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.

Stephen Hahn, FDA commissioner (AP Images)

As FDA sets the stage for the first Covid-19 vac­cine EUAs, some big play­ers are ask­ing for a tweak of the guide­lines

Setting the stage for an extraordinary one-day meeting of the Vaccines and Related Biological Products Advisory Committee this Thursday, the FDA has cleared 2 experts of financial conflicts to help beef up the committee. And regulators went on to specify the safety, efficacy and CMC input they’re looking for on EUAs, before they move on to the full BLA approval process.

All of this has already been spelled out to the developers. But the devil is in the details, and it’s clear from the first round of posted responses that some of the top players — including J&J and Pfizer — would like some adjustments and added feedback. And on Thursday, the experts can offer their own thoughts on shaping the first OKs.

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A new chap­ter in the de­cen­tral­ized clin­i­cal tri­al ap­proach

Despite the promised decentralized trial revolution, we haven’t yet moved the needle in a significant way, although we are seeing far bolder commitments to this as we continue to experience the pandemic restrictions for some time to come. The vision of grandeur is one thing, but operationalizing and execution are another and recognising that change, particularly mid-flight on studies, is worthy of thorough evaluation and consideration in order to achieve success. Here we will discuss one of the critical building blocks of a Decentralized and Remote Trial strategy: TeleConsent; more than paper under glass, it is a paradigm change and key digital enabler.

Michel Vounatsos, Biogen CEO (via YouTube)

UP­DAT­ED: Bio­gen spot­lights a pair of painful pipeline set­backs as ad­u­canum­ab show­down looms at the FDA

Biogen has flagged a pair of setbacks in the pipeline, spotlighting the final failure for a one-time top MS prospect while scrapping a gene therapy for SMA after the IND was put on hold due to toxicity.

Both failures will raise the stakes even higher on aducanumab, the Alzheimer’s drug that Biogen is betting the ranch on, determined to pursue an FDA OK despite significant skepticism they can make it with mixed results and a reliance on post hoc data mining. And the failures are being reported as Biogen was forced to cut its profit forecast for 2020 as a generic rival started to erode their big franchise drug.

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David Hung (file photo)

Mas­ter deal­mak­er David Hung re­tools a SPAC sedan in­to a fi­nanc­ing mus­cle ve­hi­cle that leaves his can­cer start­up with $850M and a place on Wall Street

It’s only right that one of the industry’s top dealmakers just completed one of the biggest SPAC-related deals in the pipeline.

David Hung, of Medivation fame, has completed a back flip into the market, merging with EcoR1 Capital’s SPAC Panacea and landing neatly on Wall Street with an $NUVB stock ticker after filling out the blank check in his name. In addition to the $144 million held in the SPAC — provided none of the investors opt out — Hung is getting ahold of $500 million more being chipped in by a slate of institutional investors who feel that Hung could have the keys to another Medivation-style success.

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UP­DAT­ED: CRISPR Ther­a­peu­tics gets a snap­shot of off-the-shelf CAR-T suc­cess in B-cell ma­lig­nan­cies — marred by the death of a pa­tient

Just days after scientific founder Emmanuelle Charpentier shared the Nobel prize for her work on CRISPR/Cas9, CRISPR Therapeutics $CRSP is showing off a snapshot of success in their early-stage study for an off-the-shelf CAR-T approach to CD19+ B cell malignancies — a snapshot marred by the death of a patient who had been given a high dose of the treatment.

Using their gene editing tech, researchers for CRISPR engineered cells from healthy donors into an attack vehicle aimed at cancer, something that has been achieved with great success using patients’ own cells — the autologous approach. But autologous CAR-T is hampered by the more complex vein-to-vein requirement that delays treatment, and now CRISPR Therapeutics along with other players like Allogene are determined to replace the pioneers with CAR-T 2.0.

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Giovanni Caforio, Bristol Myers Squibb CEO (Christopher Goodney/Bloomberg via Getty Images)

Here's how Bris­tol My­er­s' CEO Gio­van­ni Caforio com­plet­ed a $13B buy­out: He moved fast, upped the bid quick­ly and de­mand­ed every­one to keep up

Bristol Myers Squibb CEO Giovanni Caforio does not waste time. He also likes everyone around him to keep up.

Anyone reading over the insider account filed with the SEC of the back-and-forth over his $13 billion buyout of MyoKardia $MYOK could reach only one conclusion: The CEO who had willingly crafted a $74 billion Celgene acquisition had found something else he liked — and he was willing to pay a nice premium to get it.

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Derek Chalmers, Cara Therapeutics CEO

Cara lines up a $440M deal for US rights to its late-stage drug for se­vere itch, with $150M cash on the ta­ble

With plans afoot to file an NDA for what could be its first approved drug, Cara Therapeutics is pivoting its focus to commercialization. And Swiss company Vifor Pharma is willing to surrender up to $440 million to market the candidate in the US.

Cara $CARA CEO Derek Chalmers said an NDA submission is coming this quarter for their intravenous drug Korsuva in chronic kidney disease-associated pruritus (CKD-aP), a severe itching condition. The Stamford, CT-based biotech read out positive topline data from a Phase III pivotal study back in April, and announced plans to approach EMA regulators shortly after filing with the FDA.

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Pfizer CEO Albert Bourla (Drew Angerer/Getty Images)

Pfiz­er is on the verge of claim­ing a multi­bil­lion-dol­lar first-mover ad­van­tage with their Covid-19 vac­cine — an­a­lyst

From the beginning, Pfizer CEO Albert Bourla eschewed government funding for his Covid-19 vaccine work with BioNTech, willing to take all the $2 billion-plus risk of a lightning-fast development campaign in exchange for all the rewards that could fall its way with success. And now that the pharma giant has seized a solid lead in the race to the market, those rewards loom large.

SVB Leerink’s Geoff Porges has been running the numbers on Pfizer’s vaccine, the mRNA BNT162b2 program that the German biotech partnered on. And he sees a $3.5 billion peak in windfall revenue next year alone. Even after the pandemic is brought to heel, though, Porges sees a continuing blockbuster role for this vaccine as people around the world look to guard against a new, thoroughly endemic virus that will pose a permanent threat.

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RBC's Bri­an Abra­hams holds a mock ad­comm on Bio­gen's iffy ad­u­canum­ab da­ta — and most of these ex­perts don't see a path to an ap­proval

As catalysts go, few loom larger than the aducanumab adcomm slated for Nov. 6.

With its big franchise under assault, Biogen is betting the ranch that its mixed late-stage Alzheimer’s data can squeak past the experts and regulators and get onto the market. And the topic — after a decade of Alzheimer’s R&D disasters in what still represents the El Dorado of drug markets — remains in the center ring of discussions around late-stage pipeline prospects.

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