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.

Inside FDA HQ (File photo)

The FDA just ap­proved the third Duchenne MD drug. And reg­u­la­tors still don’t know if any of them work

Last year Sarepta hit center stage with the FDA’s controversial reversal of its CRL for the company’s second Duchenne muscular dystrophy drug — after the biotech was ambushed by agency insiders ready to reject a second pitch based on the same disease biomarker used for the first approval for eteplirsen, without actual data on the efficacy of the drug.

On Wednesday the FDA approved the third Duchenne MD drug, based on the same biomarker. And regulators were ready to act yet again despite the lack of efficacy data.

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Cell and Gene Con­tract Man­u­fac­tur­ers Must Em­brace Dig­i­ti­za­tion

The Cell and Gene Industry is growing at a staggering 30% CAGR and is estimated to reach $14B by 20251. A number of cell, gene and stem cell therapy sponsors currently have novel drug substances and products and many rely on Contract Development Manufacturing Organizations (CDMO) to produce them with adherence to stringent regulatory cGMP conditions. Cell and gene manufacturing for both autologous (one to one) and allogenic (one to many) treatments face difficult issues such as: a complex supply chain, variability on patient and cellular level, cell expansion count and a tight scheduling of lot disposition process. This complexity affects quality, compliance and accountability in the entire vein-to-vein process for critically ill patients.

Franz-Werner Haas, CureVac CEO

UP­DAT­ED: On the heels of a snap $1B raise, Cure­Vac out­lines plans to seek emer­gency OK for their Covid-19 vac­cine in a mat­ter of months

CureVac is going from being one of the quietest players in the race to develop a new vaccine to fight the worst public health crisis in a century to a challenger for the multibillion-dollar market that awaits the first vaccines to make it over the finish line. Typically low-key at a time of brash comments and incredibly ambitious development timelines from the leaders, CureVac now is jumping straight into the spotlight.

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US gov­ern­ment re­port­ed­ly be­gins prepar­ing for Covid-19 chal­lenge tri­als. Are they eth­i­cal?

Controversial human challenge trials for potential Covid-19 vaccines reportedly have a new booster — the US government.

Scientists working for the government have begun manufacturing a strain of the novel coronavirus that could be used in such studies, Reuters reported Friday morning. The trials would enroll healthy volunteers to be vaccinated and then intentionally infected with a weakened coronavirus.

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Sanofi vet Kather­ine Bowdish named CEO of PIC Ther­a­peu­tics; As the world Terns: Liv­er dis­ease biotech makes ex­ec­u­tive changes

PIC Therapeutics hasn’t raised much money, yet. But the fledgling biotech has attracted a high-profile player to the helm.

The Boston-based biotech has handed the reins to Katherine Bowdish as its president and CEO. Bowdish will also join the board of directors of PIC. Bowdish joins from Sanofi where she served as VP and head of R&D strategy, as well as helping launch and lead Sanofi Sunrise, a venture investment and partnering vehicle at Sanofi. Before that, Bowdish held several exec roles at Permeon Biologics, Anaphore, Alexion Pharmaceuticals and Prolifaron (acquired by Alexion).

Charlie Silver (Mission Bio)

'We want to be every­where.' Mis­sion Bio rais­es $70M be­hind re­sis­tance-hunt­ing se­quenc­ing plat­form

Charlie Silver wants to look really, really closely at a lot of your cells. And he just got a lot of money to do so.

Silver’s startup, Mission Bio, raised $70 million in a Series C round Thursday led by Novo Holdings. The money, which brings Mission Bio to $120 million raised since its 2012 founding, will be used to advance the single-cell sequencing platform they built to detect early response or resistance to new cancer therapies.

Trevor Martin (Mammoth)

Eye­ing in-vi­vo edit­ing, Mam­moth li­cens­es Jen­nifer Doud­na’s new CRISPR en­zyme

Last month, Jennifer Doudna revealed in Science a new, “hyper-compact” CRISPR enzyme that was half the size of traditional CRISPR enzymes and could, she suspected, offer a new, more versatile tool for gene editing.

Now, the University of California-Berkeley has licensed that enzyme, known as Casφ, exclusively to a biotech startup she and two former students set up three years ago: Mammoth Biosciences. It’s the second new CRISPR protein Mammoth has licensed from Doudna’s lab, after they licensed Cas14 in 2019.

Clockwise from left: Canaccord Genuity principal Michelle Gilson, Canaccord Genuity CSO Brian Mueller and BioMarin CSO Hank Fuchs (Canaccord Genuity webcast)

Bio­Marin CSO diss­es ri­vals for the he­mo­phil­ia A gene ther­a­py crown: Way be­hind, fac­ing big re­cruit­ment chal­lenges and at best a .6 on the gen-one scale

The leader in the race to a hemophilia A gene therapy does not like to be compared unfavorably to the competition. And when their top execs do the comparing, don’t look for any modesty — BioMarin, they say, owns the lead.

As Factor VIII expression wanes over time, quite a few analysts have raised questions about the kind of future BioMarin’s gene therapy — a supposed once-and-done treatment — faces if it stops working. But just 7 days away from their PDUFA date, with high odds of success, the top execs clearly feel that they are way out front, while promising their rivals will discover there’s a tough slog ahead trying to pursue trials where large numbers of patients are ineligible for new therapies.

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Stéphane Bancel speaks to President Donald Trump at the White House meeting on March 2 (AP Images)

UP­DAT­ED: Mod­er­na of­fers steep dis­count in US sup­ply deal — but still takes the crown with close to $2.5B in vac­cine con­tracts

The US pre-order for Moderna’s Covid-19 vaccine is in.

Operation Warp Speed is reserving $1.525 billion for 100 million doses of Moderna’s Phase III mRNA candidate, rounding out to about $15 per dose — including $300 million in incentive payments for timely delivery. Given that Moderna has a two-dose regimen, it’s good for vaccinating 50 million people. The US government also has the option to purchase another 400 million doses for a total of $6.6 billion, or $16.5 per dose.

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