Realizing the Potential of RNA-Targeted Oligonucleotide Therapeutic; Pipeline Progress and Partnerships
Brett Monia, PhD; Chief Executive Officer, Ionis Pharmaceuticals
Oligonucleotide therapies are set to make an impact in the neurological disease space according to Ionis Pharmaceuticals Inc., which says advances in targeting technologies are the key dynamic.
The approval of Wainua last year underlined oligonucleotides’ potential as a therapeutic class, according to Ionis CEO Brett Monia, Ph.D., who told delegates at TIDES Asia the sector is getting better at hitting a broader range of targets.
“The liver has been the hallmark if you will, the area of greatest success — the hepatocyte in particular with targeted delivery — but we’ve had great success in targeting the beta cells as well using oligonucleotides conjugated to specific peptides delivered to the beta cells muscle, cardiac myocytes, and skeletal muscle,” Monia said.“Also, we’re making great progress and using targeted delivery for CNS [central nervous system] diseases to overcome the blood brain barrier using subcutaneous routes of administration or intravenous routes of administration.”And, as a result, Monia said neurology is likely to be a growth area for the oligonucleotide sector in general and Ionis.
“We at Ionis have a proven track record in delivering first-in-class treatments for a broad range of neurological diseases using our platform.We have two drugs that are now approved targeting neurodegenerative diseases,” Monia said.
He added that the products Spinraza for spinal muscular atrophy and Qalsody for a rare genetic form of amyotrophic lateral sclerosis (ALS) are turning fatal diseases into manageable conditions.
“We have three approved medicines if you include Wainua for central nervous system disorders, neurodegenerative disorders, but we have 11 medicines in neurology currently in clinical development — some in Phase 3, some in Phase 2 development,” Monia said.“These are large indications such as Alzheimer’s disease and Parkinson’s disease as well as rare diseases like Angel Man syndrome, ALS, Huntington’s disease, and more, and we’re expecting more to enter the pipeline this year.”Ionis’ targeting technology is key to its oligo neurology pipeline, according to Monia, who said, “These drugs are administered intrathecally, and we’ve made tremendous progress over the years, decades really, validating this platform for CNS diseases to enhance potency, tolerability, and durability so that we can treat intrathecally very infrequently.”
Tau Program
Additionally, Monia discussed Ionis’ program targeting Tau proteins — neurofibrillary tangles that accumulate in Alzheimer’s disease that are linked to cognition deficit over time.
“Tau proteins are very difficult, really impossible, to target effectively with small molecules or monoclonal antibodies.And we’ve recognized that our ASO technology (antisense oligonucleotides) is perfectly suited to address Tau dementia because ASOs target all forms of Tau,” he said.
Early clinical data suggest Ionis’ ASOs significantly reduce Tau levels in CSF for periods of at least six months.
But there are other potential benefits, according to Monia. “Our partner Biogen also reported last year that there was evidence, based on a concerted effort to look at dementia readouts, that patients were improving in cognition in this study after only a hundred weeks of treatment,” Monia said.“So neurology is an area of tremendous focus for Ionis. The level of unmet need in neurodegenerative and neurodevelopmental diseases is enormous as you all know, and we’re committed to delivering more treatments like Spinraza, Qalsody, Tau and many others.”