CGAS

MAIA seeks to advance two new THIO-derived telomere-targeting molecules to clinical trials CHICAGO--(BUSINESS WIRE)-- MAIA Biotechnology, Inc., (NYSE American: MAIA) (“MAIA”, the “Company”), a clinical-stage biopharmaceutical company developing targeted immunotherapies for cancer, today announced that an abstract related to the company’s second generation of proprietary telomere-targeting THIO prodrugs has been accepted for poster presentation during the upcoming 36 th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, taking place October 23-25, 2024, in Barcelona, Spain. The Symposium is hosted by the European Organisation for Research and Treatment of Cancer (EORTC), the National Cancer Institute (NCI) and the American Association for Cancer Research (AACR). MAIA will present the results of preclinical studies for its new THIO-based prodrugs, designated as MAIA-2021-20 and MAIA-2022-12, which are lipid-conjugated compounds derived from THIO. These second-generation compounds belong to a new chemical class of molecules called telomere targeting divalent dinucleotides. These preclinical studies were designed to evaluate the efficacy of the new molecules alone and in combination with or without immune checkpoint-blocking antibodies (anti-PD-L1). MAIA’s Chief Scientific Officer Sergei Gryaznov, Ph.D. commented, “Our presentation will demonstrate that treatment with each of the prodrugs studied was highly efficacious and was shown to overcome immunotherapy resistance. Our results have shown marked activity in advanced tumors and resulted in tumor growth inhibition in preclinical models of lung cancer, colorectal carcinoma, melanoma and hepatocellular carcinoma. We are actively working to advance these candidates toward clinical development.” Presentation details: Title: New Dual-Pharmacophore Dinucleotide Prodrugs as Potent Telomere Targeting Anticancer Molecules Abstract number: ENA24-0044 Session title: New Drugs Date and time: Wednesday, October 23, 2024, at noon CEST Presenting author: Ilgen Mender, Ph.D., Director of Biology Research, MAIA Biotechnology Poster access: MAIA’s poster will be available at maiabiotech.com/publications on October 23, 2024 MAIA has designed and evaluated more than 80 THIO-like compounds to date and has submitted three U.S. patent applications for its second-generation telomere targeting agents. About THIO THIO (6-thio-dG or 6-thio-2’-deoxyguanosine) is a first-in-class investigational telomere-targeting agent currently in clinical development to evaluate its activity in Non-Small Cell Lung Cancer (NSCLC). Telomeres, along with the enzyme telomerase, play a fundamental role in the survival of cancer cells and their resistance to current therapies. The modified nucleotide 6-thio-2’-deoxyguanosine (THIO) induces telomerase-dependent telomeric DNA modification, DNA damage responses, and selective cancer cell death. THIO-damaged telomeric fragments accumulate in cytosolic micronuclei and activates both innate (cGAS/STING) and adaptive (T-cell) immune responses. The sequential treatment with THIO followed by PD-(L)1 inhibitors resulted in profound and persistent tumor regression in advanced, in vivo cancer models by induction of cancer type–specific immune memory. THIO is presently developed as a second or later line of treatment for NSCLC for patients that have progressed beyond the standard-of-care regimen of existing checkpoint inhibitors. About MAIA Biotechnology, Inc. MAIA is a targeted therapy, immuno-oncology company focused on the development and commercialization of potential first-in-class drugs with novel mechanisms of action that are intended to meaningfully improve and extend the lives of people with cancer. Our lead program is THIO, a potential first-in-class cancer telomere targeting agent in clinical development for the treatment of NSCLC patients with telomerase-positive cancer cells. For more information, please visit . Forward Looking Statements MAIA cautions that all statements, other than statements of historical facts contained in this press release, are forward-looking statements. Forward-looking statements are subject to known and unknown risks, uncertainties, and other factors that may cause our or our industry’s actual results, levels or activity, performance or achievements to be materially different from those anticipated by such statements. The use of words such as “may,” “might,” “will,” “should,” “could,” “expect,” “plan,” “anticipate,” “believe,” “estimate,” “project,” “intend,” “future,” “potential,” or “continue,” and other similar expressions are intended to identify forward looking statements. However, the absence of these words does not mean that statements are not forward-looking. For example, all statements we make regarding (i) the initiation, timing, cost, progress and results of our preclinical and clinical studies and our research and development programs, (ii) our ability to advance product candidates into, and successfully complete, clinical