RPT1G / Remedy Plan - LARVOL DELTA

RPT1G, a novel hyperbolic NAMPT inhibitor, is highly effective against B-cell non-Hodgkin's lymphoma with germinal center origin (ASH 2025) - P1 | "RPT1G is efficacious in several hematological cancers, including acute leukemias andlymphomas. RPT1G is an effective treatment for NHL cancers of GC origin as a monotherapy and incombination with SOC and targeted therapies like olaparib. RPT1G was safe and well-tolerated in a first-in-human Phase 1 trial (NCT06667765) and is currently being evaluated in R/R AML and HR-MDS patients(NCT07107126)."

B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Myelodysplastic Syndrome • Non-Hodgkin’s Lymphoma • MYC • NAMPT

Phase 1, open-label, multi-center trial of RPT1G in patients with Relapsed/Refractory Acute Myeloid Leukemia and high-risk Myelodysplastic Syndromes/neoplasms (ASH 2025) - P1 | "Patients will be excluded if they have ongoing AEs from priortherapies; have received radiation within 14 days of the first dose of study drug; have known activeinfections; or have uncontrolled cardiac issues, or other medical comorbidities that will preclude safetyevaluation. Approximately 18 patients will be enrolled across 5-10 sites across the US and Australia.RPT1G is the first NAMPT hyperbolic inhibitor to be studied for the treatment of R/R-AML and HR-MDSpatients."

Clinical • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • NAMPT

First-in-human randomized placebo-controlled Phase 1 study of RPT1G, a novel hyperbolic NAMPT inhibitor for use in acute leukemias: Safety, pharmacokinetics, and pharmacodynamics in healthy volunteers (ASH 2025) - P1 | "Together, the Phase 1 safety, PK, and PD data show that RPT1G is the first drug capable ofinhibiting NAMPT at clinically meaningful levels without significant on-target toxicity. A Phase 1 studyevaluating RPT1G in relapsed/refractory acute myeloid leukemia and high-risk myelodysplasticsyndromes/neoplasms is underway (NCT07107126)."

Clinical • First-in-human • P1 data • PK/PD data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Ophthalmology • Thrombocytopenia • NAMPT

The Hyperbolic NAMPT Inhibitor RPT1G Synergizes with BCL-2 Family Inhibitors and Helps Overcome Venetoclax Resistance in Acute Myeloid Leukemia Cells (ASH 2024) - "While RPT1G exhibits mostly additive or modestly synergistic effects with AML standard-of-care agents, cytarabine and azacitidine, the synergy between RPT1G and venetoclax was maintained in MV4; 11 cells in the presence of either agent. Moreover, RPT1G strongly synergizes with olaparib, a poly(ADP-ribose) polymerase inhibitor, and olaparib further enhanced the synergy between RPT1G and venetoclax...Of note, navitoclax or AMG-176 further enhanced the synergy between RPT1G and venetoclax in MV4; 11-VR cells...In summary, the first-in-class hyperbolic NAMPT inhibitor RPT1G exhibited strong synergy with agents targeting anti-apoptotic BCL-2 family proteins in AML cells, both alone and in the presence of other standard-of-care agents. Given the crucial roles of NAMPT and BCL-2 family proteins in the survival and treatment-resistance of LSCs, RPT1G is emerging as an ideal candidate to be included in novel combinatorial therapies to enhance treatment efficacy of BCL-2 family..."

Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • B Cell Lymphoma • Leukemia • Lymphoma • Oncology • BCL2L1 • GLI2 • NAMPT

Venetoclax As a Combination Partner with NAMPT Inhibitor Rpt-1G for T-ALL (ASH 2024) - "Additionally, we aim to characterize the effects of RPT-1G on important biological processes in T-ALL that rely on NAD+. Overall, our findings contribute to a deeper understanding of how venetoclax-insensitivity could be overcome, paving the way for new treatment strategies in T-ALL."

Acute Lymphocytic Leukemia • B Cell Lymphoma • Leukemia • Lymphoma • Oncology • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • BCL2L1 • NAMPT

RPT1G: A 1st-in-Class Small Molecule NAMPT Inhibitor As a Novel Therapeutic for Acute Lymphocytic Leukemia (ASH 2023) - "This results in selective killing of leukemic cells, without on-target toxicity seen with complete NAMPTi. RPT1G emerges as an ideal clinical candidate – its favorable efficacy and tolerability target profile in preclinical models provides robust support for its utility in treating leukemias, warranting the initiation of our phase I clinical study to assess both safety and efficacy in patients."

Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • NAMPT • TET2

Remedy Plan Therapeutics Advances RPT1G for Myeloid Cancer Patients with Phase 1 Safety Data and IND Approval (GlobeNewswire) - "RPT will present results from the Phase 1 healthy volunteer study, upcoming R/R AML and HR-MDS study, and pre-clinical data on RPT1G efficacy in lymphoma at the American Society of Hematology general meeting on December 8th in Orlando, FL."

IND • P1 data • Preclinical • Acute Myelogenous Leukemia • Myelodysplastic Syndrome

A Novel Hyperbolic NAMPT Inhibitor Reduces Fat Mass, but Not Lean Mass, in a Mouse Model of Obesity (OBESITY WEEK 2025) - P1 | "We hypothesize that partial inhibition of NAMPT will reduce adiposity without impacting healthy tissues, therefore allowing for better tolerated treatment of patients with obesity. Here, we evaluated a novel RPT1G analog in a diet-induced obesity (DIO) mouse model to investigate the impact of NAMPT inhibition on obesity and its associated-metabolic phenotype."

