BioAge Labs, Inc. (BIOA) Business

Item 1. Business.

Overview

We are a clinical-stage biopharmaceutical company developing therapeutic product candidates for metabolic diseases by targeting the biology of human aging. Our technology platform and differentiated human datasets enable us to identify promising targets based on insights into molecular changes that drive aging.

In January 2025, we announced the nomination of our lead program, BGE-102, a potent, structurally novel, orally available, brain-penetrant small-molecule NLRP3 inhibitor. BGE-102 has a distinct mechanism and binding site from other NLRP3 inhibitors in development with issued patents covering both composition of matter and claims for the unique binding site.

In December 2025, we announced that BGE-102 was well-tolerated in Single Ascending Dose (SAD) and initial Multiple Ascending Dose (MAD) cohorts, with a pharmacokinetic profile supporting once-daily oral dosing, strong target engagement and high brain penetration.

We intend to advance BGE-102 in two therapeutic areas: cardiometabolic disease and ophthalmology.

Our first therapeutic area for BGE-102 is cardiometabolic disease, with a focus on atherosclerotic cardiovascular disease (ASCVD) risk reduction. Chronic systemic inflammation, as measured by high-sensitivity C-reactive protein (hsCRP), is an independent risk factor for cardiovascular events that is not adequately addressed by current lipid-lowering and antihypertensive therapies. In January 2026, we announced additional positive interim Phase 1 data, demonstrating potential for best-in-class hsCRP reduction in participants with elevated cardiovascular risk. In obese participants with elevated hsCRP, BGE-102 demonstrated an 86% median reduction in hsCRP at Day 14, with 93% of participants achieving hsCRP levels below 2 mg/L — the threshold associated with a 25% reduction in major adverse cardiovascular events. This level of hsCRP reduction is comparable to injectable anti-IL-6 monoclonal antibodies in clinical development for ASCVD, but achieved with once-daily oral dosing. We anticipate full Phase 1 SAD / MAD clinical trial results in the first half of 2026. We plan to initiate a Phase 2a proof-of-concept trial in patients with obesity and elevated hsCRP in the first half of 2026, with results anticipated by 2026 year end.

Our second therapeutic area for BGE-102 is ophthalmology. Diabetic macular edema (DME) is our first proof-of-concept indication in this area. DME affects approximately 1 million patients in the United States, and current intravitreal therapies face significant unmet need due to high injection burden and a substantial refractory population — approximately 45% of patients demonstrate refractoriness to anti-vascular endothelial growth factor (VEGF) therapy. In a preclinical model of DME, oral BGE-102 demonstrated dose-dependent preservation of retinal vascular integrity, achieving near-complete protection from vascular leakage and up to 90% preservation of microvascular integrity. We plan to initiate a Phase 1b/2a proof-of-concept trial in DME in mid-2026 with results anticipated in mid-2027. The goal is to demonstrate ocular target engagement, supporting future development across inflammation-driven retinal diseases.

Beyond NLRP3 inhibition, we are also developing novel apelin receptor APJ agonists for obesity, including programs targeting both oral and parenteral (subcutaneous) administration. In preclinical obesity models, APJ agonism has demonstrated the ability to more than double the weight loss induced by a glucagon-like peptide-1 receptor (GLP-1R) agonist while also restoring healthy body composition and improving muscle function. In June 2025, we announced an option agreement with JiKang Therapeutics for a novel APJ agonist antibody, as well as the filing of a U.S. provisional patent for novel small molecule APJ agonists. We intend to file the first Investigational New Drug applications (INDs) for an APJ program by 2026 year end.

We are also advancing earlier stage platform-derived programs in collaboration with Eli Lilly and Company (Lilly), and have an ongoing target discovery collaboration with Novartis Pharma AG (Novartis).

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Our approach: targeting human aging biology to treat chronic metabolic diseases

The burden of many serious and chronic diseases — including cardiovascular disease and diabetes — increases with age.

Age is a key risk factor for mortality from many chronic diseases in the United States, including cardiometabolic diseases like heart disease and diabetes. (Source: National Center for Health Statistics).

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However, there is substantial natural variation in the human population, resulting in a broad range of aging trajectories and outcomes, with some people experiencing much longer lifespans as well as delayed disease onset. We created our company to identify biological pathways associated with longer, healthier human lifespans and to develop pharmaceutical products that can modulate these pathways with the intent to prevent and reverse specific diseases, focusing on cardiometabolic diseases.

We capture a range of aging outcomes in our human aging cohorts, including functional and cognitive decline, disease incidence and mortality. In this example, deep, serial profiling of circulating proteins in these participants was used to understand the biology that drives these outcomes.

Our approach starts with human data. We examine the impact of the molecular changes that happen naturally as people age and study how these changes drive both functional decline (e.g., loss of muscle strength) and disease risk (e.g., obesity, insulin resistance, dyslipidemia, and hypertension). To develop new insights into the biological drivers of aging, we have generated proprietary longitudinal human datasets based on exclusive access to a unique resource: serial biobanked human samples coupled with health records and functional measurements collected for up to 50 years, capturing individual aging trajectories measured over several decades. We analyze these samples using state-of-the-art molecular profiling technologies,

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measuring thousands of biologically relevant molecules, and then apply computational tools to the resulting data to extract potential drivers of a long and healthy lifespan.

The BioAge platform encompasses over 150 million molecular data points spanning over 25 thousand individual participant profiles and over 50 years of follow-up.

We have selected chronic cardiometabolic diseases as our primary focus within age-related chronic diseases, given their high prevalence and resulting potential for impact on population health.

Prevalence of major cardiometabolic disease in the United States

Chronic cardiometabolic diseases also represent outsized commercial opportunities. For instance, according to third-party estimates, the global market for GLP-1R agonists, including those used to treat diabetes, is expected to grow to $150 billion by 2031.

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Our Pipeline

We are building a pipeline of platform-derived therapeutics targeting chronic cardiometabolic disease.

Our lead program is BGE-102, a potent, structurally novel, orally available, brain-penetrant small-molecule NLRP3 inhibitor. We expect to announce full Phase 1 SAD / MAD clinical trial results in the first half of 2026. We are initially developing BGE-102 for patients with cardiovascular risk factors and DME.

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For cardiovascular risk, we intend to initiate a dose-ranging Phase 2a proof-of-concept trial in the first half of 2026 in patients with obesity and elevated hsCRP. Approximately 160 patients will be randomized BGE-102 or placebo for 12 weeks. The primary endpoint is percent change in hsCRP. Results are anticipated by 2026 year end.

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For DME, we intend to initiate a Phase 1b/2a proof-of-concept trial in mid-2026 in patients with DME. Approximately 90 patients will be randomized across groups; BGE-102 will be assessed as an adjunctive therapy to intravitreal anti-VEGF treatment and as a monotherapy. The goal of the trial is to demonstrate target engagement in the eye. Results are anticipated in mid-2027.

We are also developing novel apelin receptor APJ agonists for obesity, including programs targeting both oral and parenteral (subcutaneous) administration. We intend to file the first IND for an APJ program by 2026 year end.

We are advancing several additional platform targets, currently in molecule discovery stage in collaboration with Lilly, which we believe have the potential to transform treatment of cardiometabolic disease. We plan to expand this pipeline over time, both internally and through our target discovery collaboration with Novartis.

Our portfolio of product candidates and ongoing collaborations are summarized in the figure below:

Our Team

We have assembled a leadership team of experts in aging biology and drug development. Our senior team consists of the following members:

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Kristen Fortney, Ph.D., our Chief Executive Officer and co-founder. Dr. Fortney has extensive experience in aging biology, genetics and bioinformatics and systems biology from her work at Stanford and the University of Toronto.

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Eric Morgen, M.D., our Chief Operating Officer and co-founder. Dr. Morgen was previously on the faculty at the University of Toronto, where his research focused on biomarker discovery and characterization in high-dimensional datasets from human cohorts.

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Dov Goldstein, M.D., our Chief Financial Officer. Dr. Goldstein previously served as Chief Financial Officer at Vicuron Pharmaceuticals Inc. and Loxo Oncology Inc., as well as a Managing Partner at Aisling Capital. He was most recently the Chief Financial Officer and Chief Business Officer of Indapta Therapeutics, Inc.

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Paul Rubin, M.D., our Chief Medical Officer. Dr. Rubin has over 35 years of experience in the biotechnology industry and has led 12 compounds to U.S. approval, with five led from discovery through approval, including Lunesta® and Xopenex®. He most recently served as Executive Vice President Research and Development at miRagen Therapeutics, Inc. and was previously Chief Medical Officer at XOMA Corporation and Executive Vice President Research and Development at Sepracor.

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Ann Neale, our Chief Development Officer. Ms. Neale has over 30 years of experience in the biotechnology industry. She was most recently Senior Vice President of Development Operations at Principia BioPharma Inc. (acquired by Sanofi S.A.), where she led operations and resourcing strategy for multiple global early- and late-phase clinical programs.

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Peng Leong, Ph.D., our Chief Business Officer. Dr. Leong has extensive experience in the biotech industry, previously serving in healthcare investment banking at Piper Jaffray and as Head of General Medicine Business Development at Merck KgaA and Chief Business Officer at Kazia Therapeutics Limited.

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BJ Sullivan, Ph.D., our Chief Strategy Officer. Dr. Sullivan was previously in L.E.K. Consulting’s life sciences practice, where he advised biopharma companies on growth strategy and M&A.

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George Hartman, Ph.D., our Senior Vice President, Chemistry. Dr. Hartman is a co-founder of Novira Therapeutics, Inc. and previously served as executive director of medicinal chemistry at Merck & Co., Inc. where he and his group identified and brought 12 drug candidates into Phase 2 or Phase 3 clinical trials.

Our Strategy

Our goal is to develop a focused portfolio of therapies for cardiometabolic disease by targeting the biology of human aging. Below is a summary of key product candidate and platform differentiation.

Our strategy is to:

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Apply novel insights into aging biology to build a pipeline of therapeutics to transform the treatment of chronic cardiometabolic diseases. Our platform provides unique insights into human aging biology spanning over 50 years. These insights enabled the identification of NLRP3 and apelin as targets. We also have several discovery-stage programs targeting this novel biology, which we will continue to advance through our ongoing collaborations with Lilly and Novartis. We plan to grow this pipeline over time, both internally and potentially through additional partnerships with pharmaceutical companies that have complementary datasets and capabilities.

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Efficiently advance our lead program, BGE-102, a potent, structurally novel, orally available, brain-penetrant small-molecule NLRP3 inhibitor in cardiometabolic disease and ophthalmology. BGE-102 has demonstrated potential best-in-class potency and efficacy in reducing hsCRP and other inflammatory markers in our Phase 1 trial. We plan to initiate a cardiovascular risk Phase 2a proof-of-concept trial in patients with obesity and elevated hsCRP in the first half of 2026 and expect to report results by 2026 year end. We are also pursuing diabetic macular edema as a second initial indication, with a Phase 1b/2a proof-of-concept trial planned to begin in mid-2026, with results anticipated in mid-2027.

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Advance both oral and parenteral apelin receptor APJ agonists as a novel exercise mimetic approach for the treatment of obesity. We believe that APJ agonism has the potential to transform the treatment of obesity by increasing weight loss quantity and quality, including improved body composition and tolerability.

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Selectively partner our product candidates to maximize patient impact and shareholder value. According to third-party estimates, the global market opportunity for cardiometabolic diseases is very large, with GLP-1Rs and incretins for obesity alone expected to grow to $150 billion by 2031. Given the resulting activity and investment of pharmaceutical companies in the therapeutic area, we may selectively partner our product candidates to accelerate the path to market in multiple large indications and maximize shareholder value.

BGE-102: a Potential Best-in-Class NLRP3 Inhibitor

NLRP3 and inflammation — a predictor of decreased longevity

NLRP3 is a component of a multi-protein complex referred to as the inflammasome, part of the innate immune system. Activation of the NLRP3 inflammasome leads to the secretion of inflammatory cytokines interleukin 1 beta (IL-1ß) and interleukin 18 (IL-18). However, NLRP3 can become hyperactivated in certain disease states, resulting in sustained cytokine release and chronic sterile inflammation.

NLRP3 dysregulation: in certain disease states, intrinsic stimuli like cellular stress and excess nutrients can result in NLRP3 hyperactivation, resulting in sustained cytokine cleavage and a chronic inflammatory state.

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We found that increased transcription of genes for NLRP3, IL-1ß, and IL-18 in our human aging cohorts was associated with significantly increased all-cause mortality risk. These findings align with human genetic evidence from Mendelian randomization studies, which demonstrate that a one standard deviation increase in NLRP3 expression is associated with up to a 70% increase in heart failure risk. Additionally, gain-of-function mutations in NLRP3 have been associated with reduced lean mass, impaired body composition, and accelerated atherosclerosis.

Consistent with our findings that NLRP3 can have detrimental effects on human longevity, previous studies have shown that genetic deletion of NLRP3 significantly extended mouse lifespan and also improved healthspan as measured by parameters such as muscle strength including muscle size and wire hang latency to fall, and cognitive function such as preserved contextual memory.

