Leonabio, Inc. · NASDAQ:LONA
Leonabio — Athira Pharma — Investor Presentation (December 2025)
42 slides from Leonabio's investor presentation, Dec 18, 2025
Slide 1: December 2025 Corporate Presentation
December 2025 Corporate Presentation © Athira Pharma, 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: Athira Pharma: Building a pipeline to change lives
Athira Pharma Building a pipeline with the potential to change lives and create enduring value Rebranding coming soon! © Athira Pharma, Inc.
Slide 4: Management team with significant drug development and approval experience
Management team with significant drug development and approval experience LEADERSHIP Mark Litton, PhD President and CEO Mark Worthington, JD General Counsel Kevin Church, PhD CSO Javier San Martin, MD CMO Robert Renninger CFO Mark Kubik Head of BD (consultant) Collectively involved in multiple devel
Slide 5: Expected key inflection points within ~2 years
Lasofoxifene Phase 3 registrational study ongoing with >50% enrolled ATH-1105 Phase 2 POC study in ALS planned to start in 1H2026 Expected key inflection points within ~2 years Topline results expected in mid-2027 Topline results expected 2027 © Athira Pharma, Inc.
Slide 6: Late-stage program diversifies pipeline
Late-stage program diversifies pipeline Exciting opportunity in metastatic breast cancer Large Market Opportunity Differentiated Mechanism of Action Positive Phase 2 data Strategic Fit ER+/HER2- disease remains most common breast cancer subtype1 Represents approximately 70% of all breast cancers1 Gl
Slide 7: Lasofoxifene for metastatic breast cancer
7 Small molecule selective estrogen receptor modulator (SERM) Lasofoxifene for the potential treatment of metastatic breast cancer © Athira Pharma, Inc.
Slide 8: Lasofoxifene: Differentiated SERM for mESR1+ metastatic breast cancer
Lasofoxifene: Differentiated SERM for mESR1+ metastatic breast cancer Lasofoxifene + Abema combo led to a potential best-in-class median PFS in a heavily pre-treated mESR1 population in Phase 2 ELAINE-2 trial2 Potential best-in-class median PFS of 13 months in 2L/3L post-CDK4/6i setting Designed to
Slide 9: Treatment-resistant ER+ breast cancer is a critical unmet need
1. Initial Tumor ER+ tumors depend on estrogen signaling via estrogen receptor (ESR1) to grow and survive 2. Therapy response (1L) 1L endocrine therapies (AIs, SERMs, SERDs) are highly effective at shrinking and stabilizing tumor cells 3. Tumor cell dormancy In response to effective therapies, a por
Slide 10: Lasofoxifene blocks ESR1 signaling even in presence of mutations
Active ESR1 signaling drives tumor growth and metastasis in ER+ breast cancer1 Current endocrine therapies (SERDs, SERMs) aim to inhibit ESR1 signaling2 ESR1 mutations cause resistance to endocrine therapies3 Structural features of lasofoxifene inhibit mutant ESR1, overcoming resistance4,5 Lasofoxif
Slide 11: Lasofoxifene retains potency against ESR1 mutations
Lasofoxifene retains potency against ESR1 mutations, overcoming a key driver of endocrine resistance Affinity assay: Tested in luciferase reporter lines transfected with WT or mutant versions of ESR1. ESR1 was stimulated with a constant concentration of 17β-estradiol and inhibition of activation was
Slide 12: Lasofoxifene reduces tumor growth in animal models
Lasofoxifene reduces tumor growth in in vivo animal models and maintains potency in lines with mutated estrogen receptors1,2 Long half-life (6 days), excellent bioavailability, and volume of distribution optimizes receptor antagonism and tumor engagement2,3 No receptor degradation necessary and lack
Slide 13: 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 © Athira Pharma, Inc. Randomized Ph2 trial to demonstrate lasofoxifene’s targeted mechanism and establish its activity vs SoC fulvest
Slide 14: 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 Clear efficacy advantage: Lasofoxifene delivered longer progression-free survival and higher tumor response rates vs SoC fulvestrant. Validated targeted approach: ctDNA confirm lasofoxif
