Our Pipeline
Our Pipeline
Our goal is to discover and develop potentially life-changing therapeutics across a range of neurologic diseases.1
The Ionis Neurology pipeline includes investigational RNA-targeted therapeutics 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 therapeutics.2-7
With 3 FDA-approved neurologic therapeutics and more than 10 investigational RNA-targeted therapeutics 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 Therapeutics Designed to Target Genetic Sequences Associated With a Range of Rare and Prevalent Neurologic Conditions1,2,7,a,b
ION440 (MECP2 duplication syndrome)
ION440
MECP2 duplication syndrome
ION440 (MECP2 duplication syndrome)
ION440
MECP2 duplication syndrome
ION440 is an investigational RNA-targeted therapeutic (RTT) designed as a potential therapy for MECP2 duplication syndrome (MDS).1
This investigational RTT 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.2
During part 1, patients will be randomized in a 3:1 ratio to receive ION440 or sham. 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
Recruitment status2:
Estimated study start 2:
Estimated study completion 2:
| Investigational RTM | Disease State | Gene/Target | Phase 1 Phase 2 Phase 3 | |
|---|---|---|---|---|
| Ionis-owned | Zilganersen |
Alexander disease | GFAP | |
ION582c |
Angelman syndrome | UBE3A-ATS | ||
ION269d |
Alzheimer's disease |
APP | ||
ION717e |
Prion disease | PRNP | ||
ION440 |
MECP2 duplication syndrome |
MECP2 | ||
ION356 |
Pelizaeus-Merzbacher disease |
PLP1 | ||
ION859f |
Parkinson’s disease | LRRK2 | ||
ION464f |
Multiple system atrophy and |
SNCA | ||
| Investigational RTM | Disease State | Gene/Target | Phase 1 Phase 2 Phase 3 | |
|---|---|---|---|---|
| Ionis-Biogen | Tofersen |
Superoxide dismutase 1 |
SOD1 | |
IONIS-MAPTRx |
Alzheimer’s disease | TAU | ||
ION306 |
Spinal muscular atrophy | SMN2 | ||
| Investigational RTM | Disease State | Gene/Target | Phase 1 Phase 2 Phase 3 | |
|---|---|---|---|---|
| Ionis-Otsuka | Ulefnersen |
Fused in sarcoma amyotrophic |
FUS | |
| Investigational RTM | Disease State | Gene/Target | Phase 1 Phase 2 Phase 3 | |
|---|---|---|---|---|
| Ionis-Roche | Tominersen |
Huntington’s disease | HTT | |
aContent in the table subject to change pending updates to Ionis pipeline. bSafety and efficacy have not been evaluated by any regulatory authorities for the indications described. cThe US Food and Drug Administration has granted both orphan drug designation and rare pediatric disease designation for its investigational drug ION582.9 dThis investigational antisense oligonucleotide therapeutic is in a Phase 1b study. It is listed here in Phase 2 because the therapeutic is being tested in people living with Down syndrome.1 eThis investigational antisense therapeutic is in a Phase 1/2a study.1 fThis investigational antisense therapeutic is in a Phase 1 study. The primary purpose of the study is the evaluation of the therapeutic’s safety profile. It is listed here in Phase 2 because the therapeutic is being tested in patients and not healthy volunteers. This study may be categorized by partners or on regulatory sites, such as ClinicalTrials.gov, as a Phase 1 study.1
MECP2, methyl-CpG binding protein 2 gene (human).
