Daniel Nomura, Vicinitas Therapeutics founder

'Tip of the ice­berg': No­var­tis-part­nered UC Berke­ley lab churns out a start­up to tack­le pro­tein sta­bi­liza­tion

For the past decade, Daniel No­mu­ra’s lab at UC Berke­ley has been work­ing to find chem­i­cal ap­proach­es to drug the so-called “un­drug­gable,” and with the help of No­var­tis’ re­search arm for the past five years, he has built out the foun­da­tion for a new biotech in the pro­tein sta­bi­liza­tion field.

Vicini­tas Ther­a­peu­tics joins a small field of up­starts look­ing to flip the switch and fo­cus on sta­bi­liz­ing cer­tain pro­teins, rather than de­grad­ing them. Cys­tic fi­bro­sis is a good ex­am­ple of a dis­ease that could ben­e­fit from small mol­e­cules aimed at sta­bi­liz­ing the CFTR pro­tein, which is what No­mu­ra’s lab did in a re­cent Na­ture Chem­i­cal Bi­ol­o­gy pa­per, serv­ing as the ba­sis for Vicini­tas.

The biotech emerged Thurs­day morn­ing with $65 mil­lion in Se­ries A fi­nanc­ing, near­ly the same sized round that its main com­peti­tor in the sta­bi­liza­tion field, the apt­ly named Sta­blix Ther­a­peu­tics, launched with last June. A coastal chal­lenge could be brew­ing as the South San Fran­cis­co biotech thinks it can move in­to the dri­ver’s seat in a race against its Co­lum­bia Uni­ver­si­ty peer. Vicini­tas has named its plat­form the Deu­biq­ui­ti­nase Tar­get­ing Chimera, or DUB­TAC, where­as Sta­blix is call­ing its drugs RESTORACs.

“We are cer­tain­ly the first ones to pub­lish on a ful­ly syn­thet­ic small mol­e­cule-based DUB­TAC plat­form for tar­get­ed pro­tein sta­bi­liza­tion, and I be­lieve that re­al­ly puts us in a strong po­si­tion to be­come the lead­ing com­pa­ny in the space,” No­mu­ra told End­points News.

The pro­fes­sor serves as founder, sci­en­tif­ic ad­vi­sor to and board mem­ber of Vicini­tas, which is cur­rent­ly search­ing for a CEO af­ter hav­ing land­ed CSO Daniel Mar­quess, who pre­vi­ous­ly served in the same po­si­tion at Uni­ty Biotech­nol­o­gy.

In the pa­per, No­mu­ra’s lab was able to link its “deu­biq­ui­ti­nase re­cruiter on to the Ver­tex drug lumacaftor that helps to act as a chem­i­cal chap­er­one for CFTR to sub­se­quent­ly deu­biq­ui­ti­nate and sta­bi­lize the lev­els of the CFTR pro­tein, and al­so im­prove chlo­ride chan­nel func­tion in cys­tic fi­bro­sis cells,” the pro­fes­sor said. The two lead co-au­thors on the pa­per are sci­en­tists at the biotech, he added.

Com­pared to the degra­da­tion field’s PRO­TACs, No­mu­ra char­ac­ter­ized Vicini­tas’ DUB­TACs as “es­sen­tial­ly the op­po­site.” In a nod to the biotech’s name, he said the com­pa­ny’s small mol­e­cules “in­duce the prox­im­i­ty, or vicin­i­ty, of two pro­teins that usu­al­ly don’t in­ter­act in this case to sta­bi­lize the lev­els of aber­rant­ly de­grad­ed pro­teins.”

While cys­tic fi­bro­sis was one of the fo­cus­es of the lab’s pa­per, the lung and di­ges­tive dis­ease is not the on­ly area Vicini­tas will pur­sue. CF will serve as a “test­bed” for broad­en­ing the plat­form’s reach, which could go in­to can­cer, mono­genic dis­eases and hap­loin­suf­fi­cien­cy dis­eases, No­mu­ra said. The lat­ter in­volves hav­ing “on­ly one good copy of a gene, re­sult­ing in half the lev­el of the pro­tein and,” the pro­fes­sor ex­plained, “by slow­ing down the nat­ur­al turnover rate of that pro­tein, you can po­ten­tial­ly in­crease the lev­el of that pro­tein and sub­se­quent­ly con­fer ther­a­peu­tic ben­e­fit.”

