RAPA-501 / Rapa Therap - LARVOL DELTA

Interim results confirm the safety and feasibility of autologous hybrid TREG/Th2 T stem cells (RAPA-501) in ALS patients with severe respiratory insufficiency (ALS-MND 2025) - P | " RAPA-501 were manufactured from apheresis products from pwALS using mTORC1/mTORC2 inhibition (temsirolimus) and differentiation cytokines (IL-2, TGF-b, IL-4). Hybrid TREG/Th2 RAPA-501 cells were feasibly manufactured, consistently expressed an effector TREG/Th2 phenotype, and safely administered to pwALS with severe respiratory insufficiency. Pulmonary and disease activity measures were relatively stable post-RAPA-501 therapy, with a potentially favorable overall survival pattern. RAPA-501 T stem cells therefore represents a potentially new approach for therapy of advanced-stage ALS."

Clinical • Amyotrophic Lateral Sclerosis • Inflammation • Respiratory Diseases • CD4 • CD73 • CD8 • FOXP3 • GATA3 • IL2 • IL4 • ITGAE

RAPA-501 Therapy for ALS (clinicaltrials.gov) - P2/3 | N=41 | Recruiting | Sponsor: Rapa Therapeutics LLC | Not yet recruiting ➔ Recruiting | Trial completion date: Jul 2025 ➔ Jun 2027 | Trial primary completion date: Jul 2025 ➔ Jul 2026

Enrollment open • Trial completion date • Trial primary completion date • Amyotrophic Lateral Sclerosis • CNS Disorders

RAPA-501 Therapy for ALS Expanded Access Protocol (clinicaltrials.gov) - P=N/A | N=0 | Available | Sponsor: Rapa Therapeutics LLC | N=40 ➔ 0

Enrollment change • Amyotrophic Lateral Sclerosis • CNS Disorders

RAPA-501 Therapy for ALS Expanded Access Protocol (clinicaltrials.gov) - P2/3 | N=40 | Recruiting | Sponsor: Rapa Therapeutics LLC | Available ➔ Recruiting | Phase classification: P ➔ P2/3

Enrollment open • Phase classification • Trial completion date • Trial initiation date • Trial primary completion date • Amyotrophic Lateral Sclerosis • CNS Disorders

RAPA-501 Therapy for ALS EAP (clinicaltrials.gov) - P=N/A | N=0 | Available | Sponsor: Rapa Therapeutics LLC

New trial • Amyotrophic Lateral Sclerosis • CNS Disorders

Phase 1 Trial of Autologous Hybrid TREG/Th2 Cells (RAPA-501) in Patients Living With ALS: In Vivo Modulation of Immune Regulatory Molecules (ALS-MND 2023) - P2/3 | " RAPA-501 were manufactured from apheresis products from pwALS using mTORC1/mTORC2 inhibition Poster Communications Clinical Trials and Trial Design 217 (temsirolimus) and differentiation cytokines (IL-2, TGF-beta, IL-4). Hybrid TREG/Th2 RAPA-501 cells were feasibly manufactured and safely administered. RAPA501 therapy is biologically active, as evidenced by a posttreatment increase in immune regulatory molecules, including CD4þ and CD8þ T cell expression of FOXP3, CD39, CD73, and PD-1. We are now evaluating potential RAPA-501 therapeutic effects in pwALS on a protocol expansion cohort."

IO biomarker • P1 data • Preclinical • Inflammation • ENTPD1 • FOXP3 • IL2 • IL4 • NT5E • TGFB1

RAPA-501 Therapy for ALS (clinicaltrials.gov) - P2/3 | N=41 | Recruiting | Sponsor: Rapa Therapeutics LLC | Phase classification: P1/2 ➔ P2/3 | N=21 ➔ 41 | Trial completion date: Dec 2023 ➔ Jul 2025 | Trial primary completion date: Dec 2023 ➔ Jul 2025

Enrollment change • Phase classification • Trial completion date • Trial primary completion date • Amyotrophic Lateral Sclerosis • CNS Disorders • IL1B • IL6 • PD-1 • TNFA

RAPA-501 Therapy for ALS (clinicaltrials.gov) - P1/2; N=18; Recruiting; Sponsor: Rapa Therapeutics LLC; Not yet recruiting ➔ Recruiting

Enrollment open • Amyotrophic Lateral Sclerosis • CNS Disorders • Complement-mediated Rare Disorders