Spun out of George Church's lab, this biotech up­start is map­ping the AAV uni­verse for No­var­tis, Sarep­ta to gaze

In a few days, through a se­ries of video con­fer­ences, gene ther­a­py re­searchers around the world will be pre­sent­ing their lat­est find­ings at the vir­tu­al an­nu­al meet­ing of the Amer­i­can So­ci­ety of Gene & Cell Ther­a­py. Al­most every dis­cus­sion will fea­ture a top­ic that has been cen­tral to the ex­is­tence of the field but con­tin­ues to per­plex ex­perts as they seek to re­fine the modal­i­ty: the de­liv­ery of a gene to the tis­sue where it’s need­ed to fix dis­ease.

For the first time, a biotech up­start will be pub­licly out­lin­ing their take on the prob­lem — with an ar­ti­fi­cial in­tel­li­gence fla­vor that No­var­tis and Sarep­ta are gob­bling up.

Sea­soned at­ten­dees of AS­GCT would rec­og­nize the team be­hind Dyno Ther­a­peu­tics. Since Er­ic Kel­sic be­gan build­ing the plat­form in 2015 as a post­doc at George Church’s il­lus­tri­ous lab at Wyss In­sti­tute, he’s been mak­ing the rounds at sci­en­tif­ic meet­ings. At Har­vard, his group had demon­strat­ed how — by do­ing high through­put screen­ing on all cap­sid vari­ants of one par­tic­u­lar AAV serotype, mod­el­ing the space with ma­chine learn­ing, and fi­nal­ly build­ing a pro­file of each cap­sid that can be ranked by dif­fer­ent at­trib­ut­es — they could point to syn­thet­ic AAV cap­sid can­di­dates that are su­pe­ri­or to the hand­ful of nat­ur­al vari­ants cur­rent­ly in use.

Alan Crane

“This was by far the best ap­pli­ca­tion that I’d ever seen of AI in bi­ol­o­gy,” Alan Crane, an en­tre­pre­neur part­ner at Po­laris and Dyno’s ex­ec­u­tive chair­man, told End­points News. “It turns out po­ten­tial part­ners were see­ing it the same way, be­cause when Er­ic came to me back in mid-2018, he al­ready had this list of lit­er­al­ly dozens of com­pa­nies that have proac­tive­ly ap­proached him.”

Out of that pool Dyno had picked No­var­tis for a col­lab­o­ra­tion on eye dis­or­ders and Sarep­ta to team up on mus­cle dis­eases. Up­front pay­ments, sup­port, op­tion fees and mile­stones from these two deals could add up to $2 bil­lion, in­clud­ing $40 mil­lion from the re­search phase of the Sarep­ta deal.

Louise Rodi­no-Kla­pac

“We al­ways con­stant­ly try to make sure that we are ahead of the curve in terms of our tech­nol­o­gy and look­ing at next-gen­er­a­tion treat­ments,” Louise Rodi­no-Kla­pac, Sarep­ta’s head of gene ther­a­py, said. “So al­though we’re very hap­py with our cur­rent ap­proach and our cur­rent vec­tor, we’re think­ing about the fu­ture po­ten­tial tech­nolo­gies for oth­er mus­cu­lar dy­s­tro­phies.”

Cap­sids — the pro­tein shells that en­close ge­net­ic ma­te­r­i­al of a virus — is one of three core com­po­nents need­ed to form a gene ther­a­py, she ex­plained, along­side the trans­gene that’s miss­ing or de­fec­tive in a pa­tient, and a pro­mot­er that turns the gene on in the cell. And small tweaks to the cap­sid can trans­late to pro­found changes in the fi­nal prod­uct’s im­muno­genic­i­ty, man­u­fac­tura­bil­i­ty, ef­fi­cien­cy of de­liv­ery, speci­fici­ty to tar­get cells and pack­age size.

Er­ic Kel­sic

All of these met­rics are tak­en in­to con­sid­er­a­tion on Dyno’s Cap­sidMap plat­form, which takes “the most com­pre­hen­sive ap­proach to map­ping out the AAV uni­verse,” fill­ing the gaps in each galaxy and telling stars from pure void, Kel­sic said.

