Ionis Innovation

The Ionis antisense pipeline

Our antisense technology platform has served as a springboard for drug discovery and realized hope for patients with unmet needs. Our broad, diverse pipeline has more than 40 potential first-in-class and/or best-in-class medicines designed to treat a broad range of diseases.

The result of 30 years of perfecting and advancing RNA targeted drug discovery and development, our proprietary platform now provides a fast and efficient path from identification of potential causes of human diseases to the discovery of potentially life-saving medicines.

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Therapeutic Areas

Phase

Therapeutic area

Phase

Neurological

Zilganersen

(GFAP)

Alexander Disease

Ionis-Owned

Zilganersen, formerly known as ION373, is an investigational antisense medicine 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).

About Alexander Disease (AxD)

AxD is a rare, progressive and ultimately fatal neurological disease that affects a type of cell in the brain called astrocytes. Astrocytes have multiple roles in the brain to support other cells called neurons and oligodendrocytes, which maintain the myelin sheath that protects nerve fibers. AxD is caused by a gain-of-function mutation in the GFAP gene and is characterized by progressive neurologic deterioration, including loss of independence and the ability to control muscles for large movements, swallowing and airway protection. AxD usually leads to death within 15-25 years after symptom onset. There are treatments to relieve symptoms, but there is no disease modifying therapy yet available to patients.

Safety and efficacy have not been evaluated by any regulatory authorities for the indication described.

Ulefnersen

(FUS)

Amyotrophic Lateral Sclerosis

Ionis-Owned

Ulefnersen, formerly known as ION363, is an investigational antisense medicine designed to reduce the production of the fused in sarcoma (FUS) protein to treat people with amyotrophic lateral sclerosis (ALS) caused by mutations in the FUS gene. Ulefnersen is also known as Jacifusen (not an official USAN name) in honor of Jaci Hermstad, the first patient treated with the drug under an expanded access program. Because antisense-mediated reduction of mutant FUS protein in a FUS-ALS mouse model demonstrated the ability to prevent motor neuron loss, it is hypothesized that reduction of FUS protein will reverse or prevent disease progression in FUS-ALS patients.

About Fused in Sarcoma (FUS) Amyotrophic Lateral Sclerosis (ALS)

FUS-ALS is a rare, fatal, neurodegenerative disorder characterized by muscle weakness, loss of movement, and difficulty breathing and swallowing, resulting in a severely declining quality of life and eventually death. Current treatment options are extremely limited, with no medicines that significantly slow disease progression.

Safety and efficacy have not been evaluated by any regulatory authorities for the indication described.

Tofersen

(SOD1)

Amyotrophic Lateral Sclerosis

Biogen

Tofersen is an investigational antisense medicine that is designed to inhibit the production of superoxide dismutase 1 (SOD1) and is currently being studied in presymptomatic adult carriers with a SOD1 mutation, a well understood genetic cause of amyotrophic lateral sclerosis (ALS).

Tofersen is also approved in the U.S. for the treatment of patients with SOD1 ALS under the brand name QALSODY® (tofersen). Please see the full Prescribing Information.

About Superoxide Dismutase 1 (SOD1) Amyotrophic Lateral Sclerosis (ALS)

SOD1-ALS is a rare, fatal, neurodegenerative disorder caused by a mutation in the SOD1 gene leading to a progressive loss of motor neurons. As a result, people with SOD1-ALS experience increasing muscle weakness, loss of movement, difficulty breathing and swallowing and eventually succumb to the disease. SOD1-ALS is diagnosed in approximately 2% of all ALS cases, impacting about 330 people in the United States. Approximately 5-10% of people with ALS have a genetic form of the disease of whom about 20% will have a mutation of the SOD1 gene; however, they may not have a known family history of the disease.

Safety and efficacy have not been evaluated by any regulatory authorities for the SOD1-ALS indication described.

