Category Archives: Immunology

Immunology

Grant Funds Study of the Role of Fungi in Cancer Development and Immunotherapy – Weill Cornell Medicine Newsroom

Dr. Iliyan D. Iliev, an associate professor of immunology and microbiology in the Division of Gastroenterology and Hepatology and a member of the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine, has been awarded a five-year, $1.25 million CRI Lloyd J. Old STAR (Scientists Taking Risks) Program grant from Cancer Research Institute (CRI).

Dr. Iliyan D. Iliev

The non-profit CRI focuses on pursuing innovative research that could improve the way cancer patients are diagnosed and treated. The STAR program is a competitive grant that supports gifted, mid-career scientists who are working at the intersection of immunology, technology and bioinformatics. The aim of the program is to fund high-risk/high-reward research that has the potential to transform cancer patient responses to immunotherapy.

The grant will allow Dr. Ilievs lab to continue research that investigates relationships between certain types of fungi and specific cancers. His winning grant proposal stems from his study of patients with ulcerative colitis who later developed colorectal cancer. Dr. Iliev and his lab colleagues noticed that some cancer patients share unique microbiome composition where specific fungal strains prevailed.

We found that some patients carry specific fungal strains that expand and produce a toxin that affected inflammation, said Dr. Iliev, who is also co-director of the Microbiome Core Lab at Weill Cornell Medicine. One of the questions is whether the presence of these and other fungi influence cancer development and outcomes.

By isolating certain fungi and observing what they do in mouse models, Dr. Iliev and his colleagues will be learning about fungal biology within the tumor microenvironment. Those discoveries lead them back to cancer patients where these fungi originate.

This back-and-forth process, moving between mouse models and patients, is a catalyst for developing innovative ways to investigate and hopefully treat various forms of cancer. Its a new hypothesisa there are new players, Dr. Iliev said. There have been reports of certain fungal species associated with pancreatic cancer, for example. Now we have developed methodologies allowing us to assess microbial components in multiple tumor types to tune hypothesis and modeling promptly.

Dr. Iliev is excited about the opportunity to cross-fertilize the cancer field with discoveries about fungal and bacterial organisms linked to the inflammatory bowel diseases he studies. This funding is fantastic because it allows us to go in with an early hypothesis, he said, and gives us the freedom to go after what is really interesting in search of new and exciting ideas.

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Immunology

New method of inciting immunological responses is revealed – ThePrint

Washington [US], July 17 (ANI): Small proteins, called chemokines, that direct immune cells toward sites of infection can also form DNA-bound nanoparticles that can induce chronic, dysfunctional immune responses, according to a new study.

The surprising discovery of this new activity for this well-studied class of immune signalling molecules could shed light on some types of immune disorders.

The study, published May 31 in the Journal of Experimental Medicine, reveals an entirely new mode of triggering the immune system, through which chemokine-DNA nanoparticles can induce inflammation. Results in preclinical models suggest that this mechanism may play a central role in autoimmune diseases such as scleroderma and lupus.

The work was part of the scientists ongoing efforts to understand scleroderma, an autoimmune condition that causes inflammation and hardening of the skin. We had a project looking at scleroderma and it was shown by us and others a few years ago that patients with this condition have an elevated level of the chemokine CXCL4 in their blood, said senior author Dr. Franck Barrat, professor of microbiology and immunology at Weill Cornell Medicine and the Michael Bloomberg Chair and senior scientist at HSS. But the role of this chemokine in disease is unclear and we didnt expect the chemokine to provoke this particular immune response.

In setting up controls for one of their experiments, Dr. Barrats team, including first author, Dr. Yong Du, a postdoctoral associate in microbiology and immunology at Weill Cornell Medicine and a member of the HSS Research Institute, discovered that CXCL4 and several other chemokines could induce immune cells called plasmacytoid dendritic cells (pDCs) to produce interferon-alpha. Surprisingly, the induction appeared to be independent of known chemokine receptors, indicating that these molecules were activating the immune cells through some previously unknown mechanism.

Subsequent experiments revealed that the chemokines can bind pieces of DNA to form nanoparticles, which then bypass the cells chemokine receptors to induce interferon production directly. Tests in mouse models of skin inflammation suggest that this mechanism could account for the chronic immune activation that underlies scleroderma and other autoimmune diseases. The results also suggest that different DNA-chemokine nanoparticles could underlie different diseases. For example, while CXCL4 appears to be important in scleroderma, another chemokine, CXCL10, may perform a similar function in lupus.

