Rapport Therapeutics 'Fully Prepared' to Launch Novel Epilepsy Drug RAP-219 Solo, CEO Says

Rapport Therapeutics查看公司主页, a neuroscience-focused biotech formed in 2023 through a collaboration between Third Rock Ventures (搜索)搜索该词条 and Johnson & Johnson查看公司主页's strategic venture capital arm, is advancing what could become a first-of-its-kind epilepsy medication. CEO Abraham Ceesay, in a wide-ranging interview with BioPharma Dive, expressed confidence that the company is "fully prepared" to launch RAP-219查看药品详情 independently, should the drug secure regulatory approval.

The company recently began enrolling patients in a late-stage program targeting focal epilepsy (搜索)搜索该疾病, with results expected in the coming years. Rapport's approach centers on a novel mechanism of action: selectively modulating AMPA receptors via TARPγ8 (搜索)搜索该靶点, a protein that is exclusively expressed in brain regions where seizures both originate and propagate.

A Novel Mechanism Targeting Seizure-Specific Brain Regions

RAP-219查看药品详情 targets one member — gamma-8 (TARPγ8 (搜索)搜索该靶点) — of the TARP family of nervous system proteins associated with AMPA receptors. The AMPA receptor (搜索)搜索该靶点 is already validated in epilepsy treatment; perampanel查看药品详情 (Fycompa), a pan-AMPA antagonist, is approved but inhibits AMPA receptors ubiquitously throughout the brain.

"TARPs are proteins associated with AMPA receptors, and the novelty is that this family all have distinct geographic distribution. Lo and behold, the TARPγ8 (搜索)搜索该靶点 version is only expressed in the brain exactly where seizures both originate and propagate," Ceesay explained. "So if we're able to modulate AMPA receptors in only that region, we can control seizures. But by not interacting with receptors in other areas of the brain, we believe we could deliver efficacy while dialing out all of the tolerability issues associated with traditional anti-seizure medications."

Ceesay emphasized that seizures represent a distinct opportunity compared to other neuroscience indications. "Seizures are really different. It's very clearly understood what channels are going to impact the neurotransmitters that are ultimately going to slow down that excitatory process," he said, adding that epilepsy has "the strongest preclinical translation" across all fields of neuroscience.

Phase 2 Results Build Conviction

The company's confidence in RAP-219查看药品详情 stems from Phase 2 results released last year. The trial enrolled focal epilepsy (搜索)搜索该疾病 patients who also had implantable neurostimulation devices that continuously record electrographic activity in the brain — a design element that distinguished this study from traditional epilepsy trials.

"We were able to not only measure the gold standard, which is the reduction of clinical seizures — and those are what patients actually recall and write down in a book — but also corroborate all of those reductions with an objective electrographic biomarker," Ceesay said. "That gave us real conviction we have a drug."

The Phase 2 study reported a 78% reduction from baseline in clinical seizure frequency over an eight-week period. However, Ceesay noted that the Phase 3 program is powered around a more conservative effect size. "That's always the smart thing to do, to be a bit more conservative as you go into Phase 3 and give your drug the best shot at success," he said.

Phase 3 Design and Expectations

For the Phase 3 program, Rapport has designed its studies based on benchmarks observed with effective anti-seizure medications. "What you see with very effective drugs in this space, and novel anti-seizure medications, is a 30% to 40% placebo-adjusted reduction in seizures. And the placebo rate in these studies is anywhere from 10% to 20%," Ceesay explained. "What that tells you is you want to see anywhere from 40% to 50% reduction in clinical seizures on the treatment arm. That's exactly how we've powered our studies."

The FDA's interest in requisite safety exposures for epilepsy treatments also necessitated a larger sample size in the Phase 3 program.

Strategic Approach to Partnerships and Commercialization

Rapport is pursuing a targeted partnership strategy focused on China, a region historically excluded from global epilepsy development programs. "China has a very large population. There are many patients living with focal seizures there — could we find a partner that would be able to commercialize, eventually, the asset in China, but also open up China as a region to add to our global development program," Ceesay said, describing this as a "win-win collaboration."

Beyond this specific strategic partnership, Rapport intends to maintain control of its lead program. "We really want to be able to control our destiny," Ceesay stated. "Coming to a partnership from a position of strength is such an important mindset in a growing biotech organization."

On the prospect of launching RAP-219查看药品详情 independently, Ceesay pointed to precedent in the neuroscience field. "You look at neuroscience, and I think it actually has proven where emerging biotech can be very successful as a commercial entity," he said, noting that epilepsy is "an indication that is very feasible for a biotech of our size to be able to scale up and launch."

Capital Allocation Discipline

Ceesay emphasized intentional capital allocation as a core operating principle, contrasting the current investment environment with the post-COVID period. "Investors, appropriately so, have a much higher level of discretion in this current cycle than they did coming right out of COVID," he said. "My approach, whether it's frothy times or more restrictive times, is just being unbelievably intentional about capital allocation."

Rapport was aggressive early on in building a strong independent board, which Ceesay views as essential for an effective public company. The company's lead indication strategy — choosing epilepsy as a foundation — was designed to allow the organization to take more risk on its early-stage pipeline, which includes traditional CNS indications that lack the biomarker advantages of epilepsy.