ION717*

(PRNP)

Prion Disease

Ionis-Owned

ION717 is an investigational antisense medicine designed to inhibit the production of prion protein (PrP) for the potential treatment of prion disease.

About Prion Disease
Prion disease is a rare, fatal neurodegenerative disease caused by misfolding of PrP which accumulates in the brain. People with prion disease often experience progressive memory impairment, personality changes, difficulties with movement and loss of independence. There are currently no effective disease-modifying treatments for prion disease. In most cases, a person succumbs to prion disease within a year following symptom onset.

Safety and efficacy have not been evaluated by any regulatory authorities for the indication described.

^*This investigational antisense medicine is in a Phase 1/2a study.

ION356^*

(PLP1)

Pelizaeus-Merzbacher Disease

Ionis-Owned

ION356 is an investigational antisense oligonucleotide (ASO) medicine designed to decrease the production of proteolipid protein-1 (PLP1) for the potential treatment of male children with a diagnosis of Pelizaeus-Merzbacher disease (PMD).

About Pelizaeus-Merzbacher Disease (PMD)

PMD is one of a group of disorders known as leukodystrophies, which impact the growth of the myelin sheath – a protective covering that forms around nerve fibers in the brain and is vital in the sending of electrical impulses. PMD is a rare X-linked recessive leukodystrophy that is caused by duplications, mutations, or deletions in the gene that controls the production of a myelin protein called proteolipid protein-1 (PLP1). These changes can affect coordination, ability to move independently, and cognitive function. Symptoms may be present from birth, but onset and presentation can vary from person to person. There are currently no disease-modifying medicines for PMD on the market.

Safety and efficacy have not been evaluated by any regulatory authorities for the indication described.

^*This investigational antisense medicine is in a Phase 1b study. It is listed here in Phase 2 because the medicine is being tested in patients and not healthy volunteers.

IONIS-MAPT_Rx

(TAU)

Alzheimer's Disease

Biogen

IONIS-MAPT_Rx, also known as BIIB080, is an investigational antisense medicine designed to selectively inhibit production of the microtubule-associated protein tau (MAPT), or tau protein in the brain. IONIS-MAPT_Rx is being developed to treat people with Alzheimer’s disease (AD) and potentially other neurodegenerative disorders characterized by the deposition of abnormal tau protein within nerve cells in the brain.

About Alzheimer’s Disease (AD)

AD is the most common form of dementia in older individuals and is characterized by worsening impairments in memory and other cognitive functions, resulting in a person’s increasing inability to perform daily activities. AD usually progresses to death in five to 20 years after the onset of the disease.

Safety and efficacy have not been evaluated by any regulatory authorities for the indication described.

ION859*

(LRRK2)

Parkinson's Disease

Biogen

ION859 (formerly IONIS-BIIB7_Rx), also known as BIIB094, is an investigational antisense medicine designed to inhibit the production of the leucine-rich repeat kinase 2 (LRRK2) protein as a potential therapy for Parkinson’s disease (PD). The most common PD-associated genetic mutations are found in the LRRK2 gene. It is believed that increased LRRK2 protein and function could be one of the key drivers for developing PD.

About Parkinson’s Disease (PD)

PD is a progressive neurodegenerative disease characterized by loss of dopamine-producing neurons in the part of the brain that controls movement. Patients with PD can experience tremors, loss of balance and coordination, stiffness, slowing of movement, changes in speech and eventually in most cases significant cognitive decline. PD is associated with a shortened lifespan. There are treatments that can relieve symptoms for a limited period of time, but there are no approved treatments that modify the course of the disease.

Safety and efficacy have not been evaluated by any regulatory authorities for the indication described.

^*This investigational antisense medicine is in a Phase 1 study. It is listed here in Phase 2 because the medicine is being tested in patients and not healthy volunteers.

ION464*

(SNCA)

Multiple System Atrophy & Parkinson's Disease

Biogen

ION464, also known as BIIB101, is an investigational antisense medicine 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 (PD) and multiple system atrophy (MSA).

