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.

BiTE® Plat­form and the Evo­lu­tion To­ward Off-The-Shelf Im­muno-On­col­o­gy Ap­proach­es

Despite rapid advances in the field of immuno-oncology that have transformed the cancer treatment landscape, many cancer patients are still left behind.1,2 Not every person has access to innovative therapies designed specifically to treat his or her disease. Many currently available immuno-oncology-based approaches and chemotherapies have brought long-term benefits to some patients — but many patients still need other therapeutic options.3

Fangliang Zhang (Imaginechina via AP Images)

The big mon­ey: Poised to make drug R&D his­to­ry, a Chi­na biotech un­veils uni­corn rac­ing am­bi­tions in a bid to raise $350M-plus on Nas­daq

Almost exactly three years after Shanghai-based Legend came out of nowhere to steal the show at ASCO with jaw-dropping data on their BCMA-targeted CAR-T for multiple myeloma, the little player with Big Pharma connections is taking a giant step toward making it big on Wall Street. And this time they want to seal the deal on a global rep after staking out a unicorn valuation in what’s turned out to be a bull market for biotech IPOs — in the middle of a pandemic.

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IPOs abound in the time of coro­n­avirus, as For­ma Ther­a­peu­tics pen­cils in $150M Nas­daq de­but

The IPO engine is thriving, never mind the rampage of the coronavirus crisis on R&D timelines.

On Friday, along with synthetic lethality-focused biotech Repare Therapeutics, another Bristol Myers partner Forma Therapeutics also unveiled its plans to vault on to the Nasdaq — penciling in a target of $150 million.

The Watertown, Massachusetts-based company — which poached senior Genentech executive Frank Lee to take over the reins last year after more than a decade under founder Steve Tregay — raised a plump $100 million late last year, while shepherding its sickle cell disease (SCD) drug through an early-stage trial.

Gilead re­leas­es an­oth­er round of murky remde­sivir re­sults

A month after the NIH declared the first trial on remdesivir in Covid-19 a success, Gilead is out with new results on their antiviral. But although the study met one of its primary endpoints, the data are likely to only add to a growing debate over how effective the drug actually is.

In a Phase III trial, patients given a 5-day dose of remdesivir were 65% more likely to show “clinical improvement” compared to an arm given standard-of-care. The trial, though, gave little indication for whether the drug had an impact on key endpoints such as survival or time-to-recovery. And in a surprising twist, a 10-day dosing arm of remdesivir didn’t lead to a statistically significant improvement over standard of care.

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Ver­sant-backed, Bris­tol My­ers-stamped Re­pare Ther­a­peu­tics guns for $100M IPO

With a Bristol Myers Squibb endorsement in tow, Versant-backed cancer drug developer Repare Therapeutics has set its sights on a Nasdaq debut.

On Friday, the Montreal-based company with operations in Cambridge, Massachusetts that is yet to enter the clinic, unveiled plans for a $100 million IPO, banking on its “synthetic lethality” platform.

The basic idea is to target the genetic basis of tumors, a common idea across precision oncology medicines. But instead of targeting the perpetrator mutation directly, the compound is designed to go after the other gene in the gene pair. The rationale is based on the decades-old genetic principle that indicates two mutations are lethal only when combined together.

Len Schleifer (left) and George Yancopoulos, Regeneron (Vimeo)

Eyes on he­mo­phil­ia prize, Re­gen­eron adds a $100M wa­ger on joint de­vel­op­ment cam­paign with In­tel­lia

When George Yancopoulos first signed up Intellia to be its CRISPR/Cas9 partner on gene editing projects 4 years ago, the upstart smartly ramped up its IPO at the same time. Today, Regeneron $REGN is coming back in, adding $100 million in an upfront fee and equity to significantly boot up a whole roster of new development projects.

And they’re highlighting some clinical hemophilia research plans in the process.

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Covid-19 roundup: Did in­sid­ers cash in on pos­i­tive news re­port about Gilead be­fore pub­li­ca­tion?

A series of bullish trades on Gilead options just before the release of a favorable news story is raising questions among regulatory experts, Reuters reported.

On April 16, just hours before STAT published anecdotes from a Chicago hospital that served as one of the clinical sites to test Gilead’s remdesivir in Covid-19 patients, the California-based company’s shares were trading at around $75. Four large blocks of options were purchased for about $1.5 million each, betting that the stock would rise beyond that to as much as $87.5 by mid-August.

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Federico Mingozzi (Spark)

Spark touts an­i­mal da­ta for a so­lu­tion to AAV gene ther­a­py's an­ti­body prob­lem

Among all the limitations of using an adeno-associated virus as a vector to deliver a gene — still the most established modality in gene therapy given years of trial and error and finally success — the presence of neutralizing antibodies, whether pre-existing or induced, looms large.

“When I think about the immune responses in AAV, I try to sort of layer them,” Federico Mingozzi, the CSO at Spark Therapeutics, told Endpoints News. “The antibody is the first layer. It’s the first block that you find when you’re trying to do gene transfer.”

Iterum's fu­ture looks un­cer­tain, af­ter lead an­tibi­ot­ic fails con­sec­u­tive piv­otal stud­ies

While the market for antibiotics remains in tatters — unlike many of its bankrupt (or at the brink of bankruptcy) peers — Iterum is suffering not because its antibiotic isn’t selling, but because the compound has now failed back-to-back late-stage studies.

The experimental drug, sulopenem, was designed to tackle drug-resistant infections with an outpatient focus (in addition to hospitals), to avert those reimbursement challenges that incentivize hospitals to prescribe cheaper, generic broad-spectrum antibiotics.