Rapport Therapeutics (RAPP) Stifel 2024 Healthcare Conference summary

Company overview and strategy

• Focused on precision neuroscience, leveraging receptor-associated protein science for targeted therapies in CNS disorders, including epilepsy, bipolar disorder, and pain.

• Lead program RAP-219 targets gamma-8 TARP AMPA modulators, aiming for best-in-class efficacy in focal epilepsy and potential in neuropathic pain and bipolar disorder.

• Discovery platform supports additional late-stage programs, with development candidate nominations as the next milestone.

• Well-capitalized with cash runway through 2026, following a $174 million IPO in June 2024.

• Ongoing development of a long-acting injectable for epilepsy, aiming to be the first in its class.

Scientific foundation and drug rationale

• RAP-219 is based on the discovery that AMPA receptors have regionally distributed receptor-associated proteins, enabling selective modulation in the forebrain.

• Targeting gamma-8 TARP allows modulation of AMPA receptors in the hippocampus, prefrontal cortex, and amygdala, potentially reducing side effects like sedation and ataxia.

• Preclinical models, especially the corneal kindling model, support efficacy and translation to clinical success in focal epilepsy.

• The RNS patient population in the phase IIa study is demographically similar to broader focal epilepsy patients, supporting generalizability.

Clinical development and trial design

• Phase IIa proof-of-concept study for RAP-219 is enrolling refractory focal epilepsy patients with RNS devices, using reduction in long EEG episodes as the primary endpoint.

• Long episode reduction is a validated biomarker, predictive of clinical seizure reduction, with data expected mid-2025.

• Study design allows for rapid assessment of efficacy and may enable direct transition to phase III registration studies if results are positive.

• Safety data from phase I SAD-MAD studies show on-target pharmacology and improved tolerability with stepwise dosing.