Zilganersen (Alexander disease)
Zilganersen (ION373)
Alexander disease
Zilganersen, clinically known as ION373, is an investigational RNA-targeted therapeutic (RTT) that targets glial fibrillary acidic protein (GFAP) and is designed to inhibit the production of GFAP. Zilganersen is being developed as a potential therapy for Alexander disease (AxD).1
This investigational RTT 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.2
The initial participants must be at least 8 years of age at the time of screening. Some study sites will include an optional open-label sub-study in patients <2 years of age.2
Study start 2:
Study completion 2:
1. Ionis Pharmaceuticals. Pipeline. Accessed March 3, 2025. https://ionis.com/science-and-innovation/pipeline/ 2. ClinicalTrials.gov identifier: NCT04849741. Accessed March 3, 2025. https://clinicaltrials.gov/study/NCT04849741/
ION582c (Angelman syndrome)
ION582c
Angelman syndrome
ION582a is an investigational RNA-targeted therapeutic (RTT) 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
ION269 (Alzheimer's diseasein Down syndrome)
ION269d
Alzheimer's disease in Down
syndrome
ION269 is an investigational RNA-targeted therapeutic (RTT) designed to lower the amount of amyloid precursor protein for the potential treatment of Alzheimer's disease (AD), which is initially being studied in adults with Down syndrome (DS) who have a genetic risk of developing AD.1
This investigational RTT is being studied in HERO, a Phase 2,a multicenter, open-label, single ascending dose study in adult participants with DS who have evidence of brain amyloid positivity. Participants will be examined in 3 separate cohorts and will receive a single dose of the study drug during the 36-week treatment period, followed by a 4-week follow-up period.1,2
Estimated study start 2:
Estimated study completion 2:
aThis investigational antisense oligonucleotide therapeutic is in a Phase 1b study. It is listed here in Phase 2 because the therapeutic is being tested in people living with Down syndrome.1
1. Ionis Pharmaceuticals. Pipeline. Accessed March 3, 2025. https://www.ionis.com/science-and-innovation/pipeline/
2. ClinicalTrials.gov identifier: NCT06673069. Accessed February 26, 2025. https://www.clinicaltrials.gov/study/NCT06673069/
ION717e (Prion disease)
ION717e
Prion disease
ION717 is an investigational RNA-targeted therapeutic (RTT) designed to inhibit the production of prion protein as a potential therapy for prion disease (PrD).1
This investigational RTT 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
Study start 2:
Estimated study completion 2:
ION440 (MECP2 duplication syndrome)
ION440
MECP2 duplication syndrome
ION440 is an investigational RNA-targeted therapeutic (RTT) designed as a potential therapy for MECP2 duplication syndrome (MDS).1
This investigational RTT 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.2
During part 1, patients will be randomized in a 3:1 ratio to receive ION440 or sham. 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
Estimated study start 2:
Estimated study completion 2:
ION356 (Pelizaeus-Merzbacher disease)
ION356
Pelizaeus-Merzbacher disease
ION356 is an investigational RNA-targeted therapeutic (RTT) 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
This RTT is being studied in ORBIT, a Phase 2 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.1,2
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 ION356.2
Study start 2:
Estimated study completion 2:
1. Ionis Pharmaceuticals. Pipeline. Accessed March 3, 2025. https://ionis.com/science-and-innovation/pipeline/ 2. ClinicalTrials.gov identifier: NCT06150716. Accessed March 3, 2025. https://clinicaltrials.gov/study/NCT06150716
ION859f (Parkinson’s disease)
ION859f
Parkinson’s disease
ION859, clinically known as BIIB094, is an investigational RNA-targeted therapeutic (RTT) being developed as a potential therapy for Parkinson’s disease (PD).1,2
This investigational RTT is being studied in REASON, a Phase 2a 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.1,2
Study start 2:
Estimated study completion 2:
aThis investigational antisense therapeutic is in a Phase 1 study. The primary purpose of the study is the evaluation of the therapeutic’s safety profile. It is listed here in Phase 2 because the therapeutic is being tested in patients and not healthy volunteers. This study may be categorized by partners or on regulatory sites, such as ClinicalTrials.gov, as a Phase 1 study.1
1. Ionis Pharmaceuticals. Pipeline. Accessed March 3, 2025. https://ionis.com/science-and-innovation/pipeline/ 2. ClinicalTrials.gov identifier: NCT03976349. Accessed August 19, 2024. https://clinicaltrials.gov/study/NCT03976349/
ION464f (Multiple system atrophy and Parkinson's disease)
ION464f
Multiple system atrophy
and Parkinson's disease
ION464, clinically known as BIIB101, is an investigational RNA-targeted therapeutic (RTT) 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 RTT is being assessed in HORIZON, a Phase 2,a multiple-ascending-dose (MAD) study (Part 1) to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics 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.1,2
