Slide 1: Corporate Presentation
Corporate Presentation August 2026 © LeonaBio, Inc.
Slide 2: Disclaimer
Disclaimer This presentation and any accompanying oral commentary contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements are based on our management’s beliefs and assumptions and on information currently availab
Slide 3: Management team with significant drug development and approval experience
Management team with significant drug development and approval experience LEADERSHIP Mark Litton, PhD Javier San Martin, MD Kevin Church, PhD Mark Worthington, JD Robert Renninger Mark Kubik David Portman, MD President and CEO CMO CSO General Counsel CFO CBO CEO, Sermonix (consultant) Select prior c
Slide 4: Exciting opportunity in metastatic breast cancer
Exciting opportunity in metastatic breast cancer LATE-STAGE PROGRAM DIVERSIFIES PIPELINE LARGE MARKET OPPORTUNITY DIFFERENTIATED MECHANISM OF ACTION • ER+/HER2- disease remains most common breast cancer subtype1 • Designed to overcome resistance that limits current endocrine agents3,4,5 • Represents
Slide 5: Lasofoxifene for the potential treatment of metastatic breast cancer
Lasofoxifene for the potential treatment of metastatic breast cancer Small molecule selective estrogen receptor modulator (SERM) © LeonaBio, Inc. 5
Slide 6: Lasofoxifene: Differentiated SERM for mESR1+ metastatic breast cancer
Lasofoxifene: Differentiated SERM for mESR1+ metastatic breast cancer DESIGNED TO OVERCOME RESISTANCE, IMPROVE QOL, AND REDEFINE THE STANDARD OF CARE AS THE ENDOCRINE PARTNER OF CHOICE Lasofoxifene + Abema combo led to a potential best-in-class median PFS Key Differentiators: in a heavily pre-treate
Slide 7: Significant opportunity for lasofoxifene in mESR1 mBC and beyond
Significant opportunity for lasofoxifene in mESR1 mBC and beyond ~70% ofarebreast ER+ cancers ~30% develop disease metastatic ~40% develop ESR1 activating mutations ~1.6M patients globally ~480k patients globally ~192k patients globally ET start AIs, tamoxifen AIs, fulvestrant SERDs, lasofoxifene En
Slide 8: Lasofoxifene is a third-generation oral SERM addressing endocrine resistance
Lasofoxifene is a third-generation oral SERM that addresses a major mechanism of endocrine resistance UNDERSTANDING THE MECHANISM: AI vs SERM vs SERD Aromatase inhibitors (AIs) How it works Block estrogen production upstream Limitation Cannot stop estrogen-independent ER signaling driven by ESR1 mut
Slide 9: Lasofoxifene is the most potent ER-directed agent against the ESR1 mutant receptor
Lasofoxifene is the most potent ER-directed agent against the ESR1 mutant receptor Best-in-Class Potency Lasofoxifene shows the lowest High potency enables lower doses IC50 (high potency) among the ER- needed to achieve activity and directed agents tested against the disease control, contributing to
Slide 10: Unique lasofoxifene MOA and pre-clinical data establish PoC in ESR1 mutations
Unique lasofoxifene MOA and pre-clinical data establish PoC in ESR1 mutations • Lasofoxifene reduced tumor growth in in In the hardest to treat Y573S ESR1-mut MCF7 xenograft vivo animal models and maintained 1.5 mouse model, lasofoxifene demonstrated superior potency in lines with mutated estrogen a
Slide 11: ELAINE Program: Stepwise validation toward a new standard of care
ELAINE Program: Stepwise validation toward a new standard of care ESTABLISHING LASOFOXIFENE AS THE NEXT-GENERATION ENDOCRINE BACKBONE FOR ER+ METASTATIC BREAST CANCER ELAINE-1 ELAINE-2 ELAINE-3 Proof of Concept (Complete) Combination Study (Complete) Registrational Trial (Ongoing) Randomized Ph2 tri
Slide 12: ELAINE-1: Increased PFS and anti-tumor activity vs fulvestrant
ELAINE-1: Increased PFS and anti-tumor activity with lasofoxifene compared to SoC fulvestrant in mESR1 population LASOFOXIFENE CLINICAL ACTIVITY VS. FULVESTRANT (SOC) IN ESR1-MUTANT BREAST CANCER IN A POC PHASE 2 STUDY ELAINE-1 Laso Fulv Laso Fulv Proof of Concept (n=52) (n=51) CBR 37% 22% Median PF
Slide 13: ELAINE-2: Potential best-in-class 13 months PFS with abemaciclib combination