studies, (iii) the timing or likelihood of regulatory filings and approvals, (iv) our ability to develop, manufacture and commercialize our product candidates and to improve the manufacturing process, (v) the rate and degree of market acceptance of our product candidates, (vi) the size and growth potential of the markets for our product candidates and our ability to serve those markets, and (vii) our expectations regarding our ability to obtain and maintain intellectual property protection for our product candidates, are forward looking. All forward-looking statements are based on current estimates, assumptions and expectations by our management that, although we believe to be reasonable, are inherently uncertain. Any forward-looking statement expressing an expectation or belief as to future events is expressed in good faith and believed to be reasonable at the time such forward-looking statement is made. However, these statements are not guarantees of future events and are subject to risks and uncertainties and other factors beyond our control that may cause actual results to differ materially from those expressed in any forward-looking statement. Any forward-looking statement speaks only as of the date on which it was made. We undertake no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law. In this release, unless the context requires otherwise, “MAIA,” “Company,” “we,” “our,” and “us” refers to MAIA Biotechnology, Inc. and its subsidiaries. Contacts Investor Relations Contact +1 (872) 270-3518 ir@maiabiotech.com

Safety, pharmacokinetics and target engagement data from first-in-human Phase 1 clinical trial in healthy volunteers will potentially enable rapid advancement of IMSB301 into Phase 1b/2 clinical studies in Type I interferonopathies Oct. 08, 2024 -- ImmuneSensor Therapeutics, a clinical-stage biotherapeutics company focused on the development of first- and best-in-class inhibitors and agonists targeting the cGAS-STING pathway to address diverse peripheral and CNS indications in inflammation, autoimmunity and oncology, announced today that the first dose level cohort of healthy volunteers has been dosed in a Phase 1 randomized, double-blinded, placebo-controlled clinical trial of its lead oral cGAS inhibitor drug candidate, IMSB301, which is being developed for the treatment of a range of inflammatory and autoimmune diseases. The company’s approach and technology are based on the discoveries of Dr. Zhijian “James” Chen, whose groundbreaking work was recognized with the 2024 Albert Lasker Basic Medical Research Award. “The cGAS-STING pathway is a central mediator of inflammation, and inhibiting the cGAS enzyme provides a therapeutic approach that has the potential to address diverse unmet medical needs across diverse inflammatory diseases,” said Tom Dubensky, Ph.D., ImmuneSensor’s president and chief executive officer. “We anticipate having safety, pharmacokinetic, and target engagement data from our Phase 1 trial in healthy volunteers by the end of 2024, positioning us to efficiently transition into Phase 1b/2 clinical studies for patients with severe inflammatory conditions, specifically Type 1 interferonopathies. Our clinical strategy is to first evaluate IMSB301 in patients with Aicardi-Goutières syndrome (AGS), a rare inflammatory disease driven by chronic activation of the cGAS pathway. We will then assess IMSB301 in defined patient populations with cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE).” ImmuneSensor’s Phase 1 randomized, placebo-controlled, double-blinded clinical trial of IMSB301 is being conducted in healthy volunteers in Australia. The primary endpoint of the clinical study is safety and tolerability, along with pharmacokinetics (PK) and engagement (inhibition) of the cGAS target. The study will enroll cohorts of eight subjects each (two subjects receive placebo and six subjects receive IMSB301 at each dose) with up to five single ascending dose (SAD) levels, and subsequently up to three multiple ascending dose (MAD) levels. PK will be assessed in both SAD and MAD arms and cGAS target engagement will be evaluated in the MAD arm using an ex vivo whole blood DNA stimulation assay. The first dose cohort of the SAD arm has been completed with the observed exposure levels and PK as predicted from nonclinical IND-enabling studies. The cGAS-STING pathway works to detect (“sense”) both host-derived and foreign cytoplasmic DNA produced as a result of infection or cell damage due to inflammation or malignancy. In autoimmune diseases, the innate immune response is chronically activated, directly promoting inflammation and the development of autoimmunity, both in the periphery and the central nervous system (CNS). IMSB301 is a novel, orally available small molecule designed to specifically inhibit the cGAS enzyme to prevent production of the cGAMP signaling molecule and halt pathologic inflammation. In preclinical studies, IMSB301 has been demonstrated to be a potent and specific inhibitor