MARK2

Lengthens Patent Exclusivity of Plogosertib until August 2040BERKELEY HEIGHTS, N.J., June 26, 2024 (GLOBE NEWSWIRE) -- Cyclacel Pharmaceuticals, Inc. (NASDAQ: CYCC, NASDAQ: CYCCP; "Cyclacel" or the "Company"), a biopharmaceutical company developing innovative medicines based on cancer cell biology, today announced the receipt of a notice from the European Patent Office of the intention to grant a patent which includes claims to novel pharmaceutical compositions of plogosertib, a PLK1 inhibitor. Once granted, the European patent will provide exclusivity until August 2040 not including any extensions. The Company is prosecuting patent applications from the same family in other jurisdictions. "The notice further strengthens the Company’s patent portfolio and attests to the novelty of Cyclacel’s clinical pipeline, which includes plogosertib and fadraciclib, both of which were discovered in house," said Spiro Rombotis, President and Chief Executive Officer of Cyclacel. "The patent supports our switch to a new oral formulation of plogosertib with improved bioavailability. Our strategy is to test in the clinic whether certain ARID1A- and/or SMARCA-mutated cancers may benefit from treatment with plogosertib. We are also following a precision medicine approach with our lead drug candidate, fadraciclib, a CDK2/9 inhibitor, which is being evaluated in a proof of concept study initially in patients with solid tumors prospectively selected for CDKN2A/CDKN2B alterations, followed by patients with T-cell lymphoma, with initial proof of concept data expected in the second half of 2024.” 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. Cancer cells in general, 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 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, 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, transcriptional regulation and mitosis biology. The transcriptional regulation program is evaluating fadraciclib, a CDK2/9 inhibitor, and the anti-mitotic program 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 news release contains certain forward-looking statements that involve risks and uncertainties that could cause actual results to be materially different from historical results or from any future results expressed or implied by such forward-looking statements. Such forward-looking statements include statements regarding, among other things, statements related to the intended use of proceeds from the private placement, the efficacy, safety and intended utilization of Cyclacel’s product candidates, the conduct and results of future clinical trials, plans regarding regulatory filings, future research and clinical trials and plans regarding partnering activities. Factors that may cause actual results to differ materially include the risk that product candidates that appeared promising in early research and clinical trials do not demonstrate safety and/or efficacy in larger-scale or later clinical trials, trials may have difficulty enrolling, Cyclacel may not obtain approval to market its product candidates, the risks associated with reliance on outside financing to meet capital requirements, and the risks associated with reliance on collaborative partners for further clinical trials, development and commercialization of product candidates. You are urged to consider statements that include the words "may," "will," "would," "could," "should," "believes," "estimates," "projects," "potential," "expects," "plans," "anticipates," "intends," "continues," "forecast," "designed," "goal," or the negative of those words or other comparable words to be uncertain and forward-looking. For a further list and description of the risks and uncertainties the Company faces, please refer to our most recent Annual Report on Form 10-K and other periodic and other filings we file with the Securities and Exchange Commission and are available at www.sec.gov. Such forward-looking statements are current only as of the date they are made, and we assume no obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. Contacts Company:Paul McBarron, (908) 517-7330, pmcbarron@cyclacel.comInvestor Relations:Grace Kim, IR@cyclacel.com © Copyright 2024 Cyclacel Pharmaceuticals, Inc. All Rights Reserved. The Cyclacel logo and Cyclacel® are trademarks of Cyclacel Pharmaceuticals, Inc.

