Glycomimetics down and out on upro miss

Glycomimetics has pivoted once, but looks unlikely to be able to do so again. Yesterday’s phase 3 failure of its lead project, uproleselan, in relapsed/refractory acute myeloid leukaemia leaves the group in dire financial straits with no prospect of raising more cash and little else in its pipeline. No wonder the company’s market cap sank 83% to just $20m on the news.

Like many other biotechs, Glycomimetics has been scuppered by a strong placebo performance. Overall survival, the trial’s primary endpoint, totalled 13 months for uproleselan plus chemo and 12.3 months for chemo alone – the company had expected control patients to survive for 6-7 months, and for uproleselan to show a survival benefit of around three months, Glycomimetics’ chief executive, Harout Semerjian, told ApexOnco ahead of the readout.

Delays

However, failure was always a strong possibility given the delays to this study, which enrolled patients fit for intensive chemotherapy: the last subject was enrolled in November 2021, and data had initially been expected in 2022. Last year the FDA agreed to a time-based OS analysis after a defined cutoff date, if the required number of events hadn’t been reached.

Ahead of the results Semerjian said he had been “enthused” that patients were living longer and what this might mean for uproleselan; but history has told us that, often, lagging data don’t necessarily bode well for companies, precisely because all patients – not just those in the active treatment cohort – might be living longer than expected.

For now Glycomimetics isn’t disclosing much else except that adverse events were consistent with chemo, and that it plans to present full results at an upcoming medical meeting.

Uproleselan is also in an NCI-sponsored phase 2/3 trial, where it’s being tested as part of a chemo combo in first-line AML patients fit for intensive therapy. The primary endpoint is event-free survival. 

However, it’s unclear when data from the phase 2 portion of this study, which completed enrolment in December 2021, will be available; Semerjian noted that this trial has faced a similar issue as the Glycomimetics-sponsored study, with patients doing better than expected.

Sickle cell efforts

Hopes can’t be high for the future of uproleselan, one of only two E-selectin inhibitors in active clinical development, according to OncologyPipeline – with the other also in Glycomimetics’ hands. GMI-1687, in development for vaso-occlusive crises in sickle cell disease, has completed phase 1a in healthy volunteers.

While in AML hitting E-selectin was thought to release AML blasts from sequestration, rendering them more susceptible to chemo, in sickle cell disease this mechanism is designed to inhibit leukocyte adhesion.

However, Glycomimetics’ similarly acting contender, the Pfizer-partnered rivipansel, flunked phase 3 in sickle cell disease nearly five years ago.

After that failure, Glycomimetics managed to shift focus to uproselan, and was boosted by promising phase 1/2 AML data at ASH 2022. That success propelled the company to a 207% share price gain over the period of that conference.

However, after the latest readout, and with only $31m in the bank, another Lazarus-like recovery seems improbable.