Rapport Therapeutics Raises $250M in Dual Financing Rounds Backed by Star Investors, Advances Precision Neuroscience Platform

On August 23 this year, biotechnology company Rapport Therapeutics (hereinafter referred to as “Rapport”)Announces Completion of $150 Million Series B FinancingThis funding round was led by Cormorant Asset Management, with participation from Fidelity Management & Research Company, Goldman Sachs Asset Management, Third Rock Ventures, ARCH Venture Partners, and Johnson & Johnson Innovation-JJDC. The proceeds will be used to support Rapport Therapeutics’ clinical pipeline for psychiatric disorders and the development of its precision neurology R&D platform.

As a rising star in the small-molecule drug development market, Rapport completed its Series A and B financing rounds within six months. On March 7 of this year, Rapport just announced its debut with a $100 million Series A funding round.

In recent years, the small-molecule innovative drug industry has seen an influx of numerous startup biotechnology companies, leading to intense competition. Why has Rapport Therapeutics stood out among its peers and garnered favor from many investment institutions in a short period? How was it able to secure a substantial $250 million investment within just six months?

Rapport Therapeutics was founded in 2022,Its current headquarters is located in Boston, United States.Officially unveiled in March 2023 with a $100 million Series A financing round.Venture capital firm Third Rock Ventures and Johnson & Johnson’s investment arm, JJDC, jointly established Rapport., with a focus on drug development for neurological diseases,Dedicated to developing precision-targeted small-molecule drugs for the treatment of neurological disorders.Its platform leverages genomics, proteomics, and brain imaging technologies to identify receptor-associated proteins (RAPs) for precision neurotherapeutics.Identify targeted small-molecule drugs with the potential to transform the treatment of neurological disorders, thereby enhancing the efficacy and tolerability of existing therapies。

Beyond the backing of star investors, Rapport Therapeutics, a startup founded just over a year ago, has chosen to develop small-molecule drugs for neurological disorders—a highly challenging niche. Its confidence stems from its scientifically proficient advisory board.

Dr. David JuliusHe is one of the co-chairs of the committee and a member of the American Academy of Arts and Sciences, the National Academy of Medicine, and the National Academy of Sciences. With over 30 years of academic experience in physiology, biochemistry, and neuroscience, he has received numerous honors and awards, including the 2021 Nobel Prize in Physiology or Medicine, which he shared with Ardem Patapoutian for their discoveries of receptors for temperature and touch.

The other co-chair isDr. David MacMillanHe is a chemist and a Fellow of the Royal Society, who shared the 2021 Nobel Prize in Chemistry with Benjamin List for the discovery of asymmetric organocatalysis.

Rapport’s Scientific Advisory Board also includes renowned experts in ion channel signaling, epilepsy, and the origins of pain, such as Dr. Allan Basbaum, a member of the American Academy of Arts and Sciences, the National Academy of Medicine, and the National Academy of Sciences; Dr. David Clapham, the Aldo R. Castañeda Professor of Cardiovascular Research and Professor Emeritus of Neurobiology at Harvard Medical School; and Dr. Jeffrey L. Noebels, former President of the American Epilepsy Society.

Furthermore, Rapport Therapeutics is supported by a management team with an average of 20 years of experience.

Dr. David Bredt(Founder and Chief Scientific Officer) has over 20 years of experience in neuroscience drug R&D, having served as Vice President of Neuroscience at Eli Lilly and Global Head of Neuroscience R&D at Janssen Neuroscience. The founding of Rapport Therapeutics was based on his proposal to leverage RAP technology to target specific neuronal circuits.

Dr. Abraham N. Ceesay(The Chief Executive Officer) brings nearly 20 years of experience in the biopharmaceutical industry to Rapport. Prior to joining Rapport, he served as President of Cerevel Therapeutics, Chief Executive Officer of Tiburio Therapeutics, Chief Operating Officer of scPharmaceuticals, Head of Business at Keryx Biopharmaceuticals, and Vice President of Marketing at Ironwood Pharmaceuticals.

as well as Brad Galer (Chief Medical Officer), who has over 20 years of experience leading R&D and medical affairs teams for pain and epilepsy medications; Cheryl Gault (Chief Operating Officer), with over 20 years of experience in the biopharmaceutical industry; and Swamy Yeleswaram (Chief Development Officer), who has 20 years of experience at Incyte.

Neurological disorders are a heterogeneous group of conditions affecting the autonomic nervous system, peripheral nerves, and central nervous system. There are more than 600 distinct disorders, including migraine, non-migraine headaches, multiple sclerosis, Alzheimer’s disease and other dementias, Parkinson’s disease, epilepsy, and other neurological conditions. According to the World Health Organization’s report “Neurological disorders: Public health challenges,” neurological disorders—ranging from epilepsy to Alzheimer’s disease and from stroke to headache—affect up to 1 billion people worldwide, with approximately 6.8 million deaths attributed to these conditions each year.

Epilepsy is one of the most common neurological disorders. Among the 1 billion individuals affected by neurological conditions worldwide, approximately 50 million have epilepsy, corresponding to a prevalence rate of about 0.5%–1%. Although many underlying disease mechanisms can lead to epilepsy, the etiology remains unclear in approximately 50% of cases globally, posing significant challenges to its treatment.