Scientists show for the first time that bacteria can cause itch by activating nerve cells in the skin. The findings can inform new therapies to treat itch that occurs in inflammatory skin conditions like eczema and dermatitis. Scientists at Harvard Medical School have shown for the first time that a common skin bacterium -- Staphylococcus aureus -- can cause itch by acting directly on nerve cells. The findings, based on research in mice and in human cells, are reported Nov. 22 in Cell. The research adds an important piece to the long-standing puzzle of itch and helps explain why common skin conditions like eczema and atopic dermatitis are often accompanied by persistent itch. In such conditions, the equilibrium of microorganisms that keep our skin healthy is often thrown off balance, allowing S. aureus to flourish, the researchers said. Up until now, the itch that occurs with eczema and atopic dermatitis was believed to arise from the accompanying inflammation of the skin. But the new findings show that S. aureus single-handedly causes itch by instigating a molecular chain reaction that culminates in the urge to scratch. "We've identified an entirely novel mechanism behind itch -- the bacterium Staph aureus, which is found on almost every patient with the chronic condition atopic dermatitis. We show that itch can be caused by the microbe itself," said senior author Isaac Chiu, associate professor of immunology in the Blavatnik Institute at HMS. The study experiments showed that S. aureus releases a chemical that activates a protein on the nerve fibers that transmit signals from the skin to the brain. Treating animals with an FDA-approved anti-clotting medicine successfully blocked the activation of the protein to interrupt this key step in the itch-scratch cycle. The treatment relieved symptoms and minimized skin damage. The findings can inform the design of oral medicines and topical creams to treat persistent itch that occurs with various conditions linked to an imbalance in the skin microbiome, such as atopic dermatitis, prurigo nodularis, and psoriasis. The repeated scratching that is a hallmark of these conditions can cause skin damage and amplify inflammation. "Itch can be quite debilitating in patients who suffer from chronic skin conditions. Many of these patients carry on their skin the very microbe we've now shown for the first time can induce itch," said study first author Liwen Deng, a postdoctoral research fellow in the Chiu Lab. Identifying the molecular spark plug that ignites itch Researchers exposed the skin of mice to S. aureus. The animals developed intensifying itch over several days, and the repeated scratching caused worsening skin damage that spread beyond the original site of exposure. Moreover, mice exposed to S. aureus became hypersensitive to innocuous stimuli that would not typically cause itch. The exposed mice were more likely than unexposed mice to develop abnormal itching in response to a light touch. This hyperactive response, a condition called alloknesis, is common in patients with chronic conditions of the skin characterized by persistent itch. But it can also happen in people without any underlying conditions -- think of that scratchy feeling you might get from a wool sweater. To determine how the bacterium triggered itch, the researchers tested multiple modified versions of the S. aureus microbe that were engineered to lack specific pieces of the bug's molecular makeup. The team focused on 10 enzymes known to be released by this microbe upon skin contact. One after another, the researchers eliminated nine suspects -- showing that a bacterial enzyme called protease V8 was single-handedly responsible for initiating itch in mice. Human skin samples from patients with atopic dermatitis also had more S. aureus and higher V8 levels than healthy skin samples. The analyses showed that V8 triggers itch by activating a protein called PAR1, which is found on skin neurons that originate in the spinal cord and carry various signals -- touch, heat, pain, itch -- from the skin to the brain. Normally, PAR1 lies dormant but upon contact with certain enzymes, including V8, it gets activated. The research showed that V8 snips one end of the PAR1 protein and awakens it. Experiments in mice showed that once activated, PAR1 initiates a signal that the brain eventually perceives as itch. When researchers repeated the experiments in lab dishes containing human neurons, they also responded to V8. Interestingly, various immune cells implicated in skin allergies and classically known to cause itch -- mast cells and basophils -- did not drive itch after bacterial exposure, the experiments showed. Nor did inflammatory chemicals called interleukins, or white cells, which are activated during allergic reactions and are also known to be elevated in skin diseases and even in certain neurologic disorders. "When we started the