Rapport Therapeutics Shares New Phase 1 Data on RAP-219's CNS Disorder Potential

Rapport Therapeutics, a company focused on creating precision medicines for central nervous system disorders, recently shared exciting results from their clinical trials on RAP-219. This investigational drug targets a specific protein, TARP8, associated with AMPA receptors, which are significant in many neurological conditions. The trials aimed to evaluate the safety, tolerability, and effectiveness of RAP-219, particularly in treating focal epilepsy.

In a positron emission tomography (PET) trial, RAP-219 achieved its target receptor occupancy, a measure linked to drug effectiveness, within just five days of administration. The trial confirmed that TARP8 is primarily expressed in the hippocampus and cerebral cortex, with minimal presence in the cerebellum and brain stem. This specific targeting is designed to enhance drug efficacy while minimizing adverse effects. RAP-219's ability to rapidly engage its target and achieve therapeutic brain concentrations was noted without compromising patient tolerability. These findings bolster the dosing strategy for an ongoing Phase 2a trial focusing on focal epilepsy, scheduled for results in mid-2025.

A second trial, the multiple ascending dose (MAD-2) study, also demonstrated promising outcomes. This double-blind, placebo-controlled trial involved healthy volunteers and explored different dosing regimens to determine safety and tolerability while ensuring rapid attainment of therapeutic drug levels. RAP-219 was generally well tolerated, with adverse events being mild and consistent with earlier studies. Importantly, no sedation or motoric impairments, common side effects of many anti-seizure medications, were observed with RAP-219.

Collectively, these trials underscore RAP-219's potential as a treatment with a broad therapeutic index, paving the way for flexible dosing options. The drug's design focuses on maximizing efficacy while minimizing side effects, a significant advantage over current treatments, which often lead to considerable side effects that negatively affect patients' lives.

RAP-219, as a clinical-stage AMPA receptor negative allosteric modulator, is crafted to selectively target TARP8. The restricted expression of TARP8 in key brain regions offers a unique opportunity for RAP-219 to provide sustained therapeutic benefits. With its long half-life and minimal drug interactions, RAP-219 is poised for use alongside other medications, thereby expanding its applicability.

Rapport Therapeutics is advancing clinical trials for RAP-219 across several indications, including focal epilepsy, diabetic peripheral neuropathic pain, and bipolar mania. The company’s precision approach aims to address the limitations of traditional neurology drugs by focusing on receptor-associated proteins, which are crucial in brain function. This innovative strategy forms the basis of Rapport's RAP technology platform.

In addition to sharing trial outcomes, Rapport announced a change in its leadership team, with Bradley Galer, M.D., stepping down as the chief medical officer. The company is in the process of finding a successor and is confident that this transition will not impact the progress of its clinical programs. Dr. Galer will assist during this transition period, and his contributions over the past two years have been recognized and appreciated by the company.

Overall, the results from the PET and MAD-2 trials highlight RAP-219's potential to transform treatment for central nervous system disorders. With ongoing trials and a strong commitment to innovation, Rapport Therapeutics continues to make strides in developing targeted therapies that improve patient outcomes.