PIM3

PIM Kinases have emerged as promising therapeutic targets for cancer treatment, offering new avenues for the development of targeted therapies aimed at combating tumor growth and progression. As key regulators of cell survival and proliferation, dysregulated PIM kinase signaling plays a critical role in oncogenesis, making them attractive targets for intervention in various cancer types. The exploration of PIM kinases as therapeutic targets represents a significant advancement in the field of precision medicine, with the potential to improve patient outcomes and overcome resistance to conventional cancer treatments. PIM kinases belong to a family of serine/threonine protein kinases comprising thee isoforms – PIM-1, PIM-2 and PIM-3. These kinases are involved in multiple signaling pathways implicated in cancer development, and progression, including cell cycle regulation, apoptosis and cellular metabolism. Aberrant activation of PIM kinases have been observed in a wide range of cancer types where they promote tumor cell survival, proliferation and resistance to apoptosis. Additionally, PIM kinases have been associated with poor prognosis and treatment resistance in cancer patients, underscoring their significant as potential therapeutic targets. Download Insight: The dysregulated expression and activity of PIM kinases in cancer cells make them attractive targets for therapeutic interventions. By selectively inhibiting PIM kinase activity, it is possible to disrupt key signaling pathways involved in tumor growth and survival, thereby inhibiting cancer cells proliferation and inducing cell death. Moreover, targeting PIM kinases offers the potential to overcome resistance to conventional cancer therapies, such as chemotherapy and targeted therapies, by targeting alternative survival pathways utilized by cancer cells. Preclinical studies have provided compelling evidence supporting the efficacy of PIM kinase inhibitors like AZD1208, SGI-1776 and LGH447 in inhibiting tumor growth and enhancing the sensitivity of cancer cells to chemotherapy and targeted therapies. In various cancer models, including leukemia, lymphoma, myeloma and prostate cancer, PIM kinase inhibitors have demonstrated potent anticancer activity and favorable safety pro These promising preclinical findings have paved the way for the evaluation in PIM kinase inhibitors in clinical trials. Clinical trials evaluating the safety and efficacy of PIM kinase inhibitors in cancer patients are underway, with encouraging preliminary findings reported in some studies. While challenges, such as dose-limiting toxicities and patient selection criteria need to be addressed, early clinical data suggests that PIM kinase inhibitors have the potential to be valuable addition to cancer treatment repertoire. Continued research efforts are focused on optimizing dosing regiments, identifying predictive biomarkers, and exploring combination therapies to maximize the therapeutic benefits of PIM kinase targeting therapies. The global market of PIM kinase targeted therapies have also witnessed some collaborations and license agreement coming to light, presenting the determination of researchers to bring these therapies into the clinical. Examples include the license agreement that Inflection Biosciences signed with AUM Biosciences to conduct the development of IBL-302, also known as AUM302, a first-in-class triple inhibitor of pan-PIM, pan-PI3K and mTOR kinases, presently in IND-enabling trials for neuroblastoma and cancers with PI3KCA mutations. Additionally, AUM302 was granted the Rare Pediatric Disease Designation from the FDA in January 2023 for the treatment of neuroblastoma, which came right after the agency designated it as an orphan drug for the same indication in November 2022. These designations signify recognition of its anticancer activities in neuroblastoma, presenting it as a promising clinical candidate to treat this rare cancer type. Looking into the future, the prospects of PIM kinase targeted therapies market for cancer looks promising, with ongoing research aimed at refining treatment strategies and expanding the therapeutic range. Advances in drug discovery technologies are facilitating the development of next-generation PIM kinase inhibitors with improved potency, selectivity and pharmacokinetic properties. Additionally, the identification of biomarkers predictive of response to PIM kinase inhibitors may enable more personalized treatment schedules, enhancing clinical outcomes and minimizing adverse effects. Furthermore, exploring the potential of combination therapies involving PIM Kinase inhibitors with other targeted agents, immunotherapies, conventional chemotherapy or radiation therapy holds promise for overcoming resistance mechanisms and improving treatment efficacy. Collaborative efforts between universities, hospitals and cancer research centers will be essential to advance the clinical development of PIM kinase inhibitors. In conclusion, PIM kinase targeted therapies represent attractive therapeutic targets for cancer treatment, offering the potential to disrupt key cancer signaling processes. Preclinical and early clinical data support the efficacy of PIM kinase inhibitors in inhibiting tumor growth and enhancing treatment response in various cancer types, primarily hematological cancers. With research underway for optimizing the dosing and treatment strategies, PIM kinase targeted therapies are poised to transform the landscape of cancer treatment.

