On October 27, 2025 Cellectar Biosciences, Inc. (NASDAQ: CLRB), a late-stage clinical biopharmaceutical company focused on the discovery and development of drugs for the treatment of cancer, reported the U.S. Food and Drug Administration (FDA) has granted rare pediatric drug designation (RPDD) for iopofosine I 131 in inoperable relapsed or refractory pediatric high-grade glioma (r/r pHGG).

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Iopofosine I 131 is a potential first-in-class, novel cancer targeting agent utilizing a phospholipid ether as a radioconjugate monotherapy. The FDA previously granted Orphan Drug Designation for iopofosine I 131 for the treatment of pHGG.

"Receiving Rare Pediatric Disease Designation for iopofosine I 131 underscores its potential to address one of the most devastating cancers affecting children and young adults. Combined with the encouraging interim results from our CLOVER-2 pHGG study, which showed meaningful improvements in progression-free and overall survival, this designation further validates the promise of our targeted radiotherapeutic approach," stated James Caruso, president and CEO of Cellectar. "We believe iopofosine I 131 represents a compelling opportunity for strategic collaboration to accelerate development and bring a potentially first-in-class therapy to patients who urgently need new options."

The FDA’s Rare Pediatric Disease Designation program is intended to encourage the development of new therapies for serious and life-threatening diseases that primarily affect individuals under 18 years of age. If a New Drug Application (NDA) for iopofosine I 131 is approved, upon reauthorization of the program Cellectar may be eligible to receive a Priority Review Voucher (PRV), which can significantly expedite the review process for future New Drug Applications or Biologic License Applications, may be redeemed to receive priority review for another marketing application or may be sold or transferred.

Pediatric high-grade gliomas are a collection of aggressive tumors affecting the brain and central nervous system. As reported in the literature, median progression free survival (PFS) and overall survival (OS) for patients with relapsed pHGG is poor; approximately 2.25 months and 5.6 months, respectively.

Interim data from CLOVER-2, the company’s ongoing Phase 1b trial of iopofosine I 131 in children, adolescents and young adults with r/r pHGG at multiple sites in the United States and Canada, were highlighted in an oral presentation at the recent American Association for Cancer Research (AACR) (Free AACR Whitepaper) Special Conference on Pediatric Cancer that took place in late September 2025.

The company’s chief operating officer, Jarrod Longcor, delivered the update, "Precision Radiotherapy for Incurable Brain Tumors: Phase 1b Dose & Regimen Optimization Study of Iopofosine I 131 in Inoperable Relapsed or Refractory Pediatric High-Grade Glioma, Interim Data Assessment," which showed that all patients receiving a minimum of 55 mCi total administered dose (n=6) experienced an average of 5.4 months of PFS and 8.6 months of OS, ongoing. All patients experienced disease control, which according to the committee for the Response Assessment in Pediatric Neuro-Oncology (RAPNO) does correlate with survival benefit. Three patients who received additional dosing cycles (a minimum of four total infusions) had an average PFS of 8.1 months and an OS of 11.5 months (ranging from 4.9 to 14.9 months), ongoing, with two achieving an objective response (ORR).

Two case studies were highlighted in the oral presentation. Case Study 1 showed a 25-year-old male with diffuse hemispheric glioma with the H3 G34R/V mutation who had three prior therapies and who received a total administered dose of 126.6mCi of iopofosine I 131 over four doses (40mCi/m2/dose) had his target lesion reduced by more than 50% approximately eight months post screening. This patient had PFS of 10.9 months and survival is ongoing at greater than 18 months as of July 25, 2025.

Case Study 2 showed a 15-year-old female with ependymoma who had eight prior therapies and who received a total administered dose of 58.9mCi of iopofosine I 131 over four doses (20mCi/m2/dose) had her target lesion reduced from 252mm2 to approximately 141mm2. This patient had PFS of 11.2 months and her ongoing survival was greater than 17 months as of July 22, 2025.

