Nello Mainolfi via YouTube

At­las-backed Kymera grabs $102M as its pro­tein degra­da­tion tech­nol­o­gy heads in­to clin­ic

When Bruce Booth and Nel­lo Main­olfi start­ed plan­ning a pro­tein degra­da­tion com­pa­ny, the field was open and sparse, dot­ted with a cou­ple of hope­ful star­tups and larg­er play­ers mak­ing ex­plorato­ry for­ays. Booth called it a “broad new modal­i­ty with plen­ty of free­dom to op­er­ate across po­ten­tial­ly every ther­a­peu­tic area and dis­ease state.”

Four years lat­er, Kymera Ther­a­peu­tics is look­ing to be­come one of the first of what will like­ly be many pro­tein degra­da­tion com­pa­nies to en­ter the clin­ic. The com­pa­ny an­nounced $102 mil­lion in Se­ries C fund­ing and a plan to bring its lead drug tar­get­ing IRAK4 in­to the first tri­als by next year. Biotech­nol­o­gy Val­ue Fund and Red­mile Group led the round.

“We are at the cusp of tran­si­tion­ing from a re­search to a de­vel­op­ment or­ga­ni­za­tion — or, I should say, to a re­search and de­vel­op­ment or­ga­ni­za­tion,” Main­olfi, now the CEO, told End­points News.  “This fi­nanc­ing re­al­ly al­lows to build to­ward the con­cept of build­ing a ful­ly in­te­grat­ed biotech com­pa­ny around pro­tein degra­da­tion, which I think is prob­a­bly one of the most trans­for­ma­tive modal­i­ties.”

As of to­day, Kymera would like­ly be the sec­ond biotech to bring a pro­tein de­grad­er in­to the clin­ic. A year ago, Arv­inas – whose founder Craig Crews pub­lished some of the first work show­ing how pro­tein degra­da­tion could be drugged — brought what it be­lieves to be the first pro­tein de­grad­er in­to hu­man test­ing, an an­dro­gen re­cep­tor-tar­get­ing drug for prostate can­cer. C4 Ther­a­peu­tics, the oth­er ma­jor start­up that ex­ist­ed when Kymera launched, has part­ner­ships with Bio­gen, Roche, and Dana-Far­ber, but no ther­a­pies in the clin­ic.

The pro­tein is a ki­nase im­pli­cat­ed in sev­er­al can­cers. Small mol­e­cules can in­hib­it IRAK4’s prop­er­ties as a ki­nase, but the pro­tein al­so func­tions as a scaf­fold­ing pro­tein that helps build the my­d­do­some pro­tein com­plex. The com­plex is sup­posed to be ac­ti­vat­ed to re­spond to in­fec­tion but can some­times ac­ti­vate aber­rant­ly, lead­ing to in­flam­ma­to­ry or au­toim­mune dis­ease.

The idea be­hind pro­tein degra­da­tion is that in­stead of send­ing a mol­e­cule to block the pro­tein’s ki­nase bind­ing site — and leav­ing the rest of the pro­tein in­tact and func­tion­ing — re­searchers can re­move the pro­tein en­tire­ly. They do this by hi­jack­ing the body’s in­ter­nal sys­tem to re­move pro­teins that are mis­fold­ed or are in over­abun­dance. En­zymes called E3 lig­as­es tag un­want­ed pro­teins with a pro­tein called ubiq­ui­tin, like a gen­er­al pick­ing tar­gets for an air raid. Those tagged pro­teins are then tar­get­ed by pro­teas­es and un­fold­ed in the body’s mul­ti-step garbage dis­pos­al sys­tem.

Kymera us­es small mol­e­cules to drag E3 lig­as­es to the pro­tein it wants to elim­i­nate. Their pre­clin­i­cal re­search sug­gests re­mov­ing IRAK4 in this way will help treat a rare in­flam­ma­to­ry skin con­di­tion called hidradeni­tis sup­pu­ra­ti­va and B-cell lym­phomas, among oth­er dis­eases. They al­so have pro­grams tar­get­ing the tran­scrip­tion fac­tor STAT3, which is part of the JAK path­way.

Main­olfi said the gen­er­al con­cept had been ap­par­ent for years, but ad­vance­ments around 2016 made it look fea­si­ble.

“This is tech­nol­o­gy that has fas­ci­nat­ed me for years, but what was lack­ing were re­al­ly the chem­i­cal tools,” Main­olfi said.