Levels of NLRP3-associated proteins (principal component) are inversely related to mortality risk in our human aging cohorts (left). Consistently, in a third-party preclinical study, knockout of the NLRP3 gene in mice significantly extends lifespan (n = 10 mice per group) (right). (Source: Marín-Aguilar et al. 2020).

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BGE-102, our lead program

BGE-102 is a potent, orally available, structurally novel, brain-penetrant small-molecule NLRP3 inhibitor discovered through screening of a HitGen DNA-encoded chemical library and optimized through structure-activity relationship studies. Through a collaboration with Dr. Matthias Geyer at the University of Bonn, we identified a binding site on NLRP3 that is distinct from previously described inhibitors, including the reference compound MCC950, as confirmed by cryo-electron microscopy. Unlike MCC950 and related inhibitors, which have been reported to inhibit NLRP3 ATPase activity, BGE-102 has not demonstrated ATPase inhibition in our in vitro assays, suggesting a fundamentally distinct mechanism that may offer advantages in specificity or side effect profile.

BGE-102 has been shown to exhibit robust potency and favorable pharmacokinetic properties. In human ex vivo whole blood stimulation assays, BGE-102 achieves an IC90 (the concentration at which 90% target engagement is achieved) of 1.8 nanomolar for IL-1β. At 60 mg once daily, mean trough plasma concentrations provide approximately 24-hour IC90 coverage and ≥90% suppression of IL-1β. The compound penetrates the central nervous system, with a mean brain-to-plasma concentration ratio (Kp,uuCSF) of approximately 0.7 measured after 14 days of 120 mg once-daily dosing, exceeding the estimated IC90 for IL-1β suppression in the central nervous system. The safety margin at the 60 mg dose, based on exposures at Day 14 in the healthy volunteer MAD cohort, ranges from 42-fold to 90-fold relative to the no-observed-adverse-effect level (NOAEL) in 3-month GLP toxicology studies.

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Our intellectual property portfolio includes composition of matter claims and claims covering the novel NLRP3 binding site, with patent protection extending through 2045 prior to patent term restoration.

Phase 1 clinical trial results

Trial design

We are conducting a Phase 1 clinical trial designed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of BGE-102 in both healthy volunteers and individuals with obesity. The entire study has been conducted in a clinical trial unit. The trial consisted of SAD cohorts, MAD cohorts in healthy volunteers, and ongoing MAD cohorts in obese participants with elevated baseline hsCRP.

BGE-102 has met key objectives to date. We anticipate completion of all Phase 1 cohorts and a full data readout in the first half of 2026.

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Safety profile and tolerability

In our Phase 1 trials, BGE-102 has been well tolerated across all completed cohorts. All adverse events observed to date have been mild to moderate in severity, self-limited in nature, and without apparent dose-dependency. We have observed no dose-limiting toxicities in any cohort.

Pharmacokinetics

Single dose pharmacokinetic studies demonstrated dose-proportional exposure across the 10 mg to 120 mg dose range, indicating linear pharmacokinetics within the studied dose range.

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Upon multiple daily dosing, BGE-102 exhibits accumulation with once-daily dosing. Trough plasma concentrations reached approximate steady state by Day 14 of dosing, where mean trough concentrations at both the 60 mg and 120 mg once-daily doses exceeded the human IL-1β IC90.

CNS Exposure

A key differentiator of BGE-102 is its demonstrated ability to cross the blood-brain barrier and achieve therapeutically meaningful concentrations in cerebrospinal fluid (CSF). On Day 14 of MAD dosing at 60 mg once daily, mean CSF concentrations of BGE-102 approximated the human IL-1β IC90. At the 120 mg dose, mean CSF concentrations exceeded the IC90.

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This CNS exposure differentiates BGE-102 from peripherally selective NLRP3 inhibitors and potentially enables BGE-102 to address neuroinflammatory indications.

Target engagement: IL-1β suppression

Ex vivo whole blood stimulation assays confirmed robust and sustained target engagement across all dosing cohorts. In the 60 mg MAD cohort, BGE-102 achieved 90% suppression of IL-1β at trough concentrations on Day 14. In the 120 mg MAD cohort in healthy volunteers, IL-1β suppression reached 98% at trough on Day 14.

Time-course pharmacodynamic data from the 120 mg cohort demonstrate that near-maximal IL-1β suppression was achieved by Day 7 and maintained throughout the entire 24-hour dosing interval, confirming sustained target engagement with once-daily dosing.

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Inflammatory biomarkers in obese subjects with elevated baseline hsCRP

In addition to healthy volunteers, we are conducting two additional MAD cohorts in obese patients with elevated baseline hsCRP. In these cohorts, we are evaluating circulating biomarkers of systemic inflammation. Results from the first cohort, 120 mg once daily, are reported here.

In the obese subjects, IL-1β suppression measured 93% at trough on Day 14, confirming that robust target engagement is also observed in subjects with elevated baseline hsCRP.

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In obese subjects, BGE-102 achieved a median reduction in hsCRP of 86% by Day 14. The effect was evident earlier, with a median 83% reduction already observed on Day 7, suggesting rapid anti-inflammatory activity.

Note: median values, error bars show IQR (Q1-Q3); median baseline hsCRP 4.85 mg/L for active treatment and 4.25 mg/L for placebo.

By Day 14, 93% of subjects receiving BGE-102 (13 of 14 subjects) achieved hsCRP levels below 2 mg/L. This threshold is clinically significant: in the landmark CANTOS trial (Canakinumab Anti-inflammatory Thrombosis Outcomes Study), participants who achieved on-treatment hsCRP below 2 mg/L experienced a 25% reduction in major adverse cardiovascular events (MACE; hazard ratio 0.75, p0.0001), while those who failed to achieve this threshold showed no significant benefit from anti-inflammatory therapy, establishing hsCRP normalization as a meaningful marker of therapeutic response. Furthermore, 71% of participants achieved hsCRP levels at or below 1 mg/L, a level associated with the lowest tertile of inflammatory risk in population studies.

Note: median baseline hsCRP 4.85 mg/L for active treatment and 4.25 mg/L for placebo.

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IL-6, a cytokine downstream of IL-1β signaling and a driver of hsCRP production, was also substantially reduced. At Day 7, BGE-102-treated subjects exhibited a median reduction in plasma IL-6 of 69%, compared to a 5% reduction in placebo recipients. By Day 14, the median IL-6 reduction in BGE-102 recipients was 58%, whereas placebo participants showed a 13% increase in IL-6 levels.

Note: measurements performed using the Alamar NULISA platform given higher sensitivity below 2.5 pg/mL; in the median values, error bars show IQR (Q1-Q3); median baseline IL-6 2.3 pg/mL for active treatment and 1.3 pg/mL for placebo.

Fibrinogen, another circulating biomarker of systemic inflammation and an independent risk factor for thrombotic events, was reduced by a median of 30% at Day 14 in BGE-102 recipients, compared to a 1% increase in placebo recipients.

Note: median values, error bars show IQR (Q1-Q3); median baseline fibrinogen 331 mg/dL for active treatment and 290 mg/dL for placebo.

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In two participants with elevated baseline CSF IL-6 (7 pg/mL), BGE-102 reduced CSF IL-6 levels by 84% at Day 14, with a corresponding 62% reduction in plasma IL-6. This finding demonstrates functional pharmacodynamic activity within the central nervous system and suggests that BGE-102 may have utility in neuroinflammatory conditions where NLRP3 activation contributes to pathology.

Note: *IL-6 levels 7 pg/mL in the CSF are considered elevated; corresponding decrease in the plasma was 62%; measurements performed using the Alamar NULISA platform.

Anticipated development milestones

We anticipate completion of the Phase 1 trial with a full data readout in the first half of 2026.

We subsequently intend to advance BGE-102 for both cardiometabolic disease and ophthalmology. In the first half of 2026, we plan to initiate a Phase 2a cardiovascular risk proof-of-concept trial in patients with obesity and elevated hsCRP, with results expected by 2026 year end. In mid-2026, we plan to initiate a Phase 1b/2a proof-of-concept trial in patients with DME, with results anticipated in mid-2027.

Atherosclerotic cardiovascular disease opportunity

Burden of cardiovascular disease and unmet need

Cardiovascular disease remains the leading cause of death globally, responsible for approximately 20 million deaths annually. Within the spectrum of cardiovascular disease, ASCVD represents a major and growing burden. ASCVD is characterized by the progressive accumulation of cholesterol-laden plaques within arterial walls. These atherosclerotic plaques are inherently unstable and may rupture, triggering thrombotic events that manifest clinically as myocardial infarction, ischemic stroke, or sudden cardiac death.

Current therapeutic management of ASCVD focuses primarily on lipid modification through statins, PCSK9 inhibitors, and related agents; blood pressure management through antihypertensive agents; and antiplatelet therapy with aspirin and P2Y12 inhibitors. These therapies have substantially reduced cardiovascular morbidity and mortality over the past several decades. However, despite the widespread use and optimization of these evidence-based therapies, substantial residual cardiovascular risk persists in treated populations.

This residual risk — affecting patients even after optimization of lipid and blood pressure targets — is increasingly attributed to chronic systemic inflammation, a pathway that current cardiovascular therapeutics do not adequately address. The resulting patient population with residual inflammatory risk is large and clinically important, currently lacking specific anti-inflammatory therapeutics in routine cardiovascular practice.

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Inflammation and high-sensitivity C-reactive protein as independent cardiovascular risk factors

A growing body of evidence supports inflammation as an independent driver of ASCVD. hsCRP, a circulating biomarker of systemic inflammation, has emerged as a robust predictor of cardiovascular risk that is independent of traditional lipid-based risk factors.

The Women's Health Study, a prospective cohort study of approximately 28,000 women followed for 30 years and published in the New England Journal of Medicine, provides compelling evidence for the independent predictive value of hsCRP. In this study, women in the highest quintile of baseline hsCRP had a 67% increased risk of major adverse cardiovascular events (MACE) — comprising myocardial infarction, ischemic stroke, and cardiovascular death — compared to women in the lowest quintile (hazard ratio 1.67). Notably, this risk gradient exceeded the risk gradient observed for low-density lipoprotein (LDL) cholesterol (hazard ratio 1.37) and lipoprotein(a) (hazard ratio 1.32), establishing hsCRP as a powerful cardiovascular risk predictor that may exceed traditional lipid-based risk factors.

Adapted from Ridker et al. 2024. Results for Fine-Gray model, adjusted for age and covariables.

Clinical validation that targeting inflammation can reduce cardiovascular events was provided by the CANTOS trial , a large, prospective, randomized controlled trial of canakinumab, a monoclonal antibody targeting IL-1β, a cytokine directly downstream of NLRP3, in patients with prior myocardial infarction and elevated hsCRP. In CANTOS, participants who achieved on-treatment hsCRP levels below 2 mg/L experienced a 25% reduction in major adverse cardiovascular events (hazard ratio 0.75, p0.0001) compared to those who did not achieve hsCRP normalization. Importantly, participants who failed to

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normalize hsCRP to below 2 mg/L showed no significant benefit from the active treatment, establishing hsCRP normalization as a meaningful therapeutic goal for reducing cardiovascular risk.

The magnitude of residual inflammatory risk is substantial. At any given LDL cholesterol level, patients with elevated hsCRP have increased cardiovascular risk. This observation underscores that inflammation contributes to cardiovascular risk independently of dyslipidemia and, moreover, additively increases risk when elevated LDL cholesterol and elevated hsCRP coexist.

NLRP3 inhibition as a cardiovascular target: mechanistic advantages over downstream cytokine inhibition.

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The NLRP3 inflammasome occupies a unique position within the inflammatory cascade relevant to cardiovascular disease, serving as a nodal point upstream of multiple inflammatory mediators implicated in atherosclerotic disease progression. Upon activation, NLRP3 triggers the secretion of IL-1β, which in turn drives the production of IL-6, which subsequently stimulates the hepatic production of hsCRP and fibrinogen. NLRP3 inhibition therefore targets the inflammatory cascade upstream of both IL-1β and IL-6, with the potential to suppress multiple downstream inflammatory pathways more comprehensively than selective targeting of any single cytokine.

Beyond its effects on IL-1β and the IL-6/hsCRP axis, NLRP3 inhibition offers potential mechanistic advantages that may prove clinically relevant. First, NLRP3 activation also drives the production of IL-18, an inflammatory cytokine that has emerged as an independent predictor of cardiovascular risk and that is not addressed by current anti-IL-6 or anti-IL-1β therapeutic approaches. In the CANTOS trial, patients in the highest tertile of baseline IL-18 had approximately 45% higher risk of cardiovascular death compared to patients in the lowest tertile (hazard ratio 1.44, P 0.0001; Ridker et al., European Heart Journal 2020), establishing IL-18 as an independent contributor to cardiovascular mortality. A therapy that suppresses both IL-18 and the IL-6/hsCRP axis through NLRP3 inhibition may therefore provide more comprehensive anti-inflammatory benefit than selective IL-6 or IL-1β blockade.

