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Wednesday, April 7, 2021

Biotech startup Vaccitech confidentially files for U.S. IPO

 Biotech startup Vaccitech, which owns the technology behind the COVID-19 vaccine developed by Oxford and AstraZeneca PLC, has confidentially filed for an initial public offering in the United States, the Financial Times reported  on Wednesday.

The startup could price its offering as early as this month, the report said, citing people familiar with the matter.

The company did not immediately respond to a Reuters request for comment.

Vaccitech's call to go with the U.S. market as the venue for its listing over the U.K. could further undermine London's attempts to become a major financial hub, particularly after Brexit.

Last month, another UK company, car seller Cazoo Holdings, chose to merge with a U.S.- based special purpose acquisition company backed by billionaire investor Dan Och, in a $7 billion deal.

Vaccitech is co-founded by Sarah Gilbert, professor of vaccinology at Oxford University, who led AstraZeneca's COVID-19 vaccine development efforts.

It raised around $168 million in fresh capital in a funding round led by investment firm M&G Investment Management and with participation from investors including Gilead Sciences Inc and venture capital firm Future Planet Capital, among others.

The UK Treasury also has a stake in the company, the report added.

https://www.marketscreener.com/quote/stock/ASTRAZENECA-PLC-4000930/news/AstraZeneca-nbsp-Biotech-startup-Vaccitech-confidentially-files-for-U-S-IPO-FT-32902917/

FDA Extends Review on Pfizer Drug Applications for Abrocitinib, Xeljanz/Xeljanz XR

 Pfizer Inc. said the U.S. Food and Drug Administration has extended the review period for a pair of drug applications, moving the Prescription Drug User Act goal date for both out to early in the third quarter.

The FDA extended its priority review period for Pfizer's new drug application for abrocitinib for the treatment of adults and adolescents with moderate to severe atopic dermatitis, and also extended the review period for supplemental new drug applications for Xeljanz/Xeljanz XR for the treatment of adults with active ankylosing spondylitis by three months, the drug company said Wednesday.

Abrocitinib is an oral small molecule that selectively inhibits Janus kinase 1, inhibition of which is thought to modulate multiple cytokines involved in pathophysiology of atopic dermatitis, Pfizer said. Xeljanz is approved in the U.S. in four indications--adults with moderately to severely active rheumatoid arthritis after methotrexate failure, adults with active psoriatic arthritis after disease modifying antirheumatic drug failure, adults with moderately to severely active ulcerative colitis after tumor necrosis factor inhibitor failure, and patients 2 years of age or older with active polyarticular course juvenile idiopathic arthritis.

https://www.marketscreener.com/quote/stock/PFIZER-INC-23365019/news/FDA-Extends-Review-Period-on-Pfizer-Drug-Applications-for-Abrocitinib-Xeljanz-Xeljanz-XR-32903541/

Alkermes in Trial, Supply Agreement With Merck for Ovarian Cancer Treatment

 Alkermes PLC said Wednesday it has entered into a clinical trial collaboration and supply agreement with Merck & Co. to evaluate nemvaleukin alfa in combination with Keytruda in comparison with investigator choice chemotherapy in patients with platinum-resistant ovarian cancer.

Under the terms of the agreement, Alkermes is responsible for conducting the Phase 3 study, which is planned to begin in the second half of 2021.

Nemvaleukin is Alkermes's novel investigational engineered interleukin-2 variant for immunotherapy.

Alkermes said nemvaleukin in combination with Keytruda has demonstrated antitumor activity in heavily pre-treated patients with platinum-resistant ovarian cancer in an ongoing study, with durable and deepening responses observed.

https://www.marketscreener.com/quote/stock/ALKERMES-PLC-13323547/news/Alkermes-in-Trial-Supply-Agreement-With-Merck-for-Ovarian-Cancer-Treatment-32903700/

Should you still buy Ocugen?

 Would you want to buy a stock that grew by more than 2,280% over the last 12 months? If you're like most investors, you're already salivating. But you may want to suppress your appetite for juicy gains to evaluate the situation a bit more closely first. 

It's easier for small, new companies to keep growing after such a massive expansion, and that's exactly why Ocugen (NASDAQ:OCGN) is still in play for future skyrocketing. Ocugen is a very young biotech company that's already made a name for itself by being confident enough to dabble in diverse fields like gene therapy and coronavirus vaccines, and its roller coaster of a stock could still have more peaks and valleys ahead. Let's see why it might be worth buying this month and why cooler heads might want to take a year or two to mull it over.

Why it might be worth buying now

The biggest reason to buy this stock in April is that it could spike later this year as a result of reporting revenue for the first time. In February, the company struck a deal with Bharat Biotech to manufacture the Covaxin coronavirus vaccine, which was recently shown to be safe and 81% effective in a phase 3 clinical trial in India. Ocugen's agreement stipulates that it will manufacture and sell the vaccine in the U.S. and capture 45% of the profits from its sale.

