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.”

A new era of treat­ment: How bio­mark­ers are chang­ing the way we think about can­cer

AJ Patel was recovering from a complicated brain surgery when his oncologist burst into the hospital room yelling, “I’ve got some really great news for you!”

For two years, Patel had been going from doctor to doctor trying to diagnose his wheezing, only to be dealt the devastating news that he had stage IV lung cancer and only six months to live. And then they found the brain tumors.

“What are you talking about?” Patel asked. He had never seen an oncologist so happy.

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David Ricks, Eli Lilly CEO (David Paul Morris/Bloomberg via Getty Images)

Eli Lil­ly set to in­vest $2.1B in home state man­u­fac­tur­ing boost

Eli Lilly is looking to expand its footprint in its home Hoosier State by making a major investment in manufacturing.

The pharma is investing $2.1 billion in two new manufacturing sites at Indiana’s LEAP Lebanon Innovation and Research District in Boone County, northwest of Lilly’s headquarters in Indianapolis.

The two new facilities will expand Lilly’s manufacturing network for active ingredients and new therapeutic modalities, including genetic medicines, according to a press release.

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US sees spike in Paxlovid us­age as Mer­ck­'s mol­nupi­ravir and As­traZeneca's Evusheld are slow­er off the shelf

New data from HHS show that more than 162,000 courses of Pfizer’s Covid-19 antiviral Paxlovid were administered across the US over the past week, continuing a streak of increased usage of the pill, and signaling not only rising case numbers but more awareness of how to access it.

In comparison to this week, about 670,000 courses of the Pfizer pill have been administered across the first five months since Paxlovid has been on the US market, averaging about 33,000 courses administered per week in that time.

Pfiz­er and CD­MOs ramp up Paxlovid man­u­fac­tur­ing with Kala­ma­zoo plant ex­pan­sion lead­ing the way

As the Covid-19 pandemic continues to evolve, pharma companies and manufacturers are exploring how to step up production on antivirals.

Pfizer is planning to expand its Kalamazoo-area facility to increase manufacturing capabilities for the oral Covid-19 antiviral Paxlovid, according to a report from Michigan-based news site MLive. The expansion of the facility, which serves as Pfizer’s largest manufacturing location, is expected to create hundreds of “high-skilled” STEM jobs, MLive reported. No details about the project’s cost and timeline have been released, but according to MLive, Pfizer will announce the details of the expansion at some point in early June.

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FDA spells out the rules and re­stric­tions for states seek­ing to im­port drugs from Cana­da

The FDA is offering more of an explanation of the guardrails around its program that may soon allow states to import prescription drugs in some select circumstances from Canada, but only if such imports will result in significant cost reductions for consumers.

While the agency has yet to sign off on any of the 5 state plans in the works so far, and PhRMA’s suit to block the Trump-era rule allowing such imports is stalled, the new Q&A guidance spells out the various restrictions that states will have to abide by, potentially signaling that a state approval is coming.

Franz-Werner Haas, CureVac CEO (Christoph Schmidt/picture-alliance/dpa/AP Images)

Tak­ing an­oth­er shot at mR­NA glo­ry, Cure­Vac inks on­col­o­gy pact while keep­ing up with Covid work

CureVac may have lost out on the initial mRNA race to bring a Covid-19 vaccine to the market, but it’s still eager to prove that it has what it takes to be a serious player in the field.

As it updates investors on its second-generation vaccine candidates for infectious diseases in Q1 results, the German biotech says it’s beefing up its oncology pipeline.

To that end, it has struck a new collaboration with Belgium’s myNEO, which boasts of a neoantigen discovery and selection platform, to identify new targets for mRNA immunotherapies.

Pfizer CEO Albert Bourla at the World Economic Forum (Gian Ehrenzeller/Keystone via AP Images)

All about ac­cess: Pfiz­er moves to a non-prof­it mod­el for drug sales in 45 low­er-in­come coun­tries

Leading the way to increase access to cheaper drugs worldwide, Pfizer said Wednesday it will provide all current and future patent-protected medicines and vaccines available in the US or EU on a not-for-profit basis to about 1.2 billion people in 45 lower-income countries.

Rwanda, Ghana, Malawi, Senegal and Uganda are the first five countries to sign on to this accord, which will also seek to blaze new paths for quick and efficient regulatory and procurement processes to reduce the usual delays in making new medicines and vaccines available in these countries.

Almirall is tapping artificial intelligence on behalf of its sales force for insights and efficiencies. (via Shutterstock)

Almi­rall rolls out sales rep ar­ti­fi­cial in­tel­li­gence sys­tem, cut­ting pre-call prep and 'wind­shield time'

Dermatology specialty pharma Almirall is making its sales reps smarter. Not with extra training or educational courses, but instead with artificial intelligence tools.

It began a soft launch of a sales rep AI and machine learning platform it calls Polaris last August in one of its 7 US coverage regions. The platform from Aktana gathers information from across Almirall internal sources and external ones – such as claims and prescribing data – to generate insights for reps. Now, instead of spending hours prepping for a sales call, Polaris can generate details about a physician’s preferences, past behaviors and prescription habits for reps in minutes, said Almirall head of commercial operations Vincent Cerio.

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Te­va, Al­ler­gan reach yet an­oth­er opi­oid set­tle­ment — ef­fec­tive­ly end­ing WV tri­al

Teva and Allergan have reached settlements with multiple states over their involvement in the opioid crisis. Their latest is worth 9 figures.

West Virginia attorney general Patrick Morrisey announced the newest settlement, worth $161.5 million, at a press conference on Wednesday. The deal would resolve claims that the companies helped fuel the state’s opioid epidemic. If it goes through, it could become the largest state-negotiated settlement in West Virginia’s history, according to Reuters.