Oncotelic and Sapu Nano Announce DeciparticleTM Led Biomarker Framework Identifying Tumors Most Likely to Respond to IV Sapu003, an Intravenous Everolimus Nanomedicine

Rhea-AI Summary

Oncotelic (OTLC)-owned JV Sapu Nano announced a Deciparticle-led biomarker framework that identifies tumors likely to respond to IV Sapu003, an intravenous everolimus nanomedicine. The analysis evaluated >9,000 patient tumor samples across 20 cancer types and found a High-RICTOR / Low-RPTOR gene-expression signature linked to greater mTOR dependency and predicted sensitivity to IV Sapu003. The signature is enriched in HR+/HER2- breast cancer, lung adenocarcinoma, gastric, renal cell, ovarian, AML and T-cell malignancies. Sapu003 is reported to reduce GI accumulation by 67×, increase tumor tissue penetration, and enable biomarker-driven patient selection. Data will be presented at the 2025 San Antonio Breast Cancer Symposium (Dec 9-12, 2025).

Positive

• Biomarker analysis of >9,000 tumor samples
• High-RICTOR/Low-RPTOR signature identifies multiple tumor types
• 67× lower GI accumulation with IV Sapu003 versus oral everolimus
• Biomarker-driven patient selection enabled for mTOR therapy

Negative

• Reported sensitivity to Sapu003 is predictive, not a clinical efficacy readout
• No clinical trial efficacy or safety data for IV Sapu003 reported in the announcement

AGOURA HILLS, Calif., Dec. 04, 2025 (GLOBE NEWSWIRE) -- Oncotelic Therapeutics, Inc. (OTCQB: OTLC) 45% owned Joint Venture, Sapu Nano today announced new biomarker data identifying a molecular signature that predicts sensitivity to Sapu003, the company’s intravenous Deciparticle™ formulation of everolimus. These data will be presented at the 2025 San Antonio Breast Cancer Symposium (SABCS) Dec 9-12. This work describes the first prospective biomarker framework for intravenous everolimus and establishes a foundation for mTOR therapy targeted to the patient populations most likely to benefit.

The analysis, which evaluated more than 9,000 patient tumor samples across 20 cancer types, revealed that tumors exhibiting a High-RICTOR / Low-RPTOR gene-expression pattern show a significantly greater dependency on mTOR signaling and are therefore, more likely to respond to potent mTOR inhibition delivered by IV Sapu003.

High-RICTOR / Low-RPTOR Signature Identifies Patients Most Likely to Benefit

The biomarker analysis demonstrated that:

• Tumors with elevated RICTOR (mTORC2 activation) and suppressed RPTOR (limited mTORC1 scaffolding) show heightened reliance on mTORC2-AKT survival signaling.
• These tumors exhibit increased glycolytic flux, elevated metabolic stress markers, and reduced compensatory feedback, making them vulnerable to systemically distributed everolimus.
• This phenotype/genotype was strongly enriched in:
  • HR+/HER2- breast cancer
  • Lung adenocarcinoma
  • Gastric cancer
  • Renal cell carcinoma
  • Ovarian cancer
  • AML and T-cell malignancies
    
    

Across multiple datasets, patients with this signature had significantly worse survival with standard therapy, but showed predicted sensitivity to Sapu003.

Why IV Sapu003 Unlocks Biomarker-Driven mTOR Therapy

Oral everolimus is limited by:

• Low and variable bioavailability
• High GI accumulation
• mTORC1-biased inhibition
• Lack of biomarker selection

Sapu003 overcomes these barriers by delivering:

• 67× lower GI accumulation
• High tissue penetration into metabolically active tumors
• Unchanged intrinsic metabolism, preserving pharmacologic specificity
  
  

This enables, for the first time, biomarker-enriched patient selection for an mTOR inhibitor.

Management Commentary

“Up to now mTOR inhibitor therapy has lacked an empirical patient selection strategy beyond tumor type,” said Dr. Seymour Fein, Chief Medical Officer of Sapu Nano. “The High-RICTOR/Low-RPTOR signature gives us, for the first time, a molecular map of which patients are most likely to benefit. The potential for targeting a more sensitive patient population combined with the consistent pharmacokinetic profile of Sapu003 administered intravenously creates an entirely new therapeutic opportunity for mTOR-driven cancers.”

About the Biomarker Discovery Approach

The SABCS analysis integrated:

• 9,000+ TCGA and MET500 tumor transcriptomes
• mTOR pathway co-expression networks
• Metabolic clustering of glycolysis-addicted tumors
• Survival modeling across multiple cancer types
• Predictive modeling of everolimus pathway dependency
  
  

This systems-biology approach allowed identification of mTORC2-dominant tumors that would be poorly targeted by oral everolimus but potentially responsive to IV Sapu003.

About Sapu003

Sapu003 is a novel intravenous nanoparticle formulation of everolimus engineered using Sapu Nano’s proprietary Deciparticle^™ technology. It is designed to overcome the poor bioavailability, intestinal toxicity, and variable patient exposure seen with oral everolimus while enabling reliable, predictable weekly IV dosing.

About the Deciparticle^™ Platform

The Deciparticle^™ platform is a proprietary nanotechnology engineered to encapsulate hydrophobic molecules as uniform, sub-20 nm nanoparticles for intravenous administration. The platform improves systemic exposure, reduces GI deposition, and supports precision delivery while maintaining manufacturability at clinical scale.

