Remedy Plan Therapeutics has achieved a significant breakthrough in cancer drug development with RPT1G, the first NAMPT inhibitor to demonstrate safety and tolerability in human studies. The novel compound successfully completed Phase 1 testing in healthy volunteers and received FDA clearance to advance into cancer patient trials, marking a potential turning point for a therapeutic target that has eluded researchers for over two decades.
Phase 1 Safety Results Exceed Expectations
RPT1G demonstrated an exceptional safety profile in a first-in-human, Phase 1, single-center, randomized, double-blind, placebo-controlled study involving 56 healthy adult participants. Of these, 42 participants received RPT1G across single and multiple ascending dose levels, with all participants completing treatment as planned.
The study results showed no treatment emergent adverse events above Grade 2, no serious adverse events, and no adverse events leading to drug discontinuation. Target engagement data confirmed that RPT1G inhibits NAMPT in humans at doses predicted to be clinically meaningful for hematologic malignancies.
"We have achieved something the field has been trying to do for decades," said Greg Crimmins, PhD, Founder and CEO of Remedy Plan. "RPT1G is a new kind of drug, a new class of inhibitor, that targets NAMPT activity in cancer cells while avoiding toxicity in healthy cells."
FDA Clearance Opens Path to Cancer Patients
The FDA has cleared Remedy Plan's investigational new drug (IND) application to test RPT1G in a Phase 1 study targeting cancer patients with relapsed or refractory acute myeloid leukemia (R/R AML) and higher-risk myelodysplastic syndromes/neoplasms (HR-MDS). The FDA approved initial dosing at the highest dose tested in healthy volunteers, reflecting confidence in the compound's safety profile.
Steve Abella, MD, Chief Medical Officer of Remedy Plan, noted that "data from the first-in-human healthy volunteer study confirmed the favorable preclinical data package for RPT1G and supports our newly opened study in myeloid cancers. The upcoming study is being conducted at doses we believe are clinically relevant to target NAMPT, a key driver of these diseases."
Orphan Drug Designation and Regulatory Advantages
The FDA has granted RPT1G orphan drug designation for AML, providing significant regulatory and commercial advantages. Through the Orphan Drug Act, this status offers tax credits, grants, waivers of certain administrative fees for clinical trials, and the potential for seven years of market exclusivity following drug approval.
Novel Mechanism Addresses Historical Challenges
RPT1G employs a unique hyperbolic inhibition mechanism to selectively reduce NAD in malignant cells while sparing healthy tissue. This approach represents a fundamental advance over previous NAMPT inhibitor programs that were terminated due to on-target toxicities.
Drug companies have targeted the NAMPT enzyme for more than 20 years, but safe inhibition in humans had remained elusive until now. The enzyme's dysregulation across many different disorders suggests broad therapeutic potential extending beyond blood cancers to solid tumors and other conditions.
Expanding Pipeline and Future Applications
Remedy Plan is positioning RPT1G as the foundation for a broader pipeline of hyperbolic NAMPT inhibitors. "We're in an exciting place, getting our drug to R/R AML and HR-MDS patients and then expanding to treat patients with solid tumors," Crimmins said. "Looking ahead, we have a pipeline of novel hyperbolic NAMPT inhibitors for both oncology and non-oncology applications. This is just the beginning."
The company plans to present comprehensive results from the Phase 1 healthy volunteer study, details of the upcoming R/R AML and HR-MDS study, and preclinical efficacy data in lymphoma at the American Society of Hematology annual meeting on December 8th in Orlando, Florida.
