Immune System-Stimulating Nanoparticle Could Lead to More Powerful Vaccines

 

Anne Trafton | MIT News
Office

 

A common strategy to make vaccines more powerful is to deliver them along with an adjuvant — a compound that stimulates the immune system to produce a stronger response.

Researchers from MIT, the La Jolla Institute for Immunology, and other institutions have now designed a new nanoparticle adjuvant that may be more potent than others now in use. Studies in mice showed that it significantly improved antibody production following vaccination against HIV, diphtheria, and influenza.

“We started looking at this particular formulation and found that it was incredibly potent, better than almost anything else we had tried,” says Darrell Irvine, the Underwood-Prescott Professor with appointments in MIT’s departments of Biological Engineering and Materials Science and Engineering; an associate director of MIT’s Koch Institute for Integrative Cancer Research; and a member of the Ragon Institute of MGH, MIT, and Harvard.

The researchers now hope to incorporate the adjuvant into an HIV vaccine that is currently being tested in clinical trials, in hopes of improving its performance.

Irvine and Shane Crotty, a professor at the Center for Infectious Disease and Vaccine Research at the La Jolla Institute for Immunology, are the senior authors of the study, which appears today in Science Immunology. The lead authors of the paper are Murillo Silva, a former MIT postdoc, and Yu Kato, a staff scientist at the La Jolla Institute.

 

More Powerful Vaccines

Although the idea of using adjuvants to boost vaccine effectiveness has been around for decades, there are only a handful of FDA-approved vaccine adjuvants. One is aluminum hydroxide, an aluminum salt that induces inflammation, and another is an oil and water emulsion that is used in flu vaccines. A few years ago, the FDA approved an adjuvant based on saponin, a compound derived from the bark of the Chilean soapbark tree.

Saponin formulated in liposomes is now used as an adjuvant in the shingles vaccine, and saponins are also being used in a cage-like nanoparticle called an immunostimulatory complex (ISCOM) in a Covid-19 vaccine that is currently in clinical trials.

Researchers have shown that saponins promote inflammatory immune responses and stimulate antibody production, but how they do that is unclear. In the new study, the MIT and La Jolla team wanted to figure out how the adjuvant exerts its effects, and to see if they could make it more potent.

They designed a new type of adjuvant that is similar to the ISCOM adjuvant but also incorporates a molecule called MPLA, which is a toll-like receptor agonist. When these molecules bind to toll-like receptors on immune cells, they promote inflammation. The researchers call their new adjuvant SMNP (saponin/MPLA nanoparticles).

“We expected that this could be interesting because saponin and toll-like receptor agonists are both adjuvants that have been studied separately and shown to be very effective,” Irvine says.

The researchers tested the adjuvant by injecting it into mice along with a few different antigens, or fragments of viral proteins. These included two HIV antigens, as well as diphtheria and influenza antigens. They compared the adjuvant to several other approved adjuvants and found that the new saponin-based nanoparticle elicited a stronger antibody response than any of the others.

One of the HIV antigens that they used is an HIV envelope protein nanoparticle, which presents many copies of the gp120 antigen that is present on the HIV viral surface. This antigen recently completed initial testing in phase 1 clinical trials. Irvine and Crotty are part of the Consortium for HIV/AIDS Vaccine Development at the Scripps Research Institute, which ran that trial. The researchers now hope to develop a way to manufacture the new adjuvant at large scale so it can be tested along with an HIV envelope trimer in another clinical trial beginning next year.  Clinical trials that combine envelope trimers with the traditional vaccine adjuvant aluminum hydroxide are also underway.

“Aluminum hydroxide is safe but not particularly potent, so we hope that (the new adjuvant) would be an interesting alternative to elicit neutralizing antibody responses in people,” Irvine says.

 

Rapid Flow

When vaccines are injected into the arm, they travel through lymph vessels to the lymph nodes, where they encounter and activate B cells. The research team found that the new adjuvant speeds up the flow of lymph to the nodes, helping the antigen to get there before it starts to break down. It does this in part by stimulating immune cells called mast cells, which previously were not known to be involved in vaccine responses.

“Getting to the lymph nodes quickly is useful because once you inject the antigen, it starts slowly breaking down. The sooner a B cell can see that antigen, the more likely it’s fully intact, so that B cells are targeting the structure as it will be present on the native virus,” Irvine says.

Additionally, once the vaccine reaches the lymph nodes, the adjuvant causes a layer of cells called macrophages, which act as a barrier, to die off quickly, making it easier for the antigen to get into the nodes.

Another way that the adjuvant helps boost immune responses is by activating inflammatory cytokines that drive a stronger response. The TLR agonist that the researchers included in the adjuvant is believed to amplify that cytokine response, but the exact mechanism for that is not known yet.

This kind of adjuvant could also be useful for any other kind of subunit vaccine, which consists of fragments of viral proteins or other molecules. In addition to their work on HIV vaccines, the researchers are also working on a potential Covid-19 vaccine, along with J. Christopher Love’s lab at the Koch Institute. The new adjuvant also appears to help stimulate T cell activity, which could make it useful as a component of cancer vaccines, which aim to stimulate the body’s own T cells to attack tumors.

 

Suggested Content:

Cocrystal Pharma C-Suite Interview (Video)

Axcella Therapeutics C-Suite Interview (Video)

Avivagen Virtual Roadshow (Video)

Schwazze – Medicine Man Technologoies Virtual Roadshow (Video)

 

 

 

Stay up to date. Follow us:

BioSig to Participate in the Benzinga All Access Event on December 14, 2021

News and Market Data on BioSig Technologies

 

Westport, CT, Dec. 06, 2021 (GLOBE NEWSWIRE) — BioSig Technologies, Inc. (Nasdaq: BSGM) (“BioSig” or the “Company”), a medical technology company commercializing an innovative signal processing platform designed to improve signal fidelity and uncover the full range of ECG and intra-cardiac signals, today announced that Natasha Drapeau, Executive Vice President of BioSig Technologies, Inc., would be presenting at the Benzinga All Access event on Tuesday, December 14, 2021, at 9:40 am EST.

“Our Company demonstrated a solid operational performance this year despite the ongoing challenges imposed by the pandemic. I look forward to sharing some of those highlights including first commercial sales, the completion of approximately 1800 patient cases with the PURE EP™ System, and  the launching of several strategic initiatives that position us well for a new phase in our commercial growth,” commented Natasha Drapeau, Executive Vice President of BioSig Technologies, Inc.

The presentation will be broadcast live at 9:40 am EST on Tuesday, December 14^th, 2021. To watch the live event, please click here.

A replay of the presentation will also be available on the BioSig website.

The PURE EP™ is an FDA 510(k) cleared non-invasive class II device that aims to drive procedural efficiency and efficacy in cardiac electrophysiology. Clinical data acquired by the PURE EP™ System in a multi-center study at Texas Cardiac Arrhythmia Institute at St. David’s Medical Center, Mayo Clinic Jacksonville, and Massachusetts General Hospital was recently published in the Journal of Cardiovascular Electrophysiology and is available electronically with open access via the Wiley Online Library. Study results showed 93% consensus across the blinded reviewers with a 75% overall improvement in intracardiac signal quality and confidence in interpreting PURE EP™  signals over conventional sources.

One in 18 Americans suffers from a cardiac arrhythmia. Atrial fibrillation is the most common arrhythmia type, affecting over 33 million people worldwide, including over 6 million in the U.S. The number of people suffering from atrial fibrillation is expected to reach 8-12 million by 2050¹. According to the Centers for Disease Control and Prevention (CDC), atrial fibrillation causes more than 750,000 hospitalizations in the U.S. each year, resulting in approximately $6 billion in healthcare spending annually².

About Benzinga All Access
Benzinga All Access is a first-of-its-kind show: part interview, part investor presentation. On All Access, Benzinga partners with companies to bring you in-depth one-on-one conversations with executives across a wide range of industries and asset classes. From emerging biotechs, to alternative real estate investment platforms, to everything in between, guests on All Access have one thing in common: they want to tell their story to investors.

About BioSig Technologies
BioSig Technologies is a medical technology company commercializing a proprietary biomedical signal processing platform designed to improve signal fidelity and uncover the full range of ECG and intra-cardiac signals. (www.biosig.com).