study, it was unclear whether the itch was a result of inflammation or not," Deng said. "We show that these things can be decoupled, that you don't necessarily have to have inflammation for the microbe to cause itch, but that the itch exacerbates inflammation on the skin." Interrupting the itch-scratch cycle Because PAR1 -- the protein activated by S. aureus -- is involved in blood-clotting, researchers wanted to see whether an already approved anticlotting drug that blocks PAR1 would stop itch. It did. The itchy mice whose skin was exposed to S. aureus experienced rapid improvement when treated with the drug. Their desire to scratch diminished dramatically, as did the skin damage caused by scratching. Moreover, once treated with PAR1 blockers, the mice no longer experienced abnormal itch in response to innocuous stimuli. The PAR1 blocker is already used in humans to prevent blood clots and could be repurposed as anti-itch medication. For example, the researchers noted, the active ingredient in the medicine could become the basis for anti-itch topical creams. One immediate question that the researchers plan to explore in future work is whether other microbes besides S. aureus can trigger itch. "We know that many microbes, including fungi, viruses, and bacteria, are accompanied by itch but how they cause itch is not clear," Chiu said. Beyond that, the findings raise a broader question: Why would a microbe cause itch? Evolutionarily speaking, what's in it for the bacterium? One possibility, the researchers said, is that pathogens may hijack itch and other neural reflexes to their advantage. For example, previous research has shown that the TB bacterium directly activates vagal neurons to cause cough, which might enable it to spread more easily from one host to another. "It's a speculation at this point, but the itch-scratch cycle could benefit the microbes and enable their spread to distant body sites and to uninfected hosts," Deng said. "Why do we itch and scratch? Does it help us, or does it help the microbe? That's something that we could follow up on in the future." The work was funded by the National Institutes of Health (grants R01AI168005, R01AI153185, R01NS065926, R01NS102161, R01NS111929, R37AI052453, R01AR076082, U01AI152038, UM1AI151958, R01AI153185, R01JL160582, F32AI172080, T32AI049928, 1R21AG075419), Food Allergy Science Initiative (FASI), Burroughs Wellcome Fund, Drako Family Fund, Jackson-Wijaya Research Fund, Canadian Institutes of Health Research (CIHR) (grants 376560 and 469411), and ANR-PARCURE (PRCE-CE18, 2020). Chiu serves on the scientific advisory board of GSK Pharmaceuticals. Provisional patent application Serial No. 63/438,668, in which some coauthors are listed as inventors, was filed based on these findings.

The TORCH-2 study is a Phase I/II trial of the mTORC1/2 inhibitor ATG-008 plus the Anti-PD-1 monoclonal antibody toripalimab for the treatment of patients with advanced solid tumors The combination treatment produced an objective response rate (ORR ) of 52.4% in the advanced cervical cancer cohort (including 75% in PD-L1 positive and 41.7% in PD-L1 negative patients), a disease control rate (DCR) of 90.5% and a median progression-free survival (mPFS) of 7.2 months. SHANGHAI and HONG KONG, May 25, 2023 /PRNewswire/ -- Antengene Corporation Limited ( "Antengene" SEHK: 6996.HK), a leading innovative, commercial-stage global biopharmaceutical company dedicated to discovering, developing and commercializing first-in-class and/or best-in-class medicines for cancer, today announced that the latest results from the Phase I/II TORCH-2 study will be presented as a poster at the 2023 American Society for Clinical Oncology Annual Meeting (ASCO 2023) taking place from June 2nd to 6th, 2023 at the McCormick Place Convention Center in Chicago, IL. Being among the 22 China studies selected for Poster Discussions this year, the abstract will also be presented in a Poster Discussion session on June 3rd. "It is our pleasure to have the latest results from the TORCH-2 study selected for Poster Discussion at ASCO 2023," said Dr. Amily Zhang, Antengene's Chief Medical Officer. "Going forward, we will maintain close collaboration with the investigator team of the TORCH-2 study and liaise with regulatory authorities in China and other APAC markets to align on a registration path in cervical cancer and to continue evaluating the combination in additional ongoing studies in other solid tumors." The TORCH-2 study is a Phase I/II trial of the mTORC1/2 inhibitor ATG-008 plus the Anti-PD-1 monoclonal antibody toripalimab for the treatment of patients with advanced solid tumors . The study enrolled 46 patients, including 21 patients with cervical cancer, to evaluate ATG-008 at three doses (15, 20 and 30 mg) in combination with the standard dose of toripalimab. Study patients had advanced solid tumors with a baseline Eastern