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.”

Health­care Dis­par­i­ties and Sick­le Cell Dis­ease

In the complicated U.S. healthcare system, navigating a serious illness such as cancer or heart disease can be remarkably challenging for patients and caregivers. When that illness is classified as a rare disease, those challenges can become even more acute. And when that rare disease occurs in a population that experiences health disparities, such as people with sickle cell disease (SCD) who are primarily Black and Latino, challenges can become almost insurmountable.

The End­points 11: They've got mad mon­ey and huge am­bi­tions. It's time to go big or go home

These days, selecting a group of private biotechs for the Endpoints 11 spotlight begins with a sprint to get ahead of IPOs and the M&A teams at Big Pharma. I’ve had a couple of faceplants earlier this year, watching some of the biotechs on my short list choose a quick leap onto Nasdaq or into the arms of a buyer.

Vividion, you would have been a great pick for the Endpoints 11. I’m sorry I missed you.

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Dave Lennon, former president of Novartis Gene Therapies

So what hap­pened with No­var­tis Gene Ther­a­pies? Here's your an­swer

Over the last couple of days it’s become clear that the gene therapy division at Novartis has quietly undergone a major reorganization. We learned on Monday that Dave Lennon, who had pursued a high-profile role as president of the unit with 1,500 people, had left the pharma giant to take over as CEO of a startup.

Like a lot of the majors, Novartis is an open highway for head hunters, or anyone looking to staff a startup. So that was news but not completely unexpected.

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Jacob Van Naarden (Eli Lilly)

Ex­clu­sives: Eli Lil­ly out to crash the megablock­buster PD-(L)1 par­ty with 'dis­rup­tive' pric­ing; re­veals can­cer biotech buy­out

It’s taken 7 years, but Eli Lilly is promising to finally start hammering the small and affluent PD-(L)1 club with a “disruptive” pricing strategy for their checkpoint therapy allied with China’s Innovent.

Lilly in-licensed global rights to sintilimab a year ago, building on the China alliance they have with Innovent. That cost the pharma giant $200 million in cash upfront, which they plan to capitalize on now with a long-awaited plan to bust up the high-price market in lung cancer and other cancers that have created a market worth tens of billions of dollars.

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Who are the women su­per­charg­ing bio­phar­ma R&D? Nom­i­nate them for this year's spe­cial re­port

The biotech industry has faced repeated calls to diversify its workforce — and in the last year, those calls got a lot louder. Though women account for just under half of all biotech employees around the world, they occupy very few places in C-suites, and even fewer make it to the helm.

Some companies are listening, according to a recent BIO survey which showed that this year’s companies were 2.5 times more likely to have a diversity and inclusion program compared to last year’s sample. But we still have a long way to go. Women represent just 31% of biotech executives, BIO reported. And those numbers are even more stark for women of color.

FDA+ roundup: Bs­U­FA III ready for show­time, court tells FDA to re-work com­pound­ing plan, new guid­ance up­dates and more

The FDA has now spelled out what exactly will be included in the third iteration of Biosimilar User Fee Act (BsUFA) from 2023 through 2027, which similarly to the prescription drug deal, sets fees that industry has to pay for submitting applications, in exchange for firm timelines that the agency must meet.

This latest deal includes several sweeteners for the biosimilar industry, which has yet to make great strides in the US market, with shorter review timelines for safety labeling updates and updates to add or remove an indication that does not contain efficacy data.

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Paul Hudson, Sanofi CEO (Raphael Lafargue/Abaca/Sipa USA; Sipa via AP Images)

In­side look: How a po­ten­tial part­ner­ship turned in­to a $1.9B buy­out for Sanofi

A couple of months before the FDA was set to make a decision on Kadmon’s so-called “knock-your-socks-off kind of results” for its chronic graft-versus-host disease drug, Sanofi put out feelers for a potential collaboration. But an early approval triggered an offer to buy the company outright — and Sanofi didn’t win without a fight, according to an inside look.

Sanofi’s head of business development and licensing Matthieu Merlin reached out to Kadmon on June 26 with a simple request: He wanted to introduce himself and explore potential partnerships, according to an SEC filing. It had been several months since Kadmon’s belumosudil arrived on the FDA’s doorstep, and after delaying their decision once, regulators said they’d have an answer by Aug. 30. But Sanofi wasn’t the only company interested in getting to know the execs over at Kadmon.

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Jean Bennett (Brent N. Clarke/Invision/AP Images)

Lux­tur­na in­ven­tor Jean Ben­nett starts a new gene ther­a­py com­pa­ny to tack­le rare dis­eases left be­hind by phar­ma, VCs

A few years ago Jean Bennett found herself in a surprising place for a woman who invented the first gene therapy ever approved in the United States: No one, it seemed, wanted her work.

Bennett, who designed and co-developed Luxturna, approved in 2018 for a rare form of blindness, had kept building new gene therapies for eye diseases at her University of Pennsylvania lab. But although the results in animals looked promising, pharma companies and investors kept turning down the pedigreed ophthalmology professor.

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Jay Bradner (Jeff Rumans for Endpoints News)

Div­ing deep­er in­to in­her­it­ed reti­nal dis­or­ders, No­var­tis gob­bles up an­oth­er bite-sized op­to­ge­net­ics biotech

Right about a year ago, a Novartis team led by Jay Bradner and Cynthia Grosskreutz at NIBR swooped in to scoop up a Cambridge, MA-based opthalmology gene therapy company called Vedere. Their focus was on a specific market niche: inherited retinal dystrophies that include a wide range of genetic retinal disorders marked by the loss of photoreceptor cells and progressive vision loss.

But that was just the first deal that whet their appetite.

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