Cyclacel's biomarker technology shows that CYC202 induces cancer cells to commit suicide

July 14, 2003

Washington, DC, 14 July 2003 - Cyclacel Limited, the UK-based biopharmaceutical company, reported today that it demonstrated through state-of-the-art biomarker technology that CYC202 (R-roscovitine), its lead CDK inhibitor drug candidate, appears to induce cancer cell suicide or apoptosis in patients receiving the drug. Details of the biomarker data obtained with CYC202 were reported today at an oral presentation at the American Association for Cancer Research (AACR) annual meeting taking place here.

Biomarker technology is used to understand the molecular mechanism of action of novel drugs in humans, provide insights into their pharmacological properties, measure their biological effect (e.g. induce cancer cells to commit suicide) and determine susceptibility or resistance to the treatment. In the long-term biomarker analysis of tumour blood and tissues may allow selective treatment with CYC202 of those patients identified as likely to benefit from the drug based on the specific genetic profile of their tumour.

Biomarker analysis of blood samples from patients with cancer treated with CYC202 demonstrated that 54% (14 of 26 analysed) tested positive for cancer cell death or apoptosis following single agent treatment with the drug. In addition, seven CYC202 Phase I patients with various tumours, including pancreas and lung cancer, experienced long lasting tumour stabilisation. These patients received CYC202 capsules taken by mouth after exhausting other treatment options. CYC202 is presently being tested in two international, multicentre Phase IIa clinical trials for the treatment of breast and lung cancer in combination with standard chemotherapy.

Cyclacel's Biomarker Team used a novel assay technique to calculate the extent by which cancer cells are committing suicide (or apoptotic index) in different patients on the drug. An advantage of this test is that it measures cellular material released into the circulation by dying or dead cancer cells as a result of apoptosis. In this manner small blood samples can be readily obtained from patients with solid tumours rather than tissue pathology samples obtained through biopsies. Another approach taken by Cyclacel's Biomarker Team is the study of plasma proteomic profiles allowing the precise comparison of the proteins present in a patient's plasma before and after treatment with CYC202. Using this approach markers were detected that are only present in plasma following CYC202 treatment.

Phase I trials are not designed to detect efficacy of experimental drugs. Patients enrolled in Phase I studies suffer from many different types of cancer, have typically exhausted other therapeutic alternatives and usually experience low survival. In order to assess their prognosis it is necessary to wait for approximately six months post treatment to determine whether their cancer has continued to grow. The seven patients in the CYC202 Phase I study reported with stable disease included patients with adenocarcinoma, adrenal, lung, ovarian, pancreatic, parotid gland and thymus cancers. All seven showed long Times-To-Progression ("TTP") of their cancer, ranging between 7 and more than 11 months, and have been on drug for several months, ranging between 6 and more than 15 cycles each involving 3 weeks of treatment.

Dr Athos Gianella-Borradori, Cyclacel's Medical Director commented, "It is encouraging to see validation of the presumed mechanism by which CYC202 is causing the death of cancer cells through biomarker technology. It is also encouraging to see Phase I patients with poor prognosis experience long periods of stable disease after single therapy with CYC202. One should nevertheless be cautious about not over interpreting early indications of effectiveness from unscheduled efficacy assessments. Now that we have established a baseline for quantifying apoptosis in patients undergoing CYC202 monotherapy, we can use such biomarker techniques to assess the effects of the drug on patients receiving CYC202 in combination with chemotherapy."

"The results presented at AACR confirm Cyclacel's technological leadership in the emerging field of biomarkers," said Spiro Rombotis, CEO. "This is a strategic technology facilitating more efficient investments in drug development programmes. Biomarkers help determine clinical go/no go decisions very early in clinical development and are also proving invaluable in demonstrating early proof of concept in humans. We believe that biomarkers will be a source of competitive advantage in pivotal trials and market positioning by helping identify responder patients based on their genetic profile. We are excited about the work of our talented Biomarker Team and our goal of converting our understanding of biological pathways into patient treatment guidelines. We expect to use our Biomarker technology in additional drug programmes as they progress into clinical trials."
-end-
About Cyclacel Cyclacel is a biopharmaceutical company that designs and develops small molecule drugs that act on key cell cycle regulators to stop uncontrolled cell division in cancer and other diseases involving abnormal cell proliferation. The Company's discovery engines integrate cell cycle biology expertise with a large library of gene-based targets, state-of-the-art RNAi functional genomics, chemogenomics and clinical biomarker technologies to rapidly deliver new drugs. Cyclacel has six research and development programs underway. Most advanced is CYC202, a Cyclin Dependent Kinase (CDK) inhibitor, in Phase II trials for breast and lung cancer. CYC202 has also completed a Phase I trial in healthy volunteers and is being explored for use in glomerulonephritis, a disease of renal cell proliferation. Cyclacel has entered into corporate alliances with AstraZeneca, CV Therapeutics and a top 5 pharmaceutical major all in the oncology field.