Dr. Barrat believes that the DNA-chemokine nanoparticles are likely an essential component of the bodys wound healing system. Following a skin injury, such as if you cut yourself, dendritic cells infiltrate the skin and create an inflammatory environment to allow for proper closing of the wound. Our findings suggest that these cells do not need to see a pathogen a virus or bacterium and can directly sense self-DNA, he said. And that inflammation is helping to recruit other cells of the immune system. In autoimmune disease, the process goes awry, producing a chronic inflammatory state that ultimately damages tissue instead of healing it.

The researchers also collaborated on a related study, published June 14 in Nature Communications, that shows that CXCL4 can induce a similar inflammatory response in monocytes, another important class of immune cells. Taken together, the findings point toward possible strategies to shut down autoimmunity without interfering with normal immune responses.

It tells you the type of response that you have to stop, not necessarily at the DNA-chemokine level, but potentially more downstream in the cells themselves, Dr. Barrat said. (ANI)

This report is auto-generated from ANI news service. ThePrint holds no responsibility for its content.

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New method of inciting immunological responses is revealed - ThePrint

Immunology

GenFleet Receives CTAs Approval for Two Phase II Combination Studies of TGF- R1 Inhibitor (GFH018) with PD-1 Inhibitor – BioSpace

SHANGHAI, July 22, 2022 /PRNewswire/ --GenFleet Therapeutics, a clinical-stage biotechnology company focusing on cutting-edge therapies in oncology and immunology, announced China's National Medical Products Administration (NMPA) has approved the Clinical Trial Applications (CTAs) for GFH018 in two clinical studies for combination therapies.

One study is a phase Ib/II trial of GFH018 with PD-1 inhibitor treating patients with advanced solid tumors; the other study is a phase II trial of GFH018, PD-1 inhibitor with concurrent chemoradiotherapy treating patients with locally advanced & unresectable NSCLC. GenFleet has completed a phase I trial of GFH018 monotherapy treating solid tumors in early 2022, and the data will soon be published in relevant international medical conference.

"Pre-clinical in-vivo data have demonstrated desirable anti-tumor effects of GFH018 in combination with PD-1 inhibitors; the combo studyGFH018X0201being conducted in Australia and China's Taiwan has completed the dose escalation phase (phase Ib), with the dose expansion phase (phase II) currently ongoing. From this multi-regional, multi-center clinical trial, we expect to collect additional evidence to further confirm the efficacy of combination therapies with GFH018 in cancer patients. In the study of GFH018, PD-1 inhibitor with concurrent chemoradiotherapyGFH018X1202, we will investigate the combination's potential in improving the immunosuppressive microenvironment and reducing the side effects from concurrent chemoradiotherapy." said Yu Wang, M.D./Ph.D., Chief Medical Officer of GenFleet.

"GFH018 is GenFleet's first product that has moved into clinical development stage. The progress of GFH018's multi-regional studies clearly demonstrates GenFleet's capability in global regulatory registration, patient enrollment and market positioning, and will substantially accelerate GFH018's global clinical development. TGF- signaling pathway has been studied as a critical target in multiple solid tumors; however, no drugs have been approved to date for this pathway. GFH018 is a small molecule drug designed to specifically target and inhibit TGF- R1, and the discovery and development of GFH018 truly reflects GenFleet's strategy of novel mechanism-focused innovation in drug development. GenFleet expects the development of the GFH018 to bring a novel therapy with great clinical benefit to cancer patients. "said Jiong Lan, Ph.D., Chief Executive Officer of GenFleet.

Both studies are multi-center, single-arm, and open-label trials designed to evaluate the safety/tolerability and efficacy of the GFH018 in combination therapies. Shanghai Oriental Hospital and Sun Yat-Sen University Cancer Center will lead the phase Ib/II study evaluating the combination of GFH018 and anti-PD-1 monoclonal antibody conducted in over 20 domestic hospitals. The safety/tolerability and efficacy of combination of GFH018, anti-PD-1 monoclonal antibody, concurrent chemoradiotherapy will be evaluated in the phase II study, which will be conducted at over 10 hospitals including West China Hospital of Sichuan University, Peking Union Medical College Hospital.

About GFH018 and TGF- R1

Developed by GenFleet Therapeutics, GFH018 is an orally administered TGF- R1 inhibitor and entered into phase I clinical trial in 2019. Preclinical data showed evidence of GFH018's good anti-tumor properties against cancer cells in vivo and in vitro. Besides, translational and mechanistic studies confirmed it effectively acts on TGF- signaling pathway and synergizes with checkpoint inhibitors.