About Multiple System Atrophy (MSA) and Parkinson’s Disease (PD)

Altered and insoluble forms of a protein called alpha-synuclein accumulates in the brains of PD and MSA patients and is thought to be a key driver of neurodegeneration in these diseases. It is believed that decreasing the production of the alpha-synuclein protein will reduce the accumulation and toxic effects of misfolded alpha-synuclein.

Safety and efficacy have not been evaluated by any regulatory authorities for the indication described.

^*This investigational antisense medicine is in a Phase 1 study. It is listed here in Phase 2 because the medicine is being tested in patients and not healthy volunteers.

ION582*

(UBE3A-ATS)

Angelman Syndrome

Ionis-Owned

ION582 is an investigational antisense medicine designed to inhibit the expression of the UBE3A transcript (UBE3A-ATS) and increase production of UBE3A protein, for the potential treatment of Angelman syndrome (AS).

About Angelman Syndrome (AS)

AS is a rare, genetic neurological disease caused by the loss of function of the maternally inherited UBE3A gene. AS typically presents in infancy and is characterized by profound intellectual disability, balance issues, motor impairment, and debilitating seizures. Some patients are unable to walk or speak. Individuals with AS have a normal lifespan but require complete care from a caregiver. Some symptoms can be managed with existing medicines; however, there are no approved disease modifying therapies.

Safety and efficacy have not been evaluated by any regulatory authorities for the indication described.

^*This investigational antisense medicine is in a Phase 1/2a study.

Tominersen

(HTT)

Huntington’s Disease

Roche

Tominersen, formerly known as IONIS-HTT_Rx and RG6042, is an investigational antisense medicine designed to target the underlying cause of Huntington’s disease (HD) by reducing the production of all forms of the huntingtin protein (HTT), including its mutated variant (mHTT).

About Huntington’s Disease (HD)

HD is an inherited genetic brain disorder that results in the progressive loss of both mental faculties and physical control. It is caused by the expansion of the cytosine-adenine-guanine (CAG) trinucleotide sequence in the HTT gene. The resulting mutant HTT protein is toxic and gradually destroys neurons. Symptoms usually appear between the ages of 30 and 50 and worsen over a 10-to-25-year period. Ultimately, the weakened individual succumbs to pneumonia, heart failure or other complications. Presently, there is no effective treatment or cure for the disease, and currently available medicines may address some of the patient’s symptoms but do not impact disease progression.

Safety and efficacy have not been evaluated by any regulatory authorities for the indication described.

ION306

(SMN2)

Spinal Muscular Atrophy

Biogen

ION306, also known as BIIB115, is an investigational antisense medicine in development for the treatment of patients with spinal muscular atrophy (SMA). This medicine has the potential to help address additional unmet needs of patients as well as be administered with long interval dosing. ION306 is designed to target the root cause of SMA by increasing the production of functional survival motor neuron (SMN) protein.

About Spinal Muscular Atrophy (SMA)

SMA is a rare, genetic, neuromuscular disease that affects individuals of all ages. It is characterized by a loss of motor neurons in the spinal cord and lower brain stem, resulting in progressive muscle atrophy and weakness. SMA is caused by a deficiency in the production of SMN protein due to mutations and/or loss of both SMN1 genes, with a spectrum of disease severity. Some individuals with SMA may never sit; some sit but never walk; and some walk but may lose that ability over time. In the absence of disease-modifying treatment, children with the most severe form of SMA would usually not be expected to reach their second birthday.

Safety and efficacy have not been evaluated by any regulatory authorities for the indication described.

Cardiovascular

Eplontersen

(TTR)

Transthyretin-Mediated Amyloid Cardiomyopathy

AstraZeneca**

Eplontersen, formerly known as IONIS-TTR-L_Rx and AKCEA-TTR-L_Rx, is an investigational LIgand-Conjugated Antisense (LICA) medicine designed to inhibit the production of transthyretin, or TTR protein. The investigational medicine is currently being evaluated in the Phase 3 CARDIO-TTRansform study for hereditary or wild-type transthyretin-mediated amyloid cardiomyopathy (ATTR-CM), a progressive and fatal condition that typically leads to progressive heart failure and often death within three-to-five years from disease onset.

