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.

ZS Per­spec­tive: 3 Pre­dic­tions on the Fu­ture of Cell & Gene Ther­a­pies

The field of cell and gene therapies (C&GTs) has seen a renaissance, with first generation commercial therapies such as Kymriah, Yescarta, and Luxturna laying the groundwork for an incoming wave of potentially transformative C&GTs that aim to address diverse disease areas. With this renaissance comes several potential opportunities, of which we discuss three predictions below.

Allogenic Natural Killer (NK) Cells have the potential to displace current Cell Therapies in oncology if proven durable.

Despite being early in development, Allogenic NKs are proving to be an attractive new treatment paradigm in oncology. The question of durability of response with allogenic therapies is still an unknown. Fate Therapeutics’ recent phase 1 data for FT516 showed relatively quicker relapses vs already approved autologous CAR-Ts. However, other manufacturers, like Allogene for their allogenic CAR-T therapy ALLO-501A, are exploring novel lymphodepletion approaches to improve persistence of allogenic cells. Nevertheless, allogenic NKs demonstrate a strong value proposition relative to their T cell counterparts due to comparable response rates (so far) combined with the added advantage of a significantly safer AE profile. Specifically, little to no risk of graft versus host disease (GvHD), cytotoxic release syndrome (CRS), and neurotoxicity (NT) have been seen so far with allogenic NK cells (Fig. 1). In addition, being able to harness an allogenic cell source gives way to operational advantages as “off-the-shelf” products provide improved turnaround time (TAT), scalability, and potentially reduced cost. NKs are currently in development for a variety of overlapping hematological indications with chimeric antigen receptor T cells (CAR-Ts) today, and the question remains to what extent they will disrupt the current cell therapy landscape. Click for more details.

Susan Galbraith, AstraZeneca EVP, Oncology R&D

Can­cer pow­er­house As­traZeneca rolls the dice on a $75M cash bet on a buzzy up­start in the on­col­o­gy field

After establishing itself in the front ranks of cancer drug developers and marketers, AstraZeneca is putting its scientific shoulder — and a significant amount of cash — behind the wheel of a brash new upstart in the biotech world.

The pharma giant trumpeted news this morning that it is handing over $75 million upfront to ally itself with Scorpion Therapeutics, one of those biotechs that was newly birthed by some top scientific, venture and executive talent and bequeathed with a fortune by way of a bankroll to advance an only hazily explained drug platform. And they are still very much in the discovery and preclinical phase.

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Lat­est news on Pfiz­er's $3B+ JAK1 win; Pacts over M&A at #JPM22; 2021 by the num­bers; Bio­gen's Aduhelm reck­on­ing; The sto­ry of sotro­vimab; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

For those of you who attended #JPM22 in any shape or form, we hope you had a fruitful time. Regardless of how you spent the past hectic week, may your weekend be just what you need it to be.

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A $3B+ peak sales win? Pfiz­er thinks so, as FDA of­fers a tardy green light to its JAK1 drug abroc­i­tinib

Back in the fall of 2020, newly crowned Pfizer chief Albert Bourla confidently put their JAK1 inhibitor abrocitinib at the top of the list of blockbuster drugs in the late-stage pipeline with a $3 billion-plus peak sales estimate.

Since then it’s been subjected to serious criticism for the safety warnings associated with the class, held back by a cautious FDA and questioned when researchers rolled out a top-line boast that their heavyweight contender had beaten the champ in the field of atopic dermatitis — Dupixent — in a head-to-head study.

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Robert Califf, FDA commissioner nominee (Graeme Sloan/Sipa USA/Sipa via AP Images)

Rob Califf ad­vances as Biden's FDA nom­i­nee, with a close com­mit­tee vote

Rob Califf’s second confirmation process as FDA commissioner is already much more difficult than his near unanimous confirmation under the Obama administration.

The Senate Health Committee on Thursday voted 13-8 in favor of advancing Califf’s nomination to a full Senate vote. Several Democrats voted against Califf, including Sen. Bernie Sanders and Sen. Maggie Hassan. Several other Democrats who aren’t on the committee, like West Virginia’s Joe Manchin and Ed Markey of Massachusetts, also said Thursday that they would not vote for Califf. Markey, Hassan and Manchin all previously expressed reservations about the prospect of Janet Woodcock as an FDA commissioner nominee too.

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Michel Vounatsos, Biogen CEO (World Economic Forum/Ciaran McCrickard)

Bio­gen vows to fight CM­S' draft cov­er­age de­ci­sion for Aduhelm be­fore April fi­nal­iza­tion

Biogen executives made clear in an investor call Thursday they are not preparing to run a new CMS-approved clinical trial for their controversial Alzheimer’s drug anytime soon.

As requested in a draft national coverage decision from CMS earlier this week, Biogen and other anti-amyloid drugs will need to show “a meaningful improvement in health outcomes” for Alzheimer’s patients in a randomized, placebo-controlled trial to get paid for their drugs, rather than just the reduction in amyloid plaques that won Aduhelm its accelerated approval in June.

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CRO own­er pleads guilty to ob­struct­ing FDA in­ves­ti­ga­tion in­to fal­si­fied clin­i­cal tri­al da­ta

The co-owner of a Florida-based clinical research site pleaded guilty to lying to an FDA investigator during a 2017 inspection, revealing that she falsely portrayed part of a GlaxoSmithKline pediatric asthma study as legitimate, when in fact she knew that certain data had been falsified, the Department of Justice said Wednesday.

Three other employees — Yvelice Villaman Bencosme, Lisett Raventos and Maytee Lledo — previously pleaded guilty and were sentenced in connection with falsifying data associated with the trial at the CRO Unlimited Medical Research.

‘Skin­ny la­bels’ on gener­ics can save pa­tients mon­ey, re­search shows, but re­cent court de­ci­sions cloud fu­ture

New research shows how generic drug companies can successfully market a limited number of approved indications for a brand name drug, prior to coming to market for all of the indications. But several recent court decisions have created a layer of uncertainty around these so-called “skinny” labels.

While courts have generally allowed generic manufacturers to use their statutorily permitted skinny-label approvals, last summer, a federal circuit court found that Teva Pharmaceuticals was liable for inducing prescribers and patients to infringe GlaxoSmithKline’s patents through advertising and marketing practices that suggested Teva’s generic, with its skinny label, could be employed for the patented uses.

A patient in Alaska receiving an antibody infusion to prevent Covid hospitalizations in September. All but one of these treatments has been rendered useless by Omicron (Rick Bowmer/AP Images)

How a tiny Swiss lab and two old blood sam­ples cre­at­ed one of the on­ly ef­fec­tive drugs against Omi­cron (and why we have so lit­tle of it)

Exactly a decade before a novel coronavirus broke out in Wuhan, Davide Corti — a newly-minted immunologist with frameless glasses and a quick laugh — walked into a cramped lab on the top floor of an office building two hours outside Zurich. He had only enough money for two technicians and the ceiling was so low in parts that short stature was a job requirement, but Corti believed it’d be enough to test an idea he thought could change medicine.

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