Second, NLRP3 inflammasome activation can trigger pyroptosis, a form of inflammatory cell death that releases intracellular contents and may contribute to atherosclerotic plaque destabilization. NLRP3 inhibitors can prevent pyroptosis, whereas anti-IL-6 and anti-IL-1β monoclonal antibodies do not address this mechanism. Pyroptosis inhibition may therefore represent an additional mechanism through which NLRP3 inhibition reduces cardiovascular risk.

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BGE-102's 86% median hsCRP reduction (obese participants with elevated baseline hsCRP, Day 14 of 120 mg QD dosing) is comparable to biologic approaches targeting the IL-1β and IL-6 pathways, and this effect was achieved with once-daily oral dosing rather than injectable administration.

The cardiovascular market opportunity

Cardiovascular risk reduction represents a substantial and growing therapeutic market. Approximately 25 million adults in the United States have a diagnosis of ASCVD, of whom approximately 60% — representing roughly 15 million individuals — have elevated hsCRP and may be candidates for anti-inflammatory therapy. The global market for lipid-lowering therapies is expected to reach approximately $50 billion by 2035, and an oral anti-inflammatory agent that reduces cardiovascular risk through a complementary mechanism could meaningfully expand the overall cardiovascular therapeutics market.

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The distinction between an oral small-molecule inhibitor and injectable biologic therapies may represent a substantial practical and commercial advantage. All anti-IL-6 inhibitors in cardiovascular development are injectable monoclonal antibodies, administered subcutaneously on a monthly or quarterly basis. In contrast, BGE-102 is an oral, once-daily small molecule. The vast majority of patients treated for cardiovascular risk receive their care in settings where oral medications are the standard modality. An oral once-daily anti-inflammatory agent may therefore enable broader adoption and prescribing across both cardiology and primary care. Additionally, an oral formulation creates potential for fixed-dose combination products with statins, PCSK9 inhibitors, and GLP-1 receptor agonists — combinations that may improve patient convenience and treatment adherence, which are critical considerations in chronic cardiovascular disease management.

Phase 2a proof-of-concept trial in cardiovascular risk

We plan to initiate a dose-ranging Phase 2a cardiovascular risk proof-of-concept trial of BGE-102 in patients with obesity and elevated hsCRP in the first half of 2026. This trial is designed to confirm and extend the hsCRP and inflammatory biomarker effects observed in our Phase 1 obese cohorts and to further characterize the safety and tolerability of BGE-102 over an extended treatment period.

The Phase 2a trial will be a double-blind, randomized, placebo-controlled study enrolling approximately 160 patients with a 12-week treatment period. The primary endpoint is percent change in hsCRP from baseline to Week 12. Results are anticipated by 2026 year end.

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Ophthalmology — Diabetic Macular Edema and Geographic Atrophy

Our second target therapeutic area for BGE-102 is ophthalmology. NLRP3 inflammasome activation sits at the center of multiple retinal diseases, including DME and geographic atrophy (GA), which are prevalent conditions with substantial unmet needs.

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BGE-102 possesses several characteristics that may differentiate it for retinal diseases: it is administered orally as a once-daily medication, eliminating the injection burden that limits long-term adherence with current intravitreal therapies and allowing simultaneous treatment of both eyes. We have demonstrated in preclinical studies across multiple species, including non-human primates, that BGE-102 achieves therapeutic concentrations in retinal tissue following oral administration. NLRP3 inhibition addresses both systemic and local drivers of retinal disease, and oral NLRP3 inhibition has the potential to have a broader effect than intravitreal anti-IL-6 approaches by sitting upstream in the inflammatory cascade while simultaneously addressing systemic disease drivers that local intravitreal therapies do not.

DME is our first proof-of-concept indication in ophthalmology.

Diabetic macular edema

Disease burden and unmet medical need. DME represents one of the leading causes of vision loss in the working-age population, affecting approximately 1 million patients in the United States. DME develops as hyperglycemia and associated systemic inflammation drive vascular leakage within the retina, impairing central vision and reducing quality of life. Approximately 70% of DME patients develop vision-threatening edema in both eyes within one year of diagnosis.

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Current standard-of-care therapies for DME rely predominantly on intravitreal anti-VEGF injections and intravitreal corticosteroid implants. These approaches face substantial clinical and practical limitations. Approximately 45% of DME patients demonstrate refractoriness to anti-VEGF therapy despite sustained treatment, suggesting that targeting a single effector molecule does not address the full pathophysiology of the disease. Adherence to the demanding injection regimen is challenging: approximately 50% of patients discontinue anti-VEGF injections after an average of six months, resulting in suboptimal real-world outcomes. Additionally, current ocular therapies do not address insulin resistance, a systemic metabolic factor that our analysis indicates is a key driver of DME.

NLRP3 inflammasome in DME. In DME, hyperglycemia and oxidative stress activate NLRP3. Release of IL-1β and IL-18 stimulates IL-6 production in retinal tissue, which in turn promotes VEGF expression and vascular leakage; this process is exacerbated by pyroptosis in endothelial cells, compromising microvascular integrity. NLRP3 thus represents a mechanistic bridge between systemic metabolic dysregulation in diabetes and local pathological vascular permeability in the retina.

Growing clinical evidence supports the anti-inflammatory strategy in retinal disease. Several programs have explored intravitreal anti-IL-6 therapies in DME; studies by Roche, Kodiak, and EyePoint have demonstrated that reducing IL-6 in the eye can produce rapid improvements in best-corrected visual acuity and central subfield thickness within four to eight weeks of treatment. We believe that oral NLRP3 inhibition has the potential to have a broader effect by sitting upstream in the inflammatory cascade, while simultaneously addressing systemic metabolic drivers.

Preclinical evidence for BGE-102 in DME. In a streptozotocin-induced diabetic mouse model, oral BGE-102 demonstrated dose-dependent preservation of retinal vascular permeability. Additionally, BGE-102 preserved blood-retina barrier tight junction proteins, including claudin-5.

In diet-induced obese mice, BGE-102 improved insulin sensitivity as measured by HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) to a degree comparable to semaglutide, a GLP-1 receptor agonist with well-established metabolic benefits. This improvement phenocopies the metabolic phenotype of Nlrp3-knockout mice (Vandanmagsar et al.

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2011) and provides evidence that BGE-102 has the potential to address the key driver of DME that current intravitreal therapies do not.

Phase 1b/2a proof-of-concept trial in DME

We plan to initiate a Phase 1b/2a proof-of-concept trial of BGE-102 in patients with DME in mid-2026. The trial is designed to demonstrate pharmacodynamic activity of BGE-102 in the eye following oral administration and to evaluate its potential as an adjunctive therapy to anti-VEGF treatment and as a monotherapy.

The trial will be a randomized study with an 8-week treatment period. The primary endpoint is percent change in intraocular IL-6. We anticipate preliminary results in mid-2027.

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Geographic atrophy

Disease burden and unmet medical need. Geographic atrophy (GA), the advanced dry form of age-related macular degeneration (AMD), affects approximately 1.2 million patients in the United States. GA is characterized by progressive degeneration of the retinal pigment epithelium (RPE) and photoreceptors, resulting in irreversible loss of central vision. The disease progression is severe: approximately 20% of patients become legally blind within one year of diagnosis, significantly limiting independence and quality of life in an aging population.

Recent approvals of intravitreal complement inhibitors, including pegcetacoplan (Syfovre) and avacincaptad pegol (Izervay), have provided the first disease-modifying treatments for GA. However, their clinical efficacy is modest, slowing lesion growth by approximately 15% to 20% in treated eyes. Given this limited benefit relative to the burden of frequent intravitreal injections, approximately 90% of GA patients remain untreated. We believe there is substantial unmet need for oral therapies offering improved efficacy, simpler administration, and broader mechanistic activity.

NLRP3 inflammasome in GA. In GA, progressive accumulation of cellular debris (e.g. drusen, lipofuscin), along with Alu RNA, activates NLRP3 in RPE cells and resident microglia. Chronic inflammasome activation and resulting pyroptosis contribute to progressive RPE degeneration and secondary photoreceptor loss.

Systemic inflammation is increasingly recognized as a risk factor for GA progression: elevated circulating inflammatory markers, including hsCRP and IL-6, have been associated with increased risk of AMD progression in epidemiological studies. As a result, systemic NLRP3 inhibition may offer advantages over regional intravitreal approaches.

Emerging clinical and preclinical evidence. Published preclinical studies support the relevance of NLRP3 to GA. In third-party studies, Nlrp3-knockout mice were completely protected against RPE degeneration induced by both drusen-associated pathogenic stimuli (amyloid-β oligomers) and endosomal damage caused by Alu RNA.

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Adapted from Narendran et al. 2021 and Tarallo et al. 2012

In a natural aging model of AMD, oral administration of a BGE-102 analog almost completely prevented age-related lipofuscin accumulation, a cardinal feature of GA progression. These findings support the therapeutic hypothesis that NLRP3 inhibition may slow or arrest GA progression.

Clinical evidence further supports inflammasome inhibition in GA. A third-party clinical study of an inflammasome inhibitor (K8, an intravitreal implant, N=10) demonstrated a 53% reduction in GA lesion growth at three months (p=0.03 compared to fellow eye), substantially exceeding the approximately 15% reduction observed with approved complement inhibitors at 12 months. In a supporting epidemiological analysis, chronic exposure to fluoxetine, a compound with weak NLRP3 inhibitory activity at micromolar concentrations, was associated with a 22% reduction in incident AMD (hazard ratio 0.778, p0.001). While these epidemiological data are exploratory, this observation is consistent with the hypothesis that NLRP3 inhibition may slow progression of AMD/GA.

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Right panel adapted from Ambati et al. 2021

Apelin Receptor APJ Agonists: An Exercise Mimetic Approach for the Treatment of Obesity and Metabolic Disease

We are developing novel, potent agonists of the apelin receptor APJ, including both oral small-molecule and parenteral programs. Apelin is a molecule that is secreted in response to exercise, and activation of the apelin pathway has been shown to recapitulate many of the benefits of exercise. We have previously shown that the agonism of the apelin receptor APJ has the potential to double weight loss and fully restore body composition on a GLP-1R agonist background in preclinical models of obesity. We believe the combination of an APJ agonist and an incretin is a pharmacological parallel to diet and exercise: one mechanism relies largely on reducing energy intake, the other on increasing energy expenditure.

Levels of the exercise-secreted protein apelin predicted both function and metabolic health in our longitudinal human aging cohorts.

The aging process is characterized by profound dysregulation in many biological systems. Examining protein changes over decades in our longitudinal human aging cohorts, we observed that higher levels of circulating apelin were associated with both increased longevity and preservation of physical function (i.e., subjects with higher apelin levels lived longer, with improved health). We also observed that apelin levels are significantly associated with a range of metabolic traits in our human aging cohorts. These results led us to the therapeutic hypothesis that augmenting apelin signaling could provide therapeutic benefits in age-related disease.

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Higher apelin protein levels predicted improved longevity and grip strength in our human aging cohorts (left). Levels were also associated with traits related to muscle function, adiposity, glucose control, and longevity (right). Glucose and insulin control measure the ability to regulate blood glucose increases via insulin secretion after a glucose challenge.

Enhancing apelin signaling can recapitulate many of the benefits of exercise

Apelin is a peptide hormone referred to as an exerkine, a signaling molecule released by skeletal muscle in response to exercise that mediates beneficial metabolic and functional adaptations to physical activity.

Comparing the physiological effects of enhanced apelin signaling to those of exercise reveals multiple areas of overlap:

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Both apelin and exercise have a beneficial effect on body composition, improving the ratio of lean to fat mass. The proportion of lean mass is a very strong predictor of functional capacity, metabolic health, and cardiovascular outcomes (and more predictive than absolute lean mass or absolute fat mass).

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In skeletal muscle, both apelin signaling and exercise boost protein synthesis, mitochondrial biogenesis and basal metabolic rate, thereby increasing resting energy expenditure.

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In both muscle and adipose tissue, apelin and exercise increase insulin sensitivity, resulting in upregulation of glucose uptake and metabolism.

This striking congruence between the actions of apelin and exercise suggests that this peptide acts as a key molecular transducer of the systemic exercise response, and that targeting the apelin/APJ axis may be able to mimic many of the benefits of physical activity sometimes referred to as “exercise in a pill.”

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Exercise ameliorates many of the negative health outcomes associated with aging. Circulating apelin levels increase acutely after exercise, with the magnitude of this response strongly predicting physical performance in older adults.

In a third-party preclinical study, apelin levels were significantly correlated with the benefits of exercise over 6 months. Older people ( 70y) with the greatest increase in plasma apelin levels after 6 months of an exercise program had the highest improvement in Short Physical Performance Battery (SPPB) test score. Apelin measurements were taken from 34 individuals. r2 represents the correlation coefficient, a statistical measure of the strength of a linear relationship between two variables. A correlation coefficient of -1 describes a perfect negative, or inverse, correlation. A coefficient of 1 shows a perfect positive correlation, or a direct relationship. A correlation coefficient of 0 means there is no linear relationship. The p-value is used to determine the probability as to whether the difference between two data sets is due to chance. The smaller the p-value, the more likely the differences are not due to chance alone. In general, if the p-value is less than or equal to 0.05, the outcome is considered statistically significant. (Source: Vinel et al. 2018).

