On October 2, 2024 Alentis Therapeutics ("Alentis"), the clinical-stage biotechnology company developing treatments for Claudin-1 positive (CLDN1+) tumors and organ fibrosis, reported that the U.S. Food & Drug Administration (FDA) cleared an IND application for ALE.P02, an anti-CLDN1 ADC with a tubulin inhibitor payload (Press release, Alentis Therapeutics, OCT 2, 2024, View Source [SID1234646996]). A Phase 1/2 clinical trial in patients with CLDN1+ squamous tumors is expected to start during the first quarter of 2025.

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"ADCs have shown great potential in the treatment of cancer," Luigi Manenti, Chief Medical Officer of Alentis. "Squamous cancers originating in the head and neck, cervix, esophagus and lung are characterized by high CLDN1 expression, and ALE.P02 provides a first-in-class opportunity for these patients who need new therapies after first-line treatment fails."

"Anti-CLDN1 ADCs are exciting because they address the urgent need for novel targets in the ADC space," added Tony Mok, Professor of Clinical Oncology at the Chinese University of Hong Kong. "ALE.P02 is particularly promising for squamous cancers, including HNSCC and NSCLC, where CLDN1 is often overexpressed. The unmet medical need in these indications is significant, and I look forward to the results of the Phase 1/2 study."

Dr. Roberto Iacone, Chief Executive Officer of Alentis said, "ALE.P02, entering the clinic, marks a significant advancement in our oncology pipeline. We can maximize our development plan by leveraging insights from human clinical trials of lixudebart (ALE.F02), used as the backbone antibody for Alentis’ ADCs."

Dr. Iacone added, "For our second ADC program, ALE.P03, with its topoisomerase I inhibitor payload, we plan to initiate a first-in-human clinical trial in 2025."

About ALE.P02
ALE.P02 is a first-in-class ADC designed by linking a tubulin inhibitor, a potent cancer drug, to our antibody that specifically targets a unique CLDN1 epitope exposed on cancer cells. This combination could be a powerful new tool to fight the many squamous cancers that overexpress CLDN1 with less toxicity than traditional cancer drugs.

On October 1, 2024 Excellos Inc., a cell therapy contract and development manufacturing organization (CDMO) member of Blood Centers of America (BCA), reported that it has been selected to manufacture Galapagos’ CAR-T cell therapy candidate, GLPG5101, for its recently FDA cleared ATALANTA-1 clinical study in patients with relapsed/refractory non-Hodgkin lymphoma in the U.S (Press release, Galapagos, OCT 1, 2024, View Source [SID1234646992]).

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Galapagos (Euronext & Nasdaq: GLPG) is a clinical stage biotechnology company with operations in Europe and the U.S. dedicated to developing transformational medicines for more years of life and quality of life across the globe.

Excellos was selected upon completion of an extensive site audit and assessment process and will provide end-to-end manufacturing of Galapagos’ CAR-T cell therapy on Galapagos’ platform at Excellos’ new purpose-built manufacturing facility in downtown San Diego, CA.

Galapagos’ innovative, decentralized manufacturing platform could address many of the limitations that CAR-T cell therapy production is currently facing. It has the potential to offer greater speed and scalability, with the delivery of fresh, fit cells with a median vein-to-vein time of seven days and the possibility for greater physician control and improved patient experience.

"We are excited to manufacture Galapagos’ CAR-T cell therapy candidate using their decentralized manufacturing platform. This collaboration will enable the efficient production and delivery of fresh, fit CAR-T cell therapies within a median vein-to-vein time of seven days," said Thomas VanCott, CEO of Excellos. "Our team is proud to have demonstrated our agility in initiating technology transfer, our state-of-the-art facility, and our expertise in executing production and analytics, all of which are critical to advancing this groundbreaking therapy."

This project represents the first site initiation under the recently announced strategic collaboration between Galapagos’ U.S. entity GLPG US, Inc. and BCA. Under this agreement, BCA’s national network of blood centers will provide decentralized manufacturing services for Galapagos’ CAR-T cell therapy product candidates, close to cancer treatment centers across the U.S.