The Company’s first product, PURE EP ™ System is a computerized system intended for acquiring, digitizing, amplifying, filtering, measuring and calculating, displaying, recording and storing of electrocardiographic and intracardiac signals for patients undergoing electrophysiology (EP) procedures in an EP laboratory. To date, 73 physicians have completed over 1750 patient cases with the PURE EP™ System. The Company is in a focused commercial launch of the PURE EP™ System in the Northeast, Texas, and Florida. The technology is regularly used in some of the country’s highest-ranked hospitals, including St. David’s Medical Center in Austin, TX, Mayo Clinic campuses in Florida, Minnesota, and Arizona, and University of Pennsylvania in Philadelphia, PA.

Forward-looking Statements
This press release contains “forward-looking statements.” Such statements may be preceded by the words “intends,” “may,” “will,” “plans,” “expects,” “anticipates,” “projects,” “predicts,” “estimates,” “aims,” “believes,” “hopes,” “potential” or similar words. Forward- looking statements are not guarantees of future performance, are based on certain assumptions and are subject to various known and unknown risks and uncertainties, many of which are beyond the Company’s control, and cannot be predicted or quantified and consequently, actual results may differ materially from those expressed or implied by such forward-looking statements. Such risks and uncertainties include, without limitation, risks and uncertainties associated with (i) the geographic, social and economic impact of COVID-19 on our ability to conduct our business and raise capital in the future when needed, (ii) our inability to manufacture our products and product candidates on a commercial scale on our own, or in collaboration with third parties; (iii) difficulties in obtaining financing on commercially reasonable terms; (iv) changes in the size and nature of our competition; (v) loss of one or more key executives or scientists; and (vi) difficulties in securing regulatory approval to market our products and product candidates. More detailed information about the Company and the risk factors that may affect the realization of forward-looking statements is set forth in the Company’s filings with the Securities and Exchange Commission (SEC), including the Company’s Annual Report on Form 10-K and its Quarterly Reports on Form 10-Q. Investors and security holders are urged to read these documents free of charge on the SEC’s website at http://www.sec.gov. The Company assumes no obligation to publicly update or revise its forward-looking statements as a result of new information, future events or otherwise.

¹ Top 10 Things You should Know About Heart Rhythm; Scripps Health.

² Managing Atrial Fibrillation; Lisa Eramom MA, Medical Economics Journal, February 25, 2019, Volume 96, Issue 4

Source: BioSig Technologies

Helius Medical Technologies, Inc.’s Dr. Antonella Favit-Van Pelt to Present at 4th International Brain Stimulation Conference on December 9

Research, News, and Market Data on Helius Medical Technologies

 

Dr. Favit-Van Pelt will present research that led to the FDA authorization of translingual nerve stimulation for gait disturbance in multiple sclerosis

NEWTOWN, Pa., Dec. 06, 2021 (GLOBE NEWSWIRE) — Helius Medical Technologies, Inc. (Nasdaq:HSDT) (“Helius” or the “Company”), a neurotech company focused on neurological wellness, today announced that Chief Medical Officer Antonella Favit-Van Pelt, M.D., Ph.D. will be presenting at the 4th International Brain Stimulation Conference, taking place December 6 – 9 in Charleston, S.C. The conference is organized by Elsevier, a global leader in information and analytics, and brings together experts in the field of brain stimulation across a wide range of disciplines.

Alongside three other key opinion leader clinicians, Dr. Favit-Van Pelt will be part of a Thursday symposium titled “Recently authorized by the FDA—Novel Brain Stimulation treatments coming to a clinic near you.” During the session, Dr. Favit-Van Pelt will introduce the research that led to the FDA authorization of translingual nerve stimulation for gait disturbance in multiple sclerosis in a presentation titled “Portable neuromodulation stimulator (PoNS) device therapy improves gait function in patients with multiple sclerosis.” Helius received marketing authorization for the use of PoNS in the treatment of gait deficit due to mild-to-moderate symptoms of MS in March 2021 and, in August 2021, received Breakthrough Designation for the treatment of dynamic gait and balance deficits resulting from a stroke.

Dr. Favit-Van Pelt’s co-panelists will include Dr. Gregory Sahlem of Stanford University, Dr. Abraham Zangen of Ben-Gurion University in Israel, and Dr. Teresa Kimberley of MGH Institute of Health Professions. The symposium will run from 1:30 to 3:30 PM, eastern standard time.

About Antonella Favit-Van Pelt, MD, PhD

Dr. Favit-Van Pelt is a rare disease expert and pioneer in the field of applied theragnostics for the development of disease-modifying treatments. A board-certified neurologist, she holds a PhD in Pharmacology and has more than 20 years of drug development expertise in the pharmaceutical industry and academia. She started her clinical practice activity in 1994 with specialist clinics in Europe where she continues as a specialist consultant managing patients with movement disorders and rare neuromuscular disorders. Dr. Favit-Van Pelt currently serves as Chief Medical Officer of Helius.

About Helius Medical Technologies, Inc.

Helius Medical Technologies is a leading neurotech company in the medical device field focused on neurologic deficits using non-implantable platform technologies that amplify the brain’s ability to compensate and promotes neuroplasticity, aiming to improve the lives of people dealing with neurologic diseases. The Company’s first commercial product is the Portable Neuromodulation Stimulator (PoNS). For more information, visit www.heliusmedical.com.

About the PoNS Device and PoNS Therapy

The Portable Neuromodulation Stimulator (PoNS) is an innovative non-surgical medical device, inclusive of a controller and mouthpiece, which delivers electrical stimulation to the surface of the tongue to improve balance and gait. The PoNS device is indicated for use in the United States as a short-term treatment of gait deficit due to mild-to-moderate symptoms from multiple sclerosis (“MS”) and is to be used as an adjunct to a supervised therapeutic exercise program in patients 22 years of age and over by prescription only. Helius is advancing PoNS post-approval research in MS through a recently launched Therapeutic Experience Program (TEP).

PoNS is also authorized for sale in Canada for two indications: (i) PoNS is authorized as a short-term treatment (14 weeks) of chronic balance deficit due to mild-to-moderate traumatic brain injury (“mmTBI”) and is to be used in conjunction with physical therapy; and (ii) PoNS is authorized for use as a short term treatment (14 weeks) of gait deficit due to mild and moderate symptoms from MS and is to be used in conjunction with physical therapy. PoNS is also authorized for sale in Australia for short term use by healthcare professionals as an adjunct to a therapeutic exercise program to improve balance and gait.

Cautionary Disclaimer Statement

Certain statements in this news release are not based on historical facts and constitute forward-looking statements or forward-looking information within the meaning of the U.S. Private Securities Litigation Reform Act of 1995 and Canadian securities laws. All statements other than statements of historical fact included in this news release are forward-looking statements that involve risks and uncertainties. Forward-looking statements are often identified by terms such as “believe,” “expect,” “continue,” “will,” “goal,” “aim” and similar expressions.

There can be no assurance that such statements will prove to be accurate and actual results and future events could differ materially from those expressed or implied by such statements. Important factors that could cause actual results to differ materially from the Company’s expectations include risks detailed from time to time in the “Risk Factors” section of the Company’s Annual Report on Form 10-K for the year ended December 31, 2020, its Quarterly Report on Form 10-Q for the quarter ended September 30, 2021 and its other filings with the United States Securities and Exchange Commission and the Canadian securities regulators, which can be obtained from either at www.sec.gov or www.sedar.com.

The reader is cautioned not to place undue reliance on any forward-looking statement. The forward-looking statements contained in this news release are made as of the date of this news release and the Company assumes no obligation to update any forward-looking statement or to update the reasons why actual results could differ from such statements except to the extent required by law.

Investor Relations Contact

Lisa M. Wilson, In-Site Communications, Inc.
T: 212-452-2793
E: lwilson@insitecony.com

Monday, December 06, 2021

Helius Medical Technologies (HSDT)(HSM:CA)
Sell Off Too Deep; Upgrading to Outperform

Helius Medical Technologies is a neurotech company focused on neurological wellness. The Company’s purpose is to develop, license and acquire unique and non-invasive platform technologies that amplify the brain’s ability to heal itself. The Company’s first commercial product is the Portable Neuromodulation Stimulator (PoNSTM). For more information, visit www.heliusmedical.com.

