Kamel Khalili, Excision BioTherapeutics

FDA clears first-of-its-kind tri­al to see if CRISPR gene edit­ing can cure HIV

The FDA has cleared a com­pa­ny try­ing to use CRISPR gene-edit­ing to cure HIV to be­gin clin­i­cal tri­als.

Lisa Danzig

The study, run by the start­up Ex­ci­sion Bio­Ther­a­peu­tics, will like­ly be­gin ear­ly next year, CMO Lisa Danzig said, af­ter fi­nal de­tails are hashed out. It will in­volve three groups of three healthy HIV pa­tients, with each group giv­en a se­quen­tial­ly high­er dose as the com­pa­ny tests the safe­ty of the new ther­a­py.

The ther­a­py us­es CRISPR, a tool of­ten com­pared to mol­e­c­u­lar scis­sors, to snip out HIV that has coiled in­to the DNA in a pa­tient’s cells. The virus’ abil­i­ty to snake in­to DNA is one of the fea­tures that has made it so im­per­vi­ous to cu­ra­tive ef­forts, de­spite four decades of re­search, and Ex­ci­sion’s tri­al will mark one of the first ef­forts to di­rect­ly re­move the la­tent virus from DNA.

Ex­ci­sion will de­liv­er CRISPR pack­aged in AAV9, a non-path­o­gen­ic virus com­mon­ly used in gene ther­a­py. At a time when high-dose AAV is com­ing un­der scruti­ny, the com­pa­ny will stick to rel­a­tive­ly low dos­es it found worked well in an­i­mal stud­ies.

The tri­al will ini­tial­ly on­ly test safe­ty and how well the ther­a­py is ex­cis­ing the virus, but even­tu­al­ly, Ex­ci­sion hopes to test it as a cure by tak­ing pa­tients off of the stan­dard pills used to con­trol the virus and see­ing if the in­fec­tion re­turns. Danzig, how­ev­er, de­clined to say when they might take that step.

The tri­al builds off ear­ly re­search from Kamel Khalili, a Tem­ple Uni­ver­si­ty pro­fes­sor who first test­ed the con­cept in cells back in 2014. He was con­fi­dent but cau­tious about their prospects in hu­man tri­als, point­ing to an­i­mal da­ta show­ing CRISPR at­tacked cells across the body.

“This tells us the strat­e­gy has the ca­pac­i­ty to ex­cise the vi­ral DNA,” Khalili said. “The ques­tion is whether or not this reach­es the point of com­plete­ly elim­i­nat­ing the virus.”

Ex­perts are large­ly skep­ti­cal that it can, not­ing how well HIV can hide, ly­ing dor­mant in cells across the body for years. But they agreed that it could one day be a promis­ing part of a cu­ra­tive com­bi­na­tion.

Ex­ci­sion and Tem­ple re­searchers are al­so work­ing on those com­bi­na­tions, ex­per­i­ment­ing with new ap­proach­es to com­bine CRISPR with ther­a­pies that boost the im­mune sys­tem’s abil­i­ty to clear out in­fect­ed cells.

“This clin­i­cal tri­al is a huge step but it’s one step of many steps,” Tri­cia Bur­do, a pro­fes­sor at Tem­ple and ex­pert on mon­key stud­ies who led parts of the pre­clin­i­cal re­search. “What is the next step to com­bine these with oth­er tech­nolo­gies?”

2023 Spot­light on the Fu­ture of Drug De­vel­op­ment for Small and Mid-Sized Biotechs

In the context of today’s global economic environment, there is an increasing need to work smarter, faster and leaner across all facets of the life sciences industry.  This is particularly true for small and mid-sized biotech companies, many of which are facing declining valuations and competing for increasingly limited funding to propel their science forward.  It is important to recognize that within this framework, many of these smaller companies already find themselves resource-challenged to design and manage clinical studies themselves because they don’t have large teams or in-house experts in navigating the various aspects of the drug development journey. This can be particularly challenging for the most complex and difficult to treat diseases where no previous pathway exists and patients are urgently awaiting breakthroughs.

Dipal Doshi, Entrada Therapeutics CEO

Ver­tex just found the next big ‘trans­for­ma­tive’ thing for the pipeline — at a biotech just down the street

Back in the summer of 2019, when I was covering Vertex’s executive chairman Jeff Leiden’s plans for the pipeline, I picked up on a distinct focus on myotonic dystrophy Type I, or DM1 — one of what Leiden called “two diseases (with DMD) we’re interested in and we continue to look for those assets.”