Iopofosine I 131 was well tolerated and its toxicity profile was consistent with the company’s previously reported safety data. Importantly, patients on iopofosine I 131 did not experience any cardiovascular, renal, or liver toxicities, and no peripheral neuropathy or significant bleeding. The safety profile was consistent with selective targeting of tumor sites with clinically negligible off-target effect outside the hematologic system. The most frequently reported treatment emergent adverse events were hematologic in nature (thrombocytopenia, neutropenia and anemia) and were predictable and manageable. No treatment-related deaths were reported.

The complete presentation can be accessed on the company’s website here.

About Pediatric High-Grade Gliomas
Pediatric high-grade gliomas are a collection of aggressive tumors affecting the brain and central nervous system. The patients enrolled in CLOVER-2 with pHGG (n=14) were diagnosed with diffuse midline gliomas (DMG), ependymomas, diffuse intrinsic pontine gliomas (DIPG), diffuse hemispheric gliomas (DHG) and anaplastic ependymomas. As reported in the literature, median progression free survival (PFS) and overall survival (OS) for patients with relapsed pHGG is poor; approximately 2.25 months and 5.6 months, respectively. While MRI measures of tumor volume change can be helpful and are used as a surrogate in clinical trials, they often fail to predict survival.

About the CLOVER-2 Trial
The Phase 1b trial of iopofosine I 131 consists of children, adolescents and young adults with r/r pHGG at multiple sites in the United States and Canada. The study is designed to evaluate the safety and tolerability of iopofosine I 131 in two dosing cohorts, one cohort receiving two doses at 20mCi/m2 each separated by 14 days for two cycles with a third optional cycle. Patients in the second cohort will receive 10 mCi/m2 each, separated by 14 days for three cycles with a fourth optional cycle. The study will also determine therapeutic activity defined as progression free survival (PFS) and overall survival, antitumor activity defined as the reduction in tumor volume and identify the recommended Phase 2/3 dose of iopofosine I 131 in children, adolescents and young adults with r/r pHGG.

(Press release, Cellectar Biosciences, OCT 27, 2025, View Source [SID1234661196])

On October 27, 2025 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a pioneer in the development of differentiated targeted radiotherapies, reported the presentation of the first ever preclinical data of ATNM-400 in non-small cell lung cancer (NSCLC). ATNM-400 a novel, multi-indication first-in-class antibody radioconjugate armed with the potent alpha-emitter Actinium-225 (Ac-225) is Actinium’s lead solid tumor program, which is also being studied in prostate cancer. The data presented at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) studied ATNM-400 in Epithelial Growth Factor Receptor (EGFR)-mutant NSCLC models.

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ATNM-400 demonstrated superior efficacy with 3-5x greater tumor growth inhibition compared to standard-of-care therapies across EGFR-mutant NSCLC including:

Frontline: Osimertinib (TARGRISSO, AstraZeneca) an EGFR tyrosine kinase inhibitor (TKI)

Second line: Dato-DXd (DATROWAY, AstraZeneca/Daiichi Sankyo) a Trop-2 antibody drug conjugate (ADC)

Third line: Amivantamab (RYBREVANT, J&J), an EGFR-cMET bispecific antibody

ATNM-400 also demonstrated synergistic activity in combination with osimertinib with complete tumor regression in 100% of tumor-bearing animals. The synergistic mechanism of this combination is supported by increased expression of the ATNM-400 target antigen after EGFR inhibition with osimertinib. In addition, previously published data of external beam radiotherapy (EBRT) combined with osimertinib resulted in improved progression free survival (PFS) compared to osimertinib alone, providing a strong clinical rationale for combining targeted alpha-therapy via ATNM-400 with EGFR targeting therapies Sampath et al. (AstraZeneca & UT Southwestern Harold C. Simmons Comprehensive Cancer Center)1.

