Four years af­ter it im­plod­ed at Sanofi, John Hood is res­ur­rect­ing the myelofi­bro­sis drug fe­dra­tinib

Fe­dra­tinib was one of the biggest clin­i­cal drug dis­as­ters that oc­curred at Sanofi un­der the tu­mul­tuous reign of CEO Chris Viehbach­er. But af­ter im­plod­ing with spec­tac­u­lar ef­fect right at the thresh­old of a new drug ap­pli­ca­tion four years ago, one of the drug’s co-in­ven­tors — a sci­en­tist named John Hood — has pa­tient­ly picked up all the shat­tered pieces and put it to­geth­er in­to a new com­pa­ny that just scored a $22.5 mil­lion ven­ture round.

Now Hood’s lit­tle biotech is go­ing af­ter that FDA/EMA ap­proval that elud­ed the phar­ma gi­ant.

If he’s right, Hood has scored one of the biggest biotech coups of the year. But let’s start this sto­ry with a lit­tle back­ground.

Sev­en years ago, Sanofi scooped up a biotech called Targe­Gen in a $635 mil­lion deal, bag­ging a mid-stage JAK2 myelofi­bro­sis drug — then dubbed TG 101348 — that had gath­ered promis­ing ear­ly-stage hu­man da­ta. Hood, the for­mer re­search chief at Targe­Gen and a co-in­ven­tor of the drug, moved on to co-found a biotech uni­corn com­pa­ny called Sa­mumed, fo­cused on re­gen­er­a­tive med­i­cine with Hood tak­ing the CSO job.

In 2013, the FDA dropped a clin­i­cal hold on fe­dra­tinib af­ter a few pa­tients be­gan to de­vel­op Wer­nicke’s en­cephalopa­thy — a dan­ger­ous neu­ro­log­i­cal con­di­tion tied to vi­t­a­min B de­fi­cien­cy. And Sanofi’s top team quick­ly put a bul­let in it, scrap­ping a pro­gram that in­clud­ed sev­en on­go­ing clin­i­cal tri­als. The phar­ma gi­ant shoved the mor­tal­ly wound­ed pro­gram on the shelf, and that’s where it sat un­til ear­ly 2016, when Hood de­cid­ed to start his own com­pa­ny, get the rights back and pur­sue transat­lantic ap­provals.

To hear Hood tell it, af­ter the clin­i­cal tri­als end­ed, the pa­tients in­volved were shift­ed to stan­dard of care and be­gan to re­lapse.

“That’s when physi­cians and pa­tients be­gan to reach out to me,” Hood says, look­ing for some way to get the drug un­der com­pas­sion­ate use rules. That in­spired him to go for it.

I hap­pened to pick up word of what was hap­pen­ing at the time, and Hood and I start­ed ex­chang­ing oc­ca­sion­al mes­sages around his progress. Wait for it, he would write, it was grad­u­al­ly com­ing to­geth­er.

Sanofi gave up the drug for eq­ui­ty in Hood’s com­pa­ny, Im­pact Bio­med­i­cines in San Diego, which now has a lean-and-mean team of six. The pack­age in­cludes pos­i­tive Phase III re­sults (with a p-val­ue of 0.0001 says a proud Hood) da­ta from 877 pa­tients in 18 stud­ies.

“There was no out-of-pock­et,” Hood tells me. Sanofi took an eq­ui­ty stake in the biotech for its share.

The FDA came through in Au­gust, drop­ping the clin­i­cal hold af­ter Hood made the case that the side ef­fects that so alarmed in­ves­ti­ga­tors and reg­u­la­tors in 2013 could be at­trib­uted to a small num­ber of cas­es of thi­amine de­ple­tion linked to the high meta­bol­ic rate of can­cer pa­tients and mal­nour­ish­ment.

Says Hood: “It was easy enough to mit­i­gate.”

Kevin John­son

Hood’s backed by a globe-trot­ting team at Medicxi, where Kevin John­son — a buoy­ant Cam­bridge grad and sci­en­tist who had been head of re­search at the leg­endary Cam­bridge An­ti­body Tech­nol­o­gy — put to­geth­er the fi­nanc­ing round to fund what comes next.

That next part still has to be worked out, the CEO tells me. I sug­gest­ed that if any­thing, reg­u­la­tors have em­braced speed­ed up de­vel­op­ment pro­grams in on­col­o­gy, which could put him right back at the FDA’s door, knock­ing for mar­ket en­try.

Af­ter spend­ing more than 18 months putting this all to­geth­er, though, Hood is still tak­ing it one step at a time. He’ll know more about how fast he can move af­ter meet­ing with reg­u­la­tors to test their ap­petite for speed.

I asked John­son what his first thoughts were when he and Hood talked it over.

My ini­tial re­ac­tion to the sto­ry was that I couldn’t grasp the thought process that led to it be­ing put on clin­i­cal hold and there­fore not reach­ing the mar­ket. We pieced that all to­geth­er at a lat­er stage, and while it looks like a strange de­ci­sion in ret­ro­spect, at the time, with those spe­cif­ic mar­ket con­di­tions, it would have been a brave de­ci­sion to keep go­ing. Of course it’s all dif­fer­ent now.
On John him­self, he re­al­ly does think like that and I love it! It’s my ex­pe­ri­ence that the top biotech and phar­ma en­tre­pre­neurs are dri­ven by a need to do good, rather than just make mon­ey. In the end I guess it’s a be­lief sys­tem- do the right things for the right rea­sons and the mon­ey will fol­low as a con­se­quence. It does tend to work out that way. He’s al­so what I call a hand­shake guy; you shake hands on some­thing and that’s it. He could have played us but he didn’t. That too is con­sis­tent with his phe­no­type.

In most cas­es like this, Hood and his tiny band of staffers would be set­ting him­self up to do a deal on the drug. But Hood isn’t jump­ing that far ahead ei­ther. Right now, he says, he’s work­ing on the kind of fi­nan­cial pack­age that would “al­low us to take it the whole way.”

That may sound a bit far-fetched, but the whole sto­ry up to this point was im­prob­a­ble.

Hood’s just get­ting start­ed again.

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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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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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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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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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.

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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Martin Shkreli (Photo by Drew Angerer/Getty Images)

Mar­tin Shkre­li re­ceives life­time in­dus­try ban, forced to re­turn al­most $65M in prof­its af­ter an­ti­com­pet­i­tive scheme

Martin Shkreli will have to find a new nickname.

A federal judge banned the former biotech CEO and “Pharma Bro” from the drug industry on Friday, ordering him to pay nearly $65 million in illicit profits. Shkreli was convicted of securities fraud in 2017 and is currently serving a seven-year prison sentence, though he originally gained notoriety for raising the price of the antiparasitic drug Daraprim from $13.50 to $750 in 2015.