On June 18, 2025 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a late-stage pharmaceutical company with a broad portfolio of drug candidates targeting hard-to-treat cancers and viral infections, reported it has received a written response from the Office of Oncologic Diseases – Pediatric Oncology, of the U.S. Food and Drug Administration (FDA) regarding the Company’s Initial Pediatric Study Plan (iPSP), which was submitted after a June 2024 end-of-phase 1/2 meeting (Press release, Moleculin, JUN 18, 2025, View Source [SID1234653977]). The FDA has agreed to a single pediatric approval study in which Annamycin (also known as naxtarubicin) in combination with Cytarabine (also known as "Ara-C" and for which the combination of Annamycin and Ara-C is referred to as "AnnAraC") will be evaluated as second line therapy in pediatric patients with relapsed/refractory acute myeloid leukemia (R/R AML), a form of cancer.

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"We continue to be encouraged by the potential of Annamycin to change the game when it comes to the most prevalent cancer therapies in use today. This is particularly important in pediatric oncology, where about 60% of children with cancer are treated with anthracyclines that present a high risk of causing heart damage. An independent expert’s review of study data has shown no cardiotoxicity to date in 84 adult patients treated with Annamycin, which is why we’re excited about moving forward in young children with cancer. Receiving this written feedback from FDA is a crucial step in the development of Annamycin for pediatric use and provides us with helpful insight as we continue to prepare for the launch of a pediatric trial, planned for the second half of 2027," said Walter Klemp, Chairman and CEO of Moleculin. "As our team works to address and implement FDA’s feedback on our iPSP, we remain focused on the successful execution of our ongoing MIRACLE trial of AnnAraC in adult patients with R/R AML and look forward to initial data from that trial later this year."

As part of the iPSP, Moleculin proposed a single-arm study evaluating pharmacokinetics (PK), efficacy, and safety of AnnAraC in patients between 2 and 16 years of age. The FDA response calls for including patients from 6 months of age and older, with no minimum number of patients between 6 months and 2 years old. FDA also clarified that drug concentration exposure and safety profile that are comparable would allow extrapolation from efficacy in adults. Importantly, FDA said Moleculin would be able to start the pediatric trial before having the full two years of follow-up data from the adult trial.

Moleculin is in the process of updating its iPSP to incorporate FDA’s recommendations and intends to submit the revised plan to FDA later this quarter. Moleculin expects to initiate pediatric clinical study in the second half of 2027.

The Company is currently evaluating AnnAraC for the treatment of adult patients with R/R AML in the pivotal, adaptive Phase 3 MIRACLE trial (MB-108). This "MIRACLE" trial (derived from Moleculin R/R AML AnnAraC Clinical Evaluation) is a global trial, including sites in the US, Europe and the Middle East. Patient dosing has commenced, and the initial data readout is on track for the second half of 2025. For more information about the MIRACLE trial, visit clinicaltrials.gov and reference identifier NCT06788756

FDA has granted Annamycin Fast Track Status and Orphan Drug Designation for treating relapsed or refractory acute myeloid leukemia, and an additional Orphan Drug Designation for treating soft tissue sarcoma. The European Medicines Agency (EMA) has also granted Orphan Drug Designation for the treatment of relapsed or refractory acute myeloid leukemia.

On June 18, 2025 Merck reported the first patient has been dosed in the IDeate-Prostate01 phase 3 trial evaluating the efficacy and safety of investigational ifinatamab deruxtecan (I-DXd) versus docetaxel in patients with metastatic castration-resistant prostate cancer (mCRPC) with disease progression during or after treatment with an androgen receptor pathway inhibitor (Press release, Merck & Co, JUN 18, 2025, View Source [SID1234653976]).

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Ifinatamab deruxtecan is a specifically engineered, potential first-in-class B7-H3 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed by Daiichi Sankyo and Merck (NYSE: MRK), known as MSD outside of the United States and Canada.

