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.”

Biotech in­vestors and CEOs see two paths to growth, but are they equal­ly vi­able?

The dynamic in the biotech market has been highly volatile in the last few years, from the high peaks immediately after the COVID vaccine in 2021, to the lowest downturns of the last 20 years in 2022. This uncertainty makes calling the exact timing of the market’s turn something of a fool’s errand, according to Dr. Chen Yu, Founder and Managing Partner of TCG Crossover (TCG X). He speaks with RBC’s Noël Brown, Head of US Biotechnology Investment Banking, about the market’s road ahead and two possible paths for growth.

In AstraZeneca's latest campaign, wild eosinophils called Phils personify the acting up often seen in uncontrolled asthma

As­traZeneca de­buts an­noy­ing pur­ple ‘Phil’ crea­tures, per­son­i­fied asth­ma eosinophils ‘be­hav­ing bad­ly’

There are some odd-looking purple creatures lurking around the halls of AstraZenca lately. The “Phil” character cutouts are purple, personified eosinophils with big buggy eyes and wide mouths, and they’re a part of AZ’s newest awareness effort to help people understand eosinophilic asthma.

The “Asthma Behaving Badly” characters aren’t only on the walls at AZ to show the new campaign to employees, however. The “Phils” are also showing up online on the campaign website, and in digital and social ads and posts on Facebook and Instagram.

Casey McPherson shows his daughters Rose (left) and Weston around Everlum Bio, a lab that he co-founded to spark a treatment for Rose and others with ultra-rare conditions. (Ilana Panich-Linsman)

Fa­ther starts lab af­ter in­tel­lec­tu­al prop­er­ty is­sues stymie rare dis­ease drug de­vel­op­ment

Under bright lab lights, Casey McPherson holds his 6-year-old daughter, Rose. His free hand directs Rose’s gaze toward a computer screen with potential clues in treating her one-of-a kind genetic condition.

Gray specks on the screen show her cells that scientists reprogrammed with the goal of zeroing in on a custom medicine. McPherson co-founded the lab, Everlum Bio, to spark a treatment for Rose — and others like her. A regarded singer-songwriter, McPherson never imagined going into drug development.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 150,300+ biopharma pros reading Endpoints daily — and it's free.

Ying Huang, Legend CEO

Lentivi­ral vec­tor ramp-up: J&J and Leg­end to in­vest $500M in New Jer­sey man­u­fac­tur­ing to sup­port Carvyk­ti

In response to a question on manufacturing scale at Legend Biotech’s R&D day yesterday, the company’s top exec said its partnership with Johnson & Johnson will be doubling its investment in its New Jersey manufacturing center and will be investing a total of $500 million.

With an eye on their BCMA-directed CAR-T therapy Carvykti (cilta-cel), approved in February as a fifth-line treatment for multiple myeloma, Legend CEO Ying Huang said that the ramp-up in production and the decision to manufacture its own lentiviral vectors — currently in shortage worldwide — means they won’t have to deal with that shortage.

Kite Phar­ma gets FDA to sign off on new Cal­i­for­nia-based vec­tor man­u­fac­tur­ing fa­cil­i­ty

Kite Pharma just got FDA approval to kick off operations at a new manufacturing campus.

The cancer-focused, CAR-T cell therapy player made the announcement Monday, saying that the federal regulatory agency gave the green light to Kite’s 100,000 square-foot, retroviral vector manufacturing facility in Oceanside, CA.

Kite’s global head of technical operations Chris McDonald tells Endpoints News that the facility has been in the works for about four years, after Kite teamed up with its parent company Gilead. Gilead acquired Kite Pharma for just shy of $12 billion in 2017.

Mar­ket­ingRx roundup: No­var­tis re­cruits NFL coach for Leqvio cam­paign; Pfiz­er pro­motes ‘Sci­ence’ merch on so­cial me­dia

Novartis is turning to a winning coach to talk about Leqvio and the struggles of high cholesterol — including his own. Bruce Arians, the retired NFL head coach of the Arizona Cardinals and Super Bowl-winning Tampa Bay Buccaneers, is partnering with the pharma for its “Coaching Cholesterol” digital, social and public relations effort.

In the campaign, Arians talks about the potential for “great comebacks” in football and heart health. Once nicknamed a “quarterback whisperer,” he is now retired from fulltime coaching (although still a front-office consultant for Tampa Bay), and did a round of media interviews for Novartis, including one with People and Forbes.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 150,300+ biopharma pros reading Endpoints daily — and it's free.

Amy West, Novo Nordisk head of US digital innovation and transformation (Illustration: Assistant Editor Kathy Wong for Endpoints News)

Q&A: No­vo Nordisk dig­i­tal in­no­va­tion chief Amy West dis­cuss­es phar­ma pain points and a health­care 'easy but­ton’

Amy West joined Novo Nordisk more than a decade ago to oversee marketing strategies and campaigns for its US diabetes portfolio. However, her career path shifted into digital, and she hasn’t looked back. West went from leading Novo’s first digital health strategy in the US to now heading up digital innovation and transformation.

She’s currently leading the charge at Novo Nordisk to not only go beyond the pill with digital marketing and health tech, but also test, pilot and develop groundbreaking new strategies needed in today’s consumerized healthcare world.

Endpoints Premium

Premium subscription required

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

Marc Dunoyer, Alexion CEO (AstraZeneca via YouTube)

Up­dat­ed: As­traZeneca nabs a small rare dis­ease gene ther­a­py play­er for 667% pre­mi­um

AstraZeneca is kicking off the fourth quarter with a little M&A Monday for a gene editing player recently overcoming a second clinical hold to its only program in human studies.

The Big Pharma and its subsidiary Alexion are buying out little LogicBio for $2.07 per share. That’s good for a massive 667% premium over its Friday closing price, when it headed into the weekend at 27 cents and just weeks after Nasdaq said LogicBio would have to delist, which has been put on hold as the biotech requests a hearing. It’s one of two biotech deals to commence October, alongside the news of Incyte buying a vitiligo-focused biotech.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 150,300+ biopharma pros reading Endpoints daily — and it's free.

Dave Marek, Myovant CEO

My­ovant board balks as ma­jor­i­ty own­er Sum­it­o­mo swoops in with a $2.5B deal to buy them out

Three years after Sumitomo scooped up Roivant’s 46% stake in the publicly traded Myovant $MYOV as part of a 5-company, $3 billion deal, they’re coming back for the whole thing.

But these other investors at Myovant want more than what the Japanese pharma company is currently offering to pay at this stage.

Sumitomo is bidding $22.75 a share for the outstanding stock, which now represents 48% of the company after Sumitomo bumped its ownership since the original deal with Roivant. Myovant, however, created a special committee on the board, and they’re shaking their heads over the offer.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 150,300+ biopharma pros reading Endpoints daily — and it's free.