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.”

UP­DAT­ED: A small, ob­scure biotech just won big with their IPO. In this mar­ket. Are you kid­ding me?

How could a small, largely unknown biotech that emerged from stealth mode just months ago with early-stage cancer programs jump onto Wall Street in the middle of a Category 6 financial hurricane and sail through with a $165 million IPO?

And what does that mean for the rest of the industry waiting to see just how much damage global lockdowns will wreak on clinical development?

The biotech is a company called Zentalis. The crew there nabbed an $85 million crossover round late last year — notably waiting 5 years before waving the numbers around to attract attention, according to my read of a FierceBiotech story. Perceptive joined in, but the syndicate was not in general the kind of marquee affair that gets tongues wagging.

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Gilead CEO Daniel O'Day attends a meeting with the President and other biopharma leaders at the White House on March 2, 2020 (AP Photo)

Ramp­ing up glob­al pro­duc­tion of remde­sivir, Gilead CEO Dan O’Day de­tails plans to dis­trib­ute 1.5M dos­es to fight Covid-19 — for free

Gilead is still some days away from turning the card on its first round of data on remdesivir’s ability to fight severe cases of Covid-19, but the big biotech is ramping up an emergency supply of a million courses of therapy as it starts free distribution of the drug to tens of thousands of patients under their compassionate use and expanded access program as well as clinical trials.

In his latest open letter posted over the weekend, Gilead CEO Dan O’Day outlined how the company has been successful in cutting production time on remdesivir while repurposing some of their own facilities and turning to contract manufacturers to build a near-term supply of 1.5 million doses. They are still working on efficacy and dosing, but that supply could cover 140,000 courses of treatment. That supply, he added, would be more widely available following a potential approval.

Bob Nelsen at the Milken Institute Global Conference on April 29, 2019 in Beverly Hills, California. (Photo by Michael Kovac/Getty Images)

ARCH chief Bob Nelsen has $1.5B to prove 2 sim­ple points: ‘We’re in the most in­no­v­a­tive time ever’ and in­vestors are stay­ing

ARCH co-founder and managing director Bob Nelsen has a well known yen for the home run swing, betting big on potentially transformative meds and tech and the biotech teams he helps bring together. He thrives and bleeds on the cutting edge. And now Nelsen and the ARCH group have debuted 2 big funds to prove that this is the time for the best of biotech to shine — deadly pandemic be damned.

Two new funds, ARCH Venture Fund X and ARCH Venture Fund X Overage, gathered a combined $1.46 billion. And that’s a record. ARCH Venture Fund IX and ARCH Venture Fund IX Overage closed in 2016 with a combined $1.1 billion. ARCH Venture Fund VIII and ARCH Venture Fund VIII Overage closed in 2014 with a combined $560 million.

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Have a new drug that promis­es to fight Covid-19? The FDA promis­es fast ac­tion but some de­vel­op­ers aren't hap­py

After providing an emergency approval to use malaria drugs against coronavirus with little actual evidence of their efficacy or safety in that setting, the FDA has already proven that it has set aside the gold standard when it comes to the pandemic. And now regulators have spelled out a new approach to speeding development that promises immediate responses in no uncertain terms — promising a program offering the ultimate high-speed pathway to Covid-19 drug approvals.

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Once fu­ri­ous over No­var­tis’ da­ta ma­nip­u­la­tion scan­dal, the FDA now says it’s noth­ing they need to take ac­tion on

Back in the BP era — Before Pandemic — the FDA ripped Novartis for its decision to keep the agency in the dark about manipulated data used in its application for Zolgensma while its marketing application for the gene therapy was under review.

Civil and criminal sanctions were being discussed, the agency noted in a rare broadside at one of the world’s largest pharma companies. Notable lawmakers cheered the angry regulators on, urging the FDA to make an example of Novartis, which fielded Zolgensma at $2.1 million — the current record for a one-off therapy.

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Covid-19 roundup: GSK, Am­gen tai­lor R&D work to fit the coro­n­avirus age; Doud­na's ge­nomics crew launch­es di­ag­nos­tic lab

You can add Amgen and GSK to the list of deep-pocket drug R&D players who are tailoring their pipeline work to fit a new age of coronavirus.

Following in the footsteps of a lineup of big players like Eli Lilly — which has suspended patient recruitment for drug studies — Amgen and GSK have opted to take a more tailored approach. Amgen is intent on circling the wagons around key studies that are already fully enrolled, and GSK has the red light on new studies while the pandemic plays out.

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In a stun­ning set­back, Amarin los­es big patent fight over Vas­cepa IP. And its high-fly­ing stock crash­es to earth

Amarin’s shares $AMRN were blitzed Monday evening, losing billions in value as reports spread that the company had lost its high-profile effort to keep its Vascepa patents protected from generic drugmakers.

Amarin had been fighting to keep key patents under lock and key — and away from generic rivals — for another 10 years, but District Court Judge Miranda Du in Las Vegas ruled against the biotech. She ruled that:
(A)ll the Asserted Claims are invalid as obvious under 35 U.S.C.§ 103. Thus, the Court finds in favor of Defendants on Plaintiff’s remaining infringementclaim, and in their favor on their counterclaims asserting the invalidity of the AssertedClaims under 35 U.S.C. § 103.

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Aaron Royston, venBio

In­vest­ing in the time of coro­n­avirus: the good, the bad and the hope­ful, as biotech VC firms close funds worth $3B

Apart from disrupting biopharma R&D and regulatory timelines, the coronavirus pandemic has inevitably ravaged financial markets and eroded investor risk appetite. Investing in the time of coronavirus feels reckless, but if biotech venture funds are any indication, the time is ripe.

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Drug dis­cov­ery in the age of coro­n­avirus

Developing new drugs is incredibly hard. That’s why, despite superhuman efforts from the industry, we’re still looking at 12-18 months minimum before we can realistically hope for a vaccine for Covid-19, and probably months before there’s a proven viable drug treatment.

But our increasing ability to begin to industrialize the drug discovery and development process through an engineering approach means that we have more hope for speeding up this process than ever before — and not just to defeat coronavirus, but to benefit the development of all new medicines in the future.