Ocugen eyes EUA application

Shares of Ocugen (NASDAQ:OCGN) soared 43% on Thursday following positive clinical trial results and bullish analyst commentary. 

Roth Capital analyst Zegbeh Jallah reiterated his buy rating and $10 price forecast for Ocugen's stock on Wednesday after its development partner, Bharat Biotech, shared positive data from an interim analysis of a phase 3 study of Covaxin, an investigational coronavirus vaccine. 

Covaxin demonstrated overall efficacy of 78% against COVID-19 and 100% protection against severe forms of the disease. The vaccine candidate was also shown to have efficacy of 70% against asymptomatic cases, which Jallah said could help to combat the spread of the virus by people who show no symptoms and might not be aware that they're infected.

 

Based on these results, Jallah said Ocugen could soon apply for an emergency use authorization (EUA) from the Food and Drug Administration (FDA). Ocugen's deal with Bharat Biotech stipulates that it will receive 45% of any profits the vaccine earns in the U.S. market. Thus, Jallah posits that if Covaxin is authorized for sale in the U.S., Ocugen could enjoy a "significant revenue-generating opportunity." 

Judging by today's gains, many investors apparently agree with Jallah's positive outlook for Ocugen. 

https://www.fool.com/investing/2021/04/22/heres-why-ocugen-stock-skyrocketed-today/

Possible new PET tracer for early detection of Alzheimer's

 New biomarkers for Alzheimer's disease are a priority area for researchers seeking to learn more about the disease and find possible methods of early diagnosis. Researchers at Karolinska Institutet in Sweden have now studied a new PET tracer that is an important diagnostic tool for the disease. The study on the tracer substance BU99008, which is published in Molecular Psychiatry, can play a key part in the early identification of signs of Alzheimer's disease.

Alzheimer's disease is the most common form of dementia, affecting almost 47 million people around the world, according to Alzheimer's Disease International (ADI) - a figure that is expected to rise with increasing life expectancies.

The disease is as yet incurable, and causes considerable suffering for both patients and their families.

Alzheimer's is an insidious disease, with the changes in brain function onsetting 10 to 20 years before the clinically cognitive decline. It is therefore important to identify early disease markers.

One such marker is reactive astrogliosis, which provide early and rapid response to the progression of the disease. Astrocytes are the most important homeostatic cells in the central nervous system (CNS), with a broad spectrum of functions for optimal cerebral function and cellular energy supply, homeostasis.

They are also involved in disease and CNS damage through the defensive process called reactive astrogliosis.

The pathological role played by astrocytes in Alzheimer's disease is not fully understood, but several studies suggest that reactive astrogliosis may precede known early pathological signs of Alzheimer's disease, including amyloid plaque and tau tangles.

Researchers therefore need to develop tracers for astrocyte response for use in PET scans. PET imaging diagnostic technique is using selective and specific tracers - radioactive chemical molecules - for the early detection of pathological conditions and is already in routine in the detection of abnormal neuronal function and amyloid load in the brain, such as that caused by Alzheimer's disease.

Researchers at Karolinska Institutet, Uppsala University and Indiana University School of Medicine in the USA have studied a new astrocytic PET tracer, BU99008, which seems to be promising for Alzheimer's disease.

The researchers used brain tissue from six individuals who had died with Alzheimer's disease and seven healthy controls, who had died of other causes. The results provide a better understanding for BU99008-binding properties compared with other existing astrocytic Alzheimer's disease biomarkers in the brain.

"Our study shows that BU99008 can detect important reactive astrocytes with good selectivity and specificity, making it a potentially important clinical astrocytic PET tracer," says the paper's first author Amit Kumar, researcher at the Department of Neurobiology, Care Sciences and Society, Karolinska Institutet. "The results can improve our knowledge of the role played by reactive astrogliosis in Alzheimer's disease."

"As far as we can judge, this is the first time that BU99008 could visualises reactive astrogliosis in Alzheimer's disease brain," says principal investigator Agneta Nordberg, professor at the same department. "The results can have broad clinical implications that cover other disorders of reactive astroglial dysfunction."