Dr. Sandip Patel, Professor of Medicine at the University of California San Diego, an author on the poster, stated, "Targeted radiotherapy has transformed the prostate cancer treatment landscape and exemplifies what can be achieved with this technology. ATNM-400 represents a novel and differentiated development candidate for non-small cell lung cancer with EGFR mutations. The positive clinical results with EBRT and osimertinib provide strong support for combining targeted alpha-therapy via ATNM-400 and EGFR therapies to effectively deliver radiation to the target tumors and leverage mechanistic synergies while minimizing off-target effects. I am highly encouraged by these data that demonstrate the potential of ATNM-400 which would be a first-in-class radiotherapy."

Notable ATNM-400 NSCLC Data

ATNM-400 produced superior tumor growth inhibition (TGI) in animals bearing human lung cancer NCI-H1975, which carry L858R and T790M EGFR mutations

TGI with ATNM-400 was 3-5 times higher than what was achieved with the current standard of care EGFR-mutant NSCLC therapies including TAGRISSO, DATROWAY and RYBREVANT

The combination of ATNM-400 and osimertinib produced cures in all tumor-bearing animals with complete tumor regression, outperforming either agent alone and suggesting synergistic activity

The ATNM-400 target antigen is overexpressed in NSCLC and is linked to treatment resistance including to osimertinib

Osimertinib treatment significantly increased the expression of the ATNM-400 target antigen in NCI-H1975 lung cancer cells

This increased target expression post-osimertinib notably increased ATNM-400’s in vitro cytotoxic effect when combined post-osimertinib
Sandesh Seth, Actinium’s Chairman and CEO, stated, "Improving outcomes for patients with non-small cell lung cancer remains a major challenge evidenced by the significant number of therapies and modalities in development. ATNM-400 represents a truly innovative approach that leverages the potent Ac-225 alpha-emitter payload against a target that is overexpressed in lung cancer and linked to treatment resistance. These results strongly support ATNM-400’s differentiated profile and its potential for development in first, second and third-line treatment settings, alone or in combination with some of the most successful drugs that compete with each other in the EGFR-mutant segment. ATNM-400’s potential against difficult to treat and common mutations in lung cancer and the recent data updates in prostate cancer at the Prostate Cancer Foundation meeting further validate the multi-tumor potential of ATNM-400 in several disease and treatment settings that support several blockbuster drugs. We look forward to providing further updates on this exciting pipeline candidate as we progress into clinical development."

Potential for ATNM-400 in NSCLC

Lung cancer is the most common cancer worldwide with more than 200,000 new cases estimated in 2025 in the U.S. and over 2 million new cases globally. NSCLC accounts for approximately 85 percent of all lung cancer cases with EGFR mutations detected in approximately 10-15 percent of Western cases and 40-60 percent of some Asian populations. Approved therapies for EGFR-mutant NSCLC collectively generated approximately $7 billion in sales in 2024, including EGFR tyrosine kinase inhibitor osimertinib (TARGRISSO, AstraZeneca) in the frontline setting that led the class with sales of $6.6 billion in 2024, Trop-2 antibody drug conjugate Dato-DXd (DATROWAY, AstraZeneca/Daiichi Sankyo) that was approved in January 2025 in the second line setting, and the EGFR-cMET bispecific antibody amivantamab (RYBREVANT, J&J) in later lines that had sales of $0.3 billion in 2024. Despite their success, nearly all patients eventually develop resistance within two to three years, underscoring the urgent need for novel, differentiated therapies to overcome resistance and improve survival outcomes. ATNM-400 is designed to address this significant unmet need by combining the high-affinity targeting of a monoclonal antibody directed against an antigen overexpressed in NSCLC, associated with poor prognosis and osimertinib resistance, with the potent alpha-emitting isotope Ac-225, which induces irreversible double-strand DNA breaks. The preclinical data showed ATNM-400’s differentiated potential as monotherapy, combination therapy with EGFR-inhibitors like osimertinib and in post-EGFR-resistance settings.

