MASP-3 inhibitor ready for the clinic

Omeros Corp just put out an update on preclinical work done on a MASP-3 inhibiting antibody called OMS906 in non-human primates. MASP-3 is a critical protein in the cascade which activates the alternative pathway of complement. Specifically MASP-3 converts pro-factor D to factor D.

The antibody seens to be working just as expected in the primates setting:

Single-dose administration of OMS906 to cynomolgus monkeys resulted in sustained ablation of systemic APC activity for approximately 16 days. The extent of APC ablation was comparable to that achieved by complete inhibition of factor D in vitro, indicating that OMS906 fully blocked the conversion of pro-factor D to factor D. Similar results were obtained with a number of the company’s other antibodies targeting MASP-3. No safety concerns were identified.

“The OMS906 primate data bode well for the antibody’s long-acting inhibition of MASP-3 in patients, and the unique mechanism of action of MASP-3 inhibition likely has significant clinical advantages over many other alternative pathway inhibitors,” said Sir Peter Lachmann, ScD FRCP FRCPath FRS FMedSci, Emeritus Sheila Joan Smith Professor of Immunology, University of Cambridge. “In PNH, the MASP-3 inhibitor OMS906 blocks not only intravascular hemolysis, as do C5 inhibitors, but also prevents extravascular hemolysis, a problem that C5 inhibition cannot address. Other alternative pathway targets, such as factor D or factor B, turn over at extremely high rates, making them difficult to drug. In contrast, MASP-3 circulates in the body at a relatively low concentration with a slow rate of turnover, enabling sustained inhibition by either MASP-3-targeting antibodies or small molecules.”

Genentech currently studies a factor D antibody (Lampalizumab) to treat AMD in a phase 3 study, while Achillion has started to work on a small-modecule inhibitor of factor D. No other entity is working on MASP-3 as Omeros has secured exclusivity for MASP-3.

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