"Blood Centers of America is pleased to be actively engaged with Galapagos in site identification, assessment and initiation to build a nationwide decentralized cell therapy manufacturing network," stated Bill Block, President/CEO of BCA. "The Excellos project is enabled by the broader agreement between BCA and Galapagos which allowed Excellos to move efficiently from site assessment to the start of technology transfer. BCA will use the insights from this first initiation to accelerate the integration of multiple BCA sites into Galapagos’ decentralized manufacturing network, with the goal of providing patients convenient access to our local facilities and healthcare providers within their communities."

On October 1, 2024 CEL-SCI Corporation (NYSE American: CVM) reported its renewed collaboration with Ergomed Clinical Research for its upcoming U.S. Food and Drug Administration (FDA) confirmatory Registration Study of Multikine (Leukocyte Interleukin, Injection) in head and neck cancer (Press release, Cel-Sci, OCT 1, 2024, View Source [SID1234646991]).

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Ergomed will provide global comprehensive clinical operations support to ensure the timely and efficient execution of the trial, supporting CEL-SCI in bringing a new treatment option for patients with locally advanced primary head and neck cancer to the market.

This partnership marks a continuation of the successful cooperation between the two companies, building on their previous collaboration for the Phase 3 trial of Multikine, which was the largest study ever conducted in head and neck cancer.

In addition to the positive outcome from its recent meeting with the FDA regarding the path to approval for its first-line investigational cancer immunotherapy, CEL-SCI achieved other major milestones including receiving pediatric waivers from the UK’s Medicines & Healthcare Products Regulatory Agency (MHRA) and the European Medicines Agency (EMA).

This confirmatory study represents a crucial step toward potential marketing approval of Multikine. The study, set to enrol 212 newly diagnosed patients with locally advanced primary head and neck cancer, will focus on patients with no lymph node involvement and low PD-L1 tumour expression. Patients will be enrolled across multiple sites globally, underscoring the strength of Ergomed’s global clinical trial management capabilities.

Geert Kersten, CEO of CEL-CI commented, "Ergomed is a trusted partner. Our past experience taught us that they are highly competent and motivated. Their enrolment was fast and the study was clean. The plan is for the study to commence in Q1 2025 in multiple countries."

Dr. Sy Pretorius, CEO of Ergomed Group, added, "We are excited to once again partner with CEL-SCI on this significant trial for Multikine. Our prior collaboration has set a strong foundation for this new phase, and we are committed to leveraging our global expertise in oncology clinical research to support this critical confirmatory study. Together, we aim to advance innovative therapies that can make a real impact on patients’ lives."

Multikine has already demonstrated promising results in its prior studies, showing a significant improvement in survival rates. In the target population for the confirmatory study, patients treated with Multikine had a 5-year survival of 73% vs 45% survival in the control patients, with a hazard ratio of 0.35. The confirmatory study is designed to provide the final data required for regulatory approval, bringing Multikine one step closer to becoming a breakthrough treatment option for head and neck cancer patients worldwide.

On October 1, 2024 Silexion Therapeutics Corp. (NASDAQ: SLXN) ("Silexion" or the "Company"), a clinical-stage biotech developing RNA interference (RNAi) therapies for KRAS-driven cancers, reported new preclinical findings for SIL-204, its second-generation siRNA candidate, following the optimization of its extended-release formulation (Press release, Silexion Therapeutics, OCT 1, 2024, View Source [SID1234646989]). These latest findings demonstrate that the latest SIL-204-microparticle formulation can inhibit the growth and induce necrosis of the human pancreatic cell line that bears the KRAS G12D mutation xenotransplanted into mice. Given that this mutation constitutes the largest segment of pancreatic cancer subtypes, it represents a significant in the development of SIL-204.

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Key new pre-clinical findings include:

Significant Anti-tumor Activity: In recent mouse xenograft studies, SIL-204 demonstrated substantial tumor reduction in the human pancreatic tumor cell lines with the KRAS G12D (Panc -1) mutations using the innovative approach of oncogene silencing with siRNA. Previous studies showed this effect using unformulated siRNA with daily injections. The new studies further show this effect with a single administration of SIL-204 encapsulated in an extended-release formulation. Moreover, histopathological examination of treated tumors showed a very high induction of tumor necrosis.
Improved Formulation In Vivo: The transition from PLGA depot rods to PLGA microparticles (MPs) has resulted in a superior extended-release profile, enhancing the therapeutic potential. We now report in vivo results indicating that our new modified PLGA-microparticle formulation has superior properties over previous extended-release formulations (Loder).
Silexion plans to initiate toxicology studies with SIL-204 within the upcoming months and has plans to advance SIL-204 into Phase 2/3 clinical trials in the first half of 2026, focusing initially on locally advanced pancreatic cancer (LAPC) which has a notoriously high mortality rate. In parallel, the company plans to initiate preclinical studies for SIL-204, in colorectal cancer models.

