Lily Zou, Degron Therapeutics CEO

Armed with li­brary of mol­e­c­u­lar glues, De­gron launch­es out of a Shang­hai lab

A transpa­cif­ic biotech fo­cused on mol­e­c­u­lar glues now has more funds to play with as it works to vie for Big Phar­ma’s at­ten­tion.

De­gron Ther­a­peu­tics an­nounced a Se­ries A worth $22 mil­lion Thurs­day, with Chi­nese VC Med-Fine Cap­i­tal as lead in­vestor and oth­er in­vestors such as Dy­ee Cap­i­tal and Baidu Ven­ture tag­ging along. Seed in­vestors CO-WIN Ven­tures and Yuan­bio Ven­ture Cap­i­tal al­so par­tic­i­pat­ed, De­gron said in a state­ment.

The biotech was found­ed just last year out of the lab of Yong Cang, a pro­fes­sor at Shang­haiTech Uni­ver­si­ty, branch­ing out with $10 mil­lion from a seed round in April 2021. Us­ing an ar­ray of dif­fer­ent types of screen­ing, from phe­no­types to pro­teomics and AI, De­gron re­searchers seek to pre­dict ways that dif­fer­ent pro­tein tar­gets can be de­grad­ed via mol­e­c­u­lar glue.

So far, the biotech’s li­brary of po­ten­tial mol­e­c­u­lar glues is around 6,000, with the ma­jor­i­ty of them bind­ing to a ubiq­ui­tin E3 lig­ase known as Cere­blon.

While mol­e­c­u­lar glues and pro­te­ol­y­sis tar­get­ing chimeras, aka PRO­TACs, both take ad­van­tage of the hu­man body’s pro­tein de­struc­tion sys­tem, their meth­ods of ac­tion are a bit dif­fer­ent. Mol­e­c­u­lar glues, a type of mono­va­lent de­grad­er, seek to “pro­gram” a ubiq­ui­tin E3 lig­ase to at­tach to tar­get cell sur­face pro­teins and break them down. PRO­TACs, on the oth­er hand, are bi­func­tion­al small mol­e­cules that teth­er a pro­tein of in­ter­est at one end, and at the oth­er end bind to an E3 lig­ase to de­grade and ul­ti­mate­ly dis­pose of that pro­tein.

CEO Lily Zou told End­points News that what sets De­gron apart from oth­er pro­tein degra­da­tion biotechs — in a field that is still rel­a­tive­ly new along­side Nurix, Plex­i­um and Kymera — is the “scaf­fold­ing” it us­es.

“The struc­ture of the small mol­e­cule de­cides — de­ter­mines what kind of tar­get you can re­cruit. And we have a dif­fer­ent start­ing point. Our ini­tial scaf­fold was dis­cov­ered in a screen­ing that’s dif­fer­ent from most, as far as I know,” the CEO said.

Zou added that most oth­er com­pa­nies look for de­riv­a­tives from two of the main ap­proved mol­e­c­u­lar glue drugs: Cel­gene’s lenalido­mide (Revlim­id) and po­ma­lido­mide (Po­m­a­lyst).

“So they are de­riv­a­tives of that, but there is one chem­i­cal space. Imag­ine that we are in a dif­fer­ent chem­i­cal space. So be­cause we’ve dis­cov­ered this new scaf­fold, we’ve built our li­brary around that and ex­pand­ed, be­cause of that we can find dif­fer­ent tar­gets,” Zou fur­ther elab­o­rat­ed.

Zou added that the biotech cur­rent­ly has 20 pro­grams in dif­fer­ent stages of pre­clin­i­cal de­vel­op­ment in a va­ri­ety of tar­gets that Zou said were once deemed un­tar­getable. So far, the in­di­ca­tions range from most­ly on­col­o­gy to some fo­cus in in­flam­ma­tion, meta­bol­ic dis­ease and rare dis­ease.

Three of its pro­grams are in the IND-op­ti­miza­tion stage, and Zou hopes to have those three pro­grams in hu­mans in the next 18 months. In the course of the next year or two, tar­get op­ti­miza­tion and val­i­da­tion will nar­row the num­ber of pre­clin­i­cal pro­grams down.

