Bioage Labs, Inc. · NASDAQ:BIOA
Bioage Labs — Investor Day (May 2026)
106 slides from Bioage Labs's investor day presentation, May 8, 2026
Slide 1: R&D Update May 8, 2026
BIOAGE R&D Update May 8, 2026
Slide 2: Disclaimer
Disclaimer BioAge Labs, Inc. (the “Company”) does not (nor their respective affiliates, directors, members, officers, employees or agents) make any representation or warranty, express or implied, as to, and no reliance should be placed on, the fairness, accuracy, completeness or correctness of the i
Slide 3: Welcome & Introductions
~ € welcome & Introductions > ee . ea
Slide 4: Management attendees
Management attendees Kristen Fortney, PhD Paul Rubin, MD Dov Goldstein, MD, MBA Co-Founder & CEO CMO & EVP Research CFO
Slide 5: Guest presenters
Guest presenters Michael Davidson, MD Matthias Geyer, PhD Clinical Professor of Medicine Director, Institute of Structural Director, Lipid Clinic Biology University of Bonn University of Chicago Pritzker School of Medicine Brian Hafler, MD, PhD David Boyer, MD Associate Professor Senior Partner Opht
Slide 6: Agenda
Kristen Fortney, PhD Introduction Co-Founder & CEO BGE-102 Matthias Geyer, PhD Structural biology insights University of Bonn Paul Rubin, MD Phase 1 results CMO & EVP Research Michael Davidson, MD Cardiovascular University of Chicago Paul Rubin, MD Brian Hafler, MD, PhD David Boyer, MD Ophthalmology
Slide 7: Introduction
Introduction Kristen Fortney, PhD Co-Founder & CEO
Slide 8: We are harnessing the biology of human aging to develop new therapies
The BioAge discovery platform: from human data to therapeutics for metabolic aging Validated platform: ongoing partnerships with Novartis & Lilly to discover drugs and drug targets >150M molecular data points: one of the world’s largest collections of longitudinal We are human aging data and functio
Slide 9: Chronic NLRP3 activity drives disease & predicts poor human longevity
Chronic NLRP3 activity drives disease & predicts poor human longevity NLRP3 overview NLRP3 in human longevity & disease Relative mortality risk (HR) Reduced NLRP3 Normal NLRP3 Excess ● nutrients Cellular activity is stress function: innate associated with immune response to longevity danger signals
Slide 10: BGE-102 well positioned to address diseases driven by inflammation
Our lead program, BGE-102, is well positioned to address diseases driven by inflammation in both the CNS and the periphery Key attributes Potential best-in-class potency based on Phase 1 trial results CNS penetrant 1.8 nM IC90 by human ex vivo whole blood stimulation ~0.7 Kp,uuCSF (120 mg MAD, day 1
Slide 11: BioAge NLRP3 inhibitors: unique, patented binding site & novel mechanism
BioAge NLRP3 inhibitors: unique, patented binding site & novel mechanism Unique binding site Our inhibitors bind both the active & inactive inflammasome, unlike other NLRP3 inhibitors BioAge compounds MCC950 Inactive decamer Active inflammasome Collaboration with Matthias Geyer, PhD, Director, Insti
Slide 12: NLRP3 Structural biology insights
NLRP3 Structural biology insights Phase 1 results Cardiovascular Ophthalmology
Slide 13: A new way to inhibit NLRP3
Matthias Geyer, PhD A new way to Director, Institute of Structural Biology inhibit NLRP3 University of Bonn
Slide 14: BGE-102 targets a different site on NLRP3 than other inhibitors
BGE-102 targets a different site on NLRP3 than other inhibitors in development
Slide 15: BGE-102 targets a different site on NLRP3 than other inhibitors
BGE-102 targets a different site on NLRP3 than other inhibitors in development
Slide 16: BGE-102 targets a different site on NLRP3 than other inhibitors