In the microenvironment of advanced solid tumors, TGF- signaling pathway can promote epithelial mesenchymal transition (EMT) & metastasis, induce the formation of cancer stem cells and their functional maintenance, inhibit anti-tumor immunity, enhance vasculature and fibrosis, and ultimately result in tumor progression. Among patients of hepatocellular carcinoma, glioma, colorectal cancer, lung cancer, pancreatic cancer, urothelial cancer and other solid tumors, high expression of genes related to TGF- signaling pathway is frequently discovered in their blood and tumor tissues. The expression level is positively correlated to the malignancy & poor differentiation of tumor and unfavorable prognosis in patients.

About GenFleet Therapeutics

GenFleet Therapeutics, a clinical-stage biotechnology company focusing on cutting-edge therapies, is dedicated to serving significant global unmet medical needs in oncology and immunology. Based on the deep understanding of disease biology and translational medicine, GenFleet's proprietary and fully integrated R&D platform highlights multiple cutting-edge products with novel mechanisms and global IP.

Since its inception in 2017, GenFleet has built up industry-leading capabilities and expertise in developing novel drug candidates - both small molecules and biologics. Its pipeline includes over 10 programs, many of which have entered multi-regional clinical trials across China (including Taiwan), the United States and Australia. To date, GenFleet has over 5 clinical studies encompassing IND stage to phase II studies and completed co-development partnerships with 3 publicly listed companies in China or US.

GenFleet is expected to progress additional programs into the clinic, as well as transition from a clinical stage biotech company into a commercial stage biopharmaceutical company in the next 3-5 years.

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SOURCE GenFleet Therapeutics

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GenFleet Receives CTAs Approval for Two Phase II Combination Studies of TGF- R1 Inhibitor (GFH018) with PD-1 Inhibitor - BioSpace

Immunology

13-Year-Old Accepted to Medical School | MedPage Today – Medpage Today

At 13 years old, Alena Analeigh Wicker is on her way to medical school.

Wicker, who lives just outside of Forth Worth, Texas, learned in May that she had been accepted into the University of Alabama at Birmingham Heersink School of Medicine for 2024 through the Burroughs Wellcome Scholars Early Assurance Program, the Washington Post reported this week.

The child prodigy is more than 10 years younger than the average incoming medical student, the Post noted. And she is the youngest Black person to ever get accepted into a medical school in the U.S., KPNX-TV reported.

"I'm still a normal 13-year-old," Wicker, who recently began using her middle name, Analeigh, as her surname, told the Post. "I just have extremely good time management skills and I'm very disciplined."

She is currently a student at both Arizona State University and Oakwood University in Huntsville, Alabama, and is simultaneously earning two separate undergraduate degrees in biological sciences, the Post reported. She takes most of her classes online, but also spends time on campus completing labs.

Just last year, Wicker spoke with KPNX-TV about her acceptance to Arizona State University's engineering program at age 12. While she originally had hopes of working for NASA, her passion for biology shifted her focus to medicine.

"It actually took one class in engineering for me to say this is kind of not where I wanted to go," she told the news outlet. "I think viral immunology really came from my passion for volunteering and going out there engaging with the world."

"What I want from healthcare is to really show these underrepresented communities that we can help, that we can find cures for these viruses," she added.

Wicker's current timeline means that she'll become a doctor at 18, and she hopes to encourage her peers to follow in her footsteps.

About a year and a half ago, she started an organization called the Brown STEM Girl, aimed at providing opportunities to girls of color who are interested in exploring careers in science, technology, engineering, and math.

Wicker told the Post that she wanted to create the organization for girls like her "to feel like they belong somewhere."

She was also named one of Time's Top Kid of the Year Finalists for 2022.

In her spare time, Wicker plays soccer and participates in track and field, according to the Post. Some of her hobbies include going to the arcade with friends, singing, cooking, and traveling.

In a recent post on Instagram, she wrote that she was "grateful," noting that she had graduated high school just a year ago, the Birmingham Times reported.

"Statistics would have said I never would have made it," she added. "A little black girl adopted from Fontana, California. I've worked so hard to reach my goals and live my dreams. Mama, I made it. I couldn't have done it without you."

Wicker told the Post that she wants to continue to advocate for other young people.

"It feels amazing to be able to create a path for girls that look like me," she said. "It doesn't matter how old you are. You can do it. Don't let anybody tell you no."

