Eli Lil­ly, No­var­tis back a biotech start­up boast­ing 'best of both world­s' pro­tein de­graders

Since head­ing up Glax­o­SmithK­line’s pro­tein degra­da­tion unit in 2012, Ian Churcher has wit­nessed a rapid ex­plo­sion of in­ter­est in the idea of lever­ag­ing the body’s garbage dis­pos­al sys­tem to elim­i­nate prob­lem­at­ic pro­teins. Huge amounts of mon­ey are flow­ing in from biotech VCs and Big Phar­ma play­ers, bankrolling a huge vol­ume of projects — some of which have now made it to the clin­ic.

Ian Churcher

“What I would say hasn’t changed is the fo­cus is still very much on a small num­ber of mech­a­nisms, around say VHL and cere­blon, and we knew about these mech­a­nisms very ear­ly,” he told End­points News. “So I think what that sug­gests is it’s re­al­ly quite dif­fi­cult to iden­ti­fy nov­el mech­a­nisms.”

He has since moved on to oth­er dis­cov­ery fields, but that feel­ing was what got him ex­cit­ed about fo­cus­ing on tar­get­ed pro­tein degra­da­tion again and tak­ing up the CSO post at Am­phista last May, just af­ter the UK-based biotech de­buted with a $7.5 mil­lion Se­ries A.

The hy­poth­e­sis at Am­phista, in­cu­bat­ed at aca­d­e­m­ic founder Alessio Ciul­li’s lab in Scot­land, has been that you can tar­get pro­teins for degra­da­tion by en­gag­ing oth­er parts of the ubiq­ui­tin-pro­tea­some sys­tem, said CEO Nic­ki Thomp­son.

Less than a year lat­er, they’ve scored $53 mil­lion in fresh fi­nanc­ing to prove it fur­ther.

No­var­tis and Eli Lil­ly hopped on­to the syn­di­cate along­side Gilde Health­care and For­bion, co-lead­ers of the round, and Am­phista’s ex­ist­ing back­ers at Bio­Mo­tiv and Ad­vent Life Sci­ences.

Nic­ki Thomp­son

Am­phista, Churcher not­ed, isn’t the on­ly com­pa­ny re­al­iz­ing the lim­i­ta­tions of PRO­TACs as pi­o­neered by Craig Crews (with whom Ciul­li had worked as a fel­low) and oth­ers like Jay Brad­ner be­fore he be­came the chief of No­var­tis In­sti­tutes for Bio­Med­ical Re­search. Their re­spec­tive spin­outs, Arv­inas and C4 Ther­a­peu­tics, are some of the first to start Phase I stud­ies — in prostate can­cer and hema­to­log­ic ma­lig­nan­cies, re­spec­tive­ly.

There’s Ly­cia, the start­up pur­su­ing Car­olyn Bertozzi’s ideas for tar­get­ing ex­tra­cel­lu­lar pro­teins; a string of oth­ers, like Monte Rosa, are mov­ing in­to “mol­e­c­u­lar glues” — small­er com­pounds that they hope would have bet­ter drug-like prop­er­ties.

But glues would ul­ti­mate­ly on­ly work for a small num­ber of tar­gets, he added. So they chose to keep the tra­di­tion­al two-part con­struct of bi­func­tion­al de­graders, with one half bind­ing to the drug tar­get and the oth­er half be­ing a “war­head” that would re­cruit a pro­tein to ini­ti­ate the degra­da­tion. By en­gi­neer­ing the war­heads to en­list things oth­er than those E3 lig­as­es — they still can’t re­veal what ex­act­ly makes it “gen­uine­ly dif­fer­ent” — they be­lieve they will open up whole new ar­eas for ex­plo­ration.

“We think we’ve over­come a lot of those prob­lems,” Churcher said. “So our bi­func­tion­al ap­proach gives us the best of both worlds — great drug-like prop­er­ties and a broad tar­get scope.”

With a goal to bring the lead pro­gram in­to the clin­ic in 2023, Thomp­son not­ed the Se­ries B will drill down on those ini­tial on­col­o­gy in­di­ca­tions and po­ten­tial­ly ex­pand to oth­ers that are cur­rent­ly out of bounds for pro­tein degra­da­tion.

De­spite the num­ber of com­pa­nies in the space, af­ter all, Kymera is pret­ty much the on­ly one that’s pub­licly gone af­ter some­thing out­side of can­cer by ex­plor­ing in­flam­ma­tion with Sanofi.

Thomp­son and Churcher en­vi­sion go­ing even fur­ther, pro­duc­ing next-gen mol­e­cules that might even ad­dress dis­eases of the cen­tral ner­vous sys­tem.

With 15 full-time em­ploy­ees at the mo­ment, they ex­pect to at least dou­ble over the com­ing 12 to 18 months while pur­su­ing a “lim­it­ed num­ber of” strate­gic part­ner­ships.

“The field will con­tin­ue to grow — there’s a huge amount of ef­fort, very smart minds go­ing in­to the area,” Churcher said. “But we re­al­ly do need to break out of the lim­i­ta­tions that the cur­rent mech­a­nisms do bring up­on the field. I think they will be suc­cess­ful, but I think there’s so much more scope to be even more suc­cess­ful.”

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.

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.

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.

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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Take­da snaps up the Japan­ese rights to an old Shire cast-off; Boehringer In­gel­heim ac­quires Abexxa Bi­o­log­ics

A week before the FDA is set to decide on Mirum Pharmaceuticals’ lead liver disease drug — an old Shire cast-off called maralixibat — Takeda is swooping in to secure the rights in Japan.

Maralixibat’s roots trace back to Lumena, which was snapped up by Shire for $260 million-plus back in 2014. While the candidate had failed mid-stage studies at Shire, Mirum believes better trial design and patient selection will deliver the wins it needs. The drug is currently in development for Alagille syndrome (a condition called ALGS in which bile builds up in the liver), progressive familial intrahepatic cholestasis (PFIC, which causes progressive liver disease) and biliary atresia (a blockage in the ducts that carry bile from the liver to the gallbladder).

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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Af­ter sell­ing to Genen­tech, the old Je­cure team is back at an RNA-fo­cused start­up — and more en­thu­si­as­tic than ever

When Genentech swooped in to buy NASH-focused Jecure Therapeutics back in 2018, a handful of the startup’s executives weren’t quite ready to disperse.

It had been just three years since Jecure launched with a preclinical portfolio of NLRP3 inhibitors — and the takeover came sooner than anyone, including CEO Jeff Stafford, had expected. So he got talking with James Veal and Gretchen Bain, two serial entrepreneurs in charge of Jecure’s R&D.

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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Vicente Anido (University of West Virginia via YouTube)

Aerie fires CEO af­ter lead pro­gram flop, com­ments about pri­ma­ry end­points be­ing 'not re­quired'

Aerie Pharmaceuticals CEO Vicente Anido has left the company less than a week after trying to chart a Phase III study in the wake of a serious Phase IIb flop.

Anido’s last day at Aerie was Friday, the biotech announced in a news release Tuesday morning, and Benjamin McGraw is taking his place in an interim role. The now former CEO was terminated without cause, according to an SEC filing.

The board has started looking for a full-time chief to take his place.

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