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However, both basal levels of apelin and the degree of exercise-induced elevation of the peptide decline with age, coinciding with deterioration of fitness and muscle function.

In a third-party preclinical study, apelin expression in mice significantly decreased with age (n= 6 mice per group). There was also a lower magnitude increase in apelin expression in response to exercise with age, with no significant increase observed in the 24 month group. In mice, 12 months represents middle age and 24 months old age. #p 0.05; *p 0.05; ** p 0.01. (Source: Vinel et al. 2018).

The relationship between apelin, exercise and function over the lifespan, taken together with the correlation between apelin levels and muscle-related health parameters observed in our longitudinal cohorts, suggest that apelin may help mediate the beneficial anti-aging effects of exercise.

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Apelin activates key metabolic regulators AMPK, PI3K, and ERK

The molecular mechanisms of apelin pathway signaling are well characterized. As depicted in the figure below, the physiological effects of apelin in target cells are mediated by the apelin receptor (APJ/APLNR), a G protein-coupled receptor that activates multiple intracellular signaling pathways including AMP-activated protein kinase (AMPK) and PI3K. In parallel, via recruitment of ß-arrestin upon apelin binding, APJ activates extracellular signal regulated kinase (ERK). These pathways are involved in metabolic processes consistent with apelin’s role as an exerkine, including glucose uptake, mitochondrial biogenesis, and fatty acid oxidation.

APJ is a G protein-coupled receptor that signals through AMPK and PI3K. AMPK and PI3K activate downstream effectors Akt and endothelial nitric oxide synthase (eNOS), which increase cellular glucose uptake. AMPK activates transcriptional coactivator PGC-1a, which increases mitochondrial biogenesis. AMPK directly increases fatty acid oxidation. APJ also activates ERK signaling through ß-arrestin. (Source: Bertrand et al. 2015).

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Genetic evidence supports the potential of APJ agonists to improve metabolism

Genetic studies of apelin in mice published by other groups provide support for the potential role of APJ agonists in the treatment of obesity. Inactivation of the gene for apelin was shown to result in mice with a statistically significant increase in fat content compared to similarly treated wild-type mice. Apelin knockout mice fed a high fat diet for three weeks also had significantly decreased insulin sensitivity compared to similarly treated wild-type mice.

In a third-party preclinical study, inactivation of the gene for apelin (APKO) in mice led to a significant increase in fat content compared to wild-type counterparts (p0.05) (n =10–15 mice per group). In a separate third-party preclinical study, APKO mice had significantly worse performance on an insulin tolerance test (p0.01) (n= 6 –7 mice per group). (Source: Yue et al. 2010, Yue et al. 2011).

In contrast, transgenic mice with overexpressed apelin showed several metabolic benefits. Animals were significantly protected from weight gain when placed on a high fat diet. This was not due to a decrease in food intake, but instead to an increased metabolic rate. Consistent with apelin’s role as an exerkine, transgenic apelin mice also had increased skeletal muscle mitochondrial biogenesis and increased oxygen intake compared to wild-type counterparts.

In a third-party preclinical study, overexpression of apelin in a transgenic mouse (Tg) resulted in significantly reduced weight when fed a high fat diet compared to wild-type control mice (Cont) (p0.001) (n= 19–24 mice per group). Tg mice had a significantly higher basal metabolic rate than their wild-type counterparts on a high fat diet (p0.01) (n= 7-9 mice per group) with no significant difference in food intake (n= 19–24 mice per group). (Source: Yamamoto et al. 2011).

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Human genetics are consistent with findings in interventional genetic studies in mice. Significant genome-wide associations have been reported at the apelin receptor, APJ, and body mass index, lean body mass and serum lipid levels across diverse populations.

Preclinical results in a diet-induced obesity mouse model demonstrate the potential of apelin receptor APJ agonists to increase weight loss quantity and quality

We evaluated the effects of an investigational oral small molecule APJ agonist, azelaprag, on weight loss and other outcomes in a diet-induced obesity mouse model.

Azelaprag, in combination with tirzepatide, restored body weight and body composition of obese mice to lean control levels. Tirzepatide monotherapy led to a reduction in body weight of approximately 15% at the dose tested. The addition of azelaprag to tirzepatide treatment led to further significant, dose-dependent decreases in body weight, with 40% weight reduction by three weeks in the highest dose group.

In addition to correcting total weight back to lean control levels, the addition of azelaprag in combination with tirzepatide also restored the body composition of obese mice to that of lean controls in a significant, dose-dependent fashion. The proportion of lean body mass increased while that of fat decreased over the three-week dosing period.

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In the context of clinical care, body composition — and specifically the proportion of lean mass — is highly predictive of multiple health outcomes including physical function, metabolic health and cardiovascular outcomes (and more predictive than absolute levels of lean or fat mass).

The combination of azelaprag and tirzepatide resulted in significant, dose-dependent increases in overall weight loss compared to tirzepatide monotherapy in diet-induced obesity mouse model (left), as well as full restoration of body composition (% lean, % fat, lean / fat ratio) of obese mice to that of lean controls (middle, right). Lean and fat mass were measured by EchoMRI. Group size: n=6-14 per group. Tirzepatide (10nmol/kg) vs. tirzepatide (10nmol/kg) + azelaprag (1.1g/l) on day 20: p0.0001 for all measurements.

Clinical Case Study: azelaprag results demonstrate the potential of apelin receptor APJ agonists to function as an exerkine mimetic to improve body composition and metabolism

We completed a double-blind, non-randomized Phase 1b bed rest atrophy trial of apelin receptor APJ agonist, azelaprag, in 21 healthy individuals 65 years of age or older. Bed rest studies are a well-established method to model muscle and functional aging on a compressed timeline. In the trial, subjects on bed rest for 10 days received daily doses of 240 mg azelaprag or placebo delivered by intravenous infusion.

We observed that treatment with azelaprag significantly decreased (p0.05) bed-rest-induced muscle atrophy across multiple endpoints as shown in the figure below.

Overview endpoints and significance of results from the azelaprag bed rest atrophy Phase 1b trial. Thigh circumference results are shown as an example at right: 10 days of bed rest led to a mean decrease of 6.4% in thigh circumference in subjects that received placebo. By contrast, we observed no significant decrease in thigh circumference in subjects dosed with azelaprag.

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In January 2025, we terminated development of azelaprag, an orally available small molecule agonist of APJ, for obesity and other chronic diseases. The decision followed observations of liver transaminitis without clinically significant symptoms, and without clear dose dependence, in some patients in the azelaprag arms of the STRIDES Phase 2 clinical trial for obesity.

However, we believe the results of the azelaprag Phase 1 trials demonstrate the potential of apelin receptor APJ agonists; therefore, we are advancing distinct, orally available apelin receptor APJ agonists as a novel exercise mimetic approach for the treatment of obesity.

Development strategy and timelines

We are advancing APJ agonists through both oral and parenteral development pathways to maximize the potential of this therapeutic approach across different clinical contexts and patient populations.

Oral APJ agonist program. We have filed composition of matter intellectual property protecting novel small molecule APJ agonists with picomolar potency. These compounds are based on an innovative chemical scaffold and achieve agonist potency comparable to native apelin-13, the endogenous ligand. We intend to characterize these compounds further and advance the most promising candidate toward IND-enabling studies.

Parenteral APJ agonist program. In June 2025, we announced an option agreement with JiKang Therapeutics for a novel APJ agonist nanobody — a single-domain antibody derived from camelid immunoglobulin. The nanobody demonstrates approximately 10-fold greater agonist potency than native apelin and is optimized for subcutaneous administration, providing a longer-acting modality suitable for chronic obesity treatment. We are conducting preclinical characterization and advancing this program toward IND-enabling studies.

We intend to file the first IND for an APJ program by the end of 2026.

The evolving obesity treatment landscape

Obesity disease overview: a growing driver of both morbidity and healthcare spending

Obesity is a complex medical disorder that has been described as an accelerated aging condition, as it increases the risk of both morbidity and mortality from age-related chronic disease. It involves both appetite dysregulation and altered lipid and energy metabolism, which in turn result in excessive accumulation of fat tissue. Globally, over 875 million adults age 20+ are living with obesity, defined as a body mass index (BMI) of 30 or greater. Furthermore, the worldwide prevalence of obesity in

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adults 20+ more than doubled from under 7% in 1990 to over 16% in 2022. The global estimated cost of overweight and obesity is in the trillions of dollars, representing more than 2% of the global gross domestic product.

Obesity is associated with over 200 health comorbidities and complications, including many cardiometabolic disorders. Among obese patients, the prevalence of these conditions is high: 19-23% have type 2 diabetes, dyslipidemia (66-70%), hypertension (51-61%), metabolic dysfunction-associated steatohepatitis (30-36%), and heart disease (3-5% congestive heart failure, 8% ischemic heart disease, 21% myocardial infarction). Obesity is also associated with an increased risk of developing infertility and certain cancers. Weight loss leads to improvements across many comorbidities associated with obesity.

Obesity treatment landscape: incretin drugs are transforming care, creating an important clinical and commercial opportunity

The treatment landscape for obesity has undergone a fundamental transformation with the emergence of GLP-1R agonists. Injectable GLP-1R agonists, including semaglutide (Wegovy) and tirzepatide (Zepbound), have demonstrated unprecedented efficacy in achieving sustained weight loss and improving cardiometabolic risk factors. In pivotal clinical trials, injectable semaglutide produced approximately 15% weight loss; tirzepatide, a dual GLP-1R/GIP receptor agonist, produced approximately 21% weight loss.

The commercial success of injectable GLP-1R agonists has been significant. The global market for GLP-1R agonists is projected to exceed $150 billion by 2031, driven by expanding indications beyond obesity and diabetes, new oral and combination formulations, and increasing treatment penetration across broader patient populations. The scale of this market reflects both the severity of the underlying unmet need and the magnitude of the commercial opportunity for therapies that can

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address the limitations of current incretin-based approaches — limitations that we believe APJ agonism is well positioned to complement.

Key unmet needs

Despite the advances represented by GLP-1R agonist therapy, substantial unmet medical needs persist in obesity treatment. These unmet needs span three critical dimensions: oral efficacy parity with injectables, gastrointestinal tolerability, and preservation of body composition during weight loss. Current therapeutic approaches address only a subset of these needs, leaving significant therapeutic gaps.

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Oral weight loss. Oral GLP-1R agonist programs have generally underperformed relative to injectable formulations. Oral approaches employing permeation enhancers and structural modifications have achieved weight loss in the range of 7% to 12%, substantially lower than the 15% to 24% weight loss achieved by injectable GLP-1R agonists and triple agonists. This efficacy gap — representing approximately a 50% reduction in weight loss from injectable to oral formulation — limits the clinical utility of oral approaches as monotherapy and reflects fundamental challenges in achieving adequate intestinal permeability and systemic bioavailability of peptide-based GLP-1R agonists via the oral route.

Tolerability. Gastrointestinal side effects represent a substantial barrier to tolerability and adherence with incretin-based obesity therapeutics. In Phase 2 and Phase 3 clinical trials, gastrointestinal adverse events — including nausea, vomiting, constipation, and diarrhea — occur in 31% to 44% of patients treated with injectable incretin agonists and in 58% to 87% of patients treated with oral incretin programs. These side effects are dose-dependent and frequently motivate dose reductions or treatment discontinuation. In controlled clinical trials, discontinuation due to adverse events reaches approximately 17%, and real-world discontinuation rates are substantially higher, with some analyses indicating discontinuation in up to 68% of patients. The tolerability barrier thus represents a major impediment to treatment initiation, dose escalation, and treatment persistence in a substantial proportion of patients with obesity.

Body composition. A fundamental limitation of current obesity therapeutics, including GLP-1R agonists, is that weight loss achieved through appetite suppression is not accompanied by preferential loss of adipose tissue. Rather, a substantial proportion of weight loss represents loss of lean muscle mass. Clinical data indicate that up to 50% of weight lost during GLP-1R agonist treatment may comprise lean body mass rather than adipose tissue.

The loss of lean mass during weight loss carries profound physiological consequences. Lean mass, primarily skeletal muscle, is the principal contributor to basal metabolic rate — the energy expenditure required at rest to maintain basic cellular and organ function. When lean mass is lost disproportionately during weight loss, basal metabolic rate decreases, reducing daily energy expenditure. This metabolic adaptation creates a disadvantage: the patient, now at a lower body weight, has a substantially reduced caloric requirement and is thus more susceptible to weight regain even when consuming the same number of calories that previously maintained the lower weight. Furthermore, loss of lean mass increases frailty risk, impairs physical function, and may accelerate age-related physical decline, particularly in older adults with obesity.

