TGF-β2

AGOURA HILLS, Calif., March 04, 2024 (GLOBE NEWSWIRE) -- Oncotelic Therapeutics, Inc (OTCQB:OTLC) invites participation in our STOP-PC clinical trial which is now open for recruitment. Additional information can be obtained at . An explainer video is available at . STOP-PC is a Randomized Phase 2b/Phase 3 Study of the TGF-β2 Targeting Antisense Oligonucleotide OT-101 in Combination with mFOLFIRINOX Compared with mFOLFIRINOX Alone in Patients with Advanced and Unresectable or Metastatic Pancreatic Cancer. The transforming growth factor-β (TGF-β for short) is a protein that modulates the activity of immune cells. In cancer tissue it suppresses immune cell response and contributes to tumor growth and spread. OT-101 is a first-in-class RNA therapeutic designed to fight the immunosuppressive actions of TGF-β2, reduce the level of TGF-β2 in malignant tumors, and thereby delay the progression of disease. OT-101 has demonstrated notable single-agent activity, consistently surpassing reported literature data for overall survival. Importantly, the overall survival increased in a dose-dependent manner at the levels of 140mg/m2 and higher. The Phase 2/3 trial that you are being asked to participate in will compare OT-101 plus mFOLFORINOX with mFOLFORINOX alone as second line therapy in patients whose cancer progressed. "STOP-PC trial is the combination of mFOLFIRINOX and OT-101 based on our demonstration that reduced TGF- β2 resulted in outstanding improvement in survival among patients treated with Irinotecan with survival beyond 34 months for the low TGF-β2 expression cohort. The mFOLFIRINOX was chosen as the most well tolerated combination of choice through discussion with regulatory authorities and key opinion leaders. We believe this trial will deliver the decisive win against pancreatic cancer," expressed Dr. Vuong Trieu, CEO of Oncotelic. About Cromos Founded in 2004 and headquartered in the United States, Cromos Pharma is an international CRO. Cromos offers comprehensive clinical research solutions, covering all trial phases and a wide range of therapeutic areas. These areas include oncology, cardiovascular diseases, and gastroenterology. Over its almost 20-year journey, Cromos Pharma has successfully completed more than 300 clinical trials, demonstrating its commitment to excellence and precision. Its mission is to expedite the development of drugs and devices that save lives and enhance its quality. Cromos Pharma achieves this by combining innovation with validated best practices, reducing drug development time and costs while maintaining unparalleled quality standards. Cromos Pharma serves a diverse clientele, including Global Pharma, Biotechs, and other notable CROs. It has a strong operational presence across the US, Central and Eastern Europe, and Central and Southwestern Asia. Their country-specific operations cover Bulgaria, Croatia, Czech Republic, Estonia, Georgia, Hungary, Kazakhstan, Latvia, Lithuania, Moldova, Poland, Romania, Serbia, Slovak Republic, Slovenia, Türkiye, and Ukraine. For collaborations or inquiries, please contact them at inquiry@cromospharma.com. 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 (“AML” through OXi 4503). Oncotelic also 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,. 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 Relations ir@oncotelic.com