Joe Gomes, Senior Research Analyst, Noble Capital Markets, Inc.

Gregory Aurand, Senior Research Analyst, Healthcare Services & Medical Devices, Noble Capital Markets, Inc.

Refer to the full report for the price target, fundamental analysis, and rating.

Raising to Outperform. We had downgraded HSDT shares on November 15th on the heels of the capital raise as we expected a period of consolidation given the significant discount to the then market price the new shares were sold. However, the sharp drop in the shares since then is presenting investors with a favorable risk/reward opportunity, in our view, and we are raising our rating to Outperform.


Sell Off.  Helius sold shares in the capital raise at $8.00 on November 12th. After a week of trading sideways, the shares steadily moved lower, bottoming out at $5.54 on December 2nd. Volume, while higher than the historical level, was not outrageously high. We suspect there has been a fair amount of tax selling going into year-end, especially as the shares were at the $14 level just prior to the …

This Company Sponsored Research is provided by Noble Capital Markets, Inc., a FINRA and S.E.C. registered broker-dealer (B/D).

*Analyst certification and important disclosures included in the full report. NOTE: investment decisions should not be based upon the content of this research summary.  Proper due diligence is required before making any investment decision. 

Cocrystal Pharma to Discuss Progress with COVID-19 Antiviral Programs and Clinical Strategy During Noble Capital Markets’ Channelchek Virtual Roadshow

 

BOTHELL, Wash., Dec. 02, 2021 (GLOBE NEWSWIRE) — Cocrystal Pharma, Inc. (Nasdaq: COCP) (“Cocrystal” or the “Company”) announces that President and interim CEO Sam Lee, Ph.D. and CFO and interim CEO James Martin will present a company overview in the Noble Capital Markets Virtual Roadshow Series presented by Channelchek. The live presentation will be by webcast on Wednesday, December 8, 2021 at 1:00 p.m. Eastern time (10:00 a.m. Pacific time). Registration for the webcast presentation is available here.

The Cocrystal company overview will be followed by a question-and-answer session moderated by Noble Capital Markets Senior Research analyst Robert LeBoyer and will feature questions submitted by the audience. A replay of the webcast will be available within three business days of the live presentation.

“We are working diligently toward initiating clinical studies in 2022 with two promising COVID-19 protease inhibitors,” said Dr. Lee. “Our antiviral inhibitors have shown broad-spectrum activity in vitro against COVID-19 and its variants, including the now predominant Delta variant. We further intend to use our unique structure-based technology platform to demonstrate antiviral activity against newly emerging variants such as Omicron, which is more complex given its many mutations.”

Cocrystal is waiting for response from the FDA on its pre-Investigational New Drug (IND) briefing packaging for CDI-45205, its COVID-19 protease inhibitor for intranasal/pulmonary delivery. The company plans to submit a second briefing package to the FDA, this one for its orally administered COVID-19 protease inhibitor, in the first half of 2022. In a third COVID-19 program, Cocrystal is using its unique structure-based technology platform to discover COVID-19 replication inhibitors for oral administration.

About Noble Capital Markets
Noble Capital Markets, Inc. was incorporated in 1984 as a full-service SEC / FINRA registered broker-dealer, dedicated exclusively to serving underfollowed small / microcap companies through investment banking, wealth management, trading & execution, and equity research activities. Over the past 36 years, Noble has raised billions of dollars for these companies and published more than 45,000 equity research reports. More information is available at www.noblecapitalmarkets.com or via email at contact@noblecapitalmarkets.com.

About Channelchek
Channelchek (www.channelchek.com) is a comprehensive investor-centric portal featuring more than 6,000 emerging growth companies that provides advanced market data, independent research, balanced news, video webcasts, exclusive c-suite interviews, and access to virtual road shows. The site is available to the public at every level without cost or obligation. Research on Channelchek is provided by Noble Capital Markets, Inc., an SEC / FINRA registered broker-dealer since 1984. For more information email contact@channelchek.com.

About Cocrystal Pharma, Inc.
Cocrystal Pharma, Inc. is a clinical-stage biotechnology company discovering and developing novel antiviral therapeutics that target the replication process of influenza viruses, coronaviruses (including SARS-CoV-2), hepatitis C viruses and noroviruses. Cocrystal employs unique structure-based technologies and Nobel Prize-winning expertise to create first- and best-in-class antiviral drugs. For further information about Cocrystal, please visit www.cocrystalpharma.com.

Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including statements regarding our goals of initiating clinical studies and submitting a briefing package to the FDA in 2022, our attempts to discover replication inhibitors, and the potential efficacy of antiviral inhibitors against existing and new variants of COVID-19. The words “believe,” “may,” “estimate,” “continue,” “anticipate,” “intend,” “should,” “plan,” “could,” “target,” “potential,” “is likely,” “will,” “expect” and similar expressions, as they relate to us, are intended to identify forward-looking statements. We have based these forward-looking statements largely on our current expectations and projections about future events. Some or all of the events anticipated by these forward-looking statements may not occur. Important factors that could cause actual results to differ from those in the forward-looking statements include, but are not limited to, the risks arising from supply chain disruptions on our ability to obtain products including raw materials and test animals as well as similar problems with our vendors and our current CRO and future CROs and CMOs, the impact of the COVID-19 pandemic including new variants on the national and global economy, the cooperation of the FDA in accelerating development in our COVID-19 program, our collaboration partners’ technology and software performing as expected, the results of future preclinical and clinical trials, general risks arising from clinical trials, receipt of regulatory approvals, regulatory changes, and development of effective treatments and/or vaccines by competitors, including as part of the programs financed by the U.S. government. Further information on our risk factors is contained in our filings with the SEC, including our Annual Report on Form 10-K for the year ended December 31, 2020. Any forward-looking statement made by us herein speaks only as of the date on which it is made. Factors or events that could cause our actual results to differ may emerge from time to time, and it is not possible for us to predict all of them. We undertake no obligation to publicly update any forward-looking statement, whether as a result of new information, future developments or otherwise, except as may be required by law.

Investor Contact:
LHA Investor Relations
Jody Cain
310-691-7100
jcain@lhai.com

Source: Cocrystal Pharma, Inc.

	Image Credit: Navy Medicine (Flickr)

Charting Changes in a Pathogen’s Genome Yields Clues About its Past and Hints About its Future

 

More than 250 million people worldwide have tested positive for SARS-CoV-2, usually after a diagnostic nose swab. Those swabs aren’t trash, once they’ve delivered their positive result, though. For scientists like us they carry additional valuable information about the coronavirus. Leftover material from swabs can help us uncover hidden aspects of the COVID-19 pandemic.

 

This article was republished with permission from The Conversation, a news site dedicated to sharing ideas from academic experts.  It was written by and represents the thoughts of Claire Guinat, Postdoctoral Fellow in Computational Evolution, Swiss Federal Institute of Technology Zurich, Etthel Windels, Postdoctoral Fellow in Computational Evolution, Swiss Federal Institute of Technology Zurich

 

Using what are called phylodynamic methods that can track a pathogen’s travels via changes in its genes, researchers are able to pinpoint factors like where and when outbreaks start, the number of undetected infections and common routes of transmission. Phylodynamics can also aid in understanding and tracking the spread of new pathogen variants, such as the recently detected omicron variant of SARS-CoV-2.

 

What’s in a Swab?

Pathogens, just like people, each have a genome. This is RNA or DNA that contains an organism’s genetic code – its instructions for life and the information necessary for reproduction.

It’s now relatively fast and cheap to sequence a pathogen’s genome. In Switzerland, a consortium of government and academic scientists that we’re a part of as already extracted viral genome sequences from almost 80,000 SARS-CoV-2 positive swab tests.

By lining up genetic sequences obtained from different patients, scientists can see which positions in the sequence differ. These differences represent mutations, small errors incorporated into the genome when the pathogen copies itself. We can use these mutational differences as clues to reconstruct chains of transmission and learn about epidemic dynamics along the way.