While localized prostate cancer has a five-year survival rate of more than 90%, survival decreases to 31% in the advanced or metastatic stage.1 Current standard of care for patients with mCRPC includes treatment with androgen receptor pathway inhibitors followed by taxane-based chemotherapy.2-5 However, due to poor prognosis associated with previously treated mCRPC, many patients do not receive subsequent therapy, reinforcing the need for new approaches to improve outcomes.6

"Despite the emergence of new therapies, the current treatment landscape for patients with metastatic castration-resistant prostate cancer is challenging, and there is a need for new treatments," said Mark Rutstein, MD, Head, Therapeutic Area Oncology Development, Daiichi Sankyo. "Following the promising results seen in our earlier phase trial, IDeate-Prostate01 has been initiated to evaluate whether ifinatamab deruxtecan may replace standard taxane-based chemotherapy as a potential treatment strategy in patients with metastatic castration-resistant prostate cancer with disease progression during or after treatment with androgen receptor pathway inhibitors."

"IDeate-Prostate01 marks the initiation of the third pivotal trial in the ifinatamab deruxtecan development program and reinforces our commitment to addressing critical unmet needs for patients," said Marjorie Green, MD, Senior Vice President and Head of Oncology, Global Clinical Development, Merck Research Laboratories. "Our continued progress in the exploration of this potential first-in-class B7-H3 antibody drug conjugate in collaboration with Daiichi Sankyo, speaks to our pursuit of novel science in the hopes of making a difference for patients in need of new options."

The initiation of IDeate-Prostate01 is based on results from the IDeate-PanTumor01 phase 1/2 trial previously presented at the 2022 and 2023 European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congresses where ifinatamab deruxtecan showed promising responses in heavily pretreated patients with mCRPC.

About the IDeate-Prostate01 Trial

IDeate-Prostate01 is a multicenter, open-label, randomized phase 3 trial evaluating the safety and efficacy of ifinatamab deruxtecan (12 mg/kg) versus docetaxel (75 mg/m2) plus corticosteroid in patients with mCRPC. Eligible patients must have received prior treatment with one or two androgen receptor pathway inhibitors and experienced disease progression during or after at least eight weeks of treatment.

The dual primary endpoints of IDeate-Prostate01 are overall survival and radiographic progression-free survival. Secondary endpoints include objective response rate, time to first subsequent therapy, duration of response, time to pain progression, time to prostate-specific antigen (PSA) progression, PSA response, time to first symptomatic skeletal-related event and safety.

IDeate-Prostate01 will enroll approximately 1,440 patients across Asia, Europe, North America and Oceania. For more information, please visit ClinicalTrials.gov.

About Metastatic Castration-Resistant Prostate Cancer

Prostate cancer is the second most common cancer in men, and the fifth leading cause of cancer death in men worldwide.7 Nearly 1.5 million prostate cancer cases were diagnosed in 2022, with approximately 400,000 deaths globally.7

While localized prostate cancer has a five-year survival rate of more than 90%, survival decreases to 31% in advanced or metastatic stage.1 Approximately 10% to 20% of early-stage prostate cancer cases progress to metastatic disease within five years of treatment on hormonal therapies such as androgen deprivation therapy.8,9 Current standard of care for patients with mCRPC includes treatment with androgen receptor pathway inhibitors followed by taxane-based chemotherapy. However, due to poor prognosis associated with previously treated mCRPC, many patients do not receive subsequent therapy, reinforcing the need for new approaches to improve outcomes.6

About B7-H3

B7-H3 is a transmembrane protein that belongs to the B7 family of proteins, which bind to the CD28 family of receptors that includes PD-1.10,11 B7-H3 is overexpressed in a wide range of cancer types, including mCRPC and its overexpression has been shown to correlate with poor prognosis, making B7-H3 a promising therapeutic target.12-15 There are currently no B7-H3 directed medicines approved for the treatment of any cancer.