Jennifer Henderson joined MedPage Today as an enterprise and investigative writer in Jan. 2021. She has covered the healthcare industry in NYC, life sciences and the business of law, among other areas.

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Immunology

Immune Therapeutics, Inc. Appoints Dr. Stephen Wilson as Chief Executive Officer – BioSpace

ORLANDO, FL, July 22, 2022 (GLOBE NEWSWIRE) -- Immune Therapeutics Inc. (OTC Pink: IMUN) (Immune or IMUN), a specialty pharmaceutical company involved in the acquisition, development and commercialization of pharmaceutical and biotechnology products that have a short and well-defined path to market, is pleased to announce the appointment of Dr. Stephen Steve Wilson as Immunes Chief Executive Officer (CEO), President, and interim Chief Financial Officer (CFO) effective July 19, 2022; he will continue to serve as a member of the Companys Board of Directors.

Dr. Wilson brings over 20 years of experience in biomedical research, executive management, and corporate governance. He is a trained immunologist. In addition, he is, among other things, an Associate Clinical Professor at the University of California, San Diego, and he previously served as the Chief Operating Officer at the La Jolla Institute for Immunology as it grew to become an international powerhouse.

Immune also announced that Kevin Phelps has stepped down from his positions as the companys CFO, President, and CEO, but he will remain a member of Immunes Board of Directors.

The appointment of Dr. Wilson as Immunes CEO, President, and interim CFO is expected to further strengthen IMUNs global executive leadership team to drive its next phase of growth and operational success within a new operational model, initially focused on regulatory approval and commercialization of existing assets that treat patients with inflammatory disease.

Dr. Wilson stated, Our strategy is to lever the global need for affordable and effective therapeutics and modern financial tools; this hinges on acquisition, development and commercialization of pharmaceutical and biotechnology products that have a short and well-defined path to market. We have assets that fit this profile, and our business objectives fit immediate patient needs. Going forward, we will take a measured portfolio approach to investment, development and commercialization that will mandate each additional program be hyper focused, capital efficient and small-scale with clear paths to regulatory approval. Financing these programs through modern investment vehicles and partnerships, we plan to deploy in markets that include, but are not dependent upon, US commercialization.

Forward Looking Statement

This press release may contain information about our views of future expectations, plans and prospects that constitute forward-looking statements. All forward-looking statements are based on managements beliefs, assumptions, and expectations of Immunes future economic performance, taking into account the information currently available to it. These statements are not statements of historical fact. Although Immune believes the expectations reflected in such forward-looking statements are based on reasonable assumptions, it can give no assurance that its expectations will be attained. Immune does not undertake any duty to update any statements contained herein (including any forward-looking statements), except as required by law. No assurances can be made that Immune will successfully acquire its acquisition targets. Forward-looking statements are subject to a number of factors, risks, and uncertainties, some of which are not currently known to us, that may cause Immunes actual results, performance, or financial condition to be materially different from the expectations of future results, performance, or financial position. Actual results may differ materially from the expectations discussed in forward-looking statements. Factors that could cause actual results to differ materially from expectations include general industry considerations, regulatory changes, changes in local or national economic conditions and other risks set forth in Risk Factors included in our filings with the Securities and Exchange Commission.

Disclaimer

The information provided in this press release is intended for general knowledge only and is not a substitute for professional medical advice or treatment for specific medical conditions. Always seek the advice of your physician or other qualified health care provider with any questions you may have regarding a medical condition. This information is not intended to diagnose, treat, cure or prevent any disease.

Contact Data

Dr. Stephen WilsonCEOir@immunetherapeutics.com 1-888-391-9355

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Immune Therapeutics, Inc. Appoints Dr. Stephen Wilson as Chief Executive Officer - BioSpace

Immunology

Structure of Antibodies Could Be Key to More Effective Cancer Treatments – Lab Manager Magazine

Researchers at the University of Southampton have gained unprecedented new insight into the key properties of an antibody needed to fight off cancer.

The interdisciplinary study, published in Science Immunology, revealed how changing the flexibility of the antibody could stimulate a stronger immune response.

The findings have enabled the Southampton team to design antibodies to activate important receptors on immune cells to fire them up and deliver more powerful anti-cancer effects.

The scientists believe their findings could pave the way to improve antibody drugs that target cancer as well as other autoimmune diseases.

In the study, the team investigated antibody drugs targeting the receptor CD40 for cancer treatment. Clinical development has been hampered by a lack of understanding of how to stimulate the receptors to the right level. The problem being that if antibodies are too active they can become toxic.