If Covaxin gets regulatory approval in the U.S. later this year, it'll mean that Ocugen will have a significant revenue stream. Importantly, new income from vaccine sales could enable it to report positive earnings for the first time, which would likely cause the stock to rev up even more than the revenue inflows alone, at least for a while. At the moment, it only has $42,620 in trailing revenue, so any additional money could be fuel for the company's research and development (R&D) pipeline.

On that note, in terms of its financial strength, the company is in acceptable shape for an early-stage biotech. It has just over $24 million in cash, and around $2.1 million in debt. In 2020, its net losses were $21.8 million, meaning that it will need to raise cash to survive relatively soon. But it should be able to take on new debt or issue new stock to raise funds, so there's no risk of it going bankrupt anytime soon.

Why it's probably better to wait

Covaxin has a few steps ahead before it can receive emergency use authorization (EUA) in the U.S. If everything goes as planned, it'll be available on the market sometime in the latter half of this year. That's problematic, given that larger competitors like PfizerModerna, and AstraZeneca are already rolling out at mass scale. By the time Covaxin is commercialized, the U.S. might have the vast majority of its vaccine demand in the rearview mirror. Then there's the fact that the competitive landscape for coronavirus vaccines will be dramatically different next year, when even more candidates are approved for sale. At that point, Ocugen may have trouble capturing a significant share of the market unless its vaccine is significantly cheaper or more effective at combating the next strains of the virus -- and neither possibility is anywhere near guaranteed at the moment. 

But what about the company's other projects? Without exception, they're so new that they haven't entered clinical trials at any phase as of yet. As an example, Ocugen's OCU400 gene therapy project, intended to treat eye diseases like Leber congenital amaurosis, is still at the earliest stages of clinical development. Management expects that OCU400 could be approved in 2025 or 2026. There's nothing wrong with that timeline, but investors could probably have a lot more confidence in the quality of their investment if the company had at least one successful clinical trial phase in the bank.

For me, Ocugen is too far from experiencing revenue from internally developed therapy sales to buy in the short term, but I'd still consider it for the most speculative segment of my portfolio. Of course, taking a more conservative position carries a risk of missing out on the stock's potential gain from its upcoming Covaxin sales. And investing now would be the only way to capture gains from the company's future growth, which could well be quite significant. But if your goal is to invest in quality companies at the right price, I think you'll be better served by waiting until Ocugen has proven its quality with successes in the clinic and potentially in the market for coronavirus vaccines.

https://www.fool.com/investing/2021/04/04/should-you-buy-ocugen-in-april/

CytoDyn Signs Supply, Distribution Pact with Biomm S.A. in Brazil for COVID, All Other Leronlimab Indications

 CytoDyn Inc. (OTC.QB: CYDY), (“CytoDyn” or the “Company"), a late-stage biotechnology company developing leronlimab (PRO 140), a CCR5 antagonist with potential multiple therapeutic indications, announced today it has executed an exclusive supply and distribution agreement with Biomm S.A. in Brazil. This commercial agreement will enable Biomm to sell leronlimab in Brazil following regulatory clearance.

CytoDyn has committed to conduct clinical trials in Brazil for all current indications for leronlimab (i.e., Long-Hauler COVID-19, NASH and cancer).

Heraldo Marchezini, Chief Executive Officer of Biomm S.A., commented, “We are very pleased with our recently executed exclusive supply and distribution agreement with CytoDyn. Our urgent goal is to provide leronlimab to Brazilians critically ill with COVID-19.”

Nader Pourhassan, Ph.D., President and Chief Executive Officer of CytoDyn, stated, “We are excited to reach this milestone for the potential benefit of Brazilian patients. Mr. Marchezini and his team have worked tirelessly to advance our commercial agreement and we look forward to a long-term relationship with Biomm. I am very grateful to Mr. Marchezini and his team for expediting our efforts to advance the availability of leronlimab for all patients who might benefit from this immune modulator product.”

http://www.globenewswire.com/news-release/2021/04/07/2205652/19782/en/CytoDyn-Signs-Exclusive-Supply-and-Distribution-Agreement-with-Biomm-S-A-in-Brazil-for-COVID-19-and-All-Other-Leronlimab-Indications.html

Akili’s therapeutic video game will be tested as treatment for Covid ‘brain fog’

 Akili, which made history last summer by earning regulatory clearance for the first video-game based therapy, now plans to test if its software can help adults suffering from Covid “brain fog.”

Two randomized remote studies, one conducted by Weill Cornell Medicine and New York-Presbyterian Hospital and the other by Vanderbilt University Medical Center, will assess whether AKL-T01, the treatment that Akili commercially markets for ADHD as EndeavorRx, can help improve cognition symptoms in Covid survivors.

