Akarna Therapeutics Ltd. closed a $15 million series B preferred stock financing that the company said would accelerate the development of its lead farnesoid X receptor (FXR) agonist drug candidate through human proof-of-concept studies in patients with non-alcoholic steatohepatitis (NASH) and/or fatty liver disease.

New investor Forbion Capital Partners joined existing investors New Science Ventures (NSV) and Third Point Ventures to complete the round, which follows an early 2015 series A financing backed by NSV and Third Point.

Akarna CEO Raju Mohan told BioWorld Today the company expects to file the FDA investigational new drug application during the fourth quarter of this year and is about a year away from taking its lead molecule into the clinic. The company has yet to disclose the name of the program.

The small private company, which was founded in late 2014 by Mohan and NSV managing partner Somu Subramaniam, is staffed by about eight full-time employees and consultants. The company has offices in San Diego and the U.K.

Mohan started his pharmaceutical career at Berlex Biosciences, a subsidiary of Bayer/Schering AG. From 2006 to 2011, he served as vice president and head of the San Diego site for Exelixis Inc. and vice president of chemistry at X-ceptor Therapeutics Inc., which was acquired by Exelixis in 2004. Prior to Akarna, he co-founded Alexar Therapeutics Inc. in 2014, a dermatology-focused specialty pharma based on a nuclear receptor platform, where he built substantial experience discovering drugs for nuclear receptors, the family to which FXR drugs belong. He remains executive vice president of research for Alexar. (See BioWorld Today, Sept. 29, 2004.)

A BUSY CLASS

The NASH space has become increasingly active in recent years. But despite progress in the clinic, Mohan said there have been tolerability issues with some approaches, leaving an unmet need for a better compound that can hit the key pathologies of NASH. The flurry of development has also led to significant progress in diagnostic technologies for NASH in recent years, he said, noting that Akarna hopes to access those tools via its network of collaborators and partners.

Among the active competitors with FXR agonists that Akarna will face in the future are Intercept Pharmaceuticals Inc. (partnered with Sumitomo Dainippon Pharma Co Ltd.), Gilead Sciences Inc., Novartis AG and Enanta Pharmaceuticals Inc.

Intercept has the most advanced program in the class. The company is seeking FDA approval for its closely watched obeticholic acid, first for the treatment of primary biliary cirrhosis (PBC), and is awaiting a Feb. 29 meeting of an FDA advisory committee that will discuss its application ahead of a May 29 PDUFA date. The PDUFA date was extended in December after an information request from the FDA required the company to submit additional clinical data analyses.

Gilead picked up the phase II molecule Px-102 through its acquisition of privately held Phenex Pharmaceuticals AG for up to $470 million. That deal, announced in January 2015, appeared to provide Gilead a new avenue for approaching NASH alongside its efforts to develop the LOXL2-targeting monoclonal antibody simtuzumab in the indication. Phase II studies of simtuzumab are ongoing in patients with NASH and also PBC.

Gilead is also working on another FXR agonist for NASH called GS-9674, though it has said little about the program other than that a trial of the molecule, developed in-house, started during the fourth quarter of 2015. (See BioWorld Today, Jan. 7, 2015.)

A phase II program testing Novartis’ LJN-452 in PBC was initiated in October 2015, according to Thomson Reuters Cortellis Clinical Trials Intelligence. According to the company’s annual report to the SEC and additional comments, the 40-patient trial is expected to be completed in December 2017 ahead of a possible application for approval in 2020.

Enanta’s EDP-305, for the potential use in the treatment of NASH and PBC, is on track to initiate a phase I trial in the second half of 2016, the company said.

The field also has drawn significant participation from companies working on other approaches to NASH and PBC, such as Loos, France-based Genfit SA, which is developing the PPAR-alpha and -delta agonist elafibranor (GFT505); South San Francisco-based Tobira Therapeutics Inc., which is developing cenicriviroc, a dual CCR5/CCR2 antagonist; and Conatus Pharmaceuticals Inc., which on Feb. 3 gained FDA fast track status for development of emricasan for the treatment of liver cirrhosis caused by NASH. (See BioWorld Today, Nov. 17, 2015.)