Our Pipeline
Our Pipeline
Our goal is to discover and develop potentially life-changing medicines across a range of neurologic diseases.1
The Ionis Neurology pipeline includes investigational RNA-targeted medicines for severe and debilitating neurologic diseases that affect a wide range of patients with unmet needs.1,2
Our RNA-targeted drug discovery and development platform provides a fast, efficient path to identify first-in-class and/or best-in-class medicines.2-7
With 4 FDA-approved neurologic medicines and more than 10 investigational RNA-targeted medicines in mid- or late-stage development, Ionis is potentially transforming the trajectory of serious neurologic diseases.1,2,8
Ionis’ Pipeline Includes Early- and Late-Stage Investigational Medicines Designed to Target Genetic Sequences Associated With a Range of Rare and Prevalent Neurologic Conditions1,2,7,a
| Investigational RTM | Disease State | Gene/Target | Phase 1 Phase 2 Phase 3 | |
|---|---|---|---|---|
| Ionis-owned | Ulefnersen |
Fused in sarcoma amyotrophic lateral sclerosis | FUS | |
Zilganersen |
Alexander disease | GFAP | ||
ION717c |
Prion disease | PRNP | ||
ION582b |
Angelman syndrome | UBE3A-ATS | ||
ION440 |
MECP2 duplication syndrome |
MECP2 | ||
ION356 |
Pelizaeus-Merzbacher disease |
PLP1 | ||
| Investigational RTM | Disease State | Gene/Target | Phase 1 Phase 2 Phase 3 | |
|---|---|---|---|---|
| Ionis-Biogen | IONIS-MAPTRX |
Alzheimer’s disease | TAU | |
ION859d |
Parkinson’s disease | LRRK2 | ||
ION464d |
Multiple system atrophy | SNCA | ||
ION306 |
Spinal muscular atrophy | SMN2 | ||
| Investigational RTM | Disease State | Gene/Target | Phase 1 Phase 2 Phase 3 | |
|---|---|---|---|---|
| Ionis-Roche | Tominersen |
Huntington’s disease | HTT | |
Ulefnersen (Fused in sarcoma amyotrophic lateral sclerosis)
Ulefnersen, clinically known as ION363, is an investigational RNA-targeted medicine (RTM) designed to reduce the production of the fused in sarcoma (FUS) protein as a potential therapy for people with amyotrophic lateral sclerosis caused by mutations in the FUS gene.1,2
This investigational RTM is being studied in FUSION, a Phase 1-3, multicenter, three-part study evaluating the pharmacokinetics, pharmacodynamics, efficacy, and safety of ulefnersen in up to 95 patients. Part 1 will consist of patients randomized in a 2:1 ratio to receive a multidose regimen of ulefnersen or placebo for a period of 60 weeks, followed by part 2, in which patients will receive open-label ulefnersen for a period of 84 weeks. Patients may continue to receive open-label ulefnersen in part 3 for up to 3 additional years or until it becomes commercially available in the patient's country.2,3
Study start3:
Study completion3:
1. Ionis Pharmaceuticals. The Ionis Antisense Pipeline. Accessed August 15, 2024. https://www.ionis.com/ionis-technology/antisense-pipeline/ 2. Ionis Pharmaceuticals. Ionis Neurology Pipeline. Accessed August 21, 2024. https://www.ionis.com/ionis-technology/innovation/pipeline/transforming-the-management-of-neurology/
3. ClinicalTrials.gov identifier: NCT04768972. Accessed August 16, 2024. https://clinicaltrials.gov/study/NCT04768972/
Zilganersen (Alexander disease)
Zilganersen, clinically known as ION373, is an investigational RNA-targeted medicine (RTM) that targets glial fibrillary acidic protein (GFAP) mRNA and is designed to inhibit the production of GFAP. Zilganersen is being developed as a potential therapy for Alexander disease (AxD).1-3
This investigational RTM is being assessed in a Phase 1-3, double-blind, placebo-controlled, multiple ascending-dose study evaluating the safety and efficacy of zilganersen in improving or stabilizing gross motor function across the affected domains in 73 patients with AxD. Patients will be randomized in a 2:1 ratio to receive zilganersen or matching placebo for a 60-week double-blind treatment period; then all patients will receive zilganersen for a 60-week open-label treatment period followed by a 120-week open-label, long-term extension period, and a 28-week posttreatment follow-up period.3,4
Some study sites will include an optional open-label sub-study in patients <2 years of age.4
Study start4:
Study completion4:
