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Biohaven’s BHV-1200 Demonstrates Effective Neutralization Of COVID-19 Variants

 Biohaven Pharma Holding Company Ltd. (NYSE: BHVN), a commercial-stage biopharmaceutical company with a portfolio of innovative, late-stage product candidates, today announced that a hyperimmune globulin mimic (HGM) developed with Biohaven’s proprietary MATE platform has demonstrated functional binding and neutralization of the SARS-CoV-2 virus, including the strains known as the “English” and “South African” variants (also known as B.1.1.7 and B.1.351, respectively). The preliminary experiments, conducted by Biohaven Labs and an academic collaborator demonstrated that BHV-1200 substantially reduced viral entry into cells. Accelerated development of the COVID-19 MATE program has been supported by the Bill and Melinda Gates Foundation.

Vlad Coric M.D., Chief Executive Officer of Biohaven commented, “The battle against COVID-19 –like the virus itself–is dynamic and ever changing. Prophylactic and therapeutic agents with broad specificity against current and future strains will be essential in this ongoing fight to beat the virus. Results from our recent preclinical testing are an exciting advancement for this platform technology, and shows that our lead novel MATE conjugate, BHV-1200, exhibits broad and potent antiviral activity against not only wild type SARS-CoV-2 spike protein but also against mutations of growing clinical relevance, such as those associated with reduced susceptibility to therapeutic monoclonal antibodies and recent SARS-CoV-2 strains.” Dr. Coric added, “We believe that BHV-1200 could lead to enhanced efficacy and other benefits over convalescent plasma and alternative antibody-based approaches.  Biohaven is excited to advance BHV-1200 into a full clinical development program.  We are deeply grateful to the vision and critical funding support provided by The Bill & Melinda Gates Foundation that has accelerated this novel technology towards the clinic.”  

Biohaven’s proprietary MATE conjugation technology uses a new class of synthetic peptide binders to target the spike protein of SARS-CoV-2 that are then selectively conjugated to commercially available intravenous immunoglobulin (see Figure 1). The Biohaven synthetic binders for SARS-CoV-2 were designed to establish a much wider area and number of contacts with the spike protein than other agents like monoclonal antibodies. Importantly, the binding and potent neutralizing activity observed with BHV-1200 was consistent across multiple strains of the SARS-CoV-2 virus, including the “English” and “South African” variants. These variants contain multiple mutations in the spike protein that have been reported to reduce the binding and neutralizing activity of currently available antibody-based COVID-19 therapies and sera from SARS-CoV-2 vaccine recipients. In addition, the in vitro data indicate that BHV-1200 may activate important immune system components including antibody-dependent cellular phagocytosis (ADCP) and antibody dependent cellular cytotoxicity (ADCC). Biohaven’s proprietary MATE-conjugation technology could also be used against other infectious diseases by changing the targeting moiety of its antibody binders.

Dr. Charles Conway, Chief Scientific Officer at Biohaven stated, “Our recent in vitro data provide good evidence that BHV-1200 can neutralize the new strains of SARS-CoV-2 that have recently appeared across the globe. Our MATE-conjugation technology could enable commonly used and commercially available IVIG plasma products, which is not specific for the SARS-CoV-2 virus, to be redirected to target the viral spike protein. We look forward to continue to evaluate the therapeutic utility of this treatment both in the lab and in the clinic.”

(Source: Biospace, 2021)

Xencor and UCLA Enter Collaboration to Discover and Develop Novel XmAb® Therapeutics

Xencor, Inc. (NASDAQ:XNCR), a clinical-stage biopharmaceutical company developing engineered monoclonal antibodies and cytokines for the treatment of cancer and autoimmune diseases, and UCLA Technology Development Group (UCLA TDG) today announced an agreement to develop novel therapeutic antibodies, pairing novel targets proposed by scientists at UCLA and utilizing Xencor’s modular suite of XmAb® technology platforms. Xencor and UCLA have established a streamlined framework to select promising biology, perform collaborative research and license intellectual property.

