PIM2

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.

CAMBRIDGE, Mass., June 8, 2022 /PRNewswire/ -- Sumitomo Pharma Oncology, Inc., a clinical-stage company focused on novel cancer therapeutics, today announced the U.S. Food Drug and Administration (FDA) granted Orphan Drug Designation for TP-3654, the company's proprietary investigational oral inhibitor of PIM kinases, for the treatment of myelofibrosis. "This designation is an important milestone in the development of TP-3654 and highlights the need for potential new treatment options for patients with myelofibrosis," said Patricia S. Andrews, CEO and Global Head of Oncology, Sumitomo Pharma Oncology, Inc. "This rare hematologic cancer can also progress and worsen. We are excited about collaborating with investigators to advance this clinical-stage asset with the goal of improving patient outcomes." The FDA's Orphan Drug Designation is granted to investigational therapies addressing rare medical diseases or conditions that affect fewer than 200,000 people in the United States. Myelofibrosis is a rare type of bone marrow cancer which disrupts an individual's normal production of blood cells.1 Myelofibrosis has approximately 1.5 reported cases per 100,000 people each year in the United States.2 "TP-3654 is an investigational oral inhibitor of PIM kinases. PIM kinases have potential antitumor and anti-fibrotic effects through multiple pathways, including induction of apoptosis.3,4 Notably, PIM kinase expression correlates with increased cell survival and reduced apoptosis in tumors, supporting the potential of PIM kinases as novel therapeutic targets,"3 explained Jatin J. Shah, M.D, Chief Medical Officer of Sumitomo Pharma Oncology, Inc. "PIM-1 expression is significantly elevated in myelofibrosis hematopoietic cells and therefore a potential therapeutic target for myelofibrosis."4 TP-3654 is currently being evaluated in a Phase 1/2, multicenter, dose-escalation, open-label trial to assess safety, tolerability, pharmacokinetics, and pharmacodynamics in patients with intermediate or high-risk primary or secondary myelofibrosis. It is being conducted in the United States and Japan. To learn more about the study and eligibility for enrollment visit clinicaltrials.gov (NCT04176198). About TP-3654 TP-3654 is an oral investigational inhibitor of PIM kinases, which has potential antitumor and anti-fibrotic effects through multiple pathways, including induction of apoptosis.3,4 TP-3654 inhibited proliferation and increased apoptosis in murine and human hematopoietic cells expressing clinically relevant JAK2V617F mutation.4 TP-3654 alone and in combination with ruxolitinib normalized WBC and neutrophil counts, and reduced spleen size and bone marrow fibrosis in JAK2V617F and MPLW515L murine models of myelofibrosis.4 TP-3654 is currently being evaluated in two clinical trials; A Phase 1 study to treat TP-3654 in patients with advanced solid tumors (NCT03715504); A Phase 1/2 study of oral TP-3654 in patients with intermediate and high-risk myelofibrosis (NCT04176198). About Sumitomo Pharma Oncology Sumitomo Pharma Oncology, Inc., is a wholly owned subsidiary of Sumitomo Pharma Co., Ltd. As a global oncology organization with teams in the U.S. and Japan, SMP Oncology is committed to advancing purposeful science by transforming new discoveries into meaningful treatments for patients with cancer. SMP Oncology's robust and diverse pipeline of preclinical and advanced-stage assets spans multiple areas, including oncogenic pathways, survival mechanisms and novel protein interactions, which aim to address unmet clinical needs in oncology. For more information, visit . About Sumitomo Pharma Sumitomo Pharma is among the top-ten listed pharmaceutical companies in Japan, operating globally in major pharmaceutical markets, including Japan, the U.S., China, and other Asian countries with more than 7,000 employees worldwide. Sumitomo Pharma defines its corporate mission as "To broadly contribute to society through value creation based on innovative research and development activities for the betterment of healthcare and fuller lives of people worldwide." Additional information about Sumitomo Pharma is available through its corporate website at . Disclaimer Regarding Forward-Looking Statements This press release contains "forward-looking statements," as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding the research, development, and commercialization of pharmaceutical products. The forward-looking statements in this press release are based on management's assumptions and beliefs in light of information presently available and involve both known and unknown risks and uncertainties. Any forward-looking statements set forth in this press release speak only as of the date of this press release. We do not undertake to update any of these forward-looking statements to reflect events or circumstances that occur after the date hereof. Information concerning pharmaceuticals (including compounds under development) contained within this material is not intended as advertising or medical advice. References 1. "Myelofibrosis - Symptoms And Causes". Mayo Clinic, 2022, . 2. "Myelofibrosis; Causes, Symptoms, Treatment & Prevention". Cleveland Clinic, 2022, . 3. Foulks JM, Carpenter KJ, Luo B, et al. A small-molecule inhibitor of PIM kinases as a potential treatment for urothelial carcinomas. Neoplasia. 2014;16(5):403-412. 4. Nath D, Yang Y, Dutta A, Whatcott C. The PIM kinase inhibitor TP-3654 in combination with ruxolitinib exhibits marked improvement of myelofibrosis in murine models. Blood. 2018. doi:10.1182/blood-2018-99-119421. SOURCE Sumitomo Pharma Oncology, Inc.

