On June 11, 2024 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a leader in the development of Antibody Radiation Conjugates (ARCs) and other targeted radiotherapies, reported data from the completed Phase 1b combination trial of Actimab-A + CLAG-M in patients with relapsed or refractory acute myeloid leukemia (r/r AML) at the 2024 Society of Nuclear Medicine & Molecular Imaging (SNMMI) Annual Meeting held June 8 – 11, 2024, in Toronto, Canada (Press release, Actinium Pharmaceuticals, JUN 11, 2024, View Source [SID1234644267]). Actimab-A is an ARC comprised of a CD33 targeting monoclonal antibody conjugated with the alpha-particle emitter Actinium-225 isotope payload. Actimab-A has been studied as a single agent and in combination with chemotherapies and targeted therapies in Phase 1 and Phase 2 trials.

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Sandesh Seth, Actinium’s Chairman and CEO, said, "These results demonstrate the immense potential of targeted radiotherapy via ARCs from both an efficacy and safety perspective. Through the use of dosimetry, we can estimate radiation doses to the target organ and non-targeted healthy organs and as observed in this trial, we saw no safety signals for the kidneys, liver or other major organs. Together with the potent efficacy, particularly in these high-risk relapse and refractory patients, we are highly excited by the building clinical profile Actimab-A. We look forward to continuing to advance our Actimab-A program as a broad-based combination approach with targeted and non-targeted therapies in collaboration with the NCI for the benefit of AML patients who are eligible for targeted radiotherapy."

The Phase 1b Actimab-A + CLAG-M combination trial enrolled patients with high-risk r/r AML with the following features:

Median age of 62 with patients up to 73 years old
91% of patients had intermediate (n=3, 13%) or adverse cytogenetics (n=18, 78%)
Over 50% of patients had a TP53 mutation
Median of 2 lines of prior therapy (range:1-5) including:
Prior bone marrow transplant: 57%
Prior venetoclax treatment: 57%
Despite the high-risk profile of the patients on the study, the combination of Actimab-A + CLAG-M produced high rates of response and measurable residual disease negativity and improved survival outcomes across all patient subsets:

Patients

Overall Response Rate

MRD- Rate

1-year Overall Survival

All (n=23)

65 %

75 %

48 %

High-Risk (n=19)

58 %

75 %

42 %

ELN Adverse Risk
(n=17)

53 %

67 %

35 %

TP53+ (n=12)

58 %

80 %

42 %

Ven Failures (n=13)

54 %

100 %

46 %

64% of eligible patients proceeded to bone marrow transplant with these patients having a median overall survival of 24 months.

Dosimetry and Safety:

A validated pharmacokinetic model was used to estimate the biodistribution of Actimab-A based on the distribution of CD33+ AML blast cells based on data derived from patients in the Phase 1b study
Across all dose levels including 0.75 µCi/kg, which was determined to be the optimal dose, and 1.0 µCi/kg (the highest dose in the Phase 1b study) radiation doses for key organs were well below known tolerance levels with external beam radiation therapy (EBRT)
No safety signals for major organs such as liver, heart, kidneys, lungs and intestines were observed and a safety profile consistent with that expected in heavily pre-treated r/r AML patients given salvage therapy
A single 30-minute administration of Actimab-A results in rapid radiation delivery and clearance with peak concentration reached around 0.6 hours and undetectable in the blood by 48 hours after administration
The dose of 0.75 µCi/kg was identified as optimal for this combination therapy and will be further evaluated in the next stage of clinical development
About the SNMMI Annual Meeting

The SNMMI Annual Meeting is recognized as the premier educational, scientific, research, and networking event in nuclear medicine and molecular imaging. The four-day event, taking place each June, provides physicians, technologists, pharmacists, laboratory professionals, and scientists with an in-depth view of the latest research and development in the field as well as providing insights into practical applications for the clinic.

On June 11, 2024 TRACON Pharmaceuticals (NASDAQ: TCON), a clinical stage biopharmaceutical company utilizing a cost-efficient, CRO-independent Product Development Platform (PDP) to advance its pipeline of novel targeted cancer therapeutics and to partner with other life science companies, reported the publication of Phase 2 clinical data of its DNA damage repair inhibitor drug candidate, TRC102, in patients with glioblastoma in Clinical Cancer Research (Press release, Tracon Pharmaceuticals, JUN 11, 2024, View Source [SID1234644266]). The article, entitled, "Evaluating the Base Excision Repair Inhibitor TRC102 and Temozolomide for patients with Recurrent Glioblastoma in the Phase 2 Adult Brain Tumor Consortium Trial BERT," highlights the activity of TRC102 given in combination with Temodar chemotherapy in patients with recurrent glioblastoma: View Source

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TRC102 was evaluated in a Phase 2 trial in combination with Temodar in 19 patients with progressive or recurrent glioblastoma following surgical resection, Temodar and external beam radiotherapy. Extended survival was observed in two patients (progression-free survival ≥ 17 months and overall survival > 32 months), both of whom demonstrated significantly enriched signatures of DNA damage response (DDR), chromosomal instability, and cellular proliferation by RNA sequencing prior to initiating treatment with Temodar and TRC102. The study was completed by the Adult Brain Tumor Consortium and led by Manmeet Alhuwalia, MD while he was Chair of Neuro-Oncology at Cleveland Clinic prior to his appointment as Chief of Medical Oncology, Chief Scientific Officer, and Deputy Director of the Miami Cancer Institute. The authors concluded the study findings confirm the safety and feasibility of TRC102 given with Temodar for recurrent glioblastoma patients and warrant further evaluation of combination therapy in biomarker-enriched trials enrolling glioblastoma patients with baseline hyperactivated DDR pathways.

