ATXI Avenue Therapeutics Inc

Avenue Therapeutics, Inc. (Nasdaq: ATXI) (“Avenue” or the “Company”), a specialty pharmaceutical company focused on the development and commercialization of therapies for the treatment of neurologic diseases, today announced that all patients have been enrolled in the Phase 1b/2a clinical trial of AJ201 for the treatment of spinal and bulbar muscular atrophy (“SBMA”), also known as Kennedy's Disease. AJ201 is currently the lead drug candidate in the clinic for SBMA, and topline data are anticipated in the second quarter of 2024.

“We are pleased with the speed of enrollment in our Phase 1b/2a study evaluating AJ201 for the treatment of SBMA, reflecting the large unmet need in this debilitating neurodegenerative disease,” said Alexandra MacLean, M.D., Chief Executive Officer of Avenue. “We are intently focused on advancing this much needed drug for patients and their caregivers, and we look forward to reporting topline data in the second quarter of 2024.”

The 12-week, multicenter, randomized, double-blind Phase 1b/2a clinical trial of AJ201 enrolled 25 patients, randomly assigned to AJ201 (600 mg/day) or placebo. The primary endpoint of the study is to assess safety and tolerability of AJ201 in subjects with clinically and genetically defined SBMA. Although the disease is slow in progression, limiting the potential to demonstrate clinical efficacy over 12 weeks, Avenue has included as secondary endpoints various biomarkers addressing proof of target engagement, which could reflect the likelihood of clinical success. These biomarkers include the pharmacodynamic data measuring change from baseline in mutant androgen receptor protein levels in skeletal muscle and changes in the fat and muscle composition as seen on MRI scans. Further details about this study can be found at ClinicalTrials.gov (Identifier: NCT05517603).

About Spinal and Bulbar Muscular Atrophy

Spinal and bulbar muscular atrophy (“SBMA”) is a rare, X-linked genetic neuromuscular disease primarily affecting men. The condition is caused by the trinucleotide CAG repeat expansion in the androgen receptor (“AR”) which leads to production of a mutant polyglutamine (“polyQ”) AR protein that forms aggregates responsible for muscular atrophy focused in the limbs and bulbar region of the body. The weakening of the bulbar muscles affects chewing, speech and swallowing, with patients prone to choking or inhaling foods or liquids, resulting in airway infection. SBMA also affects muscles in the limbs, leading to difficulty walking and injury caused by falling. Although there is a range of cited prevalence rates in scientific literature, a recent study used genetic analysis to estimate disease prevalence of 1:6,887 males.1 Currently, there are no treatments approved by the U.S. Food and Drug Administration or European Medicines Agency available for patients. For more information about SBMA, also known as Kennedy’s Disease, please visit https://kennedysdisease.org/.

About AJ201

AJ201 is a novel, first-in-class asset in development for the treatment of spinal and bulbar muscular atrophy. It was designed to modify SBMA through multiple mechanisms including degradation of the abnormal androgen receptor protein and by stimulating the Nrf1 and Nrf2 pathways, which are involved in protecting cells from oxidative stress which can lead to cell death. A first-in-human Phase 1 study of AJ201 in 72 healthy volunteers revealed an excellent safety and pharmacokinetic profile. It is currently being studied in a Phase 1/2a multicenter, randomized, double-blind clinical trial in six clinical sites across the U.S., which aims to evaluate the safety, PK/PD data and clinical response of AJ201 in patients suffering from SBMA. AJ201 has been granted Orphan Drug Designation by the FDA for multiple polyQ diseases, including SBMA, Huntington’s disease and spinocerebellar ataxia. Avenue exclusively licensed AJ201 from AnnJi Pharmaceuticals in the United States, Canada, European Union, Great Britain, and Israel.

About Polyglutamine diseases

Polyglutamine diseases are a group of neurodegenerative disorders caused by expanded CAG repeats encoding a long polyQ tract in the affected proteins. To date, a total of nine polyQ disorders have been described. Mutant protein aggregation in affected tissues is the pathological hallmark of polyQ diseases. Neuroinflammation, oxidative stress and dysregulated protein quality control are thought to be key pathological factors that are either direct results of mutant protein aggregations and/or exacerbate the severity and progression of the diseases. Modulating multiple cellular pathways in enhancing degradation of mutant AR aggregates, inducing antioxidant and heat shock responses, and increasing proteasome expression simultaneously provide the rationale to develop AJ201 for the treatment of SBMA and potentially other polyQ diseases.

About Avenue Therapeutics

Avenue Therapeutics, Inc. (Nasdaq: ATXI) is a specialty pharmaceutical company focused on the development and commercialization of therapies for the treatment of neurologic diseases. It is currently developing three assets including AJ201, a first-in-class asset for spinal and bulbar muscular atrophy, BAER-101, an oral small molecule selective GABAA α2/3 receptor positive allosteric modulator for CNS diseases, and IV tramadol, which is in Phase 3 clinical development for the management of acute postoperative pain in adults in a medically supervised healthcare setting. Avenue is headquartered in Miami, FL and was founded by Fortress Biotech, Inc. (Nasdaq: FBIO). For more information, visit www.avenuetx.com.

Forward-Looking Statements

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Contact:

Jaclyn JaffeAvenue Therapeutics, Inc. (781) 652-4500ir@avenuetx.com

1 M. Zanovello et al., Unexpected frequency of the pathogenic ARCAG repeat 2 expansion in the general population. Brain, 2023 Jul 3;146(7):2723-2729.