DUBLIN – Early stage antibody developer Biomunex Pharmaceuticals SAS entered a license agreement with Sanofi SA for the development of multiple bi- and multispecific antibodies based on its Bixab platform. Financial terms were not disclosed.

"We will receive an up-front and will be eligible to receive clinical, regulatory and commercial milestones," Biomunex CEO and founder Pierre-Emmanuel Gerard told BioWorld. It's the first such agreement for Paris-based Biomunex. As well as cash, the deal brings it the credibility attached to big pharma validation of its Bixab (pronounced "bizab") platform. "For us, it's of the utmost importance," Gerard said.

It is also a harbinger of more agreements. "We expect to sign other deals in 2019."

Given the array of antibody technologies to which Paris-based Sanofi now has access, it's quite a coup for Biomunex, which has so far survived on seed funding and research grants.

In addition to its long-standing and wide-ranging alliance with Regeneron Pharmaceuticals Inc., of Tarrytown, N.Y., which has so far yielded three approved antibody drugs, Sanofi became the outright owner of the nanobody fragment antibody platform through its $4.8 billion acquisition last year of Ablynx NV.

That deal brought with it an advanced drug program, Cablivi (caplacizumab), the anti-von Willebrand factor nanobody for treating acquired thrombotic thrombocytopenic purpura, which subsequently gained approval in Europe and is currently undergoing FDA review. It also gave Sanofi the underlying platform, which, Ablynx has long maintained, because of its modular composition, is ideal for developing high-affinity binders with multiple specificities. Even before it decided to acquire Ablynx, Sanofi had entered a multiproduct alliance with the Belgian firm to develop nanobodies with multiple specificities for immunology indications. (See BioWorld, July 21, 2017.)

Another Ablynx-developed bispecific nanobody, M-1095, which targets interleukin-17A (IL-17A) and IL-17F, is currently undergoing a phase IIb head-to-head trial in plaque psoriasis against Novartis AG's IL-17A inhibitor, Cosentyx (secukinumab). Its original licensee, Merck KgaA, of Darmstadt, Germany, entered a co-development pact on the drug with London-based Avillion LLP in 2017.

Biomunex was, obviously, able to convince Sanofi that it had something additional to offer. The company developed its platform in-house, building on technologies it in-licensed from a number of academic collaborators. It offers a minimally engineered approach to rapidly generating bi- or multispecific molecules from parental monoclonal antibodies. "In less than three months, you'll get an antibody with excellent drug-like properties," Gerard said. The norm is one to two years, he added. Bixabs can contain domains derived from either approved, marketed antibodies, from original antibodies or from a combination of both.

For example, a patent filing on a bispecific molecule targeting CD38 and PD-L1 (CD38 x PD-L1) describes antibody sequences derived from Darzalex (daratumumab) and Tecentriq (atezolizumab). The basic bispecific format comprises four Fab fragments, joined together by proprietary peptidic linker sequences. Biomunex introduces a number of specific mutations in defined locations to ensure optimal pairing between heavy and light chains.

Under the present agreement, Sanofi will take Biomunex's Bixab technology in-house – it will be solely responsible for research, clinical development, production and commercialization of any products emerging from the alliance. The indication areas attached to the deal have not been disclosed. Biomunex has two in-house bispecific antibodies in preclinical development. BMX-002, its most advanced molecule, targets EGFR and HER2. BMX-001 targets CD38 and PD-L1. The company has several other innovations in the pipeline, including a novel way of engaging T cells that employs an undisclosed T-cell antigen instead of CD3, the standard target for both antibody-based bispecific T-cell engagers and CAR T therapies. It is also developing what Gerard described as a disruptive trispecific antibody technology.

In discussions with investors

Gerard, a medical doctor and an MBA graduate with a long background in both industry consulting and management, established the company in 2014, along with two co-founders, cancer immunotherapy scientist Jean-Pierre Mach, of the University of Lausanne, Switzerland, and Geoffroy de Ribains, a former venture capital investor who is now CEO of another Paris-based startup, Step Pharma SA. In addition to Gerard, the Biomunex leadership team includes Chief Scientific Officer Eugene Zhukovsky, the former CSO of Heidelberg, Germany-based antibody engineering and development firm Affimed Therapeutics NV, who has also held posts at Ingelheim, Germany-based Boehringer Ingelheim GmbH and Monrovia, Calif.-based antibody developer Xencor Inc. Olivier Léger, an antibody engineering veteran who was co-inventor of Tysabri (natalizumab), is an adviser to the company.

Biomunex has gotten this far on a modest level of investment, but it expects to close a series A round this year. "We are in discussions with potential investors," Gerard said.

The present deal is further evidence of big pharma's ongoing interest in bispecific antibody technologies. However, progress has been slow since the first molecules gained regulatory approval more than a decade ago. Removab (catumaxomab; epithelial cell adhesion molecule (Epcam) x CD3), a chimeric, bispecific antibody which gained European approval in 2009 for treating malignant ascites, was withdrawn from the market because of immune-related side effects arising from the presence of rodent antibody domains. More than four years on from the initial approval in acute lymphoblastic leukemia of Amgen Inc.'s Blincyto (blinatumomab; CD3 x CD19), no other Bite antibody has moved into phase III trials. Genentech Inc.'s Hemlibra (emicizumab-kxwh; factor IXa (FIXa) x FIX) gained FDA approval in November 2017 for preventing bleeding episodes in hemophilia A patients who have developed FVIII inhibitors.

Development of several high-profile molecules has stalled due to manufacturing problems, insufficient efficacy or safety issues. The list of development casualties includes Abbvie Inc.'s ABT-122 (TNF-alpha x interleukin-17), Roche Holding AG's vanucizumab (angiopoietin 2 x VEGF-A) and Amgen Inc.'s AMG-110 (Epcam x CD3). The jury is currently out on Macrogenics Inc.'s MGD-009 (B7-H3 x CD3), on which the FDA slapped a partial clinical hold in December, following the emergence of liver toxicity in a phase I monotherapy trial. (See BioWorld, Dec. 11, 2018.)