BioAge Labs (NASDAQ:BIOA) executives outlined phase I results for its oral, brain-penetrant NLRP3 inhibitor BGE-102, highlighting what the company characterized as deep reductions in inflammatory biomarkers—particularly high-sensitivity C-reactive protein (hs-CRP)—alongside a tolerability profile management said supports accelerated development into phase II studies.
Phase I program design and key objectives
Chief Medical Officer Dr. Paul Rubin said the phase I program was structured as a comprehensive dose-escalation study that began in healthy volunteers and then expanded into obese participants, which the company described as more clinically relevant to future cardiometabolic indications because obesity is associated with elevated inflammation.
- Single ascending dose (SAD): 36 healthy volunteers plus nine obese subjects.
- Multiple ascending dose (MAD): 60 mg and 120 mg cohorts dosed for 14 days.
- Obese MAD: 60 mg dosed for 21 days and 120 mg for 14 days, totaling 41 subjects.
According to Rubin, objectives included characterizing pharmacokinetics (PK), pharmacodynamics (PD), and inflammatory biomarkers including hs-CRP, with the obese MAD cohorts designed to “mirror what phase II eligibility might be.”
Biomarker effects: hs-CRP, IL-1β, and IL-6
CEO and co-founder Dr. Kristen Fortney said the company is “very excited” about the phase I readout and pointed to “profound hs-CRP reductions with a well-tolerated once-daily oral dose,” which she said gave BioAge conviction to accelerate the program. Fortney described BGE-102 as an oral “pipeline-in-a-pill,” positioning it as potentially competitive with injectable anti-inflammatory therapies.
Rubin reported that in obese participants BioAge observed up to an 86% reduction in CRP at both 60 mg and 120 mg. He said 87% of subjects at 60 mg and 93% at 120 mg had CRP reduced to below 2 mg/L, a threshold the company emphasized repeatedly as clinically meaningful. Fortney said the two doses “were indistinguishable in terms of the CRP performance” in the phase I dataset, while acknowledging the sample sizes were small.
On PD, Rubin said BGE-102 produced potent suppression of IL-1β, the “key activity of the inflammasome.” In healthy-volunteer MAD cohorts, he said trough inhibition averaged about 90% at 60 mg and reached as high as 98% at 120 mg. Rubin also described IL-1β inhibition as reversible based on day-one kinetics, but by day eight the company observed “virtually complete inhibition across a full 24-hour period,” supporting once-daily dosing.
BioAge also discussed downstream effects on IL-6. Rubin said inhibiting NLRP3 should inhibit IL-1β and in turn reduce IL-6, and the phase I study showed IL-6 reductions of up to 70% to 78% at the tested doses. Fortney noted IL-6 and fibrinogen changes appeared less pronounced than hs-CRP in the small phase I cohorts and said variability would be easier to assess in larger studies.
Rubin also highlighted an effect on fibrinogen, calling it an independent predictor of cardiovascular risk, and said BGE-102 produced up to a 30% reduction.
Safety and tolerability
Management emphasized a clean phase I safety profile to date. Rubin said adverse events were mild to moderate, self-limited, and showed no dose dependency, with no dose-limiting toxicities, drug-related discontinuations, or serious adverse events. He reported treatment-emergent adverse event rates comparable between active and placebo groups (61% versus 59%) and said there were no clinically meaningful changes in vital signs, labs, or ECGs.
In obese MAD cohorts, Rubin said there were no severe treatment-emergent adverse events, no serious adverse events, and no treatment-related discontinuations. He added that BioAge did not observe neutropenia, thrombocytopenia, or infections—areas he said can be a “hypothetical concern” for agents that affect inflammatory pathways.
Asked about specific adverse events, Rubin said headaches were among the more commonly reported events, which he attributed largely to the lumbar punctures performed to assess cerebrospinal fluid (CSF) exposure. He said a cohort without lumbar punctures experienced fewer headaches, and Fortney said there were no dose-dependent differences.
Next steps: cardiovascular proof-of-concept and ophthalmology plans
Rubin said BioAge has increased the size of its planned cardiovascular phase IIa proof-of-concept (POC) study as part of a strategy aimed at enabling a phase III start by the end of next year. He described an intended four-arm study with 160 patients total (about 40 per group), testing placebo and 30 mg, 60 mg, and 90 mg once daily for 12 weeks. Eligibility will include BMI 30–42, baseline CRP greater than 3 mg/L, and at least one additional cardiovascular risk factor beyond obesity.
Rubin said the primary endpoint will be percent change in CRP, with secondary endpoints including normalization rates to below 2 mg/L and below 1 mg/L. Exploratory assessments will include Lp(a), fibrinogen, IL-6, MRI-based liver and total-body measures, metabolic parameters (glucose and insulin), and weight. In Q&A, Rubin confirmed that background cholesterol-lowering agents or antihypertensives would be allowed if stable, while GLP-1 drugs would not be permitted.
On the rationale for the 90 mg arm, Rubin said exposures achieved with 120 mg at day seven were equivalent to what 90 mg is expected to reach at steady state, suggesting similar maximal inhibition without needing the higher dose. Fortney said BioAge plans to carry forward both 60 mg and 90 mg to evaluate longer-term differentiation.
BioAge also reiterated plans to pursue a phase II ophthalmology study in diabetic macular edema (DME). Rubin said the DME proof-of-concept study is designed primarily to test whether oral BGE-102 can suppress intraocular IL-6, with three arms (30 per arm): anti-VEGF plus oral placebo, anti-VEGF plus oral BGE-102, and sham plus BGE-102 as monotherapy. The study will run eight weeks with follow-up, and visual acuity and central subfield thickness will be assessed as secondary and exploratory outcomes.
Fortney and Rubin also discussed CNS penetration as a differentiator. Rubin said CSF measurements showed drug levels above the IC90 at both 60 mg and 120 mg, and Fortney noted higher brain exposure at 120 mg could matter for future indications. However, the company said it has not yet announced a neurodegeneration program.
Fortney closed by pointing to what she described as a strong cash position and said BioAge is prioritizing indications with clear supporting data and a strong value proposition, with cardiovascular risk and ocular disease as current focus areas.
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.
