Sapacitabine

Cyclacel has reversed on its plans for sapacitabine and is now racing forward with CDK2/9 inhibitor fadraciclib. Cyclacel Pharmaceuticals once had high hopes for sapacitabine. But, despite making it all the way to phase 3 in acute myeloid leukemia (AML) as well as midstage studies for other cancers, the biotech has decided to give up and hand the rights back to Daiichi Sankyo. The biotech first licensed the nucleoside analog back in 2003. The original deal tied Cyclacel to securing regulatory approval in a country by 2011, but the company was able to amend this before the deadline. It turned out to be a good call, as over a decade later the biotech still hasn’t been able to get the therapy over the finish line. According to the company’s website, sapacitabine has been evaluated in over 1,000 patients across phase 1, 2 and 3 trials for both hematologic cancers and solid tumors. The therapy also picked up orphan-drug tags for the treatment of both AML and myelodysplastic syndrome from the European Medicines Agency and the FDA. The best hope for the drug was the phase 3 SEAMLESS trial in AML, but the results showed a combination of sapacitabine and Johnson & Johnson’s Dacogen didn’t significantly improve survival rates compared to Dacogen alone. A phase 1 trial in BRCA-mutant metastatic breast cancer also looked promising at one point, but clearly it wasn’t enough for the company to stick with the drug. Sapacitabine is an orally available nucleoside analogue, which acts through a DNA single-strand breaking mechanism that can lead to checkpoint activation. Cyclacel made the announcement to drop the drug in its third-quarter earnings, where the company focused the spotlight on fadraciclib, a CDK2/9 inhibitor undergoing a phase 1/2 study in solid tumors and lymphoma. “We are excited about fadra’s tolerability profile, as well as clear evidence of its anticancer activity as a single agent in late-line patients with lymphoma, gynecological, liver and pancreatic cancers,” CEO Spiro Rombotis said in the release. “We expect to shortly determine the recommended phase 2 dose and advance into phase 2 proof-of-concept stage.” The biotech’s other clinical-stage program is a PLK1 inhibitor called CYC140, which is undergoing a phase 1/2 study in patients with advanced solid tumors and lymphoma.

Hovering around penny stock territory, New Jersey-based Cyclacel Pharmaceuticals $CYCC said yesterday it’s finally going to call it quits on a Daiichi Sankyo-partnered cancer drug candidate that saw a Phase III flop in acute myeloid leukemia in late 2014. First licensed from Daiichi back in 2003, Cyclacel says it now wants to terminate the development of sapacitabine, and its license agreement with Daiichi on the drug “for commercial reasons,” with the termination effective by March 23, 2023. Back in late 2014, a data and safety monitoring board called to halt that sapacitabine study in AML due to futility, but the company continued the trial into 2017, ultimately finding that it did not show an overall survival benefit. The median OS was 5.9 months on the study arm versus 5.7 months on the control arm (P = .8902), according to the results published last year. The drug was also tested in mid-stage trials for other cancers like myelodysplastic syndromes and lung cancer. Cyclacel unveils a flop in leukemia 2 years after a call on futility, but still won’t give up Meanwhile, Cyclacel said in its earnings report yesterday that it’s also working on an ongoing Phase I/II study of oral fadraciclib in solid tumors and lymphoma, and its cash runway has been extended through the end of next year.