ManRos Therapeutics SA and Cyclacel Ltd, an exclusively owned subsidiary of Cyclacel Pharmaceuticals, Inc., recently announced a partnership, supply and licensing agreement for the commercialization and development of Cyclacel’s oral seliciclib capsules by ManRos for the treatment of patients with cystic fibrosis (CF).
Under the terms of the agreement, Cyclacel’s proprietary clinical data is now licensed by ManRos for the development of seliciclib as a treatment for CF. Also under the terms of the collaboration agreement, Cyclacel will supply the investigational drug for both initial and later stage clinical studies of seliciclib for patients with CF as well as provide technical support for facilitating clinical studies. Cyclacel will receive milestone payments, tiered royalties and an up-front payment if the drug is commercialized as treatment for patients with CF. the financial details of the agreement have not been revealed.
Seliciclib is a novel, orally-available inhibitor of CDK2/E, CDK2/A, CDK7 and CDK9 — enzymes that are central to the process of cell division and cell cycle control and play pivotal roles in cancer cell growth and DNA damage repair. Inhibition of CDKs 2 and 9 may also correct aberrant cell cycle control in certain non-malignant diseases of proliferation. Seliciclib exerts an anti-proliferative effect via several key mechanisms:
- selective downregulation of proliferative and survival proteins and upregulation of p53, leading to growth arrest or apoptosis;
- decreasing phosphorylation of Rb and modulating E2F transcriptional activity leading to growth arrest or apoptosis;
- inhibiting HR and NHEJ DNA repair pathways, resulting in synergy with DNA damaging agents; and
- in sequence with chemotherapy, overcoming cell cycle related drug resistance.
Seliciclib has been evaluated in 16 clinical trials and administered to over 450 subjects including healthy volunteers. It has been found to be sparing on bone marrow, as observations of myelosuppression are rare.
“Treatment of lung disease associated with CF represents a major unmet medical need, in particular, with regard to reducing dysregulated innate immunity, chronic infections, inflammation and subsequent lung injury,” said Dr. Laurent Meijer, President of ManRos. “Seliciclib is a well-studied, orally-available, investigational medicinal product. We have shown that seliciclib acts through multiple mechanisms and may confer therapeutic benefits to CF patients. With this agreement we are leveraging Cyclacel’s extensive clinical experience with seliciclib in hundreds of cancer patients to offer patients with CF a differentiated treatment alternative. Following receipt of regulatory authorisations, we expect that proof-of-concept clinical trials in CF patients will begin in the near term.”
“The CDK field is experiencing a resurgence and CDK inhibitors are receiving a lot of attention as novel treatments in oncology and other proliferative diseases,” added Spiro Rombotis, Chief Executive Officer of Cyclacel. “Like Cyclacel, the founders of ManRos have been studying CDK inhibitors for many years and will be evaluating an innovative application of a CDK inhibitor to potentially help patients with CF. The agreement with ManRos illustrates our commitment to generate value from our portfolio of CDK inhibitors and deliver on our science-driven business strategy.”