Chris Varma, Frontier Medicines CEO

Months af­ter Am­gen's land­mark KRAS ap­proval, Chris Var­ma bags a crossover round for next-gen can­di­date

For years, mu­tant, can­cer-fu­el­ing KRAS pro­teins were con­sid­ered “un­drug­gable.” That all changed in May, when Am­gen’s KRAS-block­ing drug Lumakras snagged the FDA’s first ap­proval in the field. And now a slate of in­vestors are bet­ting $88.5 mil­lion on a Bay Area start­up’s next-gen­er­a­tion can­di­date.

Fron­tier Med­i­cines has closed a hefty Se­ries B round, co-led by Wood­line Part­ners and RA Cap­i­tal Man­age­ment, the com­pa­ny said on Mon­day. Deer­field Man­age­ment, Deep Track Cap­i­tal, Ar­row­Mark Part­ners, Driehaus Cap­i­tal Man­age­ment, Sphera Health­care, DCVC’s Bio fund, Droia Ven­tures and MPM Cap­i­tal al­so chimed in. With the lat­est round, it’s pos­si­ble CEO Chris Var­ma has an IPO on the mind.

Var­ma launched Fron­tier back in 2019 with $67 mil­lion in launch mon­ey and a mis­sion to drug pre­vi­ous­ly “un­drug­gable” pro­teins. Since then, the 10-per­son team has grown to about 60 staffers. Var­ma — who has al­so co-found­ed Blue­print Med­i­cines and built com­pa­nies at Third Rock and Flag­ship — says the team is like­ly a cou­ple years away from the clin­ic.

“We’re pro­gress­ing rapid­ly to IND-en­abling stud­ies,” he told End­points News on Mon­day morn­ing.

Back in De­cem­ber, Ab­b­Vie shelled out $55 mil­lion up­front to part­ner with Fron­tier on pro­tein degra­da­tion work, promis­ing to re­im­burse the start­up for its pre­clin­i­cal R&D costs.

Mean­while, the B round will be used to ad­vance the com­pa­ny’s pre­clin­i­cal pipeline of pre­ci­sion med­i­cines against dri­vers of can­cer. Its lead pro­gram is fo­cused on block­ing ac­tive and in­ac­tive forms of KRAS G12C, the same mu­ta­tion tar­get­ed by Am­gen’s Lumakras for non-small cell lung can­cer. What dif­fer­en­ti­ates Fron­tier’s can­di­date is that it tar­gets both ac­tive and in­ac­tive forms of the pro­tein. A ma­jor­i­ty of pa­tients who are treat­ed with in­hibitors tar­get­ing in­ac­tive forms of KRAS G12C don’t re­spond, Var­ma added.

“The abil­i­ty to tar­get both forms of KRASG12C, which in­cludes the ac­tive and in­ac­tive states of the pro­tein, with a small mol­e­cule ther­a­py would be a long-await­ed sci­en­tif­ic break­through,” said Frank Mc­Cormick, a pro­fes­sor of the UCSF He­len Diller Fam­i­ly Com­pre­hen­sive Can­cer Cen­ter, in a state­ment.

“Im­por­tant­ly for pa­tients, a drug with this dual in­hi­bi­tion may be more ef­fi­ca­cious than a drug that tar­gets just the in­ac­tive form of KRASG12C by ad­dress­ing the large ma­jor­i­ty of pa­tients who are non-re­spon­ders to first gen­er­a­tion sin­gle-form KRASG12C in­hibitors, as well as those pa­tients whose tu­mors be­come re­sis­tant to the first-gen­er­a­tion mol­e­cules,” he con­tin­ued.

At the core of Fron­tier’s plat­form is ma­chine learn­ing paired with some­thing the com­pa­ny calls chemo­pro­teomics, or find­ing new ways to bind tar­gets by ex­am­in­ing tem­po­rary pock­ets in pro­teins.