of cGAS enzymatic activity that results in a profound suppression of cytokine production and rescue of the disease phenotype and premature death in a model of AGS. ImmuneSensor is developing IMSB301 initially in cGAS-driven Type I interferonopathies including AGS, as well as CLE and selected patient populations with SLE. IMSB301 has the potential to address other diverse therapeutic areas that are characterized by cGAS-driven inflammation including diabetic kidney diseases, age-related macular degeneration, and other autoimmune disorders. About Type I interferonopathies: Aicardi Goutières Syndrome (AGS), Systemic Lupus Erythematosus (SLE) and Cutaneous Lupus Erythematosus (CLE) AGS is a rare genetic severe inflammatory disease in pediatric and adult populations, affecting the brain (demyelination) and peripheral tissues (lungs, liver, heart, skin) caused by germline mutations in upstream cytosolic nuclease genes, including TREX-1, that triggers chronic production of Type I interferon (IFN-I) and pro-inflammatory cytokines resulting from chronic activation of cGAS and the production of downstream signaling molecules. The disease has no cure and is currently treated with drugs designed to manage symptoms. SLE is a complex autoimmune disorder that can be associated with the dysregulated production of IFN-I and other pro-inflammatory cytokines, which is thought to play a pivotal role in the pathogenesis of the disease. The disease is characterized by heterogeneous clinical manifestations, involving the skin, blood vessels, kidneys and central nervous system, which can result in serious organ damage and appears to develop when individuals with a genetic predisposition for the disease come into contact with an environmental “trigger.” The CDC estimates that approximately 204,000 people in the United States have SLE, the most common type of lupus, with nine times as many women as men likely to develop the disease. Current standard of care involves treatment with anti-inflammatory drugs and immunosuppressants. CLE is an autoimmune disease that causes the body's immune system to attack healthy skin cells, resulting in a red, scaly rash. There are several types of CLE that are often triggered by sunlight, it can also arise as a complication of SLE. While it can affect people of any age or gender, it is most common among women 20 to 50 years old. There is no cure for CLE, and its symptoms are currently managed with anti-inflammatory drugs, immunosuppressants and lifestyle changes. ImmuneSensor is a privately held, clinical stage company founded on the groundbreaking discovery of cGAS and cGAMP along with their combined role in regulating immunity, by Dr. Zhijian Chen’s laboratory at the University of Texas Southwestern Medical Center, a breakthrough that has profoundly impacted both the scientific and pharmaceutical fields. ImmuneSensor is dedicated to developing best-in-class small molecule inhibitors and agonists of the cGAS-STING signaling pathway to potentially address therapeutic areas with significant unmet medical need in autoimmunity, inflammation and oncology. For more information about ImmuneSensor, visit: www.immunesensor.com The content above comes from the network. if any infringement, please contact us to modify.

Safety, pharmacokinetics and target engagement data from first-in-human Phase 1 clinical trial in healthy volunteers will potentially enable rapid advancement of IMSB301 into Phase 1b/2 clinical studies in Type I interferonopathies DALLAS, TX, USA I October 08, 2024 I ImmuneSensor Therapeutics, a clinical-stage biotherapeutics company focused on the development of first- and best-in-class inhibitors and agonists targeting the cGAS-STING pathway to address diverse peripheral and CNS indications in inflammation, autoimmunity and oncology, announced today that the first dose level cohort of healthy volunteers has been dosed in a Phase 1 randomized, double-blinded, placebo-controlled clinical trial of its lead oral cGAS inhibitor drug candidate, IMSB301, which is being developed for the treatment of a range of inflammatory and autoimmune diseases. The company’s approach and technology are based on the discoveries of Dr. Zhijian “James” Chen, whose groundbreaking work was recognized with the 2024 Albert Lasker Basic Medical Research Award. “The cGAS-STING pathway is a central mediator of inflammation, and inhibiting the cGAS enzyme provides a therapeutic approach that has the potential to address diverse unmet medical needs across diverse inflammatory diseases,” said Tom Dubensky, Ph.D., ImmuneSensor’s president and chief executive officer. “We anticipate having safety, pharmacokinetic, and target engagement data from our Phase 1 trial in healthy volunteers by the end of 2024, positioning us to efficiently transition into Phase 1b/2 clinical studies for patients with severe inflammatory conditions, specifically Type 1 interferonopathies. Our clinical strategy is to first evaluate IMSB301 in patients with