combretastatin A1 di-phosphate (OXi4503) / Oncotelic - LARVOL DELTA

Targeting the Tumor Vascular Supply to Enhance Radiation Therapy Administered in Single or Clinically Relevant Fractionated Schedules. (PubMed, Int J Mol Sci) - "There was a dose-dependent increase in radiation response when the combined with a single, stereotactic, or conventional fractionated irradiation, but these enhancements plateaued at around a drug dose of 25 mg/kg. This pre-clinical study demonstrated how VDAs should be combined with clinically applicable fractionated radiation schedules for the optimal anti-tumor effect, thus suggesting the necessary pre-clinical testing required to ultimately establish VDAs in clinical practice."

Journal • Breast Cancer • Oncology • Solid Tumor

Improving immunotherapy outcome in solid tumor by combining with other established cancer treatments (ESTRO 2023) - "Our Tumor model is generally unresponsive to Anti-CTLA-4 as a single therapy agent, even though an effect could be observed in the smallest size tumors.  An enhanced response was obtained when it was combined with either proton radiation or OXi4503. With increasing the of primary tumor size at treatment, the benefit of combinational therapy decreases, indicating negative co-relation between tumor size at treatment and the resulting efficacy of the combination therapy. There is a possibility of the enhancement being strongly dependent on the extent of damage done prior to anti-CTLA-4 treatment and further investigations are bing carried out to determine the minimum damage for the combination therapy to be effective in smaller size primary tumors."

Breast Cancer • Oncology • Solid Tumor

Results from a Phase 1b (OX1222) Dose-Ranging Study of OXi4503 Combined with Cytarabine in Patients with Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome (ASH 2017) - P1/2; "The vascular disrupting agent OXi4503 in combination with cytarabine (1 g/m2/day) is well tolerated with preliminary evidence of activity in heavily pretreated, relapsed and refractory AML patients, including those with poor risk cytogenetic profiles. This Phase 1b study at time of writing showed evidence of activity at doses from 3.75 to 9.76 mg/m2 with 17% of patients achieving CR, suggesting a re-sensitizing effect to cytarabine. Additional studies of Oxi4503 in well-controlled clinical trials to further characterize the initial safety and efficacy of this novel agent are warranted."

P1 data • Acute Myelogenous Leukemia • Biosimilar • Myelodysplastic Syndrome

ONCOTELIC ANNOUNCES US PATENT GRANT FOR CA4P AND OXI4503 COMBINATION WITH CHECKPOINT INHIBITORS (GlobeNewswire) - "Oncotelic Therapeutics, Inc...is pleased to announce the grant of patent application no. 15/753,882...by the US Patent Office. The claims of the patent are directed to a pharmaceutical composition for producing an anti-tumor effect in a subject suffering from cancer or a tumor, comprising a Vascular Disrupting Agent (VDA) comprising a combretastatin agent and one or more antibodies selected from the group consisting of: a CTLA-4 antibody, a PD-i antibody, a PD-Li antibody, and a PD-L2 antibody in amounts effective therefore in a pharmaceutical carrier, where in the VDA is combretastatin Al diphosphate (CAl P) or combretastatin A4 phosphate (CA4P) or others."

Patent • Acute Myelogenous Leukemia • Giant Cell Tumor of Bone • Hematological Malignancies • Hepatocellular Cancer • Leukemia • Liver Cancer • Myelodysplastic Syndrome • Oncology

Longitudinal photoacoustic imaging of the pharmacodynamic effect of vascular targeted therapy on tumors. (PubMed, Clin Cancer Res) - "we have shown for the first time that PAI can observe the pharmacodynamic response of tumor vasculature to drug treatment both longitudinally and at different dose levels. Assessment of differing response to treatment based on vascular pathophysiological differences between patients has the potential to provide personalised drug therapy; we have demonstrated that PAI, which is clinically translatable, could be a powerful tool for this purpose."

Journal • PK/PD data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

"#FDA Granted #PediatricDiseaseDesignation For #OXI4503 $MATN https://t.co/JG2qiA7mtj" (@1stOncology)

Clinical • Pediatrics

FDA Granted Pediatric Disease Designation for OXi-4503 (GlobeNewswire) - “Mateon Therapeutics…announced today that the US Food and Drug Administration (FDA) granted our request and designate OXi4503 (combretastatin A1-diphosphate; CA1P) for treatment of acute myeloid leukemia (AML) due to genetic mutations that disproportionately affect pediatric patients as a drug for a ‘rare pediatric disease,’ as defined in section 529(a)(3) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 360ff(a)(3)).”

