CD86

AGOURA HILLS, Calif., Jan. 16, 2024 (GLOBE NEWSWIRE) -- Oncotelic Therapeutics, Inc (OTCQB:OTLC) announced today the peer reviewed publication of Transforming Growth Factor Beta 2 (TGFB2) and Interferon Gamma Receptor 2 (IFNGR2) mRNA Levels in the Brainstem Tumor Microenvironment (TME) Significantly Impact Overall Survival in Pediatric DMG Patients in the Special Issue Gliomas: Signaling Pathways, Molecular Mechanisms and Therapeutic Approaches. "In light of our foundational discovery that elevated levels of TGF-B2 worsen mortality in various cancers, including Diffuse Midline Glioma (DMG), we have further elucidated the underlying mechanisms, particularly focusing on the impact of TGF-B2 on interferon signaling. We hope that sharing these findings from our research team will contribute to the eradication of cancer," stated Dr. Vuong Trieu, CEO and Chairman of Oncotelic. IFNGR2 is a critical component of the IFN-γ signaling pathway, playing a significant role in mediating the immune system's defense against cancer. Its function in enhancing immune surveillance and direct anti-tumor effects making its induction an attractive target for cancer immunotherapy- including suppression of TGF-B2 by OT-101. The article can be accessed for free online: https://www.mdpi.com/2227-9059/12/1/191 Abstract: This hypothesis-generating study characterized the mRNA expression profiles and prognostic impacts of antigen-presenting cell (APC) markers (CD14, CD163, CD86, and ITGAX/CD11c) in pediatric brainstem diffuse midline glioma (pbDMG) tumors. We also assessed the mRNA levels of two therapeutic targets, transforming growth factor beta 2 (TGFB2) and interferon gamma receptor 2 (IFNGR2), for their biomarker potentials in these highly aggressive pbDMG tumors. The expressions of CD14, CD163, and ITGAX/CD11c mRNAs exhibited significant decreases of 1.64-fold (p = 0.037), 1.75-fold (p = 0.019), and 3.33-fold (p < 0.0001), respectively, in pbDMG tumors relative to those in normal brainstem/pons samples. The pbDMG samples with high levels of TGFB2 in combination with low levels of APC markers, reflecting the cold immune state of pbDMG tumors, exhibited significantly worse overall survival outcomes at low expression levels of CD14, CD163, and CD86. The expression levels of IFNGR2 and TGFB2 (1.51-fold increase (p = 0.002) and 1.58-fold increase (p = 5.5 × 10−4), respectively) were significantly upregulated in pbDMG tumors compared with normal brainstem/pons samples. We performed multivariate Cox proportional hazards modelling that showed TGFB2 was a prognostic indicator (HR for patients in the TGFB2high group of pbDMG patients = 2.88 (1.12–7.39); p = 0.028) for poor overall survival (OS) and was independent of IFNGR2 levels, the age of the patient, and the significant interaction effect observed between IFNGR2 and TGFB2 (p = 0.015). Worse survival outcomes in pbDMG patients when comparing high versus low TGFB2 levels in the context of low IFNGR2 levels suggest that the abrogation of the TGFB2 mRNA expression in the immunologically cold tumor microenvironment can be used to treat pbDMG patients. Furthermore, pbDMG patients with low levels of JAK1 or STAT1 mRNA expression in combination with high levels of TGFB2 also exhibited poor OS outcomes, suggesting that the inclusion of (interferon-gamma) IFN-γ to stimulate and activate JAK1 and STAT1 in antitumor APC cells present the brainstem TME can enhance the effect of the TGFB2 blockade. 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

-- Phase 2 Study in SLE (Synergy) Ongoing -- SEATTLE--(BUSINESS WIRE)--Alpine Immune Sciences, Inc. (NASDAQ: ALPN), a leading clinical-stage immunotherapy company focused on developing innovative treatments for autoimmune and inflammatory diseases, announced today that the Company presented new translational data for acazicolcept (ALPN-101) in systemic lupus erythematosus (SLE) at the American College of Rheumatology Convergence 2023, November 10-15, 2023. Acazicolcept Presentation Highlights Include: Acazicolcept target-related genes (ICOS, CD80, CD86) are upregulated in the T and B cells of SLE patients compared to healthy adults. Acazicolcept suppresses expression of genes associated with T cell activation and/or implicated in the pathogenesis of SLE more potently than inhibitors of the CD28 or ICOS pathways. Acazicolcept reduces pathogenic hypergammaglobulinemia and glomerular IgG deposition in a mouse model of lupus. “These data reinforce the importance of multiple key pathways in the pathogenesis of SLE and further support the potential for acazicolcept, a first-in-class molecule, in its treatment,” said Stanford Peng, M.D., Ph.D., President and Head of Research and Development at Alpine. “Because CD28 and ICOS are closely related receptors that can both mediate T cell costimulation, inhibition of both may be required to provide optional outcomes in multiple autoimmune diseases. Clinical investigation of