On October 10, 2024 XENOTHERA, a Nantes-based biotech developing innovative treatments using multi-specific polyclonal glyco-humanized antibodies (GH-pAb), reported the recruitment of the first patient in its new clinical trial in onco-hematology. PALT1 is a multicenter phase I/II trial evaluating the safety and efficacy of its antibody directed against tumoral T-cells in patients with relapsed/refractory PTCL (NCT 06495723) (Press release, Xenothera, OCT 10, 2024, View Source [SID1234647145]). The PALT1 trial started at the beginning of July in five French centers.

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Meanwhile, the company received orphan drug designation (ODD) for this antibody in PTCL from the European Medicines Agency (EMA), in addition to the ODD already granted by the Food and Drug Administration (FDA).

Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of non-Hodgkin’s lymphomas for which there is a great medical need. PTCL are aggressive hematological tumors with a poor prognosis. Patients are generally treated with CHOP chemotherapy as first line, which unfortunately has limited efficacy, like other treatments, which response rate is usually less than 30%.

XENOTHERA’s antibody is derived from its platform of multi-specific glyco-humanized antibodies. In preclinical studies, it recognizes most PTCL, is more effective than CHOP on T lymphoma cells, and has a significant anti-tumor effect, reducing tumor size by up to 90% in preclinical in vivo models.

The EMA granted the clinical trial authorization for PALT1 in April 2024 and the orphan drug designation (ODD) in June 2024, confirming its interest in this innovative treatment for a serious disease. ODD provides XENOTHERA with benefits at every stage of development, including assistance with the development process, tax credit, technical assistance in preparing the application, streamlined administrative procedures, intellectual property protection and a marketing exclusivity clause once marketing authorization has been obtained. Orphan designation had already been obtained from the FDA in 2023.

The first centers to take part in the trial are the university hospitals of Caen (Professor Damaj), Clermont-Ferrand (Professor Tournilhac), Bordeaux (Professor Bouabdallah), AP-HP (Hôpital Henri-Mondor, Professor Lemonnier) and the Hospices Civils de Lyon (Hôpital Lyon-Sud, Professor Bachy). The first patient was recruited at Caen University Hospital by Professor Damaj’s teams.

PALT1 is a non-randomized, open-label phase I/II trial conducted in two stages in volunteer patients: a dose escalation phase to assess safety and tolerability and identify the maximum tolerated dose (MTD), followed by an expansion phase to assess the efficacy of PTCL treatment in relapsed/refractory patients.

"The start of this trial strengthens our position in oncology. We currently have another antibody in the clinic in solid tumors, in the FIPO trial. By entering the field of onco-hematology with the PALT1 trial, we maintain our focus on patients for whom medicine currently has no solution. I would like to thank this first patient and Professor Damaj’s teams for their confidence, and I sincerely hope that the expected benefits will be confirmed. PALT1 also supports the quality of the work done by XENOTHERA’s scientific and medical teams. Moreover, the agencies – EMA in 2024 and FDA in 2023 – are supporting our approach to patients’ needs, and reinforcing our credibility", comments Odile Duvaux, Chairman and co-founder of XENOTHERA.

On October 10, 2024 Purple Biotech Ltd. ("Purple Biotech" or "the Company") (NASDAQ/TASE: PPBT), a clinical-stage company developing first-in-class therapies that overcome tumor immune evasion and drug resistance, reported it has been selected for a poster presentation at the 36th European Organization for Research and Treatment of Cancer, National Cancer Institute, American Association for Cancer Research (AACR) (Free AACR Whitepaper) (EORTC-NCI-AACR) (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics (the "Triple Meeting") held October 23-25, 2024 in Barcelona, Spain (Press release, Purple Biotech, OCT 10, 2024, View Source;id=322854&p=2344395&I=1206939-c7Z3G6f3m8 [SID1234647146]).

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Purple Biotech’s poster titled "CAPTN-3: A novel platform of conditionally activated T cell and NK cell engagers" (Abstract # 450, poster board number: PB438) will be presented by Dr. Hadas Reuveni, VP R&D of Purple Biotech, during a ‘New therapies in immuno oncology’ poster session on Friday, 25 October 2024.