 

Phylodynamics:
Piecing Together Genetic Clues

Phylodynamic methods provide a way to describe how mutational differences relate to epidemic dynamics. These approaches allow researchers to get from the raw data about where mutations have occurred in the viral or bacterial genome to understanding all the implications. It might sound complicated, but it’s actually pretty easy to give an intuitive idea of how it works.

Mutations in the pathogen genome get passed from person to person in a transmission chain. Many pathogens acquire lots of mutations over the course of an epidemic. Scientists can summarize these mutational similarities and differences using what’s essentially a family tree for the pathogen. Biologists call it a phylogenetic tree. Each branching point represents a transmission event, when the pathogen moved from one person to another.

 

A phylogenetic tree is an approximation of the past transmission chain, based on variations in the pathogen’s genetic sequence. Guinat, Windels, Nadeau, CC BY-ND

 

The branch lengths are proportional to the number of differences between sequenced samples. Short branches mean little time between branching points – fast transmission from person to person. Studying the length of branches on this tree can tell us about pathogen spread in the past – maybe even before we knew an epidemic was on the horizon.

 

Pathogen genome sequences can be used to construct phylogenetic trees and estimate hidden epidemic dynamics. Shorter branches stand for quicker transmission. Guinat, Windels, Nadeau, CC BY-ND

 

Mathematical
Models of Disease Dynamics

Models, in general, are simplifications of reality. They try to describe core real-life processes with mathematical equations. In phylodynamics, these equations describe the relationship between epidemic processes and the phylogenetic tree.

Take, for example, tuberculosis. It’s the deadliest bacterial infection in the world, and it is getting even more threatening because of the widespread evolution of antibiotic resistance. If you catch an antibiotic-resistant version of the tuberculosis bacterium, treatment can take years.

To predict the future burden of resistant tuberculosis, we want to estimate how fast it spreads.

 

Epidemiologists work to track infections as the pathogen moves through a population. Guinat, Windels, Nadeau, CC BY-ND

 

To do this, we need a model that captures two important processes. First, there’s the course of infection, and second, there’s the development of antibiotic resistance. In real life, infected people can infect others, get treatment, and, in the end, either be cured or, in the worst case, die from the infection. On top of this, the pathogen can develop resistance.

 

Phylodynamic models capture real-life epidemiological processes into mathematical equations and parameters. Guinat, Windels, Nadeau, CC BY-ND

 

We can translate these epidemiological processes into a mathematical model with two groups of patients – one group infected with normal tuberculosis and one with antibiotic-resistant tuberculosis. The important processes – transmission, recovery and death – can happen at different rates for each group. Finally, patients whose infection develops antibiotic resistance move from the first group to the second.

This model does ignore some aspects of tuberculosis outbreaks, such as asymptomatic infections or relapses after treatment. Even so, when applied to a set of tuberculosis genomes, this model helps us estimate how fast resistant tuberculosis spreads.

 

Capturing Hidden Aspects of Epidemics

Uniquely, phylodynamic approaches can help researchers answer questions in situations where diagnosed cases do not give the full picture. For example, what about the number of undetected cases or the source of a new epidemic?

A good example of this type of genome-based investigation is our recent work on highly pathogenic avian influenza (HPAI) H5N8 in Europe. This epidemic spread to poultry farms and wild birds across 30 European countries in 2016. In the end, tens of millions of birds were culled, devastating the poultry industry.

But were poultry farms or wild birds the real driver of spread? Obviously we cannot ask the birds themselves. Instead, phylodynamic modeling based on H5N8 genomes sampled from poultry farms and wild birds helped us get an answer. It turns out that in some countries the pathogen mainly spread from farm to farm, while in others it spread from wild birds to farms.

 

Phylodynamic models can estimate the number of avian influenza virus transmissions between wild birds and poultry. C. LeGall, CC BY-NC-ND

 

In the case of HPAI H5N8, we helped animal health authorities focus control efforts. In some countries this meant limiting transmission between poultry farms while in others limiting contact between domestic and wild birds.

More recently, phylodynamic analyses helped evaluate the impact of control strategies for SARS-CoV-2, including the first border closures and strict early lockdowns. A big advantage of phylodynamic modeling is that it can account for undetected cases. The models can even describe early stages of the outbreak in the absence of samples from that time period.

Phylodynamic models are under intensive development, continuously expanding the field to new applications and larger datasets. However, there are still challenges in extending genome sequencing efforts to undersampled species and regions and upholding rapid public data sharing. Ultimately, these data and models will help everyone gain new insights on epidemics and how to control them.

 

 

Suggested Reading:

Understanding the HealthCare Vaccine Mandate Injunction

There is More than Just a Covid Variant Weighing on Investors

Dip Buying in 2021 Has Consistently Paid-Off, is it Different this Time?

Protein Infused Chewing Gum Could Cut Spread of Covid 19 and Variants

 

Stay up to date. Follow us:

Onconova Therapeutics Announces The Presentation Of Preliminary Clinical Data Providing Evidence Of Rigosertib’s Activity In RDEB-Associated Squamous Cell Carcinoma

 

Initial single patient data in this ultra-rare indication show that rigosertib monotherapy led to sustained complete response of all target lesions without signs of metastatic disease

NEWTOWN, Pa., Dec. 02, 2021 (GLOBE NEWSWIRE) — Onconova Therapeutics, Inc. (NASDAQ: ONTX), a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer, today announced that early preliminary data from an investigator-initiated Phase 2 open label trial of rigosertib monotherapy in advanced squamous cell carcinoma complicating recessive dystrophic epidermolysis bullosa (RDEB-associated SCC) were presented at the Austrian Society of Dermatology and Venerology Annual Conference 2021, which took place from November 25 – 27, 2021.

RDEB is an ultra-rare condition caused by a lack of type VII collagen protein expression. Type VII collagen protein is responsible for anchoring the skin’s inner layer to its outer layer, and its absence leads to extreme skin fragility and chronic wound formation in RDEB patients. Over time, many of these patients develop squamous cell carcinomas (SCCs) that typically arise in areas of chronic skin wounding and inflammation. Preclinical investigations demonstrated overexpression of polo like kinase 1 (PLK1) in RDEB-associated SCC tumor cells. These tumors show a highly aggressive, early metastasizing course, making them the primary cause of death for these patients, with a cumulative risk of death of 70% and 78.7% by age 45 and 55, respectively^1,2. These neoplasms show limited response rates of mostly short duration to conventional chemo- and radiotherapy as well as targeted therapy with epidermal growth factor and tyrosine kinase inhibitors^1,3.

Data from the recent presentation are from a 24-year-old RDEB patient with a history of multiple, unresectable SCCs that were unresponsive to prior treatments including cemiplimab. Results showed that intravenously administered rigosertib had an acceptable safety profile and that the patient experienced sustained clinical and histological remission of all target lesions without signs of metastatic disease following 13 treatment cycles. The patient remains on study and the trial remains ongoing. The enrollment of additional patients is anticipated at sites in Salzburg, Austria; London, UK; and Philadelphia, Pennsylvania.

“Though the trial’s currently available data are from only a single patient, they represent an exciting and powerful finding that warrants further study,” said Andrew South Ph.D., Associate Professor, Department of Dermatology & Cutaneous Biology, Thomas Jefferson University. “RDEB-associated SCC is an indication with an extremely high unmet medical need, as it is invariably fatal with treatment options that have so far yielded disappointing results. The data generated in preclinical models suggesting rigosertib’s robust activity against PLK1 have now been confirmed in the clinic and suggest that rigosertib may play a role in other more common cancers driven by PLK1.”

The physicians caring for the patient, Dr. Bauer, Principal Investigator, and Dr. Laimer, Sponsor Medical Expert of the trial, added in a joint statement, “To see a complete response in a patient that has failed multiple prior therapies is highly encouraging and, together with preclinical data, suggests that rigosertib’s ability to inhibit PLK1 may position it as a novel treatment option that can significantly improve upon the current standard-of-care. We look forward to the further evaluation of this hypothesis through the continued advancement of the trial.”

