Image: Chris Varma. Frontier

Chris Var­ma un­veils MP­M's lat­est start­up — eye­ing 'un­drug­gable' can­cer tar­gets and pow­ered by ma­chine learn­ing, $67M

Two years af­ter MPM Cap­i­tal en­list­ed Chris Var­ma on its busy on­col­o­gy team, the for­mer en­tre­pre­neur-in-res­i­dence is un­veil­ing his first ven­ture project out of his new stomp­ing grounds in the Bay Area: Fron­tier Med­i­cines.

For Var­ma, who’s al­so co-found­ed Blue­print Med­i­cines and built com­pa­nies at Third Rock and Flag­ship, this marks an­oth­er op­por­tu­ni­ty to ap­ply some cut­ting-edge sci­ence to “sev­er­al of the most im­por­tant and dif­fi­cult tar­gets in can­cer” — tar­gets that oth­ers have tried to tack­le with more clas­si­cal meth­ods and failed. The launch round comes in at $67 mil­lion, which should go some way in scaf­fold­ing a pre­clin­i­cal pipeline and push one or more as­sets in­to the clin­ic three years from now, he tells me.

Daniel No­mu­ra Fron­tier

Fron­tier’s stat­ed mis­sion — drug­ging pre­vi­ous­ly “un­drug­gable” pro­teins — comes right out of MPM’s play­book for a $408 mil­lion fund that man­ag­ing di­rec­tor Luke Evnin said would still be dom­i­nat­ed by on­col­o­gy plays. That mantra in biotech R&D re­cent­ly got a big boost when Am­gen pre­sent­ed the first cut of hu­man da­ta on its ef­fort to tar­get KRAS G12C with a small mol­e­cule drug.

Even dis­ease-caus­ing pro­teins with no known bind­ing sites, the the­o­ry at Fron­tier goes, bend and cre­ate tem­po­rary pock­ets when they move, crack­ing up a win­dow for ther­a­peu­tic in­no­va­tion.

“Drug­gable” pro­teins, Var­ma ex­plains, are like coat hang­ers: They have nice cor­ners that drugs can dock in­to. The oth­er 90% of the hu­man pro­teome ap­pear, fig­u­ra­tive­ly, more like a string. But in re­al­i­ty pro­teins are more dy­nam­ic than that.

“If you shake the string, you wig­gle it, then you see that ac­tu­al­ly curves do form and with­in those curves are cor­ners and you could imag­ine dock­ing a small mol­e­cule drug in­to those,” Var­ma says. Fron­tier’s tech then al­lows them to put a co­va­lent bind there, cre­at­ing a per­ma­nent lock in a tran­sient cor­ner.

Rober­to Zon­cu Pew

UC Berke­ley pro­fes­sors Daniel No­mu­ra and Rober­to joined CEO Var­ma in co-found­ing the biotech, with chemo­pro­teom­ic plat­forms and some ba­sic re­search on can­cer growth reg­u­la­tion in tow, re­spec­tive­ly. That com­bi­na­tion gives Fron­tier a data­base of hotspots (or bind­ing pock­ets) in hu­man pro­teins as well as a li­brary of com­pounds, to be sift­ed through by ma­chine learn­ing tech­niques. In ad­di­tion to tra­di­tion­al small mol­e­cule drugs, it al­so boasts of a “nov­el ap­proach to pro­tein degra­da­tion” — a pop­u­lar and in­creas­ing­ly crowd­ed field.

“It’s an al­ter­na­tive path­way for us to make sure that we can re­al­ly go af­ter any pro­tein tar­get of in­ter­est,” Var­ma, who left MPM a few months ago to go all in with the ven­ture, says.

While his team of 10 — he ex­pects to at least dou­ble that by the end of the year — is push­ing as hard as they can on in­ter­nal pro­grams, he added, they are open to part­ner­ing in oth­er can­cers and ther­a­peu­tic ar­eas such as neu­rode­gen­er­a­tion.

Jim Win­kler, a for­mer CSO at pro­tein degra­da­tion spe­cial­ist Arv­inas, is spear­head­ing the de­grad­er tech de­vel­op­ment while da­ta sci­ence ex­pert Jo­hannes Her­mann takes up the chief tech­nol­o­gy of­fi­cer’s role. In a re­cent stint, Her­mann head­ed up ma­chine learn­ing and ad­vanced an­a­lyt­ics at J&J’s Janssen.

To com­plete the Se­ries A, the co-founders brought in Deer­field Man­age­ment and Droia On­col­o­gy Ven­ture along­side MPM, while DCVC Bio, RA Cap­i­tal Man­age­ment and oth­er in­vestors al­so par­tic­i­pat­ed.

Has the mo­ment fi­nal­ly ar­rived for val­ue-based health­care?

RBC Capital Markets’ Healthcare Technology Analyst, Sean Dodge, spotlights a new breed of tech-enabled providers who are rapidly transforming the way clinicians deliver healthcare, and explores the key question: can this accelerating revolution overturn the US healthcare system?

Key points

Tech-enabled healthcare providers are poised to help the US transition to value, not volume, as the basis for reward.
The move to value-based care has policy momentum, but is risky and complex for clinicians.
Outsourced tech specialists are emerging to provide the required expertise, while healthcare and tech are also converging through M&A.
Value-based care remains in its early stages, but the transition is accelerating and represents a huge addressable market.