CAPTN-3 is a First-in-class platform of conditionally activated tri-specific antibodies engaging both T cells and NK cells with the tumor to create an immune synapse with enhanced anti-tumor efficacy. The NK engager arm (aNKG2A) of our lead compound also acts as a checkpoint inhibitor for both NK cells and highly cytotoxic T cell subsets, unleashing both innate and adaptive immune subsets against the tumor.

Purple Biotech’s lead CAPTN-3 platform candidate, IM1240, targets 5T4 as a tumor associated antigen (TAA), which is overexpressed in a variety of solid tumors and is correlated with advanced disease, increased invasiveness, and poor clinical outcome. 5T4, also known as trophoblast glycoprotein (TPBG), is an oncofetal surface protein that is not found on adult healthy tissues but is abnormally expressed in several cancer types. This specific expression pattern as well as the correlation with poor prognosis in different cancer diseases such as lung, gastric, head and neck and other cancers makes it an ideal TAA for various therapeutic approaches.

On October 10, 2024 Genprex, Inc. ("Genprex" or the "Company") (NASDAQ: GNPX), a clinical-stage gene therapy company focused on developing life-changing therapies for patients with cancer and diabetes, reported that its research collaborators will present at the upcoming 2024 EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics being held October 23-25, 2024 in Barcelona, Spain (Press release, Genprex, OCT 10, 2024, View Source [SID1234647147]). The collaborators will present posters on positive preclinical data from studies of its lead drug candidate, Reqorsa Gene Therapy (quaratusugene ozeplasmid), for the treatment of Ras inhibitor resistant lung cancer, mesothelioma and glioblastoma.

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"The compelling data made available today validates the potential of REQORSA as a therapeutic treatment for some of the most difficult to treat cancers and diseases, including Ras inhibitor resistant lung cancer, mesothelioma and glioblastoma," said Ryan Confer, President and Chief Executive Officer at Genprex. "We are very encouraged to see the data support potential new indications for REQORSA, which could address unmet medical need for many patient populations. We look forward to continuing our preclinical programs studying REQORSA to explore how we could expand our clinical development pipeline with future clinical studies."

Genprex has filed two provisional patent applications based on data from two of the presentations. One application involves using REQORSA to treat mesothelioma and the other uses REQORSA to treat glioblastoma. Genprex is a co-owner of the applications along with the respective institutions. TUSC2 is the tumor suppressor gene used in REQORSA.

Featured Genprex-supported posters to be presented at the 2024 EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics include:

Title: "TUSC2 Gene Therapy in KRASG12C Mutant NSCLC Overcomes Acquired Resistance to Sotorasib"
Collaborator: The University of Texas MD Anderson Cancer Center
Catalog Number: 384
Presentation Number: PB372

Acquired resistance (AR) to Lumakras (sotorasib), the first FDA-approved KRASi, poses a significant challenge in the treatment of KRASG12C mutant non-small cell lung cancer (NSCLC). Despite an initial response rate of up to 40%, patients invariably develop resistance, necessitating alternative therapeutic strategies. The mechanisms of AR include the emergence of additional mutations in the KRAS gene, reactivation of KRAS pathway, or activation of alternative signaling pathways. TUSC2, a potent tumor suppressor gene, exhibits multifunctional activities including multikinase inhibition, inhibition of growth & proliferation, induction of cell death and activation of both innate and adaptive immune responses. In this study, researchers demonstrated that TUSC2 gene therapy (REQORSA) effectively overcomes sotorasib AR in KRASG12Cmutant NSCLC mouse xenografts.

The data indicates that TUSC2 transfection significantly reduced colony formation in two AR cell lines. Transfection of TUSC2 also markedly increased apoptosis in AR cells. H23AR xenograft tumors exhibited significantly lower sensitivity to sotorasib than their parental counterparts. However, treatment with REQORSA alone or in combination with sotorasib was highly effective in controlling H23AR tumor growth in mouse xenografts. REQORSA alone also exhibited significantly strong antitumor effect on TC314AR patient-derived xenografts (PDXs) where sotorasib alone showed no significant antitumor activity. However, a synergistic antitumor effect was observed when TC314AR PDX tumors were treated with the combination of REQORSA and sotorasib.

In conclusion, researchers demonstrated that TUSC2 therapy, alone or in combination with sotorasib inhibited colony formation, induced apoptosis, and showed significant antitumor efficacy in KRASG12C mutant acquired resistant xenografts and in PDX tumor xenografts.

