- Fibrolamellar hepatocellular carcinoma (FLC) has no approved treatment and
occurs mostly in adolescents and young adults -

KUALA LUMPUR, Malaysia, July 07, 2025 (GLOBE NEWSWIRE) -- Cyclacel Pharmaceuticals, Inc. (NASDAQ: CYCC, NASDAQ: CYCCP; “Cyclacel” or the “Company”), a biopharmaceutical company developing innovative cancer medicines, highlighted a publication from independent investigators titled, “ DNAJ-PKAc fusion heightens PLK1 inhibitor sensitivity in fibrolamellar carcinoma , ” published online in the journal Gut, a leading, peer-reviewed medical journal focused on gastroenterology and hepatology. 1 The authors of the study described in the publication reported that DNAJ-PKAc, a fusion oncoprotein known to drive FLC progression, makes the cancer sensitive to treatment with plogosertib.

The researchers found that PLK1 is essential for FLC cells making them highly sensitive to loss of PLK1. A direct interaction was found between DNAJ-PKAc fusions present in the centrosome and PLK1, thus promoting mitotic progression. Pharmacologic inhibitors of PLK1, such as plogosertib, significantly reduced FLC growth but spared normal liver cells in patient-derived in vitro and in vivo xenograft models and an orthotopic model of FLC. The article suggests that plogosertib should be further evaluated as a potential treatment for FLC in further preclinical and clinical studies.

About fibrolamellar carcinoma (FLC)

According to the Fibrolamellar Cancer Foundation (FCF), FLC is a rare cancer of the liver that mainly occurs in adolescents and young adults. The National Cancer Institute estimates annual US incidence at 0.02 per 100,000. When FLC tissues from patients are examined under a microscope, distinctive fibrous bands, or lamellae, are observed. As patients initially do not have symptoms, FLC is frequently discovered at later stages or after spreading to other parts of the body. It is often misdiagnosed as HCC, hepatocellular carcinoma, the more common form of liver cancer. However, FLC is different from HCC as it is found in a younger population with normal livers and no known risk factors, such as hepatitis. Five-year survival for FLC patients is poor at approximately 30%.

The protein kinase A (PKA) enzyme is a common driver of FLC in patients. In nearly all FLC cases an abnormal form, or chimaera, is found which results from the fusion of the DNAJB1 and PKAc genes. FCF funded research at Rockefeller University identified this unique gene fusion in 2014 located at chromosome 19. The fusion is associated with breaking up of the chromosome, following which chromosomal reassembly is flawed resulting in cancer growth. Finding a DNAJB1 – PKAc fusion in patient biopsies is confirmatory of an FLC diagnosis.

FLC does not respond to chemotherapy. Although surgery can be a cure if the cancer has not spread, there is an urgent need for systemic therapies to treat non-resectable FLC.

About Polo-like Kinase and Plogosertib

Polo-like kinase 1 (PLK1) is a serine/threonine kinase that plays a central role in cell division or mitosis. PLK1 is an important regulator of the DNA damage cell cycle checkpoint, mitotic entry and exit, spindle formation and cytokinesis, or cell separation into daughter cells. In general, cancer cells, and in particular KRAS mutated and p53(-) cells, are very sensitive to PLK1 depletion. In contrast normal cells with intact cell cycle checkpoints are less sensitive. Pharmacological inhibition of PLK1 in cancer cells blocks proliferation by prolonged mitotic arrest and induces onset of apoptotic death of such cells.

Plogosertib (formerly CYC140) is a novel, small molecule, selective and potent PLK1 inhibitor. It has demonstrated impressive efficacy in human tumor xenografts at nontoxic doses. Cyclacel’s translational biology program supports the development of plogosertib in solid tumors and leukemias. Preclinical data from independent groups have shown that certain ARID1A- and/or SMARCA-mutated cancers, and cancers associated with DNAJ-PKAc fusions, may benefit from treatment with plogosertib. Additionally, recent data suggest that PLK1 inhibition may be effective in KRAS-mutated metastatic colorectal cancer. PLK1 overexpression correlates with poor patient prognosis in several tumors, including esophageal, fibrolamellar liver, gastric, leukemia, lung, ovarian, and squamous cell cancers, as well as MYC-amplified cancers.

Initial dose escalation data from a Phase 1 clinical study of oral plogosertib suggest that the compound is well tolerated with no dose limiting toxicity observed in five dosing schedules. Clinical benefit was observed in patients with adenoid cystic, biliary tract, ovarian, and squamous cell sinus cancers.

About Cyclacel Pharmaceuticals, Inc.

Cyclacel is a clinical-stage, biopharmaceutical company developing innovative cancer medicines based on cell cycle and mitosis biology. The anti-mitotic program is evaluating plogosertib, a PLK1 inhibitor, in patients with both solid tumors and hematological malignancies. Cyclacel's strategy is to build a diversified biopharmaceutical business based on a pipeline of novel drug candidates addressing oncology and hematology indications. For additional information, please visit www.cyclacel.com .

Forward-looking Statements

This press release includes forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, Section 21E of the Securities Exchange Act of 1934, as amended and the Safe Harbor provisions of the US Private Securities Litigation Reform Act of 1995, and encompasses all statements, other than statements of historical fact contained in this press release. These forward-looking statements can be identified by terminology such as “may,” “could,” “will,” “expects,” “anticipates,” “aims,” “future,” “intends,” “plans,” “believes,” “estimates,” “targets,” “likely to”, “understands” and similar statements. These forward-looking statements are based on management’s current expectations. However, it is not possible for our management to predict all risks, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements we may make. These statements are neither promises nor guarantees but involve known and unknown risks, uncertainties and other important factors and circumstances that may cause Cyclacel’s actual results, performance or achievements to be materially different from its expectations expressed or implied by the forward-looking statements, including conditions in the U.S. capital markets, negative global economic conditions, potential negative developments resulting from epidemics or natural disasters, other negative developments in Cyclacel’s business or unfavorable legislative or regulatory developments. We caution you therefore against relying on these forward-looking statements, and we qualify all of our forward-looking statements by these cautionary statements.

For a discussion of additional factors that may affect the outcome of such forward-looking statements, see our 2024 annual report on Form 10-K, and in particular the “Risk Factors” section, as well as the other documents filed with or furnished to the SEC by Cyclacel from time to time. Copies of these filings are available online from the SEC at www.sec.gov , or on the SEC Filings section of our Investor Relations website at https://investor.cyclacel.com/sec-filings . These and other important factors could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management’s estimates as of the date of this press release. These forward-looking statements should not be relied upon as representing Cyclacel’s views as of any date subsequent to the date of this press release. All forward-looking statements in this press release are based on information currently available to Cyclacel, and Cyclacel and its authorized representatives assume no obligation to update these forward-looking statements in light of new information or future events. Accordingly, undue reliance should not be placed upon the forward-looking statements.

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1 Chan M, Zhu S, Nukaya M, et al, DNAJ-PKAc fusion heightens PLK1 inhibitor sensitivity in fibrolamellar carcinoma, Gut Published Online. doi: 10.1136/gutjnl-2024-334274.