Eplontersen was recently approved in the U.S. for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults, commonly referred to as hATTR-PN or ATTRv-PN under the brand name WAINUA™ (eplontersen). Please see full Prescribing Information.

About Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR-CM)

ATTR-CM is an underdiagnosed and potentially fatal disease. It is caused by the accumulation of misfolded TTR protein in the cardiac muscle. Patients experience ongoing debilitating heart damage resulting in progressive heart failure, which results in death within three to five years from disease onset. ATTR-CM includes both the genetic and wild-type form of the disease. Worldwide, there are an estimated 300,000 – 500,000 patients with ATTR-CM.

Safety and efficacy have not been evaluated by any regulatory authorities for the ATTR-CM indication described.

^*^* Ionis is jointly developing and commercializing eplontersen.

Olezarsen

(ApoC-III)

Familial Chylomicronemia Syndrome

Ionis-Owned

Olezarsen, formerly known as IONIS-APOCIII-L_Rx and AKCEA-APOCIII-L_Rx, is an RNA-targeted investigational LIgand-Conjugated Antisense (LICA) medicine being evaluated for people at risk of disease due to elevated triglyceride levels, including those with familial chylomicronemia syndrome (FCS). Olezarsen is designed to inhibit the body’s production of apoC-III, a protein produced in the liver that regulates triglyceride metabolism in the blood.

About Familial Chylomicronemia Syndrome (FCS)

FCS is a rare, genetic form of severe hypertriglyceridemia (sHTG) and is characterized by extremely elevated triglyceride levels and corresponding build-up of large triglyceride-containing particles in the blood called chylomicrons, which can result in severe health complications. It is caused by impaired function of the enzyme lipoprotein lipase (LPL). Because of limited LPL production or function, people with FCS cannot effectively break down chylomicrons, lipoprotein particles that are 90% triglycerides. FCS is estimated to impact one to 13 people per million in the U.S. People living with FCS are at high risk of acute pancreatitis (AP) in addition to other chronic health issues such as severe, recurrent abdominal pain. People living with FCS experience debilitating psychosocial symptoms, and are sometimes unable to work, adding to the burden of disease.

Safety and efficacy have not been evaluated by any regulatory authorities for the indication described.

Olezarsen

(ApoC-III)

Severe Hypertriglyceridemia

Ionis-Owned

Olezarsen, formerly known as IONIS-APOCIII-L_Rx and AKCEA-APOCIII-L_Rx, is an RNA-targeted investigational LIgand-Conjugated Antisense (LICA) medicine being evaluated for people at risk of disease due to elevated triglyceride levels, including those with severe hypertriglyceridemia (sHTG). Olezarsen is designed to inhibit the body’s production of apoC-III, a protein produced in the liver that regulates triglyceride metabolism in the blood.

About Severe Hypertriglyceridemia (sHTG)

sHTG is a condition in which a person’s triglyceride levels are dangerously high. Although a healthy triglyceride level for adults is typically below 150 mg/dL, people living with sHTG often have levels greater than 500 mg/dL. Triglycerides are a type of fat that the body uses as an important source of energy. However, this condition leads to the build-up of large triglyceride-containing particles called chylomicrons in the blood, which can result in severe health complications, including cardiovascular disease and potentially fatal acute pancreatitis (AP). It is estimated there are greater than three million people living with sHTG in the U.S.

Safety and efficacy have not been evaluated by any regulatory authorities for the indication described.