acazicolcept for the treatment of SLE, such as in our ongoing phase 2 study, Synergy, continues to be supported.” American College of Rheumatology Convergence 2023 Date/Time: Sunday, November 12, 2023, 9:00 am – 11:00 am PT Poster Title: Dual Blockade of ICOS and CD28 with Acazicolcept (ALPN-101) Reveals Non-Redundant Roles of T Cell Co-Stimulation Pathways in Systemic Lupus Erythematosus Abstract ID: 1553700 Session Name: SLE – Treatment Poster I Location: Exhibit Hall, San Diego Convention Center, San Diego, CA Presenter: Elizabeth Repash, M.S., Alpine Immune Sciences Link to Poster: About Acazicolcept (ALPN-101) Acazicolcept (ALPN-101) is a first-in-class, dual inhibitor of the CD28 and ICOS T-cell costimulatory pathways being developed for treatment of systemic lupus erythematosus (SLE). By simultaneously blocking two key costimulatory pathways, acazicolcept has the potential to improve outcomes in patients suffering from severe autoimmune/inflammatory diseases. Preclinical studies have demonstrated efficacy in models of SLE, Sjögren’s syndrome, arthritis, inflammatory bowel disease, multiple sclerosis, type 1 diabetes, uveitis, and graft versus host disease. About Alpine Immune Sciences Alpine Immune Sciences is committed to leading a new wave of immune therapeutics. With world-class research and development capabilities, a highly productive scientific platform, and a proven management team, Alpine is seeking to create first- or best-in-class multifunctional immunotherapies via unique protein engineering technologies to improve patients’ lives. Alpine has entered into strategic collaborations with leading global biopharmaceutical companies and has a diverse pipeline of clinical and preclinical candidates in development. For more information, visit . Follow @AlpineImmuneSci on X and LinkedIn. Forward-Looking Statements This release contains 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 the Private Securities Litigation Reform Act of 1995. These forward-looking statements are not based on historical fact and include statements regarding our platform technology and potential therapies; the timing of and results from clinical trials and preclinical development activities; clinical and regulatory objectives and the timing thereof; expectations regarding the sufficiency of cash, cash equivalents, restricted cash, and investments to fund our planned operations through 2025; the potential efficacy, safety profile, future development plans, addressable market, regulatory success, and commercial potential of our product candidates; our ability to achieve additional milestones in our collaborations and proprietary programs; the progress and potential of our ongoing development programs; the timing of our public presentations and potential publication of future clinical data; the efficacy of our clinical trial designs; anticipated enrollment in our clinical trials and the timing thereof; expectations regarding our ongoing collaborations; and our ability to successfully develop and achieve milestones in our development programs. Forward-looking statements generally include statements that are predictive in nature and depend upon or refer to future events or conditions and include words such as “may,” “will,” “should,” “would,” “expect,” “plan,” “intend,” and other similar expressions, among others. These forward-looking statements are based on current assumptions that involve risks, uncertainties, and other factors that may cause actual results, events, or developments to be materially different from those expressed or implied by such forward-looking statements. These risks and uncertainties, many of which are beyond our control, include, but are not limited to: clinical trials may not demonstrate safety and efficacy of any of our product candidates; our ongoing discovery and preclinical efforts may not yield additional product candidates; our discovery-stage and preclinical programs may not advance into the clinic or result in approved products; any of our product candidates may fail in development, may not receive required regulatory approvals, or may be delayed to a point where they are not commercially viable; we may not achieve additional milestones in our proprietary or partnered programs; the impact of competition; adverse conditions in the general domestic and global economic markets; the impact of pandemics, or other related health crises on our business, research and clinical development plans and timelines and results of operations, including the impact on our clinical trial sites, collaborators, and contractors who act for or on our behalf; as well as the other risks identified in our filings with the Securities and Exchange Commission. These forward-looking statements speak only as of the date hereof and we undertake no obligation to update forward-looking statements, and readers are cautioned not to place undue reliance on such forward-looking statements.

