On June 25, 2025 Oncotelic Therapeutics, Inc. (OTCQB: OTLC) ("Oncotelic" or the "Company"), a clinical-stage biopharmaceutical company focused on RNA-based therapeutics, reported the publication of a peer-reviewed research article highlighting TGFB2 gene methylation as a positive prognostic biomarker for pancreatic ductal adenocarcinoma (PDAC) (Press release, Oncotelic, JUN 25, 2025, View Source [SID1234654112]). The paper, published in collaboration with Sapu Biosciences, LLC ("Sapu"), a wholly owned subsidiary of GMP Biotechnology Limited ("GMP Bio"), in which Oncotelic owns a 45% stake, appears in the journal International Journal of Molecular Sciences and is entitled: "TGFB2 Gene Methylation in Tumors with Low CD8+ T-Cell Infiltration Drives Positive Prognostic Overall Survival Responses in Pancreatic Ductal Adenocarcinoma."

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Access the publication online at: View Source

The study was co-authored by Dr. Sanjive Qazi, Dr. Michael Potts, Scott Myers, Dr. Stephen Richardson, and Dr. Vuong Trieu.

Key Findings

PDAC remains one of the most lethal malignancies with limited treatment options, typically restricted to cytotoxic regimens like FOLFIRINOX. This study identifies DNA methylation signatures of the TGFB2 gene as a novel biomarker for improved overall survival, particularly in immunosuppressed tumor microenvironments characterized by low CD8+ T-cell infiltration.

Notably, patients exhibiting high TGFB2 methylation along with low expression of immune markers such as CD3D, LCK, and HLA-DRA demonstrated a highly significant median overall survival exceeding 50 months. The data suggest that TGFB2 methylation is a favorable prognostic indicator and may inform patient stratification for therapies targeting TGFB2 mRNA-such as OT-101, Oncotelic’s investigational antisense oligonucleotide.

In addition, the study underscores the importance of profiling TGFB1, TGFB2, and TGFB3 methylation to better characterize tumor immune status and select candidates for immunotherapy in otherwise resistant "cold" tumors.

Leadership Commentary

"Our latest discovery significantly enhances our understanding of the TGFB gene complex in PDAC, particularly in immunologically cold tumors," said Dr. Sanjive Qazi, lead author. "These results support further clinical development of OT-101 in PDAC, especially among patients with low T-cell infiltration and high TGFB2 methylation."

"PDAOAI, our AI-powered chatbot platform, played a pivotal role in the literature mining and analysis for this paper," added Scott Myers, Product Manager. "The integration of AI into the scientific process is accelerating discovery."

"Large language models like PDAOAI are transforming how we identify, extract, and interpret biomedical insights," said Dr. Michael Potts, VP of Data Science at Oncotelic.

The underlying source data and referenced literature used in the manuscript are accessible via Oncotelic’s proprietary AI platform, PDAOAI. Engage with the research on the public PDAOAI Discord community.

On June 25, 2025 Plus Therapeutics, Inc. (Nasdaq: PSTV) (the "Company"), a clinical-stage pharmaceutical company developing targeted radiotherapeutics with advanced platform technologies for central nervous system (CNS) cancers, reported that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application (No. 168178) for REYOBIQTM (Rhenium Re186 Obisbemeda) for the treatment of pediatric patients with supratentorial recurrent, refractory, or progressive high-grade glioma (HGG) and ependymoma (Press release, Plus Therapeutics, JUN 25, 2025, View Source [SID1234654113]). The trial will be referred to as the ReSPECT-PBC trial and is funded by a $3.0M research grant from the U.S. Department of Defense.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are very excited for the opportunity to study the novel radiotherapeutic, REYOBIQ, in difficult-to-treat pediatric brain tumors. Surgery and external beam radiation have been the mainstays of treatment for pediatric high-grade glioma and, sadly, outcomes have not improved for many decades. We believe this novel therapy that may allow higher doses of radiation while limiting the exposure to normal developing brain and delivering this agent via convection enhanced delivery (CED) directly into the tumor has the potential to make a big difference in our patients’ lives and improve outcomes," said Dr. Ashley S. Plant, M.D., Principal Investigator for the trial, attending physician in Hematology, Oncology, Neuro-oncology, and Stem Cell Transplantation at Ann & Robert H. Lurie Children’s Hospital of Chicago, A.M. Khokhar Research Scholar and Associate Professor of Pediatrics at Feinberg School of Medicine Northwestern University. "I am extremely passionate about bringing this therapy into the pediatric space and hopeful about the benefits to my patients."