Pelacarsen

(Apo(a))

Cardiovascular Disease

Novartis

Pelacarsen, also known as IONIS-APO(a)-L_Rx , AKCEA-APO(a)-L_Rx, and TQJ230, is an investigational LIgand-Conjugated Antisense (LICA) medicine designed to inhibit the production of apolipoprotein(a), or apo(a), in the liver to offer a direct approach for reducing Lp(a). Elevated Lp(a) is recognized as an independent, genetic cause of cardiovascular disease (CVD).

About Lipoprotein(a) (Lp(a))

Lp(a) levels are determined at birth and lifestyle modification, including diet and exercise, do not impact Lp(a) levels. Inhibiting the production of apo(a) in the liver reduces the level of Lp(a) in blood, potentially slowing down or reversing CVD in people with hyperlipoproteinemia(a), a condition in which individuals have levels of Lp(a) greater than 50 mg/dL, the recognized threshold for risk of CVD. We believe antisense technology is well suited to address hyperlipoproteinemia(a) because it specifically targets the RNA that codes for all forms of the Apo(a) molecule. It is estimated that there are more than eight million people living with CVD and elevated levels of Lp(a).

Safety and efficacy have not been evaluated by any regulatory authorities for the indication described.

Fesomersen

(Factor XI)

Thrombotic Disorders

Ionis-Owned

Fesomersen, formerly known as IONIS-FXI-L_Rx, is an investigational LIgand-Conjugated Antisense (LICA) medicine designed to inhibit the production of Factor XI. Factor XI is a clotting factor produced in the liver that is important in the growth of blood clots.

About Thrombotic Disorders

Thrombosis, characterized by the formation of a blood clot inside blood vessels, can cause heart attacks and strokes. People who are deficient in Factor XI have a lower incidence of thromboembolic events with minimal increase in bleeding risk. Although currently available anticoagulants reduce the risk of thrombosis, physicians associate these anticoagulants with increased bleeding, which can be fatal. By inhibiting Factor XI production, fesomersen has the potential to be used for the treatment of a number of non-acute forms of thrombotic disorders where additional safe and well tolerated anti-thrombotic medicines are needed.

Safety and efficacy have not been evaluated by any regulatory authorities for the indication described.

ION904

(Angiotensinogen)

Treatment-Resistant Hypertension

Ionis-Owned

ION904 is an investigational next-generation LIgand-Conjugated Antisense (LICA) medicine designed to inhibit the production of angiotensinogen to decrease blood pressure in people with uncontrolled hypertension.

About Treatment-Resistant Hypertension

Treatment-resistant hypertension (TRH) is defined as failure to achieve a blood pressure goal of 140/90 (systolic/diastolic) despite the use of three or more antihypertensive medications. People with TRH have been found to have a three-fold higher chance of having fatal and non-fatal cardiovascular events relative to those with controlled hypertension.

Safety and efficacy have not been evaluated by any regulatory authorities for the indication described.

Specialty Rare

Donidalorsen

(PKK)

Hereditary Angioedema

Ionis-Owned

Donidalorsen, formerly known as IONIS-PKK-L_Rx, is an investigational LIgand-Conjugated Antisense (LICA) medicine designed to inhibit the production of prekallikrein (PKK). PKK plays an important role in the activation of inflammatory mediators associated with acute attacks of hereditary angioedema (HAE). By inhibiting the production of PKK, donidalorsen could be an effective prophylactic approach to preventing HAE attacks.

About Hereditary Angioedema (HAE)

HAE is a rare and life-threatening genetic disease characterized by unpredictable and frequently severe swelling of the skin, gastrointestinal (GI) tract, upper respiratory system, face, and throat. It is estimated that there are more than 20,000 patients with HAE in the U.S. and Europe.

Safety and efficacy have not been evaluated by any regulatory authorities for the indication described.

Sapablursen

(TMPRSS6 )

Polycythemia Vera

Ionis-Owned

Sapablursen, formerly known as IONIS-TMPRSS6-L_Rx, is an investigational LIgand-Conjugated Antisense (LICA) medicine designed to target the TMPRSS6 gene to modulate the production of hepcidin, which is the key regulator of iron homeostasis. By modulating hepcidin expression, sapablursen has the potential to positively impact blood diseases, such as polycythemia vera (PV).