No­vo Nordisk re­mains un­der UK scruti­ny as MHRA con­ducts its own re­view in 'in­cred­i­bly rare' case

The UK’s Medicines and Healthcare products Regulatory Agency is now reviewing Novo Nordisk’s marketing violation that resulted in its loss of UK trade group membership last week. Novo Nordisk was suspended on Thursday from the Association of the British Pharmaceutical Industry (ABPI) for two years after an investigation by its regulatory arm found the pharma broke its conduct rules.

MHRA said on Tuesday that its review of the Prescription Medicines Code of Practice Authority (PMCPA) investigation is standard practice. An MHRA spokesperson emphasized in an email to Endpoints News that the situation with Novo Nordisk is “incredibly rare” while also noting ABPI took “swift and proportionate action.”

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Andy Plump, Takeda R&D chief (Jeff Rumans for Endpoints News)

What kind of PhI­Ib da­ta is worth $4B cash? Take­da’s Andy Plump has some thoughts on that

A few months back, when Takeda caused jaws to drop with its eye-watering $4 billion cash upfront for a mid-stage TYK2 drug from Nimbus, it had already taken a deep dive on the solid Phase IIb data Nimbus had assembled from its dose-ranging study in psoriasis.

Now, it’s rolling that data out, eager to demonstrate what inspired the global biopharma to go long in a neighboring, but new, disease arena for the pipeline. And the most avid students of the numbers will likely be at Bristol Myers Squibb, who will have a multi-year head start on pioneering the TYK2 space with Sotyktu (deucravacitinib) as Takeda makes its lunge for best-in-class status.

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Francesco Marincola, newly-appointed Sonata Therapeutics CSO

Kite's head of re­search leaves for Flag­ship start­up Sonata

Another leader is departing Kite Pharma, and will to spend the “last part” of his career exploring how cancer evades the immune system.

Kite’s senior VP and global head of cell therapy research Francesco Marincola left the Gilead CAR-T unit last week for Sonata Therapeutics. Flagship last May unveiled the startup, which was pieced together from two fledgling biotechs Inzen and Cygnal Therapeutics. As CSO, Marincola will lead Sonata’s push to reprogram cancer cells to make them more immunogenic.

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FDA in­di­cates will­ing­ness to ap­prove Bio­gen ALS drug de­spite failed PhI­II study

Ahead of Wednesday’s advisory committee hearing to discuss Biogen’s ALS drug tofersen, the FDA appeared open to approving the drug, newly released briefing documents show.

Citing the need for flexibility in a devastating disease like ALS, regulators signaled a willingness to consider greenlighting tofersen based on its effect on a certain protein associated with ALS despite a failed pivotal trial. The documents come after regulatory flexibility was part of the same rationale the agency expressed when approving an ALS drug last September from Amylyx Pharmaceuticals, indicating the FDA’s openness to approving new treatments for the disease.

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FDA warns Proc­ter & Gam­ble over NyQuil la­bel's in­gre­di­ent list­ings

The FDA on Tuesday released a warning letter sent earlier this month to the Mason, OH-based site of Procter & Gamble Manufactura, raising questions about the list of ingredients on the label and in the electronic filing.

The warning says that for P&G’s over-the-counter Vicks Nyquil Severe Hot Remedy Cold and Flu Plus Congestion, there’s a “mismatched” list of active ingredients between the labeling and the electronic listing file. The listing file for the active ingredients did not match the active ingredients in the electronic file.

FTC says patent bat­tle over Parkin­son's drug could have 'sig­nif­i­cant im­pli­ca­tion­s' for pa­tients

The Federal Trade Commission has gotten involved in a patent feud over Supernus’ Parkinson’s drug Apokyn, a case the agency said may have ‘‘significant implications” for patients who rely on the drug.

Sage Chemical won the first generic approval for its Apokyn formulation (also known as apomorphine hydrochloride injection) back in 2022. The non-ergoline dopamine agonist is approved to treat Parkinson’s symptoms during “off episodes,” such as difficulty moving, tremors and intense cramping. However, regulators specified that the approval pertained to the generic drug cartridges only, not the injector pen required for administration.

Growth hor­mone from No­vo Nordisk is in short­age over man­u­fac­tur­ing de­lays

Novo Nordisk’s growth hormone Norditropin is in shortage because of manufacturing delays, according to an FDA site that tracks drug shortages as well as the American Society of Health-System Pharmacists’ shortages list.

The FDA has shortages of the drug listed for its 5, 10, 15 and 30 mg doses, while the pharmacists’ group, also known as ASHP, reported shortages of the same doses, except for the 15 mg version.

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PhRMA calls for more di­verse in­fra­struc­ture up­grades to US emer­gency tri­als frame­work

The White House’s Office of Science and Technology Policy (OSTP) last year sought to find ways to better coordinate large-scale clinical trials in the US — as the UK lead by example during the pandemic — especially for these emergency clinical trials.

The lobbying group PhRMA Tuesday called for more clinical trial diversity in underserved areas, including by making participation less of a burden, and expanding eligibility criteria when appropriate.