BriaCell demonstrates unprecedented broad immune system activation in tumor models by BriaCell’s next generation breast and prostate cancer immunotherapies Data supports further development of BriaCell’s next generation personalized immunotherapy platform with potent anti-tumor activity and favorable safety profileFDA authorizes Bria-OTS™ Investigational New Drug Application (IND) opening the path to the clinic PHILADELPHIA and VANCOUVER, British Columbia, Nov. 03, 2023 (GLOBE NEWSWIRE) -- Therapeutics Corp. (Nasdaq: BCTX, BCTXW) (TSX: BCT) (“BriaCell” or the “Company”), a clinical-stage biotechnology company that develops novel immunotherapies to transform cancer care, is pleased to report unprecedented activity of its next generation, personalized, off-the-shelf, cell-based breast and prostate cancer immunotherapies at the 2023 Society for Immunotherapy of Cancer (SITC) annual meeting. These novel immunotherapies have been shown to activate the immune system through multiple mechanisms including adaptive responses of naïve (resting) T cells and innate responses of dendritic cells and natural killer (NK) cells leading to enhanced clinical efficacy and prevention of immune escape. BriaCell’s current lead candidate, Bria-IMT™, has enhanced efficacy in human leucocyte (HLA) matched patients (LINK) and led to the development of Bria-OTS™, an off the shelf personalized immunotherapy providing HAL matched targeting to >99% of the US population. “We are extremely excited with our findings confirming unprecedented immune system responses to our novel next generation breast and prostate cancer immunotherapies - designed with additional immune activating components for superior efficacy,” stated Dr. William V. Williams, BriaCell’s President & CEO. “We expect our novel immunotherapies to boost the immune system in cancer patients leading to tumor destruction. We believe that our technology represents a significant advancement in the field of oncology and personalized immunotherapy.” BriaCell’s poster presentation highlights the development details and activities of BriaCell’s next generation off-the-shelf personalized immunotherapies for breast and prostate cancers. Abstract Title: Development and Mechanism of Action of a Novel Cellular Immunotherapeutic Platform for the Treatment of Advanced Solid Tumors Abstract Number: 419Location: San Diego Convention Center, San Diego, CASession Date and Time: Friday November 3, 2023 9:00 AM - 6:00 PMImmune system activation by BriaCell’s next generation personalized off-the-shelf immunotherapy BriaCell has developed next generation, cell-based, personalized immunotherapies, Bria-OTS+™ (for breast cancer) and Bria-PROS+™ (for prostate cancer) that produce immune system activating molecules e.g., antigen presenting cell components and granulocyte macrophage colony stimulating factor (GM-CSF), as well as newly added immune system activating factors such as costimulatory molecules and cytokines. Potential advantages of BriaCell’s next generation personalized off-the-shelf immunotherapies include: Precision Therapy: Bria-OTS+™ cell lines are precisely matched to individual patients based on their HLA antigens, encompassing over 99% of the U.S. population. This personalized approach would provide optimal compatibility and effectiveness of cancer immunotherapy. Favorable Safety Profile: Bria-OTS+™ therapies are expected to avoid the severe and potentially life-threatening adverse events often associated with current treatments. Rapid, Cost-Effective Treatments: BriaCell OTS+™ therapies are produced for “off-the-shelf” use. This novel approach allows for the immediate administration of immunotherapy following standard patient HLA genotyping. This streamlined process eliminates individualized manufacturing requirements and may offer efficient and cost-effective personalized treatment options to cancer patients in need. Potent Immune System Activation: BriaCell’s data has shown unprecedented broad immune system responses to the next generation immunotherapies compared with those of the earlier formulation. Additionally, our findings confirmed that both Bria-OTS+™ and Bria-PROS+™activate multiple components of the immune system through direct activation of naïve (resting) T- cells as well as activation of Natural killer (NK) cells via production of immune activating molecules including CD86 (a co-stimulatory molecule). Platform Technology: These findings support further development of BriaCell’s platform of next-generation cancer immunotherapies for multiple cancer types, focusing initially on breast, and prostate cancers. In summary, BriaCell’s novel next generation personalized immunotherapy delivers broad immune responses against various solid tumor models via multiple immune activating mechanisms. BriaCell’s cell-based immunotherapies may offer superior efficacy in addition to favorable safety profiles in cancer patients. Importantly, the off-the-shelf (i.e., premanufactured) nature of our immunotherapy may shorten the time to receive cancer treatment, and perhaps prevent disease progression in cancer patients. BriaCell expects the