The new studies come at a pivotal moment for Akili. EndeavorRx is being prescribed by more doctors, but the company is still hoping for widespread acceptance. As Akili labors to show EndeavorRx works, it’s also looking for new pathways to commercialization.

“The technology that we have at Akili is not very specific to one disease area,” Anil S. Jina, the company’s chief medical officer, told STAT. “It basically improves attention control, which is one of the aspects of cognition, and that is part and parcel of many different disorders.”

He said that while childhood ADHD made sense as an early commercial target, independent investigators have done many small studies on the underlying technology’s efficacy in treating adults for a range of cognitive conditions, including dementia and mild cognitive impairment.

Akili had an existing relationship with the researchers at Cornell, and late last year, Jina got an early look at data from their research on cognitive impairment in Covid-19 patients. He said that so-called Covid brain fog — an imprecise term that’s used to describe difficulty paying attention, memory loss, and a variety of other cognitive symptoms in Covid survivors — lined up with areas of cognitive impairment that Akili’s system has been effective in treating.

The link between Covid-19 infection and cognitive impairment remains unclear, but preliminary research published by the Cornell researchers is alarming. In a cohort of 57 patients in rehab following hospitalization for Covid, 81% had some cognitive impairment, 55% showed deficits in working memory, and 46% experienced divided attention. Faith Gunning, an associate professor of psychology at Weill Cornell Medicine and vice chair of research in Cornell’s psychiatry department, cautions that the study is a snapshot of the very sickest people immediately after they were in the hospital.

“We don’t expect that level of cognitive difficulty to persist in many of the people as time progresses,” she said. “I think there will be a subset that will have residual cognitive complaints and and perhaps even objective cognitive difficulties.

Still, given the prevalence of people reporting cognitive issues after Covid infection, the potential lasting impact is tremendous, and points to how a solution like Akili’s treatment could be helpful.

“I don’t think we are going to have the manpower in our healthcare system to do in-person cognitive remediation with the number of people who may need it,” said Gunning.

The Cornell-NewYork-Presbyterian and Vanderbilt studies are designed slightly differently, but share a number of the same parameters. They will both include roughly 100 Covid-19 survivors over 18 who show some measurable cognitive impairment. Half of patients in both studies will receive treatment and half will serve as control. The treatment protocol calls for patients to complete five missions per day five times a week. A day’s worth of missions takes about 25 minutes. The protocol mirrors the one used in Akili’s pivotal study for EndeavorRx as well as for a recently published adjunct study.

The Cornell study will run for six weeks with four weeks of post-treatment follow up. The Vanderbilt study will end after a four-week treatment. Both studies will evaluate patients on several cognitive measurements.

The decisions on study design were rooted in the specializations of each center and other practical considerations, but Jina said it also reflects the early stage of the research.

“We’re learning what Covid fog is and what the patients are exhibiting and what longer term outcomes are day-by-day as we’re going,” he said. “So I wanted to spread out our research net a little bit wider.”

James Jackson, assistant director of the ICU Recovery Center at Vanderbilt, said the impairment demonstrated by people Covid-19 is consistent with many long-term studies looking at people after they’ve been in intensive care, and he expects there to be lasting impacts in the population.

“I suspect when the dust settles, thoughtful people will reflect on the fact that one of the signature injuries, if you will, of Covid-19 is cognitive deficits and cognitive impairment,” said Jackson, who is also the lead psychologist for the Critical Illness, Brain Dysfunction and Survivorship Center at Vanderbilt University Medical Center,

Though Covid-19 is a singular illness, Jackson said, researchers studying how to deal with its effects aren’t totally in the dark. Many evidence-based treatments, including Akili’s tech, are designed to target similar symptoms of cognitive impairment in other conditions.

“Thankfully, a lot of the modalities that we’ve developed… whether it would be for PTSD or whether it would be for attention, until we become convinced otherwise, I think most of us imagine that they’re going to be effective and we’re hopeful,” he said.

https://www.statnews.com/2021/04/07/akili-endeavorrx-covid19-brain-fog/

1 in 3 Covid-19 patients diagnosed with neuropsychiatric condition in next 6 months

 Six months after being diagnosed with Covid-19, 1 in 3 patients also had experienced a psychiatric or neurological illness, mostly mood disorders but also strokes or dementia, a large new study shows.

About 1 in 8 of the patients (12.8%) were diagnosed for the first time with such an illness, most commonly anxiety or depression. Compared to control groups of people who had the flu or other non-Covid respiratory infections, first-ever neuropsychiatric diagnoses were almost twice as high.

