trabedersen (OT-101) / Autotelic, Oncotelic, Oncotelic-Dragon Overseas JV - LARVOL DELTA

Key Highlights From the Kyoto 2025 Presentation (GlobeNewswire) - "Dr. Trieu presented evidence that TGFβ2 is a critical driver of immunosuppression, fueling tumor progression by promoting an M2-like macrophage phenotype and blunting antitumor immunity; OT-101’s Clinical Progress and Versatility: In pancreatic ductal adenocarcinoma (PDAC), OT-101 is currently in a Phase 3 clinical trial (the STOP-PC study) combined with mFOLFIRINOX...Combination regimens with CKIs and IL-2 address multiple pathways of immune evasion, potentially amplifying therapeutic benefits; Next Studies Targeting TGF β2 and Beyond: With the newly completed OT-101 and IL-2 Phase 1 trial, Oncotelic is poised to begin further combination trials to determine the added efficacy of OT-101, IL-2, and CKIs in solid tumors such as lung cancer, melanoma, and colorectal cancer; Next wave of clinical trials aiming to knock down TGF β 2 (e.g., with OT-101) paired with intervention with a complementary therapy, checkpoint blockade..."

New trial • Trial status • Colorectal Cancer • Glioma • Lung Cancer • Melanoma • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Oncotelic CEO Vuong Trieu to Present Groundbreaking Research on Transforming Growth Factor Beta 2 (TGFB2) at SWCR 2025 Conference (GlobeNewswire) - "Oncotelic Therapeutics...is pleased to announce that Vuong Trieu, Ph.D., Chairman & CEO, will be delivering a featured presentation at the SWCR 2025 Conference on March 24th. His talk will highlight the central role of Transforming Growth Factor Beta 2 (TGFB2) in the convergence of disease pathways spanning cancer, lupus, and aging, as well as its potential as a therapeutic target in immuno-oncology....A key focus of the presentation will be the clinical development of OT-101, an antisense therapeutic targeting TGFB2, which is currently in Phase 3 clinical trials (STOP-PC study) for pancreatic ductal adenocarcinoma (PDAC). The talk will explore how TGFB2 inhibition—alone or in combination with immune checkpoint inhibitors or interferon-based strategies—may reshape the tumor microenvironment, boost immune response, and enhance therapeutic efficacy."

Clinical • Trial status • Pancreatic Ductal Adenocarcinoma

Trabedersen (OT-101) With Pembrolizumab for Newly Diagnosed Advanced NSCLC and Positive PD-L1 (clinicaltrials.gov) - P1/2 | N=45 | Not yet recruiting | Sponsor: University of Nebraska | Trial completion date: Dec 2029 ➔ Feb 2029

Trial completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Trabedersen (OT-101) With Pembrolizumab for Newly Diagnosed Advanced NSCLC and Positive PD-L1 (clinicaltrials.gov) - P1/2 | N=45 | Not yet recruiting | Sponsor: University of Nebraska

Metastases • New P1/2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

ONCOTELIC TO PRESENT AT THE 20TH ANNUAL CONGRESS OF INTERNATIONAL DRUG DISCOVERY SCIENCE & TECHNOLOGY (GlobeNewswire) - P1/2 | N=62 | NCT00844064 | Sponsor: Isarna Therapeutics GmbH | "Oncotelic Therapeutics, Inc...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....Intravenous therapy with OT-101 in melanoma, colorectal cancer, and pancreatic cancer was evaluated in P001- a phase I/II study....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."

P1/2 data • Colorectal Cancer • Gastrointestinal Cancer • Melanoma • Oncology • Pancreatic Cancer • Skin Cancer • Solid Tumor

The prognostic impact 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 in low-grade gliomas. (ASCO 2024) - "The specific abrogation of TGFB2 and not TGFB1 by OT101, a TGFB2-specific synthetic phosphorothioate antisense oligodeoxynucleotide, is a prerequisite to employing a strategy to target TGFB pathways. IRF5 and CD276/B7-H3 as prognostic markers are potential targets for combination therapies with TGFB2 inhibitors."

Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor • CD276 • CD68 • CD86 • IFNAR2 • IFNG • IFNGR1 • IRF1 • IRF5 • MSR1 • STAT1 • TGFB1 • TGFB2

STOP-PC: A Study of OT-101 With mFOLFIRINOX in Patients With Advanced and Unresectable or Metastatic Pancreatic Cancer (clinicaltrials.gov) - P2/3 | N=455 | Recruiting | Sponsor: Oncotelic Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

OT-101 in Combination With Pembrolizumab in Subjects With Malignant Pleural Mesothelioma Failing to Respond to Checkpoint Inhibition (clinicaltrials.gov) - P2 | N=63 | Not yet recruiting | Sponsor: Oncotelic Inc. | Trial completion date: Dec 2026 ➔ Dec 2029 | Trial primary completion date: Dec 2025 ➔ Dec 2028

Checkpoint inhibition • Combination therapy • Trial completion date • Trial primary completion date • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Solid Tumor

STOP-PC: A Study of OT-101 With mFOLFIRINOX in Patients With Advanced and Unresectable or Metastatic Pancreatic Cancer (clinicaltrials.gov) - P2/3 | N=455 | Not yet recruiting | Sponsor: Oncotelic Inc. | Phase classification: P2b ➔ P2/3 | Initiation date: Dec 2023 ➔ May 2024

Combination therapy • Metastases • Phase classification • Trial initiation date • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Invitation to Participate in STOP-PC Clinical Trial (GlobeNewswire) - "Oncotelic Therapeutics, Inc...invites participation in our STOP-PC clinical trial which is now open for recruitment....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."