Deer­field Man­age­ment and a16z led the Se­ries A, with ad­di­tion­al back­ing from Droia Ven­tures, GV, The Mark Foun­da­tion for Can­cer Re­search and the Berke­ley Cat­a­lyst Fund. The biotech holds the ex­clu­sive li­cense to the work from No­mu­ra’s lab in con­junc­tion with No­var­tis. Deer­field is al­so a backer of an­oth­er No­mu­ra-found­ed biotech, Fron­tier Med­i­cines, a pro­tein degra­da­tion start­up al­lied with Ab­b­Vie.

Aside from Vicini­tas, No­mu­ra will con­tin­ue work­ing with the No­var­tis In­sti­tutes for Bio­Med­ical Re­search in a sec­ond re­search col­lab­o­ra­tion, al­so un­veiled Thurs­day. He will be part of a team that in­cludes fel­low UC Berke­ley pro­fes­sors Dean Toste, Thomas Mai­mone, Ziyang Zhang, and James Olz­mann. The aim of the new No­var­tis-Berke­ley Trans­la­tion­al Chem­i­cal Bi­ol­o­gy In­sti­tute is to find small mol­e­cule com­pounds that could lay the ground­work for new prox­im­i­ty-based ther­a­peu­tics.

“This whole space of in­duced prox­im­i­ty, we’re re­al­ly just at the tip of the ice­berg of the full po­ten­tial of that gen­er­al ap­proach, be­yond degra­da­tion and sta­bi­liza­tion,” No­mu­ra said.

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In­no­v­a­tive MedTech De­mands Spe­cial­ist Clin­i­cal Tri­al Reg­u­la­to­ry Af­fairs and De­sign

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Ted Love, Global Blood Therapeutics CEO

Up­dat­ed: Pfiz­er scoops up Glob­al Blood Ther­a­peu­tics and its sick­le cell ther­a­pies for $5.4B

Pfizer is dropping $5.4 billion to acquire Global Blood Therapeutics.

Just ahead of the weekend, word got out that Pfizer was close to clinching a $5 billion buyout — albeit with other potential buyers still at the table. The pharma giant, flush with cash from Covid-19 vaccine sales, apparently got out on top.

The deal immediately swells Pfizer’s previously tiny sickle cell disease portfolio from just a Phase I program to one with an approved drug, Oxbryta, plus a whole pipeline that, if all approved, the company believes could make for a $3 billion franchise at peak.

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BREAK­ING: Math­ai Mam­men makes an abrupt ex­it as head of the big R&D group at J&J

In an after-the-bell shocker, J&J announced Monday evening that Mathai Mammen has abruptly exited J&J as head of its top-10 R&D group.

Recruited from Merck 5 years ago, where the soft spoken Mammen was being groomed as the successor to Roger Perlmutter, he had been one of the top-paid R&D chiefs in biopharma. His group spent $12 billion last year on drug development, putting it in the top 5 in the industry.

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No­vavax shares shred­ded as Covid vac­cine sales fall more than 90% in Q2

Months after Novavax celebrated its first profitable quarter as a commercial company, the Gaithersburg, MD-based company is back in the red.

Sales for Novavax’s Covid-19 vaccine slipped to $55 million last quarter, down from $586 million in Q1, CEO Stanley Erck revealed on Monday after market close. The company’s stock $NVAX plummeted more than 32% in after-hours trading.

Upon kicking off the call with analysts and investors, Erck addressed the elephant in the room:

Uğur Şahin, BioNTech CEO (Kay Nietfeld/picture-alliance/dpa/AP Images)

De­spite falling Covid-19 sales, BioN­Tech main­tains '22 sales guid­ance

While Pfizer raked in almost $28 billion last quarter, its Covid-19 vaccine partner BioNTech reported a rise in total dose orders but a drop in sales.

The German biotech reported over $3.2 billion in revenue in Q2 on Monday, down from more than $6.7 billion in Q1, in part due to falling Covid sales. While management said last quarter that they anticipated a Covid sales drop — CEO Uğur Şahin said at the time that “the pandemic situation is still very much uncertain” — Q2 sales still missed consensus by 14%.

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FDA commissioner Rob Califf (Tom Williams/CQ Roll Call via AP Images)

With drug pric­ing al­most done, Con­gress looks to wrap up FDA user fee leg­is­la­tion

The Senate won’t return from its summer recess until Sept. 6, but when it does, it officially has 18 business days to finalize the reauthorization of the FDA user fee programs for the next 5 years, or else thousands of drug and biologics reviewers will be laid off and PDUFA dates will vanish in the interim.

