Adrian Gottschalk, Foghorn CEO

Mer­ck dan­gles up to $425 mil­lion to team with Flag­ship’s Foghorn Ther­a­peu­tics on drug­ging the shape of DNA

Two years af­ter it first emerged from stealth mode, Flag­ship’s Foghorn Ther­a­peu­tics has nabbed its first Big Phar­ma part­ner as Mer­ck signs on to the biotech’s vi­sion of drug­ging the very shape of DNA.

The deal, worth up to $425 mil­lion but with the up­front cash undis­closed, comes as Foghorn nears a piv­ot to a clin­i­cal stage biotech. The Cam­bridge-based com­pa­ny has added near­ly 60 staffers from the 25 it had when it first emerged out of Flag­ship and, CEO Adri­an Gottschalk said, they have fi­nal­ly re­fined the screen­ing tech­nol­o­gy at the heart of the com­pa­ny, with plans to file their first IND to­wards the end of the year.

“In the last 6 months, ac­tu­al­ly pri­or to the con­ver­sa­tions with Mer­ck, we had in­dus­tri­al­ized our abil­i­ty to in­ter­ro­gate the bi­ol­o­gy,” Gottschalk told End­points News. “We’ve made some very nice progress, re­al­ly start­ing from scratch sev­er­al years ago.”

First found­ed in 2016, Foghorn is one of a spate of re­cent biotechs that try to treat can­cer by tar­get­ing how genes are ex­pressed, as op­posed to try­ing to change the genes them­selves or in­hib­it the pro­teins they code for. Michael Gilman’s Ar­rakis Ther­a­peu­tics is built, like Foghorn, on drug­ging DNA reg­u­la­tors called tran­scrip­tion fac­tors and ear­li­er this year got $190 mil­lion up­front and “sev­er­al bil­lion” in mile­stones for a deal with Roche. Sy­ros, an­oth­er Flag­ship-backed com­pa­ny, at­tract­ed con­sid­er­able buzz sev­er­al years ago by go­ing af­ter so-called “su­per-en­hancers,” though they have since strug­gled to find trac­tion in the clin­ic. More broad­ly, the still-ju­ve­nile field has yield­ed few ma­jor in-hu­man suc­cess­es.

Mer­ck has al­ready sig­naled its be­lief in the ap­proach, at least in cer­tain man­i­fes­ta­tions. Last year, they bought up Pelo­ton Ther­aepeu­tics and its late-stage, kid­ney can­cer tran­scrip­tion fac­tor drug for $1 bil­lion in cash and an­oth­er $1 bil­lion in mile­stones.

Foghorn’s twist, Gottschalk said, is look­ing at how these fac­tors in­ter­act with these spher­i­cal struc­tures on top of DNA, called chro­matin re­mod­el­ing com­plex­es. Ba­si­cal­ly, hu­man DNA con­tains bil­lions of genes, not all of which are turned on at any point in time or in any cell. That DNA sits in tight­ly com­pact­ed strands called chro­matin at the nu­cle­us at the cen­ter of the cell, and one of the ways the body can de­cide which genes need to be turned on is to open and close those strands.

The mol­e­c­u­lar thing that de­ter­mines whether and where genes are turned on is the in­ter­ac­tion be­tween those tran­scrip­tion fac­tors that car­ry in­struc­tions and the chro­matin re­mod­el­ing com­plex that does the open­ing and clos­ing. Foghorn com­pares it to air traf­fic con­trol, the two types of pro­teins telling the genes where to launch and where not to launch. And Gottschalk cit­ed da­ta that sug­gest around 25% of can­cers can be chalked up in part to those bi­o­log­i­cal con­trollers get­ting their sig­nals crossed.

For the last four years, Foghorn has de­vel­oped a high-through­put screen­ing sys­tem to al­low their sci­en­tists to mod­el both the tran­scrip­tion fac­tors and the re­mod­el­ing com­plex­es and fig­ure out which mol­e­cules can mod­u­late each. Though “high-through­put screen­ing” is about as com­mon a word in the drug in­dus­try these days as “pan­cakes” are in the din­er in­dus­try, Gottschalk said that was no easy feat. The chro­matin re­mod­el­ing com­plex­es are just that — com­plex — and they need­ed to set up a sys­tem that could han­dle pro­teins as much as ten times as large as the ones most screens han­dle.

Un­der the new deal, Mer­ck has es­sen­tial­ly li­censed one of the fac­tors Foghorn has just be­gun test­ing, buy­ing ex­clu­siv­i­ty on any po­ten­tial drugs that emerge to tar­get it. In­ter­nal­ly, mean­while, Gottschalk said that af­ter years build­ing their sys­tems, the com­pa­ny is prepar­ing to soon bring a few of its 10 pre­clin­i­cal and un­named pro­grams in­to the clin­ic for sev­er­al ge­net­i­cal­ly-de­fined can­cers that cur­rent­ly have few good treat­ment op­tions.

“I think this bi­ol­o­gy has been un­ex­plored and un­ex­ploit­ed as drug, and I think the time is right,” Gottschalk said.

Late Fri­day ap­proval; Trio of biotechs wind down; Stem cell pi­o­neer finds new fron­tier; Biotech icon to re­tire; 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.

