Business

Avenue Therapeutics licenses ATX-04 clenbuterol from Duke University for Pompe disease treatment

Avenue Therapeutics, Inc. (OTC: ATXI), a Miami-headquartered specialty pharmaceutical company majority-owned by Fortress Biotech, Inc. (Nasdaq: FBIO),...

Avenue Therapeutics Licenses ATX-04 from Duke University for Pompe Disease

Avenue Therapeutics, Inc. (OTC: ATXI), a Miami-headquartered specialty pharmaceutical company majority-owned by Fortress Biotech, Inc. (Nasdaq: FBIO), announced an exclusive worldwide license agreement with Duke University, based in Durham, North Carolina, for patents and know-how related to Avenue Therapeutics ATX-04 (clenbuterol), a small-molecule selective β2-adrenergic agonist in clinical development for the treatment of Pompe disease. Under the agreement, Avenue acquires global rights to develop and commercialize products covered by Duke's intellectual property portfolio for ATX-04, including an existing Investigational New Drug (IND) application and a US FDA orphan drug designation for Pompe disease. The license also includes the option to expand development into other designated neuromuscular indications.

Financial specifics of the Avenue Therapeutics license agreement were not fully disclosed. Duke University will receive an upfront payment from Avenue, along with potential development, regulatory, and commercial milestone payments, plus royalties on net sales. The precise upfront amount, milestone totals, and royalty rates were not publicized in the announcement. No equity component or profit-sharing arrangement was described. Avenue will also assume control of Duke's existing clinical and regulatory assets for ATX-04, including the IND and orphan drug designation, which together reduce the regulatory burden associated with initiating late-stage clinical work.

Deal Context

ATX-04 Pompe Disease: Mechanism and Clinical Rationale

Pompe disease is a rare, inherited lysosomal storage disorder caused by deficiency of the enzyme acid α-glucosidase (GAA). The deficiency leads to accumulation of glycogen in muscle tissue, resulting in progressive skeletal and respiratory muscle weakness. The disease spans a clinical spectrum from severe infantile-onset forms to later-onset presentations characterized by gradual loss of ambulatory and respiratory function. Enzyme replacement therapy (ERT) with recombinant GAA is the current standard of care, but patients on ERT continue to experience residual disease burden, including ongoing muscle weakness and respiratory decline.

Clenbuterol, the active compound in ATX-04, is an orally administered selective β2-adrenergic agonist with established regulatory approvals outside the United States for respiratory indications. The drug's relevance to Pompe disease rests on two pharmacologic properties. First, β2-adrenergic agonist muscle function effects include well-documented anabolic activity on skeletal muscle, increasing protein synthesis and muscle fiber size. Second, clenbuterol has been shown to enhance lysosomal biogenesis and improve intracellular trafficking of GAA, the enzyme that is deficient in Pompe disease, leading to reduced glycogen accumulation in muscle tissue. These dual actions position ATX-04 as a potential mechanistic potentiator of enzyme replacement therapy Pompe patients already receive.

Human proof-of-concept data generated at Duke University, under the direction of principal investigator Dwight D. Koeberl, M.D., Ph.D., demonstrated that ATX-04 administered to Pompe disease patients on baseline ERT was associated with improvements in six-minute walk distance, increased respiratory muscle strength (including maximal inspiratory pressure), reductions in muscle glycogen burden assessed by biopsy, increased GAA activity with improved intracellular trafficking, and normalization of disease-relevant gene expression. The therapy was reported to be generally well tolerated with chronic, titrated dosing. Avenue has stated plans to advance ATX-04 through a late-stage clinical development program leveraging the existing human safety and efficacy dataset, with an initial focus on Pompe disease treatment as an adjunct to ERT.

Strategic Fit for Avenue Therapeutics

The ATX-04 license represents a continuation of Avenue's strategy of acquiring clinical-stage assets from academic and institutional sources for development in rare and neurologic diseases. The company's pipeline has historically centered on in-licensed programs. Avenue previously held rights to intravenous tramadol for acute pain management, licensed from Revogenex, and more recently in-licensed AJ201, a clinical-stage asset for spinal and bulbar muscular atrophy (SBMA/Kennedy's Disease), from AnnJi Pharmaceutical of Taiwan. The addition of ATX-04 extends Avenue's footprint in neuromuscular disease and adds a program with existing human clinical data, an active IND, and orphan drug designation, all of which reduce development risk relative to a preclinical or early-stage asset.

