BioAge Labs Discontinues Lead Obesity Drug, Shifts Focus to NLRP3 Inhibitor Program

BioAge Labs, a California-based biotechnology company, has announced the termination of its lead obesity candidate, azelaprag, due to safety concerns. The company is now pivoting its focus to a preclinical neuroinflammation prospect, highlighting the risks and challenges inherent in drug development.

Azelaprag Development Halted Due to Liver Toxicity

BioAge Labs has ceased development of azelaprag, an oral apelin receptor agonist, following the discovery of liver-related side effects in a Phase II clinical trial. The company initially suspended the STRIDES trial in December 2024 after observing elevated liver enzymes in patients receiving the drug. Further investigation revealed that these adverse effects occurred without clear dose dependence, ultimately leading to the decision to discontinue the program.

This setback comes just months after BioAge's initial public offering (IPO) in September 2024, which raised approximately $238 million. The news has significantly impacted the company's stock price, which has fallen by 75% since the IPO, now trading at $5 per share compared to its initial $18.

Strategic Shift to NLRP3 Inhibitor Pipeline

With the termination of the azelaprag program, BioAge is redirecting its efforts towards its NLRP3 inhibitor pipeline. The company has nominated BGE-102, a brain-penetrant NLRP3 inhibitor, as its next development candidate. BioAge expects to release Phase I single-ascending dose data for BGE-102 by the end of 2025.

NLRP3 inhibition has been an active area of research in the pharmaceutical industry for the past decade, with several major players, including Bristol-Myers Squibb and Roche, pursuing this pathway for various indications. BioAge's CEO, Kristen Fortney, Ph.D., has expressed confidence in the company's NLRP3 inhibitors, claiming they are "an order of magnitude more potent than the competition."

The focus on NLRP3 inhibition is supported by longevity data linking the protein to accelerated cognitive aging and shorter lifespans. Additionally, BioAge has evidence suggesting that inhibiting NLRP3 could suppress appetite, potentially opening avenues for obesity treatment in the future.

Financial Outlook and Industry Partnerships

Despite the setback with azelaprag, BioAge maintains a strong financial position. The company's cash runway extends beyond 2029, providing ample resources to pursue its new strategic direction. Additionally, BioAge has a partnership with Novartis, worth $20 million upfront, to explore age-related pathways involved in metabolic diseases. This collaboration offers the potential for up to $530 million in milestone-based payments.

As BioAge navigates this transition, the pharmaceutical industry continues to watch closely, recognizing the inherent risks and potential rewards in the pursuit of innovative therapies for complex diseases such as obesity and neuroinflammation.