Previous Southampton research has shown that a specific type of antibody called IgG2 is uniquely suited as a template for pharmaceutical intervention, since it is more active than other antibody types. However, the reason why it is more active had not been determined.

What was known, however, is that the structure between the antibody arms, the so called hinges, changes over time.

This latest research harnesses this property of the hinge and explains how it works: the researchers call this process disulfide-switching.

In their study, the Southampton team analyzed the effect of modifying the hinge and used a combination of biological activity assays, structural biology, and computational chemistry to study how disulfide switching alters antibody structure and activity.

Dr. Ivo Tews, associate professor in structural biology at the University of Southampton, said: Our approach was to analyze the structure of the antibody in atomic detail, using the method of X-ray crystallography. While the resulting picture is very accurate, the information on how they move their arms is missing, and we needed an image of the antibody in solution, for which we used an X-ray scattering approach called SAXS. We then used mathematical models and a chemical-computing approach to analyze the data, using the Southampton High Performance Computing cluster IRIDIS.

Through this detailed study of the hinge the team revealed that more compact, rigid antibodies are more active than their flexible counterparts.

Professor Mark Cragg, of the Centre for Cancer Immunology at the University of Southampton, said: This study has given us new information about how to engineer antibodies to deliver a better immune response. We propose that more rigid antibodies enable the receptors to be bound closer together on the cell surface, promoting receptor clustering and stronger signaling for activity. This means by modifying the hinge we can now generate more or less active antibodies in a more predictable way.

Excitingly, our findings could have wider implications as it may provide a highly controlled and tractable means of developing antibodies for clinical use in future immunostimulatory antibody drugs.

The study was funded by Cancer Research UK and brought together structural biologists, immunologists, chemists and computer experts from across the University. Collaboration with the Diamond Light Source in Oxford and the University of Hamburg that Southampton is partnered with were instrumental to these studies.

- This press release was provided by the University of Southampton

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Immunology

Cuban vaccine against lung cancer makes its way into the UAS – The Point – The Point

The Cuban Molecular Immunology Center (CIM) and the Roswell Park Cancer Research Center, in Buffalo, USA, joined forces a few years ago to facilitate access to equipment and reagents, in order to promote the development of the drug, a relationship that has not been without difficulties, due to the economic blockade policy against Cuba.

The creation of the only joint venture between Cuba and the United States, the biotechnological company Innovative Immunotherapy Alliance, with the purpose of introducing the drug into American society, provided Cuba with access to equipment and reagents that are very difficult to obtain due to the limitations of the coercive measure, while the US can access a drug with excellent results and prospects.

Dr. Elia Neninger, who has participated in clinical trials of the therapeutic vaccine since the beginning, assured that the drug has two great advantages: few adverse reactions and a solution to a serious health problem on the island, such as lung cancer.

Kalet Len Monzn, deputy director of the Center for Molecular Immunology, said that the beneficiary patients recover from an advanced tumor cancer that could have a very short-term prospect of survival under normal conditions.

One of those favored with the vaccine, Miguel Creus, a patient who began receiving Cimavax 15 years ago, when the disease was in phase four and the vaccine was in clinical trials, assures that the drug has prolonged his life with a state of satisfactory health. He currently has no traces of tumors or symptoms of the disease.

Despite the effects of the economic blockade of the White House, the collaboration between both institutions does not stop, and Cimavax overcomes the challenges. There are currently clinical trials that combine this Cuban vaccine with other successful cancer treatments, and their effects are being studied in high-risk people or patients in the initial stage of the disease.

According to some studies, lung cancer is the third most common cancer in the US, but the deadliest. A promising relief could be this Cuban drug, a good example of the benefits that both nations would obtain if they had a normal relationship.

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Cuban vaccine against lung cancer makes its way into the UAS - The Point - The Point

Immunology

Key to Hepatitis A Replication Discovered – Technology Networks

The viral replication cycle is crucial for a virus to spread inside the body and cause disease. Focusing on that cycle in the hepatitis A virus (HAV), UNC School of Medicine scientists discovered that replication requires specific interactions between the human protein ZCCHC14 and a group of enzymes called TENT4 poly(A) polymerases. They also found that the oral compound RG7834 stopped replication at a key step, making it impossible for the virus to infect liver cells.

These findings, published in the Proceedings of the National Academy of Sciences, are the first to demonstrate an effective drug treatment against HAV in an animal model of the disease.