MARCO ISLAND, Fla., Feb. 22, 2023 /PRNewswire/ -- In the fight against cancer, the next step could be evolutionary. Impact BioMedical and its research partner Global Research and Discovery Group today announced that they have finished the first phase of a groundbreaking project that could give humans the edge over cancer. The BNE-1 Antibody Project is the next evolutionary step of cancer research, seeking to develop cancer-suppressing antibodies that would give the human body the ability to not only fight against most cancers, but win. Impact BioMedical and GRDG researchers said that they had successfully completed cloning three new antibody libraries and will now move ahead to advanced "tumor-killing assays" to determine the scope of efficacy against most of the cancers that are available for analysis. "I am very pleased that we now have the antibodies successfully cloned, stable in stasis and look forward to beginning the second phase of this work," said Daryl Thompson, Director of Scientific Initiatives at Global Research and Discovery Group. "As we progress, this research will give us new insights on not only the ways of fighting cancer, but also how the human body can respond and thrive in the face of threats." The BNE-1 Antibody Project got its genesis in a previous cancer-fighting effort, the CRST-1 Project. The earlier research focused on developing a natural, cancer-fighting drug, which inspired by a friendship between Thompson and Marco Island native Christy Bastian. Thompson met Christy Bastian in August 2020 through a mutual friend and the two sparked a friendship. When they met, Bastian was in her second cancer battle. She had fought breast cancer into remission in 2012, but was stricken with a rare and aggressive cancer in 2020 when she met Thompson. Despite her decade-long cancer battles, she had maintained a positive attitude, but the fight had taken its toll, she told Thompson. Her resolve to fight struck a chord with Thompson, who reasoned that instead of focusing on a person's will to fight, why not focus on cutting cancer's ability to attack. "I was literally sitting there listening to someone tell their story about how they're dealing with cancer, and I realized that it's not how hard you punch, but maybe it's more just a will to fight?" said Thompson. "If her will to fight is working for her survival, what if we could take that away cancer's 'will to fight', its tenacity. That's Pim." Pim (proviral integration site for moloney murine leukemia virus) according to the National Institutes of Health, plays a key role in the expression or activation of several cancers. According to Thompson, PIM is what stimulates a cancer cell's ability to fight against drugs that are designed to kill it. Shutting down PIM will shut down cancer's ability to live. That work led to the identification of the molecule that assists in inhibiting Pim, CRST-1 — named after Christy Bastian. "When Daryl told me about the concept of the CRST-1, and how he came to that name, I was honored," said Bastian. "To be affiliated with the initial research and to now to see how this next evolutionary phase develops gives me hope that one day cancer will be a thing of the past." CRST-1 is a non-toxic treatment that has no side effects. It is designed to accompany traditional cancer treatments to increase the effectiveness of the drugs used. It was shown to inhibit PIM 1 and PIM 3 respectively in cell phosphorylation assays. "The CRST-1 project yielded an important drug discovery," said Thompson. "The current BNE-1 project is the next step from CRST-1, to develop cancer-suppressing antibodies." And as with the CRST-1 Project, which is named after Christy, the BNE-1 Project is named in honor of a friend's wife who passed from cancer, Bonnie. "This research is personal for me, and the development of these new strategies should be personal for anyone who knows or has known someone who has fought this disease," said Thompson. The impact of this research could also have a global impact, according to Roscoe Moore, GRDG Chief Scientific Advisor Dr. Roscoe M. Moore, Jr., the retired United States Assistant Surgeon General and former Epidemic Intelligence Services (EIS) Officer at the U.S. Centers for Disease Control. "This line of research represented in BNE-1 Project is important because it is based in naturally-occurring phenomena and, as such, is easier to replicate around the world, especially in places where advanced medical cancers therapies are not readily available," said Moore. The announcement of a successful end of the first phase of research is relevant as it comes on the edge of the