BGE-102 targets a different site on NLRP3 than other inhibitors in development
Slide 17: BGE-102 targets a different site on NLRP3 than other inhibitors
BGE-102 targets a different site on NLRP3 than other inhibitors in development
Slide 18: BGE-102 inhibits both forms of NLRP3
BGE-102 inhibits both forms of NLRP3 – the resting state and the active inflammasome
Slide 19: BGE-102 inhibits both forms of NLRP3
BGE-102 inhibits both forms of NLRP3 – the resting state and the active inflammasome
Slide 20: BGE-102 is selective for NLRP3
BGE-102 is selective for NLRP3 There are 22 human NOD-like receptors
Slide 21: BGE-102 is selective for NLRP3
BGE-102 is selective for NLRP3 The BioAge compound binding site is in pocket of NLRP3 that is different from every other inflammasome
Slide 22: BGE-102 is selective for NLRP3
BGE-102 is selective for NLRP3 The BioAge compound binding site is in pocket of NLRP3 that is different from every other inflammasome NLRP3 NLRP12
Slide 23: Three structural features set BGE-102 apart
Three structural features set BGE-102 apart The BGE-102 binding site on NLRP3 is unique from every other inhibitor in the clinic
Slide 24: Three structural features set BGE-102 apart
Three structural features set BGE-102 apart The BGE-102 binding site on NLRP3 is unique from every other inhibitor in the clinic The BGE-102 binding site is accessible in the resting and active state of NLRP3
Slide 25: Three structural features set BGE-102 apart
Three structural features set BGE-102 apart The BGE-102 binding site on NLRP3 is unique from every other inhibitor in the clinic The BGE-102 binding site is accessible in the resting and active state of NLRP3 The BGE-102 binding site is selective for NLRP3 alone within the inflammasome family
Slide 26: Phase 1 results
NLRP3 Structural biology insights Phase 1 results Cardiovascular Paul Rubin, MD CMO & EVP Research Ophthalmology
Slide 27: Phase 1 clinical trial design
P3 LR N PHASE 1 RESULTS Phase 1 clinical trial design Single Ascending Dose Multiple Ascending Dose Multiple Ascending Dose HVs & obese HVs - 14 days of dosing Obese - 14-21 days of dosing Objectives Safety & tolerability, pharmacokinetics, pharmacodynamics (IL-1β, hsCRP) HVs (N=36) Obese subjects S
Slide 28: BGE-102 met key trial objectives
P3 LR N PHASE 1 RESULTS BGE-102 met key trial objectives ● Well tolerated with all mild / moderate, self-limited AEs Safety / tolerability ● No dose-limiting toxicities Pharmacokinetics ● Dose-proportional exposure with T1/2 supporting QD dosing After 14 days of dosing at 60 mg QD in healthy volunte
Slide 29: BGE-102 was well tolerated
P3 LR N PHASE 1 RESULTS BGE-102 was well tolerated ● Only mild / moderate treatment-emergent AEs All BGE-102 All placebo TEAEs (TEAEs); all self-limited with no dose dependency (N=82) (N=22) Subjects with No serious AEs 50 (61.0%) 13 (59.1%) ● at least 1 AE No TEAEs leading to discontinuation Subjec
Slide 30: Obese MAD cohorts: baseline characteristics
P3 LR N PHASE 1 RESULTS Obese MAD cohorts: baseline characteristics 60 mg obese MAD 120 mg obese MAD Obese placebo Baseline characteristic (N=19) (N=14) (N=8) Age, years, mean (SD) 41.7 (9.8) 39.4 (9.8) 38.8 (6.7) Male, n (%) 7 (36.8) 8 (57.1) 2 (25.0) Female, n (%) 12 (63.2) 6 (42.9) 6 (75.0) Race,
Slide 31: Obese MAD cohorts: safety and tolerability
P3 LR N PHASE 1 RESULTS Obese MAD cohorts: safety and tolerability 60 mg obese MAD 120 mg obese MAD Obese placebo TEAEs (N=19) (N=14) (N=8) Subjects with any related TEAE, n (%) 5 (26.3%) 2 (14.3%) 1 (12.5%) Subjects with TEAE leading to discontinuation, n 0 0 0 Subjects with SAE or severe TEAE, n 0