About Ifinatamab Deruxtecan

Ifinatamab deruxtecan (I-DXd) is an investigational potential first-in-class B7-H3 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, ifinatamab deruxtecan is comprised of a humanized anti-B7-H3 IgG1 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

Ifinatamab deruxtecan has been granted orphan drug designation by the U.S. Food and Drug Administration, European Commission, Japan Ministry of Health, Labour and Welfare and Taiwan Food and Drug Administration for the treatment of small cell lung cancer.

About the Ifinatamab Deruxtecan Clinical Development Program

A comprehensive global clinical development program is underway evaluating the efficacy and safety of ifinatamab deruxtecan across multiple B7-H3 targetable cancers. Trials in combination with other anticancer treatments also are underway.

On June 18, 2025 IMUNON, Inc. (NASDAQ: IMNN), a clinical-stage company in Phase 3 development of its DNA-mediated immunotherapy, reported the presentation of new positive translational data from the Phase 2 OVATION 2 Study of IMNN-001, its investigational gene-based interleukin-12 (IL-12) immunotherapy based on the Company’s proprietary TheraPlas technology platform, for the treatment of newly diagnosed advanced ovarian cancer (Press release, IMUNON, JUN 18, 2025, View Source [SID1234653975]). Results are being highlighted in a poster presentation at the ESMO (Free ESMO Whitepaper) Gynaecological Cancers Congress 2025, taking place June 19-21, 2025, in Vienna, Austria.

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The Phase 2 OVATION 2 Study assessed 112 participants treated with IMNN-001 (100 mg/m2 administered intraperitoneally weekly) plus standard-of-care (SoC) neoadjuvant and adjuvant chemotherapy (N/ACT). IL-12 levels were sampled in the peritoneal fluid cavity, which is the primary tumor micro-environment. Results being presented at the ESMO (Free ESMO Whitepaper) Congress showed that treatment with IMNN-001 induced substantial increases in IL-12 and interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α), key downstream anti-cancer immune cytokines. Increases in IL-12, IFN-γ and TNF-α levels in the peritoneal cavity were approximately 27-, 62- and 36-fold following treatment, respectively, demonstrating the tumor-localized effect of IMNN-001 in women with advanced ovarian cancer. IMNN-001 continues to show a favorable safety profile.

"We are encouraged by these translational data being presented at the ESMO (Free ESMO Whitepaper) Gynaecological Cancers Congress 2025, which strongly complement the compelling overall survival results from the OVATION 2 trial presented at ASCO (Free ASCO Whitepaper) 2025," said Douglas V. Faller, M.D., Ph.D., Chief Medical Officer of IMUNON. "The clinical outcomes, showing a robust increase in overall survival for women with advanced ovarian cancer treated with IMNN-001 plus standard-of-care chemotherapy, align with these pharmacological and immunopathological findings. These results validate that IMNN-001 induces IL-12 and its downstream anti-tumor effectors, IFN-γ and TNF-α, exclusively at the tumor site with minimal systemic exposure, supporting our ongoing Phase 3 OVATION 3 trial."

At the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting and in a peer-reviewed article in Gynecologic Oncology, IMUNON presented unprecedented overall survival data from the Phase 2 OVATION 2 Study. Treatment with IMNN-001 plus SoC chemotherapy in women with newly diagnosed advanced ovarian cancer demonstrated consistent, clinically meaningful improvements in overall survival, progression-free survival, chemotherapy response score, and surgical response, with a favorable safety profile. IMUNON is advancing the pivotal Phase 3 OVATION 3 Study of IMNN-001, with the first two trial sites initiated in May 2025.

