Today Bristol-Myers Squibb and BioNTech announced a strategic partnership agreement to co-develop and co-commercialize bispecific PD-L1/VEGF-A antibody BNT327 for the treatment of patients with lung cancer. Specifically, BioNTech was already in the process of evaluating this drug candidate in two potential phase 3 registrational studies targeting patients with 1st-line extensive-stage small-cell lung cancer (SCLC) and non-small cell lung cancer [NSCLC]. This was a highly sought-after candidate, and it makes sense considering that it had already been tested in more than 1,000 patients to date.
This deal is quite an extensive one that was generated, and there is a lot involved here. BioNTech itself is receiving approximately $1.5 billion as an upfront payment for this established partnership and then is also eligible to receive $2 billion in total non-contingent anniversary payments through 2028 as well. Plus, it could also earn up to an additional $7.6 billion in development, regulatory, and commercial milestones. Development and manufacturing are to be shared 50:50, and global losses and profits will also be equally shared across the board.
What’s very good about this deal generated is that both companies are going to get an opportunity to independently develop BNT327, either alone as a monotherapy or in combination with one of their own drugs to target indications. It is good that this huge deal doesn’t limit what each of them can do with respect to further testing of this bispecific PD-L1/VEGF-A antibody in the targeting of patients with solid tumors. This is highly ideal because there is a possibility of combining this candidate with antibody-drug conjugates [ADCs] and potentially other modalities to target such patients with solid tumors.
The science of PD-L1/VEGF-A targeting is a proven one with each target. The PD-L1 target takes care of the ability for T-cells to once again recognize and target tumor cells, and then the VEGF-A component has an anti-angiogenesis component of cutting off blood and oxygen supply to tumor cells. In essence, to achieve vascular remodeling of the tumor and prohibit it from expanding. One good thing about the VEGF-A targeting is that it localizes this function to only inside the tumor microenvironment (TME), which is supposed to cut down on the systemic exposure of the drug itself.
The race is definitely heating up here for sure, especially when you consider that the other big pharma companies are not just sitting around doing nothing to get on the bandwagon. Merck paid LaNova Medicines an upfront payment of $588 million to get its hands on anti-PD-1/VEGF bispecific antibody LM-299 to target patients with solid tumors. The small-cap biotech is also set up to receive up to a potential $2.7 billion in milestone payments because of this deal as well. Then, you have Pfizer obtaining ex-China rights to PD-1/VEGF bispecific antibody SSGJ-707. It handed an upfront payment of $1.25 billion to 3SBio and may also have to pony up an additional $4.8 billion in development milestones as well. While these bispecific antibodies have done well in the targeting of multiple solid tumors to date, what is going to end up being a key item will be whether or not they end up having a major impact in terms of improving overall survival (OS) for these solid tumor patients.
The point of the PD-L1 component as part of BNT327 is to inhibit the PD-1 protein component found on the cell surface of tumors that are able to block T-cells and the immune system from attacking the tumor itself. Then, the other part of this drug is to inhibit the VEGF-A component, which drives the growth of new blood vessels that tumors need to grow. That is, they rely on the oxygen and nutrients from such growths in order to continue to grow at a rapid pace and spread.