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.”

Mi­no­ryx and Sper­o­genix ink an ex­clu­sive li­cense agree­ment to de­vel­op and com­mer­cial­ize lerigli­ta­zone in Chi­na

September 23, 2020 – Hong Kong, Beijing, Shanghai (China) and Mataró, Barcelona (Spain)  

Minoryx will receive an upfront and milestone payments of up to $78 million, as well as double digit royalties on annual net sales 

Sperogenix will receive exclusive rights to develop and commercialize leriglitazone for the treatment of X-linked adrenoleukodystrophy (X-ALD), a rare life-threatening neurological condition

President Trump walks past HHS secretary Alex Azar (Getty Images)

Azar falls in line un­der Trump again. Ex­perts say he's re­in­forc­ing a dark sig­nal sent to the FDA

In the latest incident where Alex Azar has steadfastly taken the side of President Donald Trump over that of the FDA, the HHS secretary was noncommittal this morning when asked if he supports the attempt by his subordinates at the FDA to strengthen guidelines for a vaccine EUA.

Appearing on NBC’s Today Show, the HHS secretary muddied the waters, stating that the guidance that matters is the one that is “actually already out there.”

Vas Narasimhan (AP Images)

UP­DAT­ED: Still held down by clin­i­cal hold, No­var­tis' Zol­gens­ma falls fur­ther be­hind Bio­gen and Roche as FDA asks for a new piv­otal study

Last October, the FDA slowed down Novartis’ quest to extend its gene therapy to older spinal muscular atrophy patients by slapping a partial hold on intrathecal administration. Almost a year later, the hold is still there, and regulators are adding another hurdle required for regulatory submission: a new pivotal confirmatory study.

The new requirement — which departs significantly from Novartis’ prior expectations — will likely stretch the path to registration beyond 2021, when analysts were expecting a BLA submission. That could mean more time for Biogen to reap Spinraza revenues and Roche to ramp up sales of Evrysdi in the absence of a rival.

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David Berry (Flagship)

Flag­ship's next big tech­no­log­i­cal bet? The cloud

Earlier this month, Flagship announced their big bet on the software half the industry is talking about, launching the AI and machine learning startup. Now, they and a couple other investors are gambling $100 million on a software that much of the public generally thinks of as a cool, IT afterthought: cloud computing.

The idea, says founder and Flagship partner David Berry, is one of scale: The sheer magnitude of biological data that you can store on cloud technology is unprecedented. And that size, when leveraged properly, can allow you to ask questions and form insights that are similarly unprecedented.

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New York governor Andrew Cuomo (AP Images)

An­drew Cuo­mo says New York will un­der­take its own vac­cine re­view process, and wouldn’t rec­om­mend trust­ing the fed­er­al gov­ern­ment

The concerns keep mounting over President Donald Trump’s politicization of the FDA and other federal agencies guiding the development of a safe and effective vaccine. And today, the telegenic New York governor Andrew Cuomo appeared to introduce even more politics into the matter — latest in an ongoing series of incidents that have cast the proudly independent FDA in starkly political terms.

During his daily press conference Cuomo said that the state will review any coronavirus vaccines approved by the federal government, citing a lack of trust of the Trump administration. The announcement comes one day after Trump accused the FDA of making an “extremely political” move in proposing stricter vaccine guidance.

Covid-19 roundup: Op­er­a­tion Warp Speed's 7th vac­cine is live at­ten­u­at­ed; Small biotech touts big suc­cess where gi­ants have failed

Operation Warp Speed is stacking its vaccine portfolio with a “TBD” new candidate: a live attenuated vaccine that can be administered in a single dose, potentially as an oral formulation rather than an injection.

Sound familiar?

That could be because the unannounced candidate appears to match the profile of an inoculation being developed by Merck, according to Bloomberg, which first reported the development based on a presentation by Moncef Slaoui.

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On­ly five months af­ter a Se­ries A launch, Taysha goes pub­lic with $157M IPO

As has been the trend in 2020, Taysha Gene Therapies has become the latest biotech to make a quick ascent from a small, privately-funded company to enjoying its very own Nasdaq ticker.

The Dallas-based biotech raised $157 million for its IPO after pricing shares at $20 apiece Thursday, the high-point of its expected range. Initially pegging $100 million in financing, Taysha offered a little less than 8 million shares and will trade under the $TSHA symbol.

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Scoop: ARCH’s Bob Nelsen is back­ing an mR­NA up­start that promis­es to up­end the en­tire man­u­fac­tur­ing side of the glob­al busi­ness

For the past 2 years, serial entrepreneur Igor Khandros relied on a small network of friends and close insiders to supply the first millions he needed to fund a secretive project to master a new approach to manufacturing mRNA therapies.

Right now, he says, he has a working “GMP-in-a-box” prototype for a new company he’s building — after launching 3 public companies — which plans to spread this contained, precise manufacturing tech around the world with a set of partners. He’s raised $60 million, recruited some prominent experts. And not coincidentally, he’s going semi-public with this just as a small group of pioneers appears to be on the threshold of ushering in the world’s first mRNA vaccines to fight a worldwide pandemic.

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CDC’s Robert Redfield, NIAID’s Anthony Fauci, Admiral Brett Giroir at HHS, and FDA’s Stephen Hahn prepare to testify at a House hearing on June 23 (Getty)

'Ex­treme­ly po­lit­i­cal' — Trump neuters FDA's at­tempt to strength­en vac­cine EUA

Stephen Hahn went before a Senate committee Wednesday and declared he’s fighting. “Every one of the decisions we have reached has been made by career FDA scientists based on science and data, not politics,” he exclaimed, adding that “FDA will not permit any pressure from anyone to change that. I will fight for science.”

A few hours later, he was undermined by President Donald Trump when a reporter asked if he was okay with stricter vaccine guidelines that the FDA was said to be cooking up. “That has to be approved by the White House. We may or may not approve it. That sounds like a political move,” he decided.