STIFEL 2026 HEALTHCARE CONFERENCE - BIOAGE LABS INC

Explicit Guidance:

• Financials: Cash balance of >$350 million as of the last quarter, sufficient to fund all current clinical activities, including QUEL-CV, QUEL-DME, an additional BG-102 indication, and APJ programs through proof-of-concept.
• Clinical Milestones:
  • QUEL-CV: Topline data expected by the end of the current year; dosing arms include 30 mg, 60 mg, and 90 mg QD (90 mg PK equivalent to the Phase 1 120 mg dose).
  • QUEL-DME: Topline data expected by the end of the next year; trial powered for a 4-letter improvement in visual acuity for monotherapy and combination arms.
  • APJ Programs: IND submission targeted by the end of the current year; first-in-human (FIH) clinical debut expected shortly thereafter (beginning of next year); next-generation oral and parenteral programs targeting IND submission.
• Additional Indications: Plans to announce an additional NLRP3 indication in the near future once development plans are fully solidified; no specific date or financial impact provided.

Business-Segment Outlook:

• Ophthalmology: Identified as the primary "beachhead" and anchor strategy for BG-102. Priority indications include Diabetic Macular Edema (DME) and Geographic Atrophy (GA), with additional potential focus on MSLE and UVE.
• DME Strategy: Targeting two specific cohorts: (1) the ~40% of patients in a "watch and wait" category with edema but no immediate vision compromise (seeking oral alternatives to injections), and (2) patients on VEGF therapy with incomplete disease control (refractory/high-inflammatory phenotype).
• Cardiometabolic (NLRP3): ASCVD/Atherosclerotic disease is currently "on pause" and "no longer a priority" for BioAge; however, preparatory CMC work remains for Phase 3 enablement to allow rapid response if future data (e.g., Artemis trial) supports the pathway.
• APJ Platform: Second strategic pillar focusing on longevity and physical function preservation; leveraging preclinical data showing doubled weight loss when combined with incretins and full preservation of muscle mass/quality in older bed-rest models.

Market and Competitive Outlook:

• Disease Mechanism: Positioning NLRP3 as a more upstream target than IL-6 (Roche's Mickey Bar), capturing a broader biological spectrum including IL-1 beta, IL-18, and pyroptosis.
• Competitive Differentiation: Emphasizes "best-in-class" oral NLRP3 profile with deep tissue penetration (CSF, retina) and distinct binding site compared to legacy ATPase-pocket inhibitors (e.g., Pfizer's MCC950).
• Patient Value Proposition: Aims to reduce treatment burden in ophthalmology by enabling oral administration and simultaneous bilateral eye treatment, addressing a disconnect between trial outcomes and real-world patient adherence.
• Data Interpretation: Views recent negative Zeus trial results as supporting upstream biology (NLRP3) rather than invalidating the target, citing the lack of subgroup signals in Zeus compared to the clear benefit seen with upstream IL-1 beta inhibition (CANTOS).

Macro / Industry Outlook:

• Regulatory/Market Drivers: Anticipates that reducing injection frequency in DME will unlock significant value for working-age patients (under 65) who currently avoid intravitreal therapy due to burden.
• Investment Climate: Management confidence in current cash runway mitigates near-term dilution risk, allowing focus on proving pharmacodynamics in high-value indications (ophthalmology) before expanding to broader cardiometabolic uses.
• Evidence Trends: Relies on preclinical models and early pilot data (e.g., Flamazon) to validate the anti-inflammatory hypothesis in GA, drawing parallels to established success in IL-6 and IL-1 beta pathways.

Strategic Initiatives:

• Indication Pivot: Explicitly shifting focus from ASCVD to ophthalmology and APJ-mediated metabolic preservation, effectively deprioritizing the cardiovascular program unless a "decisive win" occurs in future upstream trials.
• New Target Launch: Preparing for clinical debut of APJ programs (oral and parenteral) in early 202X following IND submission at the end of the current year.
• IP Protection: Extending IP portfolio to 2045 covering both specific structures and broad ligands interacting with the novel NLRP3 binding site.
• Data Generation: Utilizing QUEL-CV and QUEL-DME trials to interrogate systemic biomarkers (glucose control, kidney function) alongside ocular endpoints to demonstrate systemic cardiometabolic benefits.

Risks and Headwinds to Outlook:

• Clinical Success: QUEL-DME and APJ IND submissions carry execution risk; success depends on demonstrating statistically significant visual acuity improvement and safe dosing.
• Signal Ambiguity: Management remains skeptical that the ASCVD pathway is viable unless future trials (Artemis) show a "decisive" signal, noting skepticism that patient selection was the primary driver of Zeus's failure.
• Market Adoption: Potential resistance or slower enrollment if oral drugs fail to demonstrate clear superiority over established anti-VEGF therapies in the refractory patient population.
• Causality vs. Correlation: Acknowledges that while CRP is a strong PD marker, its role as a surrogate for hard cardiovascular clinical benefit is not definitively proven, as evidenced by the Zeus trial.

Management Tone on the Future:

• Confidence Level: High confidence in the biological differentiation of BG-102 (unique binding site, tissue distribution) and the strategic pivot to ophthalmology.
• Strategic Clarity: Decisive tone regarding the deprioritization of ASCVD; management views the ophthalmology program as the definitive near-term path to value creation.
• Hedging: Maintains openness to a potential "surprise" upside from the ASCVD pathway (Artemis trial) but explicitly states current operations are not dependent on this outcome.
• Financial Stability: Confident tone regarding liquidity, citing >$350M cash balance as sufficient to reach proof-of-concept milestones across all active programs without immediate external financing needs.

Miscellaneous:

• Target Engagement: BG-102 achieved 98% trough inhibition of IL-1 beta and 86% CRP reduction in Phase 1 obese/inflamed cohorts with placebo-like tolerability.
• Preclinical Validation: Oral BG-102 fully rescued retinal vascular permeability in diabetic models and prevented lipofuscin accumulation in naturally aged mouse models of GA.
• Trial Design Specifics: QUEL-CV will utilize MRI imaging of the liver to assess fat and inflammation, complementing the CRP primary endpoint.