"We believe that the data generated to date provides a strong rationale for studying TRC102 in combination with Temodar and radiotherapy in newly diagnosed patients with malignant glioma," said James Freddo, M.D., Chief Medical Officer of TRACON. "The Clinical Cancer Research publication supports prior data published in Cancer Cell (View Source) that patients whose cancers demonstrate activation of DDR pathways may be particularly sensitive to the pharmacologic effects of TRC102."

Based on a 100% response rate (including a 20% complete response rate) in a Phase 1 clinical trial combining TRC102 with pemetrexed, cisplatin and radiation therapy in 15 patients with stage III non-squamous non-small cell lung cancer (View Source), TRC102 is currently being studied in a randomized Phase 2 clinical trial in combination with chemotherapy (pemetrexed, cisplatin or carboplatin) and radiation therapy for stage III non-squamous non-small cell lung cancer (NCT05198830: View Source;rank=6). This trial is sponsored by the National Cancer Institute (NCI) through a Cooperative Research and Development Agreement (CRADA). Determination of the primary endpoint of progression free survival is expected in 2025. TRACON and the NCI have a longstanding history of partnership to develop TRC102, whereby the NCI has funded six Phase 1 or Phase 2 trials through the CRADA.

About TRC102

TRC102 (methoxyamine) is a novel, clinical-stage small molecule inhibitor of the DNA base excision repair pathway, which is a pathway that causes resistance to alkylating and antimetabolite chemotherapeutics. TRC102 is currently being studied in multiple randomized Phase 2 clinical trial entitled Testing the Addition of an Anti-Cancer Drug, TRC102, to the Usual Chemotherapy Treatment (Pemetrexed, Cisplatin or Carboplatin) During Radiation Therapy for Stage III Non-Squamous Non-Small Cell Lung Cancer (NCT05198830) that is sponsored by the NCI through a CRADA. TRC102 was granted orphan drug designation by the US FDA for the treatment of malignant glioma in 2020. For more information about the clinical trials, please visit TRACON’s website at www.traconpharma.com/clinical-trials.

About Malignant Glioma and Glioblastoma
Glioblastoma (GBM) is a rapidly growing malignant glioma that develops from glial cells (astrocytes and oligodendrocytes) that support the health of the nerve cells within the brain. GBM is the most invasive type of glial tumors, rapidly growing and commonly invading into nearby brain tissue. The National Cancer Institute estimates that approximately 22,850 adults are diagnosed with brain and other nervous system cancers annually in the U.S. and approximately 15,320 of these diagnoses will result in death. GBM has an incidence of two to three per 100,000 adults per year in the U.S., and accounts for 52 percent of all primary brain tumors.

On June 11, 2024 Monopar Therapeutics Inc. (Nasdaq: MNPR), a clinical-stage radiopharma company, and NorthStar Medical Radioisotopes, LLC, a global innovator in development and commercial production of medical radioisotopes, reported an amendment and expansion to their existing collaboration (Press release, Monopar Therapeutics, JUN 11, 2024, View Source [SID1234644265]). Under terms of the revised collaboration, the Companies entered into a long-term, non-exclusive master supply agreement for NorthStar to provide Monopar with the powerful therapeutic radioisotope actinium-225 (Ac-225). The amendment builds on NorthStar’s significant investment in Ac-225 manufacturing and Monopar’s promising preclinical therapeutic results with Ac-225 in its lead MNPR-101 radiopharma program.

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The amendment also clarifies certain economic terms and those related to jointly developed intellectual property rights for Monopar’s MNPR-101 for radiopharmaceutical use. Monopar has acquired those rights from NorthStar, together with certain broad, jointly developed intellectual property pertaining to MNPR-101, giving Monopar full ownership and title to its lead MNPR-101 radiopharmaceutical platform. Both companies will share ownership of the filed patent application on the use of PCTA as a linker with Ac-225, which has shown superior binding and yield with Ac-225 over the current industry-leading linker, DOTA.

"We are excited about the evolution of our collaboration, the promising potential of the MNPR-101 radiopharma platform, and the long-term access to a high-quality source of Ac-225 that can support our current development programs and potential future commercial products," said Chandler Robinson, MD, Monopar’s Chief Executive Officer.

