Voclosporin (trans-ISA247) is a Cyclosporin A derivative and immunosuppressive compound currently being investigated for the treatment of psoriasis, lupus nephritis and for the prevention of organ rejection in kidney transplant patients. An animal study showed that a lower blood level of Voclosporin was able to produce a greater or similar inhibition of lymphocyte proliferation, expression of T-cell activation surface antigens, and T-cell cytokine production compared to Cyclosporin A. Voclosporin has been shown to be an efficacious and safe immunosuppressant in phase IIb and phase III trials in renal transplant recipients and in plaque psoriasis patients. In clinical trials, Voclosporin added to standard-of-care induction therapy for lupus nephritis increases complete renal remission (CRR) rates, but higher rates of adverse events including death were observed.

Selpercatinib (LOXO-292, ARRY-192) is a potent and specific RET (c-RET) inhibitor that was granted accelerated FDA approval on May 8, 2020, for specific RET-driven cancer indications. It is currently marketed under the brand name RETEVMO™ by Loxo Oncology Inc.

Remimazolam is an intravenous benzodiazepine sedative-hypnotic with rapid onset and offset of action. This compound undergoes organ-independent metabolism to an inactive metabolite. Like other benzodiazepines, remimazolam can be reversed with flumazenil to rapidly terminate sedation and anesthesia. Phase I and II clinical trials have shown that remimazolam is safe and effective when used for procedural sedation. Phase III clinical trials have been completed investigating efficacy and safety in patients undergoing bronchoscopy and colonoscopy. The developer of this drug has suggested that intensive care unit sedation (beyond 24 hours) could be another possible indication for further development, since it is unlikely that prolonged infusions or higher doses of remimazolam would result in accumulation and extended effect.

Amisulpride, a benzamide derivative, shows a unique therapeutic profile being atypical antipsychotic. At low doses, it enhances dopaminergic neurotransmission by preferentially blocking presynaptic dopamine D2/D3 autoreceptors. At higher doses, amisupride antagonises postsynaptic dopamine D2 and D3 receptors, preferentially in the limbic system rather than the striatum, thereby reducing dopaminergic transmission. In addition its antagonism at serotonin 5-HT7 receptors likely underlies the antidepressant actions. Amisulpride is approved for clinical use in treating schizophrenia in a number of European countries and also for treating dysthymia, a mild form of depression, in Italy.

Temsavir (BMS-626529) is an attachment inhibitor (AI) in clinical development (administered as prodrug BMS-663068) that binds to HIV-1 gp120. Temsavir displays in vitro activity against HIV-1 envelopes with C-C chemokine receptor type 5 (CCR5-), C-X-C chemokine receptor type 4 (CXCR4), and dual tropism. It also is active against almost all HIV-1 subtypes tested except for subtype CRF01-AE and possibly group O. Temsavir can inhibit both CD4-induced and CD4-independent formation of the "open state" four-stranded gp120 bridging sheet, and the subsequent formation and exposure of the chemokine co-receptor binding site. This unique mechanism of action prevents the initial interaction of HIV-1 with the host CD4+ T cell, and subsequent HIV-1 binding and entry. Temsavir is administered as a phosphonooxymethyl ester prodrug (BMS-663068), which was developed to improve the solubility and dissolution of Temsavir. Temsavir is currently being investigated clinically through the use of the prodrug BMS-663068, and a Phase III study of BMS-663068 in HIV-1-infected treatment-experienced subjects is ongoing (NCT02362503).

Capmatinib (INC280, INCB028060), is an orally bioavailable inhibitor of the proto-oncogene c-Met (hepatocyte growth factor receptor [HGFR]) with potential antineoplastic activity. Novartis acquired Incyte's capmatinib, which is in Phase II clinical trial as monotherapy in patients with advanced hepatocellular carcinoma. Capmatinib selectively binds to c-Met, thereby inhibiting c-Met phosphorylation and disrupting c-Met signal transduction pathways. This may induce cell death in tumor cells overexpressing c-Met protein or expressing constitutively activated c-Met protein. c-Met, a receptor tyrosine kinase overexpressed or mutated in many tumor cell types, plays key roles in tumor cell proliferation, survival, invasion, metastasis, and tumor angiogenesis.

Blu-285 is a potent and selective inhibitor for hematologic malignancies with KIT Exon 17 Mutations. BLU-285 has demonstrated biochemical in vitro activity on the KIT exon-17 mutant enzyme, KIT D816V. Cellular activity of BLU-285 on KIT D816 mutants was measured by autophosphorylation in the human mast cell leukemia cell line HMC1.2, and the P815 mouse mastocytoma cell line with IC50= 4 and 22 nM, respectively. In vivo BLU-285 was well tolerated and has demonstrated dose-dependent antitumor efficacy. Complete tumor growth inhibition and ≥ 75% KIT kinase inhibition was observed with 10 mg/kg once daily, oral dosing of BLU-285 in the aggressive KIT exon 17 mutant driven P815 mastocytoma model grown as a solid tumor allograft as well as in a disseminated model of the disease. BLU-285 was also well tolerated in this in vivo model and had no adverse effects on body weight at either dose.