Stan­ley and Rosanne Crooke stay fo­cused on an­ti-sense, steal­ing back pa­tients from dis­ease with N-of-1 tech

A lit­tle over a year af­ter a Boston Chil­dren’s Hos­pi­tal neu­rol­o­gist used an­ti-sense tech­nol­o­gy to cre­ate what may be the world’s first ful­ly be­spoke ther­a­py, two of the old­est and biggest names in an­ti-sense have launched a char­i­ty to make those treat­ments pos­si­ble to far more pa­tients – and free of charge.

Stan­ley Crooke

The hus­band-and-wife team of long­time Io­n­is CEO Stan­ley Crooke and long­time Io­n­is re­searcher Rosanne Crooke are launch­ing the n-Lorem foun­da­tion. The cou­ple will per­son­al­ly con­tribute $1.5 mil­lion to the project, with Io­n­is adding an­oth­er $1.5 mil­lion and Bio­gen $1 mil­lion. Stan­ley Crooke stepped down from Io­n­is’ helm last year.

Found­ed by Crooke in 1989, Io­n­is was the first com­pa­ny to launch a clin­i­cal tri­al for an­ti-sense tech­nol­o­gy, sin­gle strands of RNA that can be used to reg­u­late gene ex­pres­sion. The tech­nol­o­gy has since be­come a ver­i­fied ap­proach, lead­ing to drugs such as Spin­raza and Waylivra.

The ad­vance­ments crys­tal­lized in 2018, when, in un­der 10 months, Tim­o­thy Yu used an­ti-sense tech­nol­o­gy to cus­tomize a treat­ment for a 6-year-old girl who came in­to Boston’s Chil­dren’s Hos­pi­tal with a nev­er-be­fore-seen ge­net­ic mu­ta­tion. The news sparked hope and prompt­ed pleas for their own ther­a­pies from fam­i­lies af­fect­ed by rare mu­ta­tions.

Rosanne Crooke

The Crookes launched the new foun­da­tion to make these “N-of-1” ther­a­pies pos­si­ble for more of those fam­i­lies. Stan­ley Crooke told Chem­i­cal & En­gi­neer­ing News that he sees this n-Lo­ram as a mid­dle man who can co­or­di­nate be­tween all the parts re­quired to scale be­spoke treat­ments: Pa­tients, a clin­i­cian who can man­age a one-pa­tient tri­al, and an in­sti­tu­tion who can sub­mit an IND-en­abling ap­pli­ca­tion, among oth­er things.

“I con­ceived of n-Lorem as sort of the mid­dle man—the bro­ker of the ge­net­ics, the pa­tients, the needs, and one so­lu­tion to bring ther­a­peu­tic op­tions for these pa­tients who have ul­tra, ul­tra-rare mu­ta­tions,” Crooke told C&EN.

The foun­da­tion will con­vene an “ac­cess to treat­ment” pan­el of re­searchers, pa­tients and Bio­gen and Io­n­is ex­ec­u­tives. They will re­view US-based pa­tients who come through the Un­di­ag­nosed Dis­ease Net­work, a group of NIH-fund­ed sites with ex­per­tise in ul­tra-rare dis­eases.

There will be sig­nif­i­cant road­blocks, though. In ad­di­tion to the sci­en­tif­ic hur­dles of de­vel­op­ing in­di­vid­u­al­ized ther­a­pies, it’s still un­clear how the FDA will re­spond. When the New Eng­land Jour­nal of Med­i­cine pub­lished Yu’s work in Oc­to­ber, they ac­com­pa­nied it with an op-ed from the FDA’s Janet Wood­cock and Pe­ter Marks. The pair de­tailed 9 dif­fer­ent ques­tions reg­u­la­tors will face go­ing for­ward and pro­vid­ed few an­swers.

“In these ‘N-of-one’ sit­u­a­tions, what type of ev­i­dence is need­ed be­fore ex­pos­ing a hu­man to a new drug?” they wrote. “Even in rapid­ly pro­gress­ing, fa­tal ill­ness­es, pre­cip­i­tat­ing se­vere com­pli­ca­tions or death is not ac­cept­able, so what is the min­i­mum as­sur­ance of safe­ty that is need­ed? How per­sua­sive should the mech­a­nis­tic or func­tion­al da­ta be? How should the dose and reg­i­men be se­lect­ed? How much char­ac­ter­i­za­tion of the prod­uct should be un­der­tak­en? How should the ur­gency of the pa­tient’s sit­u­a­tion or the num­ber of peo­ple who could ul­ti­mate­ly be treat­ed af­fect the de­ci­sion-mak­ing process?”

So­cial im­age cred­it: Oligonu­cleotide Ther­a­peu­tics So­ci­ety

Biotech and Big Phar­ma: A blue­print for a suc­cess­ful part­ner­ship

Strategic partnerships have long been an important contributor to how drugs are discovered and developed. For decades, big pharma companies have been forming alliances with biotech innovators to increase R&D productivity, expand geographical reach and better manage late-stage commercialization costs.