About Polycythemia Vera (PV)

PV is a rare, clonal and potentially fatal disease characterized by overproduction of red blood cells. This overproduction leads to a thickening of the blood, which increases patients’ risk of life-threatening blood clots, including in the lungs, heart and brain. Patients with PV also experience severe iron deficiency and commonly have symptoms of fatigue.

Safety and efficacy have not been evaluated by any regulatory authorities for the indication described.

Other Medicines

Bepirovirsen

(Hepatitis B Virus)

Hepatitis B Virus Infection

GSK

Bepirovirsen, formerly known as IONIS-HBV_Rx and GSK3228836, is an investigational antisense medicine designed to inhibit the production of DNA and viral proteins associated with hepatitis B virus (HBV). These include proteins associated with infection and replication, including the hepatitis B surface antigen (HBsAg), which is present in both acute and chronic infections and is associated with a poor prognosis in people with chronic HBV infection.

About Hepatitis B Virus Infection (HBV)

Hepatitis infection is a serious health problem that can lead to significant and potentially fatal health conditions, including cirrhosis, liver failure and liver cancer. Chronic HBV infection is one of the most common persistent viral infections in the world, affecting nearly 300 million people and resulting in approximately 900,000 deaths annually. Currently available therapies, although effective in reducing circulating HBV in the blood, do not effectively inhibit HBV antigen production and secretion, which are associated with poor prognosis and increased risk of liver cancer.

Safety and efficacy have not been evaluated by any regulatory authorities for the indication described.

IONIS-FB-L_Rx

(Complement Factor B)

IgA Nephropathy

Roche

IONIS-FB-L_Rx, also known as RG6299, is an investigational LIgand-Conjugated Antisense (LICA) medicine designed to inhibit the production of complement factor B (FB), and the alternative complement pathway.

About IgA Nephropathy (IgAN)

Genetic association studies have shown that overaction of the alternative complement pathway has been associated with the development of several complement-mediated diseases, including immunoglobulin A, or IgAN.

IgAN is one of the most common causes of inflammation that impairs the filtering ability of kidneys and is an important cause of chronic kidney disease and kidney failure. Also known as Berger’s disease, IgAN is characterized by deposits of IgA-containing immune complexes in the kidneys, resulting in inflammation and tissue damage.

Safety and efficacy have not been evaluated by any regulatory authorities for the indication described.

IONIS-FB-L_Rx

(Complement Factor B)

Geographic Atrophy / Age-Related Macular Degeneration

Roche

IONIS-FB-L_Rx, also known as RG6299, is an investigational LIgand-Conjugated Antisense (LICA) medicine designed to inhibit the production of complement factor B (FB) and the alternative complement pathway. Genetic association studies have shown that overaction of the alternative complement pathway has been associated with the development of several complement-mediated diseases, including geographic atrophy (GA), secondary to age-related macular degeneration (AMD).

About Geographic Atrophy (GA) and Age-Related Macular Degeneration (AMD)

GA associated with AMD is a progressive disease of the macula (a small part of the retina in the eye) and is the leading cause of central vision impairment in people over the age of 50 years in developed countries. The disease is characterized by progressive loss of central vision, the distortion of images and straight lines, and the presence of blurry and dark areas in the central vision.

Safety and efficacy have not been evaluated by any regulatory authorities for the indication described.

ION224

(DGAT2)

Metabolic Dysfunction-Associated Steatohepatitis

Ionis-Owned

ION224 is an investigational LIgand-Conjugated Antisense (LICA) medicine designed to reduce the production of diacylglycerol acyltransferase 2 (DGAT2) to treat patients with metabolic dysfunction-associated steatohepatitis (MASH), previously referred to as nonalcoholic steatohepatitis (NASH). DGAT2 is an enzyme that catalyzes the final step in triglyceride synthesis in the liver. Reducing the production of DGAT2 should therefore decrease triglyceride synthesis in the liver. The Phase 2 trial demonstrated clinical evidence that the reduction of hepatic fat after DGAT2 inhibition correlates with MASH histological endpoints.