FDA event • Acute Myelogenous Leukemia • Hematological Malignancies • Oncology

Tumors Resistant to Checkpoint Inhibitors Can Become Sensitive after Treatment with Vascular Disrupting Agents. (PubMed, Int J Mol Sci) - "Histological assessment of CD4/CD8 expression actually showed decreased levels up to 10 days after treatment with OXi4503 (50 mg/kg). Thus, the non-immunogenic C3H mammary carcinoma was unresponsive to checkpoint inhibitors, but became responsive in mice treated with VDAs, although the mechanism remains unclear."

Checkpoint inhibition • IO Biomarker • Journal • Breast Cancer • Oncology • Solid Tumor • CD8

Safety, feasibility and preliminary efficacy of single agent combretastatin A1 diphosphate (OXi4503) in patients with relapsed or refractory acute myeloid leukemia or myelodysplastic syndromes. (PubMed, Br J Haematol) - No abstract available

Clinical • Journal

A Phase 1B Clinical Study of Combretastatin A1 Diphosphate (OXi4503) and Cytarabine (ARA-C) in Combination (OXA) for Patients with Relapsed or Refractory Acute Myeloid Leukemia. (PubMed, Cancers (Basel)) - "The median overall survival (OS) time for the four patients who achieved a CR/CRi was 528 days (95% CI: 434-NA), which was significantly longer than the median OS time of 113 days (95% CI: 77-172) for the remaining 22 patients who did not achieve a CR/CRi (Log Rank Chi Square = 11.8, p-value = 0.0006). The safety and early evidence of efficacy of the OXA regimen in R/R AML patients warrant further investigation in a Phase 2 clinical study."

Clinical • Journal • P1 data

Mateon Therapeutics team publishes a new peer-reviewed oncology article on the positive clinical study results for its lead anti-leukemia drug combretastatin A1 plus cytarabine in adult patients with relapsed acute myeloid leukemia (GlobeNewswire) - P1/2, N=105; OXI1222 (NCT02576301); Sponsor: Mateon Therapeutics; "The study showed that adding OXi4503 to the standard chemotherapy drug cytarabine was generally well tolerated by AML patients and a maximum tolerated dose level of OXi4503 was identified as the recommended dose for further clinical development of this novel two-drug combination. In 26 evaluable AML patients, there were 4 complete remissions (CR/CRi) and one partial remission (PR). The CR responses were associated with >1-year overall survival times."

P1/2 data

Mateon Therapeutics announces positive clinical study results for its lead anti-leukemia drug combretastatin A1 plus cytarabine in adult patients with relapsed acute myeloid leukemia (GlobeNewswire) - P1, N=105; NCT02576301; Sponsor: Mateon Therapeutics; "Mateon Therapeutics Inc. (OTCQB:MATN), dedicated to the development of innovative treatments for cancer, today announced that the multi-institutional OXI1222 study in people with previously treated relapsed acute myeloid leukemia (AML) met its primary endpoint....In 26 evaluable AML patients, there were 4 complete remissions (CR/CRi) and one partial remission (PR). The CR responses were associated with >1-year overall survival times."

P1 data

Oncotelic’s Patented Lead Anti-Cancer Drug Candidate as Well as Drug Delivery Platform for Brain Tumors on Track for Advanced Pivotal Phase 3 Clinical Testing (GlobeNewswire, Mateon Therapeutics) - AGOURA HILLS, Calif., July 30, 2019 (GLOBE NEWSWIRE) -- Oncotelic Inc (“Oncotelic”), a wholly owned subsidiary of Mateon Therapeutics Inc (OTCQB:MATN) dedicated to the development of innovative treatments for cancer, announced today that its team members will participate and provide clinical development updates at upcoming medical-scientific conferences regarding the clinical development plans for the portfolio drugs OT101 (target: brain tumors) and OXi4503 (target: leukemias) aimed at their regulatory approval. OT101, a first-in-class RNA therapeutic designed to abrogate the immunosuppressive actions of TGF-b2, is Oncotelic’s lead anti-brain tumor drug candidate.

Biomarker • Clinical • Commercial • New trial • Regulatory