This is the first documented deal between Avenue Therapeutics (or its parent Fortress Biotech) and Duke University. Duke has previously licensed assets to other biopharma entities, including Precision BioSciences, ImmunoForge, and Seelos Therapeutics, and has entered into research partnerships with Danaher Corporation, but none of those arrangements involved Avenue or Fortress.

Avenue's financial position is a factor in evaluating execution risk. The company's SEC filings have noted substantial doubt about its ability to continue as a going concern, and the deal's milestone and royalty structure, rather than a large upfront payment, is consistent with the economics typically available to micro-cap licensees acquiring university IP.

The AllSci BriefSystematic R&D and deal news. Daily.

Pompe Disease Treatment Landscape and Competitive Activity

The Pompe disease treatment market has been shaped by the development and commercial trajectory of enzyme replacement therapies. Sanofi Genzyme's alglucosidase alfa (Lumizyme/Myozyme) was the first approved ERT, and the company subsequently developed avalglucosidase alfa (Nexviazyme), a next-generation ERT with enhanced mannose-6-phosphate receptor targeting designed to improve cellular uptake. Amicus Therapeutics received US FDA approval for cipaglucosidase alfa (Pombiliti) administered with miglustat (an enzyme stabilizer), representing a combination approach to improving ERT efficacy.

Beyond ERT, gene therapy has attracted licensing and development activity in Pompe disease. Spark Therapeutics (a Roche subsidiary) and Asklepios BioPharmaceutical (AskBio, acquired by Bayer) have both pursued AAV-based gene therapy approaches aimed at restoring endogenous GAA production. Sarepta Therapeutics has also been active in the neuromuscular gene therapy space, though its primary focus has been Duchenne muscular dystrophy rather than Pompe disease specifically.

The approach taken with ATX-04, using a β2-adrenergic agonist as an adjunct to ERT rather than as a standalone replacement for enzyme therapy, occupies a distinct niche. The concept of pharmacologic potentiation of ERT has been explored in academic settings but has not yet yielded an approved product. Chaperone therapy, as exemplified by the miglustat component of the Amicus regimen, represents a related but mechanistically distinct strategy for enhancing enzyme function.

Selected molecules in active clinical or commercial development for Pompe disease include:

  • Avalglucosidase alfa (Nexviazyme) — Sanofi Genzyme — approved ERT with enhanced cellular uptake
  • Cipaglucosidase alfa + miglustat (Pombiliti + Opfolda) — Amicus Therapeutics — approved ERT plus enzyme stabilizer combination
  • AT845 — Astellas (via Audentes Therapeutics acquisition) — AAV-based gene therapy, Phase I/II
  • SPK-3006 — Spark Therapeutics / Roche — AAV-based gene therapy for late-onset Pompe disease, Phase I/II

Licensing activity in the broader lysosomal storage disorder space has remained steady, driven by the orphan drug economics and relatively defined patient populations that characterize rare metabolic diseases. However, deals specifically targeting β2-adrenergic receptor agonism as a therapeutic modality in rare disease have been uncommon in public deal databases, reflecting the fact that most ADRB2 agonists are legacy molecules with generic availability for respiratory indications. The Avenue-Duke transaction is unusual in that it applies a well-characterized generic pharmacology to a rare disease context through a repurposing and clinical development strategy rather than novel molecule discovery.

The ATX-04 program's path forward will depend on Avenue's ability to fund and execute a late-stage clinical program, likely a registrational trial in Pompe disease patients on background ERT, leveraging the existing IND and orphan designation. The orphan drug designation, if maintained through approval, would provide seven years of US market exclusivity. Avenue has indicated plans to use the existing human data to inform trial design, though specific registrational timelines have not been disclosed.


Spot something wrong? Report an issue with this article