ESCHBORN, Germany, May 30, 2022 Innoplexus, a global leader in AI-based drug discovery and development, and Inflection Biosciences Ltd., an innovative biotechnology company focused upon developing innovative small molecule therapeutics for the treatment of cancer, autoimmune and inflammatory diseases, are partnering to accelerate development of Inflection Biosciences’ preclinical stage, pan-PIM kinase inhibitor IBL-101. The partnership aims to optimize and expedite development of IBL-101 by using Innoplexus’ Ontology and its state-of-the-art Artificial Intelligence and Machine Learning technologies to identify the most promising and targetable indications across all therapeutic areas. During this process, Innoplexus will also d etermine combinatorial partnersfor IBL-101 and identify biomarkers that will foster the identification of the most suitable patients potentially benefiting the most from this therapy based on their pheno- and genotypes. Darren Cunningham, CEO and Co-Founder of Inflection Biosciences commented: “This collaboration with leading AI company Innoplexus will build on our expertise in PIM kinase and will allow us to identify the very best application of our IBL-101 program from across many therapeutic areas. It aims to provide insights that will allow for a more effective development strategy, shortening approval lead times and cutting down upon development cost, which should ultimately benefit those patients who are in need of new treatments.” The partnership will leverage Innoplexus’ artificial intelligence platform called Ontosight, which delves into terabytes of unstructured and structured data extracting the relevant life science information requested and required. Innoplexus’ Life Science Language Processing™, with a self-learning Ontology of over 30 million biomedical concepts and terms, is going to be used to identify the links between the target protein, signaling pathways, mechanism of action of th e drug and diseases. It will also provide data driven insights and recommendations for selecting indications for IBL-101 with high likelihood of success in clinical trials. Furthermore, Ontosight will also lay the groundwork for identifying optimal combinatorial therapy and identifying specific patient groups that are most likely to respond based on omic biomarkers. Prof. Juergen Scheele, MD, PhD, SVP and CMO at Innoplexus, highlights the importance of leveraging AI-driven insights to power drug discovery and development: “Using Innoplexus’ AI and Ontology, which possesses the capabilities to collect and structure the existing world of research on kinase inhibitors, it is possible toidentify the most promising avenues for further clinical research at incredible speed.” According to the terms of the collaboration, Innoplexus will receive upfront equity in Inflection Biosciences, along with milestone payments subject to meeting specific conditions of the collaboration. Innoplexus will also be remunerated in royalties on sales of IBL-101, once results from the collaboration are utilized in its development and commercialization. No further financial details were disclosed. About IBL-101 IBL-101 is a small molecule, orally available, pan-PIM kinase inhibitor in pre-clinical 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. In addition to being extensively studied in tumorigenesis, the role of PIM kinases has recently been revealed in inflammatory and autoimmune settings. Because the expression of PIM kinases is regulated by the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, PIM kinases are considered a downstream effector of many cytokine signalling pathways which drive inflammation/autoimmunity. In pre-clinical models, PIM kinase inhibition downregulates the production of Th1- and Th17-type cytokines and skews T-cell differentiation towards a Treg phenotype. About Innoplexus Innoplexus is a leading global AI-based company for drug discovery and development with over 300 employees and 120+ patent applications including 50+ grants in artificial intelligence, machine learning and blockchain technologies. Innoplexus' solutions can generate real-time insights from hundreds of terabytes of structured and unstructured private and public data, thereby facilitating continuous, informed decision-making for its customer base at an unparalleled speed. Founded in 2015, Innoplexus AG is headquartered in Eschborn, Germany, with offices in Pune, India, and Iselin and San Francisco, United States. For more information, please visit www.innoplexus.com 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 as a novel clinical target for the treatment of autoimmune/inflammatory diseases. IBL-101 is also in preclinical development for the treatment of solid tumors and treatment resistance. 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: Innoplexus AG Claudia M. Hausoel, Marketing Management E: claudia.hausoel@innoplexus.com T: +49 (0) 151 - 6198 7478 Inflection Biosciences Ltd Darren Cunningham, Chief Executive Officer E: dcunningham@inflectionbio.com T: +353 (0) 1 4003615