Potential best-in-class profile for an oral sphingosine-1-phosphate receptor modulator
– Dose-dependent reduction in circulating lymphocytes –
– Rapid lymphocyte recovery after cessation of dosing –
– Phase 2 study in ulcerative colitis patients in 4Q 2020 –
ENCINITAS, California and Cambridge, United Kingdom, June 23, 2020 – Oppilan Pharma, Ltd., a clinical-stage biopharmaceutical company focused on developing novel small molecule therapeutics for the treatment of autoimmune diseases, today announced that positive top-line results from a Phase 1 study of OPL-002, an oral, once-daily sphingosine 1-phosphate (S1P) receptor modulator, were recently presented at the Digestive Disease Week® (DDW) 2020 Virtual Scientific Program.
In the Phase 1 single ascending dose (SAD) and multiple ascending dose (MAD) study, OPL-002 was well tolerated in a once-daily administration to healthy subjects for up to 28 days. The study was designed to evaluate the safety, tolerability, dose-response, pharmacokinetics and pharmacodynamics of OPL-002 compared to placebo. 88 subjects were randomized into the double-blind, placebo-controlled trial. There were no serious adverse events. None of the subjects had liver function test elevations, pulmonary function or ocular exam abnormalities, or other notable safety findings.
In the MAD study, once-daily dosing of OPL-002 led to a dose-dependent steady state reduction in absolute lymphocyte count of up to 65%. Lymphocyte counts returned to normal or were rapidly returning to normal by 72 hours after the last dose of OPL-002.
There was no clinically significant first dose heart rate reduction during treatment for up to 28 days. In the MAD study, with doses up to 45 mg (preceded by 7 days of dose titration), the maximum decrease in heart rate from baseline after the initial dose at the target level was less than 4 beats per minute.
“The clean safety profile of OPL-002 in Phase 1, combined with potent and sustained lymphocyte reduction and a rapid on and off rate, sets OPL-002 apart from other S1P modulators in development,” said Chris Krueger, Chief Executive Officer of Oppilan. “We are excited to advance OPL-002 into a Phase 2 study in moderate-to-severe ulcerative colitis patients to demonstrate its differentiated efficacy and safety and establish OPL-002 as a true best-in-class drug for IBD and other indications.”
“The new class of oral S1P modulators represent a significant advancement in the treatment of IBD,” said William Sandborn, M.D., Chief of the Division of Gastroenterology of the University of California San Diego and Chairman of Oppilan’s Clinical Advisory Board. “As with any new class of pharmacologic agents, there may be differences in pharmacologic structure that impact the safety and efficacy profile for individual members of the class. I am very encouraged by the robust lymphocyte lowering and rapid lymphocyte recovery that OPL-002 has demonstrated in Phase 1. The strong pharmacodynamic signal, combined with the safety and tolerability data, position OPL-002 as a promising new potential treatment for IBD.”
The poster can be viewed in the “ePosters and ePapers” section of the DDW website. Poster can be found HERE.
Details for the presentation are as follows:
Poster Number: TU1852
Poster Title: Pharmacokinetics and Pharmacodynamics of OPL-002, a Highly Selective S1P1R Modulator, in Healthy Volunteers. VIEW POSTER
Presenter Name: William Sandborn, M.D., Chief of the Division of Gastroenterology of the University of California San Diego
Sphingosine 1-phosphate (S1P) receptor modulators have recently been proven to be highly effective for the treatment of ulcerative colitis. However, S1P modulators in development have certain limitations, including LFT elevations and first dose heart rate reduction. OPL-002 is a highly selective and orally bioavailable small molecule S1P modulator in development for ulcerative colitis that was designed to mitigate these limitations. OPL-002 has very low CNS penetration and ocular distribution, no CYP450 interactions and no active metabolites and consequently a low likelihood of liver injury or macular edema and fewer potential drug-drug interactions than other S1P modulators in development.
About S1P Receptor
S1P regulates lymphocyte trafficking from the lymph nodes to the peripheral blood. S1P modulators block the receptor’s function and thereby sequester lymphocytes in the lymph nodes. By sequestering lymphocytes in lymph nodes, fewer immune cells are available in the circulating blood to produce an immunological response and inflammation in the digestive tract.
About Inflammatory Bowel Disease
Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, affects as many as 1.6 million Americans and 11.2 million people worldwide, most of whom are diagnosed before the age of 35. These chronic, life-long conditions can be treated, but not cured. IBD is a complex disease with many contributing factors, including environmental stimuli, genetics, pathogen exposure and immune-pathogen interaction. The end result is an excessive immunological response that leads to inflammation and disruption of the gastrointestinal tract.
Oppilan Pharma Ltd is a clinical-stage biopharmaceutical company developing novel small molecule therapeutics for the treatment of inflammatory bowel disease and other autoimmune disorders. Oppilan is registered in England and Wales with offices in Cambridge, United Kingdom and Encinitas, California. www.oppilan.com.
Oppilan Pharma Contact
Corey Davis, Ph.D.