Title: "TUSC2 Suppresses Tumorigenic Properties in Malignant Pleural Mesothelioma Cells"
Collaborator: New York University Langone Health
Catalog Number: 364
Presentation Number: PB352

Malignant Pleural Mesothelioma (MPM) is a rare, highly aggressive, asbestos-associated neoplasm with a median survival of 10-12 months. TUSC2 is frequently deleted in multiple cancers and at least one allele is absent in 36% of MPM. Researchers investigated whether TUSC2 transfection could modulate MPM aggressive properties.

In this study, four MPM cell lines and tert-transformed mesothelial LP9 cells were treated with REQORSA and control liposomes for 48h. Treated cells were then evaluated for TUSC2 expression by semi quantitative RT-PCR, Western blot analysis, and functional assays including cell proliferation, invasion, and apoptosis.

The researchers demonstrated that REQORSA treatment resulted in a significant decrease in cell proliferation, cell invasion, and a significant increase in cell apoptosis in all four MPM cell lines. Data also demonstrated potent tumor suppressive activity of the TUSC2 gene delivered by REQORSA, and thus, its re-expression could serve as a potential therapeutic strategy for the treatment of MPM.

Title: "Efficacy of Quaratusugene Ozeplasmid (REQORSA) TUSC2 Gene Therapy in Glioblastoma"
Collaborator: The University of Texas Health Science Center at Houston
Catalog Number: 130
Presentation Number: PB118

Research collaborators previously reported TUSC2 as a novel tumor suppressor for glioblastoma, the most common and deadliest primary brain tumor in adults which is associated with a poor prognosis. In their latest study, patient-derived glioblastoma (GBM) cell lines and patient-derived glioma stem cell (PD-GSC) lines were used. REQORSA was used to restore TUSC2 expression.

Researchers observed that REQORSA significantly reduced GBM cell viability, and the results of a migration assay demonstrated that REQORSA suppressed GBM cell migration independent of its ability to suppress cell viability. In conclusion, REQORSA demonstrates promising in vitro efficacy in GBM and PD-GSCs, and these results support further evaluation of its in vivo anti-tumor efficacy in malignant gliomas using mouse models.

About Reqorsa Gene Therapy
REQORSA (quaratusugene ozeplasmid) consists of a plasmid containing the TUSC2 gene encapsulated in non-viral lipid-based nanoparticles in a lipoplex form (the Company’s Oncoprex Delivery System), which has a positive charge. REQORSA is injected intravenously and specifically targets cancer cells. REQORSA is designed to deliver the functioning TUSC2 gene to negatively charged cancer cells while minimizing uptake by normal tissue. Laboratory studies conducted at MD Anderson show that the uptake of TUSC2 in tumor cells in vitro after REQORSA treatment was 10 to 33 times the uptake in normal cells.

On October 10, 2024 Alpha Tau Medical Ltd. ("Alpha Tau", or the "Company") (NASDAQ: DRTS, DRTSW), the developer of the innovative alpha-radiation cancer therapy Alpha DaRT, reported that its first patient with recurrent lung cancer has been treated, in a clinical trial at Hadassah Medical Center in Jerusalem, Israel (Press release, Alpha Tau Medical, OCT 10, 2024, View Source [SID1234647132]).

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The trial is designed to treat up to ten patients with recurrent tumors in the mediastinum area of the chest, and allows for the use of concurrent chemotherapy, targeted therapy, or immunotherapy, if indicated. The study will assess the safety and feasibility of delivering Alpha DaRT sources into the lung using an endobronchial ultrasound (EBUS) procedure, including by observing the rate of successful source placement and any treatment-related adverse events. In addition, the study will also assess the efficacy of Alpha DaRT for this indication by examining tumor response at one and three months after source insertion using RECIST criteria, as well as tumor coverage. Additional information about the trial can be found at View Source

According to the WHO’s International Agency for Research on Cancer, lung cancer is the leading cause of cancer-related deaths worldwide, with almost 2.5 million new cases detected each year, and is often only diagnosed at advanced stages, when treatment options are limited. In the U.S., lung cancer is the third most common cancer, according to the Centers for Disease Control and Prevention, with an estimated 210,000 new cases per year.

