Rapport Therapeutics, a clinical-stage biotechnology company, announced advancements in its clinical programs and changes to its board of directors. The company is focused on developing small molecule precision medicines for central nervous system (CNS) disorders, with its lead program, RAP-219, currently in Phase 2a development for focal epilepsy. The company anticipates topline data from ongoing trials in 2025.
RAP-219 Clinical Development
RAP-219, a negative allosteric modulator (NAM) of the AMPAR (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor), is designed to selectively target TARPγ8, a receptor-associated protein (RAP) linked to neuronal AMPARs. Rapport believes this precision targeting approach can improve activity and tolerability compared to traditional neuroscience medications. RAP-219 is being evaluated for focal epilepsy, peripheral neuropathic pain, and bipolar disorder.
"We are pleased with the progress we’re making with RAP-219, particularly as we continue the execution of our Phase 2a proof-of-concept trial in focal epilepsy,” said Abraham N. Ceesay, chief executive officer of Rapport.
The Phase 2a trial in focal epilepsy is actively recruiting adult patients with drug-resistant focal epilepsy who have an implanted responsive neurostimulation (RNS) device. The RNS device captures intracranial electroencephalography data and records the frequency of long episodes (LEs), serving as a biomarker for clinical seizures. A 30% reduction of LEs has been shown to predict meaningful changes (≥ 50% reduction) in clinical seizure frequency.
In addition to the Phase 2a trial, Rapport is conducting a second multiple ascending dose trial (MAD-2) of RAP-219 to inform dosing for a Phase 2a trial in bipolar acute mania. A Phase 1 human positron emission tomography (PET) trial is also underway to confirm brain target receptor occupancy and brain region specificity across a range of RAP-219 dosing and exposure levels. Topline results from both the MAD-2 and PET trials are expected in Q1 2025.
Regulatory Update
The FDA has placed a clinical hold on the Investigational New Drug Application (IND) for RAP-219 in diabetic peripheral neuropathic pain (DPNP), requesting additional information and amendments to the protocol design. Rapport is addressing the FDA feedback and will provide an update on the anticipated timing of the Phase 2a trial initiation once available. The clinical hold does not affect the ongoing Phase 2a trial in focal epilepsy or the planned trial in bipolar disorder.
Board of Directors Appointments
Rapport Therapeutics has appointed Rob Perez, Raymond Sanchez, MD, Paul Silva, and Wendy B. Young, PhD, to its Board of Directors. These individuals bring extensive experience in drug discovery, neuroscience clinical development, and operational leadership. Jeff Tong, PhD, partner at Third Rock Ventures, has resigned from the Board.
Financial Position
Rapport Therapeutics reported $320.7 million in cash, cash equivalents, and short-term investments as of September 30, 2024, which is expected to fund operations through the end of 2026.
