No­var­tis co-opts Ho­mol­o­gy's gene-edit­ing tech for R&D pipeline

In the lat­est move to build up No­var­tis’ eye drug pipeline, the phar­ma gi­ant is sink­ing fresh cap­i­tal in­to a gene edit­ing com­pa­ny to work on se­cret tar­gets in oph­thal­mol­o­gy.

Fi­nan­cial de­tails weren’t dis­closed, but we do know that No­var­tis made an up­front pay­ment and an eq­ui­ty in­vest­ment in the start­up Ho­mol­o­gy Med­i­cines. The deal gets No­var­tis ac­cess to Ho­mol­o­gy’s gene edit­ing plat­form, which both com­pa­nies hope will lead to new drug tar­gets.

As part of the deal, No­var­tis will pay for fur­ther de­vel­op­ment of the plat­form, ad­vanc­ing new pro­grams and leav­ing the R&D deal some­what open-end­ed to ex­plore oth­er dis­ease ar­eas with the tech.

Arthur Tzian­a­bos

Ho­mol­o­gy’s gene edit­ing tech dif­fers from CRISPR, which us­es an en­zyme from bac­te­ria that “chops” DNA to dis­rupt a dam­aged gene. Ho­mol­o­gy’s CEO Arthur Tzian­a­bos said the CRISPR ap­proach can be prob­lem­at­ic when adding whole genes.

In­stead, Ho­mol­o­gy is em­ploy­ing vi­ral vec­tors to en­cour­age what’s called “ho­mol­o­gous re­com­bi­na­tion” — the body’s nat­ur­al re­sponse to “cor­rect­ing” genes that have been dam­aged. In short, the com­pa­ny pack­ages a sin­gle strand of syn­thet­ic DNA in­side a non-in­fec­tious virus, which then car­ries the DNA to the body’s cells.

“The DNA is de­signed to be a per­fect mir­ror im­age of the DNA you want to take out,” Tzian­a­bos said. Pair­ing the cor­rect­ed DNA with its dam­aged twin in­side the cell is what pro­motes ho­mol­o­gous re­com­bi­na­tion, or the swap­ping of nu­cleotide se­quences be­tween two sim­i­lar strands of DNA.

In the­o­ry, the healthy strand would swap or in­sert cor­rect se­quences where need­ed in pa­tients with mu­tat­ed or dam­aged genes. Out with the bad, dam­aged chunk of DNA, in with the new, cor­rect one.

The idea isn’t new. Log­icBio, based in Fos­ter City, is do­ing some­thing sim­i­lar but with a dif­fer­ent virus. Tzian­a­bos said it’s Ho­mol­o­gy’s ade­no-as­so­ci­at­ed virus (AAV) that’s unique, and it al­lows them to cor­rect “a lot more cells” than Log­icBio can.

No­var­tis par­tic­i­pat­ed in Ho­mol­o­gy’s $83.5 mil­lion Se­ries B round this Au­gust, and is now deep­en­ing its ties with the com­pa­ny with this new R&D agree­ment.

As part of the new deal with No­var­tis, Ho­mol­o­gy will be ex­plor­ing undis­closed tar­gets in oph­thal­mol­o­gy (a key re­search area for No­var­tis), as well as tar­gets in ge­net­ic blood dis­or­ders. No­var­tis has world­wide rights to Ho­mol­o­gy’s plat­form for se­lect oph­thalmic tar­gets and an undis­closed he­mo­glo­binopa­thy dis­ease. Ho­mol­o­gy gets to re­tain US com­mer­cial rights (and a share of US prof­its) for in vi­vo ap­pli­ca­tions re­lat­ed to the he­mo­glo­binopa­thy pro­gram.

The col­lab­o­ra­tion makes sense for No­var­tis, as the com­pa­ny has a strong in­ter­est in oph­thal­mol­o­gy. Its block­buster Eylea ri­val RTH258 has been tout­ed as a $1-bil­lion-plus drug for wet age-re­lat­ed mac­u­lar de­gen­er­a­tion. No­var­tis plans to seek FDA ap­proval for the drug by the end of next year.

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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