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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.

Founded in 2015, Kallyope Inc. is a biotechnology company focused on the therapeutic potential of the gut-brain axis. Kallyope recently disclosed three patents pertaining to AMPK small molecule activators.  Kallyope Inc.'s PipelineAMPK, which stands for AMP-activated protein kinase, is a key molecule in regulating energy metabolism and is at the core of research into diabetes and other metabolic-related diseases. AMPK is widely expressed in various metabolically related organs, and AMPK activators can potentially treat ailments such as allergies, cancers, depression, type 2 diabetes, malnutrition, obesity, psoriasis, and ulcerative colitis. However, the activation of AMPK through medication is challenging due to the potential existence of 12 different compound forms of AMPK in an animal's body. AMPK Structure and Activation MechanismThe AMPK mechanism is activated when the upstream kinase CAMKK2 is activated by intracellular calcium ions, and when LKB1 forms a heterotrimer with STRAD and MO25. Factors leading to the activation of AMPK include oxygen stress, glucose starvation, exercise, and mitochondrial toxins. Drugs that activate AMPK are primarily small molecule activators. AMPK, a serine/threonine kinase, is evolutionarily conserved from yeast to mammals. As an energy sensor, AMPK's activity increases when the cellular ratio of 5'-adenosine monophosphate (AMP) to adenosine triphosphate (ATP) rises due to nutrient deprivation. Activated AMPK phosphorylates downstream substrates, promoting catabolic metabolism and inhibiting anabolic metabolism, leading to ATP production and energy recovery. The activity of AMPK can change due to various physiological factors (like hormones, cytokines, and dietary nutrients) as well as pathological conditions (like obesity, chronic inflammation, and type 2 diabetes). AMPK activation can lead to reduced hepatic glucose production and plasma glucose levels. Thus, AMPK is an attractive therapeutic target for various metabolic diseases. In addition, AMPK has beneficial effects on intestinal health, such as enhancing intestinal absorption, improving barrier function, inhibiting the occurrence of colorectal cancer, reducing intestinal inflammation and metabolic-related diseases, and is very important for maintaining intestinal homeostasis. For instance, AMPK activation strengthens intercellular connections, nutrient transport, autophagy and cell apoptosis, suppressing intestinal inflammation and carcinogenesis. Hence, AMPK is related to the maintenance of tight connections of colonic epithelium, controlling the progression of colitis. In various mouse models of colitis, the direct use of AMPK activators for treatment has been proven to effectively restore intestinal barrier function. Metformin is an indirect AMPK activator with additional biological activity. However, the persistent direct activation of AMPK raises safety concerns, particularly in the heart. Chronic treatment with systemic direct activators in rodents and non-human primates can lead to cardiac hypertrophy (with increased cardiac glycogen). Moreover, human genetic polymorphisms of AMPK are associated with cardiac glycogen deposition, cardiac hypertrophy, and Wolff-Parkinson-White syndrome. Due to the risk of cardiac hypertrophy, it is not suitable to directly use known AMPK activators for the treatment of IBD, colitis, and other intestinal barrier leakage diseases. All the direct AMPK activators that have been reported into clinical studies (such as Pfizer's PF-06409577, which has been terminated in phase I) or broad preclinical evaluations (like Merck's MK-3903 and MK-8722) are systemic AMPK activators and have been developed for systemic administration. It has also been reported that a slow-release formulation, delivering a higher concentration of the indirect AMPK activator metformin to the colon for IBD treatment. However, metformin does not optimally activate AMPK, and metformin has other activities, thus this method requires specific formulation development. Therefore, it is not