While retroviral therapy now sees patients survive into their seventies, latent residual infection still condemns the HIV-infected to life time therapy, chronic health problems and shortened lives. Compelling preclinical data now supported by two Phase II human trials indicate that Abivax's ABX464 could be the first drug to drain the latent HIV reservoir. With its novel mode of action ("MoA"), the drug may not only act to reduce or even eradicate residual infection untouched by existing antiretrovirals, but also provide relief from the inflammation that blights the lives of patients with HIV as well as other major unrelated diseases such as inflammatory bowel disease ("IBD"). ABX464 has potential as an HIV curative therapy or as adjunct to existing treatments. Risk adjusted modelling suggests fair values for curative and adjunctive scenarios of €28.5 and €16.3 / share, rising to €48 and €27 respectively should on-going clinical trials in HIV and IBD yield positive results during 2018.
Latent infection resides throughout the body of HIV patients untouched by current anti-viral therapy ("ART"). Awaiting confirmation in the key intestinal reservoir, Phase II trials based on preclinical data already indicate that ABX464 may be capable of eliciting a reduction in the HIV infected cells that constitute these reservoirs in the blood; opening the door to the long term reduction in residual infection and even an effective cure.
HIV infection promotes an inflammatory response that may underpin the long term morbidity evident in many patients treated with ART. Established preclinical models indicate ABX464 has an anti-inflammatory effect on the gut; a key HIV reservoir.
Although 'curing' HIV by eradicating residual infection would be the holy grail, ABX464's action on inflammation and viral production could also provide a valuable adjunct to existing therapies.
ABX464 protects an endogenous host mechanism normally hijacked by the virus to drive its own production as well as potentially 'viruspromoting' inflammation. This same host mechanism is implicated in unrelated non-viral inflammatory responses. The use of ABX464 is already being explored in the chronic inflammatory disease IBD.
Phase II studies are on-going or in preparation to confirm the longer term impact of ABX464 on the key HIV intestinal reservoirs and inflammatory markers, as well as its potential application in IBD. These are due to report during 2018.
