Slide 1: Final Phase 2a AIR Data for Buloxibutid in IPF
VICORE PHARMA Final Phase 2a AIR Data for Buloxibutid in IPF Webinar discussing the late-breaking oral presentation at ATS 2024 May 22nd, 2024
Slide 2: Today's speakers
Today’s speakers Ahmed Mousa Bertil Lindmark Prof. Toby Maher Chief Executive Officer Chief Medical Officer Keck School of Medicine at University of Southern California Click to edit Master title style Moderator Megan Richards VP of IR, Communications, & Portfolio Strategy 2
Slide 3: Agenda
Agenda Welcome and rationale for buloxibutid in IPF Ahmed Mousa Final phase 2a AIR trial data with buloxibutid in IPF Buloxibutid, a novel angiotensin II type 2 receptor agonist in the 36-week phase 2a AIR trial Professor Maher Stabilized and improved lung function in individuals with idiopathic pul
Slide 4: Rationale for buloxibutid in IPF
Rationale for buloxibutid in IPF Ahmed Mousa Chief Executive Officer
Slide 5: AT2R agonism is an upstream intervention driving tissue repair
Angiotensin II type 2 receptor (AT2R) agonism is an upstream intervention driving tissue repair Buloxibutid • AT2R constitutively expressed in the lung, primarily on alveolar epithelial type 2 cells (AEC2) – the “alveolar repair cell” • AT2R activates tissue protective mechanisms via AEC2s, includin
Slide 6: The healthy alveolus and function of alveolar epithelial cells type 1 and 2
The healthy alveolus and function of alveolar epithelial cells type 1 and 2 Healthy alveolus • AEC2 is a progenitor cell that is critical for alveolar integrity and function: AEC2 o Proliferates to form new AEC2 o Differentiates to AEC1 that need to be replaced o Produces surfactant to maintain alve
Slide 7: Buloxibutid is an oral, selective AT2R agonist that drives tissue repair via AEC2
Buloxibutid is an oral, selective AT2R agonist that drives tissue repair via AEC2 precursor epithelial cells Alveolar compartment in IPF Effects of buloxibutid treatment Repeated Micro-injury Buloxibutid Increased AEC2 viability 1 & surfactant production 1 AEC2 dysfunction AEC2 Dysfunctional AEC2 TG
Slide 8: Buloxibutid is positioned to transform the IPF landscape
Buloxibutid is positioned to transform the IPF landscape Phase 2b ASPIRE: confirming the Upstream MoA Exceptional clinical data clinical activity in a randomized, with strong preclinical data in the phase 2a AIR trial placebo-controlled trial AT2 receptor expressed on Mean FVC change from baseline o
Slide 9: Buloxibutid in the 36-week phase 2a AIR trial
Buloxibutid, a novel angiotensin II type 2 receptor agonist in the 36-week phase 2a AIR trial Stabilized and improved lung function in individuals with idiopathic pulmonary fibrosis (IPF) Prof. Toby Maher Keck School of Medicine at University of Southern California
Slide 10: AIR - an open-label, international, phase 2a trial of oral buloxibutid
AIR - an open-label, international, phase 2a trial of oral buloxibutid 100 mg BID for up to 36 weeks in treatment-naïve IPF patients Patient population Patient population Clinic visits with FVC measurements Treatment-naïve IPF Week 2 4 6 9 12 15 18 21 24 28 32 36 patients with Screening period Follo
Slide 11: Disposition of patients
Disposition of patients Screened n=138 (86) Screen failure1 • Majority of discontinuations occurred Enrolled and Treated before treatment week 12 and during n=52 COVID-19 pandemic • Post week-12 discontinuation rate was 17% (24) Did not complete 36-week visit2 Completed 36-week visit N=28 Safety Ana
Slide 12: Demographic and baseline disease characteristics
Demographic and baseline disease characteristics Baseline demographics Baseline disease characteristics Buloxibutid Buloxibutid Characteristic 100 mg BID Characteristic 100 mg BID N=52 N=52 Time since IPF diagnosis (years); mean (SD) 1.0 (1.20) Age (years); mean (SD) 67.3 (9.38) Mean - mL (SD) 2387