“We don’t want to im­prove one prop­er­ty but have oth­er things get worse,” a chal­lenge that oth­ers who have at­tempt­ed to solve the prob­lem have faced, he added.

With a new tech­nol­o­gy that promis­es to op­ti­mize vi­ral vec­tors for in­di­vid­ual ap­pli­ca­tions like that, Crane pre­dict­ed the com­pa­ny — which Po­laris seed­ed with a mod­est $9 mil­lion — might nev­er need ad­di­tion­al ven­ture funds.

While Dyno re­tains the op­tion to cre­ate its own ther­a­pies, ex­pect part­ner­ships (and there are more com­ing) to re­main at the cen­ter for a while.

“What I’ve ob­served in the in­dus­try — not on­ly in gene ther­a­py but in all ar­eas — is as com­pa­nies start to move in­to pipelines, they usu­al­ly have to leave the plat­form be­hind,” Crane said.

Much work is to be done. Dyno cur­rent­ly has ca­pac­i­ty to screen hun­dreds of thou­sands to mil­lions of cap­sids and test them both in vit­ro and in vi­vo, but the plan is to scale up the in­fra­struc­ture even fur­ther — both on the ex­per­i­men­tal and the com­pu­ta­tion­al fronts. The head­count is dou­bling from rough­ly 20 while all the ma­chine learn­ing gets moved on­to the cloud.

A can­di­date won’t emerge any time soon, and even when it does ma­te­ri­al­ize it would have to go through rig­or­ous safe­ty test­ing at the part­ners’ own R&D op­er­a­tions — a process that could take an­oth­er one or two years. Still, Kel­sic sees it as the quick­est way to bring their work to pa­tients even while they fig­ure new things out.

“Es­pe­cial­ly when we’re think­ing about tech­nol­o­gy, some­thing George and I talked a lot about when we start­ed this project, it still feels re­al­ly ear­ly days for gene ther­a­py,” he said. “There’s so much po­ten­tial.”

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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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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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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Alon Seri-Levy, Sol-Gel Technologies CEO

Bridge­Bio com­pa­ny sells off rare dis­ease can­di­date to Gal­der­ma part­ner

Israeli biotech Sol-Gel Technologies announced Friday that it got its hands on a rare disease drug candidate from PellePharm for almost $75 million, amid claims that the drug has the potential to reach a $300 million market.

Execs said on a conference call Friday morning that patidegib, a hedgehog signaling pathway blocker, is being investigated to treat Gorlin syndrome, a rare genetic disorder that increases the risk of developing certain kinds of cancer such as basal cell skin cancer and medulloblastoma, a type of brain cancer. The disease affects around one in every 31,000 people, and an estimated 70,000 people worldwide.

Steve Harr, Sana Biotechnology CEO

Four years in, Sana gets first FDA go-ahead to bring can­cer treat­ment in­to the clin­ic

Sana Biotechnology is finally headed to the clinic.

Thursday afternoon, the biotech announced the FDA had cleared its application to start a clinical trial for its allogeneic, or “off-the-shelf,” CAR-T cell therapy targeting the antigen CD19 for patients with B-cell lymphomas and leukemias. Sana said its therapy, dubbed SC291, was designed to evade the immune system, which could help cell therapy produce a more durable response in patients, a concern that has followed such off-the-shelf therapies that use donor cells as opposed to a patient’s own cells.

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Ying Huang, Legend CEO

J&J, Leg­end say Carvyk­ti beat stan­dard ther­a­py in ear­li­er-line blood can­cer

J&J and Legend Biotech’s next step in turning their CAR-T therapy Carvykti into a potential megablockbuster has succeeded, the companies said Friday.

Carvykti achieved the primary endpoint — progression-free survival — in an open-label Phase III study testing the treatment in second- to fourth-line multiple myeloma patients. The CARTITUDE-4 trial, for which there aren’t any hard data yet, represents the biggest development for Carvykti’s ability to compete with Bristol Myers Squibb’s Abecma since its approval last February.