Our research demonstrates that targeting this protein complex with an orally delivered, small-molecule therapeutic halts viral replication and reverses liver inflammation in a mouse model of hepatitis A, providing proof-of-principle for antiviral therapy and the means to stop the spread of hepatitis A in outbreak settings, said senior author Stanley M. Lemon, MD, professor in the UNC Department of Medicine and UNC Department of Microbiology & Immunology, and member of the UNC Institute for Global Health and Infectious Diseases.

Lemon, who in the 1970s and 80s was part of a Walter Reed Army Medical Center research team that developed the first inactivated HAV vaccine administered to humans, said research on HAV tapered off after the vaccine became widely available in the mid-1990s. Cases plummeted in the 2000s as vaccination rates skyrocketed. Researchers turned their attention to hepatitis B and C viruses, both of which are very different from HAV and cause chronic disease. Its like comparing apples to turnips, Lemon said. The only similarity is that they all cause inflammation of the liver. HAV is not even part of the same virus family as hepatitis B and C viruses.

Hepatitis A outbreaks have been on the rise since 2016, even though the HAV vaccine is very effective. Not everyone gets vaccinated, Lemon pointed out, and HAV can exist for long periods of time in the environment such as on our hands and in food and water resulting in more than 44,000 cases, 27,000 hospitalizations and 400 deaths in the United States since 2016, according to the CDC.

Several outbreaks have occurred over the past several years, including in San Diego in 2017 driven largely by homelessness and illicit drug use, causing severe illness in about 600 people and killing 20. In 2022, there was a small outbreak linked to organic strawberries in multiple states, leading to about a dozen hospitalizations. Another outbreak in 2019 was linked to fresh blackberries. Globally, tens of millions of HAV infections occur each year. Symptoms include fever, abdominal pain, jaundice, nausea, and loss of appetite and sense of taste. Once sick, there is no treatment.

In 2013, Lemon and colleagues discovered that the hepatitis A virus changes dramatically inside the human liver. The virus hijacks bits of cell membrane as it leaves liver cells, cloaking itself from antibodies that would have otherwise quarantined the virus before it spread widely through the blood stream. This work was published in Nature and provided insight into how much researchers had yet to learn about this virus that was discovered 50 years ago and has likely caused disease dating back to ancient times.

A few years ago, researchers found that hepatitis B virus required TENT4A/B for its replication. Meanwhile, Lemons lab led experiments to search for human proteins that HAV needs in order to replicate, and they found ZCCHC14 a particular protein that interacts with zinc and binds to RNA.

This was the tipping point for this current study, Lemon said. We found ZCCHC14 binds very specifically to a certain part of HAVs RNA, the molecule that contains the viruss genetic information. And as a result of that binding, the virus is able to recruit TENT4 from the human cell.

In normal human biology, TENT4 is part of an RNA-modification process during cell growth. Essentially, HAV hijacks TENT4 and uses it to replicate its own genome.

This work suggested that stopping TENT4 recruitment could stop viral replication and limit disease. Lemons lab then tested the compound RG7834, which had previously been shown to actively block Hepatitis B virus by targeting TENT4. In the PNAS paper, the researchers detailed the precise effects of oral RG7834 on HAV in liver and feces and how the viruss ability to cause liver injury is dramatically diminished in mice that had been genetically modified to develop HAV infection and disease. The research suggests the compound was safe at the dose used in this research and the acute timeframe of the study.

This compound is a long way from human use, Lemon said, But it points the path to an effective way to treat a disease for which we have no treatment at all.

The pharmaceutical company Hoffmann-La Roche developed RG7834 for use against chronic hepatitis B infections and tested it in humans in a phase 1 trial, but animal studies suggested it may be too toxic for use over long periods of time.

The treatment for Hepatitis A would be short term, Lemon said, and, more importantly, our group and others are working on compounds that would hit the same target without toxic effects.

Reference: Lemon SM et al.The ZCCHC14/TENT4 complex is required for hepatitis A virus RNA synthesis. PNAS; 2022. doi:10.1073/pnas.2204511119

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Key to Hepatitis A Replication Discovered - Technology Networks

Immunology

Inmagene and HUTCHMED Announce First Participants in Global Phase I Trial of IMG-007 – Yahoo Finance

SAN DIEGO and HONG KONG and SYDNEY, July 6, 2022 /PRNewswire/ --Inmagene Biopharmaceuticals ("Inmagene") and HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM:HCM; HKEX:13) announces today that the first participant, based in Australia, was dosed in a global Phase I trial of IMG-007, an investigational OX40 antagonistic monoclonal antibody.

