Nello Mainolfi (Kymera via YouTube)

Out to re­vive R&D, a resur­gent Sanofi pays $150M cash to part­ner up with a pi­o­neer­ing pro­tein degra­da­tion play­er

Frank Nes­tle was ap­point­ed Sanofi’s glob­al head of im­munol­o­gy and in­flam­ma­tion re­search ther­a­peu­tic area just days be­fore dupilum­ab, the block­buster-to-be IL-4 an­ti­body, would be ac­cept­ed for pri­or­i­ty re­view. Af­ter four years of con­sol­i­dat­ing im­munol­o­gy ex­per­tise from mul­ti­ple cor­ners of the Sanofi fam­i­ly and re­cruit­ing new tal­ents to build the dis­cov­ery en­gine, he’s set eyes on a Phase I-ready pro­gram that he be­lieves can grow in­to a Dupix­ent-sized fran­chise.

Frank Nes­tle

And — with the bless­ing of CEO Paul Hud­son and R&D chief John Reed — he’s reach­ing deep in­to the purse.

IRAK4 is the head­lin­er for the col­lab­o­ra­tion with the pro­tein degra­da­tion spe­cial­ists at Kymera, which is bag­ging $150 mil­lion cash and $2 bil­lion in po­ten­tial mile­stones. The Cam­bridge, MA-based biotech is tasked with com­plet­ing first-in-hu­man stud­ies and re­tains the op­tion to share US de­vel­op­ment costs and rev­enue fol­low­ing the Sanofi-led Phase II.

The tar­get sits down­stream of “one of the most val­i­dat­ed path­ways in in­nate im­mu­ni­ty,” Kymera CEO Nel­lo Main­olfi said: It’s where the IL-1 cy­tokine fam­i­ly (think IL-1, IL-33, IL-36) and toll-like re­cep­tor sig­nal­ing con­verges. While ki­nase in­hibitors can take out the ki­nase func­tion, it al­so has a scaf­fold­ing func­tion which con­tin­ues to en­able sig­nal­ing.

“In or­der to ful­ly block the sig­nal­ing, you need to re­move IRAK4,” he said.

Lever­ag­ing E3 lig­as­es to tag the tar­get pro­tein for dis­pos­al, Kymera’s de­grad­er promis­es to pack the bi­o­log­i­cal ef­fect of block­ing all cy­tokine sig­nal­ing with a sin­gle oral pill.

Be­cause it sits at a crit­i­cal node, IRAK4 has been on Sanofi’s radar screen, Nes­tle said. They are al­so well aware of the in­ad­e­qua­cies of a small mol­e­cule ap­proach — such as the one tak­en by Pfiz­er.

“At the mo­ment a lot of pro­tein degra­da­tion is in can­cer, and there’s noth­ing yet in the chron­ic in­flam­ma­to­ry dis­ease space,” he said. “As far as I’m aware, there’s no oth­er com­pa­ny out there who we could have part­nered with to ex­act­ly get to that point.”

While the po­ten­tial ap­pli­ca­tions are broad, der­ma­tol­ogy looms large among the ini­tial plans. There’s atopic der­mati­tis, the itchy skin con­di­tion that ac­counts for a large por­tion of Dupix­ent’s $2.32 bil­lion an­nu­al sales. Nes­tle is al­so keen on hidradeni­tis sup­pu­ra­ti­va, which can cause long-term ab­scess­es and scar­ring.

Sanofi first added pro­tein degra­da­tion to its R&D play­book in Jan­u­ary, anti­ng up $55 mil­lion up­front to ac­cess Nurix Ther­a­peu­tics’ can­cer drug plat­form. The sub­se­quent months have proven to be boom times for the pro­tein degra­da­tion field, as Roche wad­ed in­to the race, a pi­o­neer biotech loaded up and more new play­ers emerged.