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.2
Study start 2:
Estimated study completion 2:
Tofersen (Superoxide dismutase 1 amyotrophic lateral sclerosis)
Tofersen
Superoxide dismutase 1
amyotrophic lateral sclerosis
IONIS-MAPTRx, also known as BIIB080, is an investigational RNA-targeted therapeutic (RTT) 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 RTT 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 start 1:
Estimated study completion 1:
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/
IONIS-MAPTRx (Alzheimer’s disease)
IONIS-MAPTRx
Alzheimer’s disease
IONIS-MAPTRx, clinically known as BIIB080, is an investigational RNA-targeted therapeutic (RTT) 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
This investigational RTT 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
Study start 2:
Study completion 2:
1. Ionis Pharmaceuticals. Pipeline. Accessed March 3, 2025. https://ionis.com/science-and-innovation/pipeline/ 2. ClinicalTrials.gov identifier: NCT03186989. Accessed August 19, 2024. https://clinicaltrials.gov/study/NCT03186989/
ION306 (Spinal muscular atrophy)
ION306
Spinal muscular atrophy
ION306, clinically known as BIIB115, is an investigational RNA-targeted therapeutic (RTT) 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 RTT is being studied in a Phase 2, 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 ION306.1,2
Part 1 consists of screening, treatment, and follow-up periods. The treatment and follow-up 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.2
Study start 2:
Estimated study completion 2:
1. Ionis Pharmaceuticals. Pipeline. Accessed March 3, 2025. https://ionis.com/science-and-innovation/pipeline/ 2. ClinicalTrials.gov identifier: NCT05575011. Accessed March 11, 2025. https://clinicaltrials.gov/study/NCT05575011/
Ulefnersen (ION363) Fused in sarcoma amyotrophic lateral sclerosis
Ulefnersen (ION363)
Fused in sarcoma
amyotrophic lateral sclerosis
Ulefnersen, clinically known as ION363, is an investigational RNA-targeted therapeutic (RTT) 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 RTT 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
Study start 2:
Estimated study completion 2:
1. Ionis Pharmaceuticals. Pipeline. Accessed March 3, 2025. https://ionis.com/science-and-innovation/pipeline/ 2. ClinicalTrials.gov identifier: NCT04768972. Accessed August 16, 2024. https://clinicaltrials.gov/study/NCT04768972/
Tominersen (Huntington’s disease)
Tominersen
Huntington’s disease
Tominersen, clinically known as IONIS-HTTRx and RG6042, is an investigational RNA-targeted therapeutic (RTT) being evaluated as a potential therapy for patients with Huntington’s disease (HD).1,2
This investigational RTT 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
Study start 2:
Estimated study completion 2:
1. Ionis Pharmaceuticals. Pipeline. Accessed March 3, 2025. https://ionis.com/science-and-innovation/pipeline/ 2. ClinicalTrials.gov identifier: NCT05686551. Accessed March 11, 2025. https://clinicaltrials.gov/study/NCT05686551/
aContent in the table subject to change pending updates to Ionis pipeline. bSafety and efficacy have not been evaluated by any regulatory authorities for the indications described. cThe US Food and Drug Administration has granted both orphan drug designation and rare pediatric disease designation for its investigational drug ION582.9 dThis investigational antisense oligonucleotide therapeutic is in a Phase 1b study. It is listed here in Phase 2 because the therapeutic is being tested in people living with Down syndrome.1 eThis investigational antisense therapeutic is in a Phase 1/2a study.1 fThis investigational antisense therapeutic is in a Phase 1 study. The primary purpose of the study is the evaluation of the therapeutic’s safety profile. It is listed here in Phase 2 because the therapeutic is being tested in patients and not healthy volunteers. This study may be categorized by partners or on regulatory sites, such as ClinicalTrials.gov, as a Phase 1 study.1
MECP2, methyl-CpG binding protein 2 gene (human).
Learn more about the current clinical trials for Ionis’ RNA-targeted therapeutics.
Learn more about the neurologic diseases in Ionis’ pipeline.
References
- Ionis Pharmaceuticals. Pipeline. Accessed March 3, 2025. https://ionis.com/science-and-innovation/pipeline
- Ionis Pharmaceuticals. Ionis Innovation Day. October 4, 2023. Accessed March 3, 2025. 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 March 3, 2025. 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. Medicines. Accessed March 3, 2025. https://www.ionis.com/medicines/
- Ionis reports second quarter financial results and recent business achievements. US Securities and Exchange Commission. August 9, 2022. Accessed March 4, 2025. https://www.sec.gov/Archives/edgar/data/874015/ 000114036122028849/brhc10040582_ex99-1.htm