Notes to Editors:
CYC202 (R-roscovitine) is a novel cell cycle drug belonging to the Cyclin Dependent Kinase (CDK) inhibitor class (US Patent 6,316,456). CDK inhibition is an important new approach in the quest for drugs that target the molecular mechanism of the body's own cancer stopping genes. In preclinical studies CYC202 demonstrated high specificity against CDK targets. CYC202 is supplied in capsules and is the first drug in its class that is available by mouth. Phase I clinical trials suggested that CYC202 appears to be well tolerated without the typical side effects associated with current chemotherapy and may induce lengthening of Time-To-Progression in patients with various cancers. Biomarker data showed that CYC202 is inducing cancer cell suicide or apoptosis in 54% (14/26 analysed) of patients with solid tumours. CYC202 is currently in Phase IIa trials for breast and lung cancer. CYC202 has also completed a Phase I trial in healthy volunteers and is being explored for use in glomerulonephritis, a disease of renal cell proliferation.

Because CDK inhibitors act at a different part of the cell cycle than current chemotherapies, giving these drugs in combination to patients may work synergistically to improve anti-tumour activity compared to standard therapies. It is thought that the drug acts on the G1/S or early checkpoint of the cell cycle via CDK inhibition and induces cancer cells to die by committing suicide via apoptosis. Certain conventional chemotherapies, such as the antimetabolite gemcitabine, exert their anticancer activity at the S-phase of the cell cycle. The potential therefore exists for combinations of G1/S or early cell cycle inhibitors and S-phase active drugs to act in synergy and kill more cancer cells than either drug alone.

American Association for Cancer Research (AACR), 94th Annual Meeting, 11-14 July 2003, Washington, DC (http://www.aacr.org/2003AM/2003AM.asp).

Dr Athos Gianella-Borradori, 47, joined October 2000. Previously Director Preclinical Development, Manufacturing, Clinical & Regulatory Affairs, Bavarian Nordic Research Institute GmbH; Vice President Clinical Affairs, CruCell BV; and Head, Oncology & Hematology Clinical R&D, Senior Adviser Genetic Therapy and Stem Cell Technologies, Novartis Pharma Ltd. MD University of Bern; fellow Charing Cross Hospital, London; Children's Hospital, Los Angeles; University of Glasgow Royal Infirmary; University of Lausanne; University of Zurich. Board certified in Pediatrics Hematology and Oncology.

Spiro Rombotis, 45, joined August 1997. Has 21 years of experience with pharmaceutical and biotech companies. Previously Vice President, International Operations & Business Development, Managing Director, Europe and Director Japanese joint venture, The Liposome Company, Inc.; Vice President, Pharmaceuticals, Central & Eastern Europe and Director International Marketing, Bristol-Myers Squibb Company; Head European Marketing and Sales, Head Corporate Development, Centocor, Inc.; Business Development, Novartis AG. BA, Williams College, USA. MBA and Master's degree in Hospital Management with honours, Kellogg Graduate School of Management, where he serves on the Advisory Board, Kellogg Center for Biotechnology.

© 2003 - Cyclacel Limited. Cyclacel®, Fluorescience®, Penetratin® and Polgen® are registered trademarks.

Feinstein Kean Healthcare

Related Lung Cancer Articles from Brightsurf:

State-level lung cancer screening rates not aligned with lung cancer burden in the US
A new study reports that state-level lung cancer screening rates were not aligned with lung cancer burden.

The lung microbiome may affect lung cancer pathogenesis and prognosis
Enrichment of the lungs with oral commensal microbes was associated with advanced stage disease, worse prognosis, and tumor progression in patients with lung cancer, according to results from a study published in Cancer Discovery, a journal of the American Association for Cancer Research.

New analysis finds lung cancer screening reduces rates of lung cancer-specific death
Low-dose CT screening methods may prevent one death per 250 at-risk adults screened, according to a meta-analysis of eight randomized controlled clinical trials of lung cancer screening.

'Social smokers' face disproportionate risk of death from lung disease and lung cancer
'Social smokers' are more than twice as likely to die of lung disease and more than eight times as likely to die of lung cancer than non-smokers, according to research presented at the European Respiratory Society International Congress.

Lung cancer therapy may improve outcomes of metastatic brain cancer
A medication commonly used to treat non-small cell lung cancer that has spread, or metastasized, may have benefits for patients with metastatic brain cancers, suggests a new review and analysis led by researchers at St.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Lung transplant patients face elevated lung cancer risk
In an American Journal of Transplantation study, lung cancer risk was increased after lung transplantation, especially in the native (non-transplanted) lung of single lung transplant recipients.

Proposed cancer treatment may boost lung cancer stem cells, study warns
Epigenetic therapies -- targeting enzymes that alter what genes are turned on or off in a cell -- are of growing interest in the cancer field as a way of making a cancer less aggressive or less malignant.

Are you at risk for lung cancer?
This question isn't only for people who've smoked a lot.

Read More: Lung Cancer News and Lung Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.