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AKCEA-TTR-L

Generation 2+ LICA antisense drug

AKCEA-TTR-LRx is is a Generation 2+ ligand-conjugated antisense (LICA) drug designed to reduce the production of transthyretin, or TTR protein, to treat all types of TTR amyloidosis (ATTR), a systemic, progressive and fatal disease. In patients with ATTR. Both the mutant and wild type (wt) TTR protein builds up as fibrils in tissues, such as the peripheral nerves, heart, gastrointestinal system, eyes, kidneys, central nervous system, thyroid and bone marrow. The presence of TTR fibrils interferes with the normal functions of these tissues. As the TTR protein fibrils enlarge, more tissue damage occurs and the disease worsens, resulting in poor quality of life and eventually death.

About TTR Amyloidosis (ATTR)

ATTR amyloidosis is a systemic, progressive and fatal disease in which patients experience multiple overlapping clinical manifestations caused by the inappropriate formation and aggregation of TTR amyloid deposits in various tissues and organs, including peripheral nerves, heart, intestinal tract, eyes, kidneys, central nervous system, thyroid and bone marrow. The progressive accumulation of TTR amyloid deposits in these tissues and organs leads to organ failure and eventually death.

Polyneuropathy due to hATTR is caused by the accumulation of misfolded mutated TTR protein in the peripheral nerves. Patients with polyneuropathy due to hATTR experience ongoing debilitating nerve damage throughout their body resulting in the progressive loss of motor functions, such as walking. These patients also accumulate TTR in other major organs, which progressively compromise their function and eventually leading to death within five to fifteen years of disease onset. There are an estimated 10,000 patients with polyneuropathy due to hATTR worldwide.

ATTR cardiomyopathy 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 3 to 5 years from disease onset. ATTR cardiomyopathy includes both the genetic and wild-type form of the disease. There are an estimated 240,000 patients with ATTR cardiomyopathy worldwide.

Often patients with the polyneuropathy form of TTR amyloidosis will also have TTR build up in the heart and also experience cardiomyopathy symptoms. Similarly, patients with the cardiomyopathy form of TTR amyloidosis may often have TTR build up in their peripheral nerves and can experience nerve damage and progressive difficulty with motor functions.

AKCEA-APO(a)-L

Generation 2+ LICA antisense drug

AKCEA-APO(a)-LRx, also known as TQJ230, is a Generation 2+ LICA antisense drug designed to reduce apolipoprotein(a) in the liver to offer a direct approach for reducing lipoprotein(a), or Lp(a), a very atherogenic and thrombogenic form of LDL. Elevated Lp(a) is recognized as an independent, genetic cause of coronary artery disease, heart attack, stroke and peripheral arterial disease. Currently, there is no effective drug therapy to specifically and robustly lower elevated levels of Lp(a). Lp(a) levels are determined at birth and, therefore, lifestyle modification, including diet and exercise, do not impact Lp(a) levels. Even patients who can control their LDL-C remain at high-risk of cardiovascular events if they have high levels of Lp(a).

AKCEA-APO(a)-LRx is being developed for patients who are at significant risk of CVD because of their elevated Lp(a). We believe AKCEA-APO(a)-LRx is the first and currently only drug in clinical development designed to selectively and robustly inhibit the production of Lp(a).

About Lp(a)

Lp(a) is a lipoprotein particle assembled in the liver that consists of an LDL-C-like particle and apolipoprotein(a). Lp(a) is considered a key driver for cardiovascular disease due to its association with an increased risk of coronary heart disease. There is evidence that elevated Lp(a) levels may contribute directly to heart attacks. Lp(a) levels in blood can vary greatly between individuals primarily due to genetic variations. Because elevated Lp(a) is a genetically determined condition that is not responsive to lifestyle changes, patients are unable to adequately control their Lp(a) levels through improved diet or increased physical activity. Moreover, current therapies are not able to reduce Lp(a) to recommended levels in patients who have high Lp(a). Although Lp(a) can be measured by a routine lipid blood panel, the lack of drugs to effectively lower Lp(a) has made treating patients with Lp(a)-driven cardiovascular disease difficult.

