Biohaven Pharmaceutical announced 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 8th 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.

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,

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.

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.

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.

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