Biohaven Receives FDA May Proceed Letter to Begin Phase 2 Trial of Intranasal Vazegepant to Treat Lung Inflammation After COVID-19 Infection

NEW HAVEN, Conn., April 9, 2020 /PRNewswire/ --Biohaven Pharma Holding Company Ltd. (NYSE: BHVN) (“Biohaven”) today announced that it submitted Pre-IND/IND material to the U.S. Food and Drug Administration (FDA) to initiate a Phase 2 study of vazegepant, an intranasal, high-affinity calcitonin gene-related peptide (CGRP) receptor antagonist, for the treatment of COVID-19 infection associated pulmonary complications. The IND was approved by the Division of Pulmonary, Allergy, and Critical Care at FDA on April 8^th and Biohaven was informed that the study may proceed immediately. Vazegepant is currently advancing to Phase 3 development for the acute treatment of migraine in adults under the Division of Neurology, having recently reported a successful end of Phase 2 clinical and nonclinical interaction with FDA.

Vlad Coric, M.D., Chief Executive Officer of Biohaven commented, “Given the unprecedented global threat to life that COVID-19 infection represents, there is an urgent need to test novel approaches to mitigating the consequences of the infection, including reducing the hyper-immune reaction that drives much of the morbidity and mortality in the pulmonary effects of this viral disease.” Dr. Coric added, “This pandemic is a call to action for our entire industry. I am grateful to our collaborators at the pulmonary institute at Thomas Jefferson and the team at Biohaven that moved so quickly to develop a clinical protocol and submit this IND to the FDA in the weeks after the pandemic first developed. We owe a debt of gratitude to the scientists at the NIH, FDA, academic centers and pharmaceutical companies who are working hard to study therapies that might battle this terrible disease -- the innovative efforts of the true unsung scientific heroes of this crisis will only be fully recognized once better treatments are developed to treat COVID-19.”

Jesse Roman, M.D., Professor, Jane & Leonard Korman Respiratory Institute - Jefferson Health and National Jewish Health, Thomas Jefferson University, and co-Principal Investigator in the proposed COVID-19 study commented, “Hospitals and our health care system are being overwhelmed by those patients who are progressing to serious COVID-19 infection. There is an urgent need to identify treatments that can mitigate the inflammatory process in these patients and help stabilize our response to the pandemic. It’s critical that we move quickly to test immune-modulating drugs like vazegepant and other agents as to assess if they can provide some benefit.”

Biohaven’s proposed clinical study of vazegepant is a Phase 2 double blind, randomized, placebo-controlled, safety and efficacy trial of intranasal vazegepant for COVID-19 infected hospitalized patients requiring supplemental oxygen. Data from the proposed study will allow characterization of the relative safety and efficacy of intranasal vazegpant versus placebo in the treatment of COVID-19 leading to hospitalization and the primary outcome measures will include pulmonary resolution of symptoms, or progression to ventilator support or death. The study will be overseen at Biohaven by Steven Schnittman, M.D., a seasoned infectious disease clinical researcher and pharmaceutical drug developer. Michael Baram, M.D., Thomas Jefferson University, Pulmonary Critical Care and Emergency Medicine, will be the Principal Investigator for the study.

Donnie McGrath, M.D., Chief of Corporate Strategy of Biohaven commented, “There is a solid scientific rationale supporting testing of small molecule CGRP-antagonists as a way to mitigate the neuro-immune consequences of respiratory viral infections like COVID-19. While the biology is complex and CGRP has pleotropic effects on the immune system, CGRP release as a result of viral activation of TRP channels is implicated in COVID-19 features such as cough, fever and pain, and the subsequent release of interleukin 6 (IL-6). IL-6 is an important mediator of inflammation that is elevated in the sickest of COVID-19 patients. In addition, CGRP may be involved in the polarization of the T cell response in some COVID-19 patients towards the pro-inflammatory state characterized by Th17 and IL-17 (see Figure).”

Acute lung injury is known to induce upregulation of transient receptor potential (TRP) channels which activates CGRP release contributing to acute lung injury (pulmonary edema with acute phase cytokine/mediator release, with immunologic milieu shift toward TH17 cytokines) followed by chronic lung injury with hyaline membrane formation, fibrosis and reduced diffusion capacity. Acute respiratory distress syndrome (ARDS), which is a common pathway resulting from diverse types of lung injury, is part of the pathogenic process that can occur after viral infections (see Figure). Because COVID-19 (SARS2) infection leads to an acute insult of pulmonary epithelia, it is hypothesized that a CGRP receptor antagonist may potentially blunt the severe inflammatory response at the alveolar level, delaying or reversing the path towards oxygen desaturation, ARDS, requirement for supplemental oxygenation, artificial ventilation or death.

Biohaven is also involved in COVID-19 antiviral therapy development through its investment and clinical operations support that it provides to Kleo Pharmaceuticals, Inc. Kleo Pharmaceuticals is an immune-focused, biotech company with a platform of small molecules that is working to create “synthetic vaccines” to redirect the patient’s own immune cells to attack viruses. Kleo Pharmaceuticals recently announced that it has entered into a research collaboration with South Korea-based Green Cross LabCell (GCLC), a pioneer in the next generation of allogeneic, or “off-the-shelf” natural killer (NK) cell therapies, to rapidly advance testing of both advanced technology platforms in combination as a potential therapy for COVID-19 patients.

