On June 11, 2024 Laminar Pharmaceuticals S.A., a clinical-stage biotechnological company developing novel therapies to treat diverse pathologies with unmet clinical needs, reported the recruitment of patients for the CLINGLIO (NCT04250922) study has been closed after 140 adult patients have been successfully enrolled (Press release, Laminar Pharma, JUN 11, 2024, View Source [SID1234644269]). The CLINGLIO study is a multinational, phase 2b/3, randomized, placebo-controlled, double-blind clinical trial evaluating idroxioleic acid in combination with Standard of Care (combined tumour resection and chemoradiotherapy) for the treatment of newly diagnosed glioblastoma patients. The CLINGLIO trial, funded by a European Commission Grant (H2020) is being carried out in 21 hospitals in Spain, Italy, France, and United Kingdom. The investigational study drug, idroxioleic acid (LAM561, sodium; 2-OHOA) is a synthetic fatty acid with a novel therapeutic approach, administrated orally to treat this devastating type of cancer.

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 pleased to announce that the pivotal phase 2b/3 trial recruitment is completed, as this means that the results and outcome of the trial will be soon available," said Adrian McNicholl, Chief of Clinical Operations at Laminar Pharmaceuticals. The trial is expected to reach the trigger event for interim analysis in July 2024, which would provide an unblinded readout the last quarter of this year. "If idroxioleic acid is able to show compelling evidence demonstrating significant progression free survival benefit with overall survival, it could imply the first addition to the Standard of Care for glioblastoma patients since the approval of Temozolomide in 2005, 19 years ago." These unblinded results will be submitted for EMA evaluation for Conditional Marketing Authorization in early 2025, and the trial will continue until final analysis of survival in 2026.

Pablo Escribá, CEO of Laminar Pharmaceuticals, said: "The completion of the recruitment is a huge milestone in our clinical trial and in the development of this potential new therapy for glioblastoma patients. We are excited about the possibility of offering a new treatment available for this fatal disease, which has some of the clearer unmet needs across the oncology field".

The CLINGLIO trial, which was initiated in December 2019, has enrolled 140 participants across 4 countries in Europe. Those patients were randomized 1:1 versus placebo. Idroxioleic acid or placebo is added to Standard of Care, and continued for as long as the tumour does not progress. Idroxioleic acid has shown a favorable safety profile in pre-clinical and clinical trials so far. Additionally, no safety concerns were raised by an Independent Data Monitoring Committee (IDMC) who recommended "continue without modifications" after unblinded reviews of the available safety and efficacy data. The trial will continue until the final analysis of overall survival.

The CLINGLIO trial is considered pivotal in that results showing significant clinical benefit could be sufficient for a request for conditional marketing authorization in the EU late this year; and potential full marketing authorization in 2026, for which enabling pre-submission interactions with the EMA have been initiated.

On June 11, 2024 Oncotelic Therapeutics, Inc (OTCQB:OTLC) reported that its CEO- Dr. Vuong Trieu will speak at the 20th Annual Congress of International Drug Discovery Science & Technology (IDDST) (Europe), June 17-19, 2024 at Budapest, Hungary (Press release, Oncotelic, JUN 11, 2024, View Source [SID1234644268]).

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!

Title: TGFB2 therapeutic for the treatment of CRC, GBM, and PDAC

Anirudh Kolanu, K. Khuranu, A. Mehta, T. Sanil1, G. Trieu, and Dr. Vuong Trieu*

Abstract: OT-101, an antisense against TGFB2, is being tested in phase 3 clinical trials for pancreatic cancer and glioblastoma. It was previously reported to have robust clinical activity in those indications as well as in melanoma. Here, we explore the potential application of OT-101 in colorectal cancer (CRC) through the analysis of CRC patients treated with OT-101 during its clinical development, as well as through bioinformatic. Intravenous therapy with OT-101 in melanoma, colorectal cancer, and pancreatic cancer was evaluated in P001- a phase I/II study. A total of 62 patients were enrolled; 38 patients with pancreatic cancer, 19 patients with melanoma, and 5 patients with colorectal cancer. Full pharmacokinetic evaluation of these patients demonstrated a drug effect with improved progression-free survival (PFS) with increased drug exposure defined by AUClast. The CRC patients were heavily pretreated with multiple lines of previous therapies (4,5,5,6,8), reflected in short overall survival times (2.1, 2.5, 3.0, 5.7, 7.3 months). High AUC exhibited a doubling of PFS to 84 days versus 40 days. A sample of 4259 colorectal adenocarcinoma cancer patients from cbioportal was analyzed. The low expression of two genes: TGFB2 and TGFM6 improved OS. The combination of TGFB2 and TGFM6 was superior to TGFB2 or TGFM6 alone, with TGFB2 being the dominant factor. There was strong but not overlapping sexual dimorphism among the two genes separately but not when used together. The TGFB/TGM6 impact was most significant on Mesenchymal CMS- increasing median survival from 42 months with high TGFB2/TGM6 to 132 months with low TGFB2/TGM6- a threefold improvement with a highly significant p-value of 1.4e-5. Statistical significance was not observed when the genes were used separately. Suppression of TGFB2, i.e., through OT-101, is a potential approach for the treatment of CRC.especially OT-101 treatment of TGM6 low patients.

"It is gratifying to identify what we think is the fundamental role of TGFM6 and TGFB2 in cancer," said Dr. Vuong Trieu, CEO and Chairman of Oncotelic. "Considering the work done here by our interns drawn from local high schools through Brush&Key Foundation for Young Artist, I am impressed at the quality of their outputs."

Supporting publications are as below:

1) Transforming Growth Factor Beta 2 (TGFB2) mRNA Levels, in Conjunction with Interferon-Gamma Receptor Activation of Interferon Regulatory Factor 5 (IRF5) and Expression of CD276/B7-H3, Are Therapeutically Targetable Negative Prognostic Markers in Low-Grade Gliomas.Trieu V, Maida AE, Qazi S. Cancers (Basel). 2024 Mar 19;16(6):1202. doi: 10.3390/cancers16061202. PMID: 38539537.

2) Transforming Growth Factor Beta 2 (TGFB2) and Interferon Gamma Receptor 2 (IFNGR2) mRNA Levels in the Brainstem Tumor Microenvironment (TME) Significantly Impact Overall Survival in Pediatric DMG Patients. Qazi S, Talebi Z, Trieu V. Biomedicines. 2024 Jan 15;12(1):191. doi: 10.3390/biomedicines12010191. PMID: 38255296.

3) High Intra-Tumor Transforming Growth Factor Beta 2 Level as a Predictor of Poor Treatment Outcomes in Pediatric Diffuse Intrinsic Pontine Glioma. Uckun FM, Qazi S, Trieu V. Cancers (Basel). 2023 Mar 9;15(6):1676. doi: 10.3390/cancers15061676. PMID: 36980562.

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.

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!

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

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!

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.

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 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.