BioPharma, Pharma

CNS-Focused Rapport Therapeutics Preps IPO to Back Phase 2-Ready Epilepsy Drug

Rapport Therapeutics’ lead program could offer more targeted epilepsy treatment compared to currently available anti-seizure medications, which introduce many side effects. The IPO will support plans to develop the oral small molecule in focal epilepsy as well as peripheral neuropathic pain and bipolar disorder.

Rapport Therapeutics, a young biotech company with technology from the labs of Johnson & Johnson, is now preparing to enter the public markets to finance clinical research for a lead program that could help patients whose epilepsy doesn’t respond to currently available anti-seizure medications.

Rapport’s IPO paperwork filed with securities regulators late Friday does not yet specify how many shares it plans to offer and in what price range. IPO research firm Renaissance Capital has penciled in a $100 million placeholder figure for the proposed stock offering. The biotech company, which is headquartered in Boston and maintains additional office and lab space in San Diego, has applied to list shares on the Nasdaq under the stock symbol “RAPP.”

Of the estimated 3 million adults in the U.S. who suffer from epilepsy, about 1.8 million have focal epilepsy, Rapport said in its IPO filing. In this form of epilepsy, seizures are caused by intermittent abnormal electrical activity in specific areas of the brain. The AMPA receptor is a clinically validated epilepsy target addressed by some currently available epilepsy drugs. But these anti-seizure medications bind to AMPA receptors throughout the brain, which contributes to side effects that are unrelated to epilepsy, such as cognitive impairment, sedation, lack of muscle coordination, and dizziness, Rapport said in its IPO filing.

The research of Rapport focuses on receptor-associated proteins (RAPs), which play a key role in regulating receptor expression and function. Lead program RAP-219 is designed to selectively target a neuronal RAP for the AMPA receptor. This RAP, TARP gamma-8 RAP, is found only in certain regions, such as the hippocampus, which is involved in focal epilepsy, the company said in the filing. In a Phase 1 study enrolling healthy volunteers, Rapport reported its TARP gamma-8 RAP-targeting drug was well tolerated with results that support once-daily oral dosing.

“We believe that RAP-219, as compared to currently available [anti-seizure medications], has the potential to have a greater therapeutic index, meaning a wider range of doses at which it is likely to be effective without causing unacceptable [adverse effects],” Rapport said in its filing. “If RAP-219 is approved, this could have important clinical utility for the management of focal epilepsy.”

Rapport is now planning a Phase 2a study enrolling patients with drug-resistant focal epilepsy. The company plans to begin the study in the middle of this year; preliminary data are expected in mid-2025. Rapport believes targeting TARP gamma-8 could also treat peripheral neuropathic pain and bipolar disorder. Additional Phase 2a tests for both indications are planned for later this year and in 2025. Rapport’s research has also identified a different molecule that addresses TARP gamma-8 while offering different chemical and pharmacokinetic properties. This molecule, named RAP-199, is on track for a Phase 1 study planned for the first half of 2025.

The RAP technology platform has yielded drug candidates for other targets. Rapport has discovery-stage research addressing the nicotine acetylcholine receptor (nAChR). One program for this target is in development for chronic pain and another program is for hearing disorders.

Rapport is based on the discoveries of David Bredt, the company’s scientific founder and chief scientific officer. The filing states Bredt pioneered the targeting of RAPs with small molecules in executive roles at Johnson & Johnson subsidiary Janssen Pharmaceutica and Eli Lilly, as well as an earlier role as a professor of physiology at the University of California, San Francisco. Rapport’s employee roster includes scientists who worked on the RAP platform at Janssen.

Rapport formed in 2022 with support from Third Rock Ventures and Johnson & Johnson Innovation-JJDC, the investment arm of J&J. The company licensed certain RAP programs from Janssen, including lead drug candidate RAP-219 as well as other assets stemming from the research of Bredt and his Janssen colleagues. Rapport’s CEO is Abraham Ceesay, whose experience includes serving as president of Cerevel Therapeutics, a neuroscience drug developer that is being acquired by AbbVie.

Since its founding, Rapport has raised about $250 million from investors, according to the filing. The most recent capital raise was a $150 million Series B financing last August that turned out to be a crossover round, the type of financing that includes firms that invest in both public and private companies and signals a coming IPO. Cormorant Asset Management led the round and is one of Rapport’s largest shareholders, though the filing does not yet specify how big of a stake it owns. Other large shareholders in Rapport include Arch Venture Partners, Johnson & Johnson Innovation-JJDC, and Fidelity.

At the time of the funding announcement, executives told MedCity News that the financing extended Rapport’s cash runway into 2027. As of the end of the first quarter of this year, the company reported a cash position of $74.3 million and short-term investments totaling $119 million. According to the prospectus, a yet-to-be-determined amount of the IPO proceeds will go toward Phase 2a development of RAP-219, including proof-of-concept trials in focal epilepsy, peripheral neuropathic pain, and bipolar disorder. An unspecified sum will also be used for Phase 1 testing of a long-acting injectable form of RAP-219, as well as early clinical development of RAP-199.

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