CD68

ATLANTA, GA, USA I December 11, 2024 I Expression Therapeutics, Inc., has presented the results of a Phase 1 clinical trial for its novel lentiviral vector-based gene therapy — ET3 — for hemophilia A at the Annual Meeting of the American Society of Hematology (ASH) in San Diego, California. The results of the study, “Lentiviral Gene Therapy with CD34+ Hematopoietic Cells for Hemophilia A” (Srivastava et al ), were published by the New England Journal of Medicine , timed for release with the ASH presentation. Hemophilia A results from a deficiency in blood coagulation Factor VIII (FVIII). It is the most common severe congenital bleeding disorder, with an incidence of approximately 1 in 5,000 live male births. Without treatment, severe hemophilia A is crippling and fatal by late adolescence to early adulthood. The average annual cost per patient of managing hemophilia A in the United States ranges from over $200,000 to $850,000, making it one of the most expensive treatments over a lifetime for any genetic disorder. As a result, a curative gene therapy for hemophilia A can lead to significant long-term cost savings for healthcare systems compared to current prophylaxis treatments, in addition to improved quality of life for patients. New gene therapy offers hope of a permanent cure for hemophilia A patients. The clinical trial, conducted at the Christian Medical College, Vellore, India, recruited five participants 22 to 41 years of age with severe hemophilia A. Autologous hematopoietic stem cells (HSCs) were transduced with CD68-ET3-LV — a lentiviral vector including a novel FVIII transgene (ET3) with a myeloid-directed CD68 promoter. Before gene therapy, all participants reported annualized bleeding rates of at least 20 events. No spontaneous bleeding events occurred in any participant on study. These results were consistent with measured FVIII levels, which in all five participants increased from undetectable to levels predicted to produce therapeutic efficacy. The median follow-up was 14 months (range, 9 to 27 months). Except for neutropenia and thrombocytopenia (which were expected), no adverse events greater than grade 2 occurred in any participant. Inhibitors to FVIII did not develop in any participant after drug-product infusion. Integration-site analysis performed at 4 to 22 months after drug-product infusion showed no safety concerns. The results of this Phase 1 clinical trial validate a new approach to gene therapy for hemophilia A that can provide lifelong durability of expression. The candidate CD68-ET3-LV-CD34+ gene therapy product overcomes the limitations of the AAV gene therapy approaches to hemophilia A, including lack of durability of expression, ineligibility of patients on the basis of age, and preexisting anti-AAV antibody related conditions. Expression Therapeutics lentiviral gene therapy is currently the only approach that offers the possibility of a permanent cure for hemophilia A and provides an opportunity to reach both pediatric and adult populations. “This Phase I clinical trial produced no unexpected safety issues and remarkable clinical efficacy. Lentiviral vector hematopoietic stem cell therapy offers the hope of permanent cure of hemophilia A patients that ultimately may be extended to the pediatric population,” said Pete Lollar, MD, Chairman of the Board of Expression Therapeutics and Hemophilia of Georgia Professor at Emory University School of Medicine. “We are grateful to Dr. Alok Srivastava, Christian Medical College/Centre for Stem Cell Research/inSTEM, and, most importantly, the participants and their families for collaborating on this unique therapeutic development program with curative potential. We have demonstrated safety and efficacy in our Phase 1 trial and look forward to continued development of a lentiviral mediated hematopoietic stem cell gene therapy for the benefit of hemophilia A patients worldwide,” said Mohan Rao, Ph.D., the Chief Executive Officer of Expression Therapeutics. About Expression Therapeutics, Inc.: Expression Therapeutics, Inc., headquartered in Atlanta, Georgia, with a state-of-the-art GMP manufacturing facility in Cincinnati, Ohio, is a clinical-stage gene and cell therapy company advancing curative therapies for hemophilia A and developing innovative oncology solutions targeting neuroendocrine tumors and neuroblastoma. SOURCE: Expression Therapeutics

