Genmab takes aims at immuno-oncology antibody conjugates with Bolt Bio

Genmab has enlisted the help of Bolt Biotherapeutics to develop a new class of immune-boosting antibody conjugates for cancer in a deal that could be worth up to $880 million.

Denmark-based Genmab is paying $10 million upfront to its US counterpart and making a $15 million equity investment to get the project started, funding R&D to the proof-of-concept stage in early clinical trials.

If all goes well, the intention is to take up to three immune-stimulating antibody conjugates (ISACs) forward, with Bolt in line for milestones of $285 million apiece if they reach the market. The ISACs will be bispecific, meaning they latch on to a pair of molecular targets rather than just one.

Genmab is supplying the bispecific antibody technology, while Bolt will contribute its innate immune stimulant platform, which it says can re-programme the tumour microenvironment to trigger a localised immune response against the cancer.

The approach differs from current immuno-oncology approaches like checkpoint inhibitors, which work by overcoming suppression of the immune system and – according to Bolt – could be used to tackle solid tumours like pancreatic cancer that are notoriously hard to treat.

Bolt's own ISACs consist of a single-headed antibody, linker and proprietary immune stimulant molecule, so the partnership with Genmab will allow it to add a second molecular target into the mix, which could increase the specificity of the drug or add functionality like recruiting specific immune cells.

The approach could lead to "a completely new type of ISAC with the aim to transform the way cancer is treated," according to Bolt's chief executive Randall Schatzman.

"Creating bispecific ISACs turbo-charged with potent immune stimulants is a novel concept that has tremendous potential for patients," he added.

Genmab's antibody platform has already resulted in three approved products, including Johnson & Johnson's big-selling multiple myeloma therapy Darzalex (daratumumab), and its bispecific pipeline includes several clinical stage candidates headed by AbbVie-partnered epcoritamab for blood cancers.

Many of Genmab's alliances to date have focused on deploying its own antibody platforms against targets of interest to its partners, but it has also been active in tapping into other companies technologies, as in the latest Bolt deal.

Earlier examples include 2019 agreements with CureVac for mRNA technology and BLiNK Bio on CD47-targeting, and a 2018 deal with Immatics focusing on T-cell receptors (TCRs).