A copy of the poster, titled “Rigosertib for locally advanced/metastatic EB-associated SCC,” is available on the “Scientific Presentations” section of the Onconova website.

References

1. Mellerio et al. Br J Dermatol. 2016 Jan; 174(1):56-67. doi: 10.1111/bjd.14104.
2. Fine et al. J Am Acad Dermatol. 2009 Feb; 60(2):203-11. doi: 10.1016/j.jaad.2008.09.035.
3. Stratigos et al. Eur J Cancer. 2020 Mar;128:83-102. doi: 10.1016/j.ejca.2020.01.008.
   

About Onconova Therapeutics
Onconova Therapeutics is a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer. The Company has proprietary targeted anti-cancer agents designed to disrupt specific cellular pathways that are important for cancer cell proliferation.

Onconova’s novel, proprietary multi-kinase inhibitor narazaciclib (formerly ON 123300) is being evaluated in two separate and complementary Phase 1 dose-escalation and expansion studies. These trials are currently underway in the United States and China.

Onconova’s product candidate rigosertib is being studied in an investigator-initiated study program, including in a dose-escalation and expansion Phase 1/2a investigator-initiated study with oral rigosertib in combination with nivolumab for patients with KRAS+ non-small cell lung cancer.

For more information, please visit www.onconova.com.

Forward-Looking Statements
Some of the statements in this release are forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, Section 21E of the Securities Exchange Act of 1934, as amended, and the Private Securities Litigation Reform Act of 1995, and involve risks and uncertainties. These statements relate to Onconova’s expectations regarding the timing of Onconova’s and investigator-initiated clinical development and data presentation plans, and the mechanisms and indications for Onconova’s product candidates. Onconova has attempted to identify forward-looking statements by terminology including “believes,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should,” “preliminary,” “encouraging,” “approximately” or other words that convey uncertainty of future events or outcomes. Although Onconova believes that the expectations reflected in such forward-looking statements are reasonable as of the date made, expectations may prove to have been materially different from the results expressed or implied by such forward-looking statements. These statements are only predictions and involve known and unknown risks, uncertainties, and other factors, including the success and timing of Onconova’s clinical trials, investigator-initiated trials and regulatory agency and institutional review board approvals of protocols, Onconova’s collaborations, market conditions and those discussed under the heading “Risk Factors” in Onconova’s most recent Annual Report on Form 10-K and quarterly reports on Form 10-Q. Any forward-looking statements contained in this release speak only as of its date. Onconova undertakes no obligation to update any forward-looking statements contained in this release to reflect events or circumstances occurring after its date or to reflect the occurrence of unanticipated events.

Company Contact:
Avi Oler
Onconova Therapeutics, Inc.
267-759-3680
ir@onconova.us
https://www.onconova.com/contact/

Investor Contact:
Bruce Mackle
LifeSci Advisors
929-469-3859
bmackle@lifesciadvisors.com

Onconova Therapeutics Announces The Presentation Of Preliminary Clinical Data Providing Evidence Of Rigosertib’s Activity In RDEB-Associated Squamous Cell Carcinoma

 

Initial single patient data in this ultra-rare indication show that rigosertib monotherapy led to sustained complete response of all target lesions without signs of metastatic disease

NEWTOWN, Pa., Dec. 02, 2021 (GLOBE NEWSWIRE) — Onconova Therapeutics, Inc. (NASDAQ: ONTX), a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer, today announced that early preliminary data from an investigator-initiated Phase 2 open label trial of rigosertib monotherapy in advanced squamous cell carcinoma complicating recessive dystrophic epidermolysis bullosa (RDEB-associated SCC) were presented at the Austrian Society of Dermatology and Venerology Annual Conference 2021, which took place from November 25 – 27, 2021.

RDEB is an ultra-rare condition caused by a lack of type VII collagen protein expression. Type VII collagen protein is responsible for anchoring the skin’s inner layer to its outer layer, and its absence leads to extreme skin fragility and chronic wound formation in RDEB patients. Over time, many of these patients develop squamous cell carcinomas (SCCs) that typically arise in areas of chronic skin wounding and inflammation. Preclinical investigations demonstrated overexpression of polo like kinase 1 (PLK1) in RDEB-associated SCC tumor cells. These tumors show a highly aggressive, early metastasizing course, making them the primary cause of death for these patients, with a cumulative risk of death of 70% and 78.7% by age 45 and 55, respectively^1,2. These neoplasms show limited response rates of mostly short duration to conventional chemo- and radiotherapy as well as targeted therapy with epidermal growth factor and tyrosine kinase inhibitors^1,3.

Data from the recent presentation are from a 24-year-old RDEB patient with a history of multiple, unresectable SCCs that were unresponsive to prior treatments including cemiplimab. Results showed that intravenously administered rigosertib had an acceptable safety profile and that the patient experienced sustained clinical and histological remission of all target lesions without signs of metastatic disease following 13 treatment cycles. The patient remains on study and the trial remains ongoing. The enrollment of additional patients is anticipated at sites in Salzburg, Austria; London, UK; and Philadelphia, Pennsylvania.

“Though the trial’s currently available data are from only a single patient, they represent an exciting and powerful finding that warrants further study,” said Andrew South Ph.D., Associate Professor, Department of Dermatology & Cutaneous Biology, Thomas Jefferson University. “RDEB-associated SCC is an indication with an extremely high unmet medical need, as it is invariably fatal with treatment options that have so far yielded disappointing results. The data generated in preclinical models suggesting rigosertib’s robust activity against PLK1 have now been confirmed in the clinic and suggest that rigosertib may play a role in other more common cancers driven by PLK1.”

The physicians caring for the patient, Dr. Bauer, Principal Investigator, and Dr. Laimer, Sponsor Medical Expert of the trial, added in a joint statement, “To see a complete response in a patient that has failed multiple prior therapies is highly encouraging and, together with preclinical data, suggests that rigosertib’s ability to inhibit PLK1 may position it as a novel treatment option that can significantly improve upon the current standard-of-care. We look forward to the further evaluation of this hypothesis through the continued advancement of the trial.”

A copy of the poster, titled “Rigosertib for locally advanced/metastatic EB-associated SCC,” is available on the “Scientific Presentations” section of the Onconova website.

References

1. Mellerio et al. Br J Dermatol. 2016 Jan; 174(1):56-67. doi: 10.1111/bjd.14104.
2. Fine et al. J Am Acad Dermatol. 2009 Feb; 60(2):203-11. doi: 10.1016/j.jaad.2008.09.035.
3. Stratigos et al. Eur J Cancer. 2020 Mar;128:83-102. doi: 10.1016/j.ejca.2020.01.008.
   

About Onconova Therapeutics
Onconova Therapeutics is a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer. The Company has proprietary targeted anti-cancer agents designed to disrupt specific cellular pathways that are important for cancer cell proliferation.

Onconova’s novel, proprietary multi-kinase inhibitor narazaciclib (formerly ON 123300) is being evaluated in two separate and complementary Phase 1 dose-escalation and expansion studies. These trials are currently underway in the United States and China.

Onconova’s product candidate rigosertib is being studied in an investigator-initiated study program, including in a dose-escalation and expansion Phase 1/2a investigator-initiated study with oral rigosertib in combination with nivolumab for patients with KRAS+ non-small cell lung cancer.

For more information, please visit www.onconova.com.

Forward-Looking Statements
Some of the statements in this release are forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, Section 21E of the Securities Exchange Act of 1934, as amended, and the Private Securities Litigation Reform Act of 1995, and involve risks and uncertainties. These statements relate to Onconova’s expectations regarding the timing of Onconova’s and investigator-initiated clinical development and data presentation plans, and the mechanisms and indications for Onconova’s product candidates. Onconova has attempted to identify forward-looking statements by terminology including “believes,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should,” “preliminary,” “encouraging,” “approximately” or other words that convey uncertainty of future events or outcomes. Although Onconova believes that the expectations reflected in such forward-looking statements are reasonable as of the date made, expectations may prove to have been materially different from the results expressed or implied by such forward-looking statements. These statements are only predictions and involve known and unknown risks, uncertainties, and other factors, including the success and timing of Onconova’s clinical trials, investigator-initiated trials and regulatory agency and institutional review board approvals of protocols, Onconova’s collaborations, market conditions and those discussed under the heading “Risk Factors” in Onconova’s most recent Annual Report on Form 10-K and quarterly reports on Form 10-Q. Any forward-looking statements contained in this release speak only as of its date. Onconova undertakes no obligation to update any forward-looking statements contained in this release to reflect events or circumstances occurring after its date or to reflect the occurrence of unanticipated events.