Slide 15: ELAINE-2: Potential best-in-class 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 Potential best-in-class durability: Laso+Abema delivered 13-month (56 weeks) median PFS – among the longest seen in 2L/3L post-CDK4/6i. Strong efficac
Slide 16: Treatment landscape is shifting toward combination regimen
Treatment landscape is shifting toward combination regimen © Athira Pharma, Inc. In the 2L+ space, endocrine monotherapy approaches appear to reach a ceiling of ~6 months PFS Durable disease control is increasingly pursued through biomarker-driven combination strategies, rather than next-generation
Slide 17: 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 Adapted from Goetz et. al, Future Oncology, 2025. © Athira Pharma, Inc. Stratification Factors: Vis
Slide 18: Over 50% enrolled, readout expected mid-2027
Over 50% enrolled - expected to readout in mid-2027 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 breast cancer trials Primary endpoint is determined by
Slide 19: 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 VAS, vaginal assessment scale; VuAS, vulvar assessment scale Sources: 1. Goldfarb et al. ISSWSH Annual Meeting 2023 (Poster); 2. Sermonix Conf Presentation (Slid
Slide 20: Added clinical benefits over other endocrine therapies
Lasofoxifene exhibits added clinical benefits over other endocrine therapies important to breast cancer patients and clinicians No head-to-head trials have been conducted comparing combination lasofoxifene therapy to other endocrine therapies Sources: 1. McClung et al. American Society of Bone and M
Slide 21: ELAINE-3 built on established biology and SoC benchmarks
Built on established biology, prior clinical signal, and established standard-of-care benchmarks ELAINE-3 is a registrational Phase 3 program Comparisons are based on independently published study results. No head-to-head trials have been conducted comparing lasofoxifene combination regimens to SoC
Slide 22: Competitive advantages of Laso combo in 2L/3L ESR1-mutated mBC
Competitive advantages of Laso combo in 2L/3L ESR1-mutated mBC Imlunestrant + Abema1,2 Lasofoxifene + Abema3,4 Administration Oral, 400 mg daily tablet, must be taken fasting Oral, 5 mg daily tablet, no food effect MOA SERD (ER degradation) SERM (ER modulation; tissue selectivity) Efficacy EMBER-3,
Slide 23: Endocrine backbone choice drives long-term risk and differentiation
Endocrine backbone choice drives long-term risk and differentiation Comparisons are based on independently published study results. No head-to-head trials have been conducted comparing combination lasofoxifene therapy to other combinations presented in this slide. Therefore, such data may not be dir
Slide 24: 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 Number of ER+/HER2- mBC 119k3 Number of ER+/HER2- mBC cases in 2L+ therapy 95k4 Number of patients who will develop ESR1 mutation 38k5 Global breast cancer market: $55B (2027)1 E
Slide 25: Orserdu sales illustrate the commercial opportunity
Orserdu sales illustrate the commercial opportunity for lasofoxifene’s precision oncology opportunity in 2L/3L ER+ mBC Sources: 1. IQVIA, RBC Capital Markets; 2. Bidard et al, J Clin Oncol 2022 © Athira Pharma, Inc. Orserdu (elacestrant) achieved rapid commercial uptake, validating ESR1 mutation as
Slide 26: Potential backbone endocrine candidate with expansion beyond ESR1 mutant disease
Lasofoxifene has the potential to be a backbone endocrine candidate with expansion potential beyond ESR1 mutant disease Treatment landscape schematic is illustrative and not intended to be comprehensive © Athira Pharma, Inc. ESR1 and PIK3CA wild-type ESR1 mut PIK3CA mut AI or fulvestrant + CDK4/6 in
Slide 27: Expansion potential as endocrine partner of choice
Expansion potential as endocrine partner of choice Oral administration Large unmet need Favorable safety profile and generally well-tolerated Superior PFS from Ph2 Exhibits improved QoL and clinical benefits Lasofoxifene: Ongoing registrational Phase 3 trial with readout in 2027 A differentiated the
