Pro­tein degra­da­tion 2.0? Third Rock sinks $56M in­to Cedil­la's un­usu­al ap­proach

Third Rock Ven­tures is trot­ting out the lat­est play­er in the hot space of pro­tein degra­da­tion, in­fus­ing the new start­up with $56 mil­lion in launch mon­ey to find out if its un­con­ven­tion­al ap­proach to junk­ing pro­teins works bet­ter than its ri­vals.

The up­start goes by Cedil­la Ther­a­peu­tics, and it’s en­ter­ing a field of drug de­vel­op­ment that’s pick­ing up a lot of steam this year. The con­cept be­hind the emerg­ing space is sim­ple enough: where pro­tein in­hi­bi­tion has led to some ad­vanced med­i­cines, de­grad­ing pro­teins could prove a more fruit­ful so­lu­tion. The ap­proach could have ma­jor ben­e­fits over tra­di­tion­al small-mol­e­cule strate­gies, in­clud­ing the po­ten­tial to cut down sys­temic drug ex­po­sure and the abil­i­ty to tack­le tar­get pro­teins once con­sid­ered un­drug­gable.

Many play­ers in pro­tein degra­da­tion are tack­ling the field by hi­jack­ing the ubiq­ui­tin process, es­sen­tial­ly tag­ging dis­ease-caus­ing pro­teins for de­struc­tion by re­cruit­ing an E3 lig­ase to the tar­get, which sends the pro­tein to the cell’s nat­ur­al “garbage dis­pos­al.” It’s a smart idea, but it’s al­so quite com­plex to build these mol­e­cules. Ear­ly pi­o­neers in the pro­tein degra­da­tion space are tak­ing this ap­proach now, in­clud­ing Arv­inas, Kymera, and C4 Ther­a­peu­tics, among oth­ers.

Cedil­la is tak­ing aim at a dif­fer­ent av­enue, the com­pa­ny’s CEO Alexan­dra (San­dra) Glucks­mann tells me.

“What we’re try­ing to do is up­stream of that whole process,” she said. “In­stead of start­ing with a tech­nol­o­gy and then hav­ing to find a tar­get — and be­ing lim­it­ed by the tech we have — we are in­stead start­ing with a tar­get of in­ter­est and ap­ply­ing dif­fer­ent method­olo­gies to de­grade it.”

Bri­an Jones

Third Rock has been gun­ning away on this idea for months now, re­cruit­ing Glucks­mann, a found­ing em­ploy­ee and the ex-COO of Ed­i­tas, to serve as en­tre­pre­neur-in-res­i­dence at the ven­ture firm six months ago (with plans to put her at the helm of Cedil­la straight away). Glucks­mann said the com­pa­ny al­ready em­ploys 12 peo­ple.

In short, Cedil­la is us­ing more tra­di­tion­al small mol­e­cule drugs to desta­bi­lize dis­ease-caus­ing pro­teins ahead of the ubiq­ui­ti­na­tion process. Once the pro­teins are un­sta­ble, the cell rec­og­nizes them as dys­func­tion­al and toss­es them in the garbage dis­pos­al.

One way the com­pa­ny is go­ing about this is by map­ping out the chem­i­cal bonds be­tween pro­teins. The goal, Glucks­mann says, is to “or­phan” a tar­get pro­tein by dis­rupt­ing its bonds with oth­er pro­teins, tip­ping the tar­get in­to an un­sta­ble state.

Cedil­la is al­ready run­ning 8 ear­ly-stage pro­grams in par­al­lel, Glucks­mann said, us­ing the new funds from Third Rock to ID which can­di­dates they’ll take to the clin­ic. The com­pa­ny thinks this tech could be have wide­spread ap­pli­ca­tions.

“We are ini­tial­ly fo­cused on on­col­o­gy tar­gets,” said Cedil­la’s CSO Bri­an Jones. “We al­so be­lieve our small mol­e­cule ap­proach is broad­ly ap­plic­a­ble, for ex­am­ple to ac­cess tar­gets in the cen­tral ner­vous sys­tem.”

2023 Spot­light on the Fu­ture of Drug De­vel­op­ment for Small and Mid-Sized Biotechs

In the context of today’s global economic environment, there is an increasing need to work smarter, faster and leaner across all facets of the life sciences industry.  This is particularly true for small and mid-sized biotech companies, many of which are facing declining valuations and competing for increasingly limited funding to propel their science forward.  It is important to recognize that within this framework, many of these smaller companies already find themselves resource-challenged to design and manage clinical studies themselves because they don’t have large teams or in-house experts in navigating the various aspects of the drug development journey. This can be particularly challenging for the most complex and difficult to treat diseases where no previous pathway exists and patients are urgently awaiting breakthroughs.

Kristen Hege, Bristol Myers Squibb SVP, early clinical development, oncology/hematology and cell therapy (Illustration: Assistant Editor Kathy Wong for Endpoints News)

Q&A: Bris­tol My­er­s' Kris­ten Hege on cell ther­a­py, can­cer pa­tients and men­tor­ing the next gen­er­a­tion

Kristen Hege leads Bristol Myers Squibb’s early oncology discovery program carrying on from the same work at Celgene, which was acquired by BMS in 2019. She’s known for her early work in CAR-T, having pioneered the first CAR-T cell trial for solid tumors more than 25 years ago.

