Deal Flurry Shines Spotlight On Novel Multiple Myeloma Target

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Includes: AMGN, CELG, NVS, WLXMF
by: EP Vantage

A flurry of early-stage alliances has marked the BCMA protein as one of the most interesting targets to watch in the search for novel multiple myeloma treatments.

Today’s preclinical-stage, BCMA-focused deal between Wilex (OTC:WLXMF) and the Max Delbrück Center comes shortly after Amgen (NASDAQ:AMGN) bought Boehringer Ingelheim out of rights to an anti-BCMA bispecific, and Juno licensed a BCMA CAR-T asset from Eureka Therapeutics. No doubt Celgene (NASDAQ:CELG) – a multiple myeloma powerhouse that is itself thought to be completing a BCMA-targeting asset acquisition – is paying close attention.

Celgene, of course, already has a hand in this novel antigen through a deal with Bluebird Bio covering bb2121, a CAR-T against BCMA in phase I. And last week Jefferies analysts suggested that Celgene might be about to close a deal to buy the private Swiss group Engmab.

This rumor was triggered by a notice on the FTC website citing Celgene as the acquiring party for Engmab, a biotech company developing EM801, a bispecific antibody targeting BCMA. Engmab is run by Roche’s former finance chief Erich Hunziker. So far there has been no formal announcement from either Celgene or Engmab.

Such an asset represents direct competition for Amgen, which two weeks ago bought out Boehringer’s interest in BI 836909, a phase I bispecific against BCMA derived from Micromet, which Amgen had acquired in 2012 (Behold the son of Blincyto, September 2, 2016).

Conjugate approach

The German biotech Wilex, meanwhile, is putting its money not on a bispecific project but on an antibody-drug conjugate.

This morning’s option agreement with Berlin’s Max Delbrück Center for Molecular Medicine in the Helmholtz Association is squarely focused on antibodies against BCMA. Within this the asset with the most preclinical promise seems to be HDP-101, which comprises a BCMA MAb conjugated to the toxin Amanitin via a specific linker.

Amanitin makes an interesting choice for a cytotoxic agent, as until recently it was thought to have been superseded by tubulin-inhibiting payloads. It is not easy designing antibody-drug conjugates – it is vital also to get the linker stability right, for instance; HDP-101 should enter the clinic in 2018, Wilex says.

There are other difficulties, too: BCMA is a relatively very small protein, making it tough to hit with an antibody. The protein is preferentially expressed on mature B cells and plasma cells – hence the potential for using it as a target to treat multiple myeloma, a cancer of plasma cells.

For now the most advanced anti-BCMA assets are Amgen’s BI 836909/AMG 420 and the CAR-Ts, with clinical trials ongoing of Bluebird’s bb2121, Novartis’ CART-BCMA and a third project at the NCI. These will not be alone in the clinic for long.