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The study was financed with grants from the Swedish Foundation for Strategic Research (SSF), the Swedish Research Council (VR), the Region Stockholm-Karolinska Institutet ALF scheme for clinical research and medical education, the Swedish Brain Fund, the Swedish Alzheimer's Foundation, the Foundation for Old Servants, the Gun and Bertil Stohne Foundation, the Gunvor and Josef Aner Foundation, the Loo and Hans Osterman Medical Research Foundation, the Tore Nilson Foundation, the Swedish Dementia Association and the Centre for Innovative Medicine (CIMED) Stockholm Region. There are no reported conflicts of interest.

Publication: "Astroglial tracer BU99008 visualizes astrogliosis and detects multiple binding sites in Alzheimer's disease brain". Amit Kumar, Niina A Koistinen, Mona-Lisa Malarte, Inger Nennesmo, Martin Ingelsson, Bernardino Ghetti, Laetitia Lemoine and Agneta Nordberg. Molecular Psychiatry, online 23 April 2021, doi: 10.1038/s41380-021-01101-5.

https://www.eurekalert.org/pub_releases/2021-04/ki-pn042021.php

Improving survival in pancreatic cancer

 Nagoya University researchers and colleagues in Japan have uncovered a molecular pathway that enhances chemotherapy resistance in some pancreatic cancer patients. Targeting an RNA to interrupt its activity could improve patient response to therapy and increase their overall survival.

"Pancreatic cancer is one of the most aggressive human malignancies, with an overall median survival that is less than five months," says cancer biologist Yutaka Kondo of Nagoya University Graduate School of Medicine. "This poor prognosis is partially due to a lack of potent therapeutic strategies against pancreatic cancer, so more effective treatments are urgently needed."

Kondo and his colleagues focused their attention on a long noncoding RNA (lncRNA) called taurine upregulating gene 1 (TUG1). lncRNAs are gene regulators, several of which have recently been identified for helping some cancers resist chemotherapy. TUG1 is already known for being overexpressed in gastrointestinal cancers that have poor prognosis and are resistant to chemotherapy.

The researchers found TUG1 was overexpressed in a group of patients with pancreatic ductal adenocarcinoma. These patients were resistant to the standard chemotherapy treatment 5-fluorouracil (5-FU), and died much sooner compared to cancer patients with low TUG1 expression levels.

Further laboratory tests showed TUG1 counteracts a specific microRNA, leading to increased activity of an enzyme, called dihydropyrimidine dehydrogenase, which breaks down 5-FU into a compound that can't kill cancer cells.

Kondo and his team found they could suppress TUG1 during 5-FU treatment of mice with pancreatic cancer by using antisense oligonucleotides attached to a specially designed cancer-targeting drug delivery system. Antisense oligonucleotides interfere with gene expression.

"Our data provides evidence that our therapeutic approach against pancreatic cancer could be promising," says Kondo.

The team now plans to conduct further laboratory investigations to test the effectiveness of their therapeutic strategy.

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Their study, "Cancer-specific targeting of taurine upregulated gene 1 enhances the effects of chemotherapy in pancreatic cancer," was published online in the journal Cancer Research on March 1, 2021 at DOI: 10.1158/0008-5472.CAN-20-3021.

Authors:

Yoshihiko Tasaki, Miho Suzuki, Keisuke Katsushima, Keiko Shinjo, Kenta Iijima, Yoshiteru Murofushi, Aya Naiki Ito, Kazuki Hayashi, Chenjie Qiu, Akiko Takahashi, Yoko Tanaka, Tokuichi Kawaguchi, Minoru Sugawara, Tomoya Kataoka, Mitsuru Naito, Kanjiro Miyata, Kazunori Kataoka, Tetsuo Noda, Wentao Gao, Hiromi Kataoka, Satoru Takahashi, Kazunori Kimura, and Yutaka Kondo

https://www.eurekalert.org/pub_releases/2021-04/nu-isi042021.php

New Study Shows 'Long Haul' COVID-19 Can Kill Patients Months After Infection

 Across the US, tens of thousands of people who were infected with SARS-CoV-2, the virus that causes COVID-19, have struggled with a buffet of debilitating symptoms that made it impossible for them to work or live normal lives. Many of those who were eligible sought disability as baffled scientists tried to determine the cause of the "long hauler" syndrome, as it has come to be known.