Zou said among the most ad­vanced pro­grams is a WEE1 ki­nase de­grad­er. De­gron has two choic­es for that tar­get: ei­ther a sin­gle-tar­get de­grad­er or a dual-tar­get de­grad­er, but the fi­nal de­ci­sion has not been made yet. An­oth­er tar­get re­mains undis­closed, but the CEO just called it “pro­tein A” for name’s sake.

“The most ex­cit­ing thing about pro­tein A: It’s un­drug­gable be­cause it’s not an en­zyme or some­thing you can in­hib­it the func­tion of. It’s a struc­tur­al pro­tein of a kind,” Zou said. “So, tra­di­tion­al small mol­e­cule in­hibitors can­not tar­get it. And al­so, it’s in­side the cell, so it’s not tar­get­ed by an­ti­bod­ies or oth­er things.”

As of right now, De­gron has space in the John­son & John­son-spon­sored JLABS space in Shang­hai. Zou al­so elab­o­rat­ed that the com­pa­ny has been talk­ing with J&J, and that the com­pa­ny is mov­ing to Roche Ac­cel­er­a­tor, which is Roche’s at­tempt at build­ing an “in­no­va­tion hub” in Chi­na. In the mean­time, Med-Fine Cap­i­tal part­ner Jing Yu is join­ing De­gron’s board of di­rec­tors.

Scoop: Boehringer qui­et­ly shut­ters a PhII for one of its top drugs — now un­der re­view

Boehringer Ingelheim has quietly shut down a small Phase II study for one of its lead drugs.

The private pharma player confirmed to Endpoints News that it had shuttered a study testing spesolimab as a therapy for Crohn’s patients suffering from bowel obstructions.

A spokesperson for the company tells Endpoints:

Taking into consideration the current therapeutic landscape and ongoing clinical development programs, Boehringer Ingelheim decided to discontinue our program in Crohn’s disease. It is important to note that this decision is not based on any safety findings in the clinical trials.

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Alex­ion puts €65M for­ward to strength­en its po­si­tion on the Emer­ald Isle

Ireland has been on a roll in 2022, with several large pharma companies announcing multimillion-euro projects. Now AstraZeneca’s rare disease outfit Alexion is looking to get in on the action.

Alexion on Friday announced a €65 million ($68.8 million) investment in new and enhanced capabilities across two sites in the country, including at College Park in the Dublin suburb of Blanchardstown and the Monksland Industrial Park in the central Irish town of Athlone, according to the Industrial Development Agency of Ireland.

Members of the G7 from left to right: Prime Minister of Italy Mario Draghi, European Commission President Ursula von der Leyen, President Joe Biden, German Chancellor Olaf Scholz, British Prime Minister Boris Johnson, Canadian Prime Minister Justin Trudeau, Prime Minister of Japan Fumio Kishida, French President Emmanuel Macron and European Council President Charles Michel (AP Photo/Susan Walsh)

Biden and G7 na­tions of­fer funds for vac­cine and med­ical prod­uct man­u­fac­tur­ing project in Sene­gal

Amidst recently broader vaccine manufacturing initiatives from the EU and European companies, the G7 summit in the mountains of Bavaria has brought about some positive news for closing vaccine and medical product manufacturing gaps around the globe.

According to a statement from the White House, the G7 leaders have formally launched the partnership for global infrastructure, PGII. The effort will aim to mobilize hundreds of billions of dollars to deliver infrastructure projects in several sectors including the medical and pharmaceutical manufacturing space.

State bat­tles over mifepri­s­tone ac­cess could tie the FDA to any post-Roe cross­roads

As more than a dozen states are now readying so-called “trigger” laws to kick into effect immediate abortion bans following the overturning of Roe v. Wade on Friday, these laws, in the works for more than a decade in some states, will likely kick off even more legal battles as states seek to restrict the use of prescription drug-based abortions.