I hope your weekend is off to a nice start, wherever you are reading this email. As for me, I’m trying to catch the tail of the Lunar New Year festivities.

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Pfiz­er lays off em­ploy­ees at Cal­i­for­nia and Con­necti­cut sites

Pfizer has laid off employees at its La Jolla, CA, and Groton, CT sites, according to multiple LinkedIn posts from former employees.

The Big Pharma confirmed to Endpoints News it has let go of some employees, but a spokesperson declined to specify how many workers were impacted and the exact locations affected. Earlier this month, the drug developer had confirmed to Endpoints it was sharpening its focus and doing away with some early research on areas such as rare disease, oncology and gene therapies.

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Eliot Forster, F-star CEO (Rachel Kiki for Endpoints News)

F-star gets down to the wire with $161M sale to Chi­nese buy­er as na­tion­al se­cu­ri­ty con­cerns linger

With the clock ticking on F-star Therapeutics’ takeover by a Chinese buyer, the companies are still scrambling to remove a hold on the deal from the US government’s Committee on Foreign Investment in the United States.

F-star and invoX Pharma said they are “actively negotiating” with CFIUS “about the terms of a mitigation agreement to address CFIUS’s concerns regarding potential national security risks posed by the transaction.”

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Jake Van Naarden, Loxo@Lilly CEO

Lil­ly en­ters ripe BTK field with quick FDA nod in man­tle cell lym­phoma

Eli Lilly has succeeded in its attempt to get the first non-covalent version of Bruton’s tyrosine kinase, or BTK, inhibitors to market, pushing it past rival Merck.

The FDA gave an accelerated nod to Lilly’s daily oral med, to be sold as Jaypirca, for patients with relapsed or refractory mantle cell lymphoma.

The agency’s green light, disclosed by the Indianapolis Big Pharma on Friday afternoon, catapults Lilly into a field dominated by covalent BTK inhibitors, which includes AbbVie and Johnson & Johnson’s Imbruvica, AstraZeneca’s Calquence and BeiGene’s Brukinsa.

Filip Dubovsky, Novavax CMO

No­vavax gets ready to take an­oth­er shot at Covid vac­cine mar­ket with next sea­son plans

While mRNA took center stage at yesterday’s FDA vaccine advisory committee meeting, Novavax announced its plans to deliver an updated protein-based vaccine based on new guidance.

Vaccines and Related Biological Products Advisory Committee (VRBPAC) members voted unanimously in favor of “harmonizing” Covid vaccine compositions, meaning all future vaccine recipients would receive a bivalent vaccine, regardless of whether they’ve gotten their primary series.

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Alon Seri-Levy, Sol-Gel Technologies CEO

Bridge­Bio com­pa­ny sells off rare dis­ease can­di­date to Gal­der­ma part­ner

Israeli biotech Sol-Gel Technologies announced Friday that it got its hands on a rare disease drug candidate from PellePharm for almost $75 million, amid claims that the drug has the potential to reach a $300 million market.

Execs said on a conference call Friday morning that patidegib, a hedgehog signaling pathway blocker, is being investigated to treat Gorlin syndrome, a rare genetic disorder that increases the risk of developing certain kinds of cancer such as basal cell skin cancer and medulloblastoma, a type of brain cancer. The disease affects around one in every 31,000 people, and an estimated 70,000 people worldwide.

Steve Harr, Sana Biotechnology CEO

Four years in, Sana gets first FDA go-ahead to bring can­cer treat­ment in­to the clin­ic

Sana Biotechnology is finally headed to the clinic.

Thursday afternoon, the biotech announced the FDA had cleared its application to start a clinical trial for its allogeneic, or “off-the-shelf,” CAR-T cell therapy targeting the antigen CD19 for patients with B-cell lymphomas and leukemias. Sana said its therapy, dubbed SC291, was designed to evade the immune system, which could help cell therapy produce a more durable response in patients, a concern that has followed such off-the-shelf therapies that use donor cells as opposed to a patient’s own cells.

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Ying Huang, Legend CEO

J&J, Leg­end say Carvyk­ti beat stan­dard ther­a­py in ear­li­er-line blood can­cer

J&J and Legend Biotech’s next step in turning their CAR-T therapy Carvykti into a potential megablockbuster has succeeded, the companies said Friday.

Carvykti achieved the primary endpoint — progression-free survival — in an open-label Phase III study testing the treatment in second- to fourth-line multiple myeloma patients. The CARTITUDE-4 trial, for which there aren’t any hard data yet, represents the biggest development for Carvykti’s ability to compete with Bristol Myers Squibb’s Abecma since its approval last February.

CBER Director Peter Marks (Susan Walsh/AP Images)

FDA ad­vi­so­ry com­mit­tee votes unan­i­mous­ly in fa­vor of bi­va­lent Covid shots re­plac­ing pri­ma­ry se­ries

The FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) voted unanimously in favor of “harmonizing” Covid vaccine compositions, meaning all current vaccine recipients would receive a bivalent vaccine, regardless of whether they’ve gotten their primary series.

The vote marks an effort to clear up confusion around varying formulations and dosing schedules for current primary series and booster vaccines, as well as “get closer to the strains that are circulating,” according to committee member Paul Offit, professor of pediatrics at the Children’s Hospital of Philadelphia.