Johnson & Johnson entities Janssen Pharmaceutica and Janssen Sciences Ireland have outlicensed two gastrointestinal immunology candidates to a startup launched earlier this year, under agreements whose value was not disclosed.

Provention Bio said it will launch clinical trials for the two candidates in the first half of 2018.

One candidate is PRV-6527 (JNJ-40346527), an oral colony-stimulating factor-1 receptor (CSF-1R) small-molecule inhibitor, for which Provention expects to begin patient enrollment in a Phase IIa proof-of-concept (PoC) study in Crohn's disease.

By driving myeloid cell differentiation in the bone marrow, CSF-1R stimulates the maturation of inflammatory dendritic cells and macrophages that populate the gut and other tissues, triggering inflammatory processes. The study, Provention said, will assess the drug's ability to inhibit the differentiation of these inflammatory dendritic cells and macrophages, preventing their migration to the intestinal mucosa in Crohn's disease. 

“The CSF-1R pathway is overrepresented in Crohn's disease gut tissue, and unpublished data suggest a potential beneficial effect of PRV-6527 on Crohn's-like disease in mouse models. Our goal with the Phase IIa PoC study is to confirm this observation in patients with moderate to severe Crohn's disease, who are still substantially underserved by conventional therapeutics,” Francisco Leon, M.D., Ph.D., scientific co-founder of Provention, said in a statement. 

The study is expected to enroll approximately 80 patients with moderate to severe Crohn's disease, primarily patients who previously failed one biologic drug. Patients will be treated with PRV-6527 for 12 weeks in the randomized, double-blind and placebo-controlled study. The primary endpoint will be clinical effect at week 12, with secondary proof-of-mechanism endpoints to include endoscopy and the presence of inflammatory myeloid cells in the gut.


Ulcerative Colitis and Beyond

The other candidate, PRV-300 (JNJ-42915925/CNTO 3157), is an anti-Toll-like receptor 3 (TLR3) monoclonal antibody. TLR3 is believed to play a key role in chronic inflammation triggered by nonvirally derived endogenous RNA and double-stranded RNA, with human biomarker and animal model studies showing that TLR3 appears to be involved in the pathogenesis of ulcerative colitis (UC).

Provention said it plans to initiate a Phase I/II PoC and proof-of-mechanism (PoM) study of PRV-300 in 32 patients with moderate-to-severe UC who are biologic therapy naïve or experienced. Patients randomized to PRV-300 will receive the treatment for 12 weeks. The primary endpoint will be safety, and secondary and exploratory endpoints will include endoscopic and histologic findings and mucosal mRNA signature.

“While our initial trials will target the demonstration of PoM in human patients with moderate to severe UC, we also intend to explore life-cycle expansion opportunities, including severe influenza in the hospital setting, as well as emerging viral diseases,” added Eleanor L. Ramos, M.D., Provention’s CMO and COO.

Provention was launched in the second quarter and has inlicensed three assets—the two Janssen candidates and an enterovirus vaccine platform in-licensed from Finnish biotechnology company Vactech Oy, with the goal of developing treatments to fight type 1 diabetes by targeting Coxsackievirus B infection.

On June 26, Provention said it received $28.4 million from a founding private placement of Series A Preferred Stock that closed on April 25. The financing is part of a two-step funding that according to Provention will likely include an initial public offering in 2018.

MDB Capital Group, a co-founder of Provention and the architect of the founding financing, acted as placement agent for the offering, with co-investment by Johnson & Johnson Innovation–JJDC and JDRF T1D Fund.

“The in-licensing of PRV6527 and PRV300 from Janssen continues to build momentum following our corporate launch last quarter and advances our strategic intent to source clinical-stage programs targeting the interception or prevention [emphasis in original] of immune-mediated diseases,” stated Ashleigh Palmer, Provention Bio’s co-founder and CEO.

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