Geoff McDonough, Generation Bio CEO

Hopes for non-vi­ral gene ther­a­py take a blow as Gen­er­a­tion Bio an­nounces sig­nif­i­cant set­back

Last year, dur­ing the height of the biotech IPO boom, Gen­er­a­tion Bio raised $230 mil­lion on a swing-for-the-fences ap­proach to gene ther­a­py.

Launched out of UMass Med­ical School, the com­pa­ny promised to de­vel­op the world’s first non-vi­ral gene ther­a­py. Such an ap­proach, if proven, could elim­i­nate many of the key hur­dles that have hin­dered the field over the last decade: It would al­low doc­tors to dose pa­tients who have pre-ex­ist­ing im­mu­ni­ty to the virus­es com­mon­ly used to­day, to re­dose a pa­tient if the ther­a­py ever wore off, and to avoid many of the im­mune-re­lat­ed safe­ty con­cerns that have come to the fore over the last 18 months.

But the promise al­so raised skep­ti­cism from many in the gene ther­a­py field. Re­searchers have been try­ing to make non-vi­ral de­liv­ery work since the 1990s. No one ever has.

And so far, nei­ther has Gen­er­a­tion Bio. The com­pa­ny an­nounced new an­i­mal da­ta for its lead pro­gram Tues­day morn­ing. And as in pre­vi­ous re­ports, the ther­a­py was high­ly ef­fec­tive in mice. But it failed to do much in mon­keys, set­ting back a pro­gram they had hoped to have au­tho­rized for clin­i­cal tri­als in 2022.

Gen­er­a­tion Bio’s stock $GBIO fell 42% on the news, from $13.90 to $8.06.

The com­pa­ny’s ini­tial fo­cus has been on he­mo­phil­ia A, where a re­dos­able gene ther­a­py could be par­tic­u­lar­ly ad­van­ta­geous. The lead­ing he­mo­phil­ia A pro­gram from Bio­Marin has been racked by con­cerns that the one-and-done ther­a­py might be­gin to wear off a few years af­ter ad­min­is­tra­tion.

It was al­so a nat­ur­al tar­get for Gen­er­a­tion Bio’s plat­form, be­cause he­mo­phil­ia gene ther­a­pies in­volve get­ting fac­tor VI­II — the clot­ting pro­tein he­mo­phil­ia pa­tients are miss­ing — to be ex­pressed in the liv­er. Gen­er­a­tion’s de­liv­ery tech, an ad­vanced form of the lipid-nanopar­ti­cles used in mR­NA vac­cines, traf­fics most di­rect­ly to that or­gan.

In mice, Gen­er­a­tion Bio was able to in­duce 205% of nor­mal hu­man fac­tor VI­II ex­pres­sion. But in mon­keys, the true test for both pre­dict­ing hu­man ef­fi­ca­cy and per­suad­ing the FDA to OK clin­i­cal tri­als, ex­pres­sion on­ly reached “up to 2%” — a far cry from the rough­ly 60% ex­pres­sion that Bio­Marin saw in the first year af­ter ad­min­is­ter­ing their ther­a­py in pa­tients. And sub­stan­tial­ly less than the 8.3% pa­tients were at af­ter five years.

Gen­er­a­tion in­di­cat­ed, though, that the lev­el of ex­pres­sion was less a prob­lem than the fact they kept see­ing dif­fer­ent re­sults in dif­fer­ent mon­keys, both on safe­ty and ef­fi­ca­cy.

There was “high­er-than-ex­pect­ed vari­abil­i­ty in both fac­tor VI­II ex­pres­sion and tol­er­a­bil­i­ty with­in and across stud­ies,” the com­pa­ny said in a re­lease.

That will send in­ves­ti­ga­tors back to the lab and de­lay clin­i­cal tri­als, al­though Gen­er­a­tion wouldn’t say by how much or when the com­pa­ny would have a time­line.