About Sapu Nano

Sapu Nano is a clinical-stage biotechnology company developing Deciparticle^™ nanomedicine therapeutics designed to optimize the delivery of hydrophobic oncology agents and peptide-based therapeutics. The company operates an integrated ISO-5 cGMP manufacturing facility supporting rapid progression from formulation to clinical trial supply.

For more information, visit www.sapunano.com.

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, melanoma (through CA4P), and Acute Myeloid Leukemia “AML” (through OXi 4503). Oncotelic also acquired PointR Data Inc. in November 2019.

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 ("PD"). Over 60,000 new patients are being diagnosed with PD in the United States and currently there are over 1 million patients in the US and expected to increase to over 1.2 million by 2030. In addition, approximately 10 million suffer from this disease globally. https://www.parkinson.org/Understanding-Parkinsons/Statistics. AL-101 is also being developed for Erectile Dysfunction ("ED"). ED is the most prevalent male sexual disorder globally. The percentages of men affected by ED are as follows: 14.3-70% of men aged 60 years, 6.7-48% of men aged 70 years, and 38% of men aged 80 years (Geerkens MJM et al. (2019). Eur Urol Focus. pii: S2405-4569(19)30079-3). However, with the increasing administration of PDE5 inhibitors in clinical practice, it was found that approximately 30-35% of ED patients are treatment failures (McMahon CN et al. (2006). BMJ, 332: 589-92). AL-101 is designed to target treatment failure ED patients who do not respond to PDE5 inhibitors. Through similar mechanism of action, AL-101 is being developed for Female Sexual Dysfunction ("FSD"). Female sexual dysfunction is a prevalent problem, afflicting approximately 40% of women and there are few treatment options. FSD is more typical as women age and is a progressive and widespread condition. (Allahdadi, KJ et al. (2009) Cardiovascular & hematological agents in medicinal chemistry, 7(4), 260-269). There is no available drug for the treatment of FSD. In June 2019, the U.S. Food and Drug Administration approved Vyleesi (bremelanotide) to treat acquired, generalized hypoactive sexual desire disorder ("HSDD") in premenopausal women. This is the only available drug treatment. Vyleesi has essentially replaced the only other drug for HSDD - however, it has a long list of drug-drug interactions, including commonly used antidepressants, such as fluoxetine and sertraline. In addition, it has a black box warning regarding its use with alcohol, a combination that has been associated with hypotension and syncopal episodes. Therefore, there is an urgent need for effective therapy against FSD and HSDD.

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Forward-looking statements include, but are not limited to, statements regarding our or our management’s expectations, hopes, beliefs, intentions or strategies regarding the future, such as our estimates regarding anticipated operating income or losses, future performance, future revenues and projected expense, including that to fund our clinical and other development programs; our liquidity and our expectations regarding our needs for and ability to raise additional capital; our ability to continue as a going concern; our ability to select and capitalize on commercially desirable product opportunities as a result of limited financial resources; our ability to manage our expenses effectively and raise the funds needed to continue our business; our ability to retain the services of our current or future executive officers, directors and principal consultants; the competitive nature of our industry and the possibility that our products or product candidates may become obsolete or may not generate revenues as expected or at all; our ability to obtain and maintain regulatory approval of our existing products and any future products we may develop; the development of and the process of commercializing AI/Blockchain and other technologies for supporting the development of OT- 101 and Artemisinin for COVID-19, OT-101, including development of OT-101, Artemisinin, OXi4503, CA4P and our 2021 in-licensing of apomorphine; the initiation, timing, progress and results of our preclinical and clinical trials, research and development programs; regulatory and legislative developments in the United States and foreign countries; the timing, costs and other limitations involved in obtaining regulatory approval for any product; the further preclinical or clinical development and commercialization of our product candidates; the entering into any corporate transactions to develop our products through partnerships, joint ventures or other corporate transactions; our ability to make a proposed initial public offering between us and our joint-venture partners for the joint venture, statements about future plans related to the operations of the JV, taking the JV into an initial public offering or the success thereof: building and the success of our nanoparticle platform and the related success of launching the platform; 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Contact Information:
For Oncotelic Therapeutics, Inc.:
Investor Relations
ir@oncotelic.com

FAQ

What is the High-RICTOR/Low-RPTOR signature announced by Oncotelic (OTLC) on Dec 4, 2025?

It is a gene-expression pattern (High RICTOR, Low RPTOR) that the analysis linked to greater mTOR dependency and predicted sensitivity to IV Sapu003.

How many tumor samples and cancer types were evaluated in the OTLC/Sapu Nano biomarker analysis?

The analysis evaluated more than 9,000 patient tumor samples across 20 cancer types.

Which cancers were enriched for the High-RICTOR/Low-RPTOR signature in the OTLC announcement?

Enriched tumor types include HR+/HER2- breast cancer, lung adenocarcinoma, gastric cancer, renal cell carcinoma, ovarian cancer, AML and T-cell malignancies.

What advantage does IV Sapu003 claim over oral everolimus according to the Dec 4, 2025 announcement?

Sapu003 is reported to deliver 67× lower GI accumulation, higher tumor penetration, and preserve intrinsic metabolism compared with oral everolimus.

Will Oncotelic (OTLC) present these biomarker data at a conference, and when?

Yes, the data will be presented at the 2025 San Antonio Breast Cancer Symposium taking place Dec 9-12, 2025.

Does the announcement include clinical trial results proving Sapu003 efficacy for OTLC investors?

No, the announcement reports predictive biomarker and preclinical/pharmacologic findings but does not provide clinical efficacy or safety trial readouts.