The study, published Tuesday in The Lancet Psychiatry, used real-world health data on millions of people to gauge the incidence of 13 brain disorders. Anxiety, mood, and substance use disorders were most common, but the researchers also found worrying, if lower, rates of serious neurological complications, especially in patients who had been severely ill with Covid-19. In all Covid-19 patients, 0.6% developed a  brain hemorrhage, 2.1% an ischemic stroke, and 0.7% dementia. 

“We need urgent research to better understand how and why does this occur in patients with Covid-19 and how they can be treated and [how to] prevent it,” Max Taquet, a clinical fellow in psychiatry at the University of Oxford and a study co-author, said on a call with reporters on Tuesday. “But we think that regardless of the explanation, health services need to be prepared for the increased demand that this data is showing.” 

The size of the study lends confidence to its findings, which confirm what has been hinted in smaller studies, including earlier work from the Oxford group. The researchers analyzed electronic health records of 81 million U.S. patients (both insured and uninsured), finding 236,379 people who had been diagnosed with Covid-19 and comparing them to three cohorts of similar people: one cohort had the flu, another had another respiratory illness such as sinusitis or pneumonia, and one cohort included people who were hospitalized for unrelated conditions such as bone fractures or gallstones. The researchers hoped that comparing the Covid group to the others would help isolate Covid-19 as a cause and tease out its effects on the brain.

After accounting for patients’ age, sex, ethnicity, and existing health conditions, patients overall had a 44% higher risk of neurological and mental health diagnoses after Covid-19 than after flu, and a 16% higher risk after Covid-19 than after other respiratory tract infections. 

There were two exceptions: The researchers did not see increased risk of Parkinson’s disease, a movement disorder, or Guillain-Barré syndrome, which is a rare disorder that shows up after some viral infections as tingling and weakness when the immune system attacks nerves.

Allison Navis, assistant professor in the division of neuro-infectious diseases at the Icahn School of Medicine at Mount Sinai, sounded a note of caution. The lead clinical neurologist at Mount Sinai’s post-Covid clinic, she was not involved in the Lancet study.  

“It does highlight that there is something unique going on with Covid,” she told STAT. “And the 12.8% who have a new diagnosis of something neuropsychiatric can sound very sensational. That 12.8% encompasses depression and anxiety, so it’s extremely important to not minimize that and not make that sound like a lesser diagnosis at all, but the more severe things like strokes are still fairly uncommon. I don’t want people thinking that 1 in 10 people get a stroke with Covid.”

The new study reinforces previous research that showed some brain disorders increased with the severity of illness, going up in people who needed to be hospitalized and rising further in people who needed intensive care. While 33.6% of people developed a neuropsychiatric illness overall, that risk grew to 46.4% among Covid patients treated in an ICU.

What’s new is the distinction between neurological and psychiatric complications. People with very severe Covid-19 had a higher risk of complications like stroke or dementia, but people who developed anxiety or depression spanned the spectrum of illness severity. 

While the study did not examine the mechanisms that might explain neuropsychiatric disorders associated with the virus, the authors did speculate in the call with reporters that if patients know that they have Covid-19, that and other stressors might contribute to a psychiatric illness. “It could be psychological factors and biological factors and psychosocial factors, such as, for instance, the need to isolate and the loss of income as a result of that,” Taquet said. 

It’s easier to tie neurological disorders to the virus’ effects on the brain. Scientists believe the virus can enter the brain through the olfactory bulb, where taste and smell are decoded. Inflammation throughout the body also harms blood vessels in the brain, and can lead to stroke-causing blood clots, delirium, or dementia.

While the medical records could tell the researchers whether someone had previously suffered a stroke or been diagnosed with dementia, they couldn’t surmise whether someone was going to have a recurrence anyway or whether Covid-19 caused it, Masud Husain, professor of neurology and cognitive neuroscience at Oxford and a study co-author, warned. Longer follow-up will be needed to answer that question, but the signal was too strong to ignore, he said. 

Husain also cautioned that the numbers they reported could be an underestimate if they don’t include people who were infected with Covid but did not test positive for it, or if people had no symptoms that drove them to seek medical care. On the flip side, patients with Covid-19 might be more likely to have a neurological and psychiatric disorder diagnosed simply because they were receiving more medical attention compared to patients with the flu or other respiratory infections, Taquet pointed out.

This was not a study of long-Covid, said Paul Harrison, professor of psychiatry at the University of Oxford and a study co-author, referring to the constellation of lingering symptoms that overlap with some problems caused by the neuropsychiatric illnesses described in the current paper. But the need for more research and continued clinical care is the same.

“Sadly, many of the disorders identified in this study tend to be chronic or recurrent, so we can anticipate that the impact of Covid-19 could be with us for many years,” Jonathan Rogers and Anthony David of University College London wrote in a commentary appearing with the Lancet study. 

https://www.statnews.com/2021/04/06/1-in-3-covid19-patients-get-neuropsychiatric-diagnosis-within-six-months/