Siddhartha Mukherjee, AP Images

Sid Mukher­jee's Vor taps a CAR-T de­vel­op­ment part­ner to strap to its at­tempt at bet­ter stem cell trans­plants

In the buzzy world of on­col­o­gy, few names shine brighter than Co­lum­bia on­col­o­gist and best­selling au­thor Sid­dhartha Mukher­jee, whose Vor Bio­phar­ma is look­ing to rewrite the rules of stem cell trans­plants. If his team’s tech works as planned, it would al­so rewrite the rules on how CAR-Ts can be de­ployed in blood can­cer — and now it’s part­ner­ing up with a lit­tle-known biotech to test that hy­poth­e­sis.

Robert Ang

Vor has inked a mul­ti-year dis­cov­ery deal with Abound Bio to ac­cess its plat­form of sin­gle- and mul­ti-tar­get CAR-Ts to com­bine with Vor’s pipeline of en­gi­neered blood stem cells, the part­ners said Thurs­day.

The biotechs will ini­tial­ly tar­get acute myeloid leukemia and think that a mul­ti-tar­get­ed CAR-T paired with an HSC trans­plant could be a path to bet­ter treat­ing hard-to-hit blood can­cer. The Pitts­burgh-based on­col­o­gy play­er has shown pre­clin­i­cal da­ta for a CD19/20-tar­get­ed CAR that caught Vor’s in­ter­est, CEO Robert Ang told End­points News.

Fi­nan­cial terms of the deal were not dis­closed.

The prob­lem with us­ing mul­ti-tar­get­ed CARs for years has been the off-tar­get side ef­fects on healthy blood cells. Vor is work­ing on trans­plant­i­ng stem cells in­to pa­tients’ bone mar­row that re­move or mod­i­fy the tar­get­ed anti­gens, the­o­ret­i­cal­ly al­low­ing a CAR con­struct to bet­ter tar­get tu­mors with­out the dele­te­ri­ous safe­ty risks.

Ang was un­equiv­o­cal when talk­ing about Vor’s aims: The biotech is look­ing to com­plete­ly re­place stan­dard-of-care stem cell trans­plants with its plat­form. While he couldn’t dis­cuss what fu­ture mile­stones look like for the Abound deal, Ang said the de­vel­op­ment phase of that pact would run “in par­al­lel” with Vor’s work on its stem cell plat­form.

“(Abound) is re­al­ly a team that’s al­ready demon­strat­ed sci­en­tif­ic prowess in this are­na, and we think it’s a mar­velous op­por­tu­ni­ty to work with them to­wards tar­gets that we can uti­lize in our own ap­proach,” Ang said.

John Mel­lors

Abound Bio was co-found­ed back in 2019 by Dimiter “Mitko” Dim­itrov, the com­pa­ny’s chief sci­en­tif­ic of­fi­cer and a se­nior in­ves­ti­ga­tor at the Na­tion­al Can­cer In­sti­tute, and CEO John Mel­lors. CAR-T ther­a­py re­searcher Ri­mas Orentas serves as the biotech’s VP for cel­lu­lar ther­a­py. On top of its nov­el CD19/20 bis­pe­cif­ic CAR-T, the team re­cent­ly post­ed pre­clin­i­cal da­ta on a trispe­cif­ic CAR con­struct that could show promise far down the road.

Vor, mean­while, is the brain­child of Mukher­jee, who found­ed the com­pa­ny back in 2016 and even­tu­al­ly took it pub­lic in Feb­ru­ary. The com­pa­ny’s lead pro­gram is VOR33, an HSC the biotech is study­ing so­lo and as a pair­ing with CD33 tar­get­ing CAR-T can­di­date VCAR33, which it in-li­censed from the NIH, in IND en­abling stud­ies in AML.

Ang was quick to point out the Abound deal wasn’t to be viewed as an in­ter­rup­tion or re­place­ment for the VOR33/VCAR33 pro­gram, where ini­tial da­ta is ex­pect­ed lat­er in the year to ear­ly next year.

“We’ve worked re­al­ly hard on one tar­get, and that’s CD33 … but to take this to an­oth­er lev­el to look at tar­gets out­side of CD33 and to look at tar­get­ing mul­ti­ple epi­topes … we think that is a re­al­ly at­trac­tive ap­proach,” Ang said.

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.

