Oncotelic Therapeutics Inc · OTC:OTLC
Oncotelic Therapeutics — 5th Symposium on World Cancer Research (SWCR 2025)
36 slides from Oncotelic Therapeutics's conference presentation, Mar 24, 2025
Slide 1: TGF-beta 2 in Aging, Cancer, Lupus, and Immuno-Oncology
Vuong Trieu PhD/ CEO of Oncotelic Therapeutics and Sapu Bioscience “TRANSFORMING GROWTH FACTOR BETA 2 IN AGING, CANCER, LUPUS, AND IMMUNO-ONCOLOGY: A CONVERGENCE OF DISEASE PATHWAYS AND THERAPEUTIC POTENTIAL” THE 5TH SYMPOSIUM ON WORLD CANCER RESEARCH (SWCR 2025). MAR 24TH-26TH, 2025; KYOTO, JAPAN 1
Slide 2: Oncotelic is Focusing on Antisense (ASO) as Next Generation Drugs
Oncotelic is Focusing on Antisense (ASO) as Next Generation Drugs Attributes Small Molecules mAb Antisense Inception 1850s to present 1920s to present 1990s to present Size 200-500 >150,000 5,000 to 7,000 Drug Discovery Random screening Focused screening Rationally designed Success Rate Low-~5% Mode
Slide 3: Approved oligonucleotide drugs (between 1998 and 2024)
Approved oligonucleotide drugs (between 1998 and 2024) 2023 Qalsody: ALS 2024 Izervay: Geographic Atrophy Rytelo: MDS Rivfloza: primary hyperoxaluria Tryngolza: Familial chylomicronemia syndrome WAINUA: amyloid polyneuropathy Nucleic Acids Res, Volume 51, Issue 6, 11 April 2023, Pages 2529–2573, 3 3
Slide 4: TGFB2 ASO
TGFB2 ASO OT-101 Mechanisms of ASOs. 1—inhibition of 5′ cap formation, 2—steric blocking of translation, 3—alteration of splicing, 4—activation of RNase H, and 5—inhibition of miRNA. Created with BioRender.com(accessed on 16 August 2024). Çakan, E.; Lara, O.D.; Szymanowska, A.; Bayraktar, E.; Chavez
Slide 5: TGF-beta has a long history
TGF-beta has a long history Deng, Z., Fan, T., Xiao, C. et al. TGF-β signaling in health, disease, and therapeutics. Sig Transduct Target Ther 9, 61 (2024). https://doi.org/10.1038/s41 392-024-01764-w 5
Slide 6: TGF-beta is involved in many biological processes
TGF-beta is involved in many biological processes Deng, Z., Fan, T., Xiao, C. et al. TGF-β signaling in health, disease, and therapeutics. Sig Transduct Target Ther 9, 61 (2024). https://doi.org/10.1038/s41392-024-01764-w TGF-β signaling in health. TGF-β signaling plays a critical role in physiologi
Slide 7: TGF-beta is involved in many diseases
TGF-beta is involved in many diseases Deng, Z., Fan, T., Xiao, C. et al. TGF-β signaling in health, disease, and therapeutics. Sig Transduct Target Ther 9, 61 (2024). https://doi.org/10.1038/s41392-024-01764-w. TGF-β signaling in disease. Dysfunctional TGF-β signaling is involved in numerous patholo
Slide 8: Ongoing early clinical development of TGF-β-targeting therapies
Ongoing early clinical development of TGF-β-targeting therapies Targets Strategies Treatments Diseases Clinical trials Latent TGF-β complex Monoclonal antibody SRK-181 Solid tumors NCT04291079 (phase 1) NCT05483530 (phase 1) and GARP Monoclonal antibody HLX60 Solid tumors and lymphoma NCT05606380 (p
Slide 9: Ongoing Phase 3 of TGF-β-targeting therapies
Ongoing Phase 3 of TGF-β-targeting therapies Targets Strategies Treatments Diseases Clinical trials NCT06079346 (phase 3) and TGF-β2 mRNA Antisense oligonucleotide OT-101 - TGFB2 Pancreatic ductal adenocarcinoma NCT04862767 (phase 1) NCT04935359 (phase 3), NCT04390763 (phase 2), Pancreatic cancer, c
Slide 10: OT-101 Summary
OT-101 Summary Novel antisense oligodeoxynucleotides (ODNs) - for the treatment of patients with pancreatic cancer, malignant melanoma, colorectal cancer, high-grade glioma (HGG), and other malignancies overexpressing transforming growth factor β2 (TGF-β2). A single-stranded phosphorothioate ant
Slide 11: OT-101 is designed to direct M2 tumor promoting to M1 tumor suppressing
OT-101 is designed to direct M2- tumor promoting- to M1 – Tumor suppressing. The polarization of Tumor-Associated Macrophages (TAMs) and their characteristics. The figure displays a general principle of polarized M1-like and M2-like phenotypes. M1-like and M2-like phenotypes represent two extremes o
