Kelli Luginbuhl and Ashutosh Chilkoti

Start­up sets out to tack­le the gene ther­a­py man­u­fac­tur­ing cri­sis

Af­ter Kel­li Lug­in­buhl fin­ished her PhD, her ad­vi­sor, Duke bio­engi­neer and Phase­Bio co-founder Ashutosh Chilkoti, sat her down and asked if she want­ed to launch and then run a com­pa­ny. Chilkoti had a once-ob­scure tech­nol­o­gy he and the ven­ture cap­i­tal­ist Joe McMa­hon thought could form the ba­sis of his sec­ond com­pa­ny and fi­nal­ly pay huge div­i­dends. Lug­in­buhl knew the tech from years in his lab and was al­ready look­ing for biotech jobs. It all added up.

Three years, some strate­giz­ing, and 10 or so pitch meet­ings lat­er, the trio is launch­ing Isol­ere Bio, with $7 mil­lion in seed fund­ing led by North­pond Ven­tures and tech­nol­o­gy they be­lieve can al­low gene ther­a­py com­pa­nies to vast­ly in­crease the num­ber of dos­es they can pro­duce. It’s one po­ten­tial so­lu­tion to a slow-boil­ing cri­sis that has be­come in­creas­ing­ly acute, as new com­pa­nies strug­gle to get the ma­te­ri­als they need for tri­als and some com­mon dis­eases re­main the­o­ret­i­cal­ly un­fix­able by gene ther­a­py, be­cause com­pa­nies would nev­er be able to make enough dos­es for that many pa­tients.

The prob­lem is par­tial­ly that the fa­cil­i­ties don’t yet ex­ist to pro­duce this much of gene ther­a­py. Ex­perts, how­ev­er, al­so point to an­ti­quat­ed man­u­fac­tur­ing process­es.

“In gene ther­a­py, man­u­fac­tur­ing has a lot of in­ef­fi­cien­cies to over­come, which our tech­nol­o­gy is unique­ly po­si­tioned to ad­dress,” Lug­in­buhl, who serves as CEO, told End­points News.

Large phar­ma com­pa­nies and CD­MOs have known about the gene ther­a­py man­u­fac­tur­ing short­fall for a few years, spend­ing bil­lions to retro­fit old drug-mak­ing fa­cil­i­ties or build new ones to as­sure ca­pac­i­ty for a fu­ture where hun­dreds of gene ther­a­pies are in clin­i­cal tri­als and dozens are on the mar­ket (cur­rent­ly on­ly two are ap­proved in the US, both for rare dis­eases). More re­cent­ly, though, a small hand­ful of star­tups have tried to not on­ly build new fac­to­ries but rein­vent how gene ther­a­pies are made, turn­ing a large­ly aca­d­e­m­ic process in­to an in­dus­tri­al one. That in­cludes the George Church spin­out 64xBio and the mon­strous­ly backed Bob Nelsen start­up Re­silience.

Like Re­silience and 64x, Isol­ere is try­ing to boost the pro­duc­tion of AAV, the non-dis­ease caus­ing virus that most gene ther­a­py com­pa­nies use to de­liv­er healthy or func­tion­al re­place­ment genes in­to pa­tients. They’re do­ing so by chang­ing one ob­scure process in the man­u­fac­tur­ing chain: how AAV is fil­tered out of the huge bags of cells used to pro­duce the virus.

AAVs are large, 20-sided par­ti­cles, but cur­rent­ly man­u­fac­tur­ers fil­ter the virus­es out with the same decades-old pro­ce­ses they would use for much small­er mol­e­cules: chro­matog­ra­phy columns, ver­ti­cal tubes where you mix a so­lu­tion from the cells with beads that bind to and pre­vent the AAV from pass­ing through ini­tial­ly, while every­thing else flush­es out. It’s high­ly in­ef­fi­cient, though, Lug­in­buhl said. Among oth­er is­sues, the columns have low ca­pac­i­ty. Be­tween 70% and 80% of the so­lu­tion is gen­er­al­ly lost, Lug­in­buhl said.

