Cyclacel Pharmaceuticals Inc (NASDAQ:CYCC) investors have a smile on their faces Monday, after the drug maker announced positive preclinical data for CYC065, the company’s dependent kinase (CDK) 2/9 inhibitor. CYC065 demonstrated therapeutic potential as a targeted anti-cancer agent. The data show that CYC065 substantially inhibited growth, triggered apoptosis, and induced anaphase catastrophe in murine and human lung cancer cells with known high metastatic potential. This was in marked contrast to effects in immortalized pulmonary epithelial murine and human cells. CYC065 markedly inhibited migration and invasion of lung cancer cells and affected distinctive pathways involved in DNA damage response, apoptosis, cell cycle regulation and cell migration. The data were presented at the American Association for Cancer Research (AACR) Annual Meeting 2017, April 1 – 5, 2017, in Washington, D.C.
Shares of Cyclacel reacted to the news, jumping over 70% to $6.42. Cyclacel stock has a 1-year high of $9.72 and a 1-year low of $0.40. The stock’s 50-day moving average is $4.03 and its 200-day moving average is $4.59.
“This study adds to the growing evidence of the value of CDK inhibition as an approach to treating cancer,” said Spiro Rombotis, President and Chief Executive Officer of Cyclacel. “CYC065 is in a Phase 1, first-in-human trial to evaluate safety, tolerability and pharmacokinetics in patients with solid tumors. The trial is at an expanded sixth dose escalation level with the objective of determining maximum tolerated dose and recommended dosing for Phase 2. Evidence of target engagement with prolonged Mcl-1 suppression in peripheral blood cells has been observed in patient samples from the study. We believe that CYC065 is one of the first medicines to demonstrate this in a human trial and look forward to pursuing this lead as part of our transcription regulation program.”
In the preclinical study, a group of researchers led by Professor Ethan Dmitrovsky, M.D., including Masanori Kawakami M.D., Ph.D., from The University of Texas MD Anderson Cancer Center, Houston, Texas, explored whether CYC065’s antineoplastic effects engaged anti-metastatic pathways. In vitro migration and invasion assays showed that CYC065 markedly inhibited migration and invasion of lung cancer cell lines, including KRAS mutant line. Reverse Phase Protein Arrays (RPPA) interrogated nearly 300 growth-regulatory proteins in murine and human lung cancer.
CYC065 treatment resulted in up-regulation of proteins involved in DNA damage and apoptosis, and down-regulation of ones involved in mTOR- and integrin pathways. Ingenuity pathway analysis (IPA) revealed up-regulation of pathways that engaged ATM signaling, G2/M DNA damage checkpoint regulation, or apoptosis signaling, down-regulation of pathways involved in mTOR signaling, cell cycle regulation, or integrin–mediated cell migration.
Data presented at AACR show CYC065’s potential to cause anaphase catastrophe and to inhibit migration and invasion of lung cancer cells including the one with mutant KRAS. Anaphase catastrophe is a novel mechanism of action which offers an innovative approach to combat aneuploid cancer cells containing abnormal numbers of chromosomes. The data highlight CYC065’s potential to target key molecular features of cancers.
The study concluded that CYC065 elicits marked antineoplastic effects in lung cancers despite presence of KRAS mutations through anaphase catastrophe and also inhibited migration and invasion of lung cancer cells.
On the ratings front, H.C. Wainwright analyst Andrew Fein reiterated a Buy rating on CYCC, with a price target of $7.00, in a report issued on February 24. The current price target represents a potential upside of 10% from where the stock is currently trading. According to TipRanks.com, Fein has a yearly average return of 9.9%, a 49% success rate, and is ranked #470 out of 4562 analysts.
Cyclacel Pharmaceuticals, Inc. engages in the discovery, development, and commercialization of novel, mechanism-targeted drugs to treat cancer and other serious disorders. Its lead candidate, sapacitabine, oral nucleoside analogue prodrug that acts through a novel mechanism. It also develops Seliciclib and CYC065-Second Generation CDK Inhibitor.