From L-R: Gerard Caelles, Miquel Vila-Perelló and Silvia Frutos (SpliceBio)

Some genes are too large to fit in­to AAV vec­tors. UCB, No­var­tis back $57M idea to de­liv­er them in parts in­stead

Of all the ma­jor lim­i­ta­tions of ade­no-as­so­ci­at­ed virus­es (AAV) as a vec­tor for gene ther­a­py, one is par­tic­u­lar­ly well-known and in­dis­putable: They can on­ly car­ry a trans­gene up to a cer­tain size. De­sign a pay­load larg­er than 4.7kb, and there’s sim­ply no way you can fit every­thing in.

That’s why gene ther­a­py de­vel­op­ers work­ing on, say, Duchenne mus­cu­lar dy­s­tro­phy have come up with workarounds, such as cre­at­ing short­ened ver­sions of the tar­get gene.

But a Span­ish biotech be­lieves there’s an al­ter­na­tive: What if you can de­liv­er the full gene in two parts?

Splice­Bio has raised close to $57 mil­lion (€50 mil­lion) from UCB Ven­tures, Ys­ios Cap­i­tal, New En­ter­prise As­so­ci­ates, Gilde Health­care, No­var­tis Ven­ture Fund and Asabys Part­ners to test the con­cept, start­ing with a rare ge­net­ic dis­ease of the eye.

The big idea here is pro­tein splic­ing. Miquel Vi­la-Perel­ló, co-founder and CEO, be­gan study­ing pro­tein seg­ments known as in­teins while work­ing as a re­search schol­ar with Prince­ton’s Tom Muir.

Since their dis­cov­ery in the late 1990s, in­teins have been ex­plored for var­i­ous ap­pli­ca­tions in bio­con­ju­ga­tion and pro­tein re­con­sti­tu­tion, Vi­la-Perel­ló said. But they large­ly failed to cat­alyze re­ac­tions as ef­fi­cient­ly as re­searchers were hop­ing.

Build­ing on close to two decades of work by Muir, “we ba­si­cal­ly evolved or de­vel­oped, en­gi­neered nov­el in­teins that are en­gi­neered that over­come the lim­i­ta­tions of the nat­ur­al ones,” he said.

Ap­plied to gene ther­a­py, it trans­lates to two dif­fer­ent AAV vec­tors each en­cod­ing for rough­ly half the pro­tein you want, with an in­tein tagged to each. Once the body churns out the de­sired pro­tein, the in­teins bind the two frag­ments to form a full-length pro­tein — then get cleaved off.

“Through our plat­form tech­nol­o­gy, we can go af­ter tar­gets that, you know, that were kind of off the pic­ture for gene ther­a­py … be­cause these genes were too large,” Vi­la-Perel­ló said. “So these dis­eases were kind of ruled out or peo­ple were try­ing these rather con­vo­lut­ed ap­proach­es of the mi­ni-genes or dif­fer­ent strate­gies that have not re­al­ly panned out.”

Work­ing out of Barcelona with a team of 10 — they hope to dou­ble the head­count with the new round — Splice has nom­i­nat­ed a lead pro­gram in Star­gardt dis­ease. A com­mon form of ju­ve­nile mac­u­lar dy­s­tro­phy, Star­gardt is “a very preva­lent dis­ease for a rare dis­ease,” said CBO Ger­ard Caelles, with more than 80,000 es­ti­mat­ed pa­tients in the US and EU. The con­di­tion is caused by a loss of func­tion mu­ta­tion in the AB­CA4 gene, which is 6.8kb large.

While oth­er sci­en­tists have pro­posed a dual-vec­tor ap­proach to AAV gene ther­a­py, they re­lied on DNA re­com­bi­na­tion to piece the full pro­tein to­geth­er.

“We es­ti­mate that from 20% up to 50% of all mono­genic dis­eases could ben­e­fit from our tech­nol­o­gy,” Caelles said.

With co-founder Sil­via Fru­tos head­ing the plat­form tech­nol­o­gy as CTO/COO, Splice hopes to spend the next two or three years tak­ing the lead can­di­date to­ward the clin­ic while ex­pand­ing the pipeline, ini­tial­ly in oph­thal­mol­o­gy but per­haps ex­pand­ing to oth­er or­gans as well.

By that time, Vi­la-Perel­ló hopes the boom­ing field may have solved some of the oth­er lim­i­ta­tions and is­sues — in­clud­ing se­ri­ous safe­ty con­cerns — around AAV.

“In the fu­ture, we ex­pect that there’s gonna be some im­prove­ments in vec­tors that could make sys­temic de­liv­ery less prob­lem­at­ic, so that peo­ple don’t need to re­sort to the high dos­es,” he said.

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.

Dave Marek, Myovant CEO

My­ovant board balks as ma­jor­i­ty own­er Sum­it­o­mo swoops in with a $2.5B deal to buy them out

Three years after Sumitomo scooped up Roivant’s 46% stake in the publicly traded Myovant $MYOV as part of a 5-company, $3 billion deal, they’re coming back for the whole thing.

But these other investors at Myovant want more than what the Japanese pharma company is currently offering to pay at this stage.

Sumitomo is bidding $22.75 a share for the outstanding stock, which now represents 48% of the company after Sumitomo bumped its ownership since the original deal with Roivant. Myovant, however, created a special committee on the board, and they’re shaking their heads over the offer.

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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)

Fa­ther starts lab af­ter in­tel­lec­tu­al prop­er­ty is­sues stymie rare dis­ease drug de­vel­op­ment

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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Vlad Coric, Biohaven CEO

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

What’s Biohaven without its CGRP portfolio? That’s what CEO Vlad Coric is tasked with deciding as he maps out the new Biohaven post-Pfizer takeover.

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

As­traZeneca de­buts an­noy­ing pur­ple ‘Phil’ crea­tures, per­son­i­fied asth­ma eosinophils ‘be­hav­ing bad­ly’

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.

Kite Phar­ma gets FDA to sign off on new Cal­i­for­nia-based vec­tor man­u­fac­tur­ing fa­cil­i­ty

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.

Fabrice Chouraqui, Cellarity CEO

A year and a half af­ter Cel­lar­i­ty raised $123M, the Flag­ship biotech is back — and it's ready to pick out can­di­dates

Cellarity doesn’t have any lead candidates yet. It doesn’t even have a public pipeline.

But it’s still attracting new investors. In a third round of financing announced this morning, Cellarity raised $121 million — just $2 million short of its last round — and brought on four new investors, including Kyowa Kirin and Hanwha Impact Partners.

Flagship, where the startup was first conceived, also participated in the latest round. Most of its other former investors returned as well, Cellarity CEO Fabrice Chouraqui told Endpoints News, though he would not disclose which ones.

Mar­ket­ingRx roundup: No­var­tis re­cruits NFL coach for Leqvio cam­paign; Pfiz­er pro­motes ‘Sci­ence’ merch on so­cial me­dia

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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