administration of personalized BRIA-OTS+™ and BRIA-PROS+™ immunotherapies, following a rapid and routine HLA test, to provide safe and effective treatment options for cancer patients. These findings support BriaCell’s strategy to further develop this approach as a platform technology with broad applications for multiple cancers. A copy of the poster will be posted at the following: https://briacell.com/scientific-publications/. In separate news, FDA has stated that BriaCell may proceed with the clinical study of Bria-OTS™. This opens the path to the clinic for Bria-OTS™, the first generation of BriaCell’s personalized off-the-shelf cellular immunotherapy for breast cancer. “We are gratified that the FDA has opened our IND for the first generation of Bria-OTS™,” stated Dr. William Williams. “This will enable us to begin the process of initiating the clinical study of Bria-OTS™ and will provide a roadmap for the introduction of the advanced versions of our personalized off-the-shelf cellular immunotherapies for breast cancer, prostate cancer and other cancers. Given the very exciting data presented at the SITC meeting, we believe that these immunotherapies have the potential to be a game-changer in the field of cancer treatments.” About BriaCell Therapeutics Corp. BriaCell is an immuno-oncology-focused biotechnology company developing targeted and effective approaches for the management of cancer. More information is available at https://briacell.com/. Safe Harbor This press release contains “forward-looking statements” that are subject to substantial risks and uncertainties. All statements, other than statements of historical fact, contained in this press release are forward-looking statements. Forward-looking statements contained in this press release may be identified by the use of words such as “anticipate,” “believe,” “contemplate,” “could,” “estimate,” “expect,” “intend,” “seek,” “may,” “might,” “plan,” “potential,” “predict,” “project,” “target,” “aim,” “should,” “will,” “would,” or the negative of these words or other similar expressions, although not all forward-looking statements contain these words. Examples of forward-looking statements in this news release include statements that the Company makes regarding: further development of BriaCell’s next generation personalized immunotherapy platform with broad applications for multiple cancers; whether BriaCell’s novel immunotherapies may boost the immune system in cancer patients leading to tumor destruction; whether BriaCell’s technology represents a significant advancement in the field of oncology and personalized immunotherapy; any potential advantages of BriaCell’s next generation personalized off-the-shelf immunotherapies (for example: precision therapy, favorable safety profile, rapid and cost-effective treatments, potent immune system activation, and the development of the platform technology); whether BriaCell’s cell-based immunotherapies may offer superior efficacy in addition to favorable safety profiles in cancer patients; whether the off-the-shelf (i.e., premanufactured) nature of BriaCell’s immunotherapy may shorten the time to receive cancer treatment, and perhaps prevent disease progression in cancer patients; the expectation that the administration of personalized BRIA-OTS+™ and BRIA-PROS+™ immunotherapies, following a rapid and routine HLA test, may provide safe and effective treatment options for cancer patients; whether BriaCell may begin the process of initiating the clinical study of Bria-OTS™; and whether BriaCell’s immunotherapies have the potential to be a game-changer in the field of cancer treatments. Forward-looking statements are based on BriaCell’s current expectations and are subject to inherent uncertainties, risks and assumptions that are difficult to predict. Further, certain forward-looking statements are based on assumptions as to future events that may not prove to be accurate. These and other risks and uncertainties are described more fully under the heading “Risks and Uncertainties” in the Company’s most recent Management’s Discussion and Analysis, under the heading “Risk Factors” in the Company’s most recent Annual Information Form, and under “Risks and Uncertainties” in the Company’s other filings with the Canadian securities regulatory authorities and the U.S. Securities and Exchange Commission, all of which are available under the Company’s profiles on SEDAR at www.sedar.com and on EDGAR at www.sec.gov. Forward-looking statements contained in this announcement are made as of this date, and BriaCell Therapeutics Corp. undertakes no duty to update such information except as required under applicable law. Neither Toronto Stock Exchange nor its Regulation Services Provider (as that term is defined in the policies of the Toronto Stock Exchange) accepts responsibility for the adequacy or accuracy of this release. Contact Information Company Contact:William V. Williams, MDPresident & CEO1-888-485-6340info@briacell.com Media Relations:Jules AbrahamDirector of Public RelationsCORE IR917-885-7378julesa@coreir.com Investor Relations Contact:CORE IRinvestors@briacell.com