Slide 32: Healthy volunteer SAD / MAD
NLRP3 Structural biology insights Phase 1 results Healthy volunteer SAD / MAD Obese MAD Cardiovascular Ophthalmology
Slide 33: Plasma PK: dose-proportionality observed in SAD cohorts
P3 LR N HEALTHY VOLUNTEER SAD / MAD Plasma PK: dose-proportionality observed in SAD cohorts SAD cohorts: mean plasma PK BGE-102 and active metabolite* free concentration Mean free plasma concentration Dose (ng/mL) 10 mg 30 mg 60 mg 120 mg Time (h) Note: * combined concentration of BGE-102 and its so
Slide 34: Plasma PK: MAD cohorts showed accumulation
P3 LR N HEALTHY VOLUNTEER SAD / MAD Plasma PK: MAD cohorts showed accumulation out to 14 days with near steady-state levels above the human IC90 for IL-1β inhibition MAD cohorts: mean plasma PK at trough (pre-dose) Mean free plasma concentration BGE-102 and active metabolite free concentration Dose
Slide 35: CSF PK: doses exceeded human IC90
P3 LR N HEALTHY VOLUNTEER SAD / MAD CSF PK: doses of 60 mg and above exceeded human IC90 at near steady state MAD cohorts: Day 14 CSF PK BGE-102 and active metabolite, 11-13 hours post-dose Mean CSF concentration (ng/mL) IL-1β IC90 Human ex vivo whole blood 60 mg 120 mg
Slide 36: PK / PD: 90-98% suppression of IL-1β at trough
P3 LR N HEALTHY VOLUNTEER SAD / MAD PK / PD: 90-98% suppression of IL-1β at BGE-102 trough in MAD cohorts MAD cohorts: mean IL-1β with ex vivo stimulation at trough Ex vivo whole blood stimulation baseline vs Day 14 Blood from Inflammatory participant stimulus 98% 90% IL-1β 60 mg 120 mg
Slide 37: PK / PD: 24 hours of near-maximal suppression of IL-1β
P3 LR N HEALTHY VOLUNTEER SAD / MAD PK / PD: 24 hours of near-maximal suppression of IL-1β achieved by Day 8 120 mg MAD Day 1 Day 8 Day 14
Slide 38: Obese MAD
NLRP3 Structural biology insights Phase 1 results Healthy volunteer SAD / MAD Obese MAD Cardiovascular Ophthalmology
Slide 39: Phase 1 trial included 2 obese MAD cohorts
P3 LR N OBESE MAD The Phase 1 trial included 2 obese MAD cohorts, enabling evaluation of biomarkers including hsCRP Eligibility ● Age 18+ Primary endpoints Placebo ● PK, safety / tolerability ● BMI 32-42 R Exploratory endpoints ● hsCRP > 3 mg/L BGE-102 Dose levels: 60 mg | 120 mg ● Inflammatory and
Slide 40: 86% reductions in hsCRP
P3 LR N OBESE MAD 60 mg & 120 mg doses of BGE-102 resulted in 86% reductions in hsCRP, consistent with best-in-class efficacy 60 mg MAD 120 mg MAD * Note: median values, error bars show IQR (Q1-Q3); * Day 7 placebo IQR upper limit is 115%; median baseline hsCRP 60 mg cohort 6.30 mg/L for both active
Slide 41: Similar hsCRP trajectories in both obese MAD cohorts
P3 LR N OBESE MAD Similar hsCRP trajectories in both obese MAD cohorts Dose 60 mg 120 mg Note: median values, error bars show IQR (Q1-Q3); median baseline hsCRP for subjects on active treatment 60 mg cohort 6.30 mg/L, 120 mg cohort 4.85 mg/L
Slide 42: 87-93% of subjects achieved normal hsCRP levels
P3 LR N OBESE MAD 87-93% of subjects on BGE-102 achieved normal hsCRP levels (<2 mg/L) 60 mg MAD 120 mg MAD Group / Threshold Placebo ≤1 mg/L Placebo <2 mg/L BGE-102 60 mg QD ≤1 mg/L BGE-102 60 mg QD <2 mg/L BGE-102 120 mg QD ≤1 mg/L BGE-102 120 mg QD <2 mg/L Note: median baseline hsCRP 60 mg cohort
Slide 43: Comparable IL-6 reductions
P3 LR N OBESE MAD 60 mg & 120 mg doses of BGE-102 resulted in comparable IL-6 reductions 60 mg MAD 120 mg MAD Note: median values, error bars show IQR (Q1-Q3); median baseline IL-6 60 mg cohort 2.2 pg/mL for active treatment and 2.8 pg/mL for placebo, 120 mg cohort 2.3 pg/mL for active treatment and
