Al­ler­gan/Ed­i­tas fi­nal­ly kick off CRISPR tri­al — mark­ing first in vi­vo test of the gene-edit­ing tech­nol­o­gy

More three years af­ter Al­ler­gan $AGN dipped its toes in­to the world of CRISPR/Cas9 gene edit­ing by en­list­ing Ed­i­tas $ED­IT as a part­ner — the com­pa­nies are now off to the races with a tri­al in pa­tients with a rare eye dis­ease.

This tri­al marks the first in­stance of us­ing the tech­nol­o­gy to ed­it DNA with­in the body.

Mean­while, part­ners Ver­tex $VRTX and CRISPR Ther­a­peu­tics $CR­SP kick­start­ed a tri­al ear­li­er this year that em­ployed the tech­nol­o­gy to en­gi­neer a gene-edit­ed stem cell ther­a­py to treat pa­tients suf­fer­ing from se­vere he­mo­glo­binopathies, a group of blood dis­or­ders. Sang­amo Ther­a­peu­tics $SG­MO has test­ed its old­er zinc fin­ger tech­nol­o­gy in pa­tients with two lyso­so­mal stor­age dis­eases, but a set­back dif­fused en­thu­si­asm for the pro­gram — but the com­pa­ny bounced back with en­cour­ag­ing ear­ly da­ta on its he­mo­phil­ia pro­gram part­nered with Pfiz­er.

Al­ler­gan and Ed­i­tas had orig­i­nal­ly ex­pect­ed to file an ap­pli­ca­tion to test their ther­a­py in hu­mans by the end of 2017, but man­u­fac­tur­ing trou­ble pushed that time­line to Oc­to­ber 2018. To get the FDA en­dorse­ment, Ed­i­tas fought off a stiff patent chal­lenge — and like its peers — bat­ted back per­sis­tent ques­tions about off-tar­get ef­fects to ad­e­quate­ly con­vince the reg­u­la­tor it was armed and ready to make the jump from an­i­mal stud­ies to hu­mans.

The tri­al, chris­tened Bril­liance, will eval­u­ate their ex­per­i­men­tal ther­a­py AGN-151587 (ED­IT-101) for the treat­ment of Leber con­gen­i­tal amau­ro­sis 10 (LCA10), a rare, in­her­it­ed form of blind­ness caused by mu­ta­tions in the CEP290 gene.

LCA is a group of in­her­it­ed reti­nal de­gen­er­a­tive dis­or­ders caused by mu­ta­tions in at least 18 dif­fer­ent genes, and are con­sid­ered the most com­mon cause of in­her­it­ed child­hood blind­ness, oc­cur­ring in two to three per 100,000 live births glob­al­ly. The most com­mon form of the dis­ease, LCA10, ac­counts for ap­prox­i­mate­ly 20% to 30% of all LCA pa­tients.

Ka­trine Bosley Ed­i­tas

Spark Ther­a­peu­tics’ ap­proved gene ther­a­py Lux­tur­na, which de­liv­ered via a vi­ral vec­tor, is tai­lored to treat an­oth­er rare eye dis­ease due to mu­ta­tions in both copies of the RPE65 gene. The FDA nod sparked Roche’s $4.3 bil­lion takeover of the com­pa­ny, al­though the deal is yet to be con­sum­mat­ed.

The Bril­liance study is set to en­roll 18 pa­tients — and in­clude up to five co­horts and eval­u­ate three dos­es of the drug. Each pa­tient will re­ceive a sin­gle dose of AGN-151587 ad­min­is­tered via an eye in­jec­tion aimed at pho­tore­cep­tor cells in the reti­na.

Ed­i­tas’ se­nior team has seen up­heaval in the past year. In Jan­u­ary, CEO Ka­trine Bosley, who led the com­pa­ny for near­ly five years, an­nounced her ex­it and sev­ered ties with the board, with­out ex­pla­na­tion. Chief fi­nan­cial of­fi­cer An­drew Hack an­nounced his de­ci­sion to leave by March, back in De­cem­ber 2018, and chief med­ical of­fi­cer Ger­ald Cox jumped ship at the end of last year.

Be­set by set­backs, Al­ler­gan’s Brent Saun­ders made the best of a bad sit­u­a­tion by agree­ing to be swal­lowed by Ab­b­Vie $AB­BV in an eye-wa­ter­ing $63 bil­lion deal ear­li­er this year. The US drug­mak­er was swayed by the po­ten­tial of Al­ler­gan’s block­buster Botox fran­chise to sta­bi­lize its rev­enue as its $20 bil­lion cash cow Hu­mi­ra hur­tles to­wards a patent cliff in the Unit­ed States.

So­cial im­age: Shut­ter­stock

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

An un­ortho­dox pro­pos­al for Bio­gen's Medicare-man­dat­ed Aduhelm tri­al

Biogen has gone full blitz since Medicare announced it would only cover its new Alzheimer’s drug when used in clinical trials, accusing the agency of discriminating against Alzheimer’s patients and trying to get physicians to change regulators’ minds.  Critics, meanwhile, cheered what they see as a necessary wall protecting payers and patients from an unproven and unsafe drug.

Far less attention, though, has gone to what a Medicare-funded clinical trial would actually look like. Biogen has operated as if it would be a standard late-stage Alzheimer’s trial, enrolling a couple thousand patients and giving half placebo.

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