Slide 12: OT-101 for GBM
Intracranial delivery OT-101 FOR GBM 12
Slide 13: TGF-B2 is a negative prognostic factor for survival in pediatric DMG
TGF-B2 is a negative prognostic factor for survival in pediatric DMG The Cancer Genome Atlas (TCGA) collected, characterized, and analyzed cancer samples from over 11,000 patients over a 12 year period. All data collected and processed by the program is currently available at the Genomic Data Common
Slide 14: TGF-B2 is a Negative Prognostic Factor in Adult Gliomas
TGF-B2 is a Negative Prognostic Factor in Adult Gliomas + TMZ or Radiation Gliomas treated with TMZ or Radiation exhibited increasing OS with decreasing TGF-B2 14 TGF-B1 TGF-B2 TGF-B3
Slide 15: Phase IIb G004 trial of Trabedersen (OT-101) in High Grade Gliomas
Phase IIb G004 trial of Trabedersen (OT-101) in High Grade Gliomas Study Objectives To identify the target patient population most likely to benefit from OT-101 for subsequent confirmatory Phase II/III registration trial Key patient inclusion criteria OT-101 • Supratentorial tumor 10 µM or 80 µM OS
Slide 16: G004-Phase 2b GBM Trial
G004-Phase 2b GBM Trial Title: A multi-national, multi-center, open-label, active-controlled, randomized parallel-group dose-finding study to evaluate the efficacy and safety of two doses of OT-101 in adult patients with recurrent high-grade glioma, administered intratumorally as continuous high-flo
Slide 17: OT-101 Glioma Trials: G001-G005
OT-101 Glioma Trials : G001-G005 Parameter Study No. G001 G002 G003 G004 G005 Aim Determination of the MTD/MTC, safety, and efficacy Evaluation of efficacy and safety Evaluation of efficacy and safety compared to standard compared to standard chemotherapy chemotherapy Clinical phase I/II IIb III Stu
Slide 18: Central Nervous System Drug Delivery Technology
Central Nervous System Drug Delivery Technology Meant for either long infusion with inwelling tubing or short (4.5 hr) infusion with external tubing Neurological diseases including Alzheimer, Parkinson, Baten. Neurological cancers including DIPG, DMG, Leptomeningeal metastases Patent issued March 20
Slide 19: OT-101 + mFOLFIRINOX for PDAC
Where Do We Stand with Immunotherapy for Advanced Pancreatic Ductal IV delivery Adenocarcinoma: A Synopsis of Clinical Outcomes MDPI Biomedicines. December 202210(12):3196. DOI:10.3390/biomedicines10123196 OT-101 + MFOLFIRINOX FOR PDAC 19
Slide 20: TGF-B2 is negative prognostic indicator for OS in PDAC
TGF-B2 is negative prognostic indicator for OS in PDAC PDAC has worse OS with high TGF-B2. Suggesting that treatment with OT-101 should be effective No impact of TGF-B1 nor TGF-B3 Again validating TGF-B2 as the target Note the >2X improvement in OS (15 mos with high TGF-B2 versus 37 mos with low TGF
Slide 21: Phase I/II P001 trial of OT-101
Phase I/II P001 trial of OT-101 Study objectives Title: An Open-Label, Multicenter Dose-escalation Study to Evaluate the Safety and Tolerability of OT-101 (TGF-β2-specific Phosphorothioate Antisense Oligodeoxynucleotide), Administered Intravenously in Adult Patients with Advanced Tumors Known to Ove
Slide 22: PK/PD Analysis
PK/PD Analysis Figure 2: Bivariate Fit of AUClast By Total Dose OT-101 PK is dose proportional (p<0.0001) (Figure 2). More than half of the OT-101 treated PC patients went into long 800 4/10 term disease control (21 of 37 pts, 55%) allowing them to enter 7/7 AUClast (μg*h/mL) into subsequent che
Slide 23: P201 STOP-PC Trial
P201 STOP-PC Trial P201: 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 NCT06079346 Patient population Adult patients wi
Slide 24: Phase 3 Trial Design: OT-101 + mFOLFIRINOX