Slide 44: BGE-102 reduced CSF IL-6 by 84% in elevated subjects
P3 LR N OBESE MAD In the 2 subjects with elevated baseline CSF IL-6, BGE-102 reduced levels by 84% in the Day 14 CSF CSF IL-6* Plasma IL-6 Plasma IL-6 (pg/mL) CSF IL-6 (pg/mL) Note: * IL-6 levels >7 pg/mL in the CSF are considered elevated; corresponding decrease in the plasma was 62%; measurements
Slide 45: Comparable reductions in fibrinogen
P3 LR N OBESE MAD 60 mg & 120 mg doses of BGE-102 resulted in comparable reductions in fibrinogen 60 mg MAD 120 mg MAD Note: median values, error bars show IQR (Q1-Q3); median baseline fibrinogen 60 mg cohort 362 mg/dL for active treatment and 379 mg/dL for placebo, 120 mg cohort 331 mg/dL for activ
Slide 46: Cardiovascular
NLRP3 Structural biology insights Phase 1 results Cardiovascular Paul Rubin, MD CMO & EVP Research Ophthalmology
Slide 47: BGE-102 could address cardiometabolic and neuroinflammatory disorders
P3 LR N CARDIOVASCULAR BGE-102 has the potential to address a range of cardiometabolic and neuroinflammatory disorders BGE-102 addressable diseases Neurodegeneration Ocular Neuro- inflammation Peripheral inflammation CVD Insulin MASLD / (ASCVD, HF) resistance MASH
Slide 48: The CV opportunity
P3 LR N CARDIOVASCULAR The CV opportunity Lipid-lowering Inflammation is 15M addressable Orals are highly therapies set an independent patients in the US preferable precedent for large risk factor for CVD alone market hsCRP (mg/L) <1.0 1.0-3.0 >3.0 >80% of statins are prescribed by PCPs $50B ~60% ex
Slide 49: Planned CV risk POC
P3 LR N CARDIOVASCULAR Planned CV risk POC Primary endpoint ● % change in hsCRP Placebo N=40 Key secondary endpoints Key eligibility criteria ● % normalization of hsCRP ● Age 18+ (<2 mg/L and ≤1 mg/L) BGE-102 30 mg QD N=40 BMI 32-42 Exploratory endpoints ● R ● hsCRP > 3 mg/L ● Additional CV risk fac
Slide 50: Anti-inflammatory strategies for ASCVD
Anti-inflammatory Michael Davidson, MD Clinical Professor of Medicine strategies for ASCVD Director, Lipid Clinic University of Chicago Pritzker School of Medicine
Slide 51: Role of inflammation in atherosclerosis?
Role of inflammation in atherosclerosis? - A fierce debate started in the 19th century - Both observed cellular inflammatory changes in the atherosclerotic vessel walls Carl von Rokitansky Rudolf Virchow “Inflammation accompanies atherosclerosis” “Inflammation initiates atherosclerosis” Rolitansky;
Slide 52: Chronic Inflammation is a Driver of Cardiovascular Risk
Chronic Inflammation is a Driver of Cardiovascular Risk >2-fold increase in relative ~46% of patients with inflammation despite CV risk due to inflammation maximal lipid therapy (across 4 studies) 3 Relative Risk 2 1 0 Inflammation Inflammation Absent Present Adapted from 1998_ridker_Circulation Sou
Slide 53: hsCRP and IL-6 predict MACE: STABILITY trial
hsCRP and IL-6 predict MACE, CV Death, and Total Death: results from the STABILITY trial % of CHD patients with an event over MACE by baseline hsCRP quartile 3 years by baseline IL-6 quartile 14% 14% 12% 12% Patients with event, % Cumulative risk, % 10% 10% 8% 8% 6% 6% 4% 4% 2% 2% 0% 0%
Slide 54: hsCRP more strongly associated with MACE than LDL and Lp(a)
Emerging evidence suggests that hsCRP is more strongly associated with MACE than both LDL and Lp(a)
Slide 55: Many CV disease patients have residual inflammatory risk
Many CV disease patients have residual inflammatory risk
Slide 56: Novel Targets for Reducing CRP for Atheroprotection
Novel Targets for Reducing CRP for Atheroprotection Ziltivekimab Ridker et al Circ Res 2016;118:145-156.
