Pipeline

Drawing upon our extensive experience in developing therapeutics for chronic liver diseases and viral infections, we are building a pipeline of potentially best-in-class drug candidates.  These drug candidates target multiple clinically validated mechanisms of action and are designed to achieve high rates of functional cure for CHB and become transformative treatment options for COVID-19 and NASH.

Aligos Development Pipeline

Chronic Hepatitis B

CHB is the most common viral infection in the world and an area of substantial unmet medical need.¹ There were over 290 million chronic carriers worldwide as of July 2020 and approximately 30 million individuals become newly infected every year despite the availability of a prophylactic vaccine. In 2015, there were more than 90 million cases of CHB in China alone, while the EU, United States and Japan accounted for nearly 8 million cases. Complications from CHB include cirrhosis, end-stage liver disease, and hepatocellular carcinoma, which collectively resulted in approximately 900,000 deaths in 2015, according to the World Health Organization. CHB is the primary cause of liver cancer worldwide, and the mortality associated with HBV-related liver cancer continues to increase.

We are developing a portfolio of wholly owned drug candidates targeting four distinct mechanisms of action: STOPS™, ASO, siRNA and CAM, each of which has been clinically validated in CHB patients. These drug candidates are designed to reduce S-antigen (HBsAg) and/or HBV DNA/RNA, which may lead to higher rates of functional cure in a significant percentage of CHB patients, relative to existing standard of care treatment options.

Chronic Hepatitis B

CHB is the most common viral infection in the world and an area of substantial unmet medical need.¹ There were over 290 million chronic carriers worldwide as of July 2020 and approximately 30 million individuals become newly infected every year despite the availability of a prophylactic vaccine. In 2015, there were more than 90 million cases of CHB in China alone, while the EU, United States and Japan accounted for nearly 8 million cases. Complications from CHB include cirrhosis, end-stage liver disease, and hepatocellular carcinoma, which collectively resulted in approximately 900,000 deaths in 2015, according to the World Health Organization. CHB is the primary cause of liver cancer worldwide, and the mortality associated with HBV-related liver cancer continues to increase.

We are developing a portfolio of wholly owned drug candidates targeting four distinct mechanisms of action: STOPS™, ASO, siRNA and CAM, each of which has been clinically validated in CHB patients. These drug candidates are designed to reduce S-antigen (HBsAg) and/or HBV DNA/RNA, which may lead to higher rates of functional cure in a significant percentage of CHB patients, relative to existing standard of care treatment options.

Chronic Hepatitis B

CHB is the most common viral infection in the world and an area of substantial unmet medical need.¹ There were over 290 million chronic carriers worldwide as of July 2020 and approximately 30 million individuals become newly infected every year despite the availability of a prophylactic vaccine. In 2015, there were more than 90 million cases of CHB in China alone, while the EU, United States and Japan accounted for nearly 8 million cases. Complications from CHB include cirrhosis, end-stage liver disease, and hepatocellular carcinoma, which collectively resulted in approximately 900,000 deaths in 2015, according to the World Health Organization. CHB is the primary cause of liver cancer worldwide, and the mortality associated with HBV-related liver cancer continues to increase.

We are developing a portfolio of wholly owned drug candidates targeting four distinct mechanisms of action: STOPS™, ASO, siRNA and CAM, each of which has been clinically validated in CHB patients. These drug candidates are designed to reduce S-antigen (HBsAg) and/or HBV DNA/RNA, which may lead to higher rates of functional cure in a significant percentage of CHB patients, relative to existing standard of care treatment options.

Chronic Hepatitis B

CHB is the most common viral infection in the world and an area of substantial unmet medical need.¹ There were over 290 million chronic carriers worldwide as of July 2020 and approximately 30 million individuals become newly infected every year despite the availability of a prophylactic vaccine. In 2015, there were more than 90 million cases of CHB in China alone, while the EU, United States and Japan accounted for nearly 8 million cases. Complications from CHB include cirrhosis, end-stage liver disease, and hepatocellular carcinoma, which collectively resulted in approximately 900,000 deaths in 2015, according to the World Health Organization. CHB is the primary cause of liver cancer worldwide, and the mortality associated with HBV-related liver cancer continues to increase.

We are developing a portfolio of wholly owned drug candidates targeting four distinct mechanisms of action: STOPS™, ASO, siRNA and CAM, each of which has been clinically validated in CHB patients. These drug candidates are designed to reduce S-antigen (HBsAg) and/or HBV DNA/RNA, which may lead to higher rates of functional cure in a significant percentage of CHB patients, relative to existing standard of care treatment options.