About the Phase 2 OVATION 2 Study

OVATION 2 evaluated the dosing, safety, efficacy and biological activity of intraperitoneal administration of IMNN-001 in combination with neoadjuvant and adjuvant chemotherapy (N/ACT) of paclitaxel and carboplatin in patients newly diagnosed with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer. Treatment in the neoadjuvant period is designed to shrink the tumors as much as possible for optimal surgical removal after three cycles of chemotherapy. Following N/ACT, patients undergo interval debulking surgery, followed by three additional cycles of adjuvant chemotherapy to treat any residual tumor. This open-label study enrolled 112 patients who were randomized 1:1 and evaluated for safety and efficacy to compare N/ACT plus IMNN-001 versus standard-of-care N/ACT. In accordance with the study protocol, patients randomized to the IMNN-001 treatment arm could receive up to 17 weekly doses of 100 mg/m2 in addition to N/ACT. As a Phase 2 study, OVATION 2 was not powered for statistical significance. Additional endpoints included objective response rate, chemotherapy response score and surgical response.

About IMNN-001 Immunotherapy

Designed using IMUNON’s proprietary TheraPlas platform technology, IMNN-001 is an IL-12 DNA plasmid vector encased in a nanoparticle delivery system that enables cell transfection followed by persistent, local secretion of the IL-12 protein. IL-12 is one of the most active cytokines for the induction of potent anticancer immunity acting through the induction of T-lymphocyte and natural killer cell proliferation. IMUNON previously reported positive safety and encouraging Phase 1 results with IMNN-001 administered as monotherapy or as combination therapy in patients with advanced peritoneally metastasized primary or recurrent ovarian cancer and completed a Phase 1b dose-escalation trial (the OVATION 1 Study) of IMNN-001 in combination with carboplatin and paclitaxel in patients with newly diagnosed ovarian cancer. IMUNON previously reported positive results from the recently completed Phase 2 OVATION 2 Study, which assessed IMNN-001 (100 mg/m2 administered intraperitoneally weekly) plus neoadjuvant and adjuvant chemotherapy (N/ACT) of paclitaxel and carboplatin compared to standard-of-care N/ACT alone in 112 patients with newly diagnosed advanced ovarian cancer.

About Epithelial Ovarian Cancer

Epithelial ovarian cancer is the sixth deadliest malignancy among women in the U.S. There are approximately 20,000 new cases of ovarian cancer every year and approximately 70% are diagnosed in advanced Stage III/IV. Epithelial ovarian cancer is characterized by dissemination of tumors in the peritoneal cavity with a high risk of recurrence (75%, Stage III/IV) after surgery and chemotherapy. Since the five-year survival rates of patients with Stage III/IV disease at diagnosis are poor (41% and 20%, respectively), there remains a need for a therapy that not only reduces the recurrence rate but also improves overall survival. The peritoneal cavity of advanced ovarian cancer patients contains the primary tumor environment and is an attractive target for a regional approach to immune modulation.

On June 18, 2025 Oncoinvent ASA, a clinical-stage radiopharmaceutical company developing innovative treatments for solid cancers, reported positive topline data from the Phase 1/2a clinical trial (RAD-18-002) evaluating Radspherin in patients with peritoneal metastases originating from colorectal cancer (Press release, Oncoinvent, JUN 18, 2025, https://www.oncoinvent.com/press-release/oncoinvent-announces-positive-final-data-from-phase-1-2a-trial-of-radspherin-in-patients-with-colorectal-peritoneal-metastases/?utm_source=mailpoet&utm_medium=email&utm_source_platform=mailpoet [SID1234653958]).

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Reducing peritoneal recurrence in colorectal cancer is critically important because peritoneal metastases are associated with a particularly poor prognosis and significantly lower overall survival compared to other forms of recurrence[1]. The development of peritoneal metastases is not only linked to worse survival, but also to distressing symptoms, making disease management more challenging and often resulting in treatment interruptions and repeated hospitalizations.

Standard therapies for peritoneal metastases are limited, and the only treatment option with curative intent is surgery, which aims to remove as much tumor as possible in the peritoneal cavity. However, surgical resection leaves behind microscopic deposits of cancer cells, giving rise to new peritoneal metastases and disease progression. Radspherin, direct intraperitoneal targeting with the alpha-emitter radium-224, aims to eliminate these post-surgery micro-metastases and thereby prevent or delay peritoneal recurrence.