Slide 57: CANTOS trial design
Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS) Trial Design’ IL-1 is upstream of IL-6? Canakinumab 50 mg Q3M NLRP3 n=2,170 : Se inflammasome -}-—| BGE-102 + 10,061 patients Canakinumab 150 mg Q3M IL4B [-—Ceeanakinumab _) * Stable CAD (post Ml) n= 2,284 1 * On Statin, ACE/ARB, ——+ I
Slide 58: CANTOS MACE results
Placebo SC q 3 months Canakinumab 150/300 mg SC q 3 months MACE MACE - Plus HR 0.85 HR 0.83 Cumulative Incidence (%) Cumulative Incidence (%) 95%CI 0.76-0.96 95%CI 0.74-0.92 P = 0.007 P = 0.0006 0 1 2 3 4 5 Follow-up Years Follow-up Years 35 - 40% reductions in hsCRP and IL-6 No change in LDLC Ridke
Slide 59: Achievement of CRP < 2.0mg/L and mortality reduction
Achievement of CRP < 2.0mg/L Provide 50% reduction in Mortality if CANTOS like Responses can be Achieved in CVOT On-Treatment hsCRP On-Treatment IL-6 0.25 Placebo Placebo On-treatment hsCRP ≥ 2 mg/L On-treatment IL-6 ≥ median 0.20 On-treatment hsCRP < 2 mg/L On-treatment IL-6 < median 0.15 0.10 0.05
Slide 60: Lessons from canakinumab
Lessons from canakinumab: Robust reduction of inflammation through IL-1B has transformative potential for ASCVD
Slide 61: Primary RESCUE End Point Achieved
Primary RESCUE End Point Achieved Median Percent Change in hsCRP Median (Q1, Q3) hsCRP values (mg/L) at baseline, W13 and ET Time Ziltivekimab Placebo 7.5 mg 15 mg 30 mg 5.8 5.5 5.7 5.8 Baseline (3.3 ,9.9) (3.5 ,9.3) (3.5 ,8.1) (3.7 ,8.9) (N=66) (N=66) (N=66) (N=66) 5.1 1.0 0.6 0.5 W13 (3.4 ,9.2) (0
Slide 62: Increasing Responder Rate with Increasing Dose of Zilti
Increasing Responder Rate with Increasing Dose of Zilti Superior hsCRP Responder Rate Relative to Canakinumab in CANTOS hsCRP suppression >= 50% from baseline hsCRP suppression < 2 mg/L threshold hsCRP suppression >= 50% from baseline AND below 2mg/L
Slide 63: Ziltivekimab Significantly Reduced Fibrinogen, SAA and Haptoglobin
Ziltivekimab Significantly Reduced Fibrinogen, SAA and Haptoglobin Fibrinogen SAA Haptoglobin 0% N (W13)= 55, 55, 60, 54 N (W13)= 57, 58, 60, 56 N (W13)= 57, 58, 59, 55 N(ET)= 50, 50, 54, 52 N(ET)= 52, 52, 55, 52 N(ET)= 52, 52, 54, 52 A 100 mg/dL increase is associated 3.7 mg/L decrease with 15mg do
Slide 64: Five Phase 3 CVOTs enrolling > 24,000 patients
Five Phase 3 CVOTs enrolling > 24,000 patients
Slide 65: NLRP3 inhibitors are a potential oral IL-6
NLRP3 inhibitors are a potential “oral IL-6” 0% with comparable reductions in hsCRP NLRP3 IL-1β Inflammatory cascade & IL-6 targeting modalities -25% Maximum % change in hsCRP NLRP3 inflammasome IL-1β -50% IL-6 Canakinumab 300 mg | CANTOS, 12 weeks -75% VTX3232 30 mg QD | CV risk, 12 weeks NT-0796 2
Slide 66: NLRP3 inhibition benefits beyond IL-6
NLRP3 inhibition also has potential benefits beyond IL-6, reducing IL-18 & cell death that contribute to plaque destabilization NLRP3 drives ASCVD beyond IL-6 Baseline IL-18 is a CVD risk factor in the CANTOS trial NLRP3 inflammasome IL-1β IL-18 Pyroptosis IL-6 Plaque destabilization CRP Fibrinogen
Slide 67: Ophthalmology
NLRP3 Structural biology insights Phase 1 results Cardiovascular Paul Rubin, MD CMO & EVP Research Ophthalmology
Slide 68: The retinal opportunity for BGE-102
P3 LR N OPHTHALMOLOGY The retinal opportunity for BGE-102 Greater efficacy Oral treatment to lower with new MOA treatment burden Simultaneous treatment Ocular and systemic of bilateral disease biology addressed BGE-102 has shown therapeutic retinal exposure across species, including primates
Slide 69: NLRP3 activation is central to retinal diseases DME & GA
