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.”

A new era of treat­ment: How bio­mark­ers are chang­ing the way we think about can­cer

AJ Patel was recovering from a complicated brain surgery when his oncologist burst into the hospital room yelling, “I’ve got some really great news for you!”

For two years, Patel had been going from doctor to doctor trying to diagnose his wheezing, only to be dealt the devastating news that he had stage IV lung cancer and only six months to live. And then they found the brain tumors.

“What are you talking about?” Patel asked. He had never seen an oncologist so happy.

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David Ricks, Eli Lilly CEO (David Paul Morris/Bloomberg via Getty Images)

Eli Lil­ly set to in­vest $2.1B in home state man­u­fac­tur­ing boost

Eli Lilly is looking to expand its footprint in its home Hoosier State by making a major investment in manufacturing.

The pharma is investing $2.1 billion in two new manufacturing sites at Indiana’s LEAP Lebanon Innovation and Research District in Boone County, northwest of Lilly’s headquarters in Indianapolis.

The two new facilities will expand Lilly’s manufacturing network for active ingredients and new therapeutic modalities, including genetic medicines, according to a press release.

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US sees spike in Paxlovid us­age as Mer­ck­'s mol­nupi­ravir and As­traZeneca's Evusheld are slow­er off the shelf

New data from HHS show that more than 162,000 courses of Pfizer’s Covid-19 antiviral Paxlovid were administered across the US over the past week, continuing a streak of increased usage of the pill, and signaling not only rising case numbers but more awareness of how to access it.

In comparison to this week, about 670,000 courses of the Pfizer pill have been administered across the first five months since Paxlovid has been on the US market, averaging about 33,000 courses administered per week in that time.

Pfiz­er and CD­MOs ramp up Paxlovid man­u­fac­tur­ing with Kala­ma­zoo plant ex­pan­sion lead­ing the way

As the Covid-19 pandemic continues to evolve, pharma companies and manufacturers are exploring how to step up production on antivirals.

Pfizer is planning to expand its Kalamazoo-area facility to increase manufacturing capabilities for the oral Covid-19 antiviral Paxlovid, according to a report from Michigan-based news site MLive. The expansion of the facility, which serves as Pfizer’s largest manufacturing location, is expected to create hundreds of “high-skilled” STEM jobs, MLive reported. No details about the project’s cost and timeline have been released, but according to MLive, Pfizer will announce the details of the expansion at some point in early June.

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FDA spells out the rules and re­stric­tions for states seek­ing to im­port drugs from Cana­da

The FDA is offering more of an explanation of the guardrails around its program that may soon allow states to import prescription drugs in some select circumstances from Canada, but only if such imports will result in significant cost reductions for consumers.

While the agency has yet to sign off on any of the 5 state plans in the works so far, and PhRMA’s suit to block the Trump-era rule allowing such imports is stalled, the new Q&A guidance spells out the various restrictions that states will have to abide by, potentially signaling that a state approval is coming.

Simba Gill, CEO of Evelo Biosciences

While down 87% YOY, Evelo gets Flag­ship and oth­ers to in­fuse new cap­i­tal for come­back hope

Just four years after Flagship spinout Evelo Biosciences went public in an IPO worth $85 million, the biotech has seen its share price tank from $13 a share this time last year (ultimately reaching a peak of over $17) to now under $1.50. And today, it looks like Flagship still thinks the fledging biotech, in a down market, is still worth something after initial pre-IPO backing from the likes of Google’s GV, Celgene, Mayo Clinic and Alexandria Venture.

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Peter Thompson, Terremoto Biosciences interim CEO

For­mer Prin­cip­ia team looks to shake up co­va­lent small mol­e­cules again, this time at 'earthquake' scale

Terremoto Biosciences goes back a long ways, in a sense, to about a dozen years ago when Principia Biopharma was founded by UCSF professor Jack Taunton. Peter Thompson initially helmed the biotech.

The company helped expand covalent small molecule inhibitors beyond oncology and into autoimmune disease by targeting cystine. But that amino acid is uncommon in a lot of proteins, offering fewer drug targets than, say, lysine, which is present in most proteins of interest. So, over the years, Taunton went back to the drawing board to check out that second amino acid.

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Pfizer CEO Albert Bourla at the World Economic Forum (Gian Ehrenzeller/Keystone via AP Images)

All about ac­cess: Pfiz­er moves to a non-prof­it mod­el for drug sales in 45 low­er-in­come coun­tries

Leading the way to increase access to cheaper drugs worldwide, Pfizer said Wednesday it will provide all current and future patent-protected medicines and vaccines available in the US or EU on a not-for-profit basis to about 1.2 billion people in 45 lower-income countries.

Rwanda, Ghana, Malawi, Senegal and Uganda are the first five countries to sign on to this accord, which will also seek to blaze new paths for quick and efficient regulatory and procurement processes to reduce the usual delays in making new medicines and vaccines available in these countries.

Almirall is tapping artificial intelligence on behalf of its sales force for insights and efficiencies. (via Shutterstock)

Almi­rall rolls out sales rep ar­ti­fi­cial in­tel­li­gence sys­tem, cut­ting pre-call prep and 'wind­shield time'

Dermatology specialty pharma Almirall is making its sales reps smarter. Not with extra training or educational courses, but instead with artificial intelligence tools.

It began a soft launch of a sales rep AI and machine learning platform it calls Polaris last August in one of its 7 US coverage regions. The platform from Aktana gathers information from across Almirall internal sources and external ones – such as claims and prescribing data – to generate insights for reps. Now, instead of spending hours prepping for a sales call, Polaris can generate details about a physician’s preferences, past behaviors and prescription habits for reps in minutes, said Almirall head of commercial operations Vincent Cerio.

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