• Phase 2 Clinical Data Presented at ASCO-SITC Clinical Immuno-Oncology Symposium
  • Xenogenization through chemotherapy-induced genetic mutations (alkylating agents such as temozolomide) or drug-induced immunologic cell death can be effectively leveraged to for successful immunotherapy of cancer.
  • Successive treatment of recurrent GBM during 1st, 2nd, and 3rd lines extended long term survival significantly through TMZ induced xenogenization
  • A combination with OT-101- TGF-β2 antisense- with TMZ achieved the same effect with a single line of TMZ. 
  • OT-101 combination with other chemotherapies in heavily pretreated PC achieves the same extended long term survival as observed in GBM.

AGOURA HILLS, CA., March 04, 2019 (GLOBE NEWSWIRE) -- Oncotelic - a clinical-stage biopharmaceutical company focused on the treatment of cancer first in class immune booster using TGF-β RNA therapeutic - today announced clinical data supporting the use of chemotherapy-induced Xenogenization for the in situ immunization against glioblastoma and pancreatic cancer.

Drug-Induced Xenogenization (DIX), was found to be the result of pharmacologically-driven mutational events generating tumor neoantigen(s) able to induce T-cell mediated immune responses. Alkylating agents such as TMZ possess high DIX properties, being by far more potent as compared to a number of other antitumor mutagenic compounds. The repeated mutational damage should eventually breakthrough the innate immune resistant of the tumor resulting in improved overall survival. TMZ overtreatment in recalcitrant patients indeed caused improved response and improved OS. Pts exposed to TMZ all along 1st, 2nd, 3rd line of treatment exhibit increased long term survival as expected for immunotherapy. However, xenogenization has undesired consequences including secondary tumors. Secondary Hematological Malignancies (SHM) was 7.7 ± 3.2% at 10 years with incidence increasing with subsequent exposure on 2nd line and beyond.

Treatment with OT-101 reduced required TMZ treatment to a single 3rd line following OT-101. During the G004 phase 2b clinical trial of OT-101, the 2-year survival of 64 pts treated with OT-101/TMZ increased to 46.9% versus traditional TMZ treatment of 6.3% in the same trial and 5.6% and 3.3% previously reported for TMZ in 1st recurrent glioblastoma. This treatment protocol would suggest that OT-101/TMZ is an effective in situ immunization protocol for long term survival benefits without undue risk for SHM. 

Xenogenization by chemotherapy-induced immunologically active tumor cell death was found to be effective when combining with OT-101 in Pancreatic Cancer. During the Phase 1/2 P001 trial of OT-101, 1 yr survival of metastatic pancreas cancer pts treated with OT-101/Chemotherapy combination was 33.3% versus the 7% and 6% among comparable populations treated with Onivyde+5FU/LV and 5FU/LV, respectively, (p=0.0038 and p=0.0022). These data are supportive of OT-101/Chemotherapy as an effective in situ immunization protocol. More importantly, it was also shown in the P001 trial that OT-101 and OT-101/Chemotherapy operate through a common immunologic mechanism linked together by the cytokine/IL-8 nexus. As such we also reported that IL-8 spike was predictive of survival in both sets of patients.

Detailed results were presented at the ASCO-SITC Clinical Immuno-Oncology Symposium, San Francisco, CA and available for download at www.oncotelic.com.

“These results validated our concept leveraging Xenogenization potential of approved chemotherapeutic agents with known safety and efficacy profiles for rapid in situ immunization protocol,” said Vuong Trieu, Ph.D., CEO of Oncotelic. “Countering drug resistance by new chemical entities is a long, expensive, and highly unsuccessful endeavor; therefore it is desirable to explore new properties of the approved drug against drug resistance. Indeed, TMZ Xenogenization is most active in TMZ resistance.”

About Oncotelic Inc.

Oncotelic is a privately held cancer immunotherapy company dedicated to the development of first in class in situ cancer vaccine as a durable cure for difficult to treat cancer. This therapeutic cancer vaccine does not require extraction of the tumor and isolation of the antigen for immunization- a lengthy/laborious process with limited clinical effectiveness and has broad-spectrum applicability for multiple cancer types. It showed promising clinical activity in phase 2 trials for the treatment of glioblastoma and pancreatic cancer. The company aims to translate its unique insights spanning three decades with original work at Genetic Therapy Inc using adenovirus as RNA therapeutics to the current deployment of antisense as RNA therapeutics for diseases caused by TGF-beta overexpression including cancer. The founding team of Oncotelic was responsible for the development of Abraxane as chemotherapeutic agents for breast, lung, melanoma, and pancreatic cancer. Abraxane was approved in 2005 and has $1B in sales annually and Cynviloq, a next-generation Abraxane, was acquired by NantPharma. Oncotelic will leverage its deep expertise in oncology and RNA therapeutic drug development to promote the eventual cure and eradication of cancers. The team is leveraging the antisense platform for rapid drug development while avoiding mistakes made by others in the field who targeted the wrong targets or the wrong tissues. Properly developed, antisense RNA therapeutics have the potential to be superior to the mAb platform. An example would be from mutation identification to drug into a patient in less than a year with Milasen. For more information, please visit www.oncotelic.com.

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. Words such as “hope”, “vision”, “optimism”, “design”, “exciting”, “promising”, “will be”, “conviction”, "may," "will," "expect," "plan," "anticipate," "estimate," "intend," "believe" and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. These forward-looking statements are based on Oncotelic’s expectations and assumptions as of the date of this press release. Each of these forward-looking statements involves risks and uncertainties. Actual results may differ materially from these forward-looking statements. Forward-looking statements contained in this press release include, but are not limited to, statements about the progress, timing, clinical development, and scope of clinical trials and the reporting of clinical data for Oncotelic's product candidate OT-101, and the potential use of our product candidates to treat various cancer indications. 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 Oncotelic's collaborators to support or advance collaborations or product candidates and unexpected litigation or other disputes. Except as required by law, Oncotelic assumes no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available.


David Nam