About Metabolic Dysfunction-Associated Steatohepatitis (MASH)

MASH is the more severe form of metabolic dysfunction-associated steatotic liver disease (MASLD). It is related to the epidemic of obesity, pre-diabetes and diabetes. Unlike liver disease caused by alcohol consumption, MASH is the result of an accumulation of fat in the liver, which can lead to inflammation, cirrhosis and liver-related death.

Safety and efficacy have not been evaluated by any regulatory authorities for the indication described.

ION839

(PNPLA3)

Metabolic Dysfunction-Associated Steatohepatitis

AstraZeneca

ION839 (formerly IONIS-AZ6-2.5-L_Rx), also known as AZD2693, is an investigational LIgand-Conjugated Antisense (LICA) medicine designed to inhibit the production of patatin-like phospholipase domain-containing 3 (PNPLA3) protein. PNPLA3 is a protein that is found on the surface of intracellular lipid droplets. Studies have shown that a common genetic mutation of PNPLA3 is strongly associated with an increased risk for metabolic dysfunction-associated steatohepatitis (MASH), previously known as non-alcoholic steatohepatitis (NASH), an accumulation of fat in the liver that causes liver damage. The mutant PNPLA3 protein is resistant to degradation, causing it to accumulate on the surface of lipid droplets, which disrupts the normal process for degrading lipid droplets, leading to increased liver fat accumulation, the underlying pathology of MASH. In a mouse model of MASH that results from the expression of mutant PNPLA3, intervention with an antisense drug targeting PNPLA3 reduced hepatic mutant protein expression. This inhibition of mutant protein expression reduced liver fat accumulation, inflammation, and fibrosis, all hallmarks of MASH pathology in the mutant mouse model.

About Metabolic Dysfunction-Associated Steatohepatitis (MASH)

Safety and efficacy have not been evaluated by any regulatory authorities for the indication described.

ION455

(HSD17B13)

Metabolic Dysfunction-Associated Steatohepatitis

Ionis-Owned

ION455, also known as AZD7503, is an investigational LIgand-Conjugated Antisense (LICA) medicine designed to inhibit the production of hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) protein as a potential treatment for non-alcoholic steatohepatitis.

About Metabolic Dysfunction-Associated Steatohepatitis (MASH)

Safety and efficacy have not been evaluated by any regulatory authorities for the indication described.

ION532

(APOL1)

Chronic Kidney Disease

AstraZeneca

ION532 (formerly IONIS-AZ5-2.5_Rx), also known as AZD2373, is an investigational medicine designed to reduce the production of apolipoprotein L1 (APOL1) for the treatment of APOL1-associated CKD. Genetic studies have shown that two risk alleles (termed G1 and G2) are highly associated with nondiabetic CKD and increased rate of progression towards kidney failure, providing an exciting opportunity for personalized medicine in CKD. These two variants are more frequently found in individuals of West-African ancestry. Reduction of APOL1 with ION532 in a preclinical mouse model of APOL1-related kidney disease demonstrated significantly reduced proteinuria, a hallmark of CKD. ION532 is being developed for the treatment of APOL1-associated nephropathies.

About Chronic Kidney Disease (CKD)

CKD is a worldwide public health problem, affecting about 10% of the population. Within United States, over 37 million adults have CKD and millions of others are at increased risk. CKD may be caused by diabetes, high blood pressure and other disorders. Without treatment, CKD may progress and eventually lead to kidney failure, which requires dialysis or a kidney transplant to maintain life.

Safety and efficacy have not been evaluated by any regulatory authorities for the indication described.

Ionis pipeline information updated as of May 07, 2024