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.

BY­OD Best Prac­tices: How Mo­bile De­vice Strat­e­gy Leads to More Pa­tient-Cen­tric Clin­i­cal Tri­als

Some of the most time- and cost-consuming components of clinical research center on gathering, analyzing, and reporting data. To improve efficiency, many clinical trial sponsors have shifted to electronic clinical outcome assessments (eCOA), including electronic patient-reported outcome (ePRO) tools.

In most cases, patients enter data using apps installed on provisioned devices. At a time when 81% of Americans own a smartphone, why not use the device they rely on every day?

Image: Shutterstock

Eli Lil­ly asks FDA to re­voke EUA for Covid-19 treat­ment

Eli Lilly on Friday requested that the FDA revoke the emergency authorization for its Covid-19 drug bamlanivimab, which is no longer as effective as a combo therapy because of a rise in coronavirus variants across the US.

“With the growing prevalence of variants in the U.S. that bamlanivimab alone may not fully neutralize, and with sufficient supply of etesevimab, we believe now is the right time to complete our planned transition and focus on the administration of these two neutralizing antibodies together,” Daniel Skovronsky, Lilly’s CSO, said in a statement.

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Near­ly a year af­ter Au­den­tes' gene ther­a­py deaths, the tri­al con­tin­ues. What hap­pened re­mains a mys­tery

Natalie Holles was five months into her tenure as Audentes CEO and working to smooth out a $3 billion merger when the world crashed in.

Holles and her team received word on the morning of May 5 that, hours before, a patient died in a trial for their lead gene therapy. They went into triage mode, alerting the FDA, calling trial investigators to begin to understand what happened, and, the next day, writing a letter to alert the patient community so they would be the first to know. “We wanted to be as forthright and transparent as possible,” Holles told me late last month.

The brief letter noted two other patients also suffered severe reactions after receiving a high dose of the therapy and were undergoing treatment. One died a month and a half later, at which point news of the deaths became public, jolting an emergent gene therapy field and raising questions about the safety of the high doses Audentes and others were now using. The third patient died in August.

“It was deeply saddening,” Holles said. “But I was — we were — resolute and determined to understand what happened and learn from it and get back on track.”

Eleven months have now passed since the first death and the therapy, a potential cure for a rare and fatal muscle-wasting disease called X-linked myotubular myopathy, is back on track, the FDA having cleared the company to resume dosing at a lower level. Audentes itself is no more; last month, Japanese pharma giant Astellas announced it had completed working out the kinks of the $3 billion merger and had restructured and rebranded the subsidiary as Astellas Gene Therapies. Holles, having successfully steered both efforts, departed.

Still, questions about precisely what led to the deaths of the 3 boys still linger. Trial investigators released key details about the case last August and December, pointing to a biological landmine that Audentes could not have seen coming — a moment of profound medical misfortune. In an emerging field that’s promised cures for devastating diseases but also seen its share of safety setbacks, the cases provided a cautionary tale.

Audentes “contributed in a positive way by giving a painful but important example for others to look at and learn from,” Terry Flotte, dean of the UMass School of Medicine and editor of the journal Human Gene Therapy, told me. “I can’t see anything they did wrong.”

Yet some researchers say they’re still waiting on Astellas to release more data. The company has yet to publish a full paper detailing what happened, nor have they indicated that they will. In the meantime, it remains unclear what triggered the events and how to prevent them in the future.

“Since Audentes was the first one and we don’t have additional information, we’re kind of in a holding pattern, flying around, waiting to figure out how to land our vehicles,” said Jude Samulski, professor of pharmacology at UNC’s Gene Therapy Center and CSO of the gene therapy biotech AskBio, now a subsidiary of Bayer.

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Pascal Soriot (AstraZeneca via YouTube)

Af­ter be­ing goad­ed to sell the com­pa­ny, Alex­ion's CEO set some am­bi­tious new goals for in­vestors. Then Pas­cal So­ri­ot came call­ing

Back in the spring of 2020, Alexion $ALXN CEO Ludwig Hantson was under considerable pressure to perform and had been for months. Elliott Advisers had been applying some high public heat on the biotech’s numbers. And in reaching out to some major stockholders, one thread of advice came through loud and clear: Sell the company or do something dramatic to change the narrative.

In the words of the rather dry SEC filing that offers a detailed backgrounder on the buyout deal, Alexion stated: ‘During the summer and fall of 2020, Alexion also continued to engage with its stockholders, and in these interactions, several stockholders encouraged the company to explore strategic alternatives.’

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As­traZeneca-Alex­ion merg­er slides through FTC re­view af­ter sup­posed M&A crack­down pos­es no bar­ri­ers

The AstraZeneca-Alexion megamerger received a good sign Friday, despite warning signs of the tides turning against large M&A pharma deals.

US regulators at the FTC have cleared the acquisition for approval, AstraZeneca announced, all but signing off on the deal to go through once it officially closes in the third quarter. AstraZeneca originally said it was planning to buy out Alexion back in December for $39 billion.

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J&J faces CDC ad­vi­so­ry com­mit­tee again next week to weigh Covid-19 vac­cine risks

The CDC’s Advisory Committee on Immunization Practices punted earlier this week on deciding whether or not to recommend lifting a pause on the administration of J&J’s Covid-19 vaccine, but the committee will meet again in an emergency session next Friday to discuss the safety issues further.

The timing of the meeting likely means that the J&J vaccine will not return to the US market before the end of next week as the FDA looks to work hand-in-hand with the CDC to ensure the benefits of the vaccine still outweigh the risks for all age groups.

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Osman Kibar (Samumed, now Biosplice)

Os­man Kibar lays down his hand at Sa­mumed, step­ping away from CEO role as his once-her­ald­ed an­ti-ag­ing biotech re­brands

Samumed made quite the entrance back in 2016, when it launched with some anti-aging programs and a whopping $12 billion valuation. That level of fanfare was nowhere to be found on Thursday, when the company added another $120 million to its coffers and quietly changed its name to Biosplice Therapeutics.

Why the sudden rebrand?

“We did that for obvious reasons,” CFO and CBO Erich Horsley told Endpoints News. “The name Biosplice echoes our science much more than Samumed does.”

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Sanjiv Patel, Relay CEO

In one of their first ever ac­qui­si­tions, Re­lay bets $85M cash on a new AI-based screen­ing ap­proach

Although they’ve never been short for cash, Relay Therapeutics hasn’t been one for acquisitions in its 5-year history, focusing instead on developing its own tools to study how proteins move and advancing molecules off those insights.

On Friday, though, the Third Rock-spun biotech plunked down $85 million in cash and another $185 million in milestones to acquire the small, two-year-old, Google-partnered machine learning company ZebiAI. The deal will allow Relay to add a critical new technology to its early-stage discovery tools now that, with three candidates in the clinic, they’ve shown those tools can pay off, said CEO Sanjiv Patel.

Ex­clu­sive in­ter­view: Pe­ter Marks on why full Covid-19 vac­cine ap­provals could be just months away

Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, took time out of his busy schedule last Friday to discuss with Endpoints News all things related to his work regulating vaccines and the pandemic.

Marks, who quietly coined the name “Operation Warp Speed” before deciding to stick with his work regulating vaccines at the FDA rather than join the Trump-era program, has been the face of vaccine regulation for the FDA throughout the pandemic, and is usually spotted in Zoom meetings seated in front of his wife’s paintings.

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