BioCentury, The Bernstein Report
Emerging Company Profile
Solace: Comfort in (Pain) Research
Week of July 9, 2007 (no link available)

By Matthew Mikulski, Staff Writer

Unlike typical biotech startups, which are founded by scientists-turned-entrepreneurs who have already chosen the company's founding assets, Solace Pharmaceuticals Inc. was formed by PureTech Ventures with the idea to pick development programs from a broad palette of academic research on pain modulation.

Daphne Zohar, founder and managing partner at PureTech, told BioCentury the first step in creating Solace was to identify a therapeutic area that was underserved but had a plethora of attractive academic projects that might represent solutions.

"We chose pain because of the significant unmet medical need, coupled with the relative lack of innovation on the corporate side," she said. The next step was to put together a scientific advisory board with expertise in the mechanistic origins of pain. The SAB subsequently decided what the company should work on, based on parameters such as innovation, feasibility and existing data.

"We had several brainstorming sessions, looked at about 70 different projects, including things they were working on in their own labs, and in other labs, and then chose the best to go after," Zohar said. "We were looking at ideas, not companies."

The ideas that PureTech turned into Solace include a preclinical series of GTP cyclohydrolase (GCH1) 1 inhibitors and SLC022, a compound that modulates glial cells that had completed Phase III testing in another, undisclosed indication.

The GCH1 program had its origins in work done by Solace co-founder and SAB member Clifford Woolf, who is director of the Neural Plasticity Research Group at Massachusetts General Hospital and Harvard Medical School. He discovered that the enzyme GCH1 is a key modulator of peripheral neuropathic and inflammatory pain via its function as the ratelimiting step in the production of tetrahydrobiopterin (BH4).

Woolf's team has reported that injection of BH4 exacerbated pain in animal models, and that humans with a GCH1 haplotype believed to cause impaired function or expression of the enzyme reported reduced pain sensitivity.

CEO Eliot Forster said preclinical data on use of a non-specific inhibitor of GCH1 has confirmed the effectiveness of the mechanism. Specifically, injection of a single intraperitoneal dose of diamino-hydroxypyrimidine (DAHP) reversed mechanical and cold pain sensitivity in a peripheral neuropathic pain model in rats. The data were published in the November 2006 issue of Nature Medicine.

Solace has applied for patents covering chemical series that specifically inhibit the GCH1 enzyme and has a license to Woolf's method-of-use patent describing reducing BH4 levels to relieve pain. The company plans to have a GCH1 inhibitor in the clinic in about two years.

The company's second program, SLC022, was in-licensed from an undisclosed
pharma company after being taken through Phase III testing in an undisclosed indication. The compound modulates glial cell activity through an undisclosed mechanism.

The decision to in-license SLC022 grew out of work by Joyce DeLeo, professor of anesthesiology and pharmacology and toxicology at Dartmouth Medical School, director of the school's neuroscience center and a member of Solace's SAB.

Her lab has shown that nerve damage activates toll-like receptor 4 (TLR4) on microglia, that mice lacking TLR4 have reduced microglial activation after nerve injury as well as reduced hypersensitivity to pain, and that prophylactic blocking of the receptor in normal rats produces similar results.

Forster expects to start a Phase II trial of SLC022 in 2008.

Avigen Inc. (AVGN, Alameda, Calif.) also is developing a compound for pain that is thought to work through its effect on glial cells. AV411 is in an Australian Phase IIa trial for diabetic neuropathic pain. The active ingredient, ibudilast, is approved in Japan and other parts of Asia to treat bronchial asthma and dizziness secondary to chronic cerebral stroke.

Solace (Boston, Mass.) expects the $15 million it raised in May in a series A round to get both programs into the clinic.

The company will take the two programs to proof-of-concept but has not yet decided upon the strategy that it will follow. Along the way, Solace plans to look for additional projects together with its SAB.