ELAINE-2: Demonstrated potential best-in-class 13 months PFS with lasofoxifene combination with abemaciclib in a heavily pre-treated mESR1 population LASOFOXIFENE COMBINATION WITH CDK4/6I ABEMACICLIB IN ESR1-MUTANT BREAST CANCER, 100% PRIOR CDK4/6I (PHASE 2) ELAINE-2 Median PFS of 13 months; among t
Slide 14: Treatment landscape is shifting toward combination regimen
Treatment landscape is shifting toward combination regimen EMERGING DATA SUPPORT COMBINATION ENDOCRINE APPROACHES IN CDK4/6 INHIBITOR –PRETREATED ER+ BREAST CANCER • In the 2L+ space, endocrine monotherapy approaches appear to reach a ceiling of ~6 months PFS • Durable disease control is increasingl
Slide 15: ELAINE-3: Registrational trial of lasofoxifene in mESR1 population
ELAINE-3: Registrational trial of lasofoxifene in mESR1 population FDA-ALIGNED PH3 REGISTRATIONAL TRIAL TO ESTABLISH IMPROVED EFFICACY OF LASOFOXIFENE + ABEMACICLIB COMPARED TO CURRENT SOC COMBINATION Screening (30 days) Treatment Period (up to 48 mo) Study Outcomes 5 mg QD lasofoxifene Key Inclusio
Slide 16: ELAINE-3 is on track to complete enrollment in 2H2026
ELAINE-3 is on track to complete enrollment in 2H2026 OVER 75% ENROLLED – EXPECTED TO READOUT IN 2H2027 • Global study with >200 sites Europe, North America, and APAC (including China) • Study is being executed by Medpace, a full-service global CRO with extensive experience running large, successful
Slide 17: Lasofoxifene well-tolerated with differentiated impact on quality of life
Lasofoxifene was generally well-tolerated and had a differentiated impact on women’s quality of life over standard of care in early trials • Lasofoxifene is a SERM that primarily reduces estrogen signaling in breast tissue sparing healthy signaling in other tissues such as bone and urogenital • Part
Slide 18: Lasofoxifene exhibits added clinical benefits over other endocrine therapies
Lasofoxifene exhibits added clinical benefits over other endocrine therapies important to breast cancer patients and clinicians • The effects of lasofoxifene have been extensively investigated in several clinical studies • Increased bone density and reduced vertebral and non-vertebral fractures1,2 •
Slide 19: Endocrine backbone choice drives long-term risk and differentiation
Endocrine backbone choice drives long-term risk and differentiation LASOFOXIFENE + ABEMACICLIB vs. SERD + CDK4/6I REGIMENS Safety and tolerability • While cross trial comparisons should be interpreted with caution, lasofoxifene exhibits a favorable safety and tolerability profile, specifically with
Slide 20: Billion-dollar precision oncology opportunity in 2L/3L ER+ mBC
Lasofoxifene’s targeted activity in mutant ESR1 presents a billion-dollar precision oncology opportunity in 2L/3L ER+ mBC • Global breast cancer market: $55B (2027)1 US Market • Expected payer acceptance: Fulvestrant, elacestrant Number of ER+/HER2- mBC 119k3 precedents • Favorable outlook: Physicia
Slide 21: Orserdu sales illustrate the commercial opportunity for lasofoxifene
Orserdu sales illustrate the commercial opportunity for lasofoxifene’s precision oncology opportunity in 2L/3L ER+ mBC • Orserdu (elacestrant) achieved rapid commercial uptake, Orserdu sales1 supporting ESR1 mutation as a commercially viable biomarker • Commercial success was achieved despite modest
Slide 22: Lasofoxifene: Ongoing registrational Phase 3 trial with readout expected in 2027
Lasofoxifene: Ongoing registrational Phase 3 trial with readout expected in 2027 A DIFFERENTIATED THERAPY DESIGNED TO OVERCOME RESISTANCE, IMPROVE QOL, AND ESTABLISH A NEW STANDARD OF CARE IN ER+ ESR1-MUTANT BREAST CANCER Oral administration Favorable safety profile and generally well-tolerated Exhi
Slide 23: Brelgometon (ATH-1105) for the potential treatment of ALS
Brelgometon (ATH-1105) for the potential treatment of ALS Small molecule positive modulator of HGF © LeonaBio, Inc. 23
Slide 24: Slowing neurodegeneration in ALS is a critical unmet need
Slowing neurodegeneration in ALS is a critical unmet need Burden of ALS Treatment Limitations6 ALS is a devasting neurodegenerative • There is no cure for ALS and few effective treatment options disease in which people progressively lose muscle control • Approved therapies only modestly slow progres