“Ad­di­tion­al op­ti­miza­tion is need­ed to trans­late the im­prove­ment in po­ten­cy and re­duc­tion in vari­abil­i­ty ob­served in mice to NHP, and to sup­port nom­i­na­tion of a de­vel­op­ment can­di­date for the com­pa­ny’s he­mo­phil­ia A pro­gram,” they said.

The set­back won’t kill Gen­er­a­tion’s he­mo­phil­ia pro­gram. LNPs, though, are eas­i­est to de­liv­er to the liv­er and if the com­pa­ny can’t get re­peat­able re­sults there, it doesn’t bode well for their plans in the eye and mus­cle.

Any com­pa­ny that fig­ures out non-vi­ral gene ther­a­py, or a dif­fer­ent im­prove­ment on the cur­rent ade­no-as­so­ci­at­ed virus­es that dom­i­nate the field, will be sit­ting on a gold mine. But there’s not much ev­i­dence yet to say re­searchers are close.

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.

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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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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Benjamine Liu, TrialSpark CEO

Paul Hud­son and Tri­alSpark's mu­tu­al de­sire to speed up de­vel­op­ment con­verges in three-year, six-drug goal

A unicorn startup that originally set out to hasten clinical studies for biopharma partners dug further into its revised path of internal drug development by linking arms with Sanofi in a pact that the biotech’s CEO said originated from the top.

TrialSpark and the Big Pharma on Tuesday committed to in-licensing and/or acquiring six Phase II/Phase III drugs within the next three years.

“I’ve known Paul Hudson for a while and we were discussing the opportunity to really re-imagine a lot of different parts of pharma,” TrialSpark CEO Benjamine Liu told Endpoints News, “and one of the things that we discussed was this opportunity to accelerate the development of new medicines in mutual areas of interest.”

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Al Sandrock, Voyager Therapeutics CEO

Af­ter 12 months of dig­ging, Pfiz­er opts for one of two Voy­ager cap­sids for gene ther­a­py

The path at Voyager Therapeutics keeps winding, and at the 12-month deadline, Pfizer has elected to only move forward with one of two capsids out of the preclinical biotech for the Big Pharma’s AAV gene therapies.

Last October, the Big Pharma and biotech linked arms on a deal that gave Pfizer the ability to hit the gas pedal on two capsids: one for a cardiac target and the other for a rare neurologic disease target.

Take­da to pull key hy­poparathy­roidism drug from the mar­ket en­tire­ly by end of 2024 af­ter years of man­u­fac­tur­ing woes

Takeda on Tuesday morning made an announcement that almost 3,000 people with the rare disease known as hypoparathyroidism were fearing.

Due to unresolved supply issues and manufacturing woes, Takeda said it will cut its losses and discontinue its hypoparathyroidism drug, known as Natpara (parathyroid hormone), halting all manufacturing of the drug by the end of 2024.

The decision to not re-commercialize Natpara will be a blow to not only the 2,400 people who were awaiting supplies of their reliable injection since 2019, but also the additional nearly 400 people who were accessing the drugs via the company’s Special Use Program as Takeda sought to resolve these manufacturing issues over the past five years.

Marc Dunoyer, Alexion CEO (AstraZeneca via YouTube)

Up­dat­ed: As­traZeneca nabs a small rare dis­ease gene ther­a­py play­er for 667% pre­mi­um

AstraZeneca is kicking off the fourth quarter with a little M&A Monday for a gene editing player recently overcoming a second clinical hold to its only program in human studies.

The Big Pharma and its subsidiary Alexion are buying out little LogicBio for $2.07 per share. That’s good for a massive 667% premium over its Friday closing price, when it headed into the weekend at 27 cents and just weeks after Nasdaq said LogicBio would have to delist, which has been put on hold as the biotech requests a hearing. It’s one of two biotech deals to commence October, alongside the news of Incyte buying a vitiligo-focused biotech.

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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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