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.

ZS Per­spec­tive: 3 Pre­dic­tions on the Fu­ture of Cell & Gene Ther­a­pies

The field of cell and gene therapies (C&GTs) has seen a renaissance, with first generation commercial therapies such as Kymriah, Yescarta, and Luxturna laying the groundwork for an incoming wave of potentially transformative C&GTs that aim to address diverse disease areas. With this renaissance comes several potential opportunities, of which we discuss three predictions below.

Allogenic Natural Killer (NK) Cells have the potential to displace current Cell Therapies in oncology if proven durable.

Despite being early in development, Allogenic NKs are proving to be an attractive new treatment paradigm in oncology. The question of durability of response with allogenic therapies is still an unknown. Fate Therapeutics’ recent phase 1 data for FT516 showed relatively quicker relapses vs already approved autologous CAR-Ts. However, other manufacturers, like Allogene for their allogenic CAR-T therapy ALLO-501A, are exploring novel lymphodepletion approaches to improve persistence of allogenic cells. Nevertheless, allogenic NKs demonstrate a strong value proposition relative to their T cell counterparts due to comparable response rates (so far) combined with the added advantage of a significantly safer AE profile. Specifically, little to no risk of graft versus host disease (GvHD), cytotoxic release syndrome (CRS), and neurotoxicity (NT) have been seen so far with allogenic NK cells (Fig. 1). In addition, being able to harness an allogenic cell source gives way to operational advantages as “off-the-shelf” products provide improved turnaround time (TAT), scalability, and potentially reduced cost. NKs are currently in development for a variety of overlapping hematological indications with chimeric antigen receptor T cells (CAR-Ts) today, and the question remains to what extent they will disrupt the current cell therapy landscape. Click for more details.

Graphic: Kathy Wong for Endpoints News

What kind of biotech start­up wins a $3B syn­di­cate, woos a gallery of mar­quee sci­en­tists and re­cruits GSK's Hal Bar­ron as CEO in a stun­ner? Let Rick Klaus­ner ex­plain

It started with a question about a lifetime’s dream on a walk with tech investor Yuri Milner.

At the beginning of the great pandemic, former NCI chief and inveterate biotech entrepreneur Rick Klausner and the Facebook billionaire would traipse Los Altos Hills in Silicon Valley Saturday mornings and talk about ideas.

Milner’s question on one of those mornings on foot: “What do you want to do?”

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Hal Barron, Endpoints UKBIO20 (Jeff Rumans)

'Al­tos was re­al­ly a once-in-a-life­time op­por­tu­ni­ty': Hal Bar­ron re­flects on his big move

By all accounts, Hal Barron had one of the best jobs in Big Pharma R&D. He made more than $11 million in 2020, once again reaping more than his boss, Emma Walmsley, who always championed him at every opportunity. And he oversaw a global R&D effort that struck a variety of big-dollar deals for oncology, neurodegeneration and more.

Sure, the critics never let up about what they saw as a rather uninspiring late-stage pipeline, where the rubber hits the road in the Big Pharma world’s hunt for the next big near-term blockbuster, but the in-house reviews were stellar. And Barron was firmly focused on bringing up the success rate in clinical trials, holding out for the big rewards of moving the dial from an average 10% success rate to 20%.

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Executive Director of the EMA Emer Cooke (AP Photo/Geert Vanden Wijngaert)

Eu­ro­pean Par­lia­ment signs off on strength­en­ing drug reg­u­la­tor's abil­i­ty to tack­le short­ages

The European Parliament on Thursday endorsed a plan to increase the powers of the European Medicines Agency, which will be better equipped to monitor and mitigate shortages of drugs and medical devices.

By a vote of 655 to 31, parliament signed off on a provisional agreement reached with the European Council from last October, in which the EMA will create two shortage steering groups (one for drugs, the other for devices), a new European Shortages Monitoring Platform to facilitate data collection and increase transparency, and on funding for the work of the steering groups, task force, working parties and expert panels that are to be established.

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FDA+ roundup: FDA's neu­ro­science deputy de­parts amid on­go­ing Aduhelm in­ves­ti­ga­tions; Califf on the ropes?

Amid increased scrutiny into the close ties between FDA and Biogen prior to the controversial accelerated approval of Aduhelm, the deputy director of the FDA’s office of neuroscience has called it quits after more than two decades at the agency.

Eric Bastings will now take over as VP of development strategy at Ionis Pharmaceuticals, the company said Wednesday, where he will provide senior clinical and regulatory leadership in support of Ionis’ pipeline.

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Sec­ondary patents prove to be key in biosim­i­lar block­ing strate­gies, re­searchers find

While the US biosimilars industry has generally been a disappointment since its inception, with FDA approving 33 biosimilars since 2015, just a fraction of those have immediately followed their approvals with launches. And more than a handful of biosimilars for two of the biggest blockbusters of all time — AbbVie’s Humira and Amgen’s Enbrel — remain approved by FDA but still have not launched because of legal settlements.

Hal Barron (GSK via YouTube)

GSK R&D chief Hal Bar­ron jumps ship to run a $3B biotech start­up, Tony Wood tapped to re­place him

In a stunning switch, GlaxoSmithKline put out word early Wednesday that R&D chief Hal Barron is exiting the company after 4 years — a relatively brief run for the man chosen by CEO Emma Walmsley in late 2017 to turn around the slow-footed pharma giant.

Barron is being replaced by Tony Wood, a close associate of Barron’s who’s taking one of the top jobs in Big Pharma R&D. He’ll be closer to home, though, for GSK. Barron has been running a UK and Philadelphia-based research organization from his perch in San Francisco.

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Chamath Palihapitiya and Pablo Legorreta

Bil­lion­aires Chamath Pal­i­hapi­tiya and Pablo Legor­re­ta hatch an $825M SPAC for cell ther­a­py biotech

Three years after Royalty Pharma chief Pablo Legorreta led a group of investors to buy up a pair of biotechs and create a new startup called ProKidney, the biotech is jumping straight into an $825 million public shell created by SPAC king and tech billionaire Chamath Palihapitiya.

ProKidney was founded 6 years ago but really got going at the beginning of 2019 with the $62 million acquisition of inRegen, which was working on an autologous — from the patient — cell therapy for kidney disease. After extracting kidney cells from patients, researchers expand the cells in the lab and then inject them back into patients, aiming to restore the kidneys of patients suffering from CKD.

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Troy Wilson, Kura CEO

FDA lifts par­tial hold on Ku­ra's Phase Ib AML pro­gram as biotech re­dou­bles mit­i­ga­tion ef­forts

Kura Oncology is clear to resume studies for its early-stage leukemia program after the FDA lifted a clinical hold Thursday afternoon.

Regulators had placed the hold on a Phase Ib study of KO-539, an experimental oral treatment for some genetic subsets of acute myeloid leukemia last November after a patient died while taking the drug. Kura expects to begin enrolling patients again imminently, CEO Troy Wilson told Endpoints News.