On June 11, 2024 Asgard Therapeutics, a privately held biotech company pioneering in vivo direct cell reprogramming for cancer immunotherapy, reported that it selected Exothera S.A. ("Exothera"), a leading provider of nucleic acids and viral vector development and manufacturing services, for process development up to clinical Phases I/II manufacturing of its candidate AT-108, based on viral vector technology (Press release, Asgard Therapeutics, JUN 11, 2024, View Source [SID1234644248]).

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AT-108 is a first-in-class, off-the-shelf gene therapy that leads to personalized and potent anti-cancer immune responses. AT-108 reprograms cancer cells inside the patient’s body to become conventional Type 1 Dendritic Cells (cDC1s), a rare subset of immune cells, which are critical for effective anti-tumor immunity. These induced cDC1s present the individual’s specific cancer antigens to the immune system, triggering personalized and systemic anti-cancer immune responses.

Exothera will be entrusted with the development and scale-up of a manufacturing process for the drug candidate, including development of analytical methods, GMP-grade material production, and aseptic filling.

Exothera offers a full-service model for viral vector-based biotherapeutics thanks to state-of-the-art technologies, and one of the largest viral vector facilities in Europe (15 000 m² – 161 500 ft²).

Cristiana Pires, Co-founder and Chief Executive Officer of Asgard Therapeutics, said: Following our proof-of-concept studies supporting the lead candidate AT-108, we are very happy to reach process development phase and start CMC activities. We are looking forward to work with the very knowledgeable and skilled technical team at Exothera to progress our pioneering AT-108 towards clinical development.

Hanna Lesch, Chief Technology Officer at Exothera, mentioned: We are proud to support Asgard Therapeutics in bringing these revolutionary therapeutics closer to the patients. Over the years we gained extensive experience with virus-based therapeutics production – both in suspension and in fixed bed bioreactors – and we are confident that we will use this expertise to help Asgard Therapeutics achieve clinical phase success.

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.

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"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 10, 2024 Defence Therapeutics Inc. ("Defence" or the "Company"), (CSE: DTC, OTCQB: DTCFF, FSE: DTC), a Canadian biopharmaceutical company developing novel immune-oncology vaccines and drug delivery technologies, reported its participation to the Society of Nuclear and Molecular Imaging ("SNMMI") annual meeting on June 11, 2024 at the Metro Toronto Convention Centre (Press release, Defence Therapeutics, JUN 10, 2024, View Source;utm_medium=rss&utm_campaign=defence-to-participate-to-2024-society-of-nuclear-medicine-and-molecular-imaging-annual-meeting-in-toronto-on-june-11-2024 [SID1234644251]).

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The SNMMI is a nonprofit scientific and professional organization that promotes the science, technology and practical application of nuclear medicine and molecular imaging. SNMMI strives to be a leader in unifying, advancing, and optimizing molecular imaging and radiotherapy, with a goal of improving human health. With 13,000 members worldwide, SNMMI represents nuclear and molecular imaging professionals, all of whom are committed to the advancement of the field. The SNMMI Annual Meeting is recognized as the premier educational, scientific, research, and networking event in nuclear medicine and molecular imaging. The event 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. SNMMI conference is the most recognized worldwide conference in the field of radiotherapy and molecular imaging gathering the most prestigious leader.

Defence is developing in collaboration with Orano Support SAS, a novel Radio-Immuno-Conjugate ("RIC"), named AccuTRICTM, which includes Defence’s AccuTOX resulting in increase efficacy to treat hard-to-treat cancers. The objective of this project is to develop the next generation of RIC exploiting the therapeutic dependency of Auger electron ("AE") emitter elements in closer proximity to DNA when combined with Defence’s Accum technology to induce its nuclear accumulation. AE emitters are very promising radionuclides for radiotherapy because of their very short pathlength radiation deposition, which decreases radiotoxicity on healthy tissues. The Accum moiety can overcome major limitations of RIC e.g. endosomal sequestration and poor nuclear accumulation, by destroying endosome membrane without affecting the plasma membrane nor mAbs specificity. Defence has developed a multitude of Accum variants with different biochemical properties and activities such as charged, hydrophobicity and cytotoxicity. One of these molecules is Defence’s lead molecule AccuTOX. AccuTRICTM is the combination of the synergistic activity of AccuTOX and the radiotherapeutics potential of AE. Defence’s AccuTRICTM objective is to efficiently treat hard-to-treat cancers with the potential of opening a new cancer therapy market based on a very promising radiotherapeutics implicating AE emitter radionuclides.

