Ve­rastem wins break­through nod for com­bo ther­a­py in ovar­i­an can­cer; EMA picks up speedy re­view of Bio­Mar­in's gene ther­a­py

Ve­rastem has earned the FDA’s break­through ther­a­py des­ig­na­tion for its nov­el RAF/MEK in­hibitor VS-6766 as a com­bo ther­a­py with in-house FAK in­hibitor de­fac­tinib to treat sec­ond-line, re­cur­rent low-grade serous ovar­i­an can­cer re­gard­less of KRAS mu­tant sta­tus, the com­pa­ny said Mon­day.

The com­bi­na­tion is be­ing test­ed in the in­ves­ti­ga­tor-ini­ti­at­ed Phase I/II FRAME tri­al, where ear­ly re­sults showed an ORR of 52% with KRAS mu­tant ORR at 70%, KRAS wild-type ORR at 44%, and KRAS sta­tus un­de­ter­mined ORR at 0%. The most com­mon side ef­fects seen in the study were rash, cre­a­tine ki­nase el­e­va­tion, nau­sea, hy­per­biliru­bine­mia and di­ar­rhea.

Ve­rastem’s drug takes a nov­el dual-tar­get ap­proach to the RAS path­way, which is im­pli­cat­ed in can­cer re­cur­rence with about 30% of all can­cer tu­mors ex­press­ing mu­tant RAS.

Ve­rastem is al­so test­ing the VS-6766 alone and com­bi­na­tion with de­fac­tinib as part of the phase II reg­is­tra­tion RAMP 201 study. — Kyle Blanken­ship

EMA grants Bio­Marin’s re­quest for a speedy re­view of gene ther­a­py

The Eu­ro­pean Med­i­cines Agency will speed­i­ly re­view Bio­Marin’s val­oc­toco­gene rox­a­parvovec, a gene ther­a­py to treat se­vere he­mo­phil­ia A, with an opin­ion ex­pect­ed in the first half of next year, the com­pa­ny said.

With the EMA agree­ing to give the ther­a­py a clos­er look, Bio­Marin said it plans to sub­mit an as­so­ci­at­ed mar­ket­ing ap­pli­ca­tion by June, based on piv­otal Phase III da­ta that in­cludes one-year fol­low-up re­sults as well as four and three years of fol­low-up from an on­go­ing Phase I/II dose es­ca­la­tion study.

Mean­while, Bio­Marin al­so ex­pects to sub­mit two-year fol­low-up safe­ty and ef­fi­ca­cy da­ta from that Phase III test to the FDA, with a po­ten­tial re­sub­mis­sion of its ap­pli­ca­tion sched­uled for Q2 2022.

The FDA shot down Bio­Marin’s ap­pli­ca­tion for the ther­a­py back in Au­gust, cit­ing the need to see that two-year fol­low-up da­ta. — Kyle Blanken­ship

Francesco De Ru­ber­tis’ lega­cy play Centes­sa sets terms for $285M IPO

Ahead of an ex­pect­ed IPO lat­er this week, Centes­sa is set­ting terms for what it hopes is a mas­sive raise.

The com­pa­ny ex­pects to see $285 mil­lion come in with the raise, of­fer­ing 15 mil­lion shares at a price range of $18 to $20. At the mid­point of that range, Centes­sa would have a mar­ket val­ue of about $1.8 bil­lion, ac­cord­ing to Re­nais­sance Cap­i­tal.

Centes­sa comes from the mind of Francesco De Ru­ber­tis, mak­ing a lega­cy play for a 10-in-1 hold­ing com­pa­ny. His vi­sion re­volves around tak­ing the as­set-cen­tric mind­set that he’s been preach­ing at Medicxi over the years and rolling up a bunch of biotech up­starts in­to one out­fit.

They’ll be go­ing for­ward with­out Mon­cef Slaoui, the for­mer GSK ex­ec and Op­er­a­tion Warp Speed chief fol­low­ing a “sub­stan­ti­at­ed” sex­u­al ha­rass­ment case for which he sub­se­quent­ly apol­o­gized. — Max Gel­man

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.

Graphic: Kathy Wong for Endpoints News

What kind of biotech start­up wins a $3B syn­di­cate, woos a gallery of mar­quee sci­en­tists and re­cruits GSK's Hal Bar­ron as CEO in a stun­ner? Let Rick Klaus­ner ex­plain

It started with a question about a lifetime’s dream on a walk with tech investor Yuri Milner.