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

Oral presentation highlights the resolving of inflammation and superior homing to bone marrow of CXCR4-enriched T regulatory cells. Poster presentation includes safety and efficacy data from phase 1b LIMBER-TREG108 study evaluating CK0804, CXCR4 enriched, T regulatory cells, as an add on therapy to ruxolitinib in patients with myelofibrosis who experience a suboptimal response to ruxolitinib. HOUSTON, Nov. 6, 2023 /PRNewswire/ -- Cellenkos® Inc., a clinical stage biotechnology company focused on developing allogeneic, off-the-shelf, T regulatory (Treg) cell therapies for treatment of rare inflammatory diseases and autoimmune disorders, today announces an oral presentation and poster presentation at the 65th American Society of Hematology (ASH) Annual Meeting & Exposition, which is being held December 9-12, 2023, in San Diego, California. The oral presentation will describe the differentiation and characterization of the CXCR4 enriched Treg cells and their preferential homing to bone marrow to resolve inflammation and decrease TGFβ1 and TGFβ2, in vivo, when compared to control Treg cells. This presentation has also been selected for ASH Abstract Achievement Award. The poster presentation will elaborate on the results of Company's CK0804 Phase 1b trial. The study provides first-in-human safety of multiple infusions of CK0804 in myelofibrosis patients in the ambulatory setting as well as improvement in their blood transfusion requirements and symptom burden. "We are very pleased with the breadth of our oral and poster presentations at this year's ASH meeting, which reflect the promising potential of CK0804 as the backbone for treating myelofibrosis," stated Tara Sadeghi, Chief Operating Officer of Cellenkos® Inc. "Of particular note is the convergence of our CK0804 clinical data with the strong pre-clinical hypothesis and its mechanism of action. This marks dawn of a new era of differentiated Treg cell therapy that could be tailored to specific target tissue and can be investigated in combination with existing approved therapies, especially if there are complimentary mechanisms of action and favorable side effect profiles. The ability to administer CK0804 cells in ambulatory setting without requiring lymphodepletion or hospital admission, embarks the democratization of cellular therapies such that these potentially lifesaving treatments could be made available to patients in the community setting. In addition, the improvement in blood transfusions burden allows for CK0804 to be positioned as a potential novel therapy. We look forward to examining CK0804 in a larger trial." Further details of the presentations are provided below. Oral Presentation Title: CXCR4 Enriched T Regulatory Cells Preferentially Home to Bone Marrow and Decrease Inflammation Date: Saturday, December 9, 2023. Time: 4:30 PM Location: San Diego Convention Center, Room 6A This oral presentation describes the CXCR4 enrichment of Treg cells using the CRANE™ technology platform and faster migration of CXCR4 enriched cells towards SDF1a as early as 15-minute time point. In vivo, the CXCR4 enriched Tregs preferentially trafficked to bone marrow and exhibit higher expression of CXCL12, CD62L, CD39, CD73 and CXCR5. A decrease in TGFα, TNFβ, IL-13 as well as TGFβ1 and TGFβ2 was also observed. These CXCR4 enriched Treg cells are being examined in phase 1b clinical trial (NCT05423691). Poster presentation Title: A Phase Ib, Open-Label Study of Add on Therapy with CK0804 in Participants with Myelofibrosis and Suboptimal Response to Ruxolitinib Date: Saturday, December 9, 2023 Time: 5:30 PM Location: San Diego Convention Center, Halls G-H This presentation describes the safety and efficacy data from the ongoing phase 1b LIMBER-TREG108 study evaluating CK0804, CXCR4 enriched, T regulatory cells, as an add on therapy to ruxolitinib in patients with myelofibrosis who experience a suboptimal response to ruxolitinib. This is a single arm study where patients receive 6 infusions of CK0804 at a fixed dose at 100 million Treg cells every 28 days. Clinical data from 5 patients who have completed treatment show early promising results of improvement in blood transfusion as well as relief from symptom burden. Additionally, patients report improvement in their tolerance of anemia and daily activities of life. About Cellenkos®, Inc. Cellenkos® is a clinical-stage biotechnology company located in Houston, Texas, USA, founded in 2016 with the licensing of a proprietary umbilical cord blood T-Regulatory cell therapy platform from The University of Texas at MD Anderson Cancer Center. Being derived from umbilical cord blood, Cellenkos' T-Regulatory cells are naïve, bonafide suppressor cells that resolve inflammation through multiple direct and indirect interactions. Cellenkos is dedicated to the development and commercialization of the allogeneic, off-the-shelf cell-based products for the treatment of rare inflammatory diseases and autoimmune disorders. For more information, please visit . Disclosure MD Anderson has an institutional conflict of interest with Cellenkos® related to this research and has implemented an Institutional Conflict of Interest Management and Monitoring Plan Contact: Stacy Minor [email protected] SOURCE Cellenkos, Inc.