A particularly concerning manifestation of lean mass loss during weight loss therapy is increased bone fragility and fracture risk. In the SELECT trial (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity), a large randomized controlled trial of semaglutide in patients with obesity and established cardiovascular disease, an approximately 5-fold increase in hip and pelvis fractures was observed in female participants treated with semaglutide compared to placebo, a finding that has prompted re-evaluation of the benefit-risk profile in populations at elevated baseline fracture risk.

APJ agonism in obesity

The combination of APJ agonism with GLP-1R/GIP agonists represents a therapeutically rational approach based on complementary mechanisms of action — appetite suppression plus energy expenditure enhancement — and supported by preclinical evidence of additive effects on body weight and composition. We believe this combination approach may address multiple unmet needs simultaneously: the dual oral and parenteral portfolio provides formulation flexibility, the complementary mechanism may reduce reliance on maximal doses of appetite-suppressing agents with associated GI side effects, and the energy expenditure and lean mass preservation properties may improve body composition outcomes.

Our Platform for Discovery of Novel Targets that Drive Human Metabolic Aging

We have built a target discovery capability specifically designed to identify and validate drug targets that drive metabolic aging and age-related diseases in humans. Our approach combines:

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Long-term longitudinal cohorts of naturally aging individuals. We have generated proprietary datasets based on serial biological samples from cohort studies that satisfy a set of unusual and valuable requirements for the study of aging biology: (1) being composed of healthy aging adults originally recruited decades in the past, (2) having followed subject outcomes and collected deep healthspan data continuously to the present day, and (3) having collected longitudinal biosamples that have also been maintained to the present day.

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Serial multi-omic molecular profiling. Through partnerships with companies using state-of-the-art molecular profiling techniques, we quantified thousands of components from these samples, such as proteins and metabolites, with high sensitivity.

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Data science analysis. We have developed a suite of analytic approaches allowing us to integrate longitudinal molecular profiles with clinical and health outcome data to directly decode the biology that drives disparate aging trajectories and metabolic aging and related health outcomes and identify novel drug targets for treating metabolic disease.

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Expertise in aging biology. We apply our knowledge of the aging process, including our own large colony of naturally aged rodents, to validate potential drug targets in relevant in vitro and in vivo models of age-related metabolic disorders.

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Technology-forward approach to clinical trials. We aim to maximize the value of our clinical trials by leveraging advanced analytic approaches to quantify participants’ biology and health, derive mechanistic insights, and link trial observations back to long-term healthspan outcomes from our natural aging cohorts. Examples from prior and ongoing trials include plasma proteomic profiling, wearable devices, protein synthetic rate analysis, and single-nucleus RNA sequencing of biopsy samples.

The BioAge platform encompasses over 150 million molecular data points spanning over 25 thousand individual participant profiles and over 50 years of follow-up.

Approach for identifying novel targets based on unique insights into human aging biology

We have negotiated favorable agreements with biobanks to access long-term longitudinal cohorts of individuals with serially biobanked samples who were enrolled as healthy adults and followed for up to 50 years.

In these cohorts, we have detailed medical outcomes and physiological measurements systematically collected over the course of these studies, including lifespan outcomes, such as all-cause and disease-specific mortality; functional healthspan outcomes such as grip strength and walking speed; and disease outcomes such as cognitive scores and dementia diagnoses, cardiovascular disease progression, BMI and skinfold thickness.

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The biobanks to which we have secured access are from distinct geographical regions and include samples from individuals whose demographics are representative of those regions, enabling us to identify aging processes that are conserved across populations and environmental backgrounds.

Example of longitudinal lifespan and health outcomes captured in human aging cohorts. CVD: Cardiovascular. ApoE: Apolipoprotein E.

We partner with organizations and companies leading the development of highly sensitive multi-omic molecular profiling technologies, including SomaLogic and Metabolon, to identify and quantify components of longitudinally biobanked serum and plasma specimens from our aging cohorts. The capabilities that these organizations and companies bring allow us to generate molecular profiles with more detail than had previously been possible.

We combine proteomics and metabolomics with orthogonal data such as clinical outcomes and healthspan phenotypes to obtain insights into the underlying pathways and potential targets that predispose individuals to age more quickly or be more resistant to developing multi-morbidity. Our goal as a company is to use these insights to develop pharmaceuticals that can treat a range of metabolic diseases driven by aging.

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We have previously shared the identification of apelin and NLRP3 from our platform. Beyond these targets, there are many promising targets emerging from our data sets. The figure below highlights the many proteins that have significant signals for both longevity as well as multiple health outcomes in our cohort data.

Circulating proteins are shown based on their magnitude of association with mortality (hazard ratio) in the BioAge human aging cohorts. Proteins are color coded based on significant associations (p0.05) with future healthspan outcomes representing different organ systems, including grip strength (muscle aging), cognitive scores (brain aging), renal function quantified with cystatin C (kidney aging), and cardiovascular aging. A protein was considered significant for cardiovascular aging if significantly associated with ≥2+ of the following risk factors: total cholesterol, HDL, LDL, systolic or diastolic BP, fasting glucose, CRP, MCP-1 and ICAM-1.

Our Longevity Map (as defined below) is the result of applying an aging-biology-focused analytic approach that integrates proprietary data originating from our human aging cohorts with public data on aging and target biology to generate powerful insights into human aging mechanisms and targets. Our core analytical pipeline leverages (among other approaches):

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longitudinal multi-omic and clinical data,

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relationships across multiple datasets and data modalities,

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network based propagation of biological signals, and

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causal evidence from genetic signals via a bespoke mendelian randomization analysis.

The BioAge Longevity Map integrates novel aging biology and public data to derive insights into aging biology and resulting therapeutic targets.

We are advancing several additional platform targets, currently in molecule discovery stage in collaboration with Lilly, which we believe have the potential to transform treatment of metabolic disease. We plan to expand this pipeline over time, both internally and through the target discovery collaboration with Novartis, and potentially through additional partnerships with pharmaceutical companies.

Manufacturing

We oversee and manage contract development and manufacturing organizations (CDMOs) to support development and manufacture of product candidates for our clinical trials. We expect our strategy to use CDMOs will enable us to maintain a more efficient infrastructure, avoiding the necessity to acquire our own manufacturing facility and equipment, while simultaneously enabling us to focus our expertise on the clinical development and the potential future commercialization of our products. Currently, we rely on and have agreements with multiple third-party CDMOs to manufacture and supply active pharmaceutical ingredients (APIs) and drug products (DPs) for our clinical trials. To prepare for advancement of our drug candidates to Phase 3 clinical trials, we anticipate the need to enter into a manufacture and supply agreement with, and transfer API and DP manufacture to, one or more additional third-party CDMOs with whom we would also likely enter into commercial supply agreements prior to any potential regulatory approval if any of our drug candidates are commercialized. The DP for our drug candidates is manufactured via conventional pharmaceutical processing procedures, employing commonly used and commercially available excipients and packaging materials. The procedure and equipment employed for manufacture and analysis are consistent with standard organic synthesis or pharmaceutical production, and are transferable to a range of manufacturing facilities, if needed.

Competition

The biotechnology and pharmaceutical industries are characterized by rapid evolution of technologies, fierce competition and strong defense of intellectual property. While we believe that our platform, knowledge, experience and scientific resources provide us with competitive advantages, we face competition from major pharmaceutical and biotechnology companies, academic institutions, governmental agencies and public and private research institutions, among others.

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If any of our product candidates are approved for the indications for which we expect to conduct clinical trials, they will compete with existing therapies and currently marketed drugs, as well as any drug products currently or in the future in development that are ultimately approved, that are potential treatments for metabolic diseases, such as obesity. It is also possible that we will face competition from other pharmaceutical approaches as well as other types of therapies. The key competitive factors affecting the success of all our programs, if approved, are likely to be their efficacy, safety, convenience, price, level of generic competition, and availability of reimbursement.

Many of our current or potential competitors, either alone or with their collaboration partners, have significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals and marketing approved products than we do. These competitors also compete with us in recruiting and retaining qualified scientific and management personnel and establishing clinical trial sites and patient registration for clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs. Mergers and acquisitions in the biopharmaceutical industries may result in even more resources being concentrated among a smaller number of our competitors. Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies. With respect to BGE-102, direct competition is currently limited as there are no approved NLRP3 inhibitors or other inflammasome-targeted therapeutics. However, we are aware of NLRP3 inhibitor pipeline programs including those from Ventyx Biosciences (pending acquisition by Eli Lilly), NodThera, Roche, Merck, Novo Nordisk, AstraZeneca, Neumora, Ventus, Tenvie, Insilico, Brenig, and Zydus. Our competitors for the apelin receptor APJ agonist program include Structure Therapeutics, Bristol Myers Squibb, APIE Therapeutics and Sanofi, S.A. who have or had small molecule APJ agonists in preclinical or clinical development.

We anticipate that we will continue to face increasing competition as new therapies and combinations thereof, and related data emerge. Competitors, independently or through collaboration, are developing products that potentially directly compete with our current or future product candidates and which may (i) be a longer lasting or a more efficacious treatment, or better tolerated or (ii) receive FDA or other applicable regulatory approval more rapidly than our current or future product candidates. Our commercial opportunity could be reduced or eliminated if our competitors develop and commercialize products that are safer, more effective, have fewer or less severe side effects, are more convenient or are less expensive than any products that we may develop. Our competitors also may obtain FDA or other applicable regulatory approval for their products more rapidly than we may obtain approval for ours, which could result in our competitors establishing a strong market position before we are able to enter the market.

Intellectual Property

Intellectual property is of vital importance in our field and in biotechnology generally. We seek to protect and enhance proprietary technology, inventions, and improvements that are commercially important to the development of our business by seeking, maintaining and defending patent rights, whether developed internally or licensed from third parties. We will also seek to rely on regulatory protection afforded through inclusion in expedited development and review, data exclusivity, market exclusivity and patent term extensions where available.

We have sought patent protection in the United States and internationally related to our novel drugs, including compositions of matter directed both specifically and generically to our leads and backup compounds and corresponding methods of use directed to various clinical indications of the same, and other inventions and improvements that are central to our research and development efforts. In addition, we intend to seek additional patent protection which may enhance commercial success to the extent warranted by future developments.

As of February 20, 2026, our intellectual property portfolio contained owned and in-licensed cases and contains several issued U.S. and foreign national patents, and multiple pending U.S., Patent Cooperation Treaty (PCT) and foreign national applications. These patent families are expected to expire between 2032 and 2046, excluding patent term adjustments, extensions or terminal disclaimers, and assuming payment of all appropriate maintenance fees.

APJ Agonist Program

As of February 20, 2026, we owned one patent family relating to novel apelin receptor APJ agonists and related methods. This patent family includes three U.S. provisional applications having filing dates of May 27, 2025; September 17, 2025; and January 7, 2026. Any patents that may issue and claim priority to the pending applications are expected to expire in 2046, without taking into account any patent term adjustments, extensions or terminal disclaimers, and assuming payment of all appropriate maintenance fees.

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As of February 20, 2026, we had optioned to license one patent family from JiKang Therapeutics relating to a novel APJ agonist antibody. This patent family includes one PCT non-provisional application, and any patents that may issue and claim priority to the pending application are expected to expire in 2046, without taking into account any patent term adjustments, extensions or terminal disclaimers, and assuming payment of all appropriate maintenance fees.

As of February 20, 2026, we had in-licensed one patent family from INSERM relating to use of the class of apelin receptor agonists for treating sarcopenia. This patent family includes one U.S. Patent, and foreign national patents in Japan and Europe (with validation in 5 European states), which patents are expected to expire in 2032, without taking into account any patent term adjustments, or extensions, and assuming payment of all appropriate maintenance fees.

As of February 20, 2026, we owned six patent families relating to methods of using APJ agonists, including therapeutic uses for frailty, muscle atrophy, or obesity. These patent families include six pending U.S. and PCT non-provisional applications, and 34 pending foreign national applications, including applications in Australia, Brazil, Canada, China, Europe, Israel, Japan, Korea, Mexico, New Zealand, Singapore and Taiwan. Any patents that may issue from our pending patent applications or claim priority to pending provisional applications are expected to expire between 2042 and 2045, without taking into account any patent term adjustments, extensions or terminal disclaimers, and assuming payment of all appropriate maintenance fees.

NLRP3 Inhibitor Program

As of February 20, 2026, we owned eleven patent families relating to novel NLRP3 (nucleotide binding oligomerization domain-like receptor family pyrin domain-containing 3) inhibitors and related methods. One of these patent families is co-owned with HitGen, Inc. The eleven patent families include eight issued U.S. patents (one co-owned with HitGen that is under our exclusive control, and seven solely-owned by BioAge), five pending U.S. provisional applications, nine pending U.S. and PCT non-provisional applications, and 40 pending foreign national applications, including applications in Argentina, Australia, Canada, China, Europe, Eurasia, Japan, Korea and Taiwan. Patent term is based on the effective filing date of each family. Of the eight issued patents, five will expire on March 23, 2042, two will expire on January 27, 2043, and one will expire on March 25, 2045, without taking into account any patent term adjustments, extensions or terminal disclaimers, and assuming payment of all appropriate maintenance fees. Future patents that result from pending applications in these families are projected to expire on one of March 23, 2042; January 27, 2043; September 19, 2043; September 11, 2044; October 4, 2044; or March 25, 2045, without taking into account any patent term adjustments, extensions, or terminal disclaimers, and assuming payment of all appropriate maintenance fees.