Up­on the com­pa­ny’s launch back in 2019, Var­ma told End­points that “drug­gable” pro­teins are like coat hang­ers — they have cor­ners that drugs can dock in­to. “Un­drug­gable” pro­teins on the oth­er hand ap­pear — fig­u­ra­tive­ly — more like a string.

“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,” he said.

Fron­tier is work­ing on tech that would al­low sci­en­tists to put a co­va­lent bind there, cre­at­ing a per­ma­nent lock in a tran­sient cor­ner.

A hand­ful of oth­er drug­mak­ers are pur­su­ing KRAS in­hibitors, in­clud­ing Mi­rati, which snagged break­through ther­a­py des­ig­na­tion for its ada­gra­sib in non-small cell lung can­cer back in June. Eli Lil­ly jumped in­to the hunt back in March, and said it planned to put a new small mol­e­cule in Phase I lat­er this year. And back in Oc­to­ber 2019, Boehringer In­gel­heim ad­vanced its pan-KRAS in­hibitor in­to the clin­ic.

In ad­di­tion to the fi­nanc­ing, Fron­tier has an­nounced that it’s adding a new site in Boston to com­ple­ment its South San Fran­cis­co head­quar­ters, where it will “build its em­ploy­ee ex­per­tise across re­search and de­vel­op­ment, in­clud­ing dis­cov­ery, pre-clin­i­cal de­vel­op­ment, trans­la­tion­al med­i­cine, and ear­ly clin­i­cal de­vel­op­ment.” The new site is ex­pect­ed to open be­fore the end of the year, and will be home to about 60 or so more em­ploy­ees — and Var­ma added that he’s look­ing to hire.

*A cor­rec­tion has been made to note that DCVC’s in­vest­ment came from their Bio fund.

Illustration: Assistant Editor Kathy Wong for Endpoints News

How Pur­due's $272M ad­dic­tion pay­out fund­ed a new home for its dis­card­ed non-opi­oid re­search

Don Kyle spent more than 20 years working for Purdue Pharma, right through the US opioid epidemic that led to the company’s rise and eventual infamy. But contrary to Purdue’s focus on OxyContin, Kyle was researching non-opioid painkillers — that is, until the company shelved his research.

As the company’s legal troubles mounted, Kyle found an unlikely way to reboot the project. In 2019, he took his work to an Oklahoma State University center that’s slated to receive more than two-thirds of the state’s $272 million settlement with Purdue over claims that the drugmaker’s behavior ignited the epidemic of opioid use and abuse.

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President Joe Biden at the State of the Union address with Vice President Kamala Harris and House Speaker Kevin McCarthy (Patrick Semansky/AP Images)

The drug pric­ing pres­i­dent: Biden warns of ve­to for any IRA re­peal at­tempts

President Joe Biden made clear in his “finish the job” State of the Union address last night that one of those jobs to be finished is insulin prices.

Biden’s push again to tackle insulin prices, after Republicans rebuffed the idea last summer and just after Biden won Medicare drug price negotiations/caps via the Inflation Reduction Act, shows how heavily he’s leaning into this work.

Rupert Vessey, Bristol Myers Squibb head of research and early development

Up­dat­ed: R&D tur­bu­lence at Bris­tol My­ers now in­cludes the end of a $650M al­liance and the de­par­ture of a top re­search cham­pi­on

This morning biotech Dragonfly put out word that Bristol Myers Squibb has handed back all rights to its IL-12 clinical-stage drug after spending $650 million to advance it into the clinic.

The news arrives amid a turbulent R&D stage for the pharma giant, which late last week highlighted Rupert Vessey’s decision to depart this summer as head of early-stage R&D following a crucial three-year stretch after he jumped to Bristol Myers in the big Celgene buyout. During that time he struck a series of deals for Bristol Myers, and also shepherded a number of Celgene programs down the pipeline, playing a major role for a lineup of biotechs which depended on him to champion their drugs.