Phase 1/2a Trial Design Highlights:

The Phase 1/2a trial is a two-part, single-arm, prospective study aimed at determining the maximum tolerated dose (MTD), safety, and tolerability of REYOBIQ in pediatric patients aged 6 to 21 years (with consideration for patients up to 25 years on a case-by-case basis).

Key elements of the trial design include:

Phase 1a/b (Dose Escalation): This phase will enroll an estimated 24 patients using a modified 3+3 dose escalation scheme to establish the MTD and recommended Phase 2 dose (RP2D). Safety assessment and alignment with the FDA will occur at defined intervals.

Phase 2a: This phase will enroll approximately 32 patients (12 with ependymoma and 20 with HGG) at the RP2D to assess efficacy.

Pediatric HGG including ependymoma are rare (approximately 3.3 cases per 100,000 persons) but aggressive brain tumors with limited treatment options and poor prognosis, particularly in recurrent settings. Standard treatments, including surgical resection and external beam radiation therapy, often fail to prevent recurrence, with 5-year survival rates as low as 22% for HGG, depending on tumor grade and resection extent. REYOBIQ’s targeted delivery via CED bypasses the blood-brain barrier, offering a novel approach to potentially improve outcomes for these patients.

"This pediatric FDA clearance builds on our successful track record in the safe administration and promising efficacy signals observed in adult patients with more common central nervous cancers," said Marc Hedrick, M.D., Plus Therapeutics President and Chief Executive Officer. "We expect REYOBIQ will offer much needed hope to children with aggressive and difficult-to-treat brain cancers and their families."

REYOBIQ is a novel radiotherapeutic designed to deliver high doses of beta radiation directly to brain tumors while minimizing damage to surrounding healthy tissue. The ReSPECT-PBC (pediatric brain cancer) trial builds on promising preclinical data and clinical results from the Company’s adult recurrent glioblastoma trial (ReSPECT-GBM). As recently published in Nature Communications, ReSPECT-GBM demonstrated favorable safety and clinical response with a doubling of overall survival for those patients receiving a therapeutic dose of radiation defined as > 100 Gy.

For more information, please contact @plustherapeutics.com or visit www.clinicaltrials.gov (identifier to be assigned upon registration).

About REYOBIQ (rhenium Re186 obisbemeda)
REYOBIQ (rhenium Re186 obisbemeda) is a novel injectable radiotherapy specifically formulated to deliver direct targeted high dose radiation in CNS tumors in a safe, effective, and convenient manner to optimize patient outcomes. REYOBIQ has the potential to reduce off target risks and improve outcomes for CNS cancer patients, versus currently approved therapies, with a more targeted and potent radiation dose. Rhenium-186 is an ideal radioisotope for CNS therapeutic applications due to its short half-life, beta energy for destroying cancerous tissue, and gamma energy for real-time imaging. REYOBIQ is being evaluated for the treatment of recurrent glioblastoma and leptomeningeal metastases in the ReSPECT-GBM and ReSPECT-LM clinical trials. ReSPECT-GBM is supported by an award from the National Cancer Institute (NCI), part of the U.S. National Institutes of Health (NIH), and ReSPECT-LM is funded by a three-year $17.6M grant by the Cancer Prevention & Research Institute of Texas (CPRIT). The Company’s clinical trial for pediatric brain cancer is supported by a $3 million grant from the U.S. Department of Defense’s Peer Reviewed Cancer Research Program.

On June 24, 2025 Accord Healthcare Limited (Accord) reported that the anti-PD-1 mAb, serplulimab, marketed as Hetronifly, has been approved by the MHRA to treat adults in the UK with extensive-stage small cell lung cancer (ES-SCLC), which has not previously been treated and has spread within the lungs or to other parts of the body (Press release, Accord Healthcare, JUN 24, 2025, View Source [SID1234654096]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

This approval comes in the same week as the announcement in India, bringing the total number of countries and regions in which the medicine is approved to over 40 — including Europe, China, Indonesia, and Singapore. Accord Healthcare will lead commercialisation in both the UK and India on behalf of its parent company, Intas, and its commercial partner, Henlius.

Lung cancer remains the leading cause of cancer-related death globally. Small cell lung cancer (SCLC), one of the most aggressive subtypes, accounts for approximately 15% of all lung cancer cases and is associated with limited treatment options[1].

Julian Beach, Interim Executive Director of Healthcare Quality and Access at the UK’s Medicines and Healthcare products Regulatory Agency (MHRA), commented: "As the first and only anti-PD-1 monoclonal antibody approved in the UK for small cell lung cancer, this marks an important new treatment option for patients with this aggressive type of lung cancer who currently have limited choices and face a poor prognosis."[2]

Henlius Biotech originally developed Serplulimab. In 2023, Henlius entered into a collaboration with Intas Pharmaceuticals, granting Intas exclusive rights to develop and commercialise the medicine in over 50 countries across Europe and India.