P3 LR N OPHTHALMOLOGY NLRP3 activation is a central feature of retinal diseases DME & GA Diabetic retinopathy / Dry age-related macular degeneration diabetic macular edema (DME) (AMD) / geographic atrophy (GA) hyperglycemia & oxidative stress accumulation of cellular debris (drusen, lipofuscin) and
Slide 70: DME: oral BGE-102 preserved retinal vascular integrity in preclinical model
P3 LR N OPHTHALMOLOGY DME: oral delivery of BGE-102 preserved retinal vascular integrity in a preclinical model of diabetic retinopathy Retinal vascular permeability Blood-retinal barrier integrity measured via fluorescein angiography claudin-5 IHC (endothelial tight junctions) Microvascular degener
Slide 71: DME: BGE-102 improved insulin sensitivity in obese mice
P3 LR N OPHTHALMOLOGY DME: BGE-102 improved insulin sensitivity in obese mice, recapitulating mouse genetics & establishing potential to treat the key disease driver BGE-102 Nlrp3 -/- HOMA-IR Insulin (Day 26) tolerance test (6 weeks) WT Nlrp3-/- Note: BGE-102 was dosed PO QD; semaglutide was dosed S
Slide 72: GA: BGE-102 analog prevented lipofuscin accumulation
P3 LR N OPHTHALMOLOGY GA: In a natural AMD preclinical model, oral delivery of a BGE-102 analog prevented age-related lipofuscin accumulation, a key disease feature Natural AMD model BAL-1901 prevented lipofuscin accumulation Lipofuscin punctae accumulate with age in outbred (HET3) mice with 3 mo of
Slide 73: Planned BGE-102 Phase 1b/2a POC in DME
P3 LR N OPHTHALMOLOGY Planned BGE-102 Phase 1b/2a POC in DME: goal is to demonstrate PD in the eye Anti-VEGF + oral placebo N=30 Primary endpoint ● % change in intraocular IL-6 DME R Anti-VEGF + BGE-102 N=30 Exploratory ● Additional intraocular biomarkers ● Plasma biomarkers Sham + BGE-102 N=30 ● BC
Slide 74: Targeting the NLRP3 inflammasome in DME & GA
Targeting the NLRP3 inflammasome in DME & GA Brian Hafler, MD, PhD Associate Professor Ophthalmology & Visual Science, Yale School of Medicine
Slide 75: NLRP3 inflammasome plays a key role in DME & dry AMD / GA
The NLRP3 inflammasome plays a key role in DME & dry AMD / GA Diabetic macular edema
Slide 76: NLRP3 inflammasome plays a key role in DME & dry AMD / GA
The NLRP3 inflammasome plays a key role in DME & dry AMD / GA Diabetic macular edema Geographic atrophy
Slide 77: Real-world DME remains burdensome despite anti-VEGF therapy
Real-world DME remains burdensome despite anti-VEGF therapy Why oral therapy matters Median of 9 intravitreal injections An effective oral adjunct or alternative could in year 1 across treatment arms reduce procedure burden and expand options for incompletely controlled patients. Treatment intensity
Slide 78: Human aqueous humor data support inflammation-rich DME
Human aqueous humor data support inflammation-rich DME Key findings ● Diabetic macular edema 124-patient aqueous humor study eyes showed higher IL-1β, IL-6, IL-8, MCP-1, Scientific implication IL-10, and VEGF than diabetic eyes without macular edema. An upstream inflammasome-directed ● These markers
Slide 79: Ph2 results for VEGF + IL-6 inhibition in DME
Ph2 results for VEGF + IL-6 inhibition support role of inflammation in DME N=124 Participants with ≥ 15 letter gain Sources: Roche ASOPRS / AAO 2025 Virtual IR Event; ARVO 2026 44.7% ranibizumab + vamikibart vs. 28.6% ranibizumab
Slide 80: Exploratory clinical data support inflammasome as target in DME
Exploratory clinical data support the inflammasome as a target in DME +9.8 letters -1.8 letters lamivudine at week 4 placebo at week 4 Interpretation These data support the relevance of inflammasome modulation in diabetic macular edema
Slide 81: BGE-102 is positioned upstream of inflammatory drivers in DME
