Kyowa buys into menin, but it's not Syndax's

Investors seemed sceptical of Syndax's ability to effect a solo launch of the first approved menin inhibitor, Revuforj. Syndax's arch rival Kura might be able to avoid a similar fate, having just struck a licensing deal with Japan's Kyowa Kirin for what could become the world's second menin inhibitor, ziftomenib.

This doesn't mean that some in the market won't be disappointed by such an outcome, and the fact that an outright takeover hadn't materialised sent Kura stock down 35% this morning. That said, even if Kyowa isn't the big partner some might have hoped for, the deal seems generous, and should provide an important endorsement of ziftomenib's potential.

The deal terms call for $330m up front, and a further $420m of the remaining $1.2bn biodollar amount is said to comprise "near-term milestone payments" – perhaps relating to ziftomenib's approval and/or initial market performance – and opt-in rights for solid tumours.

First-line AML

Ziftomenib's first possible setting is relapsed NMP1-mutant AML, where data are due in the first quarter, but the big opportunity could be front-line AML, where an update on the Komet-007 chemo combo trial is to be presented at next month's ASH conference. In its statement Kyowa said the front-line setting was a market worth $3bn a year in the US alone.

It's notable that the tie-up has a global scope; Kyowa is a Japanese group, but it does have offices in the US and Europe, and like many Japanese groups it will be keen to expand outside its home market. Development is to be led by Kura in the US, where a 50/50 profit share will be implemented, while ex-US activities will be Kyowa's responsibility, in return for a royalty.

One take on the deal is that its combined $1.5bn biodollar value for a 50% share of US economics endorses a $3bn valuation for ziftomenib, but this is clearly too simplistic a take. Some analysts expect the drug's sales to peak over $1bn a year, but it's still unclear how the various settings might play out.

What is clear is that ziftomenib is at least a year behind Syndax's Revuforj in reaching the market, but the initial indications differ. Revuforj was approved for KMT2A-rearranged acute leukaemia, a setting Kura is no longer pursuing with ziftomenib monotherapy, and one that's smaller than NPM1-mutant relapsed leukaemia where both projects are being developed.

Fears allayed

Broadly, however, the FDA's willingness to approve Revuforj, despite its association with QTc prolongation, has allayed some fears about menin inhibitors. This stance was also positive for Kura, since QTc prolongation hasn't been seen with ziftomenib; both are linked with differentiation syndrome.

Indeed, the approval, which occurred on Monday, might have focused the minds of interested licensees, though for a deal to have emerged just three days later suggests that talks had been ongoing for some time before. Syndax shares barely moved on the approval, having fallen 26% last week on toxicity fears arising from the Augment-101 trial in NPM1-mutant AML – a development that sent Kura up 6%. 

Still, it's quite possible that Kyowa, seeking a menin inhibitor to license, went first not to Kura but to Syndax. Such a scenario is backed by Revuforj being first to market, and by Syndax and Kyowa already being familiar with each other; the Japanese group was Syndax's partner for the since deprioritised HDAC inhibitor entinostat, under a 2015 regional tie-up.

If in the latest talks Kyowa was rebuffed for not offering to buy Syndax outright, such a consideration clearly wasn't a deal-breaker for Kura.