Welcoming the news, Paul Tredwell, Executive Vice-President EMENA, Accord Healthcare, said: "At Accord, we are dedicated to supporting patients with cancer. The MHRA’s approval of Hetronifly provides a new treatment option in the fight against extensive-stage small cell lung cancer — one of the most aggressive forms of lung cancer. This milestone reflects our ongoing commitment to providing novel specialty medicines for difficult-to-treat conditions."

Ping Cao, Chief Business Development Officer and Senior Vice President of Henlius said: "The approvals of serplulimab in the UK and India not only represent continued progress in our globalisation strategy but also reflect our concrete commitment to putting patients first. We are steadily expanding the global reach of the product, aiming to bring high-quality innovative therapies to more patients around the world."

In December 2022, serplulimab received orphan drug designation from the EC for the treatment of SCLC, this was recently reviewed by the committee and renewed.

ESMO has also scored serplulimab 4 out of 5 on their magnitude of clinical benefit scale (MCBS) in ES-SCLC.

About Serplulimab

Serplulimab (recombinant humanised anti-PD-1 monoclonal antibody injection)) is an anti-PD-1 mAb for the first-line treatment of SCLC and has been approved in China and several SEA countries. Serplulimab has been approved by the National Medicinal Products Administration (NMPA) in China for the treatment of squamous non-small cell lung cancer (sqNSCLC), extensive-stage small cell lung cancer (ES-SCLC), esophageal squamous cell carcinoma (ESCC) and non-squamous non-small cell lung cancer (nsNSCLC). Serplulimab was granted orphan drug designations by the FDA and the EC for the treatment of SCLC, and its bridging head-to-head trial in the United States to compare serplulimab to standard of care atezolizumab (anti-PD-L1 mAb) for the first-line treatment of ES-SCLC is well under way.

The results of 4 pivotal trials of serplulimab were published in the Journal of the American Medical Association (JAMA), Nature Medicine, Cancer Cell and British Journal of Cancer, respectively. Furthermore, serplulimab was respectively recommended by the CSCO Guidelines for Small Cell Lung Cancer, the CSCO Guidelines for Non-Small Cell Lung Cancer, the CSCO Guidelines for Esophageal Cancer, the CSCO Clinical Practice Guidelines on Immune Checkpoint Inhibitor, the China Guidelines for Radiotherapy of Esophageal Cancer, and other definitive guides, providing valuable references for clinical diagnosis and treatment of tumours.

The approvals were primarily based on the results of the global phase 3 clinical study ASTRUM-005, which enrolled 585 patients across 128 trial sites worldwide. At the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, the results from the final analysis of ASTRUM-005 were presented, showing a median follow-up of 42.4 months and a 4-year overall survival (OS) rate of 21.9% (95% CI: 17.6–26.6%) for the serplulimab plus chemotherapy group. These results further confirm the long-term survival benefit of this immunotherapy-based regimen for patients with ES-SCLC.

About Lung Cancer

Lung cancer is the most common cancer worldwide in terms of incidence and mortality. According to GLOBOCAN 2022, there were over 2.48 million new cases of lung cancer globally in 2022, accounting for 12.4% of all new cancer cases.[1]

Small cell lung cancer (SCLC), which accounts for 15% to 20% of all lung cancers, is characterised by high malignancy, early metastasis, rapid progression, and poor prognosis.

Among SCLC patients, approximately 30% to 40% are diagnosed at a limited stage, while the remaining cases are in an extensive stage.

Within Europe, the prevalence of SCLC ranges from 1 to 5 per 10,000 people.

On June 24, 2025 bioAffinity Technologies, Inc. (Nasdaq: BIAF; BIAFW), a biotechnology company advancing early-stage diagnostics and targeted therapeutics for cancer, reported that the China National Intellectual Property Administration (CNIPA) has issued a notification of patent grant for the company’s novel composition and method for selectively killing cancer by targeting the CD320 and LRP2 receptors on the cell membrane (Press release, BioAffinity Technologies, JUN 24, 2025, View Source [SID1234654097]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The newly allowed Chinese patent – titled "Compositions and Methods for Treating Cancer" – adds important global protection for bioAffinity’s innovative RNA-based therapeutic strategy and covers siRNAs and their use in cancer treatment, which is also protected by the Company’s new U.S. Patent No. 12,305,171.