Today, Leiden’s successor at the helm of Vertex, CEO Reshma Kewalramani, is plunking down $250 million in cash to go the extra mile on DM1. The lion’s share of that is for the upfront, with a small reserve for equity in a deal that lines Vertex up with a neighbor in Seaport that has been rather quietly going at both of Vertex’s early disease targets with preclinical assets.

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Rami Elghandour, Arcellx CEO

Up­dat­ed: Gilead, Ar­cel­lx team up on an­ti-BC­MA CAR-T as biotech touts a 100% re­sponse rate at #ASH22

Gilead and Kite are plunking down big cash to get into the anti-BCMA CAR-T game.

The pair will shell out $225 million in cash upfront and $100 million in equity to Arcellx, Kite announced Friday morning, to develop the biotech’s lead CAR-T program together. Kite will handle commercialization and co-development with Arcellx, and profits in the US will be split 50-50.

Concurrent with the deal, Arcellx revealed its latest cut of data for the program known as CART-ddBCMA, ahead of a full presentation at this weekend’s ASH conference — a 100% response rate among patients getting the therapy. Investors jumped at the dual announcements, sending Arcellx shares $ACLX up more than 25% in Friday’s morning session.

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Christian Itin, Autolus CEO (UKBIO19)

Au­to­lus tips its hand, bags $220M as CAR-T show­down with Gilead looms

The first batch of pivotal data on Autolus Therapeutics’ CAR-T is in, and execs are ready to plot a path to market.

With an overall remission rate of 70% at the interim analysis featuring 50 patients, the results set the stage for a BLA filing by the end of 2023, said CEO Christian Itin.

Perhaps more importantly — given that Autolus’ drug, obe-cel, is going after an indication that Gilead’s Tecartus is already approved for — the biotech highlighted “encouraging safety data” in the trial, with a low percentage of patients experiencing severe immune responses.

WIB22: Am­ber Salz­man had few op­tions when her son was di­ag­nosed with a rare ge­net­ic dis­ease. So she cre­at­ed a bet­ter one

This profile is part of Endpoints News’ 2022 special report about Women in Biopharma R&D. You can read the full report here.

Amber Salzman’s life changed on a cold, damp day in Paris over tiny plastic cups of lukewarm tea.

She was meeting with Patrick Aubourg, a French neurologist studying adrenoleukodystrophy, or ALD, a rare genetic condition that causes rapid neurological decline in young boys. It’s a sinister disease that often leads to disability or death within just a few years. Salzman’s nephew was diagnosed at just 6 or 7 years old, and died at the age of 12.

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Ahead of ad­comm, FDA rais­es un­cer­tain­ties on ben­e­fit-risk pro­file of Cy­to­ki­net­ic­s' po­ten­tial heart drug

The FDA’s Cardiovascular and Renal Drugs Advisory Committee will meet next Tuesday to discuss whether Cytokinetics’ potential heart drug can safely reduce the risk of cardiovascular death and heart failure in patients with symptomatic chronic heart failure with reduced ejection fraction.

The drug, known as omecamtiv mecarbil and in development for more than 15 years, has seen mixed results, with a first Phase III readout from November 2020 hitting the primary endpoint of reducing the odds of hospitalization or other urgent care for heart failure by 8%. But it also missed a key secondary endpoint analysts had pegged as key to breaking into the market.

Ab­b­Vie slapped with age dis­crim­i­na­tion law­suit, fol­low­ing oth­er phar­mas

Add AbbVie to the list of pharma companies currently facing age discrimination allegations.

Pennsylvania resident Thomas Hesch filed suit against AbbVie on Wednesday, accusing the company of passing him over for promotions in favor of younger candidates.

Despite 30 years of pharma experience, “Hesch has consistently seen younger, less qualified employees promoted over him,” the complaint states.

WIB22: Lead­ing NK cell re­searcher re­flects on roots in Iran, the UK and Texas

This profile is part of Endpoints News’ 2022 special report about Women in Biopharma R&D. You can read the full report here.

In a small but widely-cited 11-person study published in NEJM in 2020, seven patients saw signs of their cancer completely go away after getting a new therapy made from natural killer cells. The study was one of the earliest to provide clinical proof that the experimental treatment method had promise.

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Philip Astley-Sparke, Replimune CEO

Replimune looks to rope in $225M on the back of melanoma da­ta

The Massachusetts-based, oncolytic virus biotech Replimune is feeling bullish now that it has lifted the cover on data for its lead product.

Replimune said Thursday it looks to nab about $225 million from a public offering after giving a snapshot of some initial data from its IGNYTE clinical study earlier this week. The trial is investigating RP1 in combination with Opdivo, for patients with melanoma and who did not have a response when being treated with a PD-1.