Media outlets like the Washington Post and New York Times have chronicled the experiences of individuals struggling with "long hauler" syndrome months after they first contracted COVID-19. Some patients noted that, while they more or less felt fine, their sense of smell and taste had yet to return. Others complained that a persistent "brain fog" had settled over them. With doctors offering few answers, many sufferers turned to online communities to pool their experiences.

Now, the latest research published in the journal Nature shows that "long haulers" are at much higher risk of dying from their protracted symptoms.

How much higher? The data showed survivors had a 59% increased risk of dying within six months after contracting the SARS-CoV-2 virus, researchers reported Thursday in the journal Nature. This excess mortality translates into about 8 extra deaths per 1,000 patients. That's worsening the pandemic’s hidden toll amid growing recognition that many patients require readmission, and some die, weeks after the viral infection abates.

"When we are looking at the acute phase, we’re only pretty much looking at the tip of the iceberg," said Ziyad Al-Aly, chief of the research and development service at the St. Louis VA Medical Center in Missouri, who led the study, and spoke to Bloomberg in an interview. "We’re starting to see a little bit beneath that iceberg, and it’s really alarming.”

Al-Aly and his colleagues documented the cascade of debilitating symptoms that plague long haulers even months after their diagnosis: from blood clots, stroke, diabetes and breathing difficulties to heart, liver and kidney damage, depression, anxiety and memory loss.

Globally, more than 143 million people have tested positive for COVID-19, and more than 3 million have died from the disease. As for how many become long haulers, some other studies have put the number at roughly 10%, according to Bloomberg. But nobody really knows, and those who pass away months later from the condition typically aren't counted among COVID-19 deaths.

Adding to the host of risk factors, long-haulers required increased use of various medications, including antidepressants and opioids. "We worry about potential spikes in suicide or potential spikes in overdose of opioids," Al-Aly told Bloomberg in an interview.

Look at the numbers from a broader perspective, the researchers found that patients with COVID-19 who survived hospitalization had a 51% higher risk of dying compared with 13,997 influenza patients who also had been hospitalized. Al-Aly, who is also an assistant professor of medicine at the Washington University School of Medicine, said he hoped the research would provide a roadmap to inform health-system planning and care strategies to mitigate chronic ill health among Covid-19 survivors, especially in the U.S. "Let’s not act surprised two years down the road, when people start committing suicide," he said. "We did not do very well preparing and dealing with Covid. Let’s not make that mistake a second time."

Read the full study below:

s41586-021-03553-9_reference

https://www.zerohedge.com/covid-19/new-study-shows-long-haul-covid-19-kills-patients-months-after-infection

Zymer­gen's bid to dis­rupt a $3T in­dus­tri­al man­u­fac­tur­ing goes vi­ral, in $500M IPO

 It’s not a story you hear every day: A biotech company that doesn’t use its platform to develop therapeutics? Despite some raised eyebrows early on, Emeryville, CA-based Zymergen has convinced investors that its plan to disrupt industrial manufacturing is worth the bet and now it’s priced an eye-popping IPO to take its mission to the next level.

Synthetic biology firm Zymergen late Wednesday priced its 16.13 million shares at $31, good for a public offering in the range of $500 million, which would put the company in rarified air along with Sana Biotechnology as biotech companies with half-billion-dollar or more IPOs this year, according to Endpoints News’ IPO tracker.

The upsized pricing — Zymergen initially penciled in a $100 million cash raise in its S-1 filing last month  — puts Zymergen on track to continue developing its designer molecules it plans to use to disrupt a $3 trillion industrial manufacturing market with applications as far and wide as consumer care, agriculture and electronics.

The company plans to get there by using a process it calls “biofacturing,” using genetically engineered molecules to produce industrial-grade products without the need for toxic chemicals often used in the process or expensive infrastructure. All told, the company thinks it can cut costs by about 90% across the industry and produce the same materials in half the time.

It’s a focus that has often not been rewarded among biotech investors looking for a clear path to therapies, but Zymergen believes it’s found its own huge unmet need — and the case keeps on flowing in. The $500 million cash raise comes on the heels of a $400 million Series C back in 2018 and a $300 million raise in September.

All told, the company has raised somewhere in the ballpark of $1.375 billion since its initial seed round way back in 2014.

