Sam Cooper, Phenomic AI

Jim Al­li­son and Pam Shar­ma back a Cana­di­an AI up­start seek­ing to solve the tu­mor stro­ma puz­zle

Jim Al­li­son

A new com­pa­ny out of Toron­to is seek­ing to put AI and ma­chine learn­ing to the test, us­ing the ad­vanced tech­nol­o­gy to iden­ti­fy tar­gets in sol­id can­cers and oth­er chal­leng­ing dis­eases. And it has the back­ing of the in­dus­try’s res­i­dent pow­er cou­ple.

Phe­nom­ic AI of­fi­cial­ly launched Wednes­day with $6 mil­lion in seed fund­ing and an­nounced that Jim Al­li­son and Pam Shar­ma have joined its sci­en­tif­ic ad­vi­so­ry board. The biotech is al­so bring­ing on new CSO Mike Briskin, who has a pro­fes­sion­al his­to­ry with Al­li­son and Shar­ma af­ter work­ing with them and Third Rock Ven­tures to found Jounce Ther­a­peu­tics about a decade ago.

“We’ve been close over the years ever since we start­ed Jounce,” Briskin said. “We start­ed talk­ing about dif­fer­ent ar­eas to move in­to be­yond the T cell … they’ve seen some of the da­ta from some of their col­leagues at MD An­der­son, and they re­al­ly felt like this was some­thing that was worth be­ing in­volved in.”

Pad­ma­nee Shar­ma

Fi­nanc­ing was led by CTI and joined by AV8, Lu­mi­nous and Vi­va BioIn­no­va­tor. Cur­rent in­vestors Garage Cap­i­tal, Hike and Can­tos al­so joined the round.

The com­pa­ny is plan­ning on us­ing its plat­form not on­ly for drug de­vel­op­ment, but to re­search how dif­fer­ent cells act in dis­ease states, main­ly the tu­mor stro­ma. A part of the mi­croen­vi­ron­ment present in sol­id tu­mors, the stro­ma es­sen­tial­ly acts as a bar­ri­er that pre­vents a body’s im­mune sys­tem from at­tack­ing the tu­mor.

Ba­si­cal­ly, the hu­man body builds a wall to pro­tect it­self from the tu­mor, but the tu­mor then hi­jacks the wall and in­stalls its own army to keep the im­mune sys­tem out, CEO Sam Coop­er said.

“That’s re­al­ly what we’re up against, not just a brick wall but a brick wall filled with sol­diers that are fight­ing off every­thing we’re throw­ing at it,” Coop­er said. “What’s ob­vi­ous­ly clear in can­cer though is that you’ve got dif­fer­ent walls in dif­fer­ent pa­tients, there’s no sim­ple way of do­ing this.”

Mike Briskin

While the func­tion of the stro­ma has been known for some time, Briskin said, on­ly re­cent­ly did re­search come about sug­gest­ing that it’s al­so in­volved in some cell-to-cell in­ter­ac­tions and im­mune re­spons­es, such as sig­nal­ing to T cells to stay away from tu­mors. One of Phe­nom­ic’s goals is to de­vel­op drugs that don’t re­quire im­mune sys­tem re­pres­sion in or­der to break the cy­cle of those in­ter­ac­tions.

That’s where the com­pa­ny’s AI plat­form comes in­to play. Through its tech­nol­o­gy, Coop­er said Phe­nom­ic is ca­pa­ble of mod­el­ing how cells and stro­ma com­mu­ni­cate with each oth­er. Then, re­searchers ex­tract “high-di­men­sion­al read­outs” from the mod­els to de­ter­mine what the cells are do­ing and re­late it back to how a tar­get is af­fect­ed.

“This is all too dif­fi­cult to process at scale as a per­son,” Coop­er said. “Where be­fore you had a mash of dif­fer­ent cells and you’ve got no idea of what’s re­al­ly hap­pen­ing, now we can say this in­di­vid­ual cell is sup­press­ing a T cell and pre­vent­ing it from get­ting to the can­cer. And then we can tar­get that with drugs.”

Phe­nom­ic isn’t dis­clos­ing its ini­tial two tar­gets just yet, but Coop­er said the com­pa­ny’s drug can­di­dates will be fo­cused around can­cer as­so­ci­at­ed fi­brob­lasts, or CAFs. Can­cers that show the least re­sponse to im­mune ther­a­pies typ­i­cal­ly have high­er stro­mal con­tent, and Phe­nom­ic is hop­ing that at­tack­ing the CAFs may prove piv­otal for new­er drug can­di­dates.

If all goes well, Phe­nom­ic won’t be pro­duc­ing typ­i­cal check­point in­hibitor drugs. In fact, Coop­er said that due to the re­al­i­ty of can­cer, they may sign on ex­ist­ing in­hibitors to use in com­bi­na­tion with an an­ti-stro­mal com­pound.

Ul­ti­mate­ly, the com­pa­ny was in­spired by Al­li­son’s work. Should their even­tu­al drugs con­vert im­mune ther­a­py-re­sis­tant tu­mors in­to those that can be treat­ed, if even a lit­tle bit, Phe­nom­ic will con­sid­er that a suc­cess.

“The rev­o­lu­tion in this field at the start was Jim Al­li­son’s il­lus­tra­tion of us­ing a check­point in­hibitor in metasta­t­ic melanoma, re­sult­ing in what in turn were long-term re­spons­es,” Briskin said. “You can see that now in some of these pa­tients, and our goal is to ex­tend those ben­e­fits to a greater num­ber of pa­tients.”

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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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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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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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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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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Kenneth Galbraith, incoming Zymeworks CEO

Zymeworks re­places half its C-suite, aims to lay off 25% of to­tal work­force as new CEO takes over

New Zymeworks CEO Kenneth Galbraith is aiming to hit the ground running when his tenure officially begins next month, but he’ll be doing so with a much different looking team.

In a lengthy press release outlining the biotech’s 2022 goals, Galbraith said Zymeworks will be laying off at least 25% of its staff over the course of the year. Half of its C-suite will also be replaced immediately as Galbraith looks to remake the company in his image after Ali Tehrani, Zymeworks’ founder and CEO since 2003, stepped down two weeks ago.

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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.