Two Xencor approaches with questions around them receive the backing of Johnson & Johnson.
A small collaboration, worth $100m in up-front cash plus $25m in equity, today shows Johnson & Johnson getting a little closer to the bispecific antibody specialist Xencor. It concerns the anti-CD20 T-cell engager plamotamab and bispecifics targeting CD28, and raises two obvious questions.
One is why J&J should have chosen plamotamab, an asset that has so far underwhelmed, as its gamble in CD20-expressing B-cell malignancies. And the second is how the company will hope to avoid the stigma, relating to the notorious case of Tegenero, that saw CD28 relegated to a pariah for over a decade.
Perhaps the second question is easier to answer. As of last December J&J and Xencor have been working on a bispecific that hits an undisclosed prostate cancer target, thought to be PSMA, as well as agonising CD28. Clearly J&J has seen something it likes, and today felt comfortable to make a second foray.
It is not the first group to do so. In July Merck & Co endorsed Alpine Immune Sciences’ approach, after the small biotech presented data at Asco showing that agonising CD28 could be done safely. Regeneron is another player that has confidently invested in CD28-targeting bispecifics, and Sanofi is active with a trispecific, SAR442257.
Xencor argues that it has worked hard to develop a new class of CD28 T-cell engagers, by identifying a proprietary epitope with the right amount of avidity to boost T-cell activity without causing superagonism. Tegenero’s 2006 serious adverse events concerned TGN1412, a superagonist MAb.
Xencor separately has a wholly owned preclinical asset that hits CD28 as well as B7-H3. Under today’s deal with J&J the companies will work for two years to create new CD28-targeting bispecifics.
CD20 laggard
On the other hand, J&J buying into plamotamab – the more advanced focus of today’s tie-up – is a little harder to understand.
When plamotamab was still known under the lab code XmAb13676 it had been licensed to Novartis, but the Swiss firm canned the deal in early 2019. The termination might have had more to do with the second part of that tie-up, Xencor’s anti-CD123 bispecific vibecotamab/XmAb14045, which had been put on US clinical hold.
But plamotamab did not distinguish itself clinically, reporting a 39% overall remission rate in relapsed/refractory lymphoma at Ash in 2019. It did not feature at Ash the following year, when numerous other anti-CD20 bispecifics impressed and Genmab’s epcoritamab was hailed as best in class.
J&J has a significant deal with Genmab, but epcoritamab is already partnered with Abbvie. Perhaps J&J, late to the game in CD20-targeting blood cancer therapeutics and behind Roche and Regeneron as well as Abbvie, saw no other option than to pick up plamotamab, to which it now has global development and commercialisation rights.
On an analyst call today Xencor highlighted its own separate clinical work on plamotamab plus Morphosys’s Monjuvi, thus combining CD20 and CD19 antagonism, as well as on a combo of plamotamab with CD28 agonism.
Execs said plamotamab would yield more clinical data at a medical meeting this quarter. This was surely a reference to Ash in December, and the dataset will be scrutinised for signs of improvement over its last iteration.
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