STOPS™ (S-antigen Transport-inhibiting Oligonucleotide Polymers)

Suppressing HBsAg: S-antigen (HBsAg) is believed to suppress the host’s immune system and likely prevents viral clearance in a large proportion of CHB patients.⁵ ⁶ Using our novel oligonucleotide technologies, Aligos has developed STOPS molecules.⁷ These are closely related, but have demonstrated substantially improved preclinical properties when compared, to nucleic acid polymers (NAPs). NAPs have demonstrated unprecedented HBsAg reductions and functional cure rates in a phase 2 clinical trial.⁸ Our lead STOPS candidate, ALG-010133, commenced clinical evaluation in a phase 1 study that started in August 2020.

NASH

One of the effects of improper diet and insufficient exercise is the accumulation of fatty deposits in the liver, referred to as nonalcoholic fatty liver disease (“NAFLD”), which was estimated to occur in approximately 25% of the worldwide population as of 2015. At that time, an estimated 1.5% to 6.5% of the global population was estimated to have an ongoing inflammatory response to these excess fat deposits, which is referred to as nonalcoholic steatohepatitis (NASH).¹¹ In the United States alone, the prevalence of NASH is projected to increase from approximately 16.5 million in 2015 to 27.0 million in 2030.¹²

In the absence of changes in diet and exercise, the inflammation inherent in NASH persists and may result in progressive fibrosis of the liver, which may result in cirrhosis. These fibrotic changes are associated with numerous morbidities including recurrent hospitalization for complications of cirrhosis, hepatocellular carcinoma, need for liver transplant, and death.

The only widely accepted treatment for NASH is weight loss through behavioral modifications such as diet and exercise, which is difficult to achieve at the broad population level. As there are currently no approved drugs to treat NASH, many development programs are underway to identify drugs to address this epidemic. One of the promising MOAs in the NASH space appears to be drugs which preferentially target the beta subtype of the THR receptor (THR-β).

Coronavirus

SARS-CoV-2, the coronavirus responsible for the ongoing COVID-19 pandemic, has caused widespread morbidity and mortality throughout the world. We have initiated multiple discovery programs to identify purpose-built drug candidates with pan-coronavirus activity, including against SAR-CoV-2. Protease inhibitors have proved highly effective in the treatment of other viral infections such as HIV and HCV and we have initiated a collaboration with Prof. Johan Neyts and CD3 at the Rega Institute to develop a protease inhibitor. We have also initiated efforts to identify oligonucleotide drug candidates.

CAMs (Capsid Assembly Modulators)

Suppressing HBV replication: CAMs are small molecules that interfere with HBV capsid (dis)assembly and viral replication. In clinical trials, CAMs have demonstrated significant reductions in HBV DNA and RNA in patients with CHB.² ³ We have optimized a proprietary class II CAM series (those that result in the formation of non-infectious empty viral particles) that demonstrate substantially higher potency in preclinical studies compared to other CAM molecules currently in clinical development.⁴ Our lead molecule ALG-000184 will enter the clinic in the second half of 2020.

ASOs (Antisense Oligonucleotides)

Suppressing HBsAg: ASOs are a selective means of inhibiting HBV messenger RNA (mRNA) transcripts that encode HBsAg. ASOs have been shown to reduce HBsAg levels rapidly and substantially.⁹ We have selected ALG-020572, a potentially best-in-class ASO for advancement into clinical development.

siRNA (Small Interfering Ribonucleic Acids)

Suppressing HBsAg: siRNAs are a selective means of inhibiting HBV mRNA transcripts that encode HBsAg. siRNAs in clinical development have been shown to substantially reduce HBsAg levels.¹⁰ We have selected ALG-125097, a potentially best-in-class siRNA for advancement into clinical development.

THR-β (Thyroid Hormone Receptor Beta) Agonists

Several THR-β agonists are currently in the clinic and have demonstrated favorable effects on plasma lipid levels, liver fat burden, as well as liver histology in NASH patients.¹³ ¹⁴ Our lead THR-β agonist,
ALG-055009, appears to have best-in-class properties compared to other compounds currently in the clinic.¹⁵

Aligos Development Pipeline

Chronic Hepatitis B

CHB is the most common viral infection in the world and an area of substantial unmet medical need.1 There were over 290 million chronic carriers worldwide as of July 2020 and approximately 30 million individuals become newly infected every year despite the availability of a prophylactic vaccine. In 2015, there were more than 90 million cases of CHB in China alone, while the EU, United States and Japan accounted for nearly 8 million cases. Complications from CHB include cirrhosis, end-stage liver disease, and hepatocellular carcinoma, which collectively resulted in approximately 900,000 deaths in 2015, according to the World Health Organization. CHB is the primary cause of liver cancer worldwide, and the mortality associated with HBV-related liver cancer continues to increase.

We are developing a portfolio of wholly owned drug candidates targeting four distinct mechanisms of action: STOPS™, ASO, siRNA and CAM, each of which has been clinically validated in CHB patients. These drug candidates are designed to reduce S-antigen (HBsAg) and/or HBV DNA/RNA, which  may lead to higher rates of functional cure in a significant percentage of CHB patients, relative to existing standard of care treatment options.

