Genmab axes development of AXL-targeting cancer drug enapotamab vedotin

Genmab has axed development of its pipeline cancer drug enapotamab vedotin after it failed to show enough activity in a proof-of-concept trial.

The drug is an antibody-drug conjugate where a monoclonal antibody is linked to monomethyl auristatin, a cancer-killing "payload".

It is targeted against AXL, a signalling molecule that is overexpressed in several haematologic and solid malignancies.

Developing enapotamab vedotin formed a major part in the rationale behind the company’s $506 million Nasdaq IPO last year.

Genmab said it will not advance development of the drug after data from expansion cohorts showed it did not meet stringent criteria for proof-of-concept in the early trial.

There was some evidence of clinical activity but this was not “optimised by different dose schedules and/or predictive biomarkers” the company said in a statement.

The company will instead prioritise development of other drugs in its pipeline.

AXL overexpression is thought to drive several cancer processes, including metastasis, tumour angiogenesis, resistance to chemotherapy and targeted agents, and decreased antitumor immune response.

Enapotamab vedotin is fully owned by Genmab and the drug linker technology used for enapotamab vedotin was licensed from Seagen Inc, formerly known as Seattle Genetics.

Jan van de Winkel, CEO of Genmab, said: “We are committed to developing innovative antibody products for patients with cancer, however the data from the enapotamab vedotin expansion cohorts unfortunately does not support moving this product candidate forward.

“This decision will allow us to focus more of our resources and energy on other programs in our robust next-generation antibody therapeutics pipeline.”

AXL is also being targeted by the Norwegian biotech BerGenBio, which has also been looking at using the pathway to fight inflammation seen in COVID-19.

The company’s bemcentinib is under development as a combination and single agent therapy in lung cancer and leukaemia, as well as COVID-19.

It also has an anti-AXL antibody, tilvestamab, which is undergoing phase 1 testing in cancer.