Haul­ing in a $100M mega-round, gene ther­a­py start­up Gen­er­a­tion Bio builds al­ter­na­tive to po­ten­tial­ly risky vi­ral vec­tors

A gene ther­a­py com­pa­ny head­ed up by big­wigs and backed ear­ly on by At­las has pulled in a mega-round of $100 mil­lion. The 2-year-old start­up cap­tured in­vestors’ at­ten­tion by sug­gest­ing it knows a bet­ter way to do gene trans­fer than the po­ten­tial­ly tox­ic vi­ral vec­tor strate­gies of late.

Gen­er­a­tion Bio is the Boston/Cam­bridge up­start, and it’s a com­pa­ny that’s strayed from the pack when it comes to the how of gene ther­a­py. While its ri­vals in the field are buck­ling down on vi­ral ve­hi­cles like ade­no as­so­ci­at­ed virus­es (AAV), Gen­er­a­tion Bio is tak­ing a dif­fer­ent route.

Robert Kotin

Found­ed in part by ex-NIH, ex-Voy­ager ex­ec­u­tive Robert Kotin, whom you may know as one of the world’s top ex­perts on vi­ral trans­port, the new com­pa­ny cen­ters on a tech they’re call­ing close-end­ed DNA (ceD­NA). This can move from the cy­to­plasm of the cell to the nu­cle­us with­out an AAV car­ry­ing it along. Once in­side the nu­cle­us, it can cre­ate high lev­els of gene ex­pres­sion ca­pa­ble of ad­dress­ing a broad range of ge­net­ic dis­eases.

Gen­er­a­tion Bio says the hope is that this tech can ad­dress the emerg­ing con­cern re­volv­ing around vi­ral vec­tors. Well-known gene ther­a­py com­pa­nies like Spark and Sol­id Bio­sciences are us­ing AAVs as vec­tors, a method that, when used in high dos­es, has re­cent­ly been called in­to ques­tion by a pi­o­neer in the field, Penn pro­fes­sor James Wil­son.

Wil­son sur­prised the gene ther­a­py com­mu­ni­ty in Jan­u­ary when he quit the ad­vi­sor board of Sol­id and raised alarms about the po­ten­tial tox­i­c­i­ty of high-dose AAV stud­ies.

Gen­er­a­tion Bio is cap­i­tal­iz­ing on the un­cer­tain­ty cloud­ing the lead­ing tech in the field by por­tray­ing their ther­a­pies as po­ten­tial­ly safer.

Last month, the com­pa­ny’s CEO Ge­off Mc­Do­nough told End­points the com­pa­ny would start by us­ing a lipid nanopar­ti­cle to de­liv­er ceD­NA to the liv­er, where it will make sys­temic pro­teins to fight dis­eases.

“These ther­a­pies are de­signed to over­come the im­muno­genic­i­ty as­so­ci­at­ed with vi­ral-vec­tor gene ther­a­pies, which has his­tor­i­cal­ly lim­it­ed the num­ber of pa­tients that can be treat­ed and pre­vent­ed re-dos­ing,” Gen­er­a­tion Bio stat­ed in a press re­lease. “Since its found­ing in 2016, Gen­er­a­tion Bio has demon­strat­ed durable, dose-de­pen­dent ex­pres­sion and the abil­i­ty to in­crease ex­pres­sion in the liv­er with re-dos­ing in vi­vo with the Ge­neWave plat­form.”

In­vestors ap­pear to be in­trigued. The $100 mil­lion fi­nanc­ing was a Se­ries B led by Fi­deli­ty Man­age­ment & Re­search Com­pa­ny, with par­tic­i­pa­tion from In­vus, Deer­field Man­age­ment Com­pa­ny, Cas­din Cap­i­tal, Fore­site Cap­i­tal, and Leerink Part­ners’ Af­fil­i­ates.

This round comes less than two months af­ter Gen­er­a­tion Bio an­nounced its $25 mil­lion Se­ries A backed by At­las.

The new mon­ey will be used to take two ther­a­peu­tic can­di­dates through IND-en­abling stud­ies.

“This will be a crit­i­cal­ly im­por­tant year for us as we de­vel­op the Ge­neWave plat­form and work to­wards our first de­vel­op­ment can­di­dates to ad­dress rare dis­eases of the liv­er,” Mc­Do­nough said in a state­ment. “The round will al­so sup­port the de­vel­op­ment of ap­proach­es to de­liv­er ceD­NA to oth­er tis­sues such as the eye, the cen­tral ner­vous sys­tem and the lungs.”

Im­age: Gen­er­a­tion Bio’s pres­i­dent and CEO Ge­off Mc­Do­nough. Gen­er­a­tion Bio

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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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.

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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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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Jason Foster, Ori Biotech CEO

UK up­start rais­es $100M in bid to dig­i­tize and stan­dard­ize cell and gene ther­a­py man­u­fac­tur­ing

There’s a giant need for cell and gene therapy manufacturing options going forward, as companies move to invest massively into that space. Ori Biotech is the latest, as the UK-based biotech announced it has secured more than $100 million in its oversubscribed Series B funding round Tuesday.

Novalis LifeSciences led the round. The Boston-based company is led by chairman Marijn Dekkers and partner Paul Meister, who built Thermo Fisher Scientific. Dekkers went on to become the CEO of Bayer, and is currently also the chairman at Ginkgo Bioworks.