ABX-464 is being developed by Abivax, in collaboration with the Cuban Center for Genetic Engineering and Biotechnology (CIGB), for the treatment of HIV. ABX-464, has demonstrated the potential to address indications in two disease areas: treatment of inflammation in ulcerative colitis and reduction of the viral reservoir in HIV. ABX-464 is an oral, first-in-class, small molecule that has demonstrated safety and profound anti-inflammatory activity in preclinical trials and in a completed Phase 2a proof-of-concept study to treat lesions in ulcerative colitis. It also inhibited HIV replication through an entirely new mechanism of action, and has completed three Phase 2a clinical trials. ABX-464 inhibits HIV-1 replication in stimulated peripheral blood mononuclear cells (PBMCs) with an IC50 ranging between 0.1 uM and 0.5 uM. In two Phase 2a clinical trials, ABX464-004 and ABX464-005, ABX-464 demonstrated up to 50% reduction of HIV-DNA in peripheral blood mononuclear cells after 28 days of combination treatment with anti-retroviral therapy. This unique mode of action and the preclinical data to-date suggest that ABX-464 has the potential to: Reduce or eliminate the viral reservoirs in patients with HIV Induce long term control of the viral load, Prevent the emergence of HIV mutants that are resistant to treatment after six months of treatment in vitro Be less frequently administered. When evaluated in a Phase 2a Proof-of-Concept study, ABX464-101, ABX-464 demonstrated both safety and statistically significant efficacy based on both clinical and endoscopic endpoints with 35% of the patients achieving a clinical remission (placebo: 11%) and 50% of patients achieving mucosal healing (placebo: 11%), (p=0.034) Because of its ability to greatly upregulate production of a unique RNA splicing product and anti-inflammatory agent, miR-124, ABX-464’s mechanism of action is unique and has shown promise in clinical trials in its ability to bring patients to remission and heal inflammatory lesions in ulcerative colitis.

DS-3032 (Milademetan) is an orally available, potent and selective inhibitor of the p53-MDM2 (murine double minute 2) interaction. Milademetan binds to, and prevents the binding of MDM2 protein to the transcriptional activation domain of the tumor suppressor protein p53. Milademetan is 10-fold more potent than the first-generation inhibitor nutlin-3a. By preventing this MDM2-p53 interaction, the proteasome-mediated enzymatic degradation of p53 is inhibited and the transcriptional activity of p53 is restored. This results in the restoration of p53 signaling and leads to the p53-mediated induction of tumor cell apoptosis. DS-3032 is currently being evaluated in three phase 1 clinical trials for solid and hematological malignancies, including acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic myeloid leukemia (CML) in blast phase, lymphoma and myelodysplastic syndrome (MDS).

RAD140 is a potent, orally bioavailable, nonsteroidal selective androgen receptor modulator (SARM). It was developed to overcome increased risks of prostate cancer, dysfunction and disease in androgen-responsive tissues, including brain, caused by testosterone therapy in men experiencing decline in testosterone levels during normal aging. It was characterized in several rat and monkey models of anabolic androgen action and demonstrated neuroprotective actions relevant to cachexia, Alzheimer's disease and related neurodegenerative diseases. In experiments with gonadectomized, adult male rats, RAD140 was shown to exhibit peripheral tissue-specific androgen action that largely spared prostate, neural efficacy as demonstrated by activation of androgenic gene regulation effects, and neuroprotection of hippocampal neurons against cell death caused by systemic administration of the excitotoxin kainate. In cultured hippocampal neurons, RAD140 was as effective as testosterone in reducing cell death induced by apoptotic insults. RAD140 neuroprotection was dependent upon MAPK signaling, as evidenced by elevation of ERK phosphorylation and inhibition of protection by the MAPK kinase inhibitor U0126.