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.”

Da­ta Lit­er­a­cy: The Foun­da­tion for Mod­ern Tri­al Ex­e­cu­tion

In 2016, the International Council for Harmonisation (ICH) updated their “Guidelines for Good Clinical Practice.” One key shift was a mandate to implement a risk-based quality management system throughout all stages of a clinical trial, and to take a systematic, prioritized, risk-based approach to clinical trial monitoring—on-site monitoring, remote monitoring, or any combination thereof.

Mer­ck scraps Covid-19 vac­cine pro­grams af­ter they fail to mea­sure up on ef­fi­ca­cy in an­oth­er ma­jor set­back in the glob­al fight

After turning up late to the vaccine development game in the global fight against Covid-19, Merck is now making a quick exit.

The pharma giant is reporting this morning that it’s decided to drop development of 2 vaccines — V590 and V591 — after taking a look at Phase I data that simply don’t measure up to either the natural immune response seen in people exposed to the virus or the vaccines already on or near the market.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 98,700+ biopharma pros reading Endpoints daily — and it's free.

Adeno-associated virus-1 illustration; the use of AAVs resurrected the gene therapy field, but companies are now testing the limits of a 20-year-old technology (File photo, Shutterstock)

Af­ter 3 deaths rock the field, gene ther­a­py re­searchers con­tem­plate AAV's fu­ture

Nicole Paulk was scrolling through her phone in bed early one morning in June when an email from a colleague jolted her awake. It was an article: Two patients in an Audentes gene therapy trial had died, grinding the study to a halt.

Paulk, who runs a gene therapy lab at the University of California, San Francisco, had planned to spend the day listening to talks at the American Association for Cancer Research annual meeting, which was taking place that week. Instead, she skipped the conference, canceled every work call on her calendar and began phoning colleagues across academia and industry, trying to figure out what happened and why. All the while, a single name hung in the back of her head.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Jackie Fouse, Agios CEO

Agios scores its sec­ond pos­i­tive round of da­ta for its lead pipeline drug — but that won't an­swer the stub­born ques­tions that sur­round this pro­gram

Agios $AGIO bet the farm on its PKR activator drug mitapivat when it recently decided to sell off its pioneering cancer drug Tibsovo and go back to being a development-stage company — for what CEO Jackie Fouse hoped would be a short stretch before they got back into commercialization.

On Tuesday evening, the bellwether biotech flashed more positive topline data — this time from a small group of patients in a single-arm study. And the executive team plans to package this with its earlier positive results from a controlled study to make its case for a quick OK.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 98,700+ biopharma pros reading Endpoints daily — and it's free.

Vir's CMO says he's sur­prised that a low dose of their he­pati­tis B drug ap­pears promis­ing in ear­ly slice of da­ta — shares soar

Initial topline data from a Phase I study of a new therapeutic for chronic hepatitis B virus was so promising that it surprised even the CMO of the company that produces it.

Vir Biotechnology on Tuesday announced that its VIR-3434 molecule reduced the level of virus surface antigens present in a blinded patient cohort after eight days of the trial with just a single 6 mg dose. Six of the eight patients in the cohort were given the molecule, and the other two a placebo—all six who received the molecule saw a mean antigen reduction of 1.3 log10 IU/mL, Vir said.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 98,700+ biopharma pros reading Endpoints daily — and it's free.

Eli Lil­ly demon­strates that 2 an­ti­bod­ies beat 1 for guard­ing against se­vere Covid-19. But can that solve the first an­ti­body’s prob­lem amid slow up­take?

It seems safe to say that two antibodies are better than one.

Eli Lilly released the largest results yet on Tuesday for their Covid-19 neutralizing antibody cocktail, announcing that the combo reduced deaths and hospitalizations in coronavirus patients by 70%. Across 1,000 patients, there were 11 such events in the treatment group and 36 in the placebo group.

The breakdown for deaths alone was even starker: 10 in the placebo group and 0 in the treatment group. Lilly added that the drug hit secondary endpoints for reducing viral load and alleviating symptoms, although they did not disclose numbers.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 98,700+ biopharma pros reading Endpoints daily — and it's free.

George Yancopoulos (L) and Len Schleifer (Regeneron)

Re­gen­eron touts pos­i­tive pre­lim­i­nary im­pact of its Covid an­ti­body cock­tail, pre­vent­ing symp­to­matic in­fec­tions in high-risk group

Regeneron flipped its cards on an interim analysis of the data being collected for its Covid-19 antibody cocktail used as a safeguard against exposure to the virus. And the results are distinctly positive.

The big biotech reported Tuesday morning that their casirivimab and imdevimab combo prevented any symptomatic infections from occurring in a group of 186 people exposed to the virus through a family connection, while the placebo arm saw 8 of 223 people experience symptomatic infection. Symptomatic combined with asymptomatic infections occurred in 23 people among the 223 placebo patients compared to 10 of the 186 subjects in the cocktail arm.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 98,700+ biopharma pros reading Endpoints daily — and it's free.

Drug­mak­ers 'inch­ing ahead' in in­creas­ing ac­cess to drugs world­wide, with Glax­o­SmithK­line lead­ing the pack

Top drug developers are “inching ahead” in improving access to much-needed drugs around the world — an issue that has been underscored by the Covid-19 pandemic. But there’s still more work to do, Access to Medicine Foundation executive director Jayasree Iyer said.

Every two years, the Access to Medicines Index ranks the top 20 biotechs leading the push for better access to medicines in low- and middle-income countries. This year’s report, published Tuesday, looks at drug access in 106 countries.

Matt Gline (L) and Vivek Ramaswamy

Scoop: Vivek Ra­maswamy is hand­ing the CEO job to a top lieu­tenant at Roivant — but he’s not ex­act­ly leav­ing the biotech scene

Over the past 7 years since founding Roivant, Vivek Ramaswamy has been a constant blur of biotech building motion.

He launched his first biotech with an Alzheimer’s drug he picked up cheap, and watched the experiment implode in one of the highest profile pivotal disasters seen in the last decade. But it didn’t slow the 30-something exec down; if anything, he hit the accelerator. Ramaswamy blazed global paths and went on to raise billions to spur the creation of a large lineup of little Vants promising big things at a fast pace. He sold off a section of the Vant brigade to Sumitomo Dainippon for $3 billion. And more recently the relentless dealmaker has been building a computational discovery arm to add an AI-driven approach to kicking up new programs and companies, supplementing the in-licensing drive while pursuing advances that have created more than 700 jobs at Roivant, with $2 billion in reserves.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.