the optimal solution to the problem. The patented compound disclosed by Kallyope Inc. is the first discovery and development of a gut-restricted direct AMPK activator that can reach the target tissue and avoid systemic circulation without the need for complex formulation. The general formula and structure of compound 6 and MK8722 in patent WO2023/097189.The general formula disclosed in patent WO2023097189 (as shown above) represents a class of Benzimidazole-type small molecule compounds with biphenyl substituents. The patent includes 60 embodiments, with Merck's MK-8722 as a reference for comparison. In ADP-Glo assays, the most potent compound, 6, activates recombinant AMPK (EC50 = 0.2 nM), outperforming MK8722’s EC50 = 4.7 nM by 23.5 times. Compound 6 is derived from MK8722 by substituting MK8722's isosorbide substituent with a pyranic acid substituent, then extending the biphenyl substituent of MK8722 to include a nitrogen heterocyclic ethylene glycol substituent. This modification strategy aims to concentrate the drug in the intestine, decreasing systemic distribution and thereby reducing oral bioavailability. The patent also includes research on the structure-activity relationship of changing the 4-membered nitrogen heterocyclic ring to a 5-membered one and aromatic heterocyclic rings, but only reveals in vitro activity data. MK-8722 as an AMPK activator can activate all 12 types of AMPK complexes. Merck reported the discovery process of MK8722 in a 2017 Science paper, which showed its regulatory effect on glucose metabolism and promising effect on diabetes in animal models, without causing hypoglycemia. In tests on rats and marmosets over 6-8 months at high doses of MK-8722, no hypoglycemia incidents were found. However, MK-8722 can induce myocardial hypertrophy, and ultimately, it did not enter clinical trials. The general formula disclosed in patent WO2023097187, which also represents a class of Benzimidazole-type small molecule compounds with biphenyl substituents, includes 130 embodiments, with Merck's MK-8722 and MK3903 as references. The activities of most compounds in this patent exceed the previous one and uniquely, oral PK (pharmacokinetics) data are disclosed. In ADP-Glo assays, the most potent compounds, 30 and 32, activate recombinant AMPK (EC50 < 0.01 nM), compared to MK8722’s EC50 = 4.7 nM and MK3903’s EC50 = 20.9 nM. In C57BL/6 mice, oral bioavailability (F) is 4% (30 mg/kg p.o.), significantly reducing systemic distribution. Compound 32 is derived from MK3903 by substituting its chlorine benzene with difluorobenzene and extending the biphenyl substituent of MK3903 to include a nitrogen heterocyclic ethylene glycol methylester substituent. The patent also includes research on the structure-activity relationship of changing the 4-membered nitrogen heterocyclic ring to a 5-membered one, and aromatic heterocyclic rings. MK3903, also developed by Merck and currently preclinical, is reported to activate only 10 out of the 12 phosphorylated AMPK (pAMPK) complexes, with an EC50 value range from 8 to 40 nM, and max activation >50%. MK-3903 partially activates pAMPK5 (max 36%), but does not activate pAMPK6. Also, MK-3903 has low permeability and is a substrate for the human hepatic uptake transporter proteins OATP1B1 and OATP1B3. These shortcomings also led to Merck's decision not to advance it to clinical trials. See the other patent in the figure below, which primarily involves introducing a sulfonated carboxylic acid segment into a benzimidazole moiety. However, the patent only contains 21 compounds, and the strength of the activity data is merely represented by letters. As shown in the figure, the introduction of three hydroxyethyl substituents and a sulfonated carboxylic acid substituent could potentially enhance intestinal targeting and decrease oral bioavailability. In summary, Kallyope Inc. has disclosed three patents, completed over 200 implementation examples, and led in the discovery and development of MK-3903 and MK-8722 as gut-restricted, direct AMPK activators, which can reach target tissues and avoid systemic circulation without the need for complex formulations.