CAMs (Capsid Assembly Modulators)

Suppressing HBV replication: CAMs are small molecules that interfere with HBV capsid (dis)assembly and viral replication. In clinical trials, CAMs have demonstrated significant reductions in HBV DNA and RNA in patients with CHB.2,3 We have optimized a proprietary class II CAM series (those that result in the formation of non-infectious empty viral particles) that demonstrate substantially higher potency in preclinical studies compared to other CAM molecules currently in clinical development.4 Our lead molecule ALG-000184 will enter the clinic in the second half of 2020.

STOPS™* (S-antigen Transport-inhibiting Oligonucleotide Polymers)

Suppressing HBsAg: S-antigen (HBsAg) is believed to suppress the host’s immune system and likely prevents viral clearance in a large proportion of CHB patients.5,6 Using our novel oligonucleotide technologies, Aligos has developed STOPS molecules.7 These are closely related, but have demonstrated substantially improved preclinical properties when compared, to nucleic acid polymers (NAPs). NAPs have demonstrated unprecedented HBsAg reductions and functional cure rates in a phase 2 clinical trial.8 Our lead STOPS candidate, ALG-010133, commenced clinical evaluation in a phase 1 study that started in August 2020.

ASOs (Antisense oligonucleotides)

Suppressing HBsAg: ASOs are a selective means of inhibiting HBV messenger RNA (mRNA) transcripts that encode HBsAg.  ASOs have been shown to reduce HBsAg levels rapidly and substantially.9 We have selected ALG-020572, a potentially best-in-class ASO for advancement into clinical development. 

siRNA (Small interfering ribonucleic acids)

Suppressing HBsAg: siRNAs are a selective means of inhibiting HBV mRNA transcripts that encode HBsAg. siRNAs in clinical development have been shown to substantially reduce HBsAg levels.10 We have selected ALG-125097, a potentially best-in-class siRNA for advancement into clinical development.  

NASH

One of the effects of improper diet and insufficient exercise is the accumulation of fatty deposits in the liver, referred to as nonalcoholic fatty liver disease (“NAFLD”), which was estimated to occur in approximately 25% of the worldwide population as of 2015. At that time, an estimated 1.5% to 6.5% of the global population was estimated to have an ongoing inflammatory response to these excess fat deposits, which is referred to as nonalcoholic steatohepatitis (NASH).11 In the United States alone, the prevalence of NASH is projected to increase from approximately 16.5 million in 2015 to 27.0 million in 2030.12

In the absence of changes in diet and exercise, the inflammation inherent in NASH persists and may result in progressive fibrosis of the liver, which may result in cirrhosis. These fibrotic changes are associated with numerous morbidities including recurrent hospitalization for complications of cirrhosis, hepatocellular carcinoma, need for liver transplant, and death.

The only widely accepted treatment for NASH is weight loss through behavioral modifications such as diet and exercise, which is difficult to achieve at the broad population level. As there are currently no approved drugs to treat NASH, many development programs are underway to identify drugs to address this epidemic. One of the promising MOAs in the NASH space appears to be drugs which preferentially target the beta subtype of the THR receptor (THR-β).

THR-β (Thyroid hormone receptor beta) agonists

Several THR-β agonists are currently in the clinic and have demonstrated favorable effects on plasma lipid levels, liver fat burden, as well as liver histology in NASH patients.13,14 Our lead THR-β agonist,
ALG-055009, appears to have best-in-class properties compared to other compounds currently in the clinic.15

Coronavirus

SARS-CoV-2, the coronavirus responsible for the ongoing COVID-19 pandemic, has caused widespread morbidity and mortality throughout the world.  We have initiated multiple discovery programs to identify purpose-built drug candidates with pan-coronavirus activity, including against SAR-CoV-2.  Protease inhibitors have proved highly effective in the treatment of other viral infections such as HIV and HCV and we have initiated a collaboration with Prof. Johan Neyts and CD3 at the Rega Institute to develop a protease inhibitor. We have also initiated efforts to identify oligonucleotide drug candidates. 

 

References:

1. Global Hepatitis Report (2017, World Health Organization) and www.hepb.org  2. Agarwal et. al., LBP05, EASL 2020  3. Sulkowski et al, LP1, AASLD 2019  4. Zhang et. al., Poster SAT-455, EASL 2020  5. Ortega-Prieto et al., Vaccines 2017; 5(3): 24  6. Lok et al. Hepatology, 2017; 66(4):1296-1313  7. Hong et. al, Poster 0689, AASLD 2019  8. Bazinet et al, Abstract FRI-210, EASL 2019  9. Yuen et. al., AS067, EASL 2020  10. Gane et. al., GS10, EASL 2020  11. Younossi et al., Hepatology,2016; 64(1): 73-84  12. Estes et al., Hepatology, 2018; 67(1):123-133  13. Harrison et al., Oral Abstract 14, AASLD 2018  14. Loomba et al., LBP-20, EASL 2019 15. Deval et. al., Poster 2149, AASLD 2019