Maribavir (previously known as 1263W94) is a novel benzimidazole riboside compound. This drug was in phase III of clinical trial for the prevention of cytomegalovirus (CMV) infections in transplant patients, sponsored by ViroPharma. However, drug failed to demonstrate a higher efficacy rate than the placebo. Maribavir has activity against cytomegalovirus and Epstein-Barr virus (EBV), but not against other human herpesviruses. Maribavir’s mechanism of action is unique and is complex compared to the currently approved antivirals for CMV. Maribavir inhibits the viral UL97 kinase rather than the viral DNA polymerase. The UL97 kinase is important for viral DNA elongation, DNA packaging, and nuclear egress of encapsidated viral DNA. In addition, maribavir inhibits the EBV DNA polymerase processivity factor (BMRF1), reduces the level of certain EBV glycoproteins, and inhibits viral transcription. However, future work will be designed to address the interaction of MBV and BGLF4 and to evaluate the mechanisms through which maribavir downregulates viral transcripts. BGLF4 belongs to the family of conserved herpesvirus PKs, which includes HCMV UL97, HSV UL13, and HSV US3. Maribavir does need to be phosphorylated for its activity.

Tivozanib (formerly AV-951, KRN-951) is a potent and selective VEGFR tyrosine kinase inhibitor and inhibits angiogenesis and vascular permeability in tumor tissues. It completed phase III a trial investigation for the treatment of renal cell carcinomas, but has not been still approved. In addition, this drug is in the phase II of clinical trial for the investigation it in patients with glioblastoma and colorectal carcinoma.

Tepotinib is an investigational small molecule inhibitor of the c-Met receptor tyrosine kinase. Alterations of the c-Met signaling pathway are found in various cancer types and correlate with aggressive tumor behavior and poor clinical prognosis. Tepotinib is a potent and selective c-Met inhibitor, >200-fold selective for c-Met than IRAK4, TrkA, Axl, IRAK1, and Mer. Tepotinib is currently in Phase I/II trials in liver cancer and lung cancer.

Vericiguat, discovered at Bayer, is the first soluble guanylate cyclase (sGC) stimulator. Vericiguat is currently being studied in a Phase III clinical program for the treatment of heart failure with reduced ejection fraction (HFrEF).

Samidorphan was developed as a sublingually bioavailable µ-opioid receptor antagonist. This drug participated in clinical trials for the treatment of Schizophrenia, Alcohol Dependence, and Binge Eating Disorder. The oral dose pharmacokinetics, safety, and tolerability of samidorphan were evaluated in phase II double blind, placebo-controlled, randomized studies in healthy adults. In addition, the combination of samidorphan (SAM) with buprenorphine (BUP) was studied in phase III clinical trial in patients with major depressive disorder (MDM). It was shown that the long-term treatment did not reveal any new safety findings and confirmed that the risk of abuse and dependence with BUP/SAM was low.

KD025 is an orally available, selective small molecule inhibitor of ROCK2 (Rho-associated coiled-coil kinase 2), a molecular target in multiple autoimmune, fibrotic and neurodegenerative diseases. KD025 is the only ROCK2-specific inhibitor in the clinical trials. KD025 down-regulates the IL-17 and IL-21 secretion in human PBMCs, and leads to down-regulation of STAT3 phosphorylation, IRF4, and RORγt expression in CD4+ T cells. Kadmon Pharmaceuticals initiated phase II clinical trials of KD025 for the treatment of Graft-versus-host disease; Idiopathic pulmonary fibrosis; Plaque psoriasis.

Fexinidazole is an antiparasitic drug, which is in the phase III of clinical trial for the treatment of Human African Trypanosomiasis, and in the phase II for the treatment Disease, Chagas and Visceral Leishmaniosis. However, for the Visceral Leishmaniosis, studies were terminated, due to lack of efficacy. Fexinidazole rapidly metabolized to two active metabolites, a sulfone and a sulfoxide, which prolong the pharmacological action of parent drug. These metabolites retaine trypanocidal activity but are less effective in nifurtimox-resistant lines, which can lead to the potential danger in the use of fexinidazole as a monotherapy.

Viloxazine is an antidepressant drug was used to treat patients with depression. Viloxazine inhibits noradrenaline uptake. This drug was approved in some Europe countries, but not in the USA, but then it was discontinued because of competition from other drugs. In the frame of drug repositioning, Viloxazine participated in clinical trials for the treatment of attention deficit hyperactivity disorder. Phase II of trials was successfully passed.

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.