Marco Island "Imagination Ball" held later this month at the JW Marriot as a fundraiser for the American Cancer Society. The CRST-1 project — and Christy Bastian's story — was first revealed at the Imagination Ball several years ago at the Project's inception. "I am especially fond of the Imagination Ball, as I have always considered Marco Island and the Everglades home," said GRDG's Thompson. "I view this current BNE-1 project and as one of our most challenging but important projects in part because it was inspired and conceptualized at Marco Island, which I find endearing." About Impact BioMedical, Inc. Impact BioMedical, Inc. ("Impact BioMedical") is a wholly owned subsidiary of DSS. Impact BioMedical strives to leverage its scientific know-how and intellectual property rights to provide solutions that have been plaguing the biomedical field for decades. By tapping into the scientific expertise of GRDG Sciences, LLC, Impact BioMedical pledges to undertake a concerted effort in the R&D, drug discovery and development for the prevention, inhibition, and treatment of neurological, oncological and immuno -related diseases. For more information on Impact BioMedical visit . Media Contact: Don Manley 239-206-6920 354233@email4pr.com

Dublin, Ireland, December 5, 2022 Inflection Biosciences Ltd, a company developing innovative therapeutics for the treatment of cancer, autoimmune and inflammatory diseases today announced that new data on IBL-101, a pan-PIM kinase inhibitor, which is being developed for autoimmune and inflammatory disease, will be highlighted in a poster presentation at the British Society for Immunology Congress 2022 taking place from December 5-8, 2022 in Liverpool, U.K. The pre-clinical data was generated through a collaboration between Inflection Biosciences and Trinity College Dublin, led by Professor Patrick T. Walsh, Department of Clinical Medicine, School of Medicine, Trinity College Dublin (TCD). National Children's Research Centre (NCRC), Children's Health Ireland Crumlin, Dublin. The collaboration was funded by Enterprise Ireland. Professor Pat Walsh commented “The data shows that PIM genes are up-regulated in psoriatic patients’ skin and in a mouse model of psoriasis. IBL-101 was able to suppress inflammatory cytokine production and skew T helper cells towards an iTreg cell phenotype. The results provide proof of concept for IBL-101 as a potential treatment for psoriasis and other autoimmune diseases such as rheumatoid arthritis, inflammatory bowel disease and lupus nephritis.” The details for the poster presentation are as follows: Poster Title: Investigation of a novel pan-PIM kinase inhibitor, IBL-101, as a potential treatment for psoriasis Poster Session: 1 Time & Date: 6.00 pm – 7.30 pm; Tuesday 6, December 2022 Presenter: Dr. Yasmina Esther Hernández-Santana Poster Board No.: 461 Location: ACC Liverpool, Hall 2 The full abstract can be viewed here. About IBL-101 IBL-101 is a small molecule, orally available, pan-PIM kinase inhibitor in preclinical stage of development. The PIM family of serine/threonine kinases, consisting of PIM-1, PIM-2, and PIM-3, controls cell survival, proliferation, and apoptosis. PIM kinases are involved in key autoimmune and inflammatory processes through regulation of T and B cell function. Expression of PIM kinases is regulated by the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, a critical signal transduction pathway which is dysregulated in autoimmune and inflammatory disease. JAK kinase inhibitors have been successfully developed for indications such as rheumatoid arthritis, inflammatory bowel disease and psoriasis, but carry warnings due to potential severe side effects. Downstream cellular targeting of the JAK/STAT pathway via PIM kinase inhibition may reduce the risk of these side effects thus allowing for a safer therapeutic approach. About Inflection Biosciences Inflection Biosciences Ltd is developing small molecule therapeutics for the treatment of cancer, autoimmune and inflammatory diseases. IBL-101 is a pan-PIM kinase inhibitor in preclinical development for the treatment of autoimmune and inflammatory diseases. IBL-202 is a first-in-class, dual PIM kinase and PI3K inhibitor in development for aggressive B-cell malignancies, T-cell lymphoma and acute myeloid leukemia. The partnered pipeline comprises first-in-class AUM302, a PIM/PI3K/mTOR inhibitor being developed by AUM Biosciences. For more information, please visit www.inflectionbio.com For further information contact: Inflection Biosciences Ltd Darren Cunningham, Chief Executive Officer E: dcunningham@inflectionbio.com T: +353 (0)1 4003615