Anti-VEGF therapies including Avastin (bevacizumab), Lucentis (ranibizumab), Eylea (aflibercept) and conbercept have reformed the treatment of wet age-related macular degeneration (AMD). Both Lucentis and Eylea sold billions of dollars per year. Conbercept, developed by Kanghong Pharmaceutical (SZSE: 002773), also sells well in China, generating CNY 110 million in the first half of 2015.
Currently approved anti-VEGF products for AMD are monoclonal antibodies and fusion proteins. Patients require repeated eye injections of anti-VEGF biologics to control their disease. An oral treatment with similar efficacy and safety will be welcomed by many patients. That is what Tyrogenex is doing right now.
Tyrogenex’s lead compound is called X-82, which inhibits VEGFR, PDGFR, FLT3 and KIT. The compound is currently in Phase II trials for wet AMD and solid tumors. In June 2014, the company received $15 million in Series D financing from Brace Pharma. The funding is used to support the Phase II trials.
The Phase I results of X-82 for AMD were presented at the 15th EURETINA Congress. The trial enrolled 35 previously treated patients with wet AMD. Four dose levels, ranging from 50 mg to 200 mg, were evaluated. Of the 25 patients completing the full 24-week treatment, 15 required no intravitreal injections of Lucentis, and had a mean visual acuity improvement of +5.3 letters.
The Phase I results were clinical meaningful. 43% (15/35) of patients maintained or improved their visual acuity scores, and did not require any injections of Lucentis. What really concerns me is the safety profile of X-82. As we know, multikinase inhibitors (e.g., sorafenib, sunitinib) could result in various adverse events. Lucentis and Eylea are well tolerated because of their high selectivity and local injection.
X-82 is derived from sunitinib, but X-82 has a shorter half-life than sunitinib, resulting in less tissue accumulation. Indeed, X-82 caused fewer side effects than sunitinib. There were still three patients experiencing transaminase elevations within the first month of starting treatment. Only 71% (25/35) of patients completed the full 24-week treatment.
Tyrogenex and its sister company, Xcovery, were founded by Dr. Chris Liang (梁从新) who emigrated from China in 1984. Liang is credited as the co-inventor of sunitinib. In 2007, Xcovery was one of the most promising biotech companies in the world, but it looks just so-so today. In October 2014, Beta Pharma invested $20 million into Xcovery while gained China rights to X-396, an ALK inhibitor. AnewPharma, a Shanghai-based company, is responsible for developing X-82 (CM082) in China.