"Using our proprietary electron accelerator technology, NorthStar is poised to be the first commercial-scale producer of non-carrier added (n.c.a.) Ac-225. We’re delighted to continue and extend our collaboration with Monopar and support development of its exciting MNPR-101 radiopharma platform focused on therapeutic agents to treat aggressive cancers," said Frank Scholz, PhD, NorthStar’s Chief Executive Officer.

On June 11, 2024 Nykode Therapeutics ASA (OSE: NYKD), a clinical-stage biopharmaceutical company dedicated to the discovery and development of novel immunotherapies, reported updates on its mRNA platform at the Cancer Immunotherapy meeting in Boston (Press release, Nykode Therapeutics, JUN 11, 2024, View Source [SID1234644264]). The company highlighted the significant advantages of its innovative APC-targeted neoantigen vaccine, delivered in a mRNA-lipid nanoparticle (LNP) format.

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This latest study demonstrated that the APC-targeted vaccine consistently achieved a broader and more robust immune response across doses compared to an untargeted neoantigen vaccine. It also provided superior tumor control and resulted in dramatically improved survival rates in a mouse model of colorectal cancer

Chief Scientific Officer, Agnete Fredriksen, commented on the findings, "Our latest data not only emphasize the effectiveness of the APC-targeted approach but also confirm our platform’s potential across modalities to significantly advance the treatment landscape for cancer. The strong data demonstrating Nykode’s potential to improve mRNA vaccines underscore our commitment to leading the way in next-generation immunotherapies."

Nykode presented a poster detailing these findings at the meeting, with further information available on the Nykode website: View Source

On June 11th, 2024 – Orphelia Pharma, a pharmaceutical company dedicated to the development and marketing of pediatric and orphan medicines, reported that KIZFIZO, temozolomide oral suspension, will be included in the MetroWILMS-1906 study (EudraCT: 2021-002540-67, NCT05384821) (Press release, ORPHELIA Pharma, JUN 11, 2024, View Source;utm_medium=rss&utm_campaign=orphelia-pharma-to-collaborate-with-oscar-lambret-clinical-center-to-study-kizfizo-the-first-pediatric-drinkable-formulation-of-temozolomide-for-the-treatment-of-refractory-or-relapsed-nephrob [SID1234644263]). MetroWILMS is a French, multicentric, non-randomized, Phase 1-2 clinical trial to study the efficacy and safety of metronomic chemotherapy, including temozolomide, for the treatment of refractory or relapsed nephroblastoma (Wilms tumor). MetroWILMS is sponsored by the Oscar Lambret clinical center on behalf of the Société Française des Cancers de l’Enfant (SFCE), Nephroblastoma committee.

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Pediatric renal (kidney) tumors account for 4%-11% of all childhood cancers, the most common of which being nephroblastoma or Wilms tumor. It affects young children, most of the cases being diagnosed before 5 years of age. Despite a good prognosis, 10 to 15 % of patients present a refractory Wilms tumor or experience relapse and bear a dismal prognosis.

As part of the MetroWILMS protocol, KIZFIZO (under the name KIMOZO currently in use in France) will be administered for the treatment of refractory/relapsed Wilms tumors (after 1 or 2 lines of treatment or after 1 line for high risk relapse for which there would not be any curative therapy), using a metronomic schedule and in combination with other drugs (vincristine, irinotecan, etoposide and cis retinoic acid). MetroWILMS will include 28 pediatric patients, with a recruitment planned until October 2028.

"There is a major clinical need for an oral liquid form of temozolomide in various pediatric oncology indications, including in refractory or relapsed Wilms tumor", said Hélène Sudour-Bonnange, onco-pediatrician at Oscar-Lambret clinical center and principal investigator of MetroWILMS trial. "We believe that KIZFIZO oral suspension is especially well suited to treat our young patients."

"Refractory or relapsed nephroblastoma is a very rare indication, but this is well in line with Orphelia’s missions to help pediatric patients with rare cancers", said Jérémy Bastid, chief medical officer at Orphelia Pharma. "Should MetroWilms demonstrate a clinical benefit, we could consider expanding the label of KIFZIZO in this indication".

About KIZFIZO 40 mg/ml

KIZFIZO (temozolomide oral suspension, 40 mg/ml) is a ready-to-use oral liquid pediatric formulation of temozolomide developed for use in the treatment of relapsed or refractory high-risk neuroblastoma, which carry a very poor prognosis. This age-adapted and taste-masked formulation delivers an accurate dose in a small volume, while avoiding drug handling and caregiver exposure to temozolomide. It is the result of a collaboration between the pharmacists and clinicians at Gustave Roussy hospital and the development team at Orphelia Pharma.

In March 2022, KIZFIZO (under the trade name KIMOZO) was granted Early Access Authorization (Autorisation d’Accès Précoce) by the French authorities, for the treatment of refractory and relapsed high-risk neuroblastoma as monotherapy or in combination with irinotecan or topotecan.

KIZFIZO has received an Orphan Drug Designation from the EMA and the FDA and the formulation is covered by granted patents in Europe and the US. The company filed an MAA with the EMA in the summer of 2023.