Company Contact:
Avi Oler
Onconova Therapeutics, Inc.
267-759-3680
ir@onconova.us
https://www.onconova.com/contact/

Investor Contact:
Bruce Mackle
LifeSci Advisors
929-469-3859
bmackle@lifesciadvisors.com

Cocrystal Pharma to Discuss Progress with COVID-19 Antiviral Programs and Clinical Strategy During Noble Capital Markets’ Channelchek Virtual Roadshow

 

BOTHELL, Wash., Dec. 02, 2021 (GLOBE NEWSWIRE) — Cocrystal Pharma, Inc. (Nasdaq: COCP) (“Cocrystal” or the “Company”) announces that President and interim CEO Sam Lee, Ph.D. and CFO and interim CEO James Martin will present a company overview in the Noble Capital Markets Virtual Roadshow Series presented by Channelchek. The live presentation will be by webcast on Wednesday, December 8, 2021 at 1:00 p.m. Eastern time (10:00 a.m. Pacific time). Registration for the webcast presentation is available here.

The Cocrystal company overview will be followed by a question-and-answer session moderated by Noble Capital Markets Senior Research analyst Robert LeBoyer and will feature questions submitted by the audience. A replay of the webcast will be available within three business days of the live presentation.

“We are working diligently toward initiating clinical studies in 2022 with two promising COVID-19 protease inhibitors,” said Dr. Lee. “Our antiviral inhibitors have shown broad-spectrum activity in vitro against COVID-19 and its variants, including the now predominant Delta variant. We further intend to use our unique structure-based technology platform to demonstrate antiviral activity against newly emerging variants such as Omicron, which is more complex given its many mutations.”

Cocrystal is waiting for response from the FDA on its pre-Investigational New Drug (IND) briefing packaging for CDI-45205, its COVID-19 protease inhibitor for intranasal/pulmonary delivery. The company plans to submit a second briefing package to the FDA, this one for its orally administered COVID-19 protease inhibitor, in the first half of 2022. In a third COVID-19 program, Cocrystal is using its unique structure-based technology platform to discover COVID-19 replication inhibitors for oral administration.

About Noble Capital Markets
Noble Capital Markets, Inc. was incorporated in 1984 as a full-service SEC / FINRA registered broker-dealer, dedicated exclusively to serving underfollowed small / microcap companies through investment banking, wealth management, trading & execution, and equity research activities. Over the past 36 years, Noble has raised billions of dollars for these companies and published more than 45,000 equity research reports. More information is available at www.noblecapitalmarkets.com or via email at contact@noblecapitalmarkets.com.

About Channelchek
Channelchek (channelchek.vercel.app) is a comprehensive investor-centric portal featuring more than 6,000 emerging growth companies that provides advanced market data, independent research, balanced news, video webcasts, exclusive c-suite interviews, and access to virtual road shows. The site is available to the public at every level without cost or obligation. Research on Channelchek is provided by Noble Capital Markets, Inc., an SEC / FINRA registered broker-dealer since 1984. For more information email contact@channelchek.vercel.app.

About Cocrystal Pharma, Inc.
Cocrystal Pharma, Inc. is a clinical-stage biotechnology company discovering and developing novel antiviral therapeutics that target the replication process of influenza viruses, coronaviruses (including SARS-CoV-2), hepatitis C viruses and noroviruses. Cocrystal employs unique structure-based technologies and Nobel Prize-winning expertise to create first- and best-in-class antiviral drugs. For further information about Cocrystal, please visit www.cocrystalpharma.com.

Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including statements regarding our goals of initiating clinical studies and submitting a briefing package to the FDA in 2022, our attempts to discover replication inhibitors, and the potential efficacy of antiviral inhibitors against existing and new variants of COVID-19. The words “believe,” “may,” “estimate,” “continue,” “anticipate,” “intend,” “should,” “plan,” “could,” “target,” “potential,” “is likely,” “will,” “expect” and similar expressions, as they relate to us, are intended to identify forward-looking statements. We have based these forward-looking statements largely on our current expectations and projections about future events. Some or all of the events anticipated by these forward-looking statements may not occur. Important factors that could cause actual results to differ from those in the forward-looking statements include, but are not limited to, the risks arising from supply chain disruptions on our ability to obtain products including raw materials and test animals as well as similar problems with our vendors and our current CRO and future CROs and CMOs, the impact of the COVID-19 pandemic including new variants on the national and global economy, the cooperation of the FDA in accelerating development in our COVID-19 program, our collaboration partners’ technology and software performing as expected, the results of future preclinical and clinical trials, general risks arising from clinical trials, receipt of regulatory approvals, regulatory changes, and development of effective treatments and/or vaccines by competitors, including as part of the programs financed by the U.S. government. Further information on our risk factors is contained in our filings with the SEC, including our Annual Report on Form 10-K for the year ended December 31, 2020. Any forward-looking statement made by us herein speaks only as of the date on which it is made. Factors or events that could cause our actual results to differ may emerge from time to time, and it is not possible for us to predict all of them. We undertake no obligation to publicly update any forward-looking statement, whether as a result of new information, future developments or otherwise, except as may be required by law.

Investor Contact:
LHA Investor Relations
Jody Cain
310-691-7100
jcain@lhai.com

Source: Cocrystal Pharma, Inc.

Wednesday, December 01, 2021

Lineage Cell Therapeutics (LCTX)
OpRegen Benefits Four Out Of Four Patients With Retinal Restoration

Lineage Cell Therapeutics is a clinical-stage biotechnology company developing novel cell therapies for unmet medical needs. Lineage’s programs are based on its robust proprietary cell-based therapy platform and associated in-house development and manufacturing capabilities. With this platform Lineage develops and manufactures specialized, terminally differentiated human cells from its pluripotent and progenitor cell starting materials. These differentiated cells are developed to either replace or support cells that are dysfunctional or absent due to degenerative disease or traumatic injury or administered as a means of helping the body mount an effective immune response to cancer. Lineage’s clinical programs are in markets with billion dollar opportunities and include three allogeneic (“off-the-shelf”) product candidates: (i) OpRegen®, a retinal pigment epithelium transplant therapy in Phase 1/2a development for the treatment of dry age-related macular degeneration, a leading cause of blindness in the developed world; (ii) OPC1, an oligodendrocyte progenitor cell therapy in Phase 1/2a development for the treatment of acute spinal cord injuries; and (iii) VAC, an allogeneic dendritic cell therapy platform for immuno-oncology and infectious disease, currently in clinical development for the treatment of non-small cell lung cancer. For more information, please visit www.lineagecell.com or follow the Company on Twitter @LineageCell.

Robert LeBoyer, Senior Research Analyst, Noble Capital Markets, Inc.

Refer to the full report for the price target, fundamental analysis, and rating.

Data From All Four Patient Show Improvements Lineage Cell reported new data from the fourth cohort in its Phase 1/2a clinical trial for OpRegen.  The data is from the fourth patient in the cohort that received the highest quantity of OpRegen cells. The results showed restoration of cellular structure and functional improvement at 12 months. We believe this demonstrates tissue restoration and efficacy of the product.


Trial Was Designed To Show OpRegen Safety and Durability The OpRegen Phase 1/2a treated three cohorts of 12 patients to establish safety, then a fourth cohort of 12 patients to determine efficacy.  In this fourth cohort, four of the patients had the majority of their lesions covered with OpRegn cells. The new data shows all four of these patients had cellular engraftment and visual acuity …

This Company Sponsored Research is provided by Noble Capital Markets, Inc., a FINRA and S.E.C. registered broker-dealer (B/D).

*Analyst certification and important disclosures included in the full report. NOTE: investment decisions should not be based upon the content of this research summary.  Proper due diligence is required before making any investment decision. 