Kymera it­self raised $102 mil­lion dur­ing this time, ush­er­ing the IRAK4 pro­gram and an­oth­er tar­get­ing STAT3 to­ward the clin­ic — for both in­flam­ma­tion/im­munol­o­gy and on­col­o­gy.

“Ob­vi­ous­ly when you’re work­ing out­side of tar­get­ed on­col­o­gy, you ac­tu­al­ly bring a lot more com­plex­i­ty giv­en that you’re go­ing af­ter a va­ri­ety of cell pop­u­la­tion and not just the one can­cer cell pop­u­la­tion,” Main­olfi said.

But just like their re­search blue­print­ing a E3 lig­ase whole body at­las, the CTO-turned-CEO sees it as es­sen­tial in­vest­ment to cre­ate a lead­ing, ful­ly in­te­grat­ed pro­tein degra­da­tion-fo­cused com­pa­ny. He’s al­so look­ing to add some­where be­tween 20 and 40 staffers to the 60-strong team with­in the next six months or so.

For Sanofi, it’s a bet that aligns well with a new­ly re­vamped R&D struc­ture where spe­cial­i­ty care and vac­cines take cen­ter stage.

“We’re com­ing from where there was not a lot of im­munol­o­gy, but we’ve built a high qual­i­ty team and that doesn’t mean we have the not in­vent­ed here syn­drome. If we see a great com­pound, a great col­lab­o­ra­tion with some of the best in the in­dus­try like Kymera, we go for it,” he said. “As you know, phar­ma can be a slow mov­ing train, so we’re build­ing this foun­da­tion but once the foun­da­tion is built, there’s one clin­i­cal can­di­date af­ter an­oth­er which is go­ing to come in­to the im­munol­o­gy/in­flam­ma­tion space.”

The DCT-OS: A Tech­nol­o­gy-first Op­er­at­ing Sys­tem - En­abling Clin­i­cal Tri­als

As technology-enabled clinical research becomes the new normal, an integrated decentralized clinical trial operating system can ensure quality, deliver consistency and improve the patient experience.

The increasing availability of COVID-19 vaccines has many of us looking forward to a time when everyday things return to a state of normal. Schools and teachers are returning to classrooms, offices and small businesses are reopening, and there’s a palpable sense of optimism that the often-awkward adjustments we’ve all made personally and professionally in the last year are behind us, never to return. In the world of clinical research, however, some pandemic-necessitated adjustments are proving to be more than emergency stopgap measures to ensure trial continuity — and numerous decentralized clinical trial (DCT) tools and methodologies employed within the last year are likely here to stay as part of biopharma’s new normal.

Ron DePinho (file photo)

A 'fly­over' biotech launch­es in Texas with four Ron De­Pin­ho-found­ed com­pa­nies un­der its belt

In his 13 years at Genzyme, Michael Wyzga noticed something about East Coast drugmakers. Execs would often jet from Boston or New York to San Francisco to find more assets, and completely miss the work being done in flyover states, like Texas or Wisconsin.

“If it doesn’t come out of MGH or MIT or Harvard, probably not that interesting,” he said of the mindset.

Now, he and some well-known industry players are looking to change that, and they’ve reeled in just over $38 million to do it.

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Onno van de Stolpe, Galapagos CEO (Thierry Roge/Belga Mag/AFP via Getty Images)

Gala­pa­gos chops in­to their pipeline, drop­ping core fields and re­or­ga­niz­ing R&D as the BD team hunts for some­thing 'trans­for­ma­tive'

Just 5 months after Gilead gutted its rich partnership with Galapagos following a bitter setback at the FDA, the Belgian biotech is hunkering down and chopping the pipeline in an effort to conserve cash while their BD team pursues a mission to find a “transformative” deal for the company.

The filgotinib disaster didn’t warrant a mention as Galapagos laid out its Darwinian restructuring plans. Forced to make choices, the company is ditching its IPF molecule ’1205, while moving ahead with a Phase II IPF study for its chitinase inhibitor ’4617.

