Micro-cap Mei Pharma lands $100M upfront on beleaguered PI3K pathway
For Mei Pharma, the road to Morimoto — an upscale, dungeon-like sushi restaurant run by a celebrity chef, surrounded by wavy abstract walls and crowded with plexiglass booths where, last year, a micro-cap biotech could make their case to a large global partner between events at BIO’s Philadelphia convention — was long.
Nearly a decade ago, the San Diego biotech had seen a presentation at ASH on a preclinical cancer pill that targeted a cellular pathway known as PI3K, or phosphoinositide 3-kinase inhibitor. It seemed to be involved in a host of cell processes, including as a back channel for cancers blocked in other directions. Biotechs were just figuring out how to drug it.
Eventually, many drugs would get lost down that pathway, crippled by tolerability issues that rendered them commercially or medically inviable. Mei Pharma, though, stuck with theirs, betting on chemical properties they thought would enable a workaround to the safety concerns. The full data have yet to come out, but last year in Philadelphia COO David Urso managed to get Kyowa Kirin on board, leading, today, to an up-to $682 million deal for the ex-US rights, with a 50/50 cost and profit sharing on US commercialization.
The deal pays $100 million — more than half of Mei Pharma’s market value and doubling their cash-on-hand from February.
“We really had two strategic objectives: the first one was to create value in the asset by globally accelerating the development program across all B-cell malignancies, and the second was to develop our own domestic commercial capabilities,” Urso told Endpoints News. “We were able to achieve both.”
A couple years after seeing the ASH poster, Mei Pharma acquired the drug from Pathway Therapeutics, “a small private company that was essentially going out of business,” CEO Dan Gold recalled. By then, Gilead had made the major deal in the PI3K world, paying $375 million to acquire Seattle upstart Calistoga. Genentech had also invested heavily in the science, as had AstraZeneca, GlaxoSmithKline, Sanofi and a host of smaller companies. There was a similar hype, Gold said, to BTK inhibitors — the class of drugs that has since led to multiple blockbusters.
“Back then, there wasn’t a true understanding of the tolerability issues,” Gold told Endpoints.
Soon though, the Gilead drug, Zydelig, showed a diverse array of safety issues, ranging from diarrhea to, in at least one indication, possible higher mortality. Some of those issues seemed limited to Zydelig —which never got the sales Gilead hoped — but others seemed to apply to any drug targeted for PI3K. The number of FDA-approved inhibitors could be counted on one hand. Big players discarded programs.
Mei Pharma said they found themselves hurtling down a similar path. By the time they got the acquired drug — known as MEI-401 — into a Phase I trial, the efficacy results only mattered so much. Doctors weren’t going to prescribe a drug with these kinds of complications to anyone but the sickest and most drug-resistant patients.
“We believed from what we heard from physicians, if we had one that was truly more potent, it would be great but only good for salvage setting,” Gold said. “We wanted to be much broader.”
The company began experimenting with a different dosing regimen that might reduce toxicity. They said their drug entered tissues and cells and bound within cells for easier and longer than rival drugs. So the company tried an intermittent dosing regime — giving the pill for 7 days.
The early Phase Ib data, announced in October, were promising: Grade 3 adverse effects fell below 10% for intermittent dosing. Now, they’re depending on a Phase II trial they hope could land them accelerated approval. They say Covid-19 has slowed but not halted enrollment.