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.”

Jan Hatzius (Photographer: Christopher Goodney/Bloomberg via Getty Images)

When will it end? Gold­man econ­o­mist gives late-stage vac­cines a good shot at tar­get­ing 'large shares' of the US by mid-2021 — but the down­side is daunt­ing

It took decades for hepatitis B research to deliver a slate of late-stage candidates capable of reining the disease in.

With Covid-19, the same timeline has devoured all of 5 months. And the outcome will influence the lives of billions of people and a multitrillion-dollar world economy.

Count the economists at Goldman Sachs as optimistic that at least one of these leading vaccines will stay on this furiously accelerated pace and get over the regulatory goal line before the end of this year, with a shot at several more near-term OKs. That in turn should lead to the production of billions of doses of vaccines that can create herd immunity in the US by the middle of next year, with Europe following a few months later.

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UP­DAT­ED: No­vavax her­alds the lat­est pos­i­tive snap­shot of ear­ly-stage Covid-19 vac­cine — so why did its stock briefly crater?

High-flying Novavax $NVAX became the latest of the Covid-19 vaccine players to stake out a positive set of biomarker data from its early-stage look at its vaccine in humans.

Their adjuvanted Covid-19 vaccine was “well-tolerated and elicited robust antibody responses numerically superior to that seen in human convalescent sera,” the company noted. According to the biotech:

All subjects developed anti-spike IgG antibodies after a single dose of vaccine, many of them also developing wild-type virus neutralizing antibody responses, and after Dose 2, 100% of participants developed wild-type virus neutralizing antibody responses. Both anti-spike IgG and viral neutralization responses compared favorably to responses from patients with clinically significant COVID‑19 disease. Importantly, the IgG antibody response was highly correlated with neutralization titers, demonstrating that a significant proportion of antibodies were functional.

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Ver­sant de­buts Ridge­line's start­up #4, armed with $30M and al­ter­na­tive TCR cell ther­a­pies for sol­id tu­mors

For all the iterations and advances in TCR therapies for cancer, any experimental treatments involving T cell receptors share one trait: By definition, they only recognize antigens presented as peptides on the major histocompatibility complex (MHC) on cells.

Versant reckons it’s time to expand the arsenal. With $30 million in initial funding, its Ridgeline Discovery Engine in Switzerland has been working on a non-peptidic approach that it says has tumor-agnostic potential, especially in solid tumors. They’ve named it Matterhorn, after a Swiss mountain as they did with the three other companies that have emerged from the Basel-based incubator.

J&J gets a fresh OK for es­ke­t­a­mine, but is it re­al­ly the game-chang­er for de­pres­sion Trump keeps tweet­ing about?

Backed by an enthusiastic set of tweets from President Trump and a landmark OK for depression, J&J scooped up a new approval from the FDA for Spravato today. But this latest advance will likely bring fresh scrutiny to a drug that’s spurred some serious questions about the data, as well as the price.

First, the approval.

Regulators stamped their OK on the use of Spravato — developed as esketamine, a nasal spray version of the party drug Special K or ketamine — for patients suffering from major depressive disorder with acute suicidal ideation or behavior.

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Covid-19 roundup: BAR­DA qui­et­ly pulls plug on IL-6 drugs; BioN­Tech and Fo­s­un be­gin mR­NA tri­al

IL-6 inhibitors showed some early promise in potentially treating Covid-19 patients, but recent trial flops have dashed hopes. Now it appears BARDA has officially pulled the plug.

The HHS office’s website has quietly updated to reflect that it is “no longer supporting product development” for Covid-19 in both Actemra (tocilizumab) and Kevzara (sarilumab), dealing a blow to the Roche and Regeneron/Sanofi drugs. This all but assures that IL-6 drugs repurposed to treat Covid-19 are essentially dead in the water.

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CF Foun­da­tion, Long­wood team on new in­cu­ba­tor for com­pa­nies with cut­ting-edge CF treat­ments

Nine months after launching a $500 million hunt for a cure for cystic fibrosis, the Cystic Fibrosis Foundation said it will use a portion of those funds to do something it has never done before: help launch new companies.

The CF Foundation, whose venture philanthropy efforts helped fund Vertex’s line of powerful CF drugs, is teaming with Longwood Fund to create a CF incubator. The incubator will identify new companies with platforms or technologies that can be applied in the rare genetic condition. The partners can then finance early development in exchange for a commitment from the companies to focus on applications in cystic fibrosis.

Kiersten Stead, John Hamer (DCVC Bio)

Deep tech, round 2: DCVC Bio bags $350M fund to chase the tip of the life sci­ence spear

It took one trip from San Francisco to Vancouver for Kiersten Stead and her DCVC Bio crew to feel confident about throwing their weight — and cash — behind AbCellera.

CEO Carl Hansen’s academic background and the potential of the platform, which combined machine vision and robotics with microfluidics, were promising. But the site visit sealed the Series A deal, where DCVC was the lead and only investor.

Mer­ck scoops up a PhII J&J dis­card in a bar­gain-base­ment deal. And this time they’re shoot­ing at NASH

When J&J turned to South Korea’s Hanmi for a GLP-1/glucagon dual receptor agonist obesity drug, the pharma giant paid $105 million in a cash upfront for the licensing rights and plotted a big clinical trial program to test it. A year ago, like a few of Hanmi’s big partners, J&J reviewed their trial data and walked away, handing it back.

Now Merck is stepping up to grab it for their NASH pipeline — and they got it a lot cheaper than J&J.

Igor Splawski (CureVac)

Cure­Vac nabs a top No­var­tis sci­en­tist for CSO slot as mR­NA vac­cines seize the spot­light

One of the key players in the race to develop a new mRNA vaccine to fight Covid-19 has reshuffled the top spots in the executive suite. And they’re bringing in a Novartis vet out of Harvard to spearhead their work on mRNA.

CureVac, which just filed for an IPO that’s still taking shape, has formally handed Franz-Werner Haas the CEO title, after giving it to him on an interim basis. And the still rather stealthy German biotech largely owned by billionaire Dietmar Hopp has recruited Igor Splawski as its chief scientific officer.

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