Currently, more than 20 antiepileptic drugs are available for the symptomatic treatment of seizures. However, studies indicate that current pharmacological therapies remain ineffective in approximately 20%–30% of patients with epilepsy, a population considered to have drug-resistant epilepsy. Drug-resistant epilepsy not only causes structural damage to the nervous system but also leads to psychological health issues such as anxiety and depression, while increasing the morbidity and mortality rates associated with complications.

Due to the complexity of pathogenic mechanisms and the nervous system, traditional neuropharmacology faces challenges such as “broad drug action profiles,” “suboptimal efficacy,” and “pronounced side effects,” leaving a lack of highly specific therapeutic agents for neurological disorders.

Existing neuroactive drugs often lack the ability to precisely target specific receptors, as they primarily act on ubiquitous targets within the nervous system and, in some cases, on other parts of the body, whereas only specific cell types or brain regions require treatment. This indiscriminate, non-specific therapeutic approach can lead to adverse outcomes, including suboptimal efficacy, harmful side effects, and reduced safety and tolerability.

Unlike traditional therapies,Rapport Therapeutics leverages RAP to discover small-molecule therapies that selectively target genes and clinically validated targets。This approach enables targeting of receptors in specific neuroanatomical regions underlying the pathophysiology of neurological disorders with unprecedented precision.

Bredt discovered RAP and its role in regulating receptor expression and function more than two decades ago.Bredt et al. found that neurotransmitter receptors do not function in isolation; rather, RAP complexes modulate receptor expression and function. Therefore, RAP can be used to precisely guide neurotherapeutics to the neuronal tissues driving disease.

Current studies have demonstrated that RAP is a resident endoplasmic reticulum protein with a molecular weight of 39 kDa. It also functions as a molecular chaperone, binding tightly to certain newly synthesized members of the LDL receptor family in the endoplasmic reticulum and facilitating their transport to the Golgi apparatus.

Under physiological conditions, RAP interacts with cell surface receptors and acts as a molecular chaperone for these receptors, playing a role in their trafficking, activation, and signaling by preventing premature ligand-receptor interactions, thereby ensuring their safe passage through the secretory pathway. Furthermore, RAP promotes the proper folding of these receptors, a function that may be independent of its ability to inhibit ligand binding.

Although neurotransmitter receptors are widely distributed, RAPs typically function within discrete and specific cell types or brain regions. Rapport’s platform integrates cutting-edge genetics, functional proteomics, and brain imaging technologies to identify RAPs that are regionally localized and involved in disease-related signaling pathways.

Rapport integrates region-specific RAPs into the drug development process to develop precision medicines. By more precisely targeting the neural circuits and cell types at the origin of disease, Rapport has the potential to reduce off-target drug interactions, ultimately enabling modulation of neurotransmitter receptors with greater efficacy and fewer side effects.

Currently,Rapport Therapeutics has established a pipeline of psychiatric disease programs aimed at treating drug-resistant epilepsy, which is currently in Phase I clinical development.

A study on the incidence of neuroimmune diseases in China, conducted by Professor Shi Fudong and Professor Wang Yongjun’s team at the National Clinical Research Center for Neurological Diseases, reveals that at least 27,500 people in China are diagnosed with neuroimmune disorders annually, averaging 75 cases per day. Among these, there are approximately 9 million epilepsy patients, with 400,000 to 500,000 new cases reported each year. The growing demand for neurological disease treatment underscores the urgent need for more effective innovative therapies.

Currently, the major companies in China focused on drug R&D in the field of neurological therapeutics include Jiangsu Nhwa Pharmaceutical, Shandong Luye Pharma, and Shanghai Saimoluo Biopharma.

Jiangsu Nhwa Pharmaceutical’s main product categories include anesthetics, psychotropics, and neurologics. In 2022, the company’s three Investigational New Drug (IND) applications for NH130 citrate tablets were approved (via implicit approval), with the drug intended for the treatment of Parkinson’s disease psychosis. NH130 citrate is a potent 5-HT2A receptor inverse agonist. Preclinical studies have demonstrated that NH130 citrate is effective in animal models of Parkinson’s disease psychosis without impairing motor function. Meanwhile, it exhibits minimal adverse effects such as cardiotoxicity and phospholipidosis, features a wide safety margin, and possesses favorable pharmacokinetic properties.

Shandong Luye Pharma’s product portfolio spans therapeutic areas including oncology, the central nervous system (CNS), cardiovascular diseases, and digestive and metabolic disorders. Its independently developed rivastigmine transdermal patch is a core product for the treatment of mild-to-moderate dementia associated with Alzheimer’s disease. Rivastigmine is a cholinesterase inhibitor; this class of drugs improves cognitive functions such as memory and thinking by increasing the levels of certain natural substances in the brain and enhancing communication pathways between nerve cells.

SR419, a candidate drug for peripheral neuropathic pain independently developed by Shanghai Saimoluo Biopharma, is an innovative therapy for the treatment of peripheral neuropathic pain. Clinical trial results indicate that SR419’s novel mechanism can mitigate certain potential central nervous system side effects.

According to Frost & Sullivan, the market size of central nervous system (CNS) drugs in China was $29.6 billion in 2019. Over the next 15 years, China’s CNS drug market is expected to grow rapidly, reaching $57.1 billion by 2034.

References:

[1]. Wallace H, Shorvon S, Tallis R. Age-specific incidence and prevalence rates of treated epilepsy in an unselected population of 2052922 and age-specific fertility rates of women with epilepsy. Lancet. 1998;352(9145):1970–1973.

[2]. The roles of receptor-associated protein (RAP) as a molecular chaperone for members of the LDL receptor family