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.”

Mi­no­ryx and Sper­o­genix ink an ex­clu­sive li­cense agree­ment to de­vel­op and com­mer­cial­ize lerigli­ta­zone in Chi­na

September 23, 2020 – Hong Kong, Beijing, Shanghai (China) and Mataró, Barcelona (Spain)  

Minoryx will receive an upfront and milestone payments of up to $78 million, as well as double digit royalties on annual net sales 

Sperogenix will receive exclusive rights to develop and commercialize leriglitazone for the treatment of X-linked adrenoleukodystrophy (X-ALD), a rare life-threatening neurological condition

FDA chief Stephen Hahn on Capitol Hill earlier this week (Getty Images)

As FDA buck­les un­der the strain of a pan­dem­ic work­load, Trump again ac­cus­es the agency of a po­lit­i­cal hit job

Peter Marks appeared before a virtual SVB Leerink audience yesterday and said that his staff at FDA’s CBER is on the verge of working around the clock. Manufacturing inspections, policy work and sponsor communications have all been pushed down the to-do list so that they can be responsive to Covid-related interactions. And the agency’s objective right now? “To save as many lives as we can,” Marks said, likening the mortality on the current outbreak as equivalent to “a nuclear bomb on a small city.”

Daniel O'Day, Gilead CEO (Kevin Dietsch/UPI/Bloomberg via Getty Images)

Play-by-play of Gilead­'s $21B Im­munomedics buy­out de­tails a fren­zied push — and mints a new biotech bil­lion­aire

Immunomedics had not really been looking for a buyout when the year began. Excited by its BLA for Trodelvy, submitted to the FDA in late 2019, executive chairman Behzad Aghazadeh started off looking for potential licensing deals and zeroed in on four potential partners, including Gilead, following January’s JP Morgan Healthcare Conference in San Francisco. Such talks advanced throughout the year, with discussions advancing to the second round in mid-August.

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David Berry (Flagship)

Flag­ship's next big tech­no­log­i­cal bet? The cloud

Earlier this month, Flagship announced their big bet on the software half the industry is talking about, launching the AI and machine learning startup. Now, they and a couple other investors are gambling $100 million on a software that much of the public generally thinks of as a cool, IT afterthought: cloud computing.

The idea, says founder and Flagship partner David Berry, is one of scale: The sheer magnitude of biological data that you can store on cloud technology is unprecedented. And that size, when leveraged properly, can allow you to ask questions and form insights that are similarly unprecedented.

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The win­dow is wide open as four more biotechs join the go-go IPO class of 2020

It’s another day of hauling cash in the biopharma world as four more IPOs priced Friday and a fifth filed its initial paperwork.

The biggest offering comes from PMV Pharma, an oncology biotech focusing on p53 mutations, which raised $211.8 million after pricing shares at $18 apiece. Prelude Therapeutics, developing PRMT5 inhibitors for rare cancers, was next with a $158 million raise, pricing shares at $19 each. Graybug Vision raised $90 million after pricing at $16 per share for its wet AMD candidates, and breast cancer biotech Greenwich Lifesciences brought up the rear with a small, $7 million raise after pricing shares at $5.75.

J&J of­fers PhI/IIa da­ta show­ing its sin­gle-dose vac­cine can stir up suf­fi­cient im­mune re­sponse

Days after J&J dosed the first participants of its Phase III ENSEMBLE trial, the pharma giant has detailed the early-stage data that gave them confidence in a single-dose regimen.

Testing two dose levels either as a single dose or in a two-dose schedule spaced by 56 days in, the scientists from Janssen, the J&J subsidiary developing its vaccine, reported that the low dose induced a similar immune response as the high dose. The interim Phase I/IIa results were posted in a preprint on medRxiv.

President Donald Trump reacts after signing an executive order following his remarks on his healthcare policies yesterday in Charlotte, North Carolina (Getty Images)

Op-ed: Will phar­ma re­al­ly pay for Trump’s lat­est law­less promise to 33 mil­lion Medicare ben­e­fi­cia­ries? Not like­ly

Sitting atop the executive branch, President Donald Trump is the ultimate authority at the FDA. He can fast track any vaccine to approval himself. If it came to that, of course.

What he can’t do is unilaterally order the legislative branch to loosen the Treasury’s coffers for $6.6 billion. Nor can he command pharmaceutical companies to pay for $200 vouchers sent to 33 million Medicare beneficiaries for prescription drugs before the election.

Pal­la­dio bags $20 mil­lion Se­ries B to top­ple a prob­lem­at­ic kid­ney dis­ease drug

Palladio Biosciences just took one step further in its quest to topple Otsuka’s Samsca with its own — it hopes safer — autosomal dominant polycystic kidney disease (ADPKD) drug.

The Pennsylvania-based biotech announced a $20 million Series B on Friday, which will fund a 10-person Phase III trial of its vasopressin V2 receptor agonist, lixivaptan. CEO Alex Martin expects to read out data in the first half of next year, then launch straight into a larger pivotal Phase III study with about 1,200 participants.

New York governor Andrew Cuomo (AP Images)

An­drew Cuo­mo says New York will un­der­take its own vac­cine re­view process, and wouldn’t rec­om­mend trust­ing the fed­er­al gov­ern­ment

The concerns keep mounting over President Donald Trump’s politicization of the FDA and other federal agencies guiding the development of a safe and effective vaccine. And today, the telegenic New York governor Andrew Cuomo appeared to introduce even more politics into the matter — latest in an ongoing series of incidents that have cast the proudly independent FDA in starkly political terms.

During his daily press conference Cuomo said that the state will review any coronavirus vaccines approved by the federal government, citing a lack of trust in the Trump administration. The announcement comes one day after Trump accused the FDA of making an “extremely political” move in proposing stricter vaccine guidance.