AGOURA HILLS, Calif., June 11, 2024 (GLOBE NEWSWIRE) -- Oncotelic Therapeutics, Inc (OTCQB:OTLC) announced today its CEO- Dr. Vuong Trieu will speak at the 20th Annual Congress of International Drug Discovery Science & Technology (IDDST) (Europe), June 17-19, 2024 at Budapest, Hungary.
Title: TGFB2 therapeutic for the treatment of CRC, GBM, and PDAC
Anirudh Kolanu, K. Khuranu, A. Mehta, T. Sanil1, G. Trieu, and Dr. Vuong Trieu*
Abstract: OT-101, an antisense against TGFB2, is being tested in phase 3 clinical trials for pancreatic cancer and glioblastoma. It was previously reported to have robust clinical activity in those indications as well as in melanoma. Here, we explore the potential application of OT-101 in colorectal cancer (CRC) through the analysis of CRC patients treated with OT-101 during its clinical development, as well as through bioinformatic. Intravenous therapy with OT-101 in melanoma, colorectal cancer, and pancreatic cancer was evaluated in P001- a phase I/II study. A total of 62 patients were enrolled; 38 patients with pancreatic cancer, 19 patients with melanoma, and 5 patients with colorectal cancer. Full pharmacokinetic evaluation of these patients demonstrated a drug effect with improved progression-free survival (PFS) with increased drug exposure defined by AUClast. The CRC patients were heavily pretreated with multiple lines of previous therapies (4,5,5,6,8), reflected in short overall survival times (2.1, 2.5, 3.0, 5.7, 7.3 months). High AUC exhibited a doubling of PFS to 84 days versus 40 days. A sample of 4259 colorectal adenocarcinoma cancer patients from cbioportal was analyzed. The low expression of two genes: TGFB2 and TGFM6 improved OS. The combination of TGFB2 and TGFM6 was superior to TGFB2 or TGFM6 alone, with TGFB2 being the dominant factor. There was strong but not overlapping sexual dimorphism among the two genes separately but not when used together. The TGFB/TGM6 impact was most significant on Mesenchymal CMS- increasing median survival from 42 months with high TGFB2/TGM6 to 132 months with low TGFB2/TGM6- a threefold improvement with a highly significant p-value of 1.4e-5. Statistical significance was not observed when the genes were used separately. Suppression of TGFB2, i.e., through OT-101, is a potential approach for the treatment of CRC.especially OT-101 treatment of TGM6 low patients.
"It is gratifying to identify what we think is the fundamental role of TGFM6 and TGFB2 in cancer," said Dr. Vuong Trieu, CEO and Chairman of Oncotelic. "Considering the work done here by our interns drawn from local high schools through Brush&Key Foundation for Young Artist, I am impressed at the quality of their outputs."
Supporting publications are as below:
1) 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.Trieu V, Maida AE, Qazi S. Cancers (Basel). 2024 Mar 19;16(6):1202. doi: 10.3390/cancers16061202. PMID: 38539537.
2) 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. Qazi S, Talebi Z, Trieu V. Biomedicines. 2024 Jan 15;12(1):191. doi: 10.3390/biomedicines12010191. PMID: 38255296.
3) High Intra-Tumor Transforming Growth Factor Beta 2 Level as a Predictor of Poor Treatment Outcomes in Pediatric Diffuse Intrinsic Pontine Glioma. Uckun FM, Qazi S, Trieu V. Cancers (Basel). 2023 Mar 9;15(6):1676. doi: 10.3390/cancers15061676. PMID: 36980562.
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.
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