Daniel Grau, Avilar CEO

An RA-backed start­up 'AT­AC­s' a nov­el chal­lenge, look­ing to spur pro­tein degra­da­tion out­side the cell

Pro­tein degra­da­tion is one of the hot drug class­es of the fu­ture, but com­peti­tors are pil­ing in with the likes of C4, Arv­inas, Fron­tier Med­i­cines and Vi­vid­ion jostling for po­si­tion. A new start­up wants to ap­ply the lessons learned from degra­da­tion out­side the cell, and it now has the green­light from RA Cap­i­tal to steam ahead.

Avi­lar Ther­a­peu­tics launched Thurs­day with $60 mil­lion from found­ing in­vestor RA to chase a nov­el pro­tein degra­da­tion drug class the start­up is call­ing AT­ACs— short for “AS­G­PR Tar­get­ing Chimeras” — that looks to trash un­want­ed pro­teins cir­cu­lat­ing out­side the hu­man cell.

AT­ACs are the next in a line of acronymed degra­da­tion drugs, fol­low­ing the likes of PRO­TAC, LYTEC, AT­TEC and more. The big dif­fer­ence here is that Avi­lar’s plat­form looks to spur on pro­tein degra­da­tion in the ex­tra­cel­lu­lar en­vi­ron­ment, drag­ging tar­get­ed pro­teins to dis­pos­al sites on liv­er cells.

The idea be­hind AT­ACs start­ed from a sim­ple ques­tion in the halls at RA, CEO Dan Grau told End­points News: Pro­tein de­graders are great and grow­ing in­creas­ing­ly val­i­dat­ed in an­i­mals and hu­mans, but can we use the same mech­a­nism out­side the cell? That in­quiry led the Avi­lar team to the AS­G­PR re­cep­tor on the sur­faces of he­pa­to­cytes, a key tran­sit point for liv­er cells’ break­ing down en­doge­nous pro­teins.

By lever­ag­ing the liv­er’s nat­ur­al process­es, the team en­vi­sioned a drug class that could latch a vast range of pro­teins on­to those AS­G­PR re­cep­tors and kick­start degra­da­tion in the lyso­some. Such a drug, com­prised of one lig­and used to bind to a tar­get pro­tein and an­oth­er to bind to AS­G­PR, would act as an Uber to the shred­der for un­want­ed pro­teins in the blood, a mech­a­nism that could have a broad range of ap­pli­ca­tions across ther­a­peu­tic ar­eas.

“What was im­por­tant ear­ly on was the iden­ti­fi­ca­tion ear­ly on of an op­por­tu­ni­ty to de­sign small mol­e­cule lig­ands to AS­G­PR that could per­form bet­ter than his­tor­i­cal chemistries or per­form bet­ter than the way na­ture is do­ing it it­self,” Grau said. “The way we like to think about it is on the one hand we’re har­ness­ing a nat­ur­al process while al­so im­prov­ing on na­ture it­self.”

The prob­lem, Grau said, is that there was a lot of bi­o­log­i­cal and chem­i­cal ground­work still un­known be­tween con­ceiv­ing of such a project and re­al­iz­ing it. The idea be­hind AT­AC came up in ear­ly 2020 and was mov­ing quick­ly, but Grau, who came on board in May, said the com­pa­ny most­ly had to start from scratch to build its tech plat­form while al­so run­ning at full speed.

Effie Toz­zo

First, the team dove in­to the chem­istry of high-affin­i­ty AS­G­PR bind­ing, cre­at­ing a li­brary of lig­ands it could use to ef­fec­tive­ly bind to that re­cep­tor. Then, Avi­lar turned its at­ten­tion to de­vel­op­ing a mod­u­lar plat­form for AT­ACs — ef­fec­tive­ly swap­ping out lig­ands with dif­fer­ent binders to tar­get a wider range of pro­teins — and cre­at­ing math­e­mat­i­cal mod­els to best pre­dict the PK and PD ef­fects of the drugs.

Fi­nal­ly, and per­haps most promis­ing giv­en the wide range of po­ten­tial ther­a­peu­tic ap­pli­ca­tions for a plat­form like this, Avi­lar cre­at­ed a pro­teome map­ping sys­tem that would give it a grow­ing un­der­stand­ing of how ex­tra­cel­lu­lar pro­teins func­tion and how the body’s nat­ur­al degra­da­tion process works; a guide­post, if you will, for the path to clin­i­cal de­vel­op­ment.

Now, with its tech ready for show­time, Avi­lar is work­ing on con­struct­ing a pipeline as Grau looks to build a team of ex­perts around him. He took the first shot this week, hir­ing on Effie Toz­zo, a vet­er­an of Mer­ck, Roche and Astel­las, as the com­pa­ny’s first CSO.

On the pipeline front, Grau was mum, but he did say the first pro­gram would be close­ly watched as it could po­ten­tial­ly of­fer proof-of-mech­a­nism for the com­pa­ny’s en­tire plat­form.

“When we go in­to our first clin­i­cal tri­al … in that con­text, we will be mea­sur­ing the lev­els of pro­tein we wish to de­grade and will be able to show the lev­els of degra­da­tion of that pro­tein,” Grau said. “This pro­vides a very ear­ly proof of mech­a­nism and an ac­cel­er­a­tion of val­ue, but what’s nice is that it’s go­ing to be true for every AT­AC pro­gram.”

So, with no dead­line set, it’s all eyes on that first hu­man study. But there may be even more in the works over at Avi­lar: Grau not­ed the com­pa­ny is work­ing on “ad­di­tion­al tech­nolo­gies” in ex­tra­cel­lu­lar degra­da­tion that could add even more meat on the bone here.

Stay tuned.

