SiteOne Raises $100M for Non-Opioid Pain Medication Development

Opioid drugs, while effective at managing pain, carry significant risks of addiction due to their action on receptors in the central nervous system. Addressing this challenge, SiteOne Therapeutics aims to develop non-opioid pain treatments that bypass these addiction pathways. The company recently secured $100 million to propel its lead program into a Phase 2 proof-of-concept trial next year.

Based in South San Francisco, SiteOne's research is centered on sodium channels, which are crucial for transmitting electrical signals throughout the body. SiteOne's CEO, John Mulcahy, compares sodium channels to electrical wiring in buildings, emphasizing that these channels are predominantly located in the peripheral nervous system. This positioning reduces the likelihood of addiction compared to drugs targeting the central nervous system.

The human body has nine sodium channels, but NaV1.7 and NaV1.8 are specifically involved in transmitting pain signals. Although these channels have been known since the 1990s, the scientific community faced challenges in identifying small molecules that could target both effectively. Recent advancements in chemistry have enabled researchers to address these targets more precisely.

Mulcahy explains that while all sodium channels are closely related, early efforts often inadvertently affected other channels, leading to undesirable side effects on nerves, muscles, or the heart. Among the leaders in sodium channel-targeting drug development is Vertex Pharmaceuticals, which is advancing suzetrigine, a molecule designed to inhibit NaV1.8 selectively. Suzetrigine, intended for acute pain management, is under FDA review with a decision expected by January 30.

While NaV1.7 acts like a light switch for pain, NaV1.8 functions more like a dimmer, offering a nuanced approach to pain management by reducing excessive pain to manageable levels. This capability makes NaV1.8 an attractive target since maintaining some level of pain sensation can be protective. SiteOne's primary focus, however, is on NaV1.7, with its lead drug, STC-004, designed to selectively block this channel.

SiteOne's roots trace back to Stanford University, where Mulcahy, one of its scientific co-founders, investigated toxins that specifically target sodium channels. The technology developed by the company, licensed from Stanford, enables the identification of small molecules that modulate these channels selectively. This approach allows SiteOne to design highly specific drugs targeting NaV1.7 and NaV1.8, with the company's name reflecting its focus on a unique binding site for NaV1.7.

Ten years ago, SiteOne emerged quietly with minimal funding. In 2017, Amgen spearheaded a $15 million Series B investment, leading to an R&D alliance aimed at developing NaV1.7 inhibitors for various pain conditions. Although the collaboration ended when Amgen withdrew from neuroscience in 2019, the research continues under a new agreement with Vertex Pharmaceuticals, established in 2022. While details remain undisclosed, it's confirmed that Vertex's suzetrigine and SiteOne's STC-004 are outside this collaboration.

Beyond pain management, selective sodium channel targeting could have broader therapeutic applications. As these channels interface with multiple tissues and organs, SiteOne is exploring possibilities like treating coughs, which Mulcahy compares to lung pain. This approach could offer innovative solutions for respiratory conditions.

SiteOne's Series C funding round was led by Novo Holdings, with participation from OrbiMed, Wellington Management, Mission BioCapital, BSQUARED Capital, and previous investors. The fresh capital will primarily support the upcoming Phase 2 trial of STC-004, with Phase 1 data anticipated in the first quarter of the coming year.