Preclinical • Genetic Disorders • Metabolic Disorders • Obesity • NAMPT

A Study of RPT1G After Single and Multiple Doses in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=56 | Completed | Sponsor: Remedy Plan, Inc. | Active, not recruiting ➔ Completed

Trial completion

Safety and Proof-of-Concept Study of RPT1G in Adults With Acute Myeloid Leukemia and High-Risk Myelodysplastic Syndromes (clinicaltrials.gov) - P1 | N=18 | Not yet recruiting | Sponsor: Remedy Plan, Inc.

New P1 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

A Study of RPT1G After Single and Multiple Doses in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=56 | Active, not recruiting | Sponsor: Remedy Plan, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed

Remedy Plan Therapeutics Raises $18 Million Financing to Accelerate Advancement of Lead Asset RPT1G into Phase 1/2 Trials (GlobeNewswire) - "Financing includes participation from Schooner Capital, Alexandria Venture Investments, and other existing investors; Investment accelerates advancement of RPT1G, a novel NAMPT inhibitor, into a Phase 1/2 trial in patients with acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS)....A Phase 1/2 study in patients with AML or high-risk MDS alone and in combination with venetoclax will begin in the second half of 2025."

Financing • Acute Myelogenous Leukemia • Myelodysplastic Syndrome

RPT1G, a first-in-class hyperbolic NAMPT inhibitor that avoids on-target toxicity (AACR 2025) - "This first-in-human study will determine the safety and pharmacokinetics of hyperbolic NAMPT inhibition while measuring metabolic changes resulting from reduced NAMPT activity. RPT1G represents the first hyperbolic NAMPT inhibitor to be tested in humans, opening opportunities to therapeutically modulate NAD+ synthesis and providing a roadmap for the development of hyperbolic inhibitors of other essential enzyme targets."

Oncology • NAMPT

A Study of RPT1G After Single and Multiple Doses in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=56 | Recruiting | Sponsor: Remedy Plan, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open

Remedy Plan Therapeutics Showcases Preclinical Data from First-In-Class NAMPT Inhibitor, RPT1G, Demonstrating Synergy with BCL-2 Family Inhibitors in AML at the 2024 ASH Annual Meeting (GlobeNewswire) - "Remedy Plan Therapeutics...presented new data at the 66th American Society of Hematology (ASH) Annual Meeting & Exposition in San Diego, California demonstrating that RPT1G, a first-in-class hyperbolic NAMPT inhibitor, provides an eightfold reduction in acute myeloid leukemia (AML) burden when combined with B-cell lymphoma 2 protein (BCL-2) family inhibitors, including venetoclax, in preclinical models of AML. Remedy Plan's data also showed that treatment with RPT1G alone, RPT1G in combination with venetoclax, and RPT1G in a triple combination with venetoclax and the Poly (ADP-ribose) polymerase (PARP) inhibitor olaparib resulted in a fourfold increase in efficacy in venetoclax-resistant AML cells."

Preclinical • Acute Myelogenous Leukemia

Remedy Plan Therapeutics Initiates Dosing in Phase 1 Clinical Trial of RPT1G, a First-In-Class Hyperbolic NAMPT Inhibitor (GlobeNewswire) - "Remedy Plan Therapeutics...announced today the initiation of an adult healthy volunteer Phase 1 clinical trial of its first-in-class, hyperbolic NAMPT inhibitor, RPT1G....The Phase 1 randomized, double-blind, placebo-controlled clinical trial of RPT1G is being conducted in adult healthy volunteers in Australia (NCT06667765). The trial will evaluate RPT1G’s safety and pharmacokinetic properties while also exploring pharmacodynamic markers. Results from the Phase 1 clinical trial are expected in the first half of 2025 and will accelerate the company’s development of its oncology program in AML and high-risk MDS, currently planned to initiate in the second half of 2025."

New trial • P1 data • Trial status • Acute Myelogenous Leukemia • Myelodysplastic Syndrome

A Study of RPT1G After Single and Multiple Doses in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=56 | Not yet recruiting | Sponsor: Remedy Plan, Inc.

New P1 trial

Synergistic effects of RPT1G, a first-in-class small molecule NAMPT inhibitor, with venetoclax and olaparib in hematological malignancies. (ASCO 2024) - "Combination of RPT1G with either Venetoclax or Olaparib synergistically enhances killing of leukemic cells and presents as an effective strategy to improve treatment outcomes for patients with diverse malignancies."

IO biomarker • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Ovarian Cancer • Solid Tumor • HRD • NAMPT

Remedy Plan Therapeutics to Showcase Novel NAMPT Inhibitor During Oral Presentation at 2023 American Society of Hematology (ASH) Annual Meeting (PRNewswire) - "Preclinical and animal studies revealed that RPT1G is efficacious in acute leukemia, lymphoma, and solid tumor models, selectively killing cancer cells. Importantly, RPT1G was thousands-fold better tolerated by healthy cells, without the severe on-target toxicities reported for other NAMPT inhibitors....Based on the promising data presented at ASH, RPT1G will be advancing to the clinic in 2024."

New trial • Preclinical • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Solid Tumor