About ATNM-400

ATNM-400 is a highly innovative, first-in-class, and multi-indication Actinium-225 (Ac-225) targeted radiotherapy candidate in development for prostate cancer and non-small cell lung cancer (NSCLC). ATNM-400 is highly differentiated in prostate cancer as it targets a distinct non-PSMA protein strongly implicated in prostate cancer disease biology including progression and treatment resistance. Unlike 177Lu-PSMA-617, the active agent in Pluvicto and the majority of radiotherapies under development, which rely on PSMA targeting, ATNM-400 is designed to maintain efficacy in low-PSMA or high-PSMA resistant disease, a major unmet clinical need as up to 30% of patients do not respond to PSMA radioligand therapies and up to 60% of patients have at least one PSMA-negative tumor lesion. Ac-225 delivers high-linear-energy-transfer alpha particles that induce irreparable double-strand DNA breaks, offering superior potency over beta emitters like Lutetium-177 (177Lu), and has a shorter tissue path length that may reduce off-target toxicity. The receptor specifically targeted by ATNM-400 continues to be expressed at a high level even after androgen receptor inhibitor (ARPI) and ATNM-400 has shown to overcome resistance to the ARPI therapy enzalutamide and work synergistically in combination with enhanced tumor control including complete tumor regression. In NSCLC, ATNM-400 has shown superior efficacy to approved first, second and third line EGFR therapies including small molecules, antibody drug conjugates and bispecific antibodies that is synergistic with osimertinib, an EGFR tyrosine kinase inhibitor (TKI) that is a standard of care therapy approved for treatment of patients in the frontline setting, and is also able to overcome osimertinib resistance.

Prostate cancer is the most commonly diagnosed cancer in men, with ~1.5 million new cases globally and over 313,000 expected in the U.S. in 2025. While early-stage disease is typically managed with surgery, radiation, and ARPI therapy, up to 20% of cases progress to mCRPC – a lethal stage with limited treatment options. Targeted radiotherapy is a growing field in prostate cancer, dominated by PSMA-targeting agents like Pluvicto, which had sales of over $1.3 billion in 2024, yet many patients either lack PSMA expression or develop resistance to Pluvicto. In the U.S., 40,000–60,000 mCRPC patients annually progress after ARPI therapy, which as a class had sales of over $10.0 billion in 2024 including enzalutamide (Xtandi) that led the ARPI class with sales of over $5.9 billion in 2024, highlighting a significant unmet need. Lung cancer is the leading cause of cancer deaths and there are there are over 200,000 new cases expected in the U.S. in 2025 and over 2 million cases globally. NSCLC accounts for approximately 85% of all lung cancer cases. EGFR targeting therapies had sales of approximately $7 billion in 2024 with the EGFR TKI Osimertinib (TAGRISSO, AstraZeneca) generating sales of $6.6 billion in 2024. Across prostate cancer and NSCLC, there are approximately 500,000 new cases in the U.S. alone.

(Press release, Actinium Pharmaceuticals, OCT 27, 2025, View Source [SID1234657038])

On October 27, 2025 Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) reported management participation in the UBS Global Healthcare Conference. Reshma Kewalramani, President and Chief Executive Officer will participate in a fireside chat on Tuesday, November 11, 2025, at 10:15 a.m. ET.

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A live webcast of management’s remarks will be available through the Vertex website, www.vrtx.com, in the "Investors" section under the "News and Events" page. A replay of the conference webcast will be archived on the company’s website.

(Press release, Vertex Pharmaceuticals, OCT 27, 2025, View Source [SID1234657039])

On October 27, 2025 Onward Therapeutics SA, a clinical stage oncology company, reported that its French subsidiary, Onward Therapeutics France, has exercised its exclusive option and entered into a worldwide license agreement with Institut du Cancer de Montpellier (ICM), France, to further advance a breakthrough program in onco-metabolism.

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This license agreement builds upon the exclusive collaboration and option agreement signed between Onward Therapeutics France and ICM, Inserm and Université de Montpellier in June 2021, under which the company provided research funding to support the discovery program at ICM. The successful progress achieved through this collaboration has led to the identification of promising compounds and the transition of the drug discovery program into Onward Therapeutics’ development pipeline. The program is currently in lead optimization, with the goal of nominating IND-enabling candidates next year.