Chilkoti’s lab is known for its work on bio­ma­te­ri­als, the ones he put to use found­ing Phase­Bio, hop­ing to build drugs that float­ed through the body dif­fer­ent­ly and en­abled more pa­tient-friend­ly dos­ing reg­i­mens. The bio­ma­te­ri­als Isol­ere is bring­ing for­ward bind to the AAV and form the same kind of liq­uid-liq­uid sep­a­ra­tion as you see in oil in wa­ter emul­sions — like a pro­tec­tive bub­ble around AAV, sep­a­rat­ing it from the rest of the so­lu­tion.

That ma­te­r­i­al can shep­herd the AAV through the fil­tra­tion process, Lug­in­buhl said. The goal is to im­prove yields by 50%.

It’s “a huge pain point in AAV man­u­fac­tur­ing that we’re po­si­tioned to ad­dress,” she said.

Lug­in­buhl said their tech­nol­o­gy can work on any AAV and added, rel­a­tive­ly seam­less­ly, in­to ex­ist­ing man­u­fac­tur­ing process­es. So far, they’ve on­ly test­ed it on 2 liter tanks, but she said they’ve been work­ing with ma­jor gene ther­a­py com­pa­nies and hope to sign a co-de­vel­op­ment deal that would let them scale up the process.

The goal is to get to the mar­ket in 16 months. A Se­ries A is in the works, she said, but of less­er con­cern. For now, they have the run­way, she said, and the field is in dire need of new tech­niques.

“You hear that quote that we’re train­ing chil­dren for jobs that don’t ex­ist to­day,” she said. “The med­i­cines of the fu­ture are modal­i­ties we may not even know ex­ist to­day. And so it’s im­por­tant to be ready to man­u­fac­ture the next gen­er­a­tion of med­i­cines.”

“To do that we need new ideas and new in­no­va­tions in man­u­fac­tur­ing,” she added. “The down­stream pu­rifi­ca­tion field had re­al­ly re­mained quite stag­nant.“

Am­gen lays off about 300 work­ers, cit­ing 'in­dus­try head­wind­s'

Amgen has laid off about 300 employees, a company spokesperson confirmed to Endpoints News via email Sunday night.

Employees posted to LinkedIn in recent days about layoffs hitting Amgen last week. The Thousand Oaks, CA-based biopharma, which employs about 24,000 people, said the reduction “mainly” impacted US-based workers on its commercial team.

Drug developers of all sizes, including small upstarts and pharma giants, have let employees go in recent months as the biopharma market drags through a quarters-long winter doldrum.

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New York City in­vests $20M in­to biotech 'in­no­va­tion space' at the Brook­lyn Navy Yard

New York City is investing $20 million in biotech this year in the form of a 50,000-square-foot “innovation space” at the Brooklyn Navy Yard, complete with offices, research laboratories and events and programming space to grow biotech startups and companies.

Mayor Eric Adams said during his State of The City Address last Thursday that there will be an “emphasis” on making more opportunities for women and people of color to further diversify the industry. The City first reported the news.

Bob Bradway, Amgen CEO (Stephen Lam/Reuters)

Am­gen launch­es the first US Hu­mi­ra biosim­i­lar at two dif­fer­ent list prices

The bizarre dynamics of the US prescription drug market were on full display once again this morning as Amgen announced that it would launch the first US biosimilar for Humira, the best-selling drug of all time, at two completely different list prices.

One price for Amgen’s Amjevita (adalimumab-atto) will be 55% below the current Humira list price, which is about $84,000 per year, and another at a list price 5% below the current Humira list price, but presumably (pharma companies don’t disclose rebates) with high rebates to attract PBMs and payers.

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Dirk Thye, Quince Therapeutics CEO

Af­ter piv­ot­ing from Alzheimer's to bone con­di­tions, biotech piv­ots again — and halves its head­count

When troubled public biotech Cortexyme bought a private startup named Novosteo and handed the keys to its executive team, the company — which changed its name to Quince Therapeutics — said it would shift its focus from an unorthodox Alzheimer’s approach to Novosteo’s bone-targeting drug platform.

