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.

Late Fri­day ap­proval; Trio of biotechs wind down; Stem cell pi­o­neer finds new fron­tier; Biotech icon to re­tire; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

I hope your weekend is off to a nice start, wherever you are reading this email. As for me, I’m trying to catch the tail of the Lunar New Year festivities.

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Pfiz­er lays off em­ploy­ees at Cal­i­for­nia and Con­necti­cut sites

Pfizer has laid off employees at its La Jolla, CA, and Groton, CT sites, according to multiple LinkedIn posts from former employees.

The Big Pharma confirmed to Endpoints News it has let go of some employees, but a spokesperson declined to specify how many workers were impacted and the exact locations affected. Earlier this month, the drug developer had confirmed to Endpoints it was sharpening its focus and doing away with some early research on areas such as rare disease, oncology and gene therapies.

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Rodney Rietze, iVexSol CEO

Bris­tol My­ers, Charles Riv­er join Se­ries A fund­ing for iVex­Sol

Massachusetts-based iVexSol has secured funding to the tune of $23.8 million in its latest Series A round. The new investors include Bristol Myers Squibb, manufacturer Charles River Laboratories and Asahi Kasei Medical.

iVexSol is a manufacturer of lentiviral vectors (LVV), used in making gene therapies, and this latest round of fundraising brings its total Series A total over $39 million, which will be used to recruit more employees and bolster its technology.

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Jake Van Naarden, Loxo@Lilly CEO

Lil­ly en­ters ripe BTK field with quick FDA nod in man­tle cell lym­phoma

Eli Lilly has succeeded in its attempt to get the first non-covalent version of Bruton’s tyrosine kinase, or BTK, inhibitors to market, pushing it past rival Merck.

The FDA gave an accelerated nod to Lilly’s daily oral med, to be sold as Jaypirca, for patients with relapsed or refractory mantle cell lymphoma.

The agency’s green light, disclosed by the Indianapolis Big Pharma on Friday afternoon, catapults Lilly into a field dominated by covalent BTK inhibitors, which includes AbbVie and Johnson & Johnson’s Imbruvica, AstraZeneca’s Calquence and BeiGene’s Brukinsa.

Tony Johnson, Goldfinch Bio CEO (Goldfinch via YouTube)

Kid­ney dis­ease drug­mak­er Goldfinch Bio shuts down

Goldfinch Bio, attempting to make treatments for kidney diseases and diabetic nephropathy, is shutting down.

President and CEO Tony Johnson confirmed to Endpoints News Friday afternoon that the biotech shut down after “fundraising challenges in the current macro-environment.” Fierce Biotech first reported the news.

Johnson, who joined in 2017 after a stint as SVP of early clinical development at AstraZeneca, said in a text that the company “entered the ABC process recently,” referring to an assignment for the benefit of the creditors, which provides a different wind-down avenue than a bankruptcy.

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Filip Dubovsky, Novavax CMO

No­vavax gets ready to take an­oth­er shot at Covid vac­cine mar­ket with next sea­son plans

While mRNA took center stage at yesterday’s FDA vaccine advisory committee meeting, Novavax announced its plans to deliver an updated protein-based vaccine based on new guidance.

Vaccines and Related Biological Products Advisory Committee (VRBPAC) members voted unanimously in favor of “harmonizing” Covid vaccine compositions, meaning all future vaccine recipients would receive a bivalent vaccine, regardless of whether they’ve gotten their primary series.

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Eliot Forster, F-star CEO (Rachel Kiki for Endpoints News)

F-star gets down to the wire with $161M sale to Chi­nese buy­er as na­tion­al se­cu­ri­ty con­cerns linger

With the clock ticking on F-star Therapeutics’ takeover by a Chinese buyer, the companies are still scrambling to remove a hold on the deal from the US government’s Committee on Foreign Investment in the United States.

F-star and invoX Pharma said they are “actively negotiating” with CFIUS “about the terms of a mitigation agreement to address CFIUS’s concerns regarding potential national security risks posed by the transaction.”

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CBER Director Peter Marks (Susan Walsh/AP Images)

FDA ad­vi­so­ry com­mit­tee votes unan­i­mous­ly in fa­vor of bi­va­lent Covid shots re­plac­ing pri­ma­ry se­ries

The FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) voted unanimously in favor of “harmonizing” Covid vaccine compositions, meaning all current vaccine recipients would receive a bivalent vaccine, regardless of whether they’ve gotten their primary series.

The vote marks an effort to clear up confusion around varying formulations and dosing schedules for current primary series and booster vaccines, as well as “get closer to the strains that are circulating,” according to committee member Paul Offit, professor of pediatrics at the Children’s Hospital of Philadelphia.

In­vestor 'misalign­men­t' leads to tR­NA biotech's shut­ter­ing

A small biotech looking to carve a lane in the tRNA field has folded, an investor and a co-founder confirmed to Endpoints News.

Similar to Flagship’s Alltrna and other upstarts like Takeda-backed hC Bioscience, the now-shuttered Theonys was attempting to go after transfer RNA, seen as a potential Swiss Army knife in the broader RNA therapeutics space. The idea is that one tRNA drug could be used across a galaxy of disorders and diseases.

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