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.
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.
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