Noël Brown, Managing Director and Head of Biotechnology Investment Banking, and Greg Wiederrecht, Ph.D., Managing Director in the Global Healthcare Investment Banking Group at RBC Capital Markets, are no strangers to the importance of these tie-ups. Noël has over 20 years of investment banking experience in the industry. Before moving to the banking world in 2015, Greg was the Vice President and Head of External Scientific Affairs (ESA) at Merck, where he was responsible for the scientific assessment of strategic partnership opportunities worldwide.

No­var­tis' sec­ond at­tempt to repli­cate a stun­ning can­cer re­sult falls flat

Novartis’ hopes of turning one of the most surprising trial data points of the last decade into a lung cancer drug has taken another setback.

The Swiss pharma announced Monday that its IL-1 inhibitor canakinumab did not significantly extend the lives or slow the disease progression of patients with previously untreated locally advanced or metastatic non-small cell lung cancer when compared to standard of-care alone.

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How Chi­na turned the ta­bles on bio­phar­ma's glob­al deal­mak­ing

Fenlai Tan still gets chills thinking about the darkest day of his life.

Three out of eight lung cancer patients who received a tyrosine kinase inhibitor developed by his company, Betta Pharma, died in the span of a month. Tan, the chief medical officer, was summoned to Peking Union Medical College Hospital, where the head of the clinical trial department told him that the trial investigators would be conducting an autopsy to see if the patients had died of the disease — they were all very sick by the time they enrolled — or of interstitial lung disease, a deadly side effect tied to the TKI class that’s been reported in Japan.

An­gion's or­gan dam­age drug strikes out again, this time in high-risk kid­ney trans­plant pa­tients

After flopping a test in Covid-19 earlier this year, Angion’s lead organ damage drug has now hit the skids again in kidney transplant patients.

Angion and partner Vifor Pharma’s ANG-3777 failed to beat out placebo in terms of improving eGFR, a measure of kidney function, in patients who had received a deceased donor kidney transplant and were at high risk of developing what is known as delayed graft function, according to Phase III results released Tuesday.

An image of Alzheimer's brain tissue. The red show gingipains, a protein from P. gingivalis, intermixing with neurons (yellow) and glial cells (green)

An Alzheimer's dark­horse fails its first big tri­al, but of­fers hope for a long-over­looked hy­poth­e­sis

Three years ago, Cortexyme emerged out of obscurity with some big-name backers and an unorthodox approach to treating Alzheimer’s.

They moved their drug into a pivotal study the next year, offering one of the first major tests for a hypothesis that has fluttered on the outskirts of Alzheimer’s research for decades: that, in many cases, the disease is driven by infectious agents — the havoc they wreak in the brain and the inflammation the body uses to try to fend them off. And that quashing the infection could slow patients’ cognitive decline.

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No­var­tis dumps AveX­is pro­gram for Rett syn­drome af­ter fail­ing re­peat round of pre­clin­i­cal test­ing

Say goodbye to AVXS-201.

The Rett syndrome gene therapy drug made by AveXis — the biotech that was bought, kept separate, then renamed and finally absorbed by Novartis into its R&D division — has been dropped by the biopharma.

In Novartis’ third quarter financial report, the pharma had found that preclinical data did not support development of the gene therapy into IND-enabling trials and beyond. The announcement comes a year after Novartis told the Rett Society how excited it was by the drug — and its potential benefits and uses.

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Peter Nell, Mammoth Biosciences CBO

UP­DAT­ED: Jen­nifer Doud­na spin­out inks a Mam­moth CRISPR deal with Ver­tex worth near­ly $700M

When a company gets its start in gene editing pioneer Jennifer Doudna’s lab, it’s bound to make headlines. But three years in, the fanfare still hasn’t died down for Mammoth Biosciences. Now, the Brisbane, CA-based company is cheering on its first major R&D pact.

Mammoth unveiled a nearly $700 million deal with Vertex on Tuesday morning, good for the development of in vivo gene therapies for two mystery diseases. The stars of the show are Mammoth’s ultra-small CRISPR systems, including two Cas enzymes licensed from Doudna’s lab over the past couple years, Cas14 and Casɸ.

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FDA is much worse than its reg­u­la­to­ry peers at proac­tive­ly dis­clos­ing da­ta, re­searchers find

The European Medicines Agency and Health Canada continue to outpace the FDA when it comes to proactively releasing data on drugs and biologics the agency has reviewed, leading to further questions of why the American agency can’t be more transparent.

In a study published recently in the Journal of Law, Medicine, & Ethics, Yale and other academic lawyers and researchers found that between 2016 and April 2021, the EMA proactively released data for 123 unique medical products, while Health Canada proactively released data for 73 unique medical products between 2019 and April 2021. What’s more, the EMA and Health Canada didn’t proactively release the same data on the same drugs. In stark contrast, the FDA in 2018 only proactively disclosed data supporting one drug that was approved that year.

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NYU surgeon transplants an engineered pig kidney into the outside of a brain-dead patient (Joe Carrotta/NYU Langone Health)

No, sci­en­tists are not any clos­er to pig-to-hu­man trans­plants than they were last week

Steve Holtzman was awoken by a 1 a.m. call from a doctor at Duke University asking if he could put some pigs on a plane and fly them from Ohio to North Carolina that day. A motorcyclist had gotten into a horrific crash, the doctor explained. He believed the pigs’ livers, sutured onto the patient’s skin like an external filter, might be able to tide the young man over until a donor liver became available.