6.0 million shares at $16, the high end of the range of $14 to $16. Lexington, MA-based Keros upsized its offering by 1.0 million shares (20%). Keros’s lead candidate is KER-050, an engineered ligand trap, designed to increase red blood cell and platelet production in myelodysplastic syndrome and myelofibrosis patients with low blood counts.

The company was founded in 2015 and booked $10 million in collaboration revenue for the 12 months ended December 31, 2019. It lists on the Nasdaq under the symbol “KROS.” Keros filed confidentially on January 21, 2020. Jefferies, SVB Leerink and Piper Sandler are the joint bookrunners on the deal. Shares closed the week up 35% to $21.57.

And elsewhere in other international markets, three weeks after InnoCare launched its IPO on the HKEX (Hong Kong Exchange), Endpoints reports that China’s Akesobio Inc. is looking to best that company with its own $300 million (HKD$2.34 billion) raise. Partnered with Merck & Co., Akesobio’s pitch centers around a suite of in-house technologies that it says generate superior antibodies against known targets such as PD-1, CTLA-4, IL-12 and IL-23. Having kicked off pre-marketing last Monday, it expects to make a public debut this month.

Akesobio–which is based in the southeastern city of Zhongshan, a couple of hours from Hong Kong–refiled its listing application in February amid an extended Lunar New Year holiday as China rolled out drastic measures to COVID-19 outbreak. At that point, neither the new coronavirus nor the disease it causes had an official name. Two months later, there are clear indications that biopharma listings can still command considerable interest on both sides of the Pacific.

For Akesobio, the proceeds will mainly go toward a pipeline of drugs targeting cancer, autoimmune disorders and even hyperlipidemia. The rest will help expand their R&D and manufacturing facilities in Guangzhou and Zhongshan.

For 10 patients severely ill with the new coronavirus, a single dose of antibodies drawn from the blood of people who had recovered from COVID-19 appeared to save lives, shorten the duration of symptoms, improve oxygen levels and speed up viral clearance, newly published research reports.

The preliminary findings emerged from a “pilot study” published last Monday in the journal PNAS, the Proceedings of the National Academies of Sciences. Conducted at three hospitals in China, it underscored the promise of harvesting immune antibodies from recovered people (a therapy also known as convalescent plasma) and administering them to people battling a severe case of COVID-19.

But its findings offer hope that a therapy with a long history and a simple premise could be a powerful treatment for COVID-19 patients fighting for breath, says the Los Angeles Times. In the early 20th century, doctors transferred the bloodborne antibodies of patients who had recovered from polio, measles, mumps and flu to those who were still in the grips of those infections.

Armed with a veteran infectee’s immune memory of the virus, patients getting convalescent plasma appeared to recover more quickly and completely than patients who did not get the treatment, physicians observed. With a vaccine at least a year away and no clear treatments available for COVID-19, the US Food and Drug Administration on March 24 approved the use of such therapy as an experimental treatment in clinical trials and for critical patients without other options. The new pilot study signaled that the therapy will not disappoint.

In all 10 patients, the symptoms that had driven them to seek emergency care had either disappeared or largely improved within one to three days of their receiving a transfusion of antibodies from a recovered donor. Two of the three patients who had been breathing with the help of a mechanical ventilator were able to step down to oxygen delivered into the nose. None of the 10 patients died, and only one unexpected side effect–a red bruise on one patient’s face–was detected.

The study was not designed to have a comparison group of patients that got no convalescent plasma. But the authors did create a control group from a random selection of 10 COVID-19 patients treated in the same hospitals and matched to the ten study participants in age and gender and the illness severity.

An epigenetics drug developed by the Spanish biopharmaceutical company Oryzon Genomics SA (Barcelona) has reduced aggressive behavior in patients with Alzheimer’s disease and improved the experience of their caregivers in a Phase 2a trial. At the same time, an Alzheimer’s vaccine developed by the Austrian biotech Axon Neuroscience SE has lowered a key blood biomarker of neurodegeneration by almost 60% in a different Phase 2 trial, Labiotech.eu reports.

Oryzon presented clinical data from two trials at last week’s AAT-AD/PD Conference hosted online. The company was testing the effect of vafidemstat, an epigenetic drug that controls gene expression without changing the genetic code. Vafidemstat blocks an enzyme called LSD1, which modifies methylation of histones, and is thought to participate in regulating genes involved in the onset of neurodegenerative disorders, cancer, and other indications.

The first results came from a 12-patient, open-label Phase 2a study performed over six months to test the effect of vafidemstat on agitation and aggression in moderate and severe Alzheimer’s patients. Reduced aggression was significantly observed using established clinical metrics as well as improved caregiver burden. The full results were presented in an e-poster.

Another set of clinical results came from the same drug in an ongoing randomized Phase 2a study in 117 patients. At the six-month point of treatment, patients given the drug showed reductions in a key inflammatory marker of Alzheimer’s disease called YKL40.

“The significance of our results is that we have shown for the first time in human patients that we can safely reduce neuroinflammation and potentially increase synaptic plasticity, which are frequently expressed targets for treatment,” Oryzon’s CMO, Roger Bullock, said.

Alzheimer’s drug candidates have left many clinical trial failures in their wake, notably Biogen’s abrupt ending of a trial last year–though Biogen has since resurrected the program and expects to apply for FDA approval. According to Bullock, this is partially due to the uncertain relationship between the accumulation of the target protein amyloid-beta and cognitive decline in Alzheimer’s disease.

“Yet we are sure that there is an underlying clinical heterogeneity and there are epigenetic mechanisms operating. We also know that inflammation plays a role, as well in Alzheimer’s disease as in other neurological diseases,” continued Bullock.

The explosion of COVID-19 cases in the New York City area resulted largely from infected patients who flew in from Europe, genome scientists say. Researchers at NYU Langone Health said they’ve analyzed 75 samples from patients who were diagnosed with COVID-19, the disease caused by the novel coronavirus, at New York-area hospitals last month. About two-thirds of the samples appear to have European origins, said Adriana Heguy, director of the Genome Technology Center at the medical center.

The virus appears to have been imported to New York from the U.K. and several European countries, including France, Austria and the Netherlands, she said. Genome sequencers are able to roughly correlate how a virus is spreading around the world by examining small mutations in a gene sequence of the pathogen as it’s transmitted from person to person. In the case of the coronavirus, whose RNA consists of about 30,000 genetic bases, or letters, it mutates about twice a month.

Those minor mutations tend not to change the potency of the virus. But they provide clues for genetic detectives to chart how they shift subtly over time, allowing them to create sprawling family trees, or phylogenies, that show how the coronavirus has spread.

One of the first cases Heguy’s team sequenced, collected in early March, came from a Long Island resident with no travel history whose viral genome correlated with a strain circulating in England. That suggested the patient had contact with someone who had brought the virus over from the UK. The findings suggest that even after the Trump administration imposed travel restrictions from China, the virus continued to infiltrate the most populous US city via daily flights from Europe.

Not all the New York virus samples have European origins. Some appear to have come from the US West Coast, while others appear to link directly to Asia. That indicates that there are numerous chains of transmission in the metro area, as would be expected in such a large outbreak. The NYU genome center previously had been focused on sequencing for common diseases such as cancer and heart conditions. But in early March it switched to working almost exclusively on COVID-19.

“We basically turned our labs into COVID-19 labs overnight,” said Heguy. “That is all we are doing right now.”

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