The Phase I study is a multi-stage, double-blind, randomized, placebo-controlled, dose-escalation study in healthy volunteers, and a dose-escalation and parallel design, multiple-dose study in adult patients with moderate to severe atopic dermatitis. The study will be used to evaluate the safety, tolerability and efficacy of IMG-007 in patients with atopic dermatitis. Additional details will be found at clinicaltrials.gov, using identifier NCT05353972.

"Dosing the first participant is an important milestone for the IMG-007 program," said Dr Jonathan Wang, Chairman and Chief Executive Officer of Inmagene. "We hope the data will help us demonstrate that IMG-007 is one of the strongest OX40 antagonist drug candidates worldwide."

Dr Jean-Louis Saillot, Chief Development Officer of Inmagene, said, "IMG-007 blocks the OX40 activity and has demonstrated high potency in preclinical studies, indicating a best-in-class potential. We welcome the start of the IMG-007 clinical program with the hope of developing an innovative, safe and effective treatment option for patients with atopic dermatitis and other immunological diseases."

Dr Weiguo Su, Chief Executive Officer and Chief Scientific Officer of HUTCHMED, said: "This is an exciting step towards taking our novel drug candidates into immunological diseases, where Inmagene has significant expertise, as we work to maximize the impact of our drug discovery engine."

About IMG-007

IMG-007 is a novel antagonistic monoclonal antibody targeting the OX40 receptor. It was originally discovered by HUTCHMED, with Inmagene assuming development responsibility at the candidate stage. Inmagene has an exclusive option to in-license IMG-007's global rights.

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About OX-40 and Atopic Dermatitis

OX40 is a costimulatory receptor member of the tumor necrosis factor receptor (TNFR) superfamily expressed predominantly on activated T cells. The ligation of OX40 by its ligand OX40L leads to enhanced T cell survival, proliferation, and effector functions. Preclinical research results show that IMG-007 can bind to human OX40 receptor with high affinity, thereby inhibit the binding of OX40 to OX40L, reducing OX40L-dependent downstream signaling and cytokine release by OX40+ T cells. By selectively shutting down OX40+ T cell function, IMG-007 may provide a treatment option for pathological OX40+ T cell-mediated immune diseases, such as atopic dermatitis.

Atopic dermatitis is a chronic inflammatory skin condition that is estimated to affect 8-19% of children and 2-5% of adults in US, Europe, and East Asia.[1],[2],[3]

About Inmagene

Inmagene is a global clinical-stage biotechnology company focused on developing novel therapeutics for immunology-related diseases. The company is building a robust pipeline of nearly twenty drug development programs.

Inmagene's most advanced drug candidate is IMG-020 (izokibep), which has successfully met the endpoints in global phase II studies for both psoriasis and psoriatic arthritis ("PsA"). It has received the IND approval from the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) for phase III studies in plaque psoriasis. Inmagene is working with its partners to conduct global phase II studies for multiple autoimmune diseases, including PsA, ankylosing spondylitis (AS) and uveitis. In addition, IMG-004 and IMG-007, both of which with global rights, are in global phase I studies.

Believing in "Borderless Innovation", the Inmagene team strives to integrate efficient resources worldwide to develop novel therapeutics for global patients. Based on its proprietary QuadraTek drug discovery platform, Inmagene is operating 12 "Smart Innovation" programs to create and develop drug candidates with global rights. Inmagene also in-licenses drug candidates and, together with its partners, carries out global development activities, including global multi-center clinical trials. Inmagene has formed strategic partnerships with multiple partners, such as HUTCHMED and Affibody AB, to develop highly innovative drug candidates. For more information, please visit: http://www.inmagenebio.com

About HUTCHMED

HUTCHMED (Nasdaq/AIM: HCM; HKEX: 13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery and global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has more than 4,900 personnel across all its companies, at the center of which is a team of over 1,800 in oncology/immunology. Since inception it has advanced 13 cancer drug candidates from in-house discovery into clinical studies around the world, with its first three oncology drugs now approved and marketed in China. For more information, please visit: http://www.hutch-med.com or follow us on LinkedIn.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the "safe harbor" provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect Inmagene's and/or HUTCHMED's current expectations regarding future events, including expectations regarding the therapeutic potential of IMG-007 for the treatment of patients with atopic dermatitis and other immunological diseases, the further clinical development of IMG-007, expectations as to whether clinical studies of IMG-007 would meet their primary or secondary endpoints, and expectations as to the timing of the completion and the release of results from such studies. Forward-looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, assumptions regarding enrollment rates and the timing and availability of subjects meeting a study's inclusion and exclusion criteria; changes to clinical protocols or regulatory requirements; unexpected adverse events or safety issues; the ability of IMG-007 to meet the primary or secondary endpoint of a study, to obtain regulatory approval in different jurisdictions and to gain commercial acceptance after obtaining regulatory approval; the potential market of IMG-007 for a targeted indication; the sufficiency of funding; and the impact of the COVID-19 pandemic on general economic, regulatory and political conditions. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of various risks applicable to HUTCHMED, see HUTCHMED's filings with the U.S. Securities and Exchange Commission, on AIM and with The Stock Exchange of Hong Kong Limited. Neither Inmagene nor HUTCHMED undertakes to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise.