AKCEA-TTR-L

Generation 2+ LICA antisense drug

AKCEA-TTR-LRx is is a Generation 2+ ligand-conjugated antisense (LICA) drug designed to reduce the production of transthyretin, or TTR protein, to treat all types of TTR amyloidosis (ATTR), a systemic, progressive and fatal disease. In patients with ATTR. Both the mutant and wild type (wt) TTR protein builds up as fibrils in tissues, such as the peripheral nerves, heart, gastrointestinal system, eyes, kidneys, central nervous system, thyroid and bone marrow. The presence of TTR fibrils interferes with the normal functions of these tissues. As the TTR protein fibrils enlarge, more tissue damage occurs and the disease worsens, resulting in poor quality of life and eventually death.

About TTR Amyloidosis (ATTR)

ATTR amyloidosis is a systemic, progressive and fatal disease in which patients experience multiple overlapping clinical manifestations caused by the inappropriate formation and aggregation of TTR amyloid deposits in various tissues and organs, including peripheral nerves, heart, intestinal tract, eyes, kidneys, central nervous system, thyroid and bone marrow. The progressive accumulation of TTR amyloid deposits in these tissues and organs leads to organ failure and eventually death.

Polyneuropathy due to hATTR is caused by the accumulation of misfolded mutated TTR protein in the peripheral nerves. Patients with polyneuropathy due to hATTR experience ongoing debilitating nerve damage throughout their body resulting in the progressive loss of motor functions, such as walking. These patients also accumulate TTR in other major organs, which progressively compromise their function and eventually leading to death within five to fifteen years of disease onset. There are an estimated 10,000 patients with polyneuropathy due to hATTR worldwide.

ATTR cardiomyopathy 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 3 to 5 years from disease onset. ATTR cardiomyopathy includes both the genetic and wild-type form of the disease. There are an estimated 240,000 patients with ATTR cardiomyopathy worldwide.

Often patients with the polyneuropathy form of TTR amyloidosis will also have TTR build up in the heart and also experience cardiomyopathy symptoms. Similarly, patients with the cardiomyopathy form of TTR amyloidosis may often have TTR build up in their peripheral nerves and can experience nerve damage and progressive difficulty with motor functions.

Tofersen

Generation 2+ antisense drug

Tofersen (formerly IONIS-SOD1Rx), also known as BIIB067, is an antisense drug designed to reduce the production of superoxide dismutase 1 (SOD1), which is the best understood genetic cause of familial amyotrophic lateral sclerosis (ALS). ALS is a rare, fatal neurodegenerative disorder. Patients with ALS suffer progressive degeneration of the motor neurons, which results in a declining quality of life and ultimately death. A mutation in the SOD-1 gene results in an inherited form of ALS, referred to as SOD1-ALS. There is substantial evidence that mutations in the SOD1 gene are responsible for a toxic gain of function that can lead to rapid progressive loss of motor neurons in patients with SOD1-ALS. As a result, patients with SOD1-ALS experience muscle weakness, loss of movement, difficulty in breathing and swallowing and eventually succumb to their disease. Currently, treatment options for patients with ALS are extremely limited with no drugs currently available that significantly slow disease progression.

About Amyotrophic Lateral Sclerosis

ALS is a rare, fatal neurodegenerative disorder. Patients with ALS suffer progressive degeneration of the motor neurons, which results in a declining quality of life and ultimately death. There is substantial evidence that mutations in the SOD1 gene are responsible for a toxic gain of function that can lead to progressive loss of motor neurons in patients with SOD1-ALS. As a result, patients with SOD1-ALS experience muscle weakness, loss of movement, difficulty in breathing and swallowing and eventually succumb to their disease. SOD1-ALS is the second most common familial form of ALS, accounting for up to 20 percent of familial ALS. Familial ALS represents approximately 15 to 20 percent of all cases of ALS. Currently, treatment options for patients with ALS are extremely limited with no drugs that significantly slow disease progression.

Tominersen

Generation 2+ antisense drug

Tominersen, formerly known as IONIS-HTTRx, and RG6042, is an antisense drug designed to reduce the production of the huntingtin (HTT) protein, which is the genetic cause of Huntington’s disease (HD). HD is caused by expansion of the CAG trinucleotide sequence in the HTT gene, which produces a toxic protein that progressively destroys neurons in the brain. As a result, HD patients experience progressive loss of mental faculties and physical control as their disease progresses.

The European Medicines Agency has granted orphan drug designation to tominersen for the treatment of patients with HD.

About Huntington’s Disease

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 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 only mask the patient’s symptoms but do not slow down the underlying loss of neurons.