Slide 13: Safety and tolerability summary
Safety and tolerability summary Buloxibutid 100 mg BID Buloxibutid 100 mg BID Treatment emergent adverse event (TEAE) N=52 Most common TEAEs - any causality N=52 n (%) n (%) Any TEAE 37 (71.2) Hair loss 10 (19.2) Related to trial drug 10 (19.2) Rash 4 (7.7) Serious TEAEs* 5 (9.6) Cough 4 (7.7) Relat
Slide 14: Stabilization and improvement of FVC over weeks
Stabilization and improvement of FVC over 36 weeks 400 *** 300 ** *** Buloxibutid (C21) FVC change (mL) 200 28 ** mean +SEM 28 28 100 * 33 40 34 0 32 n=48 44 35 34 48 39 -100 -200 Click to edit Master title style Untreated# 0 4 8 12 16 20 24 28 32 36 Week Note: n=48 patients with 2-week FVC data. Ob
Slide 15: Buloxibutid drives a trend of decreased TGFβ1 and increases MMP-13
Buloxibutid drives a trend of decreased TGFβ1 and increases collagenase MMP-13 Plasma TGFβ1 Plasma MMP-13 20 250 ** 16 200 *** Plasma MMP-13 (% of baseline) Plasma TGFβ1 ** (ng/mL) 12 150 8 100 4 50 0 0 Baseline Week 12 Week 24 Week 36 Baseline Week 12 Week 24 Week 36 n=37 n=36 n=28 n=23 n=37 n=36 n
Slide 16: Buloxibutid in idiopathic pulmonary fibrosis
Buloxibutid in idiopathic pulmonary fibrosis Buloxibutid is an upstream intervention with a novel mechanism of action expected to drive tissue repair in IPF The safety profile shows excellent gastrointestinal tolerability and no treatment related serious adverse events Lung function stabilized and i
Slide 17: AIR data context and deep dive
AIR data context and deep dive Bertil Lindmark Chief Medical Officer
Slide 18: Baseline patient characteristics in line with other IPF trials
Baseline patient characteristics in line with other IPF trials Key Characteristics AIR INPULSIS 1&2 (N=52) (N=1,061)1 Age (years) - Mean (SD) 67 (9) 67 (8) Males 77% 80% In line with other trials. Gender Females 23% 20% White 27% 57% Enrolled study population has disease progression comparable to Et
Slide 19: Treatment emergent adverse events: better tolerability than SoC
Treatment emergent adverse events: buloxibutid shows better tolerability than SoC Ph3 INPULSIS-1 Ph2a AIR 1 52-week treatment 36-week treatment Nintedanib Placebo Buloxibutid n=309 n=204 n=52 Any AE 96% 89% 71% Common AEs (Non-exhaustive) Diarrhea 62% 19% 6% Good GI side effect profile Nausea 23% 6%
Slide 20: All subgroups show FVC stabilization and increase over baseline at 36 weeks
All subgroups show FVC stabilization and increase over baseline at 36 weeks 400 Change at week 36 vs baseline Mean FVC change at week 36 vs baseline Mean and median; ∆mL Subgroup (# patients); ∆mL Mean FVC change at +216 ml week 36 vs baseline (all) Probable UIP (n=18); 321 300 Median FVC change at
Slide 21: Increase in percent predicted FVC consistent with increase in absolute FVC
Increase in percent predicted FVC consistent with increase in absolute FVC Average ppFVC change from baseline at week 36 8 7.5% Buloxibutid also demonstrated a 6 median FVC change from baseline at week 36 of +2.2% 4 2 % 0 -2 -2.0% -4 Nintedanib2 -4.2% -6 Buloxibutid1 Untreated2 Click to edit Master
Slide 22: Buloxibutid vs historical standard of care and untreated decline
Putting it in context: buloxibutid vs historical standard of care and untreated decline Percentage of patients outperforming expected ∆FVC 100% Buloxibutid outperforms expected change in FVC of untreated patients and those treated 82% with current standard of care at 36 weeks 75% Buloxibutid Click t
Slide 23: Buloxibutid vs historical standard of care and untreated decline