Platform Technology and Discovery Program

As of February 20, 2026, we owned 3 patent families relating to platform technology for identifying pathways for healthy aging and druggable targets, and 1 patent family relating to a class of therapeutic fusion proteins that bind endogenous RAGE ligands. These patent families include 4 issued U. S. patents, one issued Japanese patent, 3 pending U.S. applications, and 3 pending foreign national applications, including applications in Canada, and Europe. U.S. Patent No. 11,881,311 expires September 23, 2041, inclusive of patent term adjustment, and without taking into account any potential future extension. U.S. Patent No. 11,445,981 expires August 11, 2039, inclusive of patent term adjustment, and without taking into account any potential future extension. U.S. Patent No. 10,913,784 expires September 13, 2039, without taking into account any potential future extension. U.S. Patent No. 11,535,661, expires September 13, 2039, inclusive of a terminal disclaimer, and without taking into account any potential future extension. Japanese Patent No. 7,307,178 expires in September 2039, without taking into account any potential future extension. The 3 pending U.S. applications are expected to expire respectively in February 2038, July 2038, and October 2038, without taking into account any potential patent term adjustment, terminal disclaimer, or future extension. The 3 pending foreign national applications are expected to expire in October 2038 or September 2039, without taking into account any potential future supplementary protection certificate or extension.

We expect to file additional patent applications in support of current and future clinical candidates as well as new platform and core technologies.

Our commercial success will depend in part on obtaining and maintaining patent protection on our current and future product candidates and their related methods of use, as well as successfully defending any such patents against third-party challenges and operating without infringing on the proprietary rights of others. Our ability to stop third parties from making, using, selling, offering to sell or importing our product candidates will depend, in part, on the extent to which we have rights under valid and enforceable patents that cover these activities. We cannot be sure that patents will be granted with respect to any of our pending patent applications or with respect to any patent applications filed by us in the future, nor can we be sure

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that any patents that may be granted to us in the future will be commercially useful in protecting our product candidates, discovery programs and processes. For this and more comprehensive risks related to intellectual property, see “Risk Factors—Risks Related to Intellectual Property.”

The terms of individual patents depend upon the legal term of the patents in the countries in which they are obtained. In most countries in which we file, including the United States, the patent term is 20 years from the earliest date of filing a non-provisional patent application. In the United States, a patent’s term may be lengthened by patent term adjustment, which compensates a patentee for administrative delays by the U.S. Patent and Trademark Office (USPTO) in examining and granting a patent, or may be shortened if a patent is terminally disclaimed over an earlier filed patent. In the United States, the term of a patent that covers a drug approved by the FDA may also be eligible for extension, which permits patent term restoration as compensation for the patent term lost during the FDA regulatory review process. The Hatch-Waxman Act permits a patent term extension of up to five years beyond the expiration of the patent. The length of the patent term extension is related to the length of time the subject drug candidate is under regulatory review. Patent term extension cannot extend the remaining term of a patent beyond a total of 14 years from the date of product approval, only one patent applicable to an approved drug may be extended and only those claims covering the approved drug, a method for using it, or a method for manufacturing it may be extended. Similar provisions to extend the term of a patent that covers an approved drug are available in Europe and other foreign jurisdictions. In the future, if and when our products receive FDA approval, we expect to apply for patent term extensions on patents covering those products. We plan to seek patent term extensions to any issued patents we may obtain in any jurisdiction where such patent term extensions are available, however there is no guarantee that the applicable authorities, including the FDA in the United States, will agree with our assessment that such extensions should be granted, and if granted, the length of such extensions. For more information regarding the risks related to intellectual property, see “Risk Factors—Risks Related to Intellectual Property.”

In most instances, we have submitted and expect to submit patent applications directly to the USPTO as provisional patent applications. Corresponding non-provisional patent applications must be filed not later than 12 months after the provisional application filing date. While we intend to timely file non-provisional patent applications relating to our provisional patent applications, we cannot predict whether any such patent applications will result in the issuance of patents that provide us with any competitive advantage.

We file U.S. non-provisional applications, PCT applications and non-PCT foreign national applications that claim the benefit of the priority date of earlier filed provisional applications, when applicable. The PCT system allows a single application to be filed within 12 months of the original priority date of the patent application, and to designate all of the PCT member states in which national patent applications can later be pursued based on the international patent application filed under the PCT. The PCT searching authority performs a patentability search and issues a non-binding patentability opinion which can be used to evaluate the chances of success for the national applications in foreign countries prior to having to incur the filing fees. Although a PCT application does not issue as a patent, it allows the applicant to seek protection in any of the member states through national-phase applications. Before the end of the period of approximately two and a half years from the first priority date of the patent application, separate patent applications can be pursued in any of the PCT member states either by direct national filing or, in some cases, by filing through a regional patent organization, such as the European Patent Office. The PCT system delays expenses, allows a limited evaluation of the chances of success for national/regional patent applications, and enables substantial savings where applications are abandoned within the first two and a half years of filing.

For all patent applications, we determine claiming strategy on a case-by-case basis. Advice of counsel and our business model and needs are always considered. We seek to file patents containing claims for protection of all useful applications of our proprietary technologies and any products, as well as all new applications and/or uses we discover for existing technologies and products, assuming these are strategically valuable. We continuously reassess the number and type of patent applications, as well as the pending and issued patent claims to pursue maximum coverage and value for our processes, and compositions, given existing patent office rules and regulations. Further, claims may be modified during patent prosecution to meet our intellectual property and business needs.

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We recognize that the ability to obtain patent protection and the degree of such protection depends on a number of factors, including the extent of the prior art, the novelty and non-obviousness of the invention, and the ability to satisfy the enablement requirement of the patent laws. In addition, the coverage claimed in a patent application can be significantly reduced before the patent is issued, and its scope can be reinterpreted or further altered even after patent issuance. Consequently, we may not obtain or maintain adequate patent protection for any of our future product candidates or for our technology platform. We cannot predict whether the patent applications we are currently pursuing will issue as patents in any particular jurisdiction or whether the claims of any issued patents will provide sufficient proprietary protection from competitors. Any patents that we hold may be challenged, circumvented or invalidated by third parties.

In addition to patent protection, we also rely on trademark registration, trade secrets, know how, other proprietary information and continuing technological innovation to develop and maintain our competitive position. We seek to protect and maintain the confidentiality of proprietary information to protect aspects of our business that are not amenable to, or that we do not consider appropriate for, patent protection. Although we take steps to protect our proprietary information and trade secrets, including through contractual means with our employees and consultants, third parties may independently develop substantially equivalent proprietary information and techniques or otherwise gain access to our trade secrets or disclose our technology. Thus, we may not be able to meaningfully protect our trade secrets. It is our policy to require our employees, consultants, outside scientific collaborators, sponsored researchers and other advisors to execute confidentiality agreements upon the commencement of employment or consulting relationships with us. These agreements provide that all confidential information concerning our business or financial affairs developed or made known to the individual during the course of the individual’s relationship with us is to be kept confidential and not disclosed to third parties except in specific circumstances. Our agreements with employees also provide that all inventions conceived by the employee in the course of employment with us or from the employee’s use of our confidential information are our exclusive property. However, such confidentiality agreements and invention assignment agreements can be breached and we may not have adequate remedies for any such breach. In addition, our trade secrets may otherwise become known or be independently discovered by competitors. To the extent that our consultants, contractors or collaborators use intellectual property owned by others in their work for us, disputes may arise as to the rights in related or resulting trade secrets, know-how and inventions. For more information regarding the risks related to our intellectual property, see “Risk Factors—Risks Related to Intellectual Property.”

The patent positions of biotechnology companies like ours are generally uncertain and involve complex legal, scientific and factual questions. Our commercial success will also depend in part on not infringing upon the proprietary rights of third parties. Third-party patents could require us to alter our development or commercial strategies, or our products or processes, obtain licenses or cease certain activities. Our breach of any license agreements or our failure to obtain a license to proprietary rights required to develop or commercialize our future products may have a material adverse impact on us. If third parties prepare and file patent applications in the United States that also claim technology to which we have rights, we may have to participate in interference or derivation proceedings in the USPTO to determine priority, or rights in, an invention. For more information, see “Risk Factors—Risks Related to Intellectual Property.”

When available to expand market exclusivity, our strategy is to obtain or license additional intellectual property related to current or contemplated development platforms, core elements of technology and/or clinical candidates.

Government Regulation

Pharmaceutical products are subject to extensive regulation by government authorities in the United States, at the federal, state and local level, and in other countries and jurisdictions. The processes for obtaining regulatory approvals in the United States and in foreign countries and jurisdictions, along with subsequent compliance with applicable statutes and regulations and other regulatory authorities, require the expenditure of substantial time and financial resources.

FDA Review and Approval Process

In the United States, pharmaceutical products are subject to extensive regulation by the FDA. The Federal Food, Drug, and Cosmetic Act (the FD&C Act) and other federal and state statutes and regulations govern, among other things, the research, development, testing, manufacture, quality control, storage, recordkeeping, approval, labeling, promotion and marketing, distribution, post-approval monitoring and reporting, sampling and import and export of pharmaceutical products. Failure to comply with applicable U.S. requirements may subject a company to a variety of administrative or judicial sanctions, such as a clinical hold, FDA refusal to approve pending new drug applications (NDAs), warning or untitled letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, civil penalties and criminal prosecution.

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Pharmaceutical product development for a new product or certain changes to an approved product in the U.S. typically involves preclinical laboratory and animal tests, the submission to the FDA of an investigational new drug application (IND), which must become effective before clinical testing may commence, and adequate and well-controlled clinical trials to establish the safety and effectiveness of the drug for each indication for which FDA approval is sought. Satisfaction of FDA pre-market approval requirements typically takes many years and the actual time required may vary substantially based upon the type, complexity and novelty of the product or disease.

Preclinical tests include laboratory evaluation of product chemistry, formulation and toxicity, as well as animal studies to assess the characteristics and potential safety and efficacy of the product, as well as in some cases to establish a rationale for therapeutic use. The conduct of the preclinical tests must comply with federal regulations and requirements, including good laboratory practices for safety/toxicology studies. The results of preclinical testing are submitted to the FDA as part of an IND along with other information, including information about product chemistry, manufacturing and controls, and a proposed clinical trial protocol. Long-term preclinical tests, such as animal tests of reproductive toxicity and carcinogenicity, may continue after the IND is submitted. An IND automatically becomes effective and the proposed clinical trial may commence 30 days after receipt of the IND by the FDA, unless before that time the FDA raises concerns or questions related to one or more proposed clinical trials and places the trial on clinical hold. In such a case, the IND sponsor must resolve the issues to the FDA’s satisfaction before the clinical trial can begin. As a result, submission of an IND may not result in the FDA allowing clinical trials to commence.

Clinical trials involve the administration of the investigational new drug to healthy volunteers or patients under the supervision of a qualified investigator. Clinical trials must be conducted: (i) in compliance with federal regulations; (ii) in compliance with good clinical practices (GCP), an international standard meant to protect the rights and health of participants and to define the roles of clinical trial sponsors, administrators and monitors; as well as (iii) under protocols detailing the objectives of the trial, the parameters to be used in monitoring safety and the effectiveness criteria to be evaluated. Each protocol involving testing on U.S. patients and subsequent protocol amendments must be submitted to the FDA as part of the IND. While the IND is active, progress reports summarizing the results, if known, of the clinical trials and preclinical studies performed since the last progress report, among other information, must be submitted at least annually to the FDA, and written IND safety reports must be submitted to the FDA and investigators in certain circumstances.

The FDA may order the temporary, or permanent, discontinuation of a clinical trial at any time, or impose other sanctions, if it believes that the clinical trial either is not being conducted in accordance with FDA requirements or presents an unacceptable risk to the clinical trial participants. The study protocol and informed consent information for participants in clinical trials must also be submitted to an institutional review board (IRB) or ethics committee at each clinical site for approval before each trial begins. An IRB monitors clinical trials through to completion and may also require the clinical trial at the site to be halted, either temporarily or permanently, for failure to comply with the IRB’s requirements, or may impose other conditions.

