Rigosertib sodium (ON 01910.Na) is a small molecule inhibitor of critical pathways important in the growth and survival of cancer cells, being developed by Onconova Therapeutics ("Onconova") for the treatment of hematologic malignancies and solid tumors. Rigosertib (ON-01910) is a non-ATP-competitive inhibitor of PLK1 with IC50 of 9 nM in a cell-free assay. It shows 30-fold greater selectivity against Plk2 and no activity to Plk3. Extensive Phase I and Phase II studies with rigosertib have been conducted at leading institutions in the U.S. and abroad in more than 450 patients with solid tumors and hematological cancers, including MDS and AML. MDS and AML are blood disorders widely recognized as difficult to manage, with limited therapeutic options available for patients, especially those with drug-resistant disease. The multi-site Phase III ONTIME trial in MDS patients is under a Special Protocol Assessment (SPA) from the U.S. FDA and is being supported by an award from the Therapeutics Acceleration Program (TAP) of the Leukemia and Lymphoma Society (LLS). FDA has granted Orphan Drug Designation for the use of rigosertib in MDS. The clinical program in solid tumors is also advancing with initiation of the Phase II/III combination ONTRAC trial (ON 01910.Na TRial in Patients with Advanced Pancreatic Cancer) and Phase II single agent trial in ovarian cancer. In Japan, SymBio is developing rigosertib for the treatment of refractory/relapsed HR-MDS (IV form) and first-line LR-MDS (oral form).

Galunisertib is a potent inhibitor of TGF beta type 1 receptor. The drug is under clinical development for the treatment of different cancers: pancreatic, hepatocellular, breast, rectal, prostate etc. and reached phase 2/3 in patients with myelodysplastic syndromes.

Talmapimod is a p38 MAPK kinase inhibitor that inhibits p38 alpha with IC50 value of 9 nM which is 10-times lower then IC50 for p38 beta. Talmapimod was under clinical development for the treatment of Myelodysplastic Syndromes, Multiple Myeloma and Rheumatoid Arthritis (phase II), however, it seems to be discontinued as no longer presents in Janssen's pipeline.

Cytarabine ocfosfate (commercial name: Starasid) is a prodrug having stearyl group attached to phosphoric acid at 5' position of arabinose moiety of cytosine arabinoside (Ara-C). This drug is given orally. The mode of action is in the inhibition of DNA synthesis after conversion to Ara-CTP as in Ara-C. The drug is metabolized in the liver, producing the intermediate metabolite, C-C3PCA which is converted to Ara-C gradually. This property results in the maintenance of relatively long time the blood Ara-C levels. This was proved to be active clinically against acute leukemia and MDS.

Cytarabine ocfosfate (commercial name: Starasid) is a prodrug having stearyl group attached to phosphoric acid at 5' position of arabinose moiety of cytosine arabinoside (Ara-C). This drug is given orally. The mode of action is in the inhibition of DNA synthesis after conversion to Ara-CTP as in Ara-C. The drug is metabolized in the liver, producing the intermediate metabolite, C-C3PCA which is converted to Ara-C gradually. This property results in the maintenance of relatively long time the blood Ara-C levels. This was proved to be active clinically against acute leukemia and MDS.

Cytarabine ocfosfate (commercial name: Starasid) is a prodrug having stearyl group attached to phosphoric acid at 5' position of arabinose moiety of cytosine arabinoside (Ara-C). This drug is given orally. The mode of action is in the inhibition of DNA synthesis after conversion to Ara-CTP as in Ara-C. The drug is metabolized in the liver, producing the intermediate metabolite, C-C3PCA which is converted to Ara-C gradually. This property results in the maintenance of relatively long time the blood Ara-C levels. This was proved to be active clinically against acute leukemia and MDS.

Cytarabine ocfosfate (commercial name: Starasid) is a prodrug having stearyl group attached to phosphoric acid at 5' position of arabinose moiety of cytosine arabinoside (Ara-C). This drug is given orally. The mode of action is in the inhibition of DNA synthesis after conversion to Ara-CTP as in Ara-C. The drug is metabolized in the liver, producing the intermediate metabolite, C-C3PCA which is converted to Ara-C gradually. This property results in the maintenance of relatively long time the blood Ara-C levels. This was proved to be active clinically against acute leukemia and MDS.

Angiotensin (1-7) [Ang 1-7] is a 7 amino acid peptide generated predominantly from Ang II by the action of Ang-converting enzyme 2. Ang 1-7 can act as a negative modulator of aldosterone secretion in vitro and in vivo. The endogenous heptapeptide angiotensin-(1-7) (Ang-(1-7)) is a RAS component that has a central role in the alternative axis. It is generated by the cleavage of Ang-II by the action of the angiotensin converting enzyme 2 (ACE 2) and acts via interaction with the G-protein coupled receptor Mas. Angiotensin (1-7) induces vasorelaxation through release of NO and prostaglandins, perhaps through activation of a non-AT1, non-AT2 receptor, Mas. Counteracts the vasoconstrictive and proliferative effects of angiotensin II and stimulates vasopressin (anti-diuretic hormone) release in vivo. Clinical uses range from treatment of cardiovascular-related diseases, ocular pathologies, metabolic dysfunctions, brain conditions and degenerative diseases to applications in cell differentiation and hematopoiesis, tumor therapy, acute lung injury, fibrosis, infection, among others. Tarix Orphan is developing TXA127 for rare neuromuscular and connective tissue diseases. TXA127 is a pharmaceutical formulation of the naturally occurring peptide, Angiotensin (1-7). TXA127 has been effective in animal models of Duchenne muscular dystrophy (DMD), Limb-girdle muscular dystrophy (LGMD), congenital muscular dystrophy MDC1A, Marfan syndrome, and Dystrophic Epidermolysis Bullosa (DEB). FDA granted rare pediatric disease designation to TXA127 from Tarix to treat recessive dystrophic epidermolysis bullosa (RDEB). TXA127 has been granted orphan drug status by FDA as a treatment for pulmonary arterial hypertension, to enhance engraftment in patients receiving a stem cell transplant, and for Myelodysplastic Syndrome (MDS). Tarix Orphan has broad IP protection for TXA127 and Orphan Drug Designations (ODDs) have been granted for DMD LGMD and DEB in the U.S., and for DMD in Europe. Tarix Orphan aims to initiate a clinical trials for both DMD and DEB in early 2018 and has an active IND for a Phase II trial in DMD, as well as Fast Track designation for DMD.