Cooperative Oncology Group (ECOG) score of 0-1 (the majority scored 1 on the ECOG scale) and a median of 2 lines of therapy (range:0-7). Median patient age was 53 years. Patients with prior PI3K/AKT/mTOR therapy were excluded. Pharmacokinetics and exploratory biomarkers of drug activity were also evaluated. The data are presented as of the cut-off date of October 21st, 2022. Poster Details Title: A phase I/II study of the TORC1/2 inhibitor onatasertib combined with toripalimab in patients with advanced solid tumors Abstract: 2526 Session: Developmental Therapeutics – Immunotherapy Poster : 368 Poster Discussion Session Date and Time: 3:00 PM - 4:30 PM, June 3, 2023 (Central Time) / 4:00 AM – 5:30 AM, June 4, 2023 (Beijing Time) 52.4% ORR in the Cervical Cancer Cohort: Among the 21 patients in the cervical cancer cohort, 1 patient with negative PD-L1 expression experienced a CR and 9 patients experienced a partial response (PR). Note that the patient who achieved a CR in this cohort remained on treatment for more than 883 days and is on treatment with single agent ATG-008 as of the cut-off date. The mPFS for the cohort was 7.2 months. Additional Responses in Patients with Nasopharyngeal Carcinoma ( NPC): The study reported one additional PR in a patient with NPC; this patient remained on study for over two years. Recommended Phase II Dose (RP2D) was Defined: The RP2D for ATG-008 was determined to be 15 mg in combination with toripalimab. Safety Evaluation Did Not Identify any Dose-Limiting Toxicity ( DLT) or Maximum Tolerated Dose (MTD) from the Dose Escalation Phase : The study did not identify any DLT or reach the MTD; 97.8% of patients had more than one treatment emergent adverse event (TEAE) and 69.6% of patients had TEAEs > grade 3, most common of which were decreased lymphocytes (23.9%), rash (10.6%) and hyperglycemia (10.9%). Pharmacokinetic profiles of ATG-008 in combination with toripalimab were similar to ATG-008 monotherapy across APAC and US patients. No new safety signals were reported. About ATG-008 ATG-008 (onatasertib) is an orally available mTORC 1/2 inhibitor. ATG-008 inhibits the activity of mTOR, which may result in the induction of tumor cell apoptosis and a decrease in tumor cell proliferation. mTOR, a serine/threonine kinase that is upregulated in a variety of tumors, has an important role in the PI3K/AKT/mTOR signaling pathway, which is frequently dysregulated in human cancers. ATG-008 has been studied in clinical trials to treat a broad range of tumor types including multiple myeloma (MM), glioblastoma (GBM), hepatocellular carcinoma (HCC), non-small cell lung cancer (NSCLC), diffuse large B-cell lymphoma (DLBCL), etc. About Antengene Antengene Corporation Limited ( "Antengene", SEHK: 6996.HK) is a leading commercial-stage R&D-driven global biopharmaceutical company focused on the discovery, development, manufacturing and commercialization of innovative first-in-class/best-in-class therapeutics for the treatment of hematologic malignancies and solid tumors, in realizing its vision of "Treating Patients Beyond Borders". Since 2017, Antengene has built a pipeline of 9 oncology assets at various stages going from clinical to commercial, including 6 with global rights, and 3 with rights for the APAC region. To date, Antengene has obtained 29 investigational new drug (IND) approvals in the U.S. and Asia, and submitted 10 new drug applications (NDAs) in multiple Asia Pacific markets, with the NDA for XPOVIO® (selinexor) already approved in Mainland China, Taiwan China, South Korea, Singapore and Australia. Forward-looking statements The forward-looking statements made in this article relate only to the events or information as of the date on which the statements are made in this article. Except as required by law, we undertake no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise, after the date on which the statements are made or to reflect the occurrence of unanticipated events. You should read this article completely and with the understanding that our actual future results or performance may be materially different from what we expect. In this article, statements of, or references to, our intentions or those of any of our Directors or our Company are made as of the date of this article. Any of these intentions may alter in light of future development. For a further discussion of these and other factors that could cause future results to differ materially from any forward-looking statement, please see the other risks and uncertainties described in the Company's Annual Report for the year ended December 31, 2022, and the documents subsequently submitted to the Hong Kong Stock Exchange. For more information, please contact: Investor Contacts: Donald Lung E-mail: [email protected] Mobile: +86 18420672158 PR Contacts: Peter Qian E-mail: [email protected] Mobile: +86 13062747000 SOURCE Antengene Corporation Limited