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Stéphane Bancel, Getty

Mod­er­na CEO brush­es off US sup­port for IP waiv­er, eyes more than $19B in Covid-19 vac­cine sales in 2021

Moderna is definitively more concerned with keeping pace with Pfizer in the race to vaccinate the world against Covid-19 than it is with Wednesday’s decision from the Biden administration to back an intellectual property waiver that aims to increase vaccine supplies worldwide.

In its first quarter earnings call on Thursday, Moderna CEO Stéphane Bancel shrugged off any suggestion that the newly US-backed intellectual property waiver would impact his company’s vaccine or bottom line. Still, the company’s stock price fell by about 9% in early morning trading.

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Joe Wiley, Amryt CEO

A biotech with a yen for pricey rare dis­ease drugs — and bar­gain base­ment shop­ping — adopts an­oth­er or­phan in lat­est M&A pact

After making it through a long, painful haul to get past a CRL and on to an FDA approval last summer, little Chiasma has found a buyer.

Amryt $AMYT, a company known for its appetite for acquiring expensive drugs for rare diseases at bargain prices, snagged Chiasma and its acromegaly drug Mycapssa (octreotide) capsules in an all-stock deal — with an exchange of 0.396 shares of Amryt for every share of Chiasma.

Ad­comm splits slight­ly in fa­vor of FDA ap­prov­ing Chemo­Cen­tryx’s rare dis­ease drug

The FDA’s Arthritis Advisory Committee on Thursday voted 10 for and 8 against the approval of ChemoCentryx’s $CCXI investigational drug avacopan as a treatment for adults with a rare and serious disease known as anti-neutrophil cytoplasmic autoantibody (ANCA)-vasculitis.

The vote on whether the FDA should approve the drug was preceded by a split vote of 9 to 9 on whether the efficacy data support approval, and 10 to 8 that the safety profile of avacopan is adequate enough to support approval.

Paul Hastings, Nkarta CEO

With no up­front pay­ment or mile­stones on the line, Nkar­ta and CRISPR join forces on CAR-NK search

Most deals in biotech come with hefty upfront payments attached, and the promise of big biobucks if a program works out. Not this one.

Nkarta has struck what CEO Paul Hastings calls a “real collaboration” with CRISPR Therapeutics to co-develop and commercialize two CAR-NK therapies, in addition to an NK+T program. The duo will split all R&D costs — and any worldwide profits — 50/50, Hastings said.

Brent Saunders (Richard Drew, AP Images)

OcuWho? Star deal­mak­er turned aes­thet­ics czar Brent Saun­ders flips back in­to biotech. But who’s he team­ing up with now?

Brent Saunders went on a tear of headline-blazing deals building Allergan, merging and rearranging a variety of big companies into one before an M&A pact with Pfizer blew up and sent him on a bout of biotech drug deals. That didn’t work so well, so under pressure, he got his buyout at AbbVie — which needed a big franchise like Botox. And it was no big surprise to see him riding the SPAC wave into a recent $1 billion-plus deal that left him in the executive chairman’s seat at an aesthetics outfit — now redubbed The Beauty Health Company — holding a big chunk of the equity.

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Drug pric­ing watch­dog joins the cho­rus of crit­ics on Bio­gen's ad­u­canum­ab: What about charg­ing $2,560 per year?

As if Biogen’s aducanumab isn’t controversial enough, the researchers at drug pricing watchdog ICER have drawn up the contours of a new debate: If the therapy does get approved for Alzheimer’s by June, what price should it command?

Their answer: At most $8,290 per year — and perhaps as little as $2,560.

Even at the top of the range, the proposed price is a fraction of the $50,000 that Wall Street has reportedly come to expect (although RBC analyst Brian Abrahams puts the consensus figure at $11.5K). With critics, including experts on the FDA’s advisory committee, making their fierce opposition to aducanumab’s approval loud and clear, the pricing pressure adds one extra wrinkle Biogen CEO Michel Vounatsos doesn’t need as he orders full-steam preparation for a launch.