	Image: Judge Terry Doughty (USA Today Network Video)  

Understanding the HealthCare Vaccine Mandate Injunction

 

Judge Terry A. Doughty, a federal Judge sitting in the U.S. District Court for the Western District of Louisiana, issued a NATIONWIDE injunction on President Biden’s vaccine mandate for healthcare workers yesterday, November 30, 2021. 

Some are heralding Judge Doughty a hero in the war waging worldwide between governments and those opposing mandatory vaccination.

The issue before the Louisiana Court was whether “the Plaintiff States” (fourteen U.S. states comprised of Louisiana, Montana, Arizona, Alabama, Georgia, Idaho, Indiana, Mississippi, Oklahoma, South Carolina, Utah, West Virginia, Kentucky, and Ohio) are entitled to a preliminary injunction against the COVID-19 vaccine mandate (“Mandate”) implemented by “the Government Defendants” (made up of Xavier Becerra, in his official capacity as Secretary of Health and Human Services, The U.S. Department of Health and Human Services (“DHH”), Chiquita Brooks–Lasure, in her official capacity as Administrator of the Center for Medicare and Medicaid Services (“CMS”)) on November 5, 2021.  The Mandate requires the staff of twenty-one types of Medicare and Medicaid healthcare providers to receive one vaccine by December 6, 2021, and the second vaccine by January 4, 2022. The failure to comply can result in penalties up to and including “termination of the Medicare/Medicaid Provider Agreement.”

According to the CMS, the Mandate regulates over 10.3 million health care workers in the United States. Of those 10.3 million, 2.4 million healthcare workers are currently unvaccinated.

In his Memorandum Opinion, Judge Doughty noted that “[i]mplicit in determining whether a preliminary injunction should be granted is determining whether the Government Defendants have the statutory and/or constitutional authority” to implement the Mandate. The Judge ultimately concluded that the Biden administration does not have the constitutional authority to go around Congress by issuing such a mandate. 

Doughty observed: “[i]f the executive branch is allowed to usurp the power of the legislative branch to make laws, two of the three powers conferred by our Constitution would be in the same hands.”

Quoting a decision from the U.S. Supreme Court from October of this year, he stated: “[i]f human nature and history teach anything, it is that civil liberties face grave risks when governments proclaim indefinite states of emergency” before adding “[d]uring a pandemic such as this one, it is even more important to safeguard the separation of powers set forth in our Constitution to avoid erosion of our liberties.”

 

Source:  STATE OF LOUISIANA ET AL CASE NO. 3:21-CV-03970 MEMORANDUM RULING (page 8)

 

Acknowledging that “the matter will ultimately be decided by a higher court than this one,” Doughty opined it is nonetheless ”important to preserve the status quo in this case. The liberty interests of the unvaccinated requires nothing less.”

The matter is before the Louisiana federal District Court Judge as case State of Louisiana, et al. v. Xavier Becerra,
et al. and involves fourteen states. Doughty’s ruling comes on the heels of a similar grant of a preliminary injunction by Judge Matthew Schlep in the U.S. District Court for the Eastern District of Missouri in the matter State of
Missouri, et al. v. Biden, Jr., et al.  Schlep’s ruling was issued on November 29, 2021, the day before Doughty’s, and pertained to only ten states (Alaska, Arkansas, Iowa, Kansas, Missouri, Nebraska, New Hampshire, North Dakota, South Dakota and Wyoming), but also temporarily halted the Biden administration’s implementation of the vaccine Mandate as to health care workers.  Judge Doughty’s ruling is more far-reaching as it has nationwide impact, and intentionally so, as explained by Doughty:

“[D]ue to the nationwide scope of the…[M]andate, a nationwide injunction is necessary due to the need for uniformity…Although this Court considered limiting the injunction to the fourteen Plaintiff States, there are unvaccinated healthcare workers in other states who also need protection. Therefore, the scope of this injunction will be nationwide, except for the states of Alaska, Arkansas, Iowa, Kansas, Missouri, New Hampshire, Nebraska, Wyoming, North Dakota, South Dakota,” since those states were already covered by Judge Schlep’s preliminary injunction.

Doughty concluded: “[t]his preliminary injunction shall remain in effect pending the final resolution of this case, or until further orders from this Court, the United States Court of Appeals for the Fifth Circuit, or the United States Supreme Court.”

Both cases are likely to be appealed.

 

About the Author:

Denese Venza, Esq.
is an attorney and freelance writer licensed to practice in both state and
federal courts in Florida and West Virginia. The information contained in this
article is provided for informational purposes only, is not legal advice, and
should not be construed as legal advice on any subject matter.

 

Suggested Reading:

There is More than Just a Covid Variant Weighing on Investors

Scientists Now Better Understand Viral Mutations

Omicron Variant Highlights Long-Term Vaccination Needs

Understanding the Robinhood Class Action Lawsuit

 

Sources:

https://www.lawd.uscourts.gov/content/judge-terry-doughty

https://www.alabamaag.gov/Documents/news/CMS%20Nationwide%20Injunction.pdf

 

Stay up to date. Follow us:

Lineage Reports Fourth Case of Retinal Tissue Restoration With OpRegen®

 

• Four Patients With Dry Age-Related Macular Degeneration Observed to Have Areas of Geographic Atrophy Which Diminished or Remained Unchanged Relative to Baseline for a Period of at Least 12 Months
• All Four Patients Exhibited Improvements in Visual Acuity at 12 Months
• Differences in Visual Acuity Between Treated and Untreated Eyes in all Cohort 4 Patients Remained Statistically Significant At 9, 12, and 15 Months

CARLSBAD, Calif.–(BUSINESS WIRE)–Nov. 30, 2021– 

Lineage Cell Therapeutics, Inc.
 (NYSE American and TASE: LCTX), a clinical-stage biotechnology company developing allogeneic cell therapies for unmet medical needs, announced today that restoration of retinal tissue was observed in a fourth patient enrolled in the Company’s Phase 1/2a clinical study of its lead product candidate, OpRegen. Retinal tissue restoration and improved visual acuity has now been observed in all four better vision patients treated in Cohort 4, where surgeons successfully covered the majority of the area of atrophy with a suspension of OpRegen cells. Outer retinal layer restoration, which was observed using clinical high-resolution Optical Coherence Tomography (OCT), was evidenced by the presence of new areas of retinal pigment epithelium (RPE) monolayer with overlying ellipsoid zone, external limiting membrane, and outer nuclear layer, which were not present at the time of baseline assessment. These new and additive findings continue to support the Company’s view that atrophic AMD is not an irreversible, degenerative condition and that some portion of diseased retinal tissue may be recoverable. OpRegen is an allogeneic RPE cell transplant in development for the treatment of age-related macular degeneration (AMD) with geographic atrophy (GA), or dry (atrophic) AMD.

“After reporting three previous cases of retinal restoration over the course of the last two years, we have been carefully examining the other Cohort 4 patients. We have put significant work into reviewing images from the remaining patient who had the majority of the area of atrophy covered by the OpRegen suspension at the time of surgical implant. I am pleased to report that at the scheduled Month 12 post-operative visit for this patient, although less prominent than the 3 previously reported cases due to a smaller area of atrophy at baseline, there is clear evidence of retinal restoration in some areas, and the total area of atrophy as calculated using square root transformation, or SQRT, is smaller than the size calculated at baseline,” stated Jordi Monés, M.D., Ph.D., Director, Institut de la Màcula and Director, Principal Investigator and Founder, 
Barcelona Macula Foundation. “The finding of a fourth case of restoration further supports our goal of showing that atrophic age-related macular degeneration can be responsive to this type of cell therapy. Dry AMD is a progressive disease and halting or reversing an area of atrophy does not occur spontaneously, which we believe makes the durability and reproducibility of these changes unprecedented within the field. With 12 months of follow-up complete, I am eager to have these cases submitted for peer-reviewed publication.”