On June 10, 2024 Pacylex Pharmaceuticals Inc. (Pacylex) is a clinical-stage pharmaceutical company developing N-myristoyltransferase (NMT) inhibitors to treat hematologic cancers and solid tumors, reported the publication of Phase 1 clinical trial results in the journal Investigational New Drugs (Press release, Pacylex Pharmaceuticals, JUN 10, 2024, View Source [SID1234645047]). The report, titled: "A First-in-Human Phase I Trial of Daily Oral Zelenirstat, a N-myristoyltransferase Inhibitor, in Patients with Advanced Solid Tumors and Relapsed/Refractory B-cell Lymphomas," describes effects of zelenirstat at various doses on cancer patients who exhausted all other therapeutic options.

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Myristoylation is a fatty acid modification critical to targeting certain proteins to cell membranes where they participate in activities essential to cancer cell survival and proliferation. Zelenirstat works by the unique mechanism of inhibiting the myristoylation required for the assembly, translocation, and function of EGFR, VEGFR, and the B-cell receptor. Last month Pacylex published in the Journal of Translational Medicine that zelenirstat also blocks Complex I formation in mitochondria of cancer cells to shut down oxidative phosphorylation, an energy generation process needed for metastases and cancer stem cell survival.

The Phase 1 dose escalation safety and tolerability study was conducted in 29 patients with refractory/relapsed (r/r) lymphoma and refractory solid tumors who averaged 4 lines of prior therapy. Zelenirstat, administered as a once daily oral medication, was well-tolerated in Phase 1 patients up to the recommended Phase 2 dose (RP2D) with no dose limiting toxicities observed in 6 dose levels. The most common treatment related adverse events were mild to moderate gastrointestinal side effects which were self-limiting and occurred in a minority of patients.

The study was designed and sponsored by Pacylex Pharmaceuticals and was conducted at the Cross Cancer Institute, Edmonton, AB, under the direction of Principal Investigator Dr. Randeep Sangha; the British Columbia Cancer Centre for Lymphoid Cancer, Vancouver, BC, by Dr. Laurie Helen Sehn; Princess Margaret Cancer Centre, Toronto, ON by Dr. John Kuruvilla; and Université de Montréal’s hospital affiliated research centre, the CRCHUM, QC by Dr. Rahima Jamal.

The 7 patients receiving the recommended Phase 2 dose had significantly better progression free and overall survival than the 17 treated at lower doses; 57% had stable disease or better for six months or longer, including patients with ovarian, appendiceal, and colorectal cancer. The sole person with colorectal cancer receiving the RP2D had experienced only short-term benefit from any of the 6 prior lines of therapy, but continues to receive the zelenirstat 450 days after starting therapy and had reductions of approximately 50% in CEA (carcinoembryonic antigen) and tumor volumes.

"These Phase 1 results are as encouraging as any cancer study I have run with an oral cancer therapy", said Dr. Randeep Sangha. "The safety profile was consistent with long-term therapy and considering how many prior lines of therapy these patients had received, the signals of potential efficacy in several different types of solid tumor cancers was surprising."

"Given the outstanding safety of zelenirstat in Phase 1 and the prolonged stable disease or better seen in patients with refractory ovarian, appendiceal and colorectal cancer who received the RP2D, we are advancing zelenirstat into two Phase 2a studies that have begun dosing patients with refractory and relapsed B-cell non-Hodgkin’s lymphoma, and advanced refractory colorectal cancer", said Dr. John Mackey, CMO of Pacylex Pharmaceuticals.

"Zelenirstat is a very unique approach to treating cancer – it inhibits proteins that have been hijacked in cancer cells for survival and proliferation signaling, tumor blood supply, cell surface receptor recycling, and energy production, all with one drug", said Dr. Michael Weickert, CEO of Pacylex. "This explains how zelenirstat has potential as an important therapeutic option across many different cancers."

About zelenirstat (PCLX-001)

Zelenirstat (formerly identified as PCLX-001) is a first-in-class, oral, small molecule NMTi being developed to treat patients with leukemia, lymphoma, and solid tumors. Zelenirstat selectively killed cancer cells in vitro and in animal models has been shown to fully regress hematologic malignancies and inhibit the growth of lung and breast cancer tumors. In AML models, zelenirstat preferentially killed leukemic stem enriched cell populations and reduced the bone marrow leukemic burden.

About zelenirstat Phase 1 and 2 studies

Pacylex completed the dose escalation phase of a Phase 1 multiple ascending dose safety, tolerability, and pharmacokinetics study on zelenirstat in people with relapsed/refractory lymphoma and refractory solid tumors (NCT04836195). A recommended Phase 2 dose was determined. Zelenirstat demonstrated an acceptable safety and tolerability profile, pharmacokinetics consistent with once daily oral dosing, and early signs of efficacy.

