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.

Roger Perl­mut­ter lines up deals, fresh fund­ing at Eikon; Sec­ond RSV vac­cine ap­proved; Sev­er­al biotechs flash­ing red; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

As you come back to our website this weekend for ASCO news, don’t forget to check out our updated event lineup at BIO, which will cover everything from the current state of VC investing in biotech to top pharma R&D chiefs discussing how to make pipeline decisions.

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Image courtesy of The Janssen Pharmaceutical Companies of Johnson & Johnson.

Pro­tect­ing the glob­al phar­ma­ceu­ti­cal in­no­va­tion ecosys­tem – what’s at stake?

We are living in a new era of healthcare that is rapidly advancing progress impacting patient outcomes and experiences. We’ve seen a remarkable pace of transformational innovation, applied research, and advanced clinical development over the last decade.

Despite this tremendous progress, there is much more work to be done, and patients are counting on us – now more than ever – to continue that momentum. At the heart of our industry is a focus on developing and delivering medicines for some of the world’s most challenging diseases, including those that have few or no effective treatments today.

Roger Perlmutter, Eikon Therapeutics CEO

Roger Perl­mut­ter builds Eikon's pipeline with deal-mak­ing flur­ry, rais­ing $106M more

Eikon Therapeutics announced three business development deals on Thursday, effectively dropping in a pipeline of cancer drugs alongside more than $100 million in fresh funding.

The Hayward, CA-based company has become one of biotech’s richest startups since its 2019 founding, having raised nearly $775 million. It’s developing a massive, automated research approach built around Nobel Prize-winning microscope science to peer inside cells and watch proteins in action. After its Series B last year, PitchBook reported a $3.02 billion valuation. And while CEO Roger Perlmutter declined to comment on that figure, he said its first tranche of nearly $106 million in Series C funding is a “meaningful step-up to our Series B valuation.”

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The Modulo Bio team with CEO Michael Horowitz (fourth from right in semicircle)

Ex­clu­sive: With $8M, neu­ro start­up Mod­u­lo Bio emerges to test small mol­e­cules for ALS, de­men­tia in CEO’s per­son­al mis­sion

Embarking on a personal mission after his best friend’s mother was diagnosed with a mutation-driven case of frontotemporal dementia, Michael Horowitz has pulled together $8 million in venture funding at Modulo Bio to create small molecules for neurodegenerative diseases.

The San Diego and Bay Area biotech will select its lead development candidate and some backup options within six months and then raise a Series A to investigate therapeutics for C9orf72 mutation-driven cases of ALS and frontotemporal dementia, Horowitz told Endpoints News.

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Grail’s blood test charts path for di­ag­nos­ing pa­tients sus­pect­ed of hav­ing can­cer in large study: #AS­CO23

Grail’s vision is simple but bold. The blood testing company has long held that people are often diagnosed with cancer too late. If seemingly healthy people were screened for early signs of the disease before symptoms appear, they may be able to get more effective treatments that nip cancer in the bud.

That premise is the basis of Grail’s commercial blood test, Galleri, which searches for the genetic fingerprints of cancer in the blood. The test, launched in 2021, reaped $55 million in sales last year, but now the company is setting its sights on a new market: patients suspected of having cancer due to symptoms such as abdominal pain, rectal bleeding or unexplained weight loss. Rather than administering expensive scans or conducting invasive biopsies right away, Grail hopes doctors will consider a simple blood test.

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Bala Venkataraman, Avego founder and managing partner (L), and Bruno Paquin, AtomVie CEO

Cana­di­an CD­MO se­cures more fund­ing to get its man­u­fac­tur­ing site up and run­ning

AtomVie Global Radiopharma Inc, a Canadian radiopharmaceutical contract manufacturer, has received additional funds to get its manufacturing facility up and running.

The manufacturer announced that it has raised an additional 90 million Canadian dollars ($66.9 million) in a “Tranche 2 Series A round,” led by the healthcare investment firm Avego Management. The company previously announced a $40 million Series A round last year, which contributed to the construction of a new 64,000-square-foot facility.

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GSK pro­motes rou­tine im­mu­niza­tions for adults amid post-pan­dem­ic vac­cine back­slide

GSK launched a new initiative on Thursday and committed up to $1 million in grant funding to improve adult routine vaccination rates.

While the pandemic spotlight was trained on the race for novel Covid-19 vaccines, other routine vaccination rates plummeted, raising concerns that missed doses may put children and even some adults at risk of preventable diseases such as measles or shingles. The World Health Organization last year reported the largest drop in childhood vaccinations in roughly three decades.

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Tammie Denyse speaks up about Black women and breast cancer inequity in Gilead's first TikTok campaign. (Gilead Sciences)

Gilead joins Tik­Tok with on­col­o­gy aware­ness cam­paign fea­tur­ing di­verse group of can­cer ad­vo­cates

Gilead Sciences is taking over the opening page on TikTok for the next two weeks. A Gilead-sponsored video, featuring cancer advocates talking about equity and other issues, will show up as the landing page, called the “For You” page, for millions of TikTok watchers.

The cancer awareness campaign will begin on Monday and run for two weeks, a Gilead spokesperson told Endpoints News. The TikTok ad debut is timed around the ASCO medical conference, but the work is aimed more broadly at healthcare professionals, as well as people touched by cancer and people interested in advancing Black and general health equity.

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Dol­lars flow with three new pub­lic of­fer­ings, two pri­vate place­ments

A handful of biotechs announced plans to raise money this week.

First up is Hookipa Pharma, which announced Wednesday night that it is looking to raise $50 million in gross earnings in a public offering — by selling 22.9 million shares of common stock at $1.31 a share. The biotech, which is developing immuno-oncology treatments and infectious disease programs, is also offering roughly 15,000 shares of non-voting preferred stock, which could be converted into 1,000 shares of common stock for a price of $1,310 each.

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