[1] Silverberg JI, Barbarot S, Gadkari A, et al. Atopic dermatitis in the pediatric population: A cross-sectional, international epidemiologic study. Ann Allergy Asthma Immunol. 2021;126(4):417-428.e2. doi:10.1016/j.anai.2020.12.020

[2] Barbarot S, Auziere S, Gadkari A, et al. Epidemiology of atopic dermatitis in adults: Results from an international survey. Allergy. 2018;73(6):1284-1293. doi:10.1111/all.13401

[3] Stnder S. Atopic Dermatitis. N Engl J Med. 2021;384(12):1136-1143. doi:10.1056/NEJMra2023911

Cision

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SOURCE Inmagene Biopharmaceuticals

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Inmagene and HUTCHMED Announce First Participants in Global Phase I Trial of IMG-007 - Yahoo Finance

Immunology

All-in-one vaccine will tackle future coronavirus threats – Innovation Origins

As of July 2022, uncertainty persists as waves of SARS-CoV-2 continue to emerge. Over time, new virus variants arise and threaten to reduce the impact of existing vaccine efforts. There is a clear need for strategies to both tackle emerging variants, and to protect populations against potential future threats to human health such as related bat viruses, writes the University of Oxford in a press release.

A new consortium aims to address these issues by establishing the first-in-human clinical proof of concept for a new vaccine design. The vaccine will target both SARS-CoV-2 and a number of related bat viruses which have the potential to spread to humans. It builds on technologies developed by the Molecular Immunology Group at the University of Oxford and by the Bjorkman Group based at Caltech led by Professor Alain Townsend at the MRC Human Immunology Unit and by Professor Pamela Bjorkman respectively.

In contrast to many existing vaccine designs that use mRNA or a viral vector to present sections of the spike protein of a single type of virus to the immune system, this new vaccine will use protein nanoparticles containing a protein glue to attach related antigenic sections of the spike proteins from eight different viruses. By incorporating a mosaic-8 vaccine design created at Caltech these nanoparticles would favour immune responses to the shared parts of each of the different types of coronaviruses within a single vaccine.

Evidence published today in Science by the researchers demonstrates that this vaccine technology not only elicits protective immune responses against SARS-like virusesbutalso against some coronaviruses not presented in the trial vaccine. This suggests that the technology could provide protection against future novel SARS-CoV-2 variants and as-yet-undiscovered coronaviruses with the potential to spill over from animal populations.

Using Artificial Intelligence to monitor and manage COVID-19

A study by researchers at the Universitat Politcnica de Valncia (UPV), part of BDSLab-ITACA group and the Institute of Pure and Applied Mathematics (IUMPA), has become an international benchmark for the reliable use of artificial intelligence in monitoring and managing COVID-19.

Alain Townsend, Oxford Lead of the consortium, Professor of Molecular Immunology at the MRC Weatherall Institute of Molecular Medicine, University of Oxford, said: The evolution of this consortium is an example of collaborative science at its best. We had been deeply impressed by the power of the glue for sticking proteins together developed by Mark Howarth (Biochemistry Oxford),and derived from his beautiful basic science investigations of the Streptococcus pyogenes bacterium.

Throughconnections made byIan Wilkinson (Absolute Antibody), we joined with colleagues at Ingenza and CPI who succeeded in making a fully functional version of the vaccine produced in microbes, thus reducing the cost of production. We have been collaborating with Prof. Pamela Bjorkman and the Caltech team, who had independently developed the brilliant concept of the mosaic version of the vaccine and are excited to continue working with this world-class consortium.

The consortium aims to commence a Phase 1 trial in 2024, led by the Oxford Vaccine Group.

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All-in-one vaccine will tackle future coronavirus threats - Innovation Origins