Regulus adds two more projects to pipeline as it works to get lead hep C drug back on track

Regulus says it intends to identify at least one new drug development candidate per year moving forward.

MicroRNA specialist Regulus has bulked up its pipeline with two new clinical candidates for liver and kidney diseases that could start human trials next year.

The two new micro RNA (miRNA) drugs—Regulus' specialty—are a drug to treat impaired bile flow (cholestasis) codenamed RGLS5040 and RGLS4326 for autosomal dominant polycystic kidney disease (ADPKD), both of which are expected to start trials before the end of 2017.

The company is keen to show that it has pipeline depth beyond RG-101, its hepatitis C virus candidate currently subject to an FDA-mandated clinical hold after serious adverse events were seen in a phase II trial. The two new drugs were highlighted at the firm's R&D event for investors yesterday.

Cholestasis therapy RGLS5040 will target diseases like primary biliary cholangitis (PBC)—which has two approved treatments—as well as primary sclerosis cholangitis and congenital disorders like Alagille syndrome which have no current therapies. 

Cholestasis typically leads to serious liver damage, and for years the only treatment was ursodeoxycholic acid, which has limited efficacy. In May Intercept picked up an FDA approval for Ocaliva (obeticholic acid), which has been tipped as a blockbuster in PBC alone, with even more potential if its use can be expanded into bigger indications such as NASH, or fatty liver disease.

RGLS5040 has a different mechanism of action from the current drugs, targeting a microRNA called miR-27, and has potential both as a monotherapy and in combination with approved therapies, according to Regulus' director of biology Zhi-Liang Chu.

ADPKD candidate RGLS4326 is also targeting an underserved market with no approved drug in the U.S. and just one therapy—Otsuka's Samsca (tolvaptan)—available for use in the EU, Japan and Canada. Regulus' drug targets miR-17 and seems to reduce cell proliferation and cyst growth in a mouse model of the disease as well as an in vitro model based on human tissue.

The disease is life-threatening and affects around 12.5 million people worldwide. Around 50% of all patients go on to develop end-stage renal disease, putting them on a path towards needing dialysis and potentially a kidney transplant.

The start of trials for the two new candidates will give Regulus five candidates in the clinic alongside RG-101, AstraZeneca-partnered RG-125 for NASH and RG-012 for Alport syndrome, which is being developed with Sanofi's rare disease subsidiary Genzyme. Both RG-012 and RG-125 are in Phase II.

Updating on progress with RG-101, Regulus' CEO Peter Grint said that the company is on track to file its responses to the FDA on RG-101 by the end of the year and is still expecting a verdict from the regulator in the first quarter of 2017.

"Today's announcement of two new drug development candidates underlines the confidence we have in our rigorous targeting and validation process, which we believe should enable us to identify at least one new drug development candidate per year moving forward," he said.