SiteOne Therapeutics, a startup focused on developing novel non-opioid pain medications, has announced the closing of $100 million in Series C financing. This funding will support the advancement of its lead program, STC-004, a selective NaV1.7 inhibitor, towards a Phase 2 proof-of-concept trial planned for next year.
Targeting Sodium Channels for Pain Relief
SiteOne's approach targets sodium channels, specifically NaV1.7 and NaV1.8, which are membrane proteins crucial for transmitting electrical signals in the peripheral nervous system. Unlike opioid drugs that target receptors in the central nervous system and carry addiction risks, SiteOne's therapies aim to selectively modulate pain signals at the source. According to SiteOne CEO John Mulcahy, sodium channels are like "electrical wiring for the body," and by targeting those primarily in the peripheral nervous system, the risk of addiction is reduced.
The Challenge of Selectivity
Developing drugs that selectively target NaV1.7 and NaV1.8 has been a significant challenge. As Mulcahy noted, these channels are closely related, and early research struggled to avoid hitting other sodium channels, which could lead to unwanted side effects affecting nerves, skeletal muscles, or the heart. SiteOne's technology, licensed from Stanford University, addresses this challenge by identifying small molecules that are highly selective modulators of these channels.
STC-004 and Clinical Development
SiteOne's lead program, STC-004, is designed to selectively block the NaV1.7 channel. While both NaV1.7 and NaV1.8 transmit pain signals, NaV1.7 acts more like a light switch, turning pain on or off, while NaV1.8 functions as a dimmer switch, modulating the intensity of pain. The company anticipates a Phase 1 data readout for STC-004 in the first quarter of next year, with plans to initiate a Phase 2 trial in both acute and chronic pain indications.
Competition and Collaborations
Vertex Pharmaceuticals is also a key player in the sodium channel-targeting space. Their most advanced pain program is suzetrigine, a small molecule designed to selectively inhibit NaV1.8 for acute pain. The FDA is currently reviewing suzetrigine, with a regulatory decision expected by January 30. SiteOne has a research collaboration with Vertex, focusing on early preclinical development of NaV1.7 inhibitors, although suzetrigine and STC-004 are not part of this collaboration.
Potential Beyond Pain
The selective targeting of sodium channels may have applications beyond pain management. The widespread distribution of these channels throughout the body suggests potential therapeutic uses in other areas, such as cough treatment. Mulcahy likened coughing to pain in the lungs, explaining that a sodium channel-targeting drug could offer a novel approach to treating cough by modulating the response to irritants.
Financial Backing and Future Plans
Novo Holdings led SiteOne's Series C round, with participation from OrbiMed, Wellington Management, Mission BioCapital, and BSQUARED Capital, among others. The funding will primarily support the Phase 2 trial of STC-004 in acute and chronic pain, as well as further exploration of sodium channel modulation for other therapeutic applications.
