Science

How does ABX464 address inflammation?

ABX464’s anti-inflammatory effect is triggered by the molecule binding to its target, the cap binding complex (CBC), located on the 5' end of every cellular non-coding RNA molecule. This binding results in the splicing of a long, non-coding RNA, that induces the overexpression of a single micro-RNA product, miR-124. miR-124 initiates a cascade which is believed to propagate the anti-inflammatory effect that has been observed in preclinical models.

IBD – a chronic disease with no cure

Inflammatory bowel disease broadly describes conditions characterized by chronic inflammation of the digestive tract. The two major types of IBD are ulcerative colitis (UC) and Crohn’s disease (CD). While CD can affect any part of the gastrointestinal tract, UC only affects the colon and causes inflammation that can lead to rectal bleeding, bloody diarrhea, abdominal cramps, and severe pain. ABX464 is being studied in UC, the exact cause of which remains unknown. However, a dysregulated immune system and genetic influence are possible causes. UC can be debilitating and can lead to life-threatening complications. Although treatment for UC has improved significantly in recent years, there is still no cure, and patients often become resistant to current treatments, demonstrating a substantial unmet need. To learn more about UC and IBD, go to:

How does ABX464 reduce the HIV reservoir?

Like in inflammatory diseases, ABX464 binds to its cellular target, the Cap Binding Complex (CBC), thereby inhibiting the production of full-length viral RNA by HIV-infected cells that is required for HIV replication. A mechanism of action never explored before, binding to the CBC of the viral mRNA molecule by ABX464 enhances splicing of HIV RNA to render it untranslatable by the cell, thereby blocking HIV replication. Therefore, unlike currently available anti-retrovirals that prevent HIV infection of new cells, ABX464 targets already-infected cells, and prevents the reservoir of integrated HIV DNA from leading to the production of new viruses.

ABX464’s mechanism of action on the HIV reservoir is currently being investigated based on the following three hypotheses: (1) the spliced viral RNA generated by treatment with ABX464 results in an immune response to HIV-infected reservoir cells (2) the induction of HIV RNA splicing leads to the generation of deficient virus (3) the accumulation of spliced viral RNA in the cells leads to cell death.

HIV/AIDS remains one of the world's most significant public health challenges.

Despite effective HIV prevention tools and methods, the number of new infections among adults worldwide has not decreased significantly. Effective antiviral therapies only have the ability to transform HIV into a chronic disease, and thus patients must take medication daily for the rest of their lives. There is an urgent medical need for innovative therapies that lead to a true functional cure for HIV. To learn more about HIV/AIDS go to:

Harnessing the immune system to treat cancer

Hepatocellular carcinoma (HCC) is the most common form (75-90%) of primary liver cancer in adults. It typically occurs in the setting of chronic liver inflammation and/or cirrhosis, and is closely linked to chronic viral infection such as hepatitis B or C, exposure to toxins such as alcohol, and to certain diseases such as non-alcoholic steato-hepatitis (NASH). The incidence of, and deaths related to HCC, are increasing in the United States and globally due to hepatitis B and C virus infections, as well as NASH. Prevalence data from 2018 show a total of 79,000 cases of HCC in the U.S. and G5 Europe (Germany, France, Italy, Spain and UK), with 67,000 new cases. Globally, there were 841,000 new cases of liver cancer (ranked 6th of all reported cancers) and 782,000 fatalities (ranked 4th) in 2018. Currently, the American Cancer Society reports five-year survival rates in the U.S. of 31% for localized HCC, 11% for regional and 2% for distant or metastatic, indicating a clear unmet medical need for improved therapies for HCC. Pharmaceutical sales in HCC (U.S., G5 Europe and Japan) were USD 616 M in 2018, up 20% from 2017 (USD 513 M).

Source: GlobalData

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