Since Friday’s SCOTUS opinion to overturn Americans’ constitutional right to an abortion after almost 50 years, reproductive rights lawyers at Planned Parenthood and other organizations have already challenged these trigger laws in Utah and Louisiana. According to the Guttmacher Institute, other states with trigger laws that could take effect include Arkansas, Idaho, Kentucky, Mississippi, Missouri, North Dakota, Oklahoma, South Dakota, Tennessee, Texas, and Wyoming.

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Deborah Dunsire, Lundbeck CEO

Af­ter a 5-year re­peat PhI­II so­journ, Lund­beck and Ot­su­ka say they're fi­nal­ly ready to pur­sue OK to use Rex­ul­ti against Alzheimer's ag­i­ta­tion

Five years after Lundbeck and their longtime collaborators at Otsuka turned up a mixed set of Phase III data for Rexulti as a treatment for Alzheimer’s dementia-related agitation, they’ve come through with a new pivotal trial success they believe will finally put them on the road to an approval at the FDA. And if they’re right, some analysts believe they’re a short step away from adding more than $500 million in annual sales for the drug, already approved in depression and schizophrenia.

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A Mer­ck part­ner is sucked in­to the fi­nan­cial quag­mire as key lender calls in a note

Another biotech standing on shaky financial legs has fallen victim to the bears.

Merck partner 4D Pharma has reported that a key lender, Oxford Finance, shoved the UK company into administration after calling in a $14 million loan they couldn’t immediately make good on. Trading in their stock was halted with a market cap that had fallen to a mere £30 million.

“Despite the very difficult prevailing market conditions,” 4D reported on Friday, the biotech had been making progress on finding some new financing and turned to Oxford with an alternative late on Thursday and then again Friday morning.

Fed­er­al judge de­nies Bris­tol My­er­s' at­tempt to avoid Cel­gene share­hold­er law­suit

Some Celgene shareholders aren’t happy with how Bristol Myers Squibb’s takeover went down.

On Friday, a New York federal judge ruled that they have a case against the pharma giant, denying a request to dismiss allegations that it purposely slow-rolled Breyanzi’s approval to avoid paying out $6.4 billion in contingent value rights (CVR).

When Bristol Myers put down $74 billion to scoop up Celgene back in 2019, liso-cel — the CAR-T lymphoma treatment now marketed as Breyanzi — was supposedly one of the centerpieces of the deal. After going back and forth on negotiations for about six months, BMS put $6.4 billion into a CVR agreement that required an FDA approval for Zeposia, Breyanzi and Abecma, each by an established date.

Chris Anzalone, Arrowhead CEO

Take­da, Ar­row­head spot­light da­ta from small tri­al show­ing RNAi works in a rare liv­er con­di­tion

Almost two years after Takeda wagered $300 million cash to partner with Arrowhead on an RNAi therapy for a rare disease, the companies are spelling out Phase II data that they believe put them one step closer to their big dreams.

In a small, open label study involving only 16 patients who had liver disease associated with alpha-1 antitrypsin deficiency (AATD), Arrowhead’s candidate — fazirsiran, previously ARO-AAT — spurred substantial reductions in accumulated mutant AAT protein in the liver, a hallmark of the condition. Investigators also tracked improvements in symptoms, with seven out of 12 who received the high, 200 mg dose seeing regression of liver fibrosis.

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No stranger to gene ther­a­py woes, Astel­las runs in­to an­oth­er safe­ty-re­lat­ed clin­i­cal hold

Astellas Pharma, which has been at the forefront of uncovering the risks associated with gene therapies delivered by adeno-associated viruses, must take another safety alarm head-on.

The FDA has slapped a clinical hold on Astellas’ Phase I/II trial of a gene therapy candidate for late-onset Pompe disease, after investigators flagged a serious case of peripheral sensory neuropathy.

It marks the latest in a streak of setbacks Astellas has encountered since making a splashy entry into the gene therapy space with its $3 billion buyout of Audentes. But the lead program, AT132 for the treatment of X-linked myotubular myopathy (XLMTM), had to be halted more than once after a total of four patients died in the trial — and the scientific community still doesn’t have all the answers of what caused the deaths.

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