1. Ionis Pharmaceuticals. The Ionis Antisense Pipeline. Accessed August 15, 2024. https://www.ionis.com/ionis-technology/antisense-pipeline/ 2. Moumne L, et al. Pharmaceutics. 2022;14(2):260. 3. Ionis Pharmaceuticals. Ionis Neurology Pipeline. Accessed August 21, 2024. https://www.ionis.com/ionis-technology/innovation/pipeline/transforming-the-management-of-neurology/ 4. ClinicalTrials.gov identifier: NCT04849741. Accessed August 19, 2024. https://clinicaltrials.gov/study/NCT04849741/
ION582 (Angelman syndrome)
ION582 is an investigational RNA-targeted medicine (RTM) designed to inhibit the expression of the UBE3A antisense transcript (UBE3A-ATS) and increase production of UBE3A protein as a potential therapy for Angelman syndrome (AS).1,2
This investigational RTM is being assessed in HALOS, a Phase 1-2a, open-label, three-part study evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple ascending doses (MAD) of ION582 administered intrathecally (IT) in up to 55 patients with AS.2,3
Part 1 of the study consists of a 13-week MAD treatment period, with a 12- to 32-week post-MAD follow-up period. Part 2 is a multicenter 49-week study where patients who completed part 1 will receive IT bolus doses of ION582 followed by a minimum 12-week follow-up period. Part 3 extends the treatment period for patients who completed part 2 for up to an additional 3 years followed by a 32-week post-long-term extension
follow-up period.3
Study start3:
Study completion3:
UBE3A, ubiquitin protein ligase E3A. 1. Ionis Pharmaceuticals. The Ionis Antisense Pipeline. Accessed August 15, 2024. https://www.ionis.com/ionis-technology/antisense-pipeline/ 2. Ionis Pharmaceuticals. Ionis Neurology Pipeline. Accessed August 21, 2024. https://www.ionis.com/ionis-technology/innovation/pipeline/transforming-the-management-of-neurology/ 3. ClinicalTrials.gov identifier: NCT05127226. Accessed August 19, 2024. https://clinicaltrials.gov/study/NCT05127226/
ION717 (Prion disease)
ION717 is an investigational RNA-targeted medicine (RTM) designed to inhibit the production of prion protein as a potential therapy for prion disease (PrD).1,2
This investigational RTM is being studied in PrProfile, a Phase 1-2a, first-in-human, randomized, multicenter study evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of intrathecally administered ION717 in approximately 56 patients with PrD. The study will consist of a screening period of up to 6 weeks, a 30-week double-blind treatment period, a 70-week open-label extension period, and a 32-week posttreatment period.2,3
Study start3:
Study completion3:
1. Ionis Pharmaceuticals. The Ionis Antisense Pipeline. Accessed August 15, 2024. https://www.ionis.com/ionis-technology/antisense-pipeline/ 2. Ionis Pharmaceuticals. Ionis Neurology Pipeline. Accessed August 21, 2024. https://www.ionis.com/ionis-technology/innovation/pipeline/transforming-the-management-of-neurology/ 3. ClinicalTrials.gov identifier: NCT06153966. Accessed August 19, 2024. https://clinicaltrials.gov/study/NCT06153966/
ION440 (MECP2 duplication syndrome)
ION440 is an investigational RNA-targeted medicine (RTM) designed as a potential therapy for MECP2 duplication syndrome (MDS).1,2
This investigational RTM is being studied in ATTUNE, a Phase 1-2 study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of intrathecally administered ION440 in pediatric and adult patients with MDS. This is a multicenter, two-part study with multiple dosing cohorts being evaluated in approximately 48 patients.1,2
During part 1, patients will be randomized in a 3:1 ratio to receive ION440 or sham for 36 weeks. Patients who complete part 1 are eligible to enter part 2, an open-label, long-term extension study, where patients will receive ION440 for up to approximately 156 weeks.2
Study start2:
Study completion2:
MECP2, methyl-CpG binding protein 2. 1. Ionis Pharmaceuticals. Ionis Neurology Pipeline. Accessed August 21, 2024. https://www.ionis.com/ionis-technology/innovation/pipeline/transforming-the-management-of-neurology/ 2. ClinicalTrials.gov identifier: NCT06430385. Accessed November 1, 2024. https://clinicaltrials.gov/study/NCT06430385/
ION356 (Pelizaeus-Merzbacher disease)
ION356 is an investigational RNA-targeted medicine (RTM) designed to decrease the production of proteolipid protein 1 (PLP1) as a potential therapy for male children with a diagnosis of Pelizaeus-Merzbacher disease (PMD).1,2