VANCOUVER, British Columbia & DALLAS--( BUSINESS WIRE )--Alpha Cognition Inc. (Nasdaq: ACOG) (CSE: ACOG) (“Alpha Cognition” [ACI], or the “Company”), a biopharmaceutical company developing novel therapies for debilitating neurodegenerative disorders, today announced interim preclinical data that supports the continued development of ALPHA-1062 for the treatment of mild traumatic brain injury (mTBI). The interim data provides evidence of benefit for ALPHA-1062, in the treatment of mTBI resulting from repetitive blast trauma, a highly relevant military injury. Blast caused mTBI is considered to be the signature injury effecting soldiers where brain injury from explosive devices and artillery fire blast exposure is highly prevalent. ACI previously documented extensive functional and neuropathological protection, provided by ALPHA-1062 administration, following a single moderate traumatic brain injury. This second pre-clinical study in a rodent model, supported by the US Department of Defense (DOD), is a collaboration with investigators at the Seattle Institute of Biomedical and Clinical Research (affiliated with both the University of Washington and the Veterans Administration). The study is ongoing, with interim data demonstrating that ALPHA-1062 administration following 3 consecutive days of blast induced mTBI, results in a reduction of TBI associated neuropathology. Key findings demonstrated that, ALPHA-1062 administration reduced levels of neuroinflammation markers and neuropathology that occurs after blast trauma. High dose ALPHA-1062 reduced the levels of myeloid cell activation [CD 68] across multiple brain regions one month after blast. High dose ALPHA-1062 also demonstrated the ability to reduce midbrain astrogliosis [GFAP]. Astrogliosis is a process where brain cells called astrocytes become larger, multiply, and change in response to injury or disease in the brain. “These outcomes indicate a protective effect of ALPHA-1062, and demonstrated a reduction of neuropathology. The data provide further support for the continued development of ALPHA-1062 for the treatment of acute mild traumatic brain injury,” said Denis Kay, ACI’s Chief Scientific Officer. Further analysis of neuropathology and neurobehavioral [functional recovery] data is ongoing with the final study report due Q2/2025. About Alpha Cognition Inc. Alpha Cognition Inc. is a clinical stage, biopharmaceutical company dedicated to developing treatments for patients suffering from neurodegenerative diseases, such as Alzheimer’s disease and Cognitive Impairment with mild Traumatic Brain Injury (“mTBI”), for which there are currently no approved treatment options. ALPHA-1062, is a patented new chemical entity being developed as a new generation acetylcholinesterase inhibitor for the treatment of Alzheimer’s disease, with expected minimal gastrointestinal side effects. ALPHA-1062’s active metabolite is differentiated from donepezil and rivastigmine in that it binds neuronal nicotinic receptors, most notably the alpha-7 subtype, which is known to have a positive effect on cognition. ALPHA-1062 is also being developed in combination with memantine to treat moderate to severe Alzheimer’s dementia. An intranasal formulation of ALPHA-1062 has demonstrated potent preservation brain structure and function in a preclinical model of moderate TBI, where enhanced recovery from the brain injury was also seen. The intranasal formulation is currently being evaluated for its ability to provide protection from a military relevant model of repeated mild TBI, in a program sponsored by the US Department of Defense. Neither Canadian Securities Exchange (the “CSE”) or the OTC Markets Group, accepts responsibility for the adequacy or accuracy of this release. Forward-looking Statements This news release includes forward-looking statements within the meaning of applicable securities laws. Except for statements of historical fact, any information contained in this news release may be a forward‐looking statement that reflects the Company’s current views about future events and are subject to known and unknown risks, uncertainties, assumptions and other factors that may cause the actual results, levels of activity, performance or achievements to be materially different from the information expressed or implied by these forward-looking statements. In some cases, you can identify forward‐looking statements by the words “may,” “might,” “will,” “could,” “would,” “should,” “expect,” “intend,” “plan,” “objective,” “anticipate,” “believe,” “estimate,” “predict,” “project,” “potential,” “target,” “seek,” “contemplate,” “continue” and “ongoing,” or the negative of these terms, or other comparable terminology intended to identify statements about the future. Forward‐looking statements may include statements regarding the TBI out-licensing plan and associated financing, the availability of funding pursuant to financings, the Company’s business strategy, market size, potential growth opportunities, capital requirements, clinical development activities, the timing and results of clinical trials, regulatory submissions, potential regulatory approval and commercialization of the Company’s products. Although the Company believes to have a reasonable basis for each forward-looking statement, we caution you that these statements are based on a combination of facts and factors currently known by us and our expectations of the future, about which we cannot be certain. The Company cannot assure that the actual results will be consistent with these forward-looking statements. These forward‐looking statements speak only as of the date of this news release and the Company undertakes no obligation to revise or update any forward‐looking statements for any reason, even if new information becomes available in the future.