The invention uses small interfering RNAs (siRNAs) to suppress the expression of CD320 and LRP2 proteins. In vitro research demonstrates this siRNA-driven double knockdown effectively targets cancer cells from multiple tumor types, including lung, breast, prostate, brain, and skin, without harming normal cells, suggesting a universal mechanism of action.

bioAffinity is exploring the application of this technology as a topical treatment specifically designed for cutaneous malignancies and neoplasms of the skin. This development aligns closely with the Company’s broader strategy of addressing cancer through both early-stage diagnostics, exemplified by CyPath Lung, and innovative therapeutic approaches.

"This newly allowed patent expands our global intellectual property portfolio and strengthens our position in developing siRNA-based therapies that exploit a fundamental vulnerability in cancer cells," said William Bauta, PhD, Chief Science Officer at bioAffinity Technologies. "Our research has shown that silencing CD320 and LRP2 leads to cancer cell death without harming normal cells – a highly selective approach with potential for broad therapeutic application."

bioAffinity continues to advance its high-growth core diagnostic platform, CyPath Lung, an accurate, noninvasive test for early-stage lung cancer detection, while simultaneously leveraging its scientific expertise toward novel therapeutic solutions that address critical unmet medical needs in oncology.

About CyPath Lung

CyPath Lung uses proprietary advanced flow cytometry and artificial intelligence (AI) to identify cell populations in patient sputum that indicate malignancy. Automated data analysis helps determine if cancer is present or if the patient is cancer-free. CyPath Lung incorporates a fluorescent porphyrin that is preferentially taken up by cancer and cancer-related cells. Clinical study results demonstrated that CyPath Lung had 92% sensitivity, 87% specificity and 88% accuracy in detecting lung cancer in patients at high risk for the disease who had small lung nodules less than 20 millimeters. Diagnosing and treating early-stage lung cancer can improve outcomes and increase patient survival. For more information, visit www.cypathlung.com.

On June 24, 2025 OS Therapies (NYSE-A: OSTX) ("OS Therapies" or "the Company"), a clinical-stage immunotherapy and Antibody Drug Conjugate (ADC) biopharmaceutical company, reported that it received positive written feedback from the US Food & Drug Administration ("FDA") Type D Meeting that occurred in mid-June 2025 regarding endpoints required to support an Accelerated Approval Program marketing application for its Phase 2b trial of OST-HER2 in the prevention or delay of recurrence in fully resected, pediatric lung metastatic osteosarcoma (Press release, OS Therapies, JUN 24, 2025, View Source [SID1234654098]). The Company reiterates that additional data from its Phase 2b trial will be presented at the major osteosarcoma conference MIB Factor in Salt Lake City on Saturday June 28, 2025 at 3:30pm MDT.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Concurrent with this announcement, the Company announced that it has submitted End of Phase 2 Meeting and Breakthrough Therapy Designation (BTD) requests to FDA based on the positive Type D Meeting feedback. The End of Phase 2 Meeting is expected to occur in the third quarter of 2025. This is in alignment with the company’s overall regulatory strategy and timelines.

"We are pleased with the feedback we received from the FDA regarding the use of external control comparators in settings where placebo-controlled randomization trials are not feasible – particularly in rare pediatric diseases such as the indication treated by OST-HER2 ," said Dr. Robert Petit, Chief Medical & Scientific Officer of OS Therapies. "Moreover, we received additional collaborative input regarding suggested statistical methods as we seek to compare OST-HER2 active treatment with external control arm(s) to support a Biologics Licensing Application (BLA) via the Accelerated Approval Program. Taken together, the feedback gives us insight on the FDA’s current position and allows us to be fully prepared for the End of Phase 2 Meeting."

OST-HER2 has received Rare Pediatric Disease Designation (RPDD) for osteosarcoma from the US FDA, and if it receives a conditional BLA via Accelerated Review prior to September 30, 2026, it will become eligible to receive a Priority Review Voucher (PRV) that it intends to immediately sell. The most recent PRV sale occurred in June 2025, valued at $160 million.

The osteosarcoma treatment market was estimated at $1.2 billion in 2022 according to Data Bridge Market Research. Approximately 50% of patients are diagnosed with a lung metastasis at some point following surgical resection and chemotherapy. 3-year survival rates in patients who were not diagnosed with a metastasis are 59%. 3-year survival rates in patients who were diagnosed with pulmonary metastasis were 30%. The Company believes the market opportunity for OST-HER2 in the prevention of lung metastases is over $500 million.

OST-HER2, an immunotherapy for osteosarcoma that uses a HER2-bioengineered form of the bacterium Listeria monocytogenes to trigger a strong immune response against HER2-expressing cancer cells, is featured in the movie Shelter Me: The Cancer Pioneers. The movie offers a look into canine comparative oncology, a field that compares treatment of cancers in dogs to those in people and covers developing treatments for rare forms of cancer. The movie is available via streaming on PBS’ website.