Bristol keeps foot on immuno-oncology gas pedal

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Bristol-Myers Squibb stock might have taken a kicking after the release of Asco abstracts two weeks ago, but the company is not about to take its foot off the accelerator when it comes to immuno-oncology deals.

A tie-up with the private group CytomX Therapeutics has seen it hand over a remarkable $50m up front for what is basically a discovery alliance, while a separate deal means Incyte has now cornered three of four major immuno-oncology players. This space will remain hot at Asco, even if, as CytomX has again shown, private companies are attracting the big money.

CytomX of course is used to big pharma attention, having struck another big preclinical oncology deal last year. That was with Pfizer, which paid it $25m up front and committed to up to another $610m in future fees.

Bristol has been attracted to CytomX’s so-called Probody technology. Probodies are monoclonal antibodies that are masked in healthy tissue but activated in the disease microenvironment – possibly conferring tolerability advantages – and the proprietary technology that is CytomX’s key asset concerns the masking of the molecules.

The tie-up will allow Bristol to develop Probodies for up to four oncology targets, including CTLA-4 – the same antigen that Bristol’s melanoma drug Yervoy targets. In addition to the $50m signing fee Bristol has agreed to pay up to $298m in milestones, plus a tiered mid-single-digit to low-double-digit royalty.

Through deals like this Bristol is shoring up its key immuno-oncology pipeline asset, the anti-PD-1 MAb nivolumab. In March the company paid $20m up front to the private group Five Prime Therapeutics in a deal targeting two undisclosed immune checkpoint pathways, and earlier this month it agreed to a phase I/II trial combining nivolumab with Celldex’s CD27-targeting MAb varlilumab.

The other deal it struck yesterday, with Incyte, runs along similar lines. It involves a phase I/II study, to begin later this year, combining nivolumab with Incyte’s oral IDO (indoleamine 2,3-dioxygenase) inhibitor INCB24360 in several tumour types.

IDO endorsement

Though financial details of the tie-up were not disclosed, implying that they were negligible, the deal is significant strategically for Incyte, since it brings yet another big pharma endorsement.

Incyte already has non-exclusive licences covering combination studies of INCB24360 with Merck & Co’s anti-PD-1 pembrolizumab and AstraZeneca’s anti-PD-L1 MEDI4736 (AstraZeneca and Incyte say IDO, May 14, 2014). With Bristol on board it only remains for Incyte to sign up Roche, with its anti-PD-L1 MAb RG7446, to have alliances with all four of the main players in this space.

Like Bristol, Incyte was hit hard when the Asco abstracts went live, and yesterday’s deal at least allowed the shares to regain some lost ground, closing up 4%. For NewLink Genetics, the only other company with a clinical-stage IDO inhibitor, Incyte’s stranglehold cannot be good news, though NewLink stock actually rose slightly yesterday.

The reason Bristol’s contribution to Asco underwhelmed was that a keenly awaited first-line lung cancer study combining Yervoy with nivolumab threw up significant toxicities, implying that Yervoy’s inherent side effects are proving hard to shake off.

Immuno-oncology combinations are designed not only to dial up efficacy through an additive effect, but also to reduce toxicities by allowing reduced dosing of the individual components. Hard results might be years away, but at least one of Bristol’s latest two deals is aimed precisely at broadening this therapeutic window.

To contact the writer of this story email Jacob Plieth in London at jacobp@epvantage.com or follow @JacobEPVantage on Twitter

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