BGE-102 is positioned upstream of inflammatory drivers in DME BGE-102 Mechanism ● Oral inhibitor of the NLRP3 inflammasome ● Intended to reduce inflammatory cytokines and vascular leakage ● Could complement anti-VEGF or potentially serve as an alternative in selected patients ● Oral dosing is the ke
Slide 82: IL-1β drives retinal VEGF in vivo
IL-1β, a downstream effector of the NLRP3 inflammasome, drives retinal VEGF in vivo Mechanistic implication If upstream NLRP3 inhibition reduces IL-1β signaling, it may also reduce VEGFA-linked vascular leakage.
Slide 83: Drusen are inflammatory drivers of the NLRP3 inflammasome in AMD
Drusen are inflammatory drivers of the NLRP3 inflammasome in AMD Drusen from donor AMD eyes activate the NLRP3 inflammasome. Doyle, S., Campbell, M., Ozaki, E. et al. Nat Med 18, 791–798 (2012). Hafler BP. Retina. 37(3):417, 2017 Dhodapkar RM, Martell D, Hafler BP. Glial-mediated neuroinflammatory m
Slide 84: NLRP3 knockout rescues RPE degeneration in mouse model of GA
NLRP3 knockout rescues RPE degeneration in mouse model of GA Wild-Type mice Nlrp3 knockout mice Subretinal injection Subretinal Control Control amyloid β injection amyloid β Healthy 100 % 0% 100 % 100 % RPE Narendran, S., Pereira, F., Yerramothu, P. et al. Nucleoside reverse transcriptase inhibitors
Slide 85: Inflammasome inhibition in humans: early signals in GA
Inflammasome inhibition in humans: promising early signals of potential efficacy in GA Phase 1 clinical trial suggests potential for Decreased incidence of AMD observed with fluoxetine, a weak NLRP3 inhibitor in a retrospective analysis inflammasome inhibitor intravitreal implant K8 53% reduction in
Slide 86: DME & GA treatment landscape
DME & GA David Boyer, MD treatment landscape Senior Partner Retina-Vitreous Associates Medical Group
Slide 87: Diabetic macular edema (DME)
Diabetic macular edema (DME)
Slide 88: DME is the leading cause of vision loss in working aged adults
DME is the leading cause of vision loss working aged adults Normal Vision Vision with DME ~27M ~25% of all diabetes patients develop DME within 10 patients years of diagnosis globally 60 years average age of diagnosis Elevated HbA1c is the largest risk factor for DME Systemic disease, progression re
Slide 89: DME progresses due to hyperglycemia-driven vascular fluid leakage
DME progresses due to hyperglycemia-driven vascular fluid leakage in the macula, directly causing central vision loss Chronic hyperglycemia Persistent fluid damages Fluid accumulates in causes breakdown of photoreceptor layer (EZ) the macula, visible on OCT the blood-retinal barrier Leads to central
Slide 90: ~45% of diagnosed patients are treated with anti-VEGFs
~45% of diagnosed patients are treated with anti-VEGFs; ~55% are observed and not actively treated Diagnosed DME patients ~55% ~45% Observed Treated ● Patients with no to mild VA impairment, but ● Anti-VEGFs are generally initiated once progressive structural damage on OCT scan disease becomes cente
Slide 91: Compliance is a key challenge
Compliance is a key challenge … Number of anti-VEGF injections received Injections are invasive Real-world (IRIS) vs aflibercept 2 mg q8W label and inconvenient; in the real world, they are not administered as frequently as they should be Aflibercept Q8W per label Real-world Number of eyes DME 124,6
Slide 92: 50-70% lower VA gains in the real world vs. trials
… that has led to 50-70% lower VA gains in the real world vs. in trials Real world Clinical trials Sources: Ciulla 2020, Wells 2015, Boyer 2015, Korobelnik 2014 92
