Aligos CEO Discusses Progress on Developing HBV Treatments
Diseases and viruses can develop resistance to different therapies and it’s for that reason that Aligos Therapeutics is developing three different treatments for hepatitis B.
Aligos Therapeutics Chief Executive Officer Lawrence Blatt told BioSpace that the different assets in development address different components of the infection. Having combination therapies is something of a necessity with a virus like hepatitis B, he said. The importance of combination therapies was something drug developers learned when investigating treatments for HIV. Blatt said monotherapies proved largely ineffective and the virus developed immunities against the medications.
“Only when we had triple therapies did we see the responses we’re seeing today,” Blatt said.
And that’s what Blatt and the Aligos team hopes to see in HBV. The three assets are designed to work together to deliver a hoped-for best response. For HBV, Aligos is developing a capsid assembly modulator (CAM), a small molecule allosteric inhibitor, an S-antigen Transport-inhibiting oligonucleotides Polymer (STOP), which has an undetermined mechanism of action and an antisense oligonucleotides, which bind to complementary messenger RNAs (mRNAs) and trigger their degradation via the enzyme Ribonuclease H. In combination, Blatt said the assets have demonstrated “synergistic knockdown” in preclinical studies and the company is hoping that will “bode well” when the products enter the clinic in 2020. Case in point, with the CAM asset, Blatt said Aligos had demonstrated the highest potency of any CAM currently in the clinic.
Looking at the company’s future development plans in HBV, Blatt said the plan is to move the three assets into the clinic for monotherapy study in 2020 and then begin combination studies. His hope with the in-house developed therapies is to find a regimen that will “achieve a sustained functional cure in HBV.” The planned timeline is for the STOP asset to enter the clinic in the second quarter of 2020, the CAM asset to enter in the third quarter and the ASO asset by the end of the fourth quarter.
Hepatitis B is a liver infection caused by the hepatitis B virus. Signs and symptoms of hepatitis B include abdominal pain, fever, joint pain, loss of appetite, nausea, weakness and fatigue, and a yellowing of the skin. If the infection becomes chronic, meaning it lasts for longer than six months, it can lead to liver failure, liver cancer or cirrhosis of the liver. Multiple companies are working on treatments for chronic hepatitis B. Gilead Sciences, which developed drugs that delivered a functional cure for hepatitis C, is developing Vemlidy for chronic hepatitis B. Roche and Dicerna teamed up to develop an RNA interference (RNAi) treatment for chronic HBV. Earlier this year, Janssen Pharmaceuticals showed off data from an ongoing Phase I/II clinical study of JNJ-3989, an RNAi asset in HBV. Janssen’s product targets the hepatitis RNA specifically and stops it from making surface antigens. GlaxoSmithKline licensed an Ionis-developed treatment for people with chronic hepatitis B virus (CHB) infection following positive Phase II results.
In addition to hepatitis B, Aligos is also developing a therapy for nonalcoholic steatohepatitis (NASH). At the Liver Meeting in South San Francisco last month, the company presented data highlighting the preclinical performance of its thyroid hormone receptor beta (THR-β) agonist for NASH. The asset, ALG-055009, reduced cholesterol in a pronounced and sustained fashion after a single dose and demonstrated excellent bioavailability when administered orally, the company said. Like the HBV assets, Aligos is planning on taking the NASH product into the clinic soon. However, unlike the HBV assets, Blatt said the company will likely look at finding a development partner for ALG-055009. Blatt said the company is in talks with some companies, but, as could be expected, Blatt did not disclose what companies Aligos is in talks with for a partnership deal. In the NASH space, there are numerous players, particularly given the fact that there are no as-of-yet approved treatments for the disease. Gilead is working in the space. The Foster City, Calif.-based company has selonsertib, firsocostat and cilfexor in various combinations to treat NASH in several clinical trials. Other companies, such as Genentech, Curis, Viking Therapeutics, Intercept Pharma and more are also tackling the disease.
NASH is estimated to affect more than 16 million people in the U.S. alone. If untreated, NASH patients face serious consequences, including end-stage liver disease, liver cancer and the need for liver transplantation. Current treatment standards for NASH are lifestyle changes, including diet, weight loss and exercise. GlobalData speculated the NASH market will hit $18.3 billion by 2026.