"Alpha Tau continues to forge ahead with the application of Alpha DaRT to a broader set of indications, particularly in tumors in visceral organs and other complex cases," said Alpha Tau Chief Executive Officer Uzi Sofer. "As we see continued clinician excitement and demand for use of the Alpha DaRT in an ever-increasing set of cancers, the ability to start treating patients in as terrible and widespread an illness as lung cancer is particularly meaningful."

"The Institute of Pulmonology of Hadassah Medical Center is excited to utilize this groundbreaking EBUS-guided implantable alpha radiation technology to treat a patient with lung cancer for the first time," noted Prof. Neville Berkman, MD, the study principal investigator and Director of the Institute of Pulmonology and Head of Adults and Invasive Pulmonology Unit, Hadassah Medical Center, who treated the patient. "The treatment makes use of bronchoscopic endobronchial ultrasound to insert the Alpha DaRT sources. We look forward to further examining the promise of what the Alpha DaRT treatment can offer lung cancer patients and their families."

"Treating the first lung patient with the Alpha DaRT is a very exciting moment. We have already demonstrated the advantages of the Alpha DaRT technology in a number of other tumor types, but examining its application to an organ such the lung, given its proximity to vital healthy organs, may hopefully open new doors to a global population of patients with otherwise poor treatment options," commented Alpha Tau Chief Medical Officer Robert Den, MD.

"Treating the first patient with lung cancer using Alpha DaRT marks a significant advancement, introducing a novel approach that combines the precision of alpha-emitting particles with the ability to selectively target and destroy tumor cells while minimizing damage to surrounding healthy tissues," added Dr. Philip Blumenfeld, study co-investigator and Senior Radiation Oncologist and Head of Thoracic Radiation Oncology Services at Hadassah Medical Center. "In this specific case, the patient had already undergone conventional radiation therapy to the lung and lymph nodes, and additional radiation would have posed a high risk of serious harm to nearby structures, particularly the esophagus and bronchus."

About Alpha DaRT

Alpha DaRT (Diffusing Alpha-emitters Radiation Therapy) is designed to enable highly potent and conformal alpha-irradiation of solid tumors by intratumoral delivery of radium-224 impregnated sources. When the radium decays, its short-lived daughters are released from the sources and disperse while emitting high-energy alpha particles with the goal of destroying the tumor. Since the alpha-emitting atoms diffuse only a short distance, Alpha DaRT aims to mainly affect the tumor, and to spare the healthy tissue around it.

On October 10, 2024 Oncoinvent, a clinical stage, radiopharmaceutical company developing innovative treatments for solid cancers, reported that the first patient has been dosed in its Phase 2 study of Radspherin in patients with peritoneal carcinomatosis from ovarian cancer (Press release, Oncoinvent, OCT 10, 2024, View Source [SID1234647148]). Radspherin is a novel alpha-radiation therapy candidate designed for targeted, local treatment of cancers that have spread to body cavities. The Phase 2 trial is a randomized controlled study designed to assess progression-free survival (PFS) in primary advanced ovarian cancer patients treated with Radspherin following complete surgical resection and pre-operative chemotherapy.

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"We are pleased to announce the dosing of the first patient in our Phase 2 study of Radspherin in ovarian cancer patients, representing another pivotal achievement that underscores the potential of our clinical program," said Oystein Soug, Chief Executive Officer of Oncoinvent. "This milestone builds upon the highly encouraging data from our Phase 1/2a trials in ovarian and colorectal cancer patients, where Radspherin demonstrated promising safety and efficacy. This follows the FDA’s recently granted Fast Track designation, bringing us closer to demonstrating the therapeutic potential of Radspherin. We look forward to advancing this clinical study as part of our mission to improve outcomes for patients suffering from peritoneal carcinomatosis."

The Phase 2 trial (NCT06504147) is a randomized controlled study assessing the efficacy and safety of Radspherin in patients with peritoneal metastasis from ovarian cancer. The primary objective is to compare PFS between patients who receive Radspherin after complete surgical resection following pre-operative chemotherapy, and patients who only undergo pre-operative chemotherapy and surgery. The study is being conducted at six centers in the US, UK, Norway, Spain and Belgium. Positive Phase 1/2a data from the safety interim analysis demonstrated that Radspherin was well tolerated with no dose-limiting toxicity observed at the recommended dose of 7MBq.