While the company has broad ambitions for its pipeline, it has just one product on the market: Hyaline, a high-quality optical film used in electronics. Meanwhile, the biotech is pursuing candidates across a trio of electronics, agriculture and consumer care. Those areas alone, it believes, offer a market opportunity of about $1.2 trillion.

Zymergen plans a slate of rollouts in those markets in 2022 and 2023 and will use Hyaline as its canary in the coal mine in terms of consumer interest. If all goes to plan, Zymergen thinks its biofacturing model could prove disruptive across a range of industries, potentially cracking open its lofty $3 trillion market goals.

“Our pipeline of products has been designed with rapid market adoption in mind,” the company said in its prospectus. “In addition, these products demonstrate our biofacturing platform’s ability to develop commercially relevant products across multiple major distinct chemical classes.”

https://endpts.com/zymergens-bid-to-disrupt-a-3t-industrial-manufacturing-market-goes-viral-earning-a-massive-500m-ipo/

Sen­a­tors to NIH: Do more to pro­tect US bio­med­ical re­search from for­eign in­flu­ence

 Although Thursday’s Senate health committee hearing was focused on how foreign countries and adversaries might be trying to steal or negatively influence biomedical research in the US, the only country mentioned by the senators and expert witnesses was China.

Committee chair Patty Murray (D-WA) made clear in her opening remarks that the US cannot “let the few instances of bad actors” overshadow the hard work of the many immigrant researchers in the US, many of which have won Nobel prizes for their work. But she also said, “There is more the NIH can be doing here.”

The hearing follows a series of high profile convictions of scientists for stealing intellectual property from top biomedical research institutions.

Just this week, Yu Zhou of Ohio was sentenced to 33 months in prison after he pleaded guilty to stealing scientific trade secrets related to exosomes and exosome isolation from Nationwide Children’s Hospital’s Research Institute, which he sought to sell in China.

Song Guo Zheng, A professor of internal medicine and researcher at The Ohio State University and Pennsylvania State University, also pleaded guilty in late 2020 to making false statements to federal authorities as part of an immunology research grant fraud scheme. He admitted to lying on applications in order to use more than $4 million in NIH grants to develop China’s expertise around rheumatology and immunology, according to written testimony Thursday from Gary Cantrell, deputy inspector general at HHS’ Office of Inspector General.

“The threat is significant,” Michael Lauer, deputy director for extramural research at NIH, told the senators. He said NIH has identified more than 500 scientists of concern, and reached out to the institutions where over 200 of them work, although each one requires a tremendous amount of work.

But Lauer also noted instances where research institutions are discovering problems on their own. For instance, Alan List, president and CEO of the Moffitt Cancer Center in Florida, resigned in late 2019 after the center conducted an internal review on collaborations with research institutions in China.

Candice Wright, acting director of science, technology assessment, and analytics at GAO, also explained how non-financial conflicts, such as access to certain research labs or biologic materials, can pose risks too. “Non-financial conflicts can be great risks and we don’t see a lot of attention paid to those,” she said.

But progress has been made in recent years to be more vigilant of potential crimes, even as critics have raised questions about whether this crackdown has unfairly targeted Chinese researchers. Last year, two representatives, Jamie Raskin (D-MD) and Judie Chu (D-CA) wrote letters to the FBI and NIH, raising concerns that innocent Chinese scientists were being profiled, and asked for information on the demographic makeup of scientists under investigation.

Sen. Richard Burr (R-NC) conceded that the NIH has come a long way since 2018, when NIH Director Francis Collins sent a letter to more than 10,000 research institutions, urging them to ensure NIH grantees were reporting their links with foreign governments. But he and other senators specifically took issue with China.

“It’s a concerted effort from those in China, backed by their government, to bring back anything they can learn, store or steal,” Burr said. Other Republicans on the committee like Sen. Bill Cassidy (LA) questioned whether 23andMe’s operations in China might be worrisome, but none of the witnesses on the panel offered any specifics.

As anti-Asian sentiment has reached a fever pitch in recent months in the US, Lauer also sought to make clear that the overwhelming majority of Chinese-born scientists working in the US are not bad actors. He said NIH has identified criminals who are Americans too.