– Results demonstrate melanocortin agonists may represent a new therapeutic avenue to treat diabetic nephropathy – Open Label Phase 2 clinical study in diabetic kidney disease enrolling patients CRANBURY, N.J., May 30, 2023 /PRNewswire/ -- Palatin Technologies, Inc. (NYSE American: PTN), a biopharmaceutical company developing first-in-class medicines based on molecules that modulate the activity of the melanocortin receptor system, today announced the presentation of the poster "MC1R Agonist PL8177 Protects Against Podocyte Loss in a Streptozotocin-Induced Rat Model of Diabetic Nephropathy" at the International Podocyte Conference May 24-26, 2023 in Philadelphia, PA. The poster was presented by Luipa Khandker, Ph.D., Senior Scientist – Biology, at Palatin. The poster can be found on Palatin's website . The data shows PL8177 treatment of streptozotocin-induced diabetic rats preserved the expression of WT1 protein and the number of podocytes and proximal tubule cells compared to vehicle-treated controls. The data also demonstrated that glomerular hypertrophy, a characteristic of kidney injury, trended toward reduction in PL8177-treated kidneys. "This data in a kidney disease model using a potent melanocortin-1 receptor agonist is yet another example of the potential of the melanocortin system as a target for novel treatments for inflammatory diseases," said Carl Spana, Ph.D., President and CEO of Palatin. "Palatin's research team continues to contribute significant mechanism of action data to the melanocortin field through state-of-the art science and we look forward to the efficacy data from our Phase 2 BREAKOUT clinical study in diabetic kidney disease." A Phase 2 study being conducted by Palatin using bremelanotide, a pan-agonist, which includes potent melanocortin-1 agonism, the BREAKOUT Study, is currently enrolling patients. Additional trial information, including inclusion and exclusion criteria, can be found at via the identifier NCT05709444. About Diabetic (Nephropathy) Kidney Disease Diabetic nephropathy (DN) is the most common cause of end-stage renal disease in the United States and other developed countries. Approximately 30 million US patients have chronic kidney disease (CKD) secondary to the combination of hypertension and Type II diabetes mellitus. Despite this remarkable prevalence, clinicians have little consensus on what comprises optimal therapy. While the widespread use of RAAS blockade and other maneuvers have slowed disease progression, approximately one-third of patients with Type II diabetic nephropathy will progress to end-stage renal disease (ESRD). As a result, much effort has been devoted to understanding the mechanisms by which the diabetic condition leads to the typical histopathologic changes, including mesangial expansion, thickened basement membranes, and loss of podocyte density and functionality. There is evidence that injury to the glomerular podocyte is central to the pathogenesis of diabetic nephropathy and that clinical treatments should be directed toward maintaining podocyte viability. Podocytes are highly differentiated neuron-like cells with limited cell division and replacement capacity. They are central to the support and maintenance of glomerular capillary networks and function as the final barrier in glomerular filtration. Evidence from pre-clinical animal model studies suggests that podocyte losses precede and contribute to progressive diabetic glomerulopathy. About Melanocortins and Kidney Disease Melanocortin receptors comprise a complex system comprised of 5 different receptors with broad and varying physiologic functions. MC1r signals through a G-protein coupled pathway that leads to activation of adenylate cyclase and ultimately stimulation of the serine-threonine kinase activity of protein kinase A. A growing body of work in cell signaling and function of the glomerular podocyte suggests that protein kinase A regulates the formation of footplate processes, cell attachment, and apoptosis. MC1r activation may stabilize podocyte function and survival in diabetes and other conditions of glomerular diseases. About Palatin Palatin is a biopharmaceutical company developing first-in-class medicines based on molecules that modulate the activity of the melanocortin receptor systems, with targeted, receptor-specific product candidates for the treatment of diseases with significant unmet medical need and commercial potential. Palatin's strategy is to develop products and then form marketing collaborations with industry leaders to maximize their commercial potential. For additional information regarding Palatin, please visit Palatin's website at and follow Palatin on Twitter at @PalatinTech. Forward-looking Statements Statements in this press release that are not historical facts, including statements about future expectations of Palatin, such as statements about PL8177 preclinical and clinical results for ulcerative colitis and gastrointestinal inflammatory diseases, are "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933, Section 21E of the Securities Exchange Act of 1934 and as that term is defined in the Private Securities Litigation Reform Act of 1995. Palatin intends that such forward-looking statements be subject to the safe harbors created thereby. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that could cause Palatin's actual results to be materially different from its historical results or from any results expressed or implied by such forward-looking statements. Palatin's actual results may differ materially from those discussed in the forward-looking statements for reasons including, but not limited to, results of clinical trials, regulatory actions by the FDA and other regulatory and the need for regulatory approvals, Palatin's ability to fund development of its technology and establish and successfully complete clinical trials, the length of time and cost required to complete clinical trials and submit applications for regulatory approvals, products developed by competing pharmaceutical, biopharmaceutical and biotechnology companies, commercial acceptance of Palatin's products, and other factors discussed in Palatin's periodic filings with the Securities and Exchange Commission. Palatin is not responsible for updating events that occur after the date of this press release. Palatin Technologies® is a registered trademark of Palatin Technologies, Inc. Company Codes: AMEX:PTN