Putting it in context: buloxibutid vs historical standard of care and untreated decline Percentage of patients with improved lung function (FVC) vs baseline 70% 60% 50% Most patients treated with buloxibutid experience 40% improved lung function at 36 weeks, outperforming 65% historical SoC and untr
Slide 24: Physicians determined to keep patients on therapy rather than move to SoC
Physicians overwhelmingly determined to keep patients on therapy rather than move to SoC Clinic visits with FVC measurements Week 2 4 6 9 12 15 18 21 24 28 32 36 Screening period Follow-up period Buloxibutid (C21) 100 mg B.I.D (<4 weeks) (2-4 weeks) 36-week treatment period Risk/Benefit Risk/Benefit
Slide 25: Putting it together & the phase 2b ASPIRE trial
Putting it together & the phase 2b ASPIRE trial Ahmed Mousa Chief Executive Officer
Slide 26: Buloxibutid drives a trend of decreased TGFβ1 and increases MMP-13
Buloxibutid drives a trend of decreased TGFβ1 and increases collagenase MMP-13 Plasma TGFβ1 Plasma MMP-13 20 250 ** 16 200 *** Plasma MMP-13 (% of baseline) Plasma TGFβ1 ** (ng/mL) 12 150 8 100 4 50 0 0 Baseline Week 12 Week 24 Week 36 Baseline Week 12 Week 24 Week 36 n=37 n=36 n=28 n=23 n=37 n=36 n
Slide 27: Reduction in plasma TGFβ1 supported by preclinical human lung slice data
The reduction in plasma TGFβ1 seen clinically is supported by preclinical data showing decrease of TGFβ1 in human lung slices TGFβ1 is a potent fibrogenic cytokine TGFβ1 protein levels in PCLuS1 ✱✱ • Stimulates extracellular matrix formation 150 ✱✱ • Drives differentiation of AEC2s to fibroblasts an
Slide 28: MMP13 demonstrates antifibrotic activity and is crucial for lung repair in IPF
MMP13 demonstrates antifibrotic activity and is crucial for lung repair in IPF Bleomycin-Challenged MMP13 -/- vs. WT Mice Cabrera et al., 2019 MMP dysregulation contributes to IPF pathogenesis WT MMP13 KO • MMP13 is an enzyme able to cleave fibrillar collagens and plays a significant role in ECM rem
Slide 29: Buloxibutid protects AEC2s and drives increased surfactant production
Buloxibutid protects AEC2s and drives increased surfactant production Surfactant protein expression increased by buloxibutid in ex Buloxibutid (C21) protects AEC2 cells against apoptosis1 vivo human IPF precision cut lung slices2 50 % Increase vs Control 42% +120% 40 31% %Cell death 30 29% +70% 20 1
Slide 30: Buloxibutid has a potentially disease modifying MoA
Buloxibutid has a potentially disease modifying MoA Effects of buloxibutid treatment Buloxibutid Increased AEC2 viability 1 & surfactant production AEC2 • AT2R agonism increases AEC2 viability and surfactant production • Restoring surfactant production can address alveolar collapse, Inhibition of TG
Slide 31: Buloxibutid in IPF: Phase 2b ASPIRE trial design
Buloxibutid (C21) in IPF: Phase 2b ASPIRE trial design • A randomized, double-blind, placebo-controlled, parallel-group multicenter, dose-finding trial • IPF patients on stable nintedanib/SoC or not on SoC (no access, refused, intolerant or failed) • 52-week treatment duration; N=270 (90 per arm) S
Slide 32: ASPIRE is a global trial powered to demonstrate FVC stabilization
ASPIRE is a global trial powered to demonstrate FVC stabilization Large, conservatively powered study Global footprint with a broad range of countries Powered to detect FVC stabilization at 52 weeks Over 90 sites across 14 countries vs. conservative placebo arm assumption Transformative relative to
Slide 33: Q&A Session
Q&A Session yy” } y q [A L \ FR 0 0 f= q vcore pharma
Slide 34: Contact us
Contact us Visiting addresses www.vicorepharma.com Stockholm Copenhagen Boston Kornhamnstorg 53 Agern Allé 5A Cambridge Innovation Center, 14th floor, info@vicorepharma.com SE-111 27 Stockholm DK-2970 Hørsholm One Broadway, Cambridge Sweden Denmark MA 02142, USA