Phase 3 Trial Design: OT-101 + mFOLFIRINOX TGFB2 suppression synergizes only with Irinotecan – not paclitaxel Gemcitabine (11% pts treated with irinotecan) Fluorouracil (35% pts treated with irinotecan) nor gemcitabine. Note- NIS793 chose ABX/Gem. Subsets of pts treated with various drug/drug combin
Slide 25: OT-101 + Keytruda for Lung Cancer and Melanoma
IV delivery OT-101 + KEYTRUDA FOR LUNG CANCER AND MELANOMA 25
Slide 26: OT-101 Checkpoint inhibitor combination therapies
OT-101 Checkpoint inhibitor combination therapies Box = PD-1 which is only present in M2 TAMs OT-101 + PD1 Inhibitor combination / External collaborations with Merck and others. OT-101 + PD1 Inhibitor + IL-2/ External collaborations with Regneneron and others OT-101 suppression of TGF-B2 suppresses
Slide 27: A case for PD-1 Combination
A case for PD-1 Combination TGFB1 versus TGFB2: Bintrafusp alfa is inhibiting TGF-beta 1 by binding to the TGFB1 protein only with no affinity for TGFB2. TGFB2 (not TGFB1)- is upregulated in advance stage tumors; TGFB2 (not TGFB1) is associate with worse prognosis across multiple cancer types; TGFB2
Slide 28: OT-101 With Pembrolizumab for Newly Diagnosed Advanced NSCLC
OT-101 With Pembrolizumab for Newly Diagnosed Advanced NSCLC and Positive PD- L1/ ClinicalTrials.gov ID NCT06579196/ University of Nebraska FPI expecting April 2025 Phase I: Dose Finding. Dose Limiting toxicity (DLT) and Maximum Tolerated Dose (MTD) Experimental: Arm I: Dose Finding: Participants re
Slide 29: Synergy of TGFB2 low (OT-101) and IL2 high
Synergy of TGFB2 low (OT-101) and IL2 high (IL2) Combining low TGFB2 (denominator) to show effect of OT-101 suppression of TGFB2 and high IL2 (as numerator) to show effect of IL-2 therapy clearly demonstrate synergy between the two therapeutics when used in conjunction with CKIs – specifically PD-1
Slide 30: OT-101 in Combination With Recombinant Interleukin-2
OT-101 in Combination With Recombinant Interleukin-2(Aldesleukin) in Advanced or Metastatic Solid Tumor. ClinicalTrials.gov ID NCT04862767 Study Completed The study was divided into two cohorts based on the dosage of the investigational product. It started with Cohort 1 (Level 1: TASO-001 140 mg/m²/
Slide 31: OT-101 for CRC
IV delivery Cervena, Klara & Siskova, Anna & Buchler, Tomas & Vodicka, Pavel & Vymetalkova, Veronika. (2020). Methylation-Based Therapies for Colorectal Cancer. Cells. 9. 1540. 10.3390/cells9061540. OT-101 FOR CRC 31
Slide 32: Synergistic effect of TGFB2 and TGM6 on survival in CRC
Synergistic effect of TGFB2 and TGM6 on survival in CRC Bioinformatic analyses were performed to determine the impact of TGFB2 expression on survival in CRC. TGFB2 exhibits sexual dimorphism in CRC patients; Its impact on OS was minimal except for RFS. The impact of combined TGFB2 and TGFM6 were syn
Slide 33: TGFB2 and TGM6 OS response is Mesenchymal specific
TGFB2 and TGM6 OS response is Mesenchymal specific Consensus Molecular Subtypes (CMS) of colorectal cancer. OS- All pts OS- Mesenchymal 1. CMS1: Microsatellite Instability Immune (MSI Immune): microsatellite instability (MSI-H). Immune Activation 2. CMS2: Canonical: Epithelial: CMS2 tumors are p
Slide 34: TGM6 has the highest impact on OS
TGM1 (ns also for TGM2, TGM3, and TGM7) TGM4 TGM6 has the highest impact on OS Different isoforms of TGM were examined and only TGM4, 5, and 6 were active with TGM6 being the most active. Median survival Median survival Low expression High expression Low expression High expression cohort (months) co
Slide 35: Upcoming pipeline
Upcoming pipeline ONCOTELIC~ High Intra-Tumor Transforming Growth Factor Beta 2 Level as a Predictor of Poor Treatment Outcomes in Pediatric Diffuse Intrinsic Pontine Glioma by Fatih M. Uckun 1.2.* 30, Sanjive Qazi 1.2 and Vuong Trieu 2 Transforming Growth Factor Beta 2 (TGFB2) and Interferon Gamma
Slide 36: Thank You
Vuong Trieu PhD CEO/ Chairman vtrieu@oncotelic.com www.oncotelic.com THANK YOU 36
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