Clinical trials to support NDAs for marketing approval are typically conducted in three sequential phases, but the phases may overlap. In Phase 1, the initial introduction of the drug into healthy human subjects or patients, the drug is tested to assess metabolism, pharmacokinetics, pharmacological actions, side effects associated with increasing doses, and, if possible, early evidence of effectiveness. Phase 2 usually involves trials in a limited patient population to determine the effectiveness of the drug for a particular indication, dosage tolerance and optimum dosage, and to identify common adverse effects and safety risks. If a drug demonstrates evidence of effectiveness and an acceptable safety profile in Phase 2 evaluations, Phase 3 trials are undertaken to obtain the additional information about clinical efficacy and safety in a larger number of patients, typically at geographically dispersed clinical trial sites, to permit the FDA to evaluate the overall benefit-risk relationship of the drug and to provide adequate information for the labeling of the drug. In many cases, particularly for prevalent diseases, the FDA requires two adequate and well-controlled Phase 3 clinical trials to demonstrate the efficacy of the drug. A single adequate and well-controlled Phase 3 trial in conjunction with confirmatory evidence may be sufficient in many other instances, particularly for rare disease therapies. A single adequate and well-controlled trial may also be sufficient, though it is less common, when the trial is a large multicenter trial demonstrating internal consistency and a statistically very persuasive finding of a clinically meaningful effect on mortality, irreversible morbidity or prevention of a disease with a potentially serious outcome and confirmation of the result in a second trial would be practically or ethically impossible.

The manufacturer of an investigational new drug in a Phase 2 or 3 clinical trial for a serious or life-threatening disease is required to make available, such as by posting on its website, its policy on evaluating and responding to requests for expanded access.

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After completion of the required clinical testing, an NDA is prepared and submitted to the FDA. FDA approval of the NDA is required before marketing and distribution of the product may begin in the U.S. The NDA must include the results of all preclinical, clinical and other testing and a compilation of data relating to the product’s pharmacology, chemistry, manufacture and controls, as well as any proposed labeling. The cost of preparing and submitting an NDA is substantial and includes an application user fee (unless a waiver applies) as well as an annual program fee, and the fees are typically increased annually.

The FDA has 60 days from its receipt of an NDA to conduct a preliminary review and determine whether the application will be filed based on the agency’s threshold determination that it is sufficiently complete to permit substantive review. If the FDA determines the application is incomplete because it does not on its face contain required information, the FDA may refuse to file the application and request additional information rather than file the NDA. In this event, the NDA must be resubmitted with the additional information. The resubmitted application is subject to preliminary review before the FDA files it. Once the submission is filed, the FDA begins an in-depth review. The FDA has agreed to certain performance goals in the review of NDAs to encourage timeliness. Applications for new molecular entity (NME) standard review drug products are reviewed within twelve months of the date of submission of the NDA to the FDA; applications for priority review NMEs are reviewed within eight months of the date of submission of the NDA to the FDA. Priority review can be applied to drugs that the FDA determines offer major advances in treatment or provide a treatment where no adequate therapy exists. The review process for both standard and priority review may be extended by the FDA for three additional months to consider certain late-submitted information, or information intended to clarify information already provided in the submission.

The FDA may also refer applications for novel drug products, or drug products that present difficult questions of safety or efficacy, to an outside advisory committee—typically a panel that includes clinicians and other experts—for review, evaluation and a recommendation as to whether the application should be approved. The FDA is not bound by the recommendation of an advisory committee, but it generally follows such recommendations.

Before approving an NDA, the FDA will typically inspect one or more clinical sites to assure compliance with GCP. Additionally, the FDA will inspect the facility or the facilities at which the drug is manufactured. The FDA will not approve the product unless compliance with current good manufacturing practices (cGMPs) is satisfactory and the NDA contains data that provide substantial evidence that the drug is safe and effective in the indication studied.

After the FDA evaluates the NDA and completes any clinical and manufacturing facility inspections, it issues either an approval letter or a complete response letter (CRL). A CRL generally outlines the deficiencies the FDA identified during its review of the submission and may require substantial additional testing, or information, in order for the FDA to reconsider the application for approval. If, or when, those deficiencies have been addressed to the FDA’s satisfaction in a resubmission of the NDA, the FDA will issue an approval letter. The FDA has committed to reviewing such resubmissions in two or six months depending on the type of information included. Even if such data and information are submitted, the FDA may decide that the NDA does not satisfy the criteria for approval.

An approval letter authorizes commercial marketing and distribution of the drug with specific prescribing information for specific indications. As a condition of NDA approval, the FDA may require a risk evaluation and mitigation strategy (REMS) to help ensure that the benefits of the drug outweigh the potential risks. REMS can include medication guides, communication plans for healthcare professionals, and elements to assure safe use (ETASU). ETASU can include, but are not limited to, special training or certification for prescribing or dispensing, dispensing only under certain circumstances, special monitoring and the use of patient registries. The requirement for a REMS can materially affect the potential market and profitability of the drug. Moreover, product approval may require substantial post-approval testing and surveillance to monitor the drug’s safety or efficacy and may limit further marketing of the product based on the results of this post-approval testing or surveillance.

Once granted, product approvals may be withdrawn if compliance with regulatory standards is not maintained or problems are identified following initial marketing. Changes to some of the conditions established in an approved application, including changes in indications, labeling, or manufacturing processes or facilities, require submission and FDA approval of a new NDA or NDA supplement before the change can be implemented. An NDA supplement for a new indication typically requires clinical data similar to that in the original application, and the FDA uses the same procedures and actions in reviewing NDA supplements as it does in reviewing NDAs.

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Disclosure of Clinical Trial Information

Sponsors of clinical trials of FDA regulated products, including drugs, are required to register and disclose certain clinical trial information on ClinicalTrials.gov. Information related to the product, patient population, phase of investigation, study sites and investigators, and other aspects of the clinical trial is then made public as part of the registration. Sponsors are also obligated to disclose the results of their clinical trials after completion. Disclosure of the results of these trials can be delayed in certain circumstances for up to two years after the date of completion of the trial. Competitors may use this publicly available information to gain knowledge regarding the progress of development programs.

Pediatric Information

Under the Pediatric Research Equity Act (PREA), NDAs or supplements to NDAs must contain data to assess the safety and effectiveness of the drug for the claimed indications in all relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which the drug is safe and effective. The FD&C Act requires that a sponsor who is planning to submit a marketing application for a product that includes a new active ingredient, new indication, new dosage form, new dosing regimen or new route of administration submit an initial Pediatric Study Plan (PSP), within 60 days of an end-of-Phase 2 meeting or as may be agreed between the sponsor and FDA. The FDA and the sponsor must reach agreement on the PSP. The FDA may grant full or partial waivers, or deferrals, for submission of data.

The Best Pharmaceuticals for Children Act (BPCA) provides NDA holders a six-month extension of any exclusivity—patent or nonpatent—for a drug if certain conditions are met. Conditions for exclusivity include the FDA’s determination that information relating to the use of a new drug in the pediatric population may produce health benefits in that population, the FDA making a written request for pediatric studies, and the applicant agreeing to perform, and reporting on, the requested studies within the statutory timeframe. Applications under the BPCA are treated as priority applications, with all of the benefits that designation confers.

Post-Approval Requirements

Once an NDA is approved, a product will be subject to certain post-approval requirements. For instance, the FDA closely regulates the post-approval marketing and promotion of drugs, including standards and regulations for direct-to-consumer advertising, off-label promotion, industry-sponsored scientific and educational activities and promotional activities involving the internet. Drugs may be marketed only for the approved indications and in accordance with the provisions of the approved labeling. The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses, and a company that is found to have improperly promoted off-label uses may be subject to significant liability, including investigation by federal and state authorities.

Adverse event reporting and submission of periodic reports are required following FDA approval of an NDA. The FDA also may require post-marketing testing, sometimes referred to as Phase 4 testing, REMS, and surveillance to monitor the effects of an approved product, or the FDA may place conditions on an approval that could restrict the distribution or use of the product. In addition, quality control, drug manufacture, packaging and labeling procedures must continue to conform to cGMPs after approval. Drug manufacturers and certain of their subcontractors are required to register their establishments with the FDA and certain state agencies. Registration with the FDA subjects entities to periodic unannounced inspections by the FDA, during which the Agency inspects manufacturing facilities to assess compliance with cGMPs. Accordingly, manufacturers must continue to expend time, money and effort in the areas of production and quality-control to maintain compliance with cGMPs. FDA may withdraw product approvals or request product recalls if a company fails to comply with regulatory standards, if it encounters problems following initial marketing, or if previously unrecognized problems are subsequently discovered.

The Hatch-Waxman Amendments

Orange Book Listing

Under the Drug Price Competition and Patent Term Restoration Act of 1984, commonly referred to as the Hatch Waxman Amendments, NDA applicants are required to list with the FDA each patent whose claims cover the applicant’s product or approved method of using the product. Upon approval of a drug, each of the patents listed in the application for the drug is then published in the FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations, commonly known as the Orange Book. Drugs listed in the Orange Book can, in turn, be cited by potential generic competitors in support of approval of an abbreviated new drug application (ANDA). An ANDA provides for marketing of a drug product that has the same active

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ingredients in the same strengths and dosage form as the listed drug and has been shown through bioequivalence testing to be therapeutically equivalent to the listed drug. Other than the requirement for bioequivalence testing, ANDA applicants are not required to conduct, or submit results of, preclinical or clinical tests to prove the safety or effectiveness of their drug product. Drugs approved in this way are commonly referred to as “generic equivalents” to the listed drug and can often be substituted by pharmacists under prescriptions written for the original listed drug.

The ANDA applicant is required to certify to the FDA concerning any patents listed for the approved product in the FDA’s Orange Book. Specifically, the applicant must certify that (i) the required patent information has not been filed; (ii) the listed patent has expired; (iii) the listed patent has not expired but will expire on a particular date and approval is sought after patent expiration; or (iv) the listed patent is invalid or will not be infringed by the new product. The ANDA applicant may also elect to submit a Section VIII statement certifying that its proposed ANDA label does not contain (or carve out) any language regarding the patented method-of-use rather than certify to a listed method-of-use patent. If the applicant does not challenge the listed patents, the ANDA application will not be approved until all the listed patents claiming the referenced product have expired.

A certification that the new product will not infringe the already approved product’s listed patents, or that such patents are invalid, is called a Paragraph IV certification. If the ANDA applicant has provided a Paragraph IV certification to the FDA, the applicant must also send notice of the Paragraph IV certification to the NDA and patent holders once the ANDA has been accepted for filing by the FDA. The NDA and patent holders may then initiate a patent infringement lawsuit in response to the notice of the Paragraph IV certification. The filing of a patent infringement lawsuit within 45 days of the receipt of a Paragraph IV certification automatically prevents the FDA from approving the ANDA until the earlier of 30 months, expiration of the patent, settlement of the lawsuit, or a decision in the infringement case that is favorable to the ANDA applicant.

Exclusivity

Market exclusivity provisions under the FD&C Act also can delay the submission or the approval of certain applications. An ANDA application will not be approved until any applicable non-patent exclusivity listed in the Orange Book for the referenced product has expired. Upon NDA approval of a new chemical entity (NCE), which is a drug that contains no active moiety that has been approved by the FDA in any other NDA, that drug receives five years of marketing exclusivity during which the FDA cannot receive any ANDA seeking approval of a generic version of that drug. An ANDA may be submitted one year before NCE exclusivity expires if a Paragraph IV certification is filed. If there is no listed patent in the Orange Book, there may not be a Paragraph IV certification, and, thus, no ANDA may be filed before the expiration of the exclusivity period. Certain changes to a drug, such as the approval of a new indication, new strength, or new condition of use, can be the subject of a three-year period of exclusivity from the date of approval if the application contains reports of new clinical investigations (other than bioavailability studies) conducted or sponsored by the sponsor that were essential to the approval of the application. The FDA cannot approve an ANDA for a generic drug that includes the change during the exclusivity period. In some instances, an ANDA applicant may receive approval prior to expiration of certain non-patent exclusivity if the applicant seeks, and FDA permits, the omission of such exclusivity-protected information from the ANDA prescribing information.

Patent Term Restoration

After NDA approval, the owner of a relevant drug patent may apply for up to a five-year patent extension. Only one patent may be extended for each regulatory review period, which is composed of two parts: a testing phase and an approval phase. The allowable patent term extension is generally calculated as half of the drug’s testing phase (the time between IND application and NDA submission) and all of the review phase (the time between NDA submission and approval) up to a maximum of five years. If the extended patent was issued during the development or review period, the calculation begins from the date of patent issuance. The review period can be shortened if the FDA determines that the applicant did not pursue approval with due diligence. The total patent term after the extension may not exceed 14 years.

For patents that might expire during the application phase, the patent owner may request an interim patent extension. An interim patent extension increases the patent term by one year and may be renewed up to four times. For each interim patent extension granted, the post-approval patent extension is reduced by one year. The director of the United States Patent and Trademark Office must determine that approval of the drug covered by the patent for which a patent extension is being sought is likely. Interim patent extensions are not available for a drug for which an NDA has not been submitted.

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Coverage and Reimbursement

Sales of a product in the U.S. will depend, in part, on the extent to which such products will be covered by third-party payors, such as government healthcare programs, commercial insurance and managed healthcare organizations. These third-party payors are increasingly limiting coverage and/or reducing reimbursements for medical products and services. The process for determining whether a payor will provide coverage for a drug product may be separate from the process for setting the reimbursement rate that the payor will pay for the drug. Third-party payors may limit coverage to specific drug products on an approved list, or formulary, which might not include all of FDA-approved drugs for a particular indication. Further, one payor’s determination to provide coverage for a drug product does not ensure that other payors will also provide coverage for the drug product. Coverage policies and third-party payor reimbursement rates may change at any time and can differ significantly from payor to payor.

