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.”

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His­toric drug pric­ing re­forms pass; Pfiz­er ac­quires GBT; The long search for non-opi­oid pain drugs; 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.

The Endpoints Weekly has officially crossed the 60,000 mark on subscribers — thanks to all of your support. As the editorial team grows, we’ve been able to do a lot more, with many of those on display this week. Be sure to check out Lei Lei Wu’s deep dive on pain R&D. If you missed it, you may also rewatch her companion panel here.

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Gold for adults, sil­ver for in­fants: Pfiz­er's Pre­vnar 2.0 head­ed to FDA months af­ter Mer­ck­'s green light

Pfizer was first to the finish line for the next-gen pneumococcal vaccine in adults, but Merck beat its rival with a jab for children in June.

Now, two months after Merck’s 15-valent Vaxneuvance won the FDA stamp of approval for kids, Pfizer is out with some late-stage data on its 20-valent shot for infants.

Known as Prevnar 20 for adults, Pfizer’s 20vPnC will head to the FDA by the end of this year for an approval request in infants, the Big Pharma said Friday morning. Discussions with the FDA will occur first and more late-stage pediatric trials are expected to read out soon, informing the regulatory pathway in other countries and regions.

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Seagen interim CEO Roger Dansey and Daiichi Sankyo CEO Sunao Manabe

Paving the way for Mer­ck­'s buy­out, Seagen los­es ar­bi­tra­tion dis­pute with Dai­ichi over ADC tech

As Seagen awaits a final buyout offer from Merck that could be in the territory of $40 billion, Seagen revealed Friday afternoon that it lost an arbitration dispute with Daiichi Sankyo relating to the companies’ 2008 collaboration around the use of antibody-drug conjugate (ADC) technology.

But that loss likely won’t matter much when it comes to Merck’s deal.

After breaking off its pact with Daiichi in mid-2015, the two companies battled over “linker” tech — a chemical bridge between an ADC’s antibody component and the cytotoxic payload — that Seagen claims Daiichi would improve upon and implement in its current generation of ADCs.

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Benjamin Oakes, Scribe Therapeutics CEO

CEO of Doud­na spin­out: With­in five years, genome ed­i­tors will have a 're­al­ly big im­pact' on pa­tients' lives

“CRISPR-by-design” is the idea behind Scribe Therapeutics, a company spun out from Jennifer Doudna’s Nobel-winning lab that’s competing in a closely-tracked field of genome editor companies just starting to make their way to the clinic.

After nabbing $100 million last March for its Series B funding round, Scribe is taking a different tack from some of its competitors, crafting a new enzyme isolated from bacteria called CasX, which has now been tweaked extensively and may be targeted to a range of genome-related diseases, offering a plethora of therapeutic options.

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Alessandro Maselli, Catalent CEO

Catal­ent ac­quires North Car­oli­na CD­MO for $475M, boost­ing oral solids work

As Catalent has been expanding its reach in the US this year, as well as recently completing a C-suite shuffle, the company announced last night that it has acquired the CDMO Metrics Contract Services for $475 million from Mayne Pharma Group.

The acquisition will increase Catalent’s capabilities in oral solid formulation development, manufacturing and packaging as well as expand its capacity to handle more highly potent compounds.

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House pass­es his­toric drug pric­ing re­forms, lin­ing up decades-in-the-mak­ing win for Biden and De­moc­rats

The US House of Representatives today voted along party lines (all Dems voted for it), 220-207 to pass new, wide-ranging legislation that will allow Medicare drug price negotiations for the first time ever, and cap seniors’ drug expenses to $2,000 per year and seniors’ insulin costs at $35 per month.

Setting up a major victory for President Joe Biden, representatives returned from their summer recess to pass the Inflation Reduction Act, even as many noted the bill would only modestly reduce inflation.

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Senate Finance Committee Chair Ron Wyden (D-OR) (Francis Chung/E&E News/POLITICO via AP Images)

Sen­ate Fi­nance chair con­tin­ues his in­ves­ti­ga­tion in­to phar­ma tax­es with re­quests for Am­gen

Amgen is the latest pharma company to appear on the radar of Senate Finance Committee Chair Ron Wyden (D-OR), who is investigating the way pharma companies are using subsidiaries in low- or zero-tax countries to lower their tax bills.

Like its peers Merck, AbbVie and Bristol Myers Squibb, Wyden notes how Amgen uses its Puerto Rico operations to consistently pay tax rates that are substantially lower than the U.S. corporate tax rate of 21%, with an effective tax rate of 10.7% in 2020 and 12.1% in 2021.

FDA ap­proves sec­ond in­di­ca­tion for As­traZeneca and Dai­ichi's En­her­tu in less than a week

AstraZeneca and Daiichi Sankyo’s antibody-drug conjugate Enhertu scored its second approval in less than a week, this time for a subset of lung cancer patients.

Enhertu received accelerated approval on Thursday to treat adults with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations, and who have already received a prior systemic therapy.

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