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Xencor’s XmAb platforms are precisely engineered antibody Fc domains, which enable the creation of stable new protein structures, such as bispecific antibodies and engineered cytokines, or amplification of natural immune functions, such as extending circulating half-life or enhancing immune cell cytotoxicity. Xencor and its pharmaceutical partners are now advancing 20 clinical-stage XmAb-engineered drug candidates for the treatment of patients with life-threatening and debilitating diseases. Two of these antibodies have been approved by the U.S. FDA, one for the treatment of patients with rare blood disorders and the other for an aggressive form of non-Hodgkin lymphoma.

“The creation of exciting new therapeutic modalities requires advancing innovative biological concepts together with state-of-the-art molecular platforms to build best-in-class biologics,” said John Desjarlais, Ph.D., senior vice president and chief scientific officer at Xencor. “The inherent modularity and stability provided by our XmAb platforms, and our ability to precisely tune a molecule’s target-binding capability, opens the door to evaluate the clinical potential of biology that was previously considered intractable. We look forward to collaborating with UCLA’s investigators to translate their biological insights into potential medicines.”

The UCLA Technology Development Group, the campus’ gateway to innovation, research and entrepreneurship, will work with faculty to propose potential antibody drug candidates. For selected candidates, the collaborators will use a framework with predefined terms to enter sponsored research agreements and potential license agreements.

“Many revolutionary medical breakthroughs discovered by UCLA’s world-class investigators have vastly improved the care of patients, including engineered T cells, therapeutic antibodies and small molecules that are now approved to treat many types of cancer,” said Amir Naiberg, Associate Vice Chancellor, Chief Executive Officer and President of the UCLA Technology Development Group.

“With this collaboration, we aim to accelerate the development of potential new biologic medicines, leveraging Xencor’s protein engineering technologies and expertise and the ongoing scientific discoveries and insights into disease biology made at UCLA, with the ultimate goal to improve patient outcomes and quality of life,” added Mark A. Wisniewski, Senior Director of Biopharmaceuticals at UCLA TDG.

(Source: Biospace, 2021)

Monoclonal antibodies against MERS coronavirus show promise in Phase 1 NIH-sponsored trial

A randomized, placebo-controlled Phase 1 clinical trial of two monoclonal antibodies (mAbs) directed against the coronavirus that causes Middle East respiratory syndrome (MERS) found that they were well tolerated and generally safe when administered simultaneously to healthy adults. The experimental mAbs, REGN3048 and REGN3051, target the MERS coronavirus (MERS CoV) spike protein used by the virus to attach to and infect target cells. The mAbs were discovered and developed by scientists at the biopharmaceutical company Regeneron, located in Tarrytown, New York. The trial was sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

The trial was the first to test the experimental antibodies in people. Conducted at WCCT Global, a clinical trial site in California, the study enrolled 48 healthy adults, 36 of whom received the mAbs. All volunteers were followed for 121 days after receiving mAbs (or placebo) by intravenous infusion. No serious adverse events occurred.

In preclinical studies, investigators at Regeneron and the University of Maryland, College Park, also administered REGN3048 and REGN3051 sequentially and in combination to genetically modified mice that, unlike wild-type mice, can be infected with MERS CoV. When administered one day prior to coronavirus exposure, both REGN3048 and REGN3051 reduced the levels of virus later detected in the lungs, with co-administration providing more potent protective effects than either mAb alone. Similarly, co-administering the mAbs one day after MERS CoV exposure provided a therapeutic benefit in mice by lowering viral levels and lessening tissue damage in the lungs as compared to mice that received placebo.

Together, the findings from the clinical trial and the preclinical mouse studies “demonstrate the potential efficacy and utility of monoclonal antibody therapy for the prevention or treatment of MERS-CoV and lays the groundwork for the development of spike-targeted mAb therapies for other infectious disease threats, including SARS-CoV-2,” which causes COVID-19, the authors conclude.

(Source: National Institutes of Health, 2021)