“We have treated 24 patients with OpRegen, 12 of which were not legally blind at baseline and represent our intended treatment population. Among these 12 patients, four received thorough coverage of OpRegen cells across the majority of the atrophic area and experienced a cessation or reversal of their areas of atrophy at 12 months and continue to be followed. These patients also experienced increases in their visual acuity in their treated eye. We believe these four patients represent the only examples of an experimental treatment for dry AMD which can reduce an area of atrophy in humans, rather than simply slow its growth,” added  Brian M. Culley, Lineage CEO. “Restoration of retinal tissue using cell therapy represents a paradigm shift compared to conventional approaches, which to date have only shown an unremarkable slowing of progression. In addition to being well tolerated to date, the durability of changes to areas of atrophy and improvements in visual acuity support the continued and rapid clinical development of OpRegen. Alongside our advisors, we currently are preparing for multiple engagements with FDA to discuss aspects of OpRegen’s designation, our manufacturing plans, and the design of a later-stage clinical trial to begin next year. We anticipate the first of these engagements will begin next month and continue in the first quarter of 2022.”

OpRegen Phase 1/2a Interim Clinical Trial Results

• Retinal restoration, reported in four patients to date, persisted from over 12 months to greater than 3 years following treatment and continues to be followed.
• Restoration was evidenced by the presence of new areas of RPE monolayer with overlying ellipsoid zone, external limiting membrane, and outer nuclear layer, which were not present at the time of baseline assessment.
  • Reductions, or no progression for at least 1 year, was observed in the total area of GA in all four of these better vision Cohort 4 patients.

• Overall, using the Early Treatment Diabetic Retinopathy Study (EDTRS) assessment of best corrected visual acuity (BCVA), 7/12 (58%) of each of Cohort 4 patients’ treated eye were at baseline or better at 15 months or last time point, which extends beyond 3 years in some patients. In comparison, at the same time points, 8/12 (67%) were below baseline in those same patients’ fellow untreated eyes.
  • All four retinal restoration patients reported improvements in their visual acuity, which has been maintained for at least 12 months in all four of those patients.

• Across the study, in patients with previously reported structural improvements in the retina, decreases in drusen density, and a trend toward slower GA progression in treated compared to untreated eyes continue to be present.
• Evidence of durable engraftment of OpRegen RPE cells has extended to more than 5 years in the earliest treated patients, supporting the potential for OpRegen to be a one-time treatment.

Overall, OpRegen has been well tolerated to date and there have been no new, unexpected ocular or systemic adverse events or serious adverse events that have not been previously reported.

About OpRegen

OpRegen is currently being evaluated in a Phase 1/2a open-label, dose escalation safety and efficacy study of a single injection of human retinal pigment epithelium cells derived from an established pluripotent cell line and transplanted subretinally in patients with advanced dry AMD with GA. The study enrolled 24 patients into 4 cohorts. The first 3 cohorts enrolled only legally blind patients with best corrected visual acuity (BCVA) of 20/200 or worse. The fourth cohort enrolled 12 better vision patients (BCVA from 20/65 to 20/250 with smaller mean areas of GA). Cohort 4 also included patients treated with a new “thaw-and-inject” formulation of OpRegen, which can be shipped directly to sites and used immediately upon thawing, removing the complications and logistics of having to use a dose preparation facility. The primary objective of the study is to evaluate the safety and tolerability of OpRegen as assessed by the incidence and frequency of treatment emergent adverse events. Secondary objectives are to evaluate the preliminary efficacy of OpRegen treatment by assessing the changes in ophthalmological parameters measured by various methods of primary clinical relevance. OpRegen is a registered trademark of 
Cell Cure Neurosciences Ltd., a majority-owned subsidiary of 
Lineage Cell Therapeutics, Inc.

About Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is an eye disease that can blur the sharp, central vision in patients and is the leading cause of vision loss in people over the age of 60. There are two forms of AMD: dry (atrophic) AMD and wet (neovascular) AMD. Dry (atrophic) AMD is the more common of the two forms, accounting for approximately 85-90% of all cases. In atrophic AMD, parts of the macula get thinner with age and accumulations of extracellular material between Bruch’s membrane and the RPE, known as drusen, increase in number and volume, leading to a progressive loss of central vision, typically in both eyes. Global sales of the two leading wet AMD therapies were in excess of 
$10 billion in 2019. Nearly all cases of wet AMD eventually will develop the underlying atrophic AMD if the newly formed blood vessels are treated correctly. There are currently no 
U.S. Food and Drug Administration (FDA), or 
European Medicines Agency, approved treatment options available for patients with atrophic AMD.

About Lineage Cell Therapeutics, Inc.

Lineage Cell Therapeutics is a clinical-stage biotechnology company developing novel cell therapies for unmet medical needs. Lineage’s programs are based on its robust proprietary cell-based therapy platform and associated in-house development and manufacturing capabilities. With this platform Lineage develops and manufactures specialized, terminally differentiated human cells from its pluripotent and progenitor cell starting materials. These differentiated cells are developed to either replace or support cells that are dysfunctional or absent due to degenerative disease or traumatic injury or administered as a means of helping the body mount an effective immune response to cancer. Lineage’s clinical programs are in markets with billion dollar opportunities and include three allogeneic (“off-the-shelf”) product candidates: (i) OpRegen^®, a retinal pigment epithelium transplant therapy in Phase 1/2a development for the treatment of dry age-related macular degeneration, a leading cause of blindness in the developed world; (ii) OPC1, an oligodendrocyte progenitor cell therapy in Phase 1/2a development for the treatment of acute spinal cord injuries; and (iii) VAC2, an allogeneic dendritic cell therapy produced from Lineage’s VAC technology platform for immune-oncology and infectious disease, currently in Phase 1 clinical development for the treatment of non-small cell lung cancer. For more information, please visit www.lineagecell.com or follow the Company on Twitter @LineageCell.

Forward-Looking Statements

Lineage cautions you that all statements, other than statements of historical facts, contained in this press release, are forward-looking statements. Forward-looking statements, in some cases, can be identified by terms such as “believe,” “may,” “will,” “estimate,” “continue,” “anticipate,” “design,” “intend,” “expect,” “could,” “can,” “plan,” “potential,” “predict,” “seek,” “should,” “would,” “contemplate,” “project,” “target,” “tend to,” or the negative version of these words and similar expressions. Such statements include, but are not limited to, statements relating to the potential benefits of treatment with OpRegen in dry AMD patients with GA, the significance of clinical data reported to date from the ongoing Phase 1/2a study of OpRegen, including the findings of retinal tissue restoration, Lineage’s plans to meet with the FDA to discuss OpRegen’s clinical development, the potential utilization of OCT imaging to measure efficacy in a pivotal clinical trial of OpRegen for the treatment of dry AMD with GA, and the potential for Lineage’s investigational allogeneic cell therapies to provide safe and effective treatment for multiple, diverse serious or life threatening conditions. Forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause Lineage’s actual results, performance or achievements to be materially different from future results, performance or achievements expressed or implied by the forward-looking statements in this press release, including the risk that treatment with OpRegen in dry AMD patients with GA may not provide the benefits anticipated, the risk that interim results from clinical trials may not be predictive of future results, including later clinical trial results, and that interim data from clinical trials may change as more patient data become available and are subject to audit and verification procedures, and risks and uncertainties inherent in Lineage’s business and other risks in Lineage’s filings with the 
Securities and Exchange Commission (SEC). Lineage’s forward-looking statements are based upon its current expectations and involve assumptions that may never materialize or may prove to be incorrect. All forward-looking statements are expressly qualified in their entirety by these cautionary statements. Further information regarding these and other risks is included under the heading “Risk Factors” in Lineage’s periodic reports with the 
SEC, including Lineage’s most recent Annual Report on Form 10-K and Quarterly Report on Form 10-Q filed with the 
SEC and its other reports, which are available from the SEC’s website. You are cautioned not to place undue reliance on forward-looking statements, which speak only as of the date on which they were made. Lineage undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law.

Lineage Cell Therapeutics, Inc. IR
Ioana C. Hone
(ir@lineagecell.com)
(442) 287-8963

Solebury Trout IR
Mike Biega
(Mbiega@soleburytrout.com)
(617) 221-9660

Russo Partners – Media Relations
Nic Johnson or  David Schull
Nic.johnson@russopartnersllc.com
David.schull@russopartnersllc.com
(212) 845-4242

Source: 
Lineage Cell Therapeutics, Inc.