“We cannot reject brilliant minds that are working honestly,” Lauer added. “Legitimate international collaborations are great, and this is extremely important, but that’s different from lying, cheating and stealing.”

https://endpts.com/senators-to-nih-do-more-to-protect-us-biomedical-research-from-foreign-influence/

Covid vaccines may protect against new strains—and maybe the common cold

 A new study by Johns Hopkins Medicine researchers provides evidence that CD4+ T lymphocytes—immune system cells also known as helper T cells—produced by people who have received either of the two messenger RNA (mRNA) vaccines for COVID-19 caused by the original SARS-CoV-2 strain also will recognize the mutant variants of the coronavirus that are rapidly becoming the dominant types worldwide.

The researchers say this suggests that T cell responses elicited or enhanced by the vaccines should be able to control the current SARS-CoV-2 variants without needing to be updated or modified. They also found that the same T cells may provide some protection from another member of the coronavirus family that is responsible for one type of the common cold.

The findings were reported April 6, 2021, in the Journal of Clinical Investigation.

CD4+ T cells get their "helper" nickname because they assist another type of immune cell, the B lymphocyte (B cell), in responding to surface proteins—antigens—on cells infected by invaders that include viruses such as SARS-CoV-2. Activated by the CD4+ T cells, immature B cells become either plasma cells that produce antibodies to mark infected cells for disposal from the body or memory cells that "remember" the antigen's biochemistry for a faster response to future infections.

In the case of SARS-CoV-2, the antigen is the protein making up the spikes that protrude from the surface of the virus. The mRNA vaccines—known by their manufacturer's names, Pfizer-BioNTech and Moderna—provide genetic instructions to a vaccinated person's immune system to recognize the spike protein and start production of antibodies against SARS-CoV-2.

CD4+ T cells also send out chemical messengers that attract another type of T cell—known as the CD8+ T cell (or "killer T cell")—so that the virus-infected cells can be removed.

To conduct their helper T cell study, the researchers evaluated blood samples from 30 healthy health care workers and laboratory donors who had not previously tested positive for SARS-CoV-2—both before and after two doses of a COVID-19 mRNA vaccine. The participants, 12 women and 18 men, ranged in age from 20 to 59.

CD4+ T cells extracted from the blood samples were analyzed for their responses to various components (protein fragments known as peptides) from the original strain SARS-CoV-2 spike protein and three common cold coronaviruses.

The researchers discovered that vaccine recipients—as expected—had broad T cell responses to the original strain SARS-CoV-2 spike peptides.

"We identified 23 distinct T cell-targeted peptides, of which only four appear affected by the mutations that created the variant coronaviruses first seen in the United Kingdom and South Africa," says study senior author Joel Blankson, M.D., Ph.D., professor of medicine at the Johns Hopkins University School of Medicine. "That means the other 19 peptides are the same in the original SARS-CoV-2 and the newer strains, so the mRNA vaccines should induce T cells that respond well to the variants."

Blankson says this is important because previous studies showed that antibodies don't recognize the SARS-CoV-2 variants as well as the CD4+ T cells.

"So the T cells may help prevent the variant viruses from causing severe COVID-19 disease even if antibodies don't stop them from infecting a person," he explains.

When the researchers looked at the vaccine-induced T cell response to the spike proteins of three common cold coronaviruses, they saw a three-fold increase for one, HCoV-NL63, but not the other two.

"Further studies are needed to determine why this occurred," says Blankson. "We suspect that HCoV-NL63 may have more epitopes [peptides that elicit an immune response] in common with SARS-CoV-2 than the other common cold coronaviruses."

In a recent and related study, Blankson and Johns Hopkins Medicine colleagues looked at blood from convalescent patients who had recovered from a SARS-CoV-2 infection and identified the unique receptors on memory CD4+ T cell that recognize the spike proteins of both the original strain of SARS-CoV-2 and four common cold coronaviruses.

Blankson says that characterizing these T cell receptors may be helpful in guiding development of future vaccines for a variety of coronaviruses.

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Explore further

T cells recognize recent SARS-CoV-2 variants

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More information: Bezawit A. Woldemeskel et al. SARS-CoV-2 mRNA vaccines induce broad CD4+ T cell responses that recognize SARS-CoV-2 variants and HCoV-NL63, Journal of Clinical Investigation (2021). DOI: 10.1172/JCI149335

https://medicalxpress.com/news/2021-04-vaccines-covid-strainsand-common-cold.html