Aicardi-Goutières syndrome (AGS), a rare inflammatory disease driven by chronic activation of the cGAS pathway. We will then assess IMSB301 in defined patient populations with cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE).” ImmuneSensor’s Phase 1 randomized, placebo-controlled, double-blinded clinical trial of IMSB301 is being conducted in healthy volunteers in Australia. The primary endpoint of the clinical study is safety and tolerability, along with pharmacokinetics (PK) and engagement (inhibition) of the cGAS target. The study will enroll cohorts of eight subjects each (two subjects receive placebo and six subjects receive IMSB301 at each dose) with up to five single ascending dose (SAD) levels, and subsequently up to three multiple ascending dose (MAD) levels. PK will be assessed in both SAD and MAD arms and cGAS target engagement will be evaluated in the MAD arm using an ex vivo whole blood DNA stimulation assay. The first dose cohort of the SAD arm has been completed with the observed exposure levels and PK as predicted from nonclinical IND-enabling studies. About IMSB301 The cGAS-STING pathway works to detect (“sense”) both host-derived and foreign cytoplasmic DNA produced as a result of infection or cell damage due to inflammation or malignancy. In autoimmune diseases, the innate immune response is chronically activated, directly promoting inflammation and the development of autoimmunity, both in the periphery and the central nervous system (CNS). IMSB301 is a novel, orally available small molecule designed to specifically inhibit the cGAS enzyme to prevent production of the cGAMP signaling molecule and halt pathologic inflammation. In preclinical studies, IMSB301 has been demonstrated to be a potent and specific inhibitor of cGAS enzymatic activity that results in a profound suppression of cytokine production and rescue of the disease phenotype and premature death in a model of AGS. ImmuneSensor is developing IMSB301 initially in cGAS-driven Type I interferonopathies including AGS, as well as CLE and selected patient populations with SLE. IMSB301 has the potential to address other diverse therapeutic areas that are characterized by cGAS-driven inflammation including diabetic kidney diseases, age-related macular degeneration, and other autoimmune disorders. About Type I interferonopathies: Aicardi Goutières Syndrome (AGS), Systemic Lupus Erythematosus (SLE) and Cutaneous Lupus Erythematosus (CLE) AGS is a rare genetic severe inflammatory disease in pediatric and adult populations, affecting the brain (demyelination) and peripheral tissues (lungs, liver, heart, skin) caused by germline mutations in upstream cytosolic nuclease genes, including TREX-1, that triggers chronic production of Type I interferon (IFN-I) and pro-inflammatory cytokines resulting from chronic activation of cGAS and the production of downstream signaling molecules. The disease has no cure and is currently treated with drugs designed to manage symptoms. SLE is a complex autoimmune disorder that can be associated with the dysregulated production of IFN-I and other pro-inflammatory cytokines, which is thought to play a pivotal role in the pathogenesis of the disease. The disease is characterized by heterogeneous clinical manifestations, involving the skin, blood vessels, kidneys and central nervous system, which can result in serious organ damage and appears to develop when individuals with a genetic predisposition for the disease come into contact with an environmental “trigger.” The CDC estimates that approximately 204,000 people in the United States have SLE, the most common type of lupus, with nine times as many women as men likely to develop the disease. Current standard of care involves treatment with anti-inflammatory drugs and immunosuppressants. CLE is an autoimmune disease that causes the body’s immune system to attack healthy skin cells, resulting in a red, scaly rash. There are several types of CLE that are often triggered by sunlight, it can also arise as a complication of SLE. While it can affect people of any age or gender, it is most common among women 20 to 50 years old. There is no cure for CLE, and its symptoms are currently managed with anti-inflammatory drugs, immunosuppressants and lifestyle changes. About ImmuneSensor Therapeutics ImmuneSensor is a privately held, clinical stage company founded on the groundbreaking discovery of cGAS and cGAMP along with their combined role in regulating immunity, by Dr. Zhijian Chen’s laboratory at the University of Texas Southwestern Medical Center, a breakthrough that has profoundly impacted both the scientific and pharmaceutical fields. ImmuneSensor is dedicated to developing best-in-class small molecule inhibitors and agonists of the cGAS-STING signaling pathway to potentially address therapeutic areas with significant unmet medical need in autoimmunity, inflammation and oncology. For more information about ImmuneSensor, visit: www.immunesensor.com SOURCE: ImmuneSensor Therapeutics