Slide 25: Brelgometon: A CNS-penetrant positive modulator of HGF for ALS
Brelgometon: A CNS-penetrant positive modulator of HGF as a potential treatment for ALS • Brelgometon enhances activity of HGF, a critical neurotrophic factor in the nervous system • Activation of HGF signaling through MET (HGF receptor) on the surface of neurons and glia initiates processes that co
Slide 26: Brelgometon enhanced MET activation and survival in ALS-patient derived motor neurons
Brelgometon enhanced MET activation and survival in ALS-patient derived motor neurons CELLS DERIVED FROM FOUR PEOPLE WITH SPORADIC ALS MET activation Neuronal survival ALS donors ALS donors 1.6 Neuronal survival on Day 6 ALS 1 ALS 1 pMET/Total MET Level 4 ALS 2 ALS 2 1.4 (Fold-change) ALS 3 3 ALS 3
Slide 27: Brelgometon preserved motor function and prolonged survival in preclinical ALS model
Brelgometon preserved motor function and prolonged survival in preclinical model of ALS PRP-TDP43 A315T TRANSGENIC MOUSE MODEL OF ALS Motor Function Survival Treatment initiated 28 days 10 **** **** **** Grip strength (Newtons) 85 days 129 days **** Probability of Survival 8 100 75% survival 6 75 4
Slide 28: Brelgometon protected against degeneration of large motor axons in ALS mouse model
Brelgometon protected against degeneration and demyelination of large motor axons in an ALS mouse model PRP-TDP43 A315T TRANSGENIC MOUSE MODEL OF ALS ALS + WT + Vehicle ALS + Vehicle Brelgometon Sciatic nerve histopathology 20 mg/kg In ALS mice (center), axons in the sciatic nerve are smaller, fewer
Slide 29: Disease progression attenuated in ALS mice with early or delayed treatment
Disease progression was attenuated in ALS mice following early or delayed treatment initiation with brelgometon Balance beam 20 **** ^^^^ **** ^^^^ +++ WT + Vehicle PRP-TDP43 A315T TRANSGENIC MOUSE MODEL OF ALS **** ++ ALS + Vehicle 15 ^^^^ Cross time (s) ALS + ATH-1105 20 mg/kg (Early) 10 ALS + ATH
Slide 30: Phase 1 results support continued development of brelgometon for ALS
Phase 1 results support continued development of brelgometon for the treatment of ALS COMPLETED PHASE 1 SINGLE AND MULTIPLE DOSE STUDIES IN HEALTHY VOLUNTEERS • All doses studied were generally well tolerated Brelgometon Plasma Concentration-Time Profiles Following with no dose-limiting adverse even
Slide 31: Biomarker results indicated a biological effect of brelgometon in humans
Biomarker results indicated a biological effect of brelgometon in humans and suggest potential to improve protein pathology in ALS EXPLORATORY ANALYSIS OF NEURONAL-DERIVED EXOSOMES (NDE) IN THE PLASMA FROM PHASE 1 STUDIES Mechanism In vitro (spinal motor neurons) NDEs in human plasma Phospho-GSK3β (
Slide 32: Brelgometon is ready for a Phase 2 study in people living with ALS
Brelgometon is ready for a Phase 2 study in people living with ALS • Planning underway for a Phase 2 proof-of concept study to explore functional measures, biomarkers, and safety in people living with ALS • Design considerations: • ≥ 6 months treatment duration • Biomarkers, including plasma NfL and
Slide 33: Brelgometon is a Phase 2 ready asset for the treatment of ALS
Brelgometon is a Phase 2 ready asset for the treatment of ALS A NOVEL THERAPY DESIGNED TO ADDRESS THE COMPLEX PATHOLOGY AND MITIGATE NEURODEGENERATION IN ALS Oral administration Favorable safety profile and generally well-tolerated Biomarker signals in Neuroprotective* Phase 1 Reduces plasma NfL* Ex
Slide 34: Transforming our future
Transforming our future Advancing 2 programs that have the potential to deliver life-changing therapies in breast cancer and ALS Compelling clinical Multibillion-dollar market Key clinical readouts development programs in opportunities targeted within 2 years areas of profound need © LeonaBio, Inc.
Slide 35: PIPE financing up to $236 million
PIPE financing up to $236 million • Financing up to $236M would support lasofoxifene development program through topline data, with sufficient capital runway into 2028: • $90M upfront priced at a greater than 50% premium to our December 17, 2025 closing price of $6.35/share • If exercised, warrants
Slide 36: Thank You
Thank You @©LeonaBio, Inc. 36