Since then, Kymera has built up a plat­form they say dif­fer­en­ti­ates them from some of their com­peti­tors by us­ing in­for­mat­ics to iden­ti­fy new E3 lig­as­es and the best drugs in im­munol­o­gy and on­col­o­gy. And last year they signed a $70 mil­lion col­lab­o­ra­tion with Ver­tex. Main­olfi, who stepped in­to the CEO job in No­vem­ber af­ter Lau­rent Au­doly’s de­par­ture, said it helps them ap­ply their tech­nol­o­gy in in­di­ca­tions be­yond the two they’ve fo­cused on to date.

Even­tu­al­ly, he said, pro­tein degra­da­tion is go­ing to be every­where.

“When I look at pro­tein degra­da­tion, I look at a field just like an­ti­body or RNA ther­a­peu­tics 20 years ago,” Main­olfi said. “It is a field that will trans­form med­i­cine.”

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.

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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So what hap­pened with No­var­tis' gene ther­a­py group? 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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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.

David Meek, new Mirati CEO (Marlene Awaad/Bloomberg via Getty Images)

Fresh off Fer­Gene's melt­down, David Meek takes over at Mi­rati with lead KRAS drug rac­ing to an ap­proval

In the insular world of biotech, a spectacular failure can sometimes stay on any executive’s record for a long time. But for David Meek, the man at the helm of FerGene’s recent implosion, two questionable exits made way for what could be an excellent rebound.

Meek, most recently FerGene’s CEO and a past head at Ipsen, has become CEO at Mirati Therapeutics, taking the reins from founding CEO Charles Baum, who will step over into the role of president and head of R&D, according to a release.

Volker Wagner (L) and Jeff Legos

As Bay­er, No­var­tis stack up their ra­dio­phar­ma­ceu­ti­cal da­ta at #ES­MO21, a key de­bate takes shape

Ten years ago, a small Norwegian biotech by the name of Algeta showed up at ESMO — then the European Multidisciplinary Cancer Conference 2011 — and declared that its Bayer-partnered targeted radionuclide therapy, radium-223 chloride, boosted the overall survival of castration-resistant prostate cancer patients with symptomatic bone metastases.

In a Phase III study dubbed ALSYMPCA, patients who were treated with radium-223 chloride lived a median of 14 months compared to 11.2 months. The FDA would stamp an approval on it based on those data two years later, after Bayer snapped up Algeta and christened the drug Xofigo.

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Mi­rati tri­umphs again in KRAS-mu­tat­ed lung can­cer with a close­ly watched FDA fil­ing now in the cards

After a busy weekend at #ESMO21, which included a big readout for its KRAS drug adagrasib in colon cancer, Mirati Therapeutics is ready to keep the pressure on competitor Amgen with lung cancer data that will undergird an upcoming filing.

In topline results from a Phase II cohort of its KRYSTAL-1 study, adagrasib posted a response rate of 43% in second-line-or-later patients with metastatic non-small cell lung cancer containing a KRAS-G12C mutation, Mirati said Monday.

When ef­fi­ca­cy is bor­der­line: FDA needs to get more con­sis­tent on close-call drug ap­provals, agency-fund­ed re­search finds

In the exceedingly rare instances in which clinical efficacy is the only barrier to a new drug’s approval, new FDA-funded research from FDA and Stanford found that the agency does not have a consistent standard for defining “substantial evidence” when flexible criteria are used for an approval.

The research comes as the FDA is at a crossroads with its expedited-review pathways. The accelerated approval pathway is under fire as the agency recently signed off on a controversial new Alzheimer’s drug, with little precedent to explain its decision. Meanwhile, top officials like Rick Pazdur have called for a major push to simplify and clarify all of the various expedited pathways, which have grown to be must-haves for sponsors of nearly every newly approved drug.

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Ted White, Verrica CEO

Ver­ri­ca hits an­oth­er bump in the road with CMO re­lat­ed let­ter from FDA

The FDA has rejected Verrica’s new drug application for VP-102 again, with the company pinning the CRL on problems at a CMO that it was partnered with, the company announced Monday.

The FDA didn’t raise issues that directly relate to the manufacturing of VP-102, the company said, but raised “general quality issues” at the CMO’s facility. There were also no clinical concerns, it said, or need to collect more data.