AstraZeneca Opts In To ROR Gamma T Inhibitor Space With Orca Collaboration

BioMotiv spinout could realize up to $122.5 million under arrangement giving AstraZeneca global option rights to a late-stage preclinical program for producing drugs that regulate production of IL-17.

Just one week after Sanofi entered the ROR gamma T inhibitor drug discovery and development space, AstraZeneca PLC found its way in by signing an exclusive option agreement with Orca Pharmaceuticals Ltd., the first spinout of specialty pharma incubator BioMotiv LLC.

Based in Oxford, U.K., Orca gets an undisclosed upfront payment and the opportunity to earn milestones for a preclinical ROR gamma T program it says should enter clinical development in the next 12 months – total earnings under the partnership could reach $122.5 million. [See Deal]

Inhibition of retinoic acid-related orphan nuclear receptor (ROR) gamma, which regulates the production of pro-inflammatory cytokine interleukin-17, is believed to offer significant potential as a therapy for numerous autoimmune disorders, including psoriasis, arthritis, multiple sclerosis and inflammatory bowel disease.

Sanofi teamed up with Dutch biotech Lead Pharma in a deal unveiled Feb. 18 (Also see "Deal Watch: After Novartis Deal, GSK Increases Vaccine Emphasis With GlycoVaxyn Buyout" - Pink Sheet, 23 Feb, 2015.). The two firms will collaborate on early-stage R&D with a goal of producing clinical candidates for development within three to four years. Lead gets undisclosed upfront cash and will be eligible for R&D cost reimbursement, regulatory and commercial milestones and royalties on global sales of any products resulting from the partnership. Sanofi will be responsible for clinical development and gets worldwide marketing and commercial rights to such products [See Deal].

Other big pharmas trying to produce a drug targeting the ROR gamma T pathway’s effect on T-cell differentiation include Merck & Co. Inc., GlaxoSmithKline PLC, Pfizer Inc. and Janssen Pharmaceutical Cos. In addition, the space is a primary focus of drug-discovery specialist Vitae Pharmaceuticals Inc., which is nearing the clinic with its lead ROR gamma T inhibitor VTP-43742 (Also see "Vitae Obtains Proof-Of-Mechanism Data For BACE Inhibition In Alzheimer’s" - Pink Sheet, 23 Oct, 2014.). Vitae, which netted $48.4 million in an initial public offering last September, initially planned to partner its ROR gamma T program, but since has decided to keep it in-house (Also see "Autoimmune RORγt Program May Portend Change Of Direction For Vitae" - Pink Sheet, 29 Jul, 2013.).

While the target is potentially lucrative, the competition is fierce also because it has proven so difficult to drug, explained Orca Chief Scientific Officer Roy Pettipher, who co-founded the firm with CEO Michael Hunter.

“It’s been possible to find inhibitors of ROR gamma that are selective, but the challenge has been finding compounds with drug-like properties in terms of their metabolic stability and oral bioavailability,” he said in an interview.

Building Upon NYU Research

Orca’s work stems from a collaboration with New York University and researcher Dan Littman, who Pettipher called “one of the fathers of the field” (Also see "Emergings In Brief, May 2013" - Scrip, 9 May, 2014.). NYU Innovation Fund joined with Cleveland-based BioMotiv in providing $800,000 in seed funding for Orca in 2013, which they topped off with another $1.3 million in April 2014 [See Deal].

“We found some compounds that are potent and selective and also have good drug-like properties; they’re metabolically stable and well absorbed after oral administration,” Pettipher said. “That’s quite valuable in this space, so that’s what has driven this collaboration. And of course the collaboration with AstraZeneca will bring to bear a lot more resources in terms of the chemistry to take it further. It’s still preclinical, but we think the compounds we have are quite advanced leads and should be in development in due course.”

Pettipher predicted that the partners might be able to advance a lead candidate into clinical development in the next year or sooner. Specific indications won’t be determined until a lead compound is selected, he said. ROR gamma inhibition is Orca’s only R&D focus at present and this collaboration is an exclusive one with AstraZeneca, with the U.K. pharma holding an option to acquire the candidates at the end of the partnership work. Pettipher said Orca will not be looking to sign any other partnerships.

AstraZeneca’s focus in the collaboration will be medicinal chemistry, Pettipher explained, while his company will focus on developing biomarkers.

“Our main contribution going forward will be to identify biomarkers that identify patients who have a ROR gamma-dependent form of disease,” the exec explained. “In other words, ROR gamma is involved in driving their pathogenic Th27 cells, and so there are markers we are working on in that respect, and also markers which also will highlight drug response.”

Pettipher conceded that Merck and GSK are in the lead in terms of patents filed in the ROR gamma domain, but asserted that his company’s science is in a strong position to succeed in this highly competitive and challenging space.

“Even with the best compounds, what’s not optimal at this point are the drug-like properties – how the compound is absorbed and metabolized,” he said. “That’s not really been fixed in order to deliver a compound that would cover the target in a profile where you could give a fairly low dose once a day. … If you look at the competitor compounds, they tend to be quite high molecular weight, which means they won’t be well absorbed. Also, they’re quite lipophilic – quite likely to be highly metabolized.”

BioMotiv launched in 2012 with $21 million in seed funding from the Harrington Project for Discovery and Development and University Hospitals of Cleveland [See Deal]. With a business model of acquiring early-stage drug projects from academic institutions and developing them to be out-licensed later in development, BioMotiv raised $25 million in Series A funding from returning backers and Nationwide Mutual insurance in 2013 [See Deal].

Japanese pharma Takeda Pharmaceutical Co. Ltd. invested $25 million in BioMotiv last September, obtaining exclusive rights to projects in immunology, inflammation and cardio-metabolic disease, but Pettipher said Orca and its programs were kept separate from that arrangement [See Deal].