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.

It’s fi­nal­ly over: Bio­gen, Ei­sai scrap big Alzheimer’s PhI­I­Is af­ter a pre­dictable BACE cat­a­stro­phe rais­es safe­ty fears

Months after analysts and investors called on Biogen and Eisai to scrap their BACE drug for Alzheimer’s and move on in the wake of a string of late-stage failures and rising safety fears, the partners have called it quits. And they said they were dropping the drug — elenbecestat — after the independent monitoring board raised concerns about…safety.

We don’t know exactly what researchers found in this latest catastrophe, but the companies noted in their release that investigators had determined that the drug was flunking the risk/benefit analysis.

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Lisa M. DeAngelis, MSKCC

MSK picks brain can­cer ex­pert Lisa DeAn­ge­lis as its next CMO — fol­low­ing José Basel­ga’s con­tro­ver­sial ex­it

It’s official. Memorial Sloan Kettering has picked a brain cancer expert as its new physician-in-chief and CMO, replacing José Baselga, who left under a cloud after being singled out by The New York Times and ProPublica for failing to properly air his lucrative industry ties.

His replacement, who now will be in charge of MSK’s cutting-edge research work as well as the cancer care delivered by hundreds of practitioners, is Lisa M. DeAngelis. DeAngelis had been chair of the neurology department and co-founder of MSK’s brain tumor center and was moved in to the acting CMO role in the wake of Baselga’s departure.

Penn team adapts CAR-T tech, reengi­neer­ing mouse cells to treat car­diac fi­bro­sis

After establishing itself as one of the pioneer research centers in the world for CAR-T cancer therapies, creating new attack vehicles to eradicate cancer cells, a team at Penn Medicine has begun the tricky transition of using the basic technology for heart repair work.

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Tal Zaks. Moderna

The mR­NA uni­corn Mod­er­na has more ear­ly-stage hu­man da­ta it wants to show off — reach­ing new peaks in prov­ing the po­ten­tial

The whole messenger RNA field has attracted billions of dollars in public and private investor cash gambled on the prospect of getting in on the ground floor. And this morning Boston-based Moderna, one of the leaders in the field, wants to show off a few more of the cards it has to play to prove to you that they’re really in the game.

The whole hand, of course, has yet to be dealt. And there’s no telling who gets to walk with a share of the pot. But any cards on display at this point — especially after being accused of keeping its deck under lock and key — will attract plenty of attention from some very wary, and wired, observers.

“In terms of the complexity and unmet need,” says Tal Zaks, the chief medical officer, “this is peak for what we’ve accomplished.”

Moderna has two Phase I studies it wants to talk about now.

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It's not per­fect, but it's a good start: FDA pan­elists large­ly en­dorse Aim­mune's peanut al­ler­gy ther­a­py

Two days after a fairly benign review from FDA staff, an independent panel of experts largely endorsed the efficacy and safety of Aimmune’s peanut allergy therapy, laying the groundwork for approval with a risk evaluation and mitigation strategy (REMS).

Traditionally, peanut allergies are managed by avoidance, but the threat of accidental exposure cannot be nullified. Some allergists have devised a way to dose patients off-label with peanut protein derived from supermarket products to wean them off their allergies. But the idea behind Aimmune’s product was to standardize the peanut protein, and track the process of desensitization — so when accidental exposure in the real world invariably occurs, patients are less likely to experience a life-threatening allergic reaction.

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Rit­ter bombs fi­nal PhI­II for sole lac­tose in­tol­er­ance drug — shares plum­met

More than two years ago Ritter Pharmaceuticals managed to find enough silver lining in its Phase IIb/III study — after missing the top-line mark — to propel its lactose intolerance toward a confirmatory trial. But as it turned out, the enthusiasm only set the biotech and its investors up to be sorely disappointed.

This time around there’s little left to salvage. Not only did RP-G28 fail to beat placebo in reducing lactose intolerance symptoms, patients in the treatment group actually averaged a smaller improvement. On a composite score measuring symptoms like abdominal pain, cramping, bloating and gas, patients given the drug had a mean reduction of 3.159 while the placebo cohort saw a 3.420 drop on average (one-sided p-value = 0.0106).

Ear­ly snap­shot of Ad­verum's eye gene ther­a­py sparks con­cern about vi­sion loss

An early-stage update on Adverum Biotechnologies’ intravitreal gene therapy has triggered investor concern, after patients with wet age-related macular degeneration (AMD) saw their vision deteriorate, despite signs that the treatment is improving retinal anatomy.

Adverum, on Wednesday, unveiled 24-week data from the OPTIC trial of its experimental therapy, ADVM-022, in six patients who have been administered with one dose of the therapy. On average, patients in the trial had severe disease with an average of 6.2 anti-VEGF injections in the eight months prior to screening and an average annualized injection frequency of 9.3 injections.

Alex Ar­faei trades his an­a­lyst's post for a new role as biotech VC; Sanofi vet heads to Vi­for

Too often, Alex Arfaei arrived too late. 

An analyst at BMO Capital Markets, he’d meet with biotech or pharmaceutical heads for their IPO or secondary funding and his brain, trained on a biology degree and six years at Merck and Endo, would spring with questions: Why this biomarker? Why this design? Why not this endpoint? Not that he could do anything about it. These execs were coming for clinical money; their decisions had been made and finalized long ago.

Arde­lyx bags its first FDA OK for IBS, set­ting up a show­down with Al­ler­gan, Iron­wood

In the first of what it hopes will be a couple of major regulatory milestones for its new drug, Ardelyx has bagged an FDA approval to market Ibsrela (tenapanor) for irritable bowel syndrome.

The drug’s first application will be for IBS with constipation (IBS-C), inhibiting sodium-hydrogen exchanger NHE3 in the GI tract in such a way as to increase bowel movements and decrease abdominal pain. This comes on the heels of two successful Phase III trials.