What lured Hal Bar­ron away?; Top FDA minds on ac­cel­er­at­ed ap­proval re­forms; ‘Dead wrong’ Aduhelm ad blitz; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

Nothing can really compete with Hal Barron’s departure from GlaxoSmithKline as the news of the week, but we do have plenty of original reporting and analysis from the Endpoints team in this edition. Enjoy and have a nice weekend.

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Hal Barron, Endpoints UKBIO20 (Jeff Rumans)

'Al­tos was re­al­ly a once-in-a-life­time op­por­tu­ni­ty': Hal Bar­ron re­flects on his big move

By all accounts, Hal Barron had one of the best jobs in Big Pharma R&D. He made more than $11 million in 2020, once again reaping more than his boss, Emma Walmsley, who always championed him at every opportunity. And he oversaw a global R&D effort that struck a variety of big-dollar deals for oncology, neurodegeneration and more.

Sure, the critics never let up about what they saw as a rather uninspiring late-stage pipeline, where the rubber hits the road in the Big Pharma world’s hunt for the next big near-term blockbuster, but the in-house reviews were stellar. And Barron was firmly focused on bringing up the success rate in clinical trials, holding out for the big rewards of moving the dial from an average 10% success rate to 20%.

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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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Mer­ck wins le­gal bat­tle over in­sur­ance cov­er­age af­ter ran­somware at­tack

Merck has emerged victorious from a years-long legal battle with insurers over the coverage of more than a billion dollars in losses from the malware NotPetya, with a New Jersey Superior Court judge concluding that the responsibility is on insurers to clarify their policies around cyber attacks.

The pharma giant was one of several victims of a global cyber attack back in 2017 that also hit Danish shipping company Maersk, American food company Mondelēz, French construction giant Saint-Gobain and even the systems monitoring the Chernobyl nuclear power stations, Bloomberg reported back in 2019.

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Crit­ics push back on Alzheimer’s As­so­ci­a­tion ad blitz to get Medicare to change its Aduhelm rul­ing: 'Dead wrong'

The latest Alzheimer’s Association advertising campaign encourages people to fight.

Not against the disease or for more research or treatments, but against the Centers for Medicare and Medicaid Services. More specifically, CMS’ recent reimbursement decision to only pay for Biogen and Eisai’s controversial Alzheimer’s drug Aduhelm for patients in clinical trials.

With CMS’ preliminary decision now in a 30-day comment period, patient advocates’ goal is to convince CMS to reverse its decision with a marketing blitz and public pressure.

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Dan O'Day, Gilead CEO (Jim Watson/AFP via Getty Images)

Fail­ing to con­firm clin­i­cal ben­e­fit, Gilead pulls 2 ac­cel­er­at­ed ap­proval in­di­ca­tions for can­cer drug

Gilead recently decided to pull two indications for its cancer drug Zydelig — in relapsed follicular B-cell non-Hodgkin lymphoma (FL) and relapsed small lymphocytic leukemia (SLL) — after failing to complete the confirmatory trials required as part of the accelerated approvals from 2014.

“As the treatment landscape for FL and SLL has evolved, enrollment into the confirmatory study has been an ongoing challenge,” Gilead said in a statement, noting it formally notified the FDA of its decision to voluntarily withdraw these indications.

Richard Pazdur (via AACR)

Time lim­its on ac­cel­er­at­ed ap­provals? FDA's on­col­o­gy chief Rick Paz­dur eyes po­ten­tial re­forms via in­ter­na­tion­al ap­proach­es

The spotlight on the accelerated approval pathway continues to shine bright, with the FDA’s top oncology official writing in an opinion that the pathway may be strengthened with bits and pieces of what other regulators in Europe and elsewhere have done with their expedited approval pathways, such as adding expiration dates for these faster approvals to ensure they confirm clinical benefit in a timely manner.

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Executive Director of the EMA Emer Cooke (AP Photo/Geert Vanden Wijngaert)

Eu­ro­pean Par­lia­ment signs off on strength­en­ing drug reg­u­la­tor's abil­i­ty to tack­le short­ages

The European Parliament on Thursday endorsed a plan to increase the powers of the European Medicines Agency, which will be better equipped to monitor and mitigate shortages of drugs and medical devices.

By a vote of 655 to 31, parliament signed off on a provisional agreement reached with the European Council from last October, in which the EMA will create two shortage steering groups (one for drugs, the other for devices), a new European Shortages Monitoring Platform to facilitate data collection and increase transparency, and on funding for the work of the steering groups, task force, working parties and expert panels that are to be established.

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