Expect Immunogen to have had a busy weekend: for one, it will likely have been working the phones with its bankers after last week’s wounding setback for its lead asset, mirvetuximab. But discussions should also have turned to how Jazz Pharmaceuticals might be persuaded to opt in to two early assets, IMGN779 and IMGN632.
It is those two projects that some now see as key to Immunogen’s future, but despite promising phase I data in December Jazz, which two years ago bought opt-in rights, has still not bitten the bullet. True, mirvetuximab combo data at Asco could provide a financing window, but in the longer term this asset is a no-hoper.
None of this is to say that Immunogen is desperate; the group ended its first quarter with $270m of cash and virtually no debt. But, as every investor should know, biotechs raise money not when they need it but when they can, and Immunogen has admitted that it is starting an operational review to extend its cash reach.
This was prompted by the US FDA’s refusal to allow a datadredge of the Forward I study to support approval of mirvetuximab monotherapy for platinum-resistant ovarian cancer. Forward I had resoundingly failed to extend progression-free survival in the overall population of folate receptor α (FRα) positive patients.
However, the group had argued that it had seen efficacy in a subgroup of those patients with high levels of FRα, though even here the PFS benefit failed to hit a prespecified level of significance. Still, Immunogen talked up the prospects of the FDA approving mirvetuximab on these data alone, causing its stock to climb nearly 40% at the start of this month.
But last week the shares lost all these gains and more when the FDA refused to entertain such a plan, instead demanding a new prospective pivotal study in FRα-high subjects. The problem was not only the subgroup’s underwhelming PFS data, but the overall remission figures, which were statistically stronger but which the agency said could not be extrapolated to support clinical benefit.
Thus Immunogen must now decide whether to devote more attention to the back-up antibody-drug conjugates (ADCs) IMGN779 and IMGN632, whose main attraction is the use of novel class of indolinobenzodiazeprine pseudodimer cytotoxic payloads.
Two years ago Jazz, seeking to boost its oncology presence, paid Immunogen $75m for an option on these and an undisclosed asset. Formally there are two points at which Jazz can opt in to full development: just before pivotal trial start, triggering a “mid double-digit million” milestone, or on regulatory filing, making a “low triple-digit million” fee payable.
Still, licensing deals can be done at any point, and Immunogen would do well to urge Jazz to strike sooner rather than later. An obvious way to do this could be to shop the assets around other companies – the ADC specialist Seattle Genetics springs immediately to mind – and then, assuming that there is interest from these rivals, to impress on Jazz the urgency of the situation.
True, mirvetuximab is far more advanced, and as it is by no means dead it will continue to preoccupy Immunogen and its advisors. A separate study, Forward II, tests the agent alongside other drugs including Keytruda and Avastin – data from the Avastin arm are due to be updated at Asco next month, giving the possibility of a share price uplift.
But the main reason for deep scepticism about mirvetuximab concerns its mechanism of action. The project’s folate receptor target has a proven track record of failure that is due largely to its expression on healthy as well as cancerous cells. Immunogen says 40% of ovarian cancer patients have high levels of FRα, but doubts have been raised about the receptor’s value as a prognostic factor.
A small trial to support accelerated approval might have been affordable, but the worst thing about the Forward I knockback is that the FDA has sent Immunogen a clear message that response rate cannot be used as a surrogate to support mirvetuximab.
The company is thus obliged to run a whole new multicentre study with a survival endpoint. It risks throwing good money after bad.
|Selected studies of mirvetuximab in ovarian cancer|
|Forward II||Combination||Avastin combo expansion cohort data at Asco||NCT02606305|