Slide 93: ~50% of patients have persistent fluid on anti-VEGF therapy
Even with strong compliance, ~50% of patients have persistent fluid on anti-VEGF therapy % of eyes with persistent DME* *Note: Persistent DME was defined as central subfield thickness ≥ 250 µm Source: Bressler 2018 93
Slide 94: An effective oral therapy could benefit more patients
An effective oral therapy could benefit not only patients currently treated with anti-VEGFs but could allow for treatment of earlier-stage disease not currently treated Disease progression Sums to 100% of diagnosed DME patients Observed Treated ~15% ~40% ~25% ~20% No VA Mild VA Inadequately Well con
Slide 95: Geographic atrophy (GA)
Geographic atrophy (GA)
Slide 96: Geographic atrophy is a leading cause of blindness in the elderly
Geographic atrophy is a leading cause of blindness in the elderly, characterized by irreversible central vision loss GA vision loss progression >8M Most severe form of AMD (~20% of all cases) At risk Early patients Est. 18M patients by 2040: rapidly growing globally Age 75: median age of onset Chara
Slide 97: GA is characterized by continuous neurodegenerative decline
GA is characterized by continuous neurodegenerative decline Expansion of atrophic RPE cell death leads to Drusen build up & initial RPE lesions photoreceptor degeneration dysfunction Lesions signal established GA Photoreceptors convert light and lead to VA loss when they into vision signals cover th
Slide 98: Effects of GA on quality of life can be devastating
The effects of GA on quality of life can be devastating, making it difficult or impossible for independent living Source: Bakri 2024,: Global Geographic Atrophy Insights Survey (N=203) 98
Slide 99: Approved complement inhibitors reduce lesion growth by 15-20%
Approved complement inhibitors have been shown to reduce lesion growth by 15-20%, no vision preservation shown to date Lesion growth Syfovre OAKS/DERBY Pooled Analysis- Showed declines in VA similar to sham but significant lesion growth rate reduction Visual acuity Source: Khanani 2023 99
Slide 100: Complement inhibitors prescribed in ~10% of patients
Complement inhibitors are currently prescribed in ~10% of patients Lesion growth in GA Efficacy Treatment Burden Modest slowing of lesion growth Intravitreal RoA Office visits & caregiver burden Injection site complications An effective oral therapy could rebalance efficacy and treatment burden Sour
Slide 101: An oral therapy could be used in earlier stages of dry AMD
An oral therapy could be used in earlier stages of dry AMD patients to slow GA progression GA Intravitreal injections only ~1M Complement inhibitors (~10% penetration) waterline Dry AMD ~10M Already taking oral AREDS supplements, a prophylactic treatment recommended by all ophthalmologists 101
Slide 102: Emerging approvable endpoint: the ellipsoid zone (EZ)
Emerging approvable endpoint: the ellipsoid zone (EZ) ● Definition: The EZ is a hyperreflective, photoreceptor rich band observed on OCT, serving as a crucial biomarker for assessing retinal health and vision loss ● Clinical relevance: EZ attenuation (loss) precedes GA formation and is the strongest
Slide 103: Summary & Q&A
Summary & Q&A Kristen Fortney, PhD Co-Founder & CEO
Slide 104: Pipeline overview
Pipeline overview Leveraging the BioAge platform to address key unmet needs in metabolic aging Mechanism Target IND- Program of action dosing Indication Discovery Lead op enabling Phase 1 Phase 2 Anticipated milestones CV risk CV risk Phase 2 results H2:2026 NLRP3 inhibitor BGE-102 (CNS penetrant) O
Slide 105: Q&A
BIOAGE Q&A
Slide 106: BIOAGE
BIOAGE