Less than a year later, Quince is pivoting again.

The biotech has decided to out-license its bone-targeting drug platform and its lead drug, NOV004, and instead look for clinical-stage programs to in-license or acquire, according to a press release.

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Boehringer In­gel­heim touts pre­ven­tion re­sults in rarest form of pso­ri­a­sis

Boehringer Ingelheim uncorked some positive results suggesting that Spevigo can help prevent flare-ups in patients with a severe form of psoriasis, months after the drug was approved to treat existing flares.

Spevigo, an IL-36R antibody also known as spesolimab, met its primary and a key secondary endpoint in the Phase IIb EFFISAYIL 2 trial in patients with generalized pustular psoriasis (GPP), Boehringer announced on Monday. While the company is keeping the hard numbers under wraps until later this year, it said in a news release that it anticipates sharing the results with regulators.

As­traZeneca, No­vo Nordisk and Sanofi score 340B-re­lat­ed ap­peals court win over HHS

AstraZeneca, Novo Nordisk, and Sanofi won an appeals court win on Monday, as the US Court of Appeals for the Third Circuit found that the companies cannot be forced to provide 340B-discounted drugs purchased by hospitals from an unlimited number of community and specialty pharmacies.

“Legal duties do not spring from silence,” the decision says as the court makes clear that the federal government’s interpretation of the “supposed requirement” that the 340B program compels drugmakers to supply their discounted drugs to an unlimited number of contract pharmacies is not correct, noting:

Ap­peals court toss­es J&J's con­tro­ver­sial 'Texas two-step' bank­rupt­cy case

A US appeals court has ruled against Johnson & Johnson’s use of bankruptcy to deal with mounting talc lawsuits, deciding that doing so would “create a legal blind spot.”

The Third Circuit Court of Appeals reversed a previous bankruptcy court decision on Monday, calling for the dismissal of a Chapter 11 filing by J&J’s subsidiary LTL Management.

Faced with more than 38,000 lawsuits alleging its talc-based products caused cancer, J&J spun its talc liabilities into a separate company called LTL Management back in October 2021 and filed for bankruptcy, a controversial move colloquially referred to as a “Texas two-step” bankruptcy. Claimants argued that the strategy is a misuse of the US bankruptcy code — and on Monday, a panel of judges agreed.

Chad Mirkin, Flashpoint co-founder

‘The field is at a flash­point’: New Chad Mirkin-found­ed biotech hopes to make more ef­fec­tive can­cer vac­cines

Following the success of the mRNA Covid vaccines, cancer vaccines are seeing renewed interest after years of middling results. But a group of researchers suggests that more attention needs to be paid not to what goes into those vaccines, but how the parts are put together.

In a recent paper published in Nature Biomedical Engineering, researchers led by Northwestern University’s Chad Mirkin describe how the placement of different antigens in a cancer vaccine impacts its efficacy. The paper builds on past work done by Mirkin’s lab that suggests the structure, or how the parts of a vaccine are arranged, impact a vaccine’s efficacy, not just its components.

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#JPM23: Reg­u­la­to­ry un­cer­tain­ty? What about M&A? Da­ta rule? Alessan­dro Masel­li and John Car­roll take out their crys­tal balls

Endpoints editor and founder John Carroll sat down the Catalent CEO Alessandro Maselli to talk about what’s ahead in 2023. Right or wrong, this covers all the big issues faced by biopharma. This transcript has been edited for brevity and clarity.

John Carroll:

I think 2022 had to be one of the worst years ever for crystal balls. You went into 2022 thinking all sorts of nice things about what was ahead, not thinking about a European land war, maybe not thinking that the Federal Reserve was going to be jacking up interest rates as fast as they could to get ahead of inflation. Just a tremendous number of macroeconomic issues that were out there. The sudden and complete collapse of support on the markets in Nasdaq for biotech. A lot of darlings in the industry that had been out there for a while suddenly found themselves moving from a really hot market to a really cold market all of a sudden and had to make a lot of different changes in terms of strategizing.

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