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Bill Haney, Dragonfly CEO (Dave Pedley/Getty Images for SXSW)

Drag­on­fly chief: Bris­tol My­ers shouldn’t blame IL-12’s clin­i­cal per­for­mance for de­ci­sion to scrap the deal — eco­nom­ics played a key role

Bristol Myers Squibb says the IL-12 drug they were developing out of Dragonfly Therapeutics was scrubbed from the pipeline for a simple reason: It didn’t measure up on clinical performance.

But Bill Haney, the CEO of Dragonfly, is taking issue with that.

The early-stage drug, still in Phase I development, has passed muster with Bristol Myers’ general clinical expectations, advancing successfully while still in Phase I, he says.

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Utpal Koppikar, new Verily CFO

Ex­clu­sive: Ver­i­ly wel­comes Atara Bio­ther­a­peu­tics vet­er­an as new CFO

Verily, Alphabet’s life sciences outfit, has plucked a new CFO from the ranks of Atara Biotherapeutics, the company announced on Wednesday.

Utpal Koppikar joins Verily after a nearly five-year stint as CFO and senior VP at Atara, though his résumé also boasts roles at Gilead and Amgen.

The news follows a major reshuffling at Verily, including several senior departures earlier this year and a round of layoffs.

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Singer Nick Jonas is back at work for Dexcom, this time for its new G7 glucose monitor.

Dex­com's spokescelebri­ty Nick Jonas re­turns to Su­per Bowl in new glu­cose mon­i­tor com­mer­cial

Dexcom is going back to the Super Bowl with its pop singer and patient spokesperson Nick Jonas. Jonas takes center stage as the lone figure in the 30-second commercial showcasing Dexcom’s next-generation G7 continuous glucose monitoring (CGM) device.

Jonas’ sleight-of-hand tricks populate the commercial — he pinches his empty fingers together and pops them open to reveal the small CGM — even as he ends the ad, saying, “It’s not magic. It just feels that way.” Jonas then disappears in a puff of smoke.

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Richard Francis, newly-appointed Teva CEO (Novartis via Facebook)

New Te­va CEO Richard Fran­cis repri­or­i­tizes to 'get back to growth'

Six weeks into his new role at the helm of Teva Pharmaceutical, Richard Francis said it’s time to “get back to growth,” starting with a good look at the company’s priorities.

The chief executive has kicked off a strategic review, he announced during Teva’s quarterly call, which will continue over the next several months and produce results sometime in the middle of 2023. That means some pipeline cuts may be in store, he told Endpoints News, while declining to offer much more detail.

FDA Commissioner Robert Califf on Capitol Hill, Feb. 8, 2023 (Drew Angerer/Getty Images)

FDA com­mis­sion­er floats ideas on how to bet­ter han­dle the pan­dem­ic

FDA Commissioner Rob Califf joined the heads of the CDC and NIH in the hot seat today before a key House subcommittee, explaining that there needs to be a much faster, more coordinated way to oversee vaccine safety, and that foreign biopharma inspections, halted for years due to the pandemic, are slowly ramping up again.

Califf, who stressed to the House Energy and Commerce’s Subcommittee on Health that the CDC also needs better data, made clear that the FDA’s ability to monitor the safety of vaccines “would also benefit greatly by a coordinated federal public health data reporting authority.”

Sanofi is renewing its #VaccinesForDreams campaign with more stories, such as Juan's in Argentina (Sanofi)

Sanofi re­news so­cial cam­paign to re­mind that vac­cines let peo­ple ‘Dream Big’

Sanofi is highlighting people’s dreams — both big and small — to make the point that vaccines make them possible.

The renewed “Dream Big” global social media campaign’s newest dreamer is Juan, a teacher in the Misiones rainforest in Argentina whose story is told through videos on Instagram and Sanofi’s website with the hashtag #VaccinesForDreams.

The campaign ties to Sanofi’s broader umbrella initiative “Vaccine Stories” to promote the value of vaccines and drive awareness of the need for improved vaccination coverage.

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