As intractable leukaemia treatments emerge, so do deals

A flurry of US approvals for acute myelogenous leukaemia has prompted a surge of interest in this once intractable disease, and one of the beneficiaries, Jazz Pharmaceuticals, is not letting the grass grow under its feet.

An option deal signed yesterday with Immunogen could give Jazz three new AML-focused assets to go with its recently approved Vyxeos. And it will not have gone unnoticed that all three are antibody-drug conjugates, which as a drug class is undergoing something of a resurgence of its own.

The poster child for antibody-drug conjugates (ADCs) is Seattle Genetics’ Adcetris, and Seattle did a separate deal yesterday with Genmab, though this did not specify AML. Rather, Genmab’s tisotumab vedotin, an ADC targeting tissue factor, will now be developed on a 50/50 basis for solid tumours.

Seattle has its own presence in AML, though this is at present stalled: vadastuximab talirine’s phase III study was scrapped and all other studies are on hold after toxicity and patient deaths.

Caveat emptor

This is a possible red flag for Jazz investors, since vadastuximab targets CD33, the same antigen that is hit by IMGN779, the first of the three assets under option from Immunogen.

On the plus side, Pfizer’s Mylotarg also hits CD33, and looks likely to get US approval this week after a positive adcom vote for first-line, CD33-expressing AML (Leukaemia options begin to improve for elderly patients, July 13, 2017). Nevertheless, Bernstein analysts today wrote that clinical validity of CD33 was still an open question.

Either way, it is unlikely that AML is about to dry up as a source of licensing deals. Jazz had earlier bought Celator, Vyxeos’s originator, after the project remarkably demonstrated a clinical and statistical benefit in its pivotal trial, sending it on the path to US approval this month.

Jazz now looks set to capitalise on its position here, and it is possible that it might use Vyxeos as an AML backbone in future combinations.

Still, the CD123 antigen targeted by the second Immunogen ADC, IMGN632, is no slam dunk either. A patient death hit Stemline Therapeutics’ CD123-targeting asset SL-401 earlier this year, while JNJ-63709178, Johnson & Johnson’s anti-CD123 bispecific, was until recently on clinical hold.

The Jazz/Immunogen deal is worth $75m up front, plus $100m of research support over seven years. A third AML-focused asset from Immunogen has yet to be selected for inclusion in the tie-up.

AML quartet?

If Mylotarg is approved this week it would join Vyxeos, Novartis’s Rydapt and Celgene/Agios’s Idhifa among AML drugs to get the green light this year.

It will be interesting to watch for any response from Seattle, either in AML specifically or in other ADC work. The group is keen to reduce its focus on Adcetris, and presumably this was one reason behind it exercising the Genmab option yesterday.

In the broader ADC world it is still not clear, for instance, what will happen to Immunomedics’ sacituzumab govitecan, which Seattle had tried but failed to license in (Venbio completes its Immunomedics rout, May 5, 2017).

With Seattle failing to complete that deal, and its CD33-directed AML project dead in the water, the company can hardly be expected to sit on its hands.

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

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