In addition, the U.S. government, state legislatures and foreign governments have continued implementing cost-containment programs, including price controls, restrictions on reimbursement and requirements for substitution of generic products. Third-party payors are increasingly challenging the prices charged for medical products and services, examining the medical necessity, and reviewing the cost effectiveness of pharmaceutical or biological products, medical devices, and medical services, in addition to questioning safety and efficacy. Adoption of price controls and cost-containment measures, and adoption of more restrictive policies in jurisdictions with existing controls and measures, could further limit sales of any product that receives approval. Decreases in third-party payor reimbursement or a decision by a third-party payor to not cover a product could reduce physician usage and patient demand for the product.

Other Healthcare Laws

In addition to FDA restrictions on marketing of pharmaceutical products, several other types of state and federal laws have been applied to restrict certain general business and marketing practices in the pharmaceutical industry in recent years. These laws include anti-kickback statutes, false claims statutes, price transparency and reporting, privacy and cybersecurity laws, and other healthcare laws and regulations.

The federal Anti-Kickback Statute prohibits, among other things, knowingly and willfully offering, paying, soliciting or receiving remuneration to induce, or in return for, purchasing, leasing, ordering or arranging for the purchase, lease or order of any healthcare item or service reimbursable under Medicare, Medicaid, or other federally financed healthcare programs. The Patient Protection and Affordable Care Act as amended by the Health Care and Education Reconciliation Act (collectively, the ACA) amended the intent element of the federal statute so that a person or entity no longer needs to have actual knowledge of the statute or specific intent to violate it in order to commit a violation. This statute has been interpreted to apply to arrangements between pharmaceutical manufacturers on the one hand and prescribers, purchasers and formulary managers, among others, on the other. Violations of the federal Anti-Kickback Statute are punishable by imprisonment, criminal fines, civil monetary penalties, and exclusion from participation in federal healthcare programs. Although there are a number of statutory exceptions and regulatory safe harbors protecting certain common activities from prosecution or other regulatory sanctions, the exceptions and safe harbors are drawn narrowly, and practices that involve remuneration intended to induce prescribing, purchases or recommendations may be subject to scrutiny if they do not qualify for an exception or safe harbor. Additionally, a violation of the federal Anti-Kickback Statute can serve as a basis for liability under the federal civil False Claims Act.

Federal civil and criminal false claims laws, including the federal civil False Claims Act, prohibit any person or entity from knowingly presenting, or causing to be presented, a false claim for payment to the federal government, or knowingly making, or causing to be made, a false statement to have a false claim paid. This includes claims made to programs where the federal government reimburses, such as Medicare and Medicaid, as well as programs where the federal government is a direct purchaser, such as when it purchases off the Federal Supply Schedule. Pharmaceutical and other healthcare companies have been prosecuted under these laws for allegedly inflating drug prices they report to pricing services, which in turn were used by the government to set Medicare and Medicaid reimbursement rates, and for allegedly providing free product to customers with the expectation that the customers would bill federal programs for the product. In addition, certain marketing practices, including off-label promotion, may also violate false claims laws. Additionally, the ACA amended the federal Anti-Kickback Statute such that a violation of that statute can serve as a basis for liability under the federal civil False Claims Act. Most states also have statutes or regulations similar to the federal Anti-Kickback Statute and civil False Claims Act, which apply to items and services reimbursed under Medicaid and other state programs, or, in several states, apply regardless of the payor.

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Other federal statutes pertaining to healthcare fraud and abuse include the civil monetary penalties statute, which prohibits, among other things, the offer or payment of remuneration to a Medicaid or Medicare beneficiary that the offeror or payor knows or should know is likely to influence the beneficiary to order a receive a reimbursable item or service from a particular supplier, and the additional federal criminal statutes created by the Health Insurance Portability and Accountability Act of 1996 (HIPAA), which prohibits, among other things, knowingly and willfully executing or attempting to execute a scheme to defraud any healthcare benefit program or obtain by means of false or fraudulent pretenses, representations or promises any money or property owned by or under the control of any healthcare benefit program in connection with the delivery of or payment for healthcare benefits, items or services.

In addition, HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009 (HITECH), and their respective implementing regulations, impose obligations on certain healthcare providers, health plans, and healthcare clearinghouses, known as covered entities, as well as their business associates and subcontractors that perform certain services involving the storage, use or disclosure of individually identifiable health information, including mandatory contractual terms, with respect to safeguarding the privacy, security, and transmission of individually identifiable health information, and require notification to affected individuals and regulatory authorities of certain breaches of security of individually identifiable health information. HITECH increased the civil and criminal penalties that may be imposed against covered entities, business associates and possibly other persons, and gave state attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce the federal HIPAA laws and seek attorney’s fees and costs associated with pursuing federal civil actions. In addition, many state laws govern the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and may not have the same effect, and often are not pre-empted by HIPAA. Each of these laws may increase the complexity, variation in requirements, restrictions and potential legal risks, and could require increased compliance costs and changes in business practices and policies. For example, the California Consumer Privacy Act of 2018 (CCPA), imposes obligations on businesses to which it applies, including, but not limited to, providing specific disclosures in privacy notices and affording California residents certain rights related to their personal data, although it exempts some data processed in the context of clinical trials. In addition, the California Privacy Rights Act of 2020 (CPRA), which went into effect on January 1, 2023, imposes additional obligations on companies covered by the legislation and significantly modifies the CCPA, including by expanding consumers’ rights with respect to certain sensitive personal information. The CPRA also creates a new state agency that is vested with authority to implement and enforce the CCPA and CPRA. Other states have also enacted, proposed, or are considering proposing, data privacy laws, which could further complicate compliance efforts, increase our potential liability and adversely affect our business.

Further, pursuant to the federal Physician Payments Sunshine Act, enacted as part of the ACA, the Centers for Medicare & Medicaid Services (CMS), has issued a final rule that requires manufacturers of approved prescription drugs that are reimbursable under Medicare, Medicaid, or the Children’s Health Insurance Program, with certain exceptions, to collect and report information on certain payments or transfers of value to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), certain non-physician practitioners (such as physician assistants and nurse practitioners) and teaching hospitals, as well as investment interests held by physicians and their immediate family members. The reports must be submitted on an annual basis. The reported data is made available in searchable form on a public website on an annual basis. Failure to submit required information may result in civil monetary penalties.

In addition, several states now require prescription drug companies to report certain expenses relating to the marketing and promotion of drug products and to report gifts and payments to individual healthcare practitioners in these states. Other states prohibit various marketing-related activities, such as the provision of certain kinds of gifts or meals. Several states, including California, Connecticut, Nevada, and Massachusetts, require pharmaceutical companies to implement compliance programs and/or marketing codes. Still other states require the posting of information relating to clinical studies and their outcomes. A growing number of states require the reporting of certain drug pricing information, including information pertaining to and justifying price increases and the prices of newly launched drugs, or prohibit prescription drug price gouging. In addition, certain states require pharmaceutical companies to implement compliance programs and/or marketing codes. Certain states and local jurisdictions also require the registration of pharmaceutical sales and medical representatives. Compliance with these laws is difficult and time consuming, and companies that do not comply with these state laws face civil penalties.

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Efforts to ensure that business arrangements with third parties comply with applicable healthcare laws and regulations involve substantial costs. If a drug company’s operations are found to be in violation of any such requirements, it may be subject to significant penalties, including civil, criminal and administrative penalties, damages, fines, disgorgement, imprisonment, the curtailment or restructuring of its operations, loss of eligibility to obtain approvals from the FDA, exclusion from participation in government contracting, healthcare reimbursement or other federal or state government healthcare programs, including Medicare and Medicaid, integrity oversight and reporting obligations, imprisonment, and reputational harm. Any action for an alleged or suspected violation can cause a drug company to incur significant legal expenses and divert management’s attention from the operation of the business, even if such action is successfully defended.

U.S. Healthcare Reform

In the United States there have been, and continue to be, proposals by the federal government, state governments, regulators and third-party payors to control or manage the increased costs of health care and, more generally, to reform the U.S. healthcare system. The pharmaceutical industry has been a particular focus of these efforts and has been significantly affected by major legislative initiatives. For example, in March 2010, the ACA was enacted, which was intended to broaden access to health insurance, reduce or constrain the growth of healthcare spending, enhance remedies against fraud and abuse, add new transparency requirements for the healthcare and health insurance industries, impose new taxes and fees on the health industry and impose additional health policy reforms.

Several healthcare reform proposals culminated in the enactment of the Inflation Reduction Act (IRA) in August 2022, which, among other things, allows HHS to directly negotiate the selling price of a statutorily specified number of drugs and biologics each year that CMS reimburses under Medicare Part B and Part D. The negotiated price may not exceed a statutory ceiling price. Only high-expenditure single-source drugs that have been approved for at least 7 years (11 years for single-source biologics) are eligible to be selected by CMS for negotiation, with the negotiated price taking effect two years after the selection year. For 2026, the first year in which negotiated prices become effective, CMS selected 10 high-cost Medicare Part D products in 2023, negotiations began in 2024, and the negotiated maximum fair price for each product has been announced. In addition, CMS has selected and announced the negotiated maximum fair price for 15 additional Medicare Part D drugs, which will become effective in 2027. For 2028, CMS has selected an additional 15 drugs, comprised of drugs covered under Medicare Part D and, for the first time, drugs payable under Medicare Part B. For 2029 and subsequent years, 20 Part B or Part D drugs will be selected. The IRA also imposes rebates on Medicare Part B and Part D drugs whose prices have increased at a rate greater than the rate of inflation and in November 2024, CMS finalized regulations for these inflation rebates. In addition, the law eliminated the “donut hole” under Medicare Part D beginning in 2025 by significantly lowering the beneficiary maximum out-of-pocket cost through a newly established manufacturer discount program, which requires manufacturers, in order for their drugs to be covered by Medicare Part D, to provide statutorily defined discounts on their brand (approved NDA or BLA) drugs dispensed to Part D enrollees. The IRA permits the Secretary of HHS to implement many of these provisions through guidance, as opposed to regulation, for the initial years. Manufacturers that fail to comply with the IRA may be subject to various penalties, including civil monetary penalties. These provisions began taking effect progressively starting in 2023 and may be subject to legal challenges. For example, the provisions related to the negotiation of selling prices of high-expenditure single-source drugs and biologics have been challenged in multiple lawsuits brought by pharmaceutical manufacturers. The outcome of these lawsuits is uncertain. Thus, while it is unclear how the IRA will be implemented, it will likely have a significant impact on the pharmaceutical industry and the pricing of prescription drug products.

Employees and Human Capital Resources

As of December 31, 2025, we had 62 employees, 60 of whom were full-time and 44 of whom were engaged in research and development activities. Approximately 44% of our employees hold Ph.D. or M.D. degrees. Women comprise approximately 50% of our employees, and individuals from underrepresented ethnic groups comprise approximately 31%. Women comprise approximately 39% of our senior leadership team and 25% of our board of directors. None of our employees are represented by a labor union or covered under a collective bargaining agreement. We consider our relationship with our employees to be good.

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Our human capital resources objectives include, as applicable, identifying, recruiting, retaining, incentivizing and integrating our existing and new employees, advisors and consultants. It is important that we not only attract and retain the best and brightest diverse talent, but also ensure they remain engaged and can thrive in an environment that is committed to helping them grow, succeed and contribute directly to achieving our purpose. The principal purposes of our equity and cash incentive plans are to attract, retain and reward personnel through the granting of stock-based and cash-based compensation awards, in order to increase the success of our Company by motivating such individuals to perform to the best of their abilities and achieve our objectives.

Facilities

Our headquarters are located in Emeryville, California where we lease and occupy 10,479 square feet of office and laboratory space.

We believe that our existing facilities and new facilities under construction are sufficient to meet our near-term needs.

Additional Information

We were incorporated under the laws of the State of Delaware in April 2015 under the name BioAge Labs, Inc. Our principal executive office is located at 5885 Hollis Street Suite 370 Emeryville California, 94608, and our telephone number is (510) 806-1445. Our website address is www.bioagelabs.com. The information contained on, or that can be accessed through, our website is not part of, and is not incorporated by reference into, this Annual Report.

We file annual, quarterly and current reports, proxy statements and other documents with the Securities and Exchange Commission, or SEC, under the Securities Exchange Act of 1934, as amended, or Exchange Act. The SEC maintains an Internet website that contains reports, proxy and information statements, and other information regarding issuers, including us, that file electronically with the SEC. The public can obtain any documents that we file with the SEC at www.sec.gov. Copies of each of our filings with the SEC can also be viewed and downloaded free of charge at our website, https://ir.bioagelabs.com, after the reports and amendments are electronically filed with or furnished to the SEC.