The program, designated OT-S00X by Onward Therapeutics, is an innovative onco-metabolism project aimed at expanding therapeutic possibilities in cancer treatment. Proof-of-principle studies have demonstrated strong preclinical efficacy, and promising candidates from two distinct chemical series have already been identified, and compounds with improved physico-chemical properties will be generated through artificial intelligence approaches.

"OT-S00X represents a breakthrough in targeting tumor onco-metabolism. Preclinical studies have shown that the efficacy of these compounds strongly correlates with a predictive biomarker of response across multiple tumor types, providing a clear rationale for this novel mechanism of action." said Dr. Armand de Gramont, Chief Scientific Officer of Onward Therapeutics."OT-S00X introduces a differentiated metabolic strategy that broadens our pipeline and primarily provides an innovative way to tackle cancer resistance," added Dr Alain Herrera, President of Onward Therapeutics France and Chief Medical Officer of Onward Therapeutics.

"We are delighted to strengthen our collaboration with Onward Therapeutics," said Prof. Marc Ychou, Directeur Général of ICM. "The innovative OT-S00X program, initially developed by our research teams together with Inserm and Université de Montpellier, demonstrates the potential of translational science to generate novel therapeutic strategies in oncology. It also highlights the international reach of ICM and the strength of the Montpellier MedVallée ecosystem in driving cancer innovation."

(Press release, Onward Therapeutics, OCT 27, 2025, View Source [SID1234657041])

On October 27, 2025 Diakonos Oncology Corp., a clinical-stage biotechnology company developing a new generation of immunotherapies to treat challenging and aggressive cancers, reported a poster presentation at the upcoming Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 40th Annual Meeting, being held November 5-9 in National Harbor, MD.

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"DOC1021 represents a novel and highly targeted approach to activating the patient’s own immune system against cancer cells," said Jay Hartenbach, President and COO of Diakonos Oncology. "Building on promising results in glioblastoma, we are now excited to share preliminary data in pancreatic cancer. Based on this early data, we believe this patient-derived immunotherapy holds great potential for pancreatic cancer and other indications with a high unmet need."

Presentation Details
Title: Phase I Trial of DOC1021 Cell-Based Immunotherapy for Resectable or Borderline Resectable Pancreatic Ductal Adenocarcinoma
Presenting Author: William Decker, PhD, Baylor College of Medicine, Houston, TX
Abstract Number: 540
Session Type: Poster Presentation Session
Session Date: Saturday, November 8, 2025
Location: Prince George ABC Exhibit Halls, Gaylord National Resort and Convention Center

About DOC1021
DOC1021 is a first-in-class, patient-derived double-loaded dendritic cell therapy that uniquely combines tumor lysate and amplified tumor-derived mRNA. The immunotherapy is made with a patient’s dendritic cells combined with mRNA and proteins prepared from freshly obtained patient tumor specimens.

The unique double-loading approach, which mimics a viral infection, unlocks a synergistic and exponentially more powerful tumor killing TH1 response driven by dual protein and RNA antigen sourcing, and it allows targeting of the complete cancer antigen pool. Moreover, the approach does not require any molecular modification of the patient’s immune cells for manufacturing, and does not require preconditioning chemotherapy or high dose IL-2 for administration. DOC1021 allows for a simple administration in the outpatient setting and broad reach via community cancer centers.

In addition to the Phase I pancreatic cancer study (NCT04157127), Diakonos recently opened a Phase 2 glioblastoma (GBM) study with DOC1021 (NCT06805305). Diakonos has received Fast Track designations from the FDA for both the GBM and pancreatic cancer programs, in October 2023 and May 2024, respectively. The company has also received Orphan Drug Designation for the GBM program in January 2024.

(Press release, Diakonos Oncology, OCT 27, 2025, View Source [SID1234657042])