Aytu BioPharma Announces FDA Clearance of Investigational New Drug (IND) Application for AR101/Enzastaurin in Vascular Ehlers-Danlos Syndrome

Pivotal clinical trial will begin in first half of 2022

Aytu BioPharma, Inc. (Nasdaq: AYTU), a pharmaceutical company focused on commercializing novel therapeutics and consumer healthcare products, announced on December 13, 2021, that the U.S. Food and Drug Administration (FDA) has cleared the IND application for AR101/enzastaurin, enabling the company to proceed with initiating a pivotal clinical trial for AR101 in vascular Ehlers-Danlos Syndrome (VEDS). The company plans to initiate the PREVEnt Trial in VEDS in the first half of 2022. The PREVEnt Trial will assess the safety and efficacy of enzastaurin in COL3A1-confirmed individuals with VEDS. There are currently no FDA-approved therapies for VEDS.

“The FDA’s clearance of the AR101 IND is a significant milestone for VEDS patients and the rare disease community at large as we move one step closer to initiating the PREVEnt Trial,” said Josh Disbrow, chief executive officer of Aytu BioPharma. “This clearance enables us to initiate this important study in VEDS, a life-shortening genetic disease for which there is no approved treatment. The entire Aytu BioPharma team is committed to initiating this pivotal trial as quickly as possible. We thank our scientific advisory board and clinical and regulatory advisors in helping us get to this point so quickly. We’re now positioned to start the PREVEnt Trial in the first half of 2022 and look forward to taking that next step for the benefit of these patients in need of a new treatment for this catastrophic disease.”

About Vascular Ehlers-Danlos Syndrome (VEDS)

Vascular Ehlers Danlos Syndrome (VEDS) is a severe subtype of Ehlers-Danlos Syndrome, affecting 1 in 50,000 people worldwide and results from pathogenic variants in the COL3A1 gene, which encodes the chains of type III procollagen, a major protein in vessel walls and hollow organs. VEDS can be diagnosed in childhood and is characterized by arterial aneurysm, dissection and rupture, bowel rupture and rupture of the gravid uterus. Twenty-five percent of individuals with VEDS have a first complication by the age of 20 years, and more than eighty percent have at least one complication by the age of 40. VEDS is a devastating condition, and people with VEDS have a median lifespan of 51 years.

About AR101 (enzastaurin)

AR101 (enzastaurin) is an orally available investigational first-in-class small molecule, serine/threonine kinase inhibitor of the PKC beta, PI3K and AKT pathways. AR101 has been studied in more than 3,300 patients and over 50 clinical and pharmacological studies across a range of solid and hematological tumor types. Dr. Hal Dietz developed the first preclinical model that mimics the human condition and recapitulates VEDS. This knock-in model has the same genetic mutation most prevalent in people with VEDS and is representative of the human condition in both the timing and location of vascular events. The model has generated identical structural histology and mechanical characteristics, and unbiased findings demonstrated that structure alone does not lead to vascular events. Objective comparative transcriptional profiling by high-throughput RNA sequencing of the aorta displayed a molecular signature for excessive PKC/ERK cell signaling that is the driver of disease. PKC inhibition proved efficacious in multiple pre-clinical models and prevented death due to vascular rupture.

The U.S. Food and Drug Administration (FDA) has granted Orphan Drug designation to AR101 (enzastaurin) for the treatment of Ehlers-Danlos Syndrome. Treatment of vascular Ehlers-Danlos Syndrome (VEDS) is within the scope of this orphan drug designation.

About the PREVEnt Trial

The company expects to initiate the PREVEnt Trial in the first half of 2022 and enroll approximately 260 COL3A1-positive VEDS patients. The study will randomize patients 1:1, with half receiving enzastaurin 500 mg once daily along with standard of care and half receiving placebo once daily along with standard of care. The study’s primary endpoint is reduction in fatal and non-fatal arterial events (ruptures, dissections, pseudo-aneurysms).

For more information about the trial, and to get updates directly from Aytu BioPharma, visit PREVEntVEDSTrial.com and sign up for updates.