Committing more than $6 billion in potential milestone payments, Sanofi said it will partner with IGM Biosciences to create, develop, manufacture, and commercialize six immunoglobulin M (IgM) antibody agonists—three against oncology targets, the other three against immunology/inflammation targets.
The companies have signed an exclusive worldwide collaboration agreement to develop engineered IgM antibodies, a new class of potential therapeutics designed to combine the multi-valency of IgM antibodies possessing 10 binding sites, five times the number of target binding sites on conventional IgG antibodies.
Headquartered in Mountain View, CA, IGM develops antibodies using a proprietary platform based on the IgM antibody, one of five classes of naturally occurring human antibodies. Since the IgM antibody has 10 binding units, it can bind to more targets, as well as more difficult targets and targets less common on the surface of targeted cells. That results in a greater avidity or total binding power, for the antibody—and thus could yield better clinical responses and greater efficacy, IGM reasoned.
The company also said its 10 binding units of an IgM antibody can neutralize the ability of viruses to cells, enhancing their abilities against infectious disease. In oncology, IgM antibodies can bind to multiple targets simultaneously on the surface of tumor cells and create apoptotic signals that ultimately lead to the death of cancer cells, according to IGM.
“The IGM Biosciences technology platform offers an exciting approach to developing high-avidity IgM antibodies that can efficiently bind and stimulate the activity of cell surface receptors,” John Reed, MD, PhD, Sanofi’s global head of research and development, said in a statement. “This unique platform has the potential to overcome historical limitations of conventional IgG antibodies when seeking agonists of some classes of receptors.”
Investors roared their approval of the Sanofi collaboration with a buying surge that sent IGM shares more than doubling this morning, up 120% to $33.03 as of 11:09 am, from yesterday’s close of $14.99.
In the latest collaboration, Sanofi has agreed to pay IGM $150 million upfront, and “has expressed interest,” in buying up to $100 million of IGM non-voting common stock through a public financing, the companies said.
The oncology focus of the Sanofi/IGM collaboration comes nearly four months after IGM presented disappointing data for its lead cancer candidate at the American Society of Hematology’s 63rd ASH Annual Meeting and Exposition. The data was for IGM-2323, an IgM antibody targeting CD20 x CD3 and designed to treat B cell non-Hodgkin’s lymphoma (NHL) and other B cell malignancies.
Complete response rates
Of 10 patients treated in the 100 mg cohort of a Phase I trial (NCT04082936), 3 of 6 diffuse large B cell lymphoma (DLBCL) patients had a complete response while 2 of 3 follicular lymphoma (FL) patients had a complete response. Of 38 patients evaluable for efficacy, 11 patients (21%) showed a response, 8 of which were complete responses. By contrast, higher complete response rates were reported at the same conference for antibody candidates of Roche and its Genentech subsidiary (60% for mosunetuzumab in relapsed or refractory (R/R) FL) and Regeneron (21% in R/R DLBCL post-CAR-T to 70% in R/R FL for odronextamab).
IGM shares fell 41% the day of the data release (December 11, 2021) to $29.25 from $49.84 the previous day.
For each oncology target program covered by the collaboration, the companies said, IGM has agreed to lead R&D activities, and assume related costs, through approval of the first biologics license application (BLA) for a product directed to that oncology target by the FDA or European Medicines Agency (EMA).
In return, Sanofi agreed to pay IGM up to $940 million in payments tied to achieving development and regulatory milestones per oncology target—up to $2.82 billion overall.
After the first marketing approval for a product designed against an oncology target, Sanofi has agreed to lead all subsequent development and commercialization activities for that target. For each oncology target, the companies will share profits 50:50 in certain major markets, while IGM will be eligible to receive tiered royalties on net sales in the rest of world.
For each immunology/inflammation target program covered by the collaboration, IGM has agreed to lead R&D activities, and assume related costs, through the completion of a Phase I clinical trial for up to two constructs directed to each immunology/inflammation target. Afterward, Sanofi has agreed to oversee all future development and related costs.
In return, Sanofi agreed to pay IGM up to $1.065 billion in development, regulatory, and commercial milestone payments per immunology/inflammation target—up to $3.195 billion overall.
Following the completion of a Phase I clinical trial for each immunology/inflammation target, Sanofi has agreed to oversee subsequent development activities, commercialization efforts, and related costs. Also, IGM is eligible to receive tiered high single-digit to low-teen royalties on global net sales.
Closing of the collaboration is contingent on completion of review under antitrust laws, including the Hart-Scott-Rodino Antitrust Improvements Act of 1976 in the United States, and customary closing conditions.