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.

David Ur­so

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.

Daniel Gold

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.

Dan Skovronsky, Eli Lilly CSO

UP­DAT­ED: An­a­lysts are quick to pan Eli Lil­ly's puz­zling first cut of pos­i­tive clin­i­cal da­ta for its Covid-19 an­ti­body

Eli Lilly spotlighted a success for one of 3 doses of their closely-watched Covid-19 antibody drug Wednesday morning. But analysts quickly highlighted some obvious anomalies that could come back to haunt the pharma giant as it looks for an emergency use authorization to launch marketing efforts.

The pharma giant reported that LY-CoV555, developed in collaboration with AbCellera, significantly reduced the rate of hospitalization among patients who were treated with the antibody. The drug arm of the study had a 1.7% hospitalization rate, compared to 6% in the control group, marking a 72% drop in risk.

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Secretary of health and human services Alex Azar speaking in the Rose Garden at the White House (Photo: AFP)

Trump’s HHS claims ab­solute au­thor­i­ty over the FDA, clear­ing path to a vac­cine EUA

The top career staff at the FDA have vowed not to let politics get in the way of science when looking at vaccine data this fall. But Alex Azar, who happens to be their boss’s boss, apparently won’t even give them a chance to stand in the way.

In a new memorandum issued Tuesday last week, the HHS chief stripped health agencies under his purview — including the FDA — of their rulemaking ability, asserting all such power “is reserved to the Secretary.” Sheila Kaplan of the New York Times first obtained and reported the details of the September 15 bulletin.

Eli Lilly CSO Dan Skovronsky (file photo)

#ES­MO20: Eli Lil­ly shows off the da­ta for its Verzenio suc­cess. Was it worth $18 bil­lion?

The press release alone, devoid of any number except for the size of the trial, added nearly $20 billion to Eli Lilly’s market cap back in June. Now investors and oncologists will get to see if the data live up to the hype.

On Sunday at ESMO, Eli Lilly announced the full results for its Phase III MonarchE trial of Verzenio, showing that across over 5,000 women who had had HR+, HER2- breast cancer, the drug reduced the odds of recurrence by 25%. That meant 7.8% of the patients on the drug arm saw their cancers return within 2 years, compared with 11.3% on the placebo arm.

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Greg Friberg (File photo)

#ES­MO20: Am­gen team nails down sol­id ear­ly ev­i­dence of AMG 510’s po­ten­tial for NSCLC, un­lock­ing the door to a wave of KRAS pro­grams

The first time I sat down with Amgen’s Greg Friberg to talk about the pharma giant’s KRAS G12C program for sotorasib (AMG 510) at ASCO a little more than a year ago, there was high excitement about the first glimpse of efficacy from their Phase I study, with 5 of 10 evaluable non-small cell lung cancer patients demonstrating a response to the drug.

After decades of failure targeting KRAS, sotorasib offered the first positive look at a new approach that promised to open a door to a whole new approach by targeting a particular mutation to a big target that had remained “undruggable” for decades.

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#ES­MO20: Out to beat Tagris­so, J&J touts 100% ORR for EGFR bis­pe­cif­ic/TKI com­bo — fu­el­ing a quick leap to PhI­II

J&J’s one-two punch on EGFR-mutant non-small cell lung cancer has turned up some promising — although decidedly early — results, fueling the idea that there’s yet room to one up on third-generation tyrosine kinase inhibitors.

Twenty out of 20 advanced NSCLC patients had a response after taking a combination of an in-house TKI dubbed lazertinib and amivantamab, a bispecific antibody targeting both EGFR and cMET engineered on partner Genmab’s platform, J&J reported at ESMO. All were treatment-naïve, and none has seen their cancer progress at a median follow-up of seven months.

#ES­MO20: As­traZeneca aims to spur PRO­found shift in prostate can­cer treat­ment with Lyn­parza OS da­ta

AstraZeneca has unveiled the final, mature overall survival data that cemented Lynparza’s first approval in prostate cancer approval — touting its lead against rivals with the only PARP inhibitor to have demonstrated such benefit.

But getting the Merck-partnered drug to the right patients remains a challenge, something the companies are hoping to change with the new data cut.

The OS numbers on the subgroup with BRCA1/2 or ATM-mutated metastatic castration-resistant prostate cancer are similar to the first look on offer when the FDA expanded the label in May: Lynparza reduced the risk of death by 31% versus Xtandi and Zytiga. Patients on Lynparza lived a median of 19.1 months, compared to 14.7 months for the anti-androgen therapies (p = 0.0175).

Exelixis CEO Michael Morrissey (file photo)

#ES­MO20: Look out Mer­ck. Bris­tol My­ers and Ex­elix­is stake out their com­bo’s claim to best-in-class sta­tus for front­line kid­ney can­cer

Now that the PD-(L)1 checkpoints are deeply entrenched in the oncology market, it’s time to welcome a wave of combination therapies — beyond chemo — looking to extend their benefit to larger numbers of patients. Bristol Myers Squibb ($BMY} and Exelixis {EXEL} are close to the front of that line.

Today at ESMO the collaborators pulled the curtain back on some stellar data for their combination of Opdivo (the PD-1) and Cabometyx (the TKI), marking a significant advance for the blockbuster Bristol Myers franchise while offering a big leg up for the team at Exelixis.

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#ES­MO20: It’s not just Keytru­da any­more — Mer­ck spot­lights 3 top ear­ly-stage can­cer drugs

Any $12 billion megablockbuster in the portfolio tends to overshadow everything else in the pipeline. Which is something Merck can tell you a little bit about.

Keytruda not only dominates the PD-(L)1 field, it looms over everything Merck does, to the point some analysts wonder if Merck is a one-trick pony.

There’s no shortage of Keytruda data on display at ESMO this weekend, but now the focus is shifting to the future role of new drugs and combos in maintaining that lead position for years to come. And the pharma giant has a special focus for 3 early-stage efforts where Roger Perlmutter’s oncology team is placing some big bets.

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#ES­MO20: Trodelvy da­ta show that Gilead­'s $21B buy­out may have been worth the big pre­mi­um

Gilead CEO Dan O’Day has been on a shopping spree. And while some analysts gawked at the biotech’s recent $21 billion Immunomedics buyout, new data released at virtual ESMO 2020 suggest the acquisition may have been worth the hefty price.

The deal, announced last weekend, will give California-based Gilead $GILD Trodelvy, which was recently approved for metastatic triple-negative breast cancer (mTNBC).

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