Slide 28: ATH-1105 for the potential treatment of ALS
28 ATH-1105 for the potential treatment of ALS Small molecule positive modulator of HGF © Athira Pharma, Inc.
Slide 29: Slowing neurodegeneration in ALS is a critical unmet need
Slowing neurodegeneration in ALS is a critical unmet need Sources: 1. Packard Center. Retrieved from https://packardcenter.org/answer-als-partners-to-launch-the-end-als-challenge-digital-competition; 2. CDC. Retrieved from https://www.cdc.gov/als/php/abstracts-publications-reports/prevalence-2022-20
Slide 30: ATH-1105 enhances activity of HGF
ATH-1105 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 counteract neurodegeneration Strong rationale from literature to support HGF modulation in ALS Im
Slide 31: ATH-1105 MET activation and neuronal survival in motor neurons
MET activation: Data presented as mean ± SEM. Statistical significance was determined via paired t-test comparing MET activation (pMET/Total MET) in motor neurons treated with vehicle or ATH-1105 10 nM for 24 hours ; n = 2-3 technical replicates from each donor Neuronal survival: Representative imag
Slide 32: ATH-1105 preserved motor function and prolonged survival in ALS model
Prp-TDP43A315T transgenic mouse model of ALS ATH-1105 preserved motor function and prolonged survival in preclinical model of ALS Motor Function: Data presented as mean ± SEM. Statistics applied: 2-way ANOVA with the Dunnett’s test versus ALS + vehicle. ****p < 0.0001. n=10 mice per group Survival:
Slide 33: ATH-1105 protected against neurodegeneration
ATH-1105 protected against neurodegeneration Two months of treatment, Prp-TDP43A315T transgenic mice, ²ALS² or ²ALS mice.². WT = wild type (healthy control). Sciatic nerve sections stained with toluene blue to highlight axon structure. Scale bar = 10 µm. Data presented as mean ± SEM. Statistics appl
Slide 34: Disease progression attenuated with early or delayed treatment
Delayed treatment start Delayed treatment start Prp-TDP43A315T transgenic mouse model of ALS Disease progression was attenuated in ALS mice following early or delayed treatment initiation with ATH-1105 Data presented as mean ± SEM. Statistics applied: 2-way ANOVA with the Dunnett’s test versus ALS +
Slide 35: Phase 1 results support continued development of ATH-1105
Phase 1 results support continued development of ATH-1105 for the treatment of ALS Completed Phase 1 single and multiple dose studies in healthy volunteers Source: Ooi et al. NEALS Annual Meeting 2025 (Poster). All doses studied were generally well tolerated with no dose-limiting adverse events All
Slide 36: Exploratory analysis of neuronal-derived exosomes in Phase 1
Exploratory analysis of neuronal-derived exosomes (NDE) in the plasma from Phase 1 studies Biomarker results indicated a biological effect of ATH-1105 in humans and suggest potential to improve protein pathology in ALS In vitro data: **p<0.01, ***p<0.001 vs. glutamate alone. One-way ANOVA with Fishe
Slide 37: Planning underway for Phase 2 proof-of-concept study in 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 NDEs Functional measures ALSFRS-R Vital capacity Grip strength Aim is to e
Slide 38: ATH-1105 is a Phase 2-ready asset for ALS
Expansion potential ATH-1105 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 Neuroprotective* Favorable safety profile and generally well-tolerated Reduces plasma NfL* Biomarker sign
Slide 39: Advancing programs in breast cancer and ALS
Advancing 2 programs that have the potential to deliver life-changing therapies in breast cancer and ALS Transforming our future Compelling clinical development programs in areas of profound need Multibillion-dollar market opportunities Key clinical readouts within 2 years © Athira Pharma, Inc.
Slide 40: $90M upfront financing provides cash runway into 2028
$90M upfront financing provides cash runway through data readout and into 2028 Up front financing supports 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 [$6.35/sh
Slide 41: Expected key inflection points within ~2 years
Lasofoxifene Phase 3 registrational study ongoing with >50% enrolled ATH-1105 Phase 2 POC study in ALS planned to start in 1H2026 Expected key inflection points within ~2 years Topline results expected in mid-2027 Topline results expected 2027 © Athira Pharma, Inc.
Slide 42: Thank You
Thank You © Athira Pharma, Inc.
Athira Pharma — Investor Presentation (December 2025) on 6ix