However, the eminent physician-scientist is more than just a drug developer mastermind. She’s also a practicing physician, mother to two young women, an avid backpacker and intersecting all those interests — a champion of young women and people of color in STEM and life sciences.

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Rick Modi, Affinia Therapeutics CEO

Ver­tex-part­nered gene ther­a­py biotech Affinia scraps IPO plans

Affinia Therapeutics has ditched its plans to go public in a relatively closed-door market that has not favored Nasdaq debuts for the drug development industry most of this year. A pandemic surge in 2020 and 2021 opened the doors for many preclinical startups, which caught Affinia’s attention and gave the gene therapy biotech confidence in the beginning days of 2022 to send in its S-1.

But on Friday, Affinia threw in the S-1 towel and concluded now is not the time to step onto Wall Street. The biotech has put out few public announcements since the spring of this year. Endpoints News picked the startup as one of its 11 biotechs to watch last year.

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Gossamer Bio CEO Faheem Hasnain at Endpoints' #BIO22 panel (J.T. MacMillan Photography for Endpoints News)

Gos­samer’s Fa­heem Has­nain de­fends a round of pos­i­tive PAH da­ta as a clear win. But can these PhII re­sults stand up to scruti­ny?

Gossamer Bio $GOSS posted a statistically significant improvement for its primary endpoint in the key Phase II TORREY trial for lead drug seralutinib on Tuesday morning. But CEO Faheem Hasnain has some explaining to do on the important secondary of the crucial six-minute walk distance test — which will be the primary endpoint in Phase III — as the data on both endpoints fell short of expectations, missing one analyst’s bar on even modest success.

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Jay Lichter, Arialys Therapeutics CEO (Avalon Ventures)

Scoop: Aval­on, MPM back new CNS biotech with sci­en­tif­ic chops from Astel­las

A preclinical central nervous system biotech is in the works in La Jolla, CA, and the drug developer has reeled in capital from a syndicate of investors, Endpoints News has learned.

Arialys Therapeutics filed incorporation documents in the Golden State last December and applied its name for trademark protection with the US Patent and Trademark Office the week prior to that. Paperwork with the SEC also outlines plans to offer up equity in exchange for $55 million.

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Bob Duggan, Summit Therapeutics co-CEO

Bounc­ing from ma­jor set­back, Sum­mit hands out $500M cash for can­cer drug — thanks to a loan from bil­lion­aire CEO

After hitting a dead end with Summit Therapeutics’ lead program, Bob Duggan has found the drug that he believes will usher into a compelling second act. So compelling, in fact, that it involves $500 million cash — and he’s taking money out of his own pocket to fund the deal.

Striking a partnership with Akeso Therapeutics out of China, Summit is bringing in a bispecific antibody that blocks both PD-1 and VEGF called ivonescimab. Akeso, which has a PD-1/CTLA-4 bispecific approved in China, has already taken ivonescimab into multiple clinical trials, including a Phase III in lung cancer.

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Eu­ro­pean Com­mis­sion lays ground­work to un­wind Il­lu­mi­na's $7B+ Grail merg­er

The European Commission has recommended steps that — though not yet final — would require Illumina to “swiftly” unwind its controversial $7.1 billion Grail buyout.

The Commission delivered a “statement of objections” on Monday, detailing the process Illumina would need to take in divesting Grail, its blood testing spinout launched in 2016. Illumina re-acquired Grail back in August, despite criticism from both the FTC and EU.

US sup­ports ex­ten­sion for Covid-19 IP waiv­er de­ci­sion

After much debate, the US government is now calling for a deadline extension to discuss a controversial potential IP waiver for Covid-19 diagnostics and therapeutics.

Over the last five months, the Office of the United States Trade Representative said it has consulted with members of Congress, public health advocates, organized labor groups, academics, think tanks, companies and trade associations on the WTO’s recent TRIPS agreement, which established a 5-year waiver of certain patent requirements on Covid-19 vaccines.

Mar­ket­ingRx roundup: Phar­mas lay off Twit­ter ads for an­oth­er week; WPP un­cov­ers LGBTQ+ mar­ket­ing find­ings

When Twitter’s new owner Elon Musk tweeted this weekend, “Just a note to thank advertisers for returning to Twitter,” he likely wasn’t talking about big pharma companies. The vast majority of the top spending pharma advertisers had not returned last week, according to updated tracking data Pathmatic for Endpoints News.

Only three pharma advertisers spent any money at all, which is about the same as the past several weeks. AstraZeneca rejoined the active advertiser list, although at $700 spent hardly worth a personal Musk expression of gratitude. GSK remained active with $3,500 spent ad much lower than its previous spending, according to the Pathmatics data. Only Bayer spent any significant amount in advertising, with $244,000 spent last week, but that’s a considerable drop from almost $500,000 spent on OTC, prescription and corporate Twitter ads in each of the previous two weeks.

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