Sanofi and the biopharmaceutical company, Regeneron Pharmaceuticals, Inc. have formed a $2.2 billion global collaboration to discover, develop, and commercialize new antibody cancer treatments in immuno-oncology. As part of the agreement, the two companies will jointly develop a programmed cell death protein 1 (PD-1) inhibitor currently in Phase I testing, and plan to initiate clinical trials in 2016 with new therapeutic candidates based on ongoing, preclinical programs.

Under the deal, Sanofi will make an upfront payment to Regeneron of $640 million and the companies will invest $1 billion for discovery through proof of concept (POC) development (usually a Phase IIa study) of monotherapy and combinations of immuno-oncology antibody candidates to be funded 25% by Regeneron ($250 million) and 75$ by Sanofi ($750 million). The companies have also committed to equally fund an additional $650 million (or $325 million per company) for development of REGN2810, a PD-1 inhibitor. In addition, Sanofi will pay to Regeneron a one-time milestone of $375 million in the event that sales of a PD-1 product and any other collaboration antibody sold for use in combination with a PD-1 product exceed, in the aggregate, $2 billion in any consecutive 12-month period. Finally, the two companies have agreed to re-allocate $75 million (over three years) for immuno-oncology antibodies from Sanofi’s $160 million annual contribution to their existing antibody collaboration that otherwise continues as announced in November 2009. Beyond the committed funding, additional funding will be allocated as programs enter post-POC development.

The new agreement covers both monoclonal antibodies and new bi-specific antibodies, a variation of standard antibody therapeutics, in which two distinct targets within the body can be bound by the same molecule, usually the cancer cell and an immune cell. Regeneron has developed manufacturing platform for production of bi-specific antibodies that are otherwise similar to natural antibodies. Beyond PD-1, other targets in preclinical development include antibodies to lymphocyte-activation gene 3 (LAG3) and glucocorticoid-induced tumor-necrosis-factor-receptor-related protein (GITR) and a programmed death-ligand 1 (PD-L1) inhibitor. Finally, the collaboration is advancing bi-specific antibodies that target hematologic and solid cancers, either as mono therapies or in combination regimens with other immune modulating treatments.

Regeneron will be responsible for discovery, antibody generation and development through POC, at which time Sanofi will have the ability to opt-in to further development and commercialization. In the existing antibody collaboration, Sanofi has the opportunity to opt-in at the time of an investigational new drug application (IND). The companies will alternate serving as the lead development and commercialization organization after Sanofi opts-in to an antibody program.

For programs where Regeneron is the lead, including REGN2810, Regeneron will serve as the US commercial lead, including recording US sales, and the companies will equally fund post-POC development Sanofi will record sales and serve as the commercial lead for all countries outside the US. Sanofi will retain the right to co-promote in the US, and Regeneron will retain the right to co-promote outside the U.S.

For programs where Sanofi is the lead, Sanofi will serve as the US commercial lead and fund 100% of post-POC development, with Regeneron reimbursing up to 50% of such costs through the IO collaboration development balance, which represents the amount of development funding that Regeneron is obligated to repay out of its share of profits as described below. Sanofi will record sales and serve as the commercial lead for all countries outside the US. Regeneron will retain the right to co-promote in the US and outside the US.

Sanofi and Regeneron will share equally in worldwide profits from sale of collaboration immuno-oncology antibodies. As in the existing antibody agreement, Regeneron will repay the immuno-oncology collaboration development balance from its share of overall profits of the immuno-oncology antibodies, in an annual amount equal to 10% of the Regeneron share of profits.

The exclusive collaboration to discover and develop potential monotherapy or combination immuno-oncology antibody candidates through POC will last five years with an ability to extend the collaboration for selected ongoing programs for an additional three years. The agreement does not include chimeric antigen receptors. Additional terms, including potential therapeutic targets or mechanisms, were not disclosed.

Source: Sanofi