In this single-arm trial of 47 patients, 36 received Radspherin at a 7 MBq dose. The primary endpoint—peritoneal recurrence-free survival (pRFS)—yielded remarkable results:

Only 27.8%(10 of 36) experienced peritoneal disease recurrence at 18 months, a marked reduction compared to published data for standard of care, where approximately 50% of patients typically see peritoneal recurrence at this stage[2]
At 18 months, 61.1%(22 of 36) of patients had experienced any recurrence, but notably, just 22.7% (5 of 22) had peritoneum as the first site of recurrence
Final data from all 47 treated patients across dose levels further reinforce the favorable safety profile of Radspherin
Additional results will be published upon completion of the full dataset analysis.

"It’s highly encouraging to see patients treated with Radspherin achieving outcomes that exceed expectations for this challenging population. As a clinician, I’m hopeful that this promising therapy will become an option I can offer to future patients in need," said Dr. Stein Gunnar Larsen, Principal Investigator at the Oslo University Hospital, Norway.

Prof. Dr. Wilhelm Graf, Principal Investigator at Uppsala University Hospital, Sweden, added: "Colorectal peritoneal metastases present a major therapeutic challenge with limited effective options, and these findings support the potential of a novel approach that demonstrates both clinical promise and a favorable safety profile."

"We are inspired and motivated by these compelling data. They reinforce our belief in Radspherin’s potential as a novel treatment targeting peritoneal metastases and justify continued advancement of the program," said Oystein Soug, CEO of Oncoinvent. "We extend our deepest gratitude to the patients, investigators, and clinical teams who made this trial possible."

Radspherin is currently investigated in an ongoing phase 2 trial evaluating the treatment of peritoneal carcinomatosis from ovarian cancer. A positive safety review of the lead-in cohort was announced in Q1 2025, and the trial is currently recruiting patients according to plan in European and US sites in the randomized phase.

About RAD-18-002

RAD-18-002 was an open label Phase 1/2a trial conducted in patients with colorectal peritoneal metastases. The trial was designed to evaluate dosing, safety and tolerability, and signal of efficacy of intraperitoneally administered Radspherin following complete surgical resection and Hyperthermic Intraperitoneal Chemotherapy (HIPEC). A total of 47 patients were enrolled across sites in Norway and Sweden, with 36 patients receiving the recommended dose of 7 MBq.

About Radspherin

Radspherin is an investigational radiopharmaceutical designed for the local treatment of cancer that has spread to body cavities. It consists of calcium carbonate microparticles containing the radioactive material radium-224. The mode of action is the decay of radium-224 emitting alpha-particles, a highly potent form of ionizing radiation. Radspherin is investigated in ongoing clinical studies to treat peritoneal carcinomatoses from ovarian and colorectal cancer and it is administered intraperitoneally after surgical resection with removal of all macroscopic tumors.

On June 18, 2025 Imugene Limited (ASX: IMU), a clinical-stage immuno oncology company, reported it has received a Notice of Allowance from the US Patent and Trademark Office (USPTO) for patent application number 16/637,909 which protects its oncolytic virotherapy CF33-CD19 and its combination with CD19 targeting CAR T cell therapies (Press release, Imugene, JUN 18, 2025, View Source [SID1234653957]).

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The patent titled "ONCOLYTIC VIRUS EXPRESSING A CAR T CELL TARGET AND USES THEREOF" (inventors Yuman Fong, Saul Priceman, Stephen Forman, Nanhai Chen and Anthony Park from the City of Hope) protects the method of composition and method of use of Imugene’s onCARlytics technology through to August 10 2038.

Leslie Chong, Managing Director and CEO of Imugene, said:

"Imugene receiving this US patent allowance for the CF33-CD19 onCARlytics platform is a crucial step forward for our IP position, with the US being the largest healthcare market in the world. This follows patent allowance in China, an equally large cell therapy market, earlier in 2025."