BioAge Labs (NASDAQ:BIOA) used its R&D Day event to provide an update on its lead program, BGE-102, an oral, brain-penetrant inhibitor of the NLRP3 inflammasome that the company is developing across cardiovascular and retinal disease. Management highlighted phase I clinical results, plans for near-term proof-of-concept studies, and the rationale for pursuing inflammation as a therapeutic target.
Company overview and focus on NLRP3
Chief Executive Officer and co-founder Kristen Fortney said BioAge is “harnessing the biology of human aging” to develop therapies for cardiometabolic diseases, built on longitudinal human aging datasets and supported by partnerships with Novartis and Lilly. Fortney positioned BGE-102 as a “pipeline-in-a-pill,” arguing that the program could deliver efficacy comparable to injectable anti-inflammatory drugs across multiple indications.
Structural biology: a novel binding site and selectivity
Matthias Geyer, founding director of the Institute of Structural Biology at the University of Bonn, described three features he said differentiate BGE-102 from other clinical-stage NLRP3 inhibitors. According to Geyer, BGE-102 binds at a site near a regulatory helix involved in membrane attachment, distinct from the hinge region associated with the MCC950 binding site targeted by other compounds.
Geyer said BioAge determined a cryo-EM structure of BGE binding to NLRP3 and described the compound as “gluing” the regulatory helix to inhibit its rotation. He also said the BGE-102 binding site is accessible across multiple NLRP3 conformations—resting, activated, and signaling-competent assemblies—suggesting the potential to target even hyperactive mutant forms. Finally, Geyer emphasized selectivity, noting differences in binding-site residues among related NOD-like receptors that could prevent binding to non-NLRP3 family members.
Phase I results: safety, PK/PD, hs-CRP and cytokine effects
Chief Medical Officer and EVP of Research Paul Rubin said the phase I program included dose escalation in healthy volunteers and obese participants, designed to evaluate pharmacokinetics, pharmacodynamics, and biomarkers including hs-CRP. The program included single ascending dose cohorts, multiple ascending dose cohorts in healthy volunteers, and obese multiple ascending dose cohorts with baseline CRP greater than 3 mg/L.
Rubin said the study met key objectives: “The drug was safe,” “well-tolerated,” and exhibited dose-proportional pharmacokinetics supportive of once-daily dosing. He reported that treatment-emergent adverse events were mild to moderate, self-limited, not dose-dependent, with no serious adverse events and no discontinuations due to adverse events. In the obese MAD cohorts, Rubin said BioAge did not observe neutropenia, thrombocytopenia, or infections.
On pharmacodynamics, Rubin said BGE-102 achieved greater than 90% IL-1β suppression for 24 hours after a single dose at both 60 mg and 120 mg, and that cerebrospinal fluid (CSF) levels measured by lumbar puncture exceeded the IC90 at both doses. He highlighted a reported Kp,uu,CSF of 0.7 and said this supported the potential to explore CNS-related inflammatory conditions.
In obese participants, Rubin said BioAge observed an 86% median hs-CRP reduction at both 60 mg and 120 mg relative to placebo. He said 87% of subjects at 60 mg and 93% at 120 mg achieved hs-CRP below 2 mg/L, and noted that 60%–71% were below 1 mg/L. Rubin also described IL-6 reductions in the obese cohort and said BGE-102 reduced fibrinogen by roughly 23%–30%.
Cardiovascular development strategy and the “residual inflammatory risk” thesis
Rubin said BioAge has increased the size of its planned phase IIa cardiovascular study to support dose selection and “enabling a phase III start by the end of next year.” The planned phase IIa proof-of-concept trial is designed to characterize the hs-CRP dose response with four arms: placebo, 30 mg, 60 mg, and 90 mg once daily, with 40 participants per arm and 12 weeks of treatment. The primary endpoint is percent change in hs-CRP, with key secondary endpoints including the proportion of patients normalized below 2 mg/L and below 1 mg/L.
External speaker Michael Davidson, professor and director of the Lipid Clinic at the University of Chicago Pritzker School of Medicine and CEO of New Amsterdam Pharma, argued that inflammation is causal in heart disease, pointing to CANTOS as a turning point. Davidson emphasized “residual inflammatory risk” as common and clinically meaningful, and said elevated CRP and IL-6 predict cardiovascular events and mortality across trials. He also described how upstream inhibition at NLRP3 could theoretically affect multiple downstream mediators beyond IL-6, including IL-18 and pyroptosis-related pathways.
Ophthalmology strategy: DME proof of concept and rationale for GA
Rubin outlined BioAge’s second focus area: retinal disease, where he argued oral therapy could reduce treatment burden relative to intraocular injections and potentially improve adherence. He said BGE-102 has demonstrated therapeutic retinal exposure across preclinical species including primates.
Rubin described BioAge’s DME proof-of-concept study as a translational pharmacodynamic trial designed to test whether oral BGE-102 can suppress intraocular IL-6, citing prior validation of anti-IL-6 approaches in DME. The three-arm trial will enroll 30 patients per arm: anti-VEGF plus oral placebo, anti-VEGF plus BGE-102, and sham plus BGE-102. The primary endpoint will be percent change in intraocular IL-6, with exploratory endpoints including additional biomarkers, best-corrected visual acuity (BCVA), and central subfield thickness, over eight weeks of treatment.
Yale ophthalmologist Brian Hafler said DME remains high burden despite anti-VEGF therapy, and highlighted aqueous humor studies showing elevated inflammatory markers such as IL-1β and IL-6 that correlate with anatomic disease measures. Hafler said an oral NLRP3 inhibitor could act upstream of multiple mediators and potentially complement anti-VEGF therapy. Retina specialist David Boyer added that real-world compliance challenges and persistent fluid in clinical trials leave room for new approaches, and said an effective oral agent could enable earlier treatment in patients who are currently observed.
On geographic atrophy, Boyer described complement inhibitors as reducing lesion growth but not improving vision and said the injection burden limits use. Hafler discussed preclinical and early human signals suggesting inflammasome biology could be relevant in GA, while noting clinical trials are needed to determine whether NLRP3 inhibition works better in DME or GA.
Fortney closed by outlining near-term catalysts, including initiation of a cardiovascular risk study expected to read out by the end of the year and a DME study expected to start mid-year and read out mid-next year. Chief Financial Officer Dov Goldstein said BioAge ended the first quarter with $385 million in cash, adding that the company is “very well financed” and has resources to run an additional phase II proof-of-concept study for BGE-102.
About BioAge Labs (NASDAQ:BIOA)
BioAge Labs (NASDAQ: BIOA) is a clinical-stage biotechnology company focused on discovering and developing therapies that address age-associated diseases. The company leverages its proprietary analytics platform to mine large-scale human biological data for insights into the molecular mechanisms of aging. By targeting fundamental aging pathways, BioAge aims to create interventions that extend healthspan and treat conditions that disproportionately affect older populations.
At the core of BioAge’s operations is its integrated drug discovery platform, which combines human omics datasets, machine learning algorithms and experimental validation to identify novel drug targets.