Enrollment open • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Oncotelic Therapeutics Announces Opening of GMP Manufacturing Plant (GlobeNewswire) - "Oncotelic Therapeutics, Inc...unveils a state-of-the-art GMP Manufacturing Plant, a significant stride in biopharmaceutical innovation, through its joint venture Sapu Biosciences LLC. Situated in San Diego biotechnology hub, this cutting-edge, AI-driven facility marks a pivotal expansion in the company's clinical pipeline, advancing beyond its OT-101 development."

Clinical • Oncology

Oncotelic Reports Q3 2023 Compared to Q3 2022 Financial Results (GlobeNewswire) - "Highlights for Q3 2023 and thereafter....As previously stated, the JV has absorbed most of our R&D and G&A expenditures related to OT-101, which are primarily compensation related and other operational expenses. Going forward, this should permit us to continue our development efforts of OT-101, through the JV, at no cash cost to us, thereby freeing up valuable cash resources for exploring potential partnering of our remaining pipeline products."

Commercial • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Glioma • Oncology • Solid Tumor

STOP-PC: A Study of OT-101 With FOLFIRINOX in Patients With Advanced and Unresectable or Metastatic Pancreatic Cancer (clinicaltrials.gov) - P2b | N=468 | Not yet recruiting | Sponsor: Oncotelic Inc.

Combination therapy • Metastases • New P2b trial • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

OT-101 in Combination With Atezolizumab for the Treatment of Metastatic or Recurrent Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: University of Washington | N=30 ➔ 0 | Not yet recruiting ➔ Withdrawn

Combination therapy • Enrollment change • Metastases • Trial withdrawal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • BRAF • CD4 • HER-2 • NTRK • RET • ROS1

Sapu BioScience and Cromos Pharma initiating P201 – A Registrational trial for OT-101 in Pancreatic Cancer (GlobeNewswire) - "Oncotelic Therapeutics, Inc...announced today its joint venture partner, GMP Biotechnology Limited’s wholly owned subsidiary – Sapu Bioscience, LLC ('Sapu'), together with with Cromos Pharma, LLC ('Cromos'), a US-based international contract research organization ('CRO'), to conduct Sapu’s registrational trial for OT-101 in Pancreatic Cancer. P201: A Randomized Phase 2b/Phase 3 Study of the TGF-β2 Targeting Antisense Oligonucleotide OT-101 in Combination with FOLFIRINOX Compared with FOLFIRINOX Alone in Patients with Advanced and Unresectable or Metastatic Pancreatic Cancer."

New P2/3 trial • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

OT-101 in Combination With Atezolizumab for the Treatment of Metastatic or Recurrent Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=30 | Not yet recruiting | Sponsor: University of Washington

Combination therapy • Metastases • New P2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • BRAF • CD4 • HER-2 • NTRK • RET • ROS1

Oncotelic Participating at 2023 BIO International Convention (GlobeNewswire) - "Oncotelic Inc...is thrilled to announce their participation in the BIO International Convention....Key points of the presentation include: The significant role of TGF-β2 as the primary driver of survival, outpacing the influence of TGF-β1 and TGF-β3. The ongoing advancement of clinical trials for OT-101 in conjunction with P201 in Pancreatic Cancer, set to commence in the second half of 2023. Additional combination trials with various checkpoint inhibitors involving multiple cancer types are also slated to begin within the same timeframe."

New trial • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

High Intra-Tumor TGF-β2 Predicts Poor Survival in Pediatric Cancer of the Brainstem (GlobeNewswire) - "Oncotelic Therapeutics...announced the publication of High Intra-Tumor Transforming Growth Factor β2 Level as a Predictor of Poor Treatment Outcomes in Pediatric Cancer of the brainstem....Our findings provide the first evidence that high level TGFβ2 expression is associated with a poor treatment outcome....'OT-101 is the only TGFβ2 inhibitor that is in late clinical development'....A clinical study protocol looking at treatment of pediatric cancer of brainstem with OT-101 has been accepted onto the National Institute for Health and Care Research ('NIHR') portfolio."

Biomarker • Clinical protocol • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Glioma • Oncology • Solid Tumor

High Intra-Tumor TGF-β2 Predicts Poor Survival in Pediatric Cancer of the Brainstem (GlobeNewswire) - P=NA | N=NA | "Oncotelic Therapeutics, Inc...announced the publication of High Intra-Tumor Transforming Growth Factor β2 Level as a Predictor of Poor Treatment Outcomes in Pediatric Cancer of the brainstem....Our findings provide the first evidence that high level TGFβ2 expression is associated with a poor treatment outcome. The reported results also support the notion that further evaluation of the clinical potential of new strategies targeting TGFβ2 in pediatric cancer of the brainstem is warranted....A clinical study protocol looking at treatment of pediatric cancer of brainstem with OT-101 has been accepted onto the National Institute for Health and Care Research ('NIHR') portfolio."