AGOURA HILLS, Calif., March 25, 2024 (GLOBE NEWSWIRE) -- Oncotelic Therapeutics, Inc (OTCQB:OTLC) announced today the peer reviewed publication of Transforming Growth Factor Beta 2 (TGFB2) mRNA Levels, in Conjunction with Interferon-Gamma Receptor Activation of Interferon Regulatory Factor 5 (IRF5) and Expression of CD276/B7-H3, Are Therapeutically Targetable Negative Prognostic Markers in Low-Grade Gliomas: Past, Present, and Future Strategies in the Treatment and Management of Gliomas. Dr. Vuong Trieu, CEO and Chairman of Oncotelic, stated, ”Our R&D team has discovered crosstalk between the TGF-β and IFN signaling pathways, linking gliomas and Systemic Lupus Erythematosus (SLE). This publication has identified IRF5 as a common target for both diseases, opening up a new avenue for combating cancer,” Our findings place IRF5 at the intersection of inflammation and cancer. Understanding the role of IRF5 in both SLE and cancer opens an avenue for targeting IRF5 or its downstream pathways. This could offer new strategies for treating SLE and various cancers by modulating the immune response. The article can be accessed for free online: https://www.mdpi.com/2072-6694/16/6/1202 Abstract: Gliomas develop in the central nervous system from the glial cells that support it. Low-grade gliomas (LGGs) are characterized by a reduced number of immune cells infiltrating the tumor, requiring immune-boosting therapies to release the immunosuppressive environment of the tumor. We conducted a bioinformatics-led study to evaluate the prognostic impact of cell surface receptor markers for tumor-associated macrophages (TAMs) that produce transforming growth factor beta (TGFB) ligands and interferon-gamma receptor activation to maintain the tumor microenvironment in an immunosuppressed state. Detailed investigation of messenger RNA levels and their impact on OS in LGG patients demonstrated that low mRNA levels of a specific TGFB ligand, TGFB2, and the receptor along with the signaling molecules from interferon-gamma receptor activation (IFNGR2, IRF1, IRF5, and STAT1) result in improved survival of LGG patients. LGG patients expressing high levels of TGFB2 and IFNGR2 are over-represented in IDH wild-type tumor samples, suggesting that TGFB2 and IFNGR2 mRNA can be therapeutically targeted in these high-risk patients. Furthermore, demethylation of TFGB2, IFNGR2, IRF1, IRF5, STAT1, and CD276 genes also results in worse survival outcomes, pointing to a molecular mechanism that increases the negative prognostic effects of increased mRNA levels of these target genes. We observed that significant upregulation of mRNA expression levels for three TAM markers, MSR1/CD204, CD86, and CD68, suggested that TGFB2 is pivotal in establishing a pro-tumorigenic TME in gliomas mediated through TAMs. Interestingly, a tumor-associated antigen CD276/B7-H3 mRNA expression increased in tumor tissue, giving further insights into the roles of macrophages and tumor cells in the immunosuppressive TME. Therefore, to improve OS in LGG patients, combination therapies must target TGFB2 and IFN-γ activation (via IRF5 inhibition) or immune therapies targeted against CD276/B7-H3 About Oncotelic Oncotelic (f/k/a Mateon Therapeutics, Inc.), was formed in the State of New York in 1988 as OXiGENE, Inc., was reincorporated in the State of Delaware in 1992, and changed its name to Mateon Therapeutics, Inc. in 2016, and Oncotelic Therapeutics, Inc. in November 2020. Oncotelic is seeking to leverage its deep expertise in oncology drug development to improve treatment outcomes and survival of cancer patients with a special emphasis on rare pediatric cancers. Oncotelic has rare pediatric designation for Diffuse Intrinsic Pontine Glioma (“DIPG” through OT-101) through its 45% joint venture, GMP Biotechnology Limited, melanoma (through CA4P), and Acute Myeloid Leukemia (through OXi 4503). Oncotelic acquired PointR Data Inc. in November 2019 to build an AI driven biotechnology company. Further, Oncotelic acquired AL-101, during the 4th quarter of 2021, for the intranasal delivery of apomorphine. We intend to develop AL-101 for the treatment of Parkinson Disease, erectile dysfunction, female sexual disorder and hypoactive sexual desire disorder. All these ailments have a very large population suffering from them and there is a need for treatments for each. For more information on AL-101, refer to our Annual Report on Form 10-K/A filed with the SEC on April 19, 2023. Oncotelic's Cautionary Note on Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical facts, included in this communication regarding strategy, future operations, future financial position, prospects, plans and objectives of management are forward-looking statements. Words such as "may", "expect", "anticipate" "hope", "vision", "optimism", "design", "exciting", "promising", "will", "conviction", "estimate," "intend," "believe", "quest for a cure of cancer", "innovation-driven", "paradigm-shift", "high scientific merit", "impact potential" and similar expressions are intended to identify forward-looking statements. Forward looking statements contained in this press release include, but are not limited to, statements about future plans related to the operations of the JV, taking the JV into an initial public offering or the success thereof, the progress, timing of clinical development, scope and success of future clinical trials, the reporting of clinical data for the Company’s product candidates and the potential use of the Company's product candidates to treat various cancer indications as well as obtaining required regulatory approval to conduct clinical trials and upon granting of approval by the regulatory agencies, the successful marketing of the products; building and the success of our nanoparticle platform and the related success of launching the platform, the development of the Company’s AI suite including but not limited to AI Chatbots, the public access to the Company’s AI suite, the success of the development of the AI suite or any other AI technologies and whether if any or portion thereof the Company’s AI suite or technologies will be commercialized and launched for sale. Each of these forward-looking statements involves risks and uncertainties, and actual results may differ materially from these forward-looking statements or may not occur at all. Many factors may cause differences between current expectations and actual results, including unexpected safety or efficacy data observed during preclinical or clinical studies, clinical trial site activation or enrollment rates that are lower than expected, changes in expected or existing competition, changes in the regulatory environment, failure of collaborators to support or advance collaborations or product candidates and unexpected litigation or other disputes, taking the Company or its affiliates through initial public offerings. These risks are not exhaustive, the company faces known and unknown risks, including the risk factors described in the Company's Annual Report on Form 10-K/A filed with the SEC on April 19, 2023 and in the company's other periodic filings. Forward-looking statements are based on expectations and assumptions as of the date of this press release. Except as required by law, the company does not assume any obligation to update forward-looking statements contained herein to reflect any change in expectations, whether because of new information, future events, or otherwise. Contact Information: For Oncotelic Therapeutics, Inc.:Investor Relationsir@oncotelic.com