FDA commissioner Rob Califf recently sent agency staff a memo explaining how, “Our latest estimates are that we have carryover for PDUFA [Prescription Drug User Fee Act], the user fee funding program that will run out of funding first, to cover only about 5 weeks into the next fiscal year.”

Pascal Soriot, AstraZeneca CEO (David Zorrakino/Europa Press via AP Images)

As­traZeneca and Dai­ichi Sankyo sprint to mar­ket af­ter FDA clears En­her­tu in just two weeks

Regulators didn’t keep AstraZeneca and Daiichi Sankyo waiting long at all for their latest Enhertu approval.

The partners pulled a win on Friday in HER2-low breast cancer patients who’ve already failed on chemotherapy, less than two weeks after its supplemental BLA was accepted. While this isn’t the FDA’s fastest approval — Bristol Myers Squibb won an OK for its blockbuster checkpoint inhibitor Opdivo in just five days back in March — it comes well ahead of Enhertu’s original Q4 PDUFA date.

Bernhardt Zeiher, outgoing Astellas CMO (Astellas)

Q&A: Astel­las' re­tir­ing head of de­vel­op­ment re­flects on gene ther­a­py deaths

For anyone who’s been following discussions about the safety alarms surrounding the adeno-associated viruses (AAV) commonly used to deliver gene therapy, Astellas should be a familiar name.

The Japanese pharma — which bought out Audentes Therapeutics near the end of 2019 and later built a gene therapy unit around the acquisition — rocked the field when it reported three patient deaths in a trial testing AT132, the lead program from Audentes designed to treat a rare muscle disease called X-linked myotubular myopathy (XLMTM).

When the company restarted the trial, it adjusted the dose and instituted a battery of other measures to try to prevent the same thing from happening again. But tragically, the first patient to receive the new regimen died just weeks after administration. The therapy remains under clinical hold, and just weeks ago, Astellas flagged another safety-related hold for a separate gene therapy candidate. In the process of investigating the deaths, the company has also taken flak about the way it disclosed information.

Big questions remain — questions that can have big implications about the future of AAV gene therapies.

Bernhardt Zeiher did not imagine any of it when he first joined Astellas as the therapeutic area leader in inflammation, immunology and infectious diseases. But his ascent to chief medical officer and head of development coincided almost exactly with Astellas’ big move into gene therapy, putting him often in the driver’s seat to grapple with the setbacks.

As Zeiher prepares to retire next month after a 12-year tenure — leaving the unfinished tasks to his successor, a seasoned cancer drug developer — he chatted with Endpoints News, in part, to discuss the effort to understand what happened, lessons learned and the criticism along the way.

The transcript has been lightly edited for length and clarity.

Endpoints: I want to also ask you a bit about the gene therapy efforts you’ve been working on. Astellas has really been at the forefront of discovering the safety concerns associated with AAV gene therapy. What’s that been like for you?

Zeiher: Well, I have to admit, it’s been a bit of a roller coaster. We acquired Audentes. Huge amount of enthusiasm. What we saw with AT132 — that was the lead program in XLMTM — was just remarkable efficacy. I mean, kids who went from being on ventilators, not able to eat for themselves, sit up, do things like that, to off ventilators, walking, you know, really — one investigator called it this Lazarus-like effect. It was just really dramatic efficacy. And then to have the safety events that occurred. So they actually occurred within that first year of the acquisition. So we had the three patient deaths. Me and my organization became very, very much involved. In fact, Ed Conner, who had been the chief medical officer, he left after some of the deaths, but I stepped in as the kind of acting chief medical officer, we had another chief medical officer who was involved, and then we had a fourth death, and I became acting again for a period of time.

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Steve Paul, Karuna Therapeutics CEO (Third Rock)

Karuna's schiz­o­phre­nia drug pass­es a close­ly-watched PhI­II test, will head to FDA in mid-2023

An investigational pill that combines a former Eli Lilly CNS compound with an overactive bladder drug was better than placebo at reducing a scale of symptoms experienced by patients with schizophrenia in a Phase III trial.

Karuna Therapeutics’ drug passed the primary goal in EMERGENT-2, the Boston biotech said early Monday morning, alongside quarterly earnings. The study is the first of Karuna’s four Phase III clinical trials to read out in schizophrenia and will provide the backbone to the biotech’s first drug approval application, slated for mid-2023.

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