Talazoparib (BMN 673) demonstrates excellent potency, inhibiting PARP1 and PARP2 enzyme activity. It inhibits PARP-mediated PARylation in a whole-cell assay and prevents proliferation of cancer cells carrying mutant BRCA1/2. Talazoparib is orally available, displaying favorable pharmacokinetic properties and remarkable antitumor efficacy in the BRCA1 mutant MX-1 breast cancer xenograft model following oral administration as a single-agent or in combination with chemotherapy agents such as temozolomide and cisplatin. Medivation (a subsidiary of Pfizer) is developing talazoparib (MDV 3800, formerly BMN 673 and LT 673) for the treatment of genetically defined cancers. On October 16, 2018, the FDA approved talazoparib (TALZENNA, Pfizer Inc.) for patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm), HER2‑negative locally advanced or metastatic breast cancer.

Encorafenib, also known as BRAFTOVI or LGX818, is an orally available mutated BRaf V600E inhibitor with potential antineoplastic activity, which was developed by Novartis. LGX818 possesses selective anti-proliferative and apoptotic activity in cells expressing BRAFV600E. In the A375 (BRAFV600E) human melanoma cell line LGX818 suppresses phospho-ERK (EC50 = 3 nM) leading to potent inhibition of proliferation (EC50 = 4 nM). No significant activity was observed against a panel of 100 kinases (IC50 > 900 nM) and LGX818 did not inhibit proliferation of > 400 cell lines expressing wild-type BRAF. On June 27, 2018, the Food and Drug Administration approved encorafenib and Binimetinib (BRAFTOVI and MEKTOVI, Array BioPharma Inc.) in combination for patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, as detected by an FDA-approved test. Encorafenib and binimetinib target two different kinases in the RAS/RAF/MEK/ERK pathway. Compared with either drug alone, co-administration of encorafenib and binimetinib result in greater anti-proliferative activity in vitro in BRAF mutation-positive cell lines and greater anti-tumor activity with respect to tumor growth inhibition in BRAF V600E mutant human melanoma xenograft studies in mice. In addition to the above, the combination of encorafenib and binimetinib acted to delay the emergence of resistance in BRAF V600E mutant human melanoma xenografts in mice compared with the administration of either drug alone. Encorafenib is in phase III for Metastatic Colorectal Cancer and in phase II for Relapsed or Refractory Multiple Myeloma.

Lutetium Lu 177 dotatate binds to somatostatin receptors with highest affinity for subtype 2 receptors (SSRT2). Upon binding to somatostatin receptor expressing cells, including malignant somatostatin receptor-positive tumors, the compound is internalized. The beta emission from Lu 177 induces cellular damage by formation of free radicals in somatostatin receptor-positive cells and in neighboring cells. LUTATHERA® (lutetium Lu 177 dotatate) is indicated for the treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults.

Sarecycline (SC1401, WC3035) is a novel, once-daily, tetracycline-derived compound being developed by Paratek Pharmaceuticals and Allergan (previously Actavis) for use in the treatment of acne and rosacea. In preclinical studies, Sarecycline possesses favorable anti-inflammatory activity, plus narrow-spectrum antibacterial activity relative to other tetracycline-derived molecules. Sarecycline has been used in Phase III clinical trials studying the treatment of Acne Vulgaris. The primary objective was to evaluate the efficacy and safety of oral Sarecycline 1.5 mg/kg per day compared to placebo in treating inflammatory acne lesions in subjects with moderate to severe acne. Sarecycline was statistically significantly superior to placebo with respect to primary efficacy endpoints. The most common adverse events (>2%) reported in the sarecycline group were nausea (3.2%), nasopharyngitis (2.8%), and headache (2.8%). The rate of discontinuation due to adverse events among sarecycline-treated patients in the two studies combined was 1.4%.