Biotech in­vestors and CEOs see two paths to growth, but are they equal­ly vi­able?

The dynamic in the biotech market has been highly volatile in the last few years, from the high peaks immediately after the COVID vaccine in 2021, to the lowest downturns of the last 20 years in 2022. This uncertainty makes calling the exact timing of the market’s turn something of a fool’s errand, according to Dr. Chen Yu, Founder and Managing Partner of TCG Crossover (TCG X). He speaks with RBC’s Noël Brown, Head of US Biotechnology Investment Banking, about the market’s road ahead and two possible paths for growth.

Vlad Coric, Biohaven CEO

Vlad Coric charts course for 'New Bio­haven' with neu­ro­science push and Big Phar­ma vets on board

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Pfizer officially scooped up Biohaven’s CGRP assets on Monday, including blockbuster migraine drug Nurtec and the investigational zavegepant, for $11.6 billion. As a result, Coric spun the broader pipeline into an independent company on Tuesday — with the same R&D team behind Nurtec but about 1,000 fewer staffers and a renewed focus on neuroscience and rare disease.

In AstraZeneca's latest campaign, wild eosinophils called Phils personify the acting up often seen in uncontrolled asthma

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There are some odd-looking purple creatures lurking around the halls of AstraZenca lately. The “Phil” character cutouts are purple, personified eosinophils with big buggy eyes and wide mouths, and they’re a part of AZ’s newest awareness effort to help people understand eosinophilic asthma.

The “Asthma Behaving Badly” characters aren’t only on the walls at AZ to show the new campaign to employees, however. The “Phils” are also showing up online on the campaign website, and in digital and social ads and posts on Facebook and Instagram.

Casey McPherson shows his daughters Rose (left) and Weston around Everlum Bio, a lab that he co-founded to spark a treatment for Rose and others with ultra-rare conditions. (Ilana Panich-Linsman)

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Under bright lab lights, Casey McPherson holds his 6-year-old daughter, Rose. His free hand directs Rose’s gaze toward a computer screen with potential clues in treating her one-of-a kind genetic condition.

Gray specks on the screen show her cells that scientists reprogrammed with the goal of zeroing in on a custom medicine. McPherson co-founded the lab, Everlum Bio, to spark a treatment for Rose — and others like her. A regarded singer-songwriter, McPherson never imagined going into drug development.

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Ying Huang, Legend CEO

Lentivi­ral vec­tor ramp-up: J&J and Leg­end to in­vest $500M in New Jer­sey man­u­fac­tur­ing to sup­port Carvyk­ti

In response to a question on manufacturing scale at Legend Biotech’s R&D day yesterday, the company’s top exec said its partnership with Johnson & Johnson will be doubling its investment in its New Jersey manufacturing center and will be investing a total of $500 million.

With an eye on their BCMA-directed CAR-T therapy Carvykti (cilta-cel), approved in February as a fifth-line treatment for multiple myeloma, Legend CEO Ying Huang said that the ramp-up in production and the decision to manufacture its own lentiviral vectors — currently in shortage worldwide — means they won’t have to deal with that shortage.

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Kite Pharma just got FDA approval to kick off operations at a new manufacturing campus.

The cancer-focused, CAR-T cell therapy player made the announcement Monday, saying that the federal regulatory agency gave the green light to Kite’s 100,000 square-foot, retroviral vector manufacturing facility in Oceanside, CA.

Kite’s global head of technical operations Chris McDonald tells Endpoints News that the facility has been in the works for about four years, after Kite teamed up with its parent company Gilead. Gilead acquired Kite Pharma for just shy of $12 billion in 2017.

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Novartis is turning to a winning coach to talk about Leqvio and the struggles of high cholesterol — including his own. Bruce Arians, the retired NFL head coach of the Arizona Cardinals and Super Bowl-winning Tampa Bay Buccaneers, is partnering with the pharma for its “Coaching Cholesterol” digital, social and public relations effort.

In the campaign, Arians talks about the potential for “great comebacks” in football and heart health. Once nicknamed a “quarterback whisperer,” he is now retired from fulltime coaching (although still a front-office consultant for Tampa Bay), and did a round of media interviews for Novartis, including one with People and Forbes.

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Amy West, Novo Nordisk head of US digital innovation and transformation (Illustration: Assistant Editor Kathy Wong for Endpoints News)

Q&A: No­vo Nordisk dig­i­tal in­no­va­tion chief Amy West dis­cuss­es phar­ma pain points and a health­care 'easy but­ton’

Amy West joined Novo Nordisk more than a decade ago to oversee marketing strategies and campaigns for its US diabetes portfolio. However, her career path shifted into digital, and she hasn’t looked back. West went from leading Novo’s first digital health strategy in the US to now heading up digital innovation and transformation.

She’s currently leading the charge at Novo Nordisk to not only go beyond the pill with digital marketing and health tech, but also test, pilot and develop groundbreaking new strategies needed in today’s consumerized healthcare world.

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Marc Dunoyer, Alexion CEO (AstraZeneca via YouTube)

Up­dat­ed: As­traZeneca nabs a small rare dis­ease gene ther­a­py play­er for 667% pre­mi­um

AstraZeneca is kicking off the fourth quarter with a little M&A Monday for a gene editing player recently overcoming a second clinical hold to its only program in human studies.

The Big Pharma and its subsidiary Alexion are buying out little LogicBio for $2.07 per share. That’s good for a massive 667% premium over its Friday closing price, when it headed into the weekend at 27 cents and just weeks after Nasdaq said LogicBio would have to delist, which has been put on hold as the biotech requests a hearing. It’s one of two biotech deals to commence October, alongside the news of Incyte buying a vitiligo-focused biotech.

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