At the beginning of the great pandemic, former NCI chief and inveterate biotech entrepreneur Rick Klausner and the Facebook billionaire would traipse Los Altos Hills in Silicon Valley Saturday mornings and talk about ideas.

Milner’s question on one of those mornings on foot: “What do you want to do?”

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FDA+ roundup: FDA's neu­ro­science deputy de­parts amid on­go­ing Aduhelm in­ves­ti­ga­tions; Califf on the ropes?

Amid increased scrutiny into the close ties between FDA and Biogen prior to the controversial accelerated approval of Aduhelm, the deputy director of the FDA’s office of neuroscience has called it quits after more than two decades at the agency.

Eric Bastings will now take over as VP of development strategy at Ionis Pharmaceuticals, the company said Wednesday, where he will provide senior clinical and regulatory leadership in support of Ionis’ pipeline.

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Sec­ondary patents prove to be key in biosim­i­lar block­ing strate­gies, re­searchers find

While the US biosimilars industry has generally been a disappointment since its inception, with FDA approving 33 biosimilars since 2015, just a fraction of those have immediately followed their approvals with launches. And more than a handful of biosimilars for two of the biggest blockbusters of all time — AbbVie’s Humira and Amgen’s Enbrel — remain approved by FDA but still have not launched because of legal settlements.

Hal Barron (GSK via YouTube)

GSK R&D chief Hal Bar­ron jumps ship to run a $3B biotech start­up, Tony Wood tapped to re­place him

In a stunning switch, GlaxoSmithKline put out word early Wednesday that R&D chief Hal Barron is exiting the company after 4 years — a relatively brief run for the man chosen by CEO Emma Walmsley in late 2017 to turn around the slow-footed pharma giant.

Barron is being replaced by Tony Wood, a close associate of Barron’s who’s taking one of the top jobs in Big Pharma R&D. He’ll be closer to home, though, for GSK. Barron has been running a UK and Philadelphia-based research organization from his perch in San Francisco.

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Chamath Palihapitiya and Pablo Legorreta

Bil­lion­aires Chamath Pal­i­hapi­tiya and Pablo Legor­re­ta hatch an $825M SPAC for cell ther­a­py biotech

Three years after Royalty Pharma chief Pablo Legorreta led a group of investors to buy up a pair of biotechs and create a new startup called ProKidney, the biotech is jumping straight into an $825 million public shell created by SPAC king and tech billionaire Chamath Palihapitiya.

ProKidney was founded 6 years ago but really got going at the beginning of 2019 with the $62 million acquisition of inRegen, which was working on an autologous — from the patient — cell therapy for kidney disease. After extracting kidney cells from patients, researchers expand the cells in the lab and then inject them back into patients, aiming to restore the kidneys of patients suffering from CKD.

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CBO: Medicare ne­go­ti­a­tions will ham­per drug de­vel­op­ment more than pre­vi­ous­ly thought

As President Biden’s Build Back Better Act — and, with it, potentially the Democrats’ last shot at major drug pricing reforms in the foreseeable future — remains on life support, the Congressional Budget Office isn’t helping their case.

The CBO last week released a new slide deck, outlining an update to its model on how Medicare negotiations might take a bite out of new drugs making it to market. The new model estimates a 10% long-term reduction in the number of new drugs, whereas a previous CBO report from August estimated that 8% fewer new drugs will enter the market over 30 years.

Joshua Brumm, Dyne Therapeutics CEO

FDA or­ders DMD tri­al halt, rais­ing ques­tions about a whole class of promis­ing drugs

Dyne Therapeutics’ stock took a nasty hit this morning after the biotech put out word that the FDA had slapped a clinical hold on their top program for Duchenne muscular dystrophy. And now speculation is bouncing around Biotwitter that there could be a class effect at work here that would implicate other drug developers in the freeze.

Dyne execs didn’t have a whole lot to say about why the FDA sidelined their IND for DYNE-251 in DMD while “requesting additional clinical and non-clinical information for” the drug.

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Chi­nese biotech teams with Lil­ly on car­diometa­bol­ic dis­eases; Sen­ate fi­nance chair goes af­ter BMS

Chinese biotech Abbisko Therapeutics is teaming up with Eli Lilly on a new collaboration.

The pair announced Monday they will partner on cardiometabolic diseases and go after an unnamed target, with Abbisko eligible for up to $258 million in milestones. Abbisko will handle primarily the discovery work with input from Lilly, after which Lilly will have the option to further develop and potentially bring the program to market.