About COVID-19
COVID-19 is a novel, highly contagious coronavirus that was first identified in December 2019. As of April 8, 2020,^, there are over 1.5 million confirmed cases worldwide, and over 420,000 cases in the US alone. Over 14,000 people in the US have died to date. The disease causes a respiratory illness (like the flu) with symptoms such as a cough, fever, loss of smell, and in more severe cases, difficulty breathing. The mainstay of clinical management is largely symptomatic treatment, with organ support in intensive care for seriously ill patients. There is evidence that progression to the most serious type of COVID-19 infection is related to a hyper-immune response.

About Vazegepant
Vazegepant is a third generation, high affinity, selective and structurally unique, small molecule CGRP receptor antagonist from Biohaven’s NOJECTION™ Migraine Platform and the only intranasal CGRP receptor antagonist in late stage development. The efficacy and safety profile of vazegepant for the acute treatment of migraine, as compared to placebo, was shown in a randomized controlled Phase 2/3 dose-ranging trial with a total of over 1000 patients who received vazegepant. More information about vazegepant can be found at the Biohaven’s website: https://www.biohavenpharma.com/science-pipeline/cgrp/bhv-3500

About Kleo Pharmaceuticals, Inc.
Kleo Pharmaceuticals is a unique immuno-oncology company developing next-generation bispecific compounds designed to emulate or enhance the activity of biologics based on the groundbreaking research of its scientific founder Dr. David Spiegel at Yale University. Similar to complex biologic drugs, Kleo’s compounds recruit the immune system to destroy cancer cells, with the advantage of being smaller and more versatile, leading to potentially improved safety and efficacy over biologics. They are also much faster and more efficient to design and produce, particularly against novel targets. Kleo is advancing several drug candidates based on its proprietary technology platforms, all of which are modular in design and enable rapid generation of novel immunotherapies that can be optimized against certain cancers, or enhance the properties of existing immunotherapies. These include ARMs™ Antibody Recruiting Molecules , MATEs™ Monoclonal Antibody Therapy Enhancers , and SyAMs™ Synthetic Antibody Mimics. Biohaven Pharmaceutical Holding Company (NYSE:BHVN) and PeptiDream Inc. (Nikkei: PPTDF) are investors in Kleo Pharmaceuticals. For more information visit http://kleopharmaceuticals.com.

About Biohaven
Biohaven is a biopharmaceutical company focused on the development and commercialization of innovative best-in-class therapies to improve the lives of patients with debilitating neurological and neuropsychiatric diseases. Biohaven’s neuroinnovation portfolio includes FDA-approved NURTEC™ ODT (rimegepant) for the acute treatment of migraine and a broad pipeline of late-stage product candidates across three distinct mechanistic platforms: CGRP receptor antagonism for the acute and preventive treatment of migraine; glutamate modulation for obsessive-compulsive disorder, Alzheimer’s disease, and spinocerebellar ataxia; and myeloperoxidase (MPO) inhibition for multiple system atrophy and amyotrophic lateral sclerosis. For more information, visit http://biohavenpharma.com.

Forward-looking Statement
This news release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. The use of certain words, including “may”, “advancing” and “will” and similar expressions, are intended to identify forward-looking statements. These forward-looking statements involve substantial risks and uncertainties, including statements that are based on the current expectations and assumptions of the Biohaven’s management about vazegepant as an acute treatment for patients with migraine or COVID-19. Forward-looking statements include those related to: the Biohaven’s ability to advance vazegepant to a Phase 3 clinical trial, complying with applicable U.S. regulatory requirements, the expected timing, commencement and outcomes of the Biohaven’s planned and ongoing clinical trials, the timing of planned interactions and filings with the FDA, the timing and outcome of expected regulatory filings, the potential commercialization of vazegepant and the Biohaven’s other product candidates, the potential for the Biohaven’s product candidates to be first in class or best in class therapies and the effectiveness and safety of the Biohaven’s product candidates. Various important factors could cause actual results or events to differ materially from those that may be expressed or implied by our forward-looking statements. Additional important factors to be considered in connection with forward-looking statements are described in the “Risk Factors” section of the Biohaven’s Annual Report on Form 10-K filed with the Securities and Exchange Commission on February 26, 2020. The forward-looking statements are made as of this date and the Biohaven does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

Biohaven Contact
Vlad Coric, M.D.
Chief Executive Officer
Vlad.Coric@biohavenpharma.com

Kleo Contact
Doug Manion, M.D.
Chief Executive Officer
dmanion@kleopharmaceuticals.com

NURTEC is a trademark of Biohaven Pharmaceutical Holding Company Ltd.

ARMs, MATEs and SyAMs are trademarks of Kleo Pharmaceuticals, Inc.

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SOURCE Biohaven Pharmaceutical Holding Company Ltd.