Genmab brings on Abbvie for bispecific boost

Abbvie pays handsomely to join the CD20 bispecific brawl, handing over $750m to Genmab for access to a project that trails the competition.

Genmab has been promising a deal on its lead R&D project, epcoritamab, for some time now and today unveiled Abbvie as its new partner. The CD20-targeting bispecific sits in a field where Roche and Regeneron are ahead with similar agents, so the Danish biotech was always going to need help competing.

With Abbvie's big presence in haematological cancers, thanks to Imbruvica and Venclexta, partnering certainly makes sense. The deal terms point to the promise seen with bispecifics in this area: $750m up front and up to $3.2bn in milestones for Genmab, which also gets to keep a healthy portion of the profits should epcoritamab make it to market.

The bispecific promise

Highly encouraging response rates with Regeneron’s REGN1979 and Roche’s mosunetuzumab across various lymphomas have raised hopes that using a bispecific to hit CD20 might boost the effectiveness of this well-established mechanism. The hope is that these agents might offer a more tolerable and convenient option than Car-T in later settings.

While there are several CD20 bispecific projects in development, Roche and Regeneron are considered to be in front. Both presented substantial datasets at Ash last year, suggesting that what REGN1979 gained in efficacy over mosunetuzumab it lost in safety (Ash 2019 – Regeneron takes the bispecific baton and runs, December 10, 2019).

As a huge player in the CD20 space with Rituxan and Gazyva Roche should not be ruled out here, of course, but this is a race that is far from over.

Genmab presented the latest cut from an ongoing trial of epcoritamab at Asco this month, and this appeared to show competitive efficacy. And on safety, which is more easily judged at this stage, epcoritamab certainly holds it own, with a much lower rate of severe cytokine release, albeit in fewer patients so far.

CD20 bispecific safety comparison
  REGN1979 (Regeneron) Mosunetuzumab (Roche) Epcoritamab (Genmab/Abbvie)
N 110 270 58
CRS 59% 29% 57%
CRS grade 3-4 6.4% 1.1% 0.0%
CRS=cytokine release syndrome. Source: Ash 2019 & Asco 2020.

Regeneron and Roche have already started much larger phase II programmes with their respective candidates, and on a call with investors this afternoon Genmab and Abbvie said they were keeping specific plans for epcoritamab “close to their chests”. While they acknowledged that they were behind, plans are afoot to catch up, they insisted, and hinted that a huge pivotal programme was on the cards.

A “Darzalex-type development programme” should be expected, they revealed, involving multiple thousands of patients; combinations with Imbruvica and Venclexta are also likely. Considering that epcoritamab data in only 58 patients have been published to date, some might find this talk premature.

The broad deal also involves two other clinical-stage bispecifics and potentially four other projects down the road, so some of the fees will relate to progress elsewhere. A big proportion will be linked to epcoritamab, however, which Genmab will jointly market with Abbvie in the US and Japan.

Profits will be shared equally in these countries; elsewhere Genmab will receive 22-26% royalties. The terms are broadly similar for the other two bispecifics: the anti-CD37 MAb GEN3009, which is in a phase I trial, and a T-cell engager against 5T4, a target expressed on a variety of solid tumours. An IND on the latter has only just been filed. 

On the call the deal was repeatedly described as a “50:50 partnership” and “transformational” by Genmab executives, although Abbvie’s management are also probably hopes for pretty big things. The company has fired several blanks in oncology – think Rova-T and veliparib – and shares in the company opened up almost 2% today.

With an $18bn market cap Genmab can hardly be described as a small biotech, though this valuation is largely due to a substantial rally over the past few months. The stock touched a record high in late May and has surged 64% so far this year, which probably explains a relatively muted response to the deal: shares were trading 5% higher on the news.

However, it is clear that in Abbvie a motivated and ambitious partner has been found. 

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