Fluorocyclopentenylcytosine (RX-3117) is a novel small molecule nucleoside compound that is incorporated into DNA or RNA of cancer cells and inhibits both DNA and RNA synthesis which induces apoptotic cell death of tumor cells. Fluorocyclopentenylcytosine also mediates the down-regulation of DNA methyltransferase 1 (DNMT1), an enzyme responsible for the methylation of cytosine residues on newly synthesized DNA and also a target for anticancer therapies. Preclinical studies have shown Fluorocyclopentenylcytosine to be effective in both inhibiting the growth of various human cancer xenograft models, including colon, lung, renal and pancreas, as well as overcoming chemotherapeutic drug resistance. Fluorocyclopentenylcytosine has demonstrated a broad spectrum anti-tumor activity against 50 different human cancer cell lines and efficacy in 12 different mouse xenograft models. The efficacy in the mouse xenograft models was superior to that of gemcitabine. In addition, in human cancer cell lines made resistant to the anti-tumor effects of gemcitabine, Fluorocyclopentenylcytosine still retains its full anti-tumor activity. In August 2012, Rexahn reported the completion of an exploratory Phase I clinical trial of Fluorocyclopentenylcytosine in cancer patients conducted in Europe, to investigate the oral bioavailability, safety and tolerability of the compound. In this study, oral administration of Fluorocyclopentenylcytosine demonstrated an oral bioavailability of 34-58% and a plasma half-life (T1/2) of 14 hours. In addition, Fluorocyclopentenylcytosine was safe and well tolerated in all subjects throughout the dose range tested. Fluorocyclopentenylcytosine is in phase I/II clinical trials by Rexahn for the treatment of bladder cancer and pancreatic cancer. This compound was granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) for the treatment of patients with pancreatic cancer in September 2014.

F2BMET (redaporfin or LUZ11), a fluorinated sulfonamide bacteriochlorin, is photosensitizer, with antineoplastic activity upon photodynamic therapy. F2BMET is a third generation bacteriochlorin molecule which has a greater ability to absorb light and convert it into active molecular species (reactive oxygen species), better depth penetration, and improved efficacy. F2BMET has promising Phase I/IIA POC clinical data in advanced head and neck cancer which clearly reinforces the favorable results from non-clinical studies. It has received Orphan Drug Designation (ODD) from EMA in Europe for Biliary tract cancer.

N-[2-[(2-amino-2-oxoethyl)-[3-(2-oxopyrrolidin-1-yl)propyl]amino]-2-oxoethyl]-2-[2-(2-fluorophenyl)ethylamino]-N-(2-methylpropyl)acetamide (BN201) is a small peptide molecule, a first-in-class neuroprotective compound. BN201 promotes the survival of cultured neural cells when subjected to oxidative stress or when deprived of trophic factors. BN201 promotes neuronal differentiation, the differentiation of precursor cells to mature oligodendrocytes in vitro, and the myelination of new axons. BN201 modulates several kinases participating in the insulin growth factor 1 pathway including serum-glucocorticoid kinase and midkine, inducing the phosphorylation of NDRG1 and the translocation of the transcription factor Foxo3 to the cytoplasm. In vivo, BN201 prevents axonal and neuronal loss, and it promotes remyelination in models of multiple sclerosis, chemically induced demyelination, and glaucoma. Bionure, a spin-off from Hospital Clínic de Barcelona that is based in California, is developing BN201 for multiple sclerosis, acute optic neuritis (AON) and glaucoma. BN201 was granted with orphan designation status for optic neuritis by the FDA. Optic neuritis is often an early sign of multiple sclerosis. The efficacy, safety, and capacity of the drug to cross the blood-brain barrier have been demonstrated in animal models, but the drug has not yet entered clinical testing.

H3B-6527 is a highly selective covalent FGFR4 inhibitor with at least 250-fold selectivity over FGFR1-3. H3B-6527 inhibits FGFR4 signaling, proliferation, and leads to apoptosis in Hepatocellular carcinoma (HCC) cell line. Treatment on Hep3B cells leads to robust activation of caspase-3/7, an apoptotic marker, in a concentration-dependent manner, indicating FGFR4 inhibition by H3B-6527 leads to cell death in HCC cell lines. In the Hep3B human HCC xenograft mouse model, H3B-6527 shows dose-proportional plasma exposures and greater than dose-proportional tumor exposures within the dose range evaluated (30, 100, and 300 mg/kg). Oral treatment of H3B-6527, twice daily, inhibits xenograft growth in a dose-dependent manner in nude mice, with the 300 or 100 mg/kg twice daily, significantly inhibiting tumor growth in both Hep3B subcutaneous and orthotopic xenograft model and causing tumor regressions in the subcutaneous xenograft model.

Ajulemic acid, designated as Resunab™, is being developed by Corbus Pharmaceuticals, for the treatment of cystic fibrosis, systemic sclerosis, systemic lupus erythematosus.Ajulemic acid (AJA) is a first-in-class, synthetic, orally active, cannabinoid-derived drug that preferentially binds to the CB2 receptor and is nonpsychoactive. In preclinical studies, and in Phase 1 and 2 clinical trials, AJA showed a favorable safety, tolerability, and pharmacokinetic profile. It also demonstrated significant efficacy in preclinical models of inflammation and fibrosis. It suppresses tissue scarring and stimulates endogenous eicosanoids that resolve chronic inflammation and fibrosis without causing immunosuppression. AJA is currently being developed for use in 4 separate but related indications including systemic sclerosis (SSc), cystic fibrosis, dermatomyositis (DM), and systemic lupus erythematosus. Phase 2 clinical trials in the first 3 targets demonstrated that it is safe, is a potential treatment for these orphan diseases and appears to be a potent inflammation-resolving drug with a unique mechanism of action, distinct from the nonsteroidal anti-inflammatory drug (NSAID), and will be useful for treating a wide range of chronic inflammatory diseases.

Pinometostat, also known as EPZ-5676, is a small molecule inhibitor of histone methyltransferase with potential antineoplastic activity. Upon intravenous administration, EPZ-5676 specifically blocks the activity of the histone lysine-methyltransferase DOT1L, thereby inhibiting the methylation of nucleosomal histone H3 on lysine 79 (H3K79) that is bound to the mixed lineage leukemia (MLL) fusion protein which targets genes and blocks the expression of leukemogenic genes. Epizyme is developing pinometostat, a small molecule inhibitor of DOT1L, for the treatment of patients with MLL-r, a genetically defined acute leukemia. Epizyme is conducting a phase 1 clinical trial in pediatric patients. Epizyme is evaluating preclinical combinations of pinometostat with other anti-cancer agents in MLL-r leukemia. Pinometostat is being developed in collaboration with Celgene. Epizyme retains all U.S. rights to pinometostat and has granted Celgene an exclusive license to pinometostat outside of the U.S.

Acebilustat (formerly CTX-4430) is an investigational oral drug under development by Celtaxsys. It is a potent inhibitor of the enzyme leukotriene A4 hydrolase (LTA4H), which catalyzes the rate‐limiting step in the formation of leukotriene B4 (LTB4), a potent chemoattractant and activator of inflammatory immune cells including neutrophils. Acebilustat is currently being tested in Phase 2 clinical trial as a modulator of inflammation in patients with cystic fibrosis (CF). The U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have granted orphan drug status to acebilustat as a treatment for cystic fibrosis.