"These optimizations represent a significant step forward in our development of SIL-204," said Ilan Hadar, Chairman and CEO of Silexion. "The improvements in cellular uptake and the enhanced extended-release formulation further strengthen our confidence in SIL-204’s potential. We look forward to commencing our next set of studies in preparation for our Phase 2/3 clinical trial."

On October 1, 2024 GeneCentric Therapeutics, a company making precision medicine more precise through RNA-based diagnostics, reported that results from the GARNER (Genomic Analysis of high-Risk Non-muscle invasive bladder cancER) study were published in Clinical Cancer Research (Press release, GeneCentric Therapeutics, OCT 1, 2024, View Source [SID1234646988]). The GARNER study, the largest high-risk non-muscle invasive bladder cancer (HR-NMIBC) patient cohort ever assembled with both clinical and genomic detail, investigated fibroblast growth factor receptor (FGFR) DNA alteration (ALT) frequency and activation in HR-NMIBC and the clinical outcomes associated with standard-of-care Bacillus Calmette-Guérin (BCG) treatment. The study was conducted by the Erasmus MC Urothelial Cancer Research Group (EUCRG) at the Erasmus MC Cancer Institute. Janssen Research & Development, LLC, a Johnson & Johnson company, and GeneCentric collaborated to perform genomic testing.

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Although many HR-NMIBC patients respond to BCG treatment, 50-70% have a recurrence, and up to 20% progress to muscle-invasive bladder cancer (MIBC) or locally advanced/metastatic disease. Alternative therapies including FGFR-targeting agents are being investigated. While eligibility for FGFR-targeted therapies has focused on patients who are FGFR ALT (+), DNA alterations may not fully identify all patients who could potentially benefit from FGFR-targeted therapy. In this study, GeneCentric’s novel RNA-based FGFR-PRS identified approximately two-fold more patients with an activated FGFR pathway compared to those who were FGFR ALT (+).

"GeneCentric is intensely focused on developing RNA-based signatures, because DNA alterations and other biomarkers may have limitations in identifying all patients who could potentially benefit from targeted therapies," said Kirk Beebe, PhD, Chief Scientific Officer at GeneCentric. "The GARNER study allowed us to apply the FGFR-PRS to tumors from a high-risk group of patients with bladder cancer to show that the prevalence of FGFR-PRS positive tumors was much higher than the number of tumors identified with FGFR DNA alterations. Beyond HR-NMIBC, we have developed gene signatures for a broad range of targeted therapies, with a vision for this approach eventually becoming the paradigm for patient selection as an adjunct or in place of DNA alteration testing."

Findings related to the FGFR-PRS from the study include:

The FGFR alteration frequency (i.e., FGFR ALT (+)) in HR-NMIBC tumors was 31%.
The frequency of FGFR-activated tumors using the FGFR-PRS was more than twice as high as FGFR ALT+ at 75%.
This enrichment of tumors that may be FGFR-activated identified by the FGFR-PRS compared to FGFR-altered tumors was also observed in more advanced-stage disease (muscle-invasive and metastatic urothelial cancer).
About the GARNER Study

The GARNER study is the largest HR-NMIBC real-world patient cohort ever assembled with both clinical and genomic detail and the first study of the broader GARNER Bladder Cancer Program. The study is comprised of a cohort of almost 1,200 NMIBC patients who underwent surgery and adjuvant BCG treatment. The study was conducted by Tahlita Zuiverloon, MD, PhD, Principal Investigator at the Department of Urology at Erasmus MC Urothelial Cancer Research Group (EUCRG) at the Erasmus MC Cancer Institute. Janssen Research & Development, LLC, a Johnson & Johnson company, and GeneCentric Therapeutics performed retrospective genomic analysis of longitudinal samples collected in this study.