This RTM is being studied in ORBIT, a Phase 1b study to evaluate the safety, pharmacokinetics, and pharmacodynamics of intrathecally administered ION356 in male patients with PMD. This is a multicenter, multiple ascending-dose (MAD), multipart study enrolling approximately 24 pediatric patients.2,3
The study will have two parts: a 48-week MAD part followed by an open-label, long-term extension (LTE) part of 109 weeks. During the MAD portion of the study, eligible patients will receive doses of ION356 and upon completion will transition to the open-label LTE to receive doses of ION356.3
Study start3:
Study completion3:
1. Ionis Pharmaceuticals. The Ionis Antisense Pipeline. Accessed August 15, 2024. https://www.ionis.com/ionis-technology/antisense-pipeline/ 2. Ionis Pharmaceuticals. Ionis Neurology Pipeline. Accessed August 21, 2024. https://www.ionis.com/ionis-technology/innovation/pipeline/transforming-the-management-of-neurology/ 3. ClinicalTrials.gov identifier: NCT06150716. Accessed August 19, 2024. https://clinicaltrials.gov/study/NCT06150716/
IONIS-MAPTRx (Alzheimer’s disease)
IONIS-MAPTRx, also known as BIIB080, is an investigational RNA-targeted medicine (RTM) designed to selectively inhibit the production of the microtubule-associated protein tau (MAPT), or tau protein in the brain. IONIS-MAPTRx is being developed as a potential therapy for patients with Alzheimer’s disease (AD) and potentially other neurodegenerative disorders characterized by the deposition of abnormal tau protein within nerve cells in the brain.1,2
This investigational RTM was evaluated in a Phase 1-2, randomized, double-blind, placebo-controlled study followed by an open-label extension to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple ascending doses of intrathecally administered IONIS-MAPTRx in patients with mild AD.2,3
Study start3:
Study completion3:
1. Ionis Pharmaceuticals. The Ionis Antisense Pipeline. Accessed August 15, 2024. https://www.ionis.com/ionis-technology/antisense-pipeline/ 2. Ionis Pharmaceuticals. Ionis Neurology Pipeline. Accessed August 21, 2024. https://www.ionis.com/ionis-technology/innovation/pipeline/transforming-the-management-of-neurology/ 3. ClinicalTrials.gov identifier: NCT03186989. Accessed August 19, 2024. https://clinicaltrials.gov/study/NCT03186989/
ION859 (Parkinson’s disease)
ION859, also known as BIIB094, is an investigational RNA-targeted medicine (RTM) being developed as a potential therapy for Parkinson’s disease (PD).1,2
This investigational RTM is being studied in REASON, a Phase 1 study evaluating the safety, tolerability, and pharmacokinetics of single and multiple doses of ION859 administered via intrathecal injection in patients with PD. This is a randomized, blinded, placebo-controlled, multiple ascending-dose study open to patients with PD with verified presence or absence of variation in the leucine-rich repeat kinase 2 gene (LRRK2), but also to patients without any verified PD-related genetic variant.2,3
Study start3:
Study completion3:
1. Ionis Pharmaceuticals. The Ionis Antisense Pipeline. Accessed August 15, 2024. https://www.ionis.com/ionis-technology/antisense-pipeline/ 2. Ionis Pharmaceuticals. Ionis Neurology Pipeline. Accessed August 21, 2024. https://www.ionis.com/ionis-technology/innovation/pipeline/transforming-the-management-of-neurology/ 3. ClinicalTrials.gov identifier: NCT03976349. Accessed November 1, 2024. https://clinicaltrials.gov/study/NCT03976349/
ION464 (Multiple system atrophy)
ION464, also known as BIIB101, is an investigational RNA-targeted medicine (RTM) designed to inhibit the production of the alpha-synuclein protein as a potential therapy for a group of neurodegenerative disorders that include Parkinson’s disease and multiple system atrophy (MSA).1,2
This investigational RTM is being assessed in HORIZON, a Phase 1, multiple-ascending-dose (MAD) study (Part 1) to evaluate the safety, tolerability, PK, and PD of ION464 in adult participants diagnosed with MSA with a long-term extension (LTE) (Part 2). This is a first-in-human, randomized, blinded, placebo-controlled, multiple ascending-dose study of approximately 40 patients.2,3
Part 1 of the study will consist of a screening period of up to 6 weeks, a treatment period of 12 weeks, and a follow-up period of 24 weeks. The study duration for each patient in part 2 will be approximately 96 weeks, consisting of a 72-week treatment period and a 24-week follow-up period.3
Study start3:
Study completion3:
1. Ionis Pharmaceuticals. The Ionis Antisense Pipeline. Accessed August 15, 2024. https://www.ionis.com/ionis-technology/antisense-pipeline/ 2. Ionis Pharmaceuticals. Ionis Neurology Pipeline. Accessed August 21, 2024. https://www.ionis.com/ionis-technology/innovation/pipeline/transforming-the-management-of-neurology/ 3. ClinicalTrials.gov identifier: NCT04165486. Accessed November 1, 2024. https://clinicaltrials.gov/study/NCT04165486/
ION306 (Spinal muscular atrophy)
ION306, also known as BIIB115, is an investigational RNA-targeted medicine (RTM) in development as a potential therapy for patients with spinal muscular atrophy (SMA). ION306 is designed to target the root cause of SMA by increasing the production of functional survival motor neuron protein.1,2
This investigational RTM is being studied in a Phase 1, randomized, blinded, placebo-controlled, single
ascending-dose study in healthy adult male volunteers and an open-label multiple ascending-dose study in pediatric patients with SMA previously treated with onasemnogene abeparvovec. This study will evaluate the safety, tolerability, and pharmacokinetics of ION306.2,3
Part 1 consists of screening, treatment, and follow-up periods that will last for 13 months. Part 2 will consist of a treatment and follow-up period for children with SMA and will last for 25 months.3
Study start3:
Study completion3:
1. Ionis Pharmaceuticals. The Ionis Antisense Pipeline. Accessed August 15, 2024. https://www.ionis.com/ionis-technology/antisense-pipeline/ 2. Ionis Pharmaceuticals. Ionis Neurology Pipeline. Accessed August 21, 2024. https://www.ionis.com/ionis-technology/innovation/pipeline/transforming-the-management-of-neurology/ 3. ClinicalTrials.gov identifier: NCT05575011. Accessed August 19, 2024. https://clinicaltrials.gov/study/NCT05575011/
Tominersen (Huntington’s disease)
Tominersen, clinically known as IONIS-HTTRx and RG6042, is an investigational RNA-targeted medicine (RTM) being evaluated as a potential therapy for patients with Huntington’s disease (HD).1,2
This investigational RTM is being studied in GENERATION HD2, a Phase 2 randomized, double-blind, placebo-controlled, dose-finding study to evaluate the safety, biomarkers, and efficacy of tominersen in patients with prodromal and early manifest HD.2,3
Study start3:
Study completion3:
1. Ionis Pharmaceuticals. The Ionis Antisense Pipeline. Accessed August 15, 2024. https://www.ionis.com/ionis-technology/antisense-pipeline/ 2. Ionis Pharmaceuticals. Ionis Neurology Pipeline. Accessed August 21, 2024. https://www.ionis.com/ionis-technology/innovation/pipeline/transforming-the-management-of-neurology/ 3. ClinicalTrials.gov identifier: NCT05686551. Accessed August 19, 2024. https://clinicaltrials.gov/study/NCT05686551/
Learn more about the current clinical trials for Ionis’ RNA-targeted medicines.
Learn more about the neurologic diseases in Ionis’ pipeline.
References
- Ionis Pharmaceuticals. The Ionis antisense pipeline. Accessed August 19, 2024. https://www.ionis.com/ionis-technology/antisense-pipeline/
- Ionis Pharmaceuticals. Ionis Innovation Day. October 4, 2023. Accessed August 19, 2024. https://ir.ionis.com/static-files/8b71dc65-dad9-4368-9014-604c5b203ca1/
- Partridge W, Xia S, Kwoh TJ, Bhanot S, Geary RS, Baker BF. Improvements in the tolerability profile of 2′-O-methoxyethyl chimeric antisense oligonucleotides in parallel with advances in design, screening, and other methods. Nucleic Acid Ther. 2021;31(6):417-426.
- Ionis Pharmaceuticals. The creation of RNA targeting technology. December 2019. Accessed August 19, 2024. https://ir.ionispharma.com/static-files/1cada39c-0fa4-4e90-afdf-e85fa258e03b/
- Crooke ST, Liang XH, Baker BF, Crooke RM. Antisense technology: a review. J Biol Chem. 2021;296:100416.
- Crooke ST, Witztum JL, Bennett CF, Baker BF. RNA-targeted therapeutics [published correction appears in Cell Metab. 2019 Feb 5;29(2):501. doi: 10.1016/j.cmet.2019.01.001]. Cell Metab. 2018;27(4):714-739.
- Ionis Pharmaceuticals. Data on file.
- Ionis Pharmaceuticals. Our Medicines. Accessed August 19, 2024. https://www.ionis.com/medicines/
- Ionis reports second quarter financial results and recent business achievements. US Securities and Exchange Commission. August 9, 2022. Accessed August 19, 2024. https://www.sec.gov/Archives/edgar/data/874015/000114036122028849/brhc10040582_ex99-1.htm