Clinical data • Clinical protocol • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Glioma • Oncology • Solid Tumor

Treatment of recurrent/refractory (R/R) anaplastic astrocytoma (AA, WHO grade 3) patients with anti-TGFß2 RNA therapeutic OT-101 versus temozolomide is associated with improved overall survival (SNO 2019) - P2b; No abstract available.

Clinical

Anti-TGFß2 RNA therapeutic OT-101 induces durable objective responses in patients with recurrent/refractory (R/R) glioblastoma multiforme (GBM, WHO grade 4) or anaplastic astrocytoma (AA, WHO grade 3) (SNO 2019) - P2b; " 26 patients (33.8%) had marked reductions of their tumor volume after receiving OT-101: 19 achieved durable objective responses (CR: 3, PR: 16).  The median time for 90% reduction of the baseline tumor volume was 11.7 months (Range: 4.9-57.7 months).    The mean log reduction of the tumor volume was 2.2 ± 0.4 (Median = 1.4: Range: 0.4-4.5) logs. 7 had stable disease (SD) lasting > 6 months.  The median PFS (1109d [95% CI: 992 - > 1423] vs. 37d [95% CI: 35 – 59]  (Log-rank Chi Square = 69.9, P-value 1743] vs. 240d [95% CI: 169 – 361]  (Log-rank Chi Square = 47.0, P-value < 0.0001) of these 26 patients was significantly better than the PFS or OS of the remaining 51 patients.  CONCLUSION.  Anti-TGFß2 RNA therapeutic OT-101 exhibits clinically meaningful single-agent activity and induces durable CR/PR/SD in R/R HGG patients."

Clinical

Clinical predictors of response for recurrent/refractory glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA, WHO grade III) patients treated with the anti-TGF ß 2 RNA therapeutic OT-101 (SNO 2019) - P2b; "The best fit model was chosen utilizing both Akaike information criterion (AIC)  and Bayesian information criterion (BIC) from assessing Weibull, lognormal, exponential, Fréchet, and loglogistic distributions of the survival probabilities (JMP 10.02, SAS, Cary NC).  RESULTS.  In both models, time from last chemo-/radiation therapy, time from first diagnosis and baseline hematological measurements (ALC, ANC and WBC) were removed from the model as they lacked significant predictive value.  The final GLM (chi-square value = 39.7, df = 12, P< 0.0001) and OS (chi-square value = 56.0, df = 12, P< 0.0001)  models contained 7 predictor variables measured in 67 evaluable patients: Baseline Karnofsky performance scale (KPS) score; composition of previous therapy;  cancer subtype; steroid use; total OT-101 dose; age; and baseline 3D tumor volume for the target lesion. Three significant predictors were identified: Baseline KPS score (P[BOR] =..."

Clinical

Mechanism of Action for OT-101 TGF-ß immunotherapy (SITC 2022) - P1 | "Methods Pharmacokinetic analysis of OT-101/trabedersen for P001 study was assessed over the first two cycles of 7- or 4-day intravenous infusions, separated by 7- or 10-day treatment-free interval, respectively, at doses of 40, 80, 140, 160, 190, 240, 250, and 330 mg/m 2 /day to demonstrated dose exposure response...OT-101 is currently being combined with IL2, PD-1, and PDL-1 agents in multiple phase 2 trials. Trial Registration NCT00844064- Safety and Tolerability of AP 12009, Administered I.V. in Patients With Advanced Tumors Known to Overproduce TGF-beta-2"

Brain Cancer • CNS Tumor • Colorectal Cancer • Gastrointestinal Cancer • Glioblastoma • Melanoma • Oncology • Pancreatic Cancer • Solid Tumor • IL2 • PD-L1 • TGFB1 • TGFB2

IL-8 as PD biomarker for TGF-b antisense (OT-101) therapy: Results of a phase II trial. (ASCO 2017) - P1; "...Background: Trabedersen (OT-101) is a phosphorothioate antisense specific for human TGF-β2 mRNA... Peak of IL-8 response on Day 2 of OT-101 treatment was correlated with OS in PAC patients. The correlation existed between OS whether patients received subsequent chemo or not suggesting that the IL-8 spike is a PD biomarker for OT-101."

Biomarker • Clinical • P2 data • Biosimilar • Pancreatic Cancer

Second-line treatment of recurrent/refractory (R/R) glioblastoma multiforme (GBM, WHO grade 4) and anaplastic astrocytoma (AA, WHO grade 3) with a first-in-class anti-TGFβ2 RNA therapeutic administered intratumorally via convection-enhanced delivery (AACR-NCI-EORTC 2019) - P2b; "CONCLUSION. Anti-TGFβ2 RNA therapeutic OT-101 administered intratumorally via CED as second line therapy exhibits clinically meaningful single-agent activity and induces durable CR/PR/SD in R/R HGG patients."

Clinical