Repotrectinib (TPX-0005) Is a Next-Generation ROS1/TRK/ALK Inhibitor. It represents an effective therapeutic option for patients with ROS1-, NTRK1-3-, or ALK-rearranged malignancies who have progressed on earlier-generation tyrosine kinase inhibitors. In June 2017, The US Food and Drug Administration (FDA) granted orphan drug designation to this drug for the treatment of Non–small cell lung adenocarcinoma with an ALK, ROS1, or NTRK mutation.

Omaveloxolone (RTA-408) is a synthetic triterpenoid exerting antioxidant inflammation modulator properties. It activates the transcription factor Nrf2 and inhibits NF-κB signaling. Omaveloxolone demonstrated antioxidant, anti-inflammatory, and anticancer activities. Reata Pharmaceuticals is developing omaveloxolone for the treatment of cancers, Friedreich's ataxia and mitochondrial disorders.

BioLineRx Ltd has developed BL-8040, a short peptide for the treatment of solid tumors, acute myeloid leukemia, or AML, and stem-cell mobilization for bone-marrow transplantation. BL-8040 acts as CXCR4 antagonist. CXCR4 is a chemokine receptor that is directly involved in tumor progression, angiogenesis, metastasis, and cell survival. In February 2019 US Food and Drug Administration (FDA) has granted Orphan Drug Designation to BL-8040, for the treatment of pancreatic cancer. Previously FDA had granted Orphan Drug Designation for the treatment of acute myeloid leukemia and stem-cell mobilization.

Biafungin (formerly SP 3025 or CD101), a highly stable echinocandin and an antifungal drug that was studied against panels of Candida and Aspergillus clinical isolates. Biafungin was involved in phase II clinical trials in the treatment of acute moderate to severe vulvovaginal candidiasis. Seachaid Pharmaceuticals invented this drug. Then Cidara Therapeutics acquired a worldwide exclusive license to develop and commercialize the drug.

APD-334 (Etrasimod) was discovered as part of our internal effort to identify potent, centrally available, functional antagonists of the S1P1 receptor for use as next generation therapeutics for treating multiple sclerosis (MS) and other autoimmune diseases. APD334 is a potent functional antagonist of S1P1 and has a favorable PK/PD profile, producing robust lymphocyte lowering at relatively low plasma concentrations in several preclinical species. This new agent was efficacious in a mouse experimental autoimmune encephalomyelitis (EAE) model of MS and a rat collagen induced arthritis (CIA) model and was found to have appreciable central exposure. APD-334 has therapeutic potential in immune and inflammatory-mediated diseases such as ulcerative colitis, Crohn’s disease, and atopic dermatitis.

Elacestrant (ER-306323 or RAD 1901 [6R)-6-(2-(N-(4-(2-(ethylamino)ethyl)benzyl)-N-ethylamino)-4-methoxyphenyl)-5,6,7,8-tetrahydronaphthalen-2-ol dihydrochloride]) is a selective estrogen receptor (ER) degrader. Elacestrant induces the degradation of ER, inhibits ER-mediated signaling and growth of ER+ breast cancer cell lines in vitro and in vivo, and significantly inhibits tumor growth in breast cancer xenograft models. Elacestrant has the potential for use as a single agent or in combination with other therapies for the treatment of breast cancer. Elacestrant is being developed by Radius Health, for the treatment of estrogen receptor positive breast cancer.

Fruquintinib is a highly selective small molecule drug candidate that has been shown to inhibit VEGFR 24 hours a day via an oral dose, with lower off-target toxicities compared to other targeted therapies. Mechanistically, Fruquintinib selectively blocks VEGF-mediated receptor autophosphorylation, thus inhibiting endothelial cell proliferation and migration. In preclinical in vitro studies using a 32P-ATP assay, Fruquintinib selectively inhibited the tyrosine kinase activity associated with VEGFR-1, VEGFR-2, and VEGFR-3 at concentrations in the nanomolar range, but showed little inhibition against a panel of 254 kinases related to cell cycle or cell proliferation, including cyclin-dependent kinase (CDK1, 2, 5), the epidermal growth factor receptor (EGFR), the mesenchymal-epithelial transition factor (c-Met), and platelet-derived growth factor receptor β (PDGFRβ) kinase. In cellular assays, Fruquintinib potently inhibited VEGF-stimulated VEGFR phosphorylation and proliferation in human umbilical vein endothelial cells. Fruquintinib demonstrated potent antiangiogenic effect and anti-tumor activity in xenograft models of colon adenocarcinoma (HT-29), non-small cell lung cancer (NSCLC; NCI-H460), renal clear cell carcinoma (Caki-1), and gastric carcinoma (BGC823) in mice treated for 3 weeks. Fruquintinib is currently under joint development in China by Chi-Med and its partner Eli Lilly and Company (“Lilly”). Chi-Med and Lilly jointly announced top-line results from the FRESCO CRC trial on March 3, 2017. In addition, Fruquintinib is being studied in China in Phase III pivotal trial in non-small cell lung cancer (“NSCLC”), known as FALUCA; and a Phase II study using Fruquintinib combined with Iressa® (gefitinib) in the first-line setting for patients with advanced or metastatic NSCLC.

Sparsentan (RE-021; BMS-346567; PS433540; DARA-a) is a novel candidate in development by Retrophin for the treatment of focal segmental glomerulosclerosis (FSGS), a serious kidney disorder that often leads to end-stage renal disease (ESRD). Sparsentan is a first-in-class, orally active, dual-acting angiotensin receptor blocker (ARB) and highly selective endothelin Type A receptor antagonist. Sparsentan has been used in trials studying the treatment of focal segmental glomerulosclerosis. The FDA and European Commission have granted sparsentan orphan drug designation for FSGS. Retrophin also is advancing sparsentan for the treatment of immunoglobulin A nephropathy (IgAN) , or Berger’s disease, which also can lead to ESRD. Retrophin is examining the ability of sparsentan to slow the decline of kidney function in patients with FSGS and IgAN.