Slide 1: Initial Results of Zovegalisib (RLY-2608), a Mutant-Selective PI3Kα Inhibitor
Initial Results of Zovegalisib (RLY-2608), a Mutant-Selective PI3Kα Inhibitor in Adult and Adolescent Patients with PIK3CA-Driven Vascular Malformations Bryan Sisk1, Ionela Iacobas2, Ahmad Al-Huniti3, Eulalia Baselga4, Daniel Willis1, Joana Mack5, Vivian Y. Chang6, Sarah Mc Dermott7, Adrienne Hammil
Slide 2: Disclosure slide
Disclosure slide Dr. Sisk is a consultant for Relay Therapeutics, Novartis, Kaken Pharmaceuticals, Palvella Therapeutics, Palinos Therapeutics, and VasqueBio. #488 2
Slide 3: Slow-Flow Vascular Malformations are Highly Symptomatic Diseases Driven by Somatic Mosaic PIK3CA Mutations
Slow-Flow Vascular Malformations are Highly Symptomatic Diseases Driven by Somatic Mosaic PIK3CA Mutations • Isolated and syndromic slow-flow vascular malformations, such as LMs and PROS, are driven by somatic mosaic PIK3CA mutations • Non-mutant selective PI3Kα pathway inhibitors can have dose limi
Slide 4: Zovegalisib (RLY-2608) is a Novel, Oral, Allosteric Mutant-Selective PI3Kα Inhibitor
Zovegalisib (RLY-2608) is a Novel, Oral, Allosteric Mutant-Selective PI3K⍺ Inhibitor • Zovegalisib (RLY-2608) is a novel, pan-mutant-selective PI3Kα inhibitor that binds an allosteric pocket in activated PI3Kα • Zovegalisib has demonstrated 8-12 fold selectivity for PI3Kα helical and kinase mutants
Slide 5: ReInspire: a Phase 2 Trial of Zovegalisib in Pediatric and Adult Patients
ReInspire: a Phase 2 Trial of Zovegalisib in Pediatric and Adult Patients with PIK3CA-driven Vascular Malformations Part 1: Dose Selection Part 2: Dose Expansion (Data shown today) 400mg BID • In Part 1 Group 1 patients ≥12 yo Group 1: (n=10) were randomized to 3 Adults and biologically active doses
Slide 6: Zovegalisib – ReInspire Trial Demographics (Part 1, Group 1)
Zovegalisib – ReInspire Trial Demographics (Part 1, Group 1) Total 100mg BID 300mg BID 400mg BID (N=32) (N=11) (N=11) (N=10) Age (years), median (range) 24.5 (12, 63) 31 (13, 50) 24 (13, 54) 19.5 (12, 63) 12-17 / ≥18, n (%) 10 (31) / 22 (69) 4 (36) / 7 (64) 2 (18) / 9 (82) 4 (40) / 6 (60) Sex, M/F,
Slide 7: Zovegalisib – 60% Volumetric Response Rate by BICR Across All Doses
Zovegalisib – 60% Volumetric Response Rate by BICR Across All Doses Volumetric Response Rate (VRR)1 100mg BID 300mg BID 400mg BID Overall: 60% (12/20) 29% (2/7) 100% (6/6) 57% (4/7) Consistent benefit across subgroups Volumetric Response: Overall 60% ≥20% reduction PROS 60% Best % Change Three 100mg
Slide 8: Zovegalisib - Volumetric Response Over Time (BICR)
Zovegalisib - Volumetric Response Over Time (BICR) 100mg VRR: 300mg VRR: 400mg VRR: 29% (2/7) 100% (6/6) 57% (4/7) Three 100mg pts Overall VRR1: with lesion reduction 60% (12/20) between 18.2-19.8% (all ongoing) All patients ongoing Reductions generally deepened over time at all doses 1. Includes bo
Slide 9: Zovegalisib Efficacy Data – Clear Symptomatic Benefit
Zovegalisib Efficacy Data – Clear Symptomatic Benefit Investigator-Reported (IGIC) Patient-Reported (PGIC) Pain (IADRSS) 89% 79% 71% of patients improved by week 12 of patients improved by week 12 of pain symptoms improved by week 12 Very much Mean Change by timepoint Mean Change by timepoint Mean C
Slide 10: Zovegalisib – Treatment-Related Adverse Events ≥15% of Patients
Zovegalisib – Treatment-Related Adverse Events ≥15% of Patients No discontinuations for any reason 100mg BID (N=11) 300mg BID (N=11) 100mg+300mg BID (N=22) 400mg BID (N=10) All Gr Gr1 Gr2 Gr3+ All Gr Gr1 Gr2 Gr3+ All Gr Gr1 Gr2 Gr3+ All Gr Gr1 Gr2 Gr3+ Any TRAE 82% 36% 45% - 91% 55% 18% 18% 86% 45%
Slide 11: Part 1 Group 1 of ReInspire: Conclusions
Part 1 Group 1 of ReInspire: Conclusions • Zovegalisib (RLY-2608) is the first known mutant-selective PI3Kα inhibitor studied in patients with vascular anomalies • Across all doses, investigators assessed average overall symptoms to be between much and very much improved at 20 weeks with 60% achievi
Slide 12: Acknowledgments
Acknowledgments We would like to thank the patients and their families and caregivers, study investigators, sub-investigators, and research staff. ReInspire: A Phase 2 Study of Mutant-selective PI3Kα Inhibitor, RLY-2608, in Adults and Children with PIK3CA Related Overgrowth Spectrum (PROS) and Malfo