Zelenirstat is currently being studied in a Phase 2a open-label study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and clinical activity of zelenirstat in patients with relapsed/refractory B-cell non-Hodgkin Lymphoma (NHL) and a separate Phase 2a cohort in patients with refractory metastatic colorectal cancer that has progressed despite all available standard therapies.

On June 10, 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 multiple abstracts that were presented at the 2024 Society of Nuclear Medicine & Molecular Imaging (SNMMI) Annual Meeting being held June 8 – 11, 2024, in Toronto, Canada (Press release, Actinium Pharmaceuticals, JUN 10, 2024, View Source [SID1234644229]). The presentations featured results from the Phase 3 SIERRA trial of Iomab-B, a CD45 targeting ARC with the Iodine-131 payload, intended for conditioning to prepare patients with active relapsed or refractory acute myeloid leukemia (r/r AML) for a potentially curative bone marrow transplant (BMT). The Phase 3 SIERRA trial enrolled 153 r/r AML patients. Iomab-B achieved the primary endpoint of durable Complete Remission (dCR) with high statistical significance (p<0.0001). Additionally, Actinium’s novel linker technology was highlighted in a presentation demonstrating high tumor uptake and in vivo stability in preclinical models with significantly lower kidney and liver uptake compared to standard DOTA linkers.

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Actinium’s Iomab-B SNMMI presentations and highlights:

Survival Outcomes and Dosimetric Analysis of Iomab-B (131I-apamistamab) Followed by Allogeneic Hematopoietic Cell Transplant for Patients with TP53 Mutated Relapsed/Refractory AML

37 patients (24%) enrolled on SIERRA had a TP53 mutation with 27 patients receiving Iomab-B (either through randomization or cross over) and 10 patients on the control arm
For patients with TP53 mutation who received Iomab-B, the median OS was 5.49 months compared to a median 1.66 months in pts who did not receive Iomab-B (HR=0.23; 95% CI [0.10, 0.52])
These results support Iomab-B’s differentiated mechanism of action to overcome the negative impact of TP53 mutation typically associated with a dismal prognosis in these patients
Exploratory Analysis of Bone Marrow Dosimetry from the Randomized Phase 3 SIERRA Trial of Iomab-B (131I-apamistamab) Prior to HCT in Relapsed/Refractory Acute Myeloid Leukemia

Iomab-B safely delivers high doses of myeloablative targeted radiation to the diseased bone marrow at greater amounts than what would be achieved with total body irradiation
Myeloablative doses were safely delivered to patients irrespective of age, performance status and other metrics
A median of 16Gy of radiation was delivered to the bone marrow while normal healthy organs received significantly less exposure, including the heart (2.6 Gy), lungs (2.5 Gy), small intestine (2.4 Gy), stomach (3.6 Gy), kidneys (4.1 Gy) and the whole body (3.3 Gy)
Mathematical Modeling of Exposure Measurements Following High-Dose Targeted Therapy Using 131I-apamistamab: Analysis From the Large Multicenter Phase III SIERRA Trial

SIERRA patients received up to 1,030 mCi (range: 300-1,030) of Iodine-131 via Iomab-B
Iomab-B is administered via a single infusion 12 days prior to BMT
Data from SIERRA show that the median time for patients to reach the release criteria was 5 days, including in patients receiving greater than 800 mCi
Actinium’s Proprietary Linker Technology SNMMI presentation and highlights:

Evaluation of novel DOTA-based linkers for improved targeted radiotherapy delivery to solid tumors

Novel linkers showed significantly lower kidney and liver uptake compared to standard DOTA linkers
SPECT/CT imaging showed high tumor uptake and in vivo stability in preclinical models
Successful design, efficient conjugation and pharmacological properties support further advancement of these novel linkers
Actinium has two wholly owned U.S. patents covering its novel bifunctional linker technology with each having a patent term extending into 2043 and a pending international patent application
Sandesh Seth, Actinium’s Chairman and CEO, said, "At this year’s SNMMI, we are proud to highlight Actinium’s broad ARC pipeline and capabilities. Building on our leadership position in hematology focused ARCs through Iomab-B and Actimab-A, we are excited to highlight the potential to treat patients with high-risk relapsed or refractory AML and overcome TP53 mutations or extensive prior therapy including Venetoclax. Hematology represents an area with potential for significant growth for the field of nuclear medicine and there is great excitement from the community around our efforts. Consistent with our vision to build a leading specialty radiotherapeutics company, we are also eager to highlight our novel linker technology for solid tumor ARCs. Finally, SNMMI provides the opportunity to showcase our proprietary Actinium-225 cyclotron-based manufacturing technology that has the potential to produce highly pure medical grade Actinium-225 at a scale and cost that is not currently achievable, which has been met with great enthusiasm given the industry emphasis on Actinium-225 supply."

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.