Globenewswire | May 26, 2023
Xilio Therapeutics, Inc. (Nasdaq: XLO), a clinical-stage biotechnology company discovering and developing tumor-activated immuno-oncology therapies for people living with cancer, today announced preliminary data from its Phase 1 clinical trial evaluating XTX101, an investigational tumor-activated, Fc-enhanced anti-CTLA-4, in patients with advanced solid tumors.
“We are encouraged by the preliminary data from the Phase 1 trial for XTX101 showing evidence of tumor-selective activation,” said Martin Huber, M.D., president and head of research and development at Xilio. “Following treatment with XTX101 monotherapy at the recommended Phase 2 dose of 150 mg once every six weeks, we observed a partial response in a patient with PD-L1 negative advanced non-small cell lung cancer. Importantly, this anti-tumor activity occurred in the absence of meaningful observed activation of the immune system in the periphery, suggesting tumor-selective activation of XTX101. Based on these Phase 1 data, we plan to explore opportunities to evaluate XTX101 in combination with an anti-PD-(L)1 in historically immunotherapy-resistant tumor types.”
Data from the Ongoing Phase 1 Clinical Trial for XTX101
As of a data cutoff date of May 2, 2023, 25 patients had been treated with XTX101, including dose levels ranging from 7 mg to 180 mg administered once every three weeks (Q3W) and one dose level at 150 mg administered once every six weeks (Q6W). Of these patients, 20 patients were dosed in monotherapy dose-escalation (Part 1A) and five patients were dosed in monotherapy dose-expansion (Part 1B).
Patients had a wide range of advanced and treatment-refractory solid tumors, including colorectal cancer (CRC), non-small cell lung cancer (NSCLC) and pancreatic cancer. In addition, 76% of patients had been previously treated with at least three prior lines of anti-cancer therapy, and 44% had been previously treated with at least one immuno-oncology (I-O) agent. As of the data cutoff date, three patients were continuing on treatment with XTX101, and 22 patients had discontinued treatment with XTX101.
Preliminary Safety Data
A recommended Phase 2 dose (RP2D) and schedule of 150 mg Q6W was determined based on the favorable preliminary safety, pharmacokinetic (PK) and pharmacodynamic (PD) data for XTX101. At the RP2D, no dose-limiting toxicities were observed, and there was no reported evidence of immune-related endocrine or skin adverse events (AEs) that are commonly associated with systemically active anti-CTLA-4 agents. In addition, evidence of effective masking of XTX101 was demonstrated by low levels of unmasked drug detected in peripheral circulation, and XTX101 achieved target PK exposure at the RP2D, reaching the targeted area under the curve (AUC) and peak concentration (Cmax).
As of the data cutoff date:
Across all dosing levels and dosing intervals, no Grade 4 or Grade 5 treatment-related AEs were reported by investigators.
Among seven patients who received XTX101 administered at the RP2D of 150 mg on a Q6W dosing schedule, the most common treatment-related AEs (≥10% incidence) of any grade reported by investigators were diarrhea (14%), fatigue (14%) and decreased appetite (14%). In these patients, no treatment-related colitis or infusion related reaction of any grade was observed. Investigators reported only one Grade 3 treatment-related AE of diarrhea, which occurred after two doses and resolved after five days without steroid use. This patient tolerated two additional doses of XTX101 after dose reduction to 75 mg Q6W without any symptom recurrence. At the RP2D of 150 mg Q6W, this was the only patient with a dose reduction due to an AE, and no patients discontinued treatment due to a treatment-related AE.
Among 18 patients who received XTX101 administered on a Q3W dosing schedule, the most common treatment-related AEs (≥10% incidence) of any grade reported by investigators were diarrhea (28%), colitis (28%), infusion related reaction (28%), nausea (17%), vomiting (17%) and abdominal pain (11%). Of these, investigators reported the following Grade 3 treatment-related AEs: diarrhea (6%), colitis (22%) and infusion related reaction (17%). Infusion related reactions were associated with antidrug antibodies. Across all dose levels administered Q3W, two patients had dose reductions due to AEs, and four patients discontinued treatment due to an infusion related reaction.
Preliminary Anti-Tumor Activity
A partial response was observed at nine weeks in one patient with advanced PD-L1 negative NSCLC with hepatic metastases treated with XTX101 at the 150 mg Q6W dose level and confirmed after the data cutoff date at week 27. The only treatment-related AE reported for this patient was Grade 1 fatigue. In addition, PD markers for anti-CTLA-4 reported for this patient showed minimal immune activation in peripheral circulation, demonstrating evidence of tumor-selective activation of XTX101. The patient is currently continuing on treatment with XTX101.
Clinical Development Plan for XTX101
Enrollment in monotherapy dose-expansion (Part 1B) of the Phase 1 trial is currently ongoing, with the goal of further characterizing the safety, PK and PD of XTX101 at the RP2D of 150 mg Q6W. In addition, mandatory tumor biopsies will be obtained from patients in Part 1B to examine intra-tumoral PK and PD for XTX101.
Xilio plans to continue to explore strategic opportunities to advance XTX101 with a partner beyond the current Phase 1 monotherapy cohorts, including in potential Phase 1 dose escalation evaluating XTX101 in combination with a PD-(L)1 and in a potential Phase 2 trial evaluating XTX101 in combination with a PD-(L)1 in patients with microsatellite stable CRC.
About XTX101 (anti-CTLA-4) and the Phase 1 Clinical Trial
XTX101 is an investigational tumor-activated, Fc-enhanced anti-CTLA-4 monoclonal antibody designed to deplete regulatory T cells when activated (unmasked) in the tumor microenvironment (TME). The Phase 1 clinical trial is a first-in-human, multi-center, open-label trial designed to evaluate the safety and tolerability of XTX101 for the treatment of patients with advanced solid tumors. The primary outcome measures were the incidence of dose-limiting toxicities (DLTs) and the incidence of treatment-related adverse events, and changes in clinical laboratory abnormalities. Please refer to NCT04896697 on www.clinicaltrials.gov for additional details.
About Xilio Therapeutics
Xilio Therapeutics is a clinical-stage biotechnology company discovering and developing tumor-activated immuno-oncology (I-O) therapies with the goal of significantly improving outcomes for people living with cancer without the systemic side effects of current I-O treatments. The company is using its proprietary geographically precise solutions (GPS) platform to build a pipeline of novel, tumor-activated molecules, including cytokines and other biologics, which are designed to optimize their therapeutic index and localize anti-tumor activity within the tumor microenvironment. Xilio is currently advancing multiple programs for tumor-activated I-O treatments in clinical development, as well as programs in preclinical development. Learn more by visiting www.xiliotx.com and follow us on Twitter (@xiliotx) and LinkedIn (Xilio Therapeutics, Inc.).
INDUSTRIAL IMPACT, MEDICAL
Synthego | March 17, 2023
Synthego Corp., a leading genome engineering solutions provider, announced today the launch of its service partner ecosystem, CRISPR Discovery Partners, designed to accelerate drug discovery by providing a seamless research workflow from CRISPR editing to phenotypic data and downstream services. The ecosystem brings together high-value partners including Arctoris, BrainXell, Curia, PhenoVista, and Pluristyx to offer a coordinated solution for CRISPR-driven drug discovery.
The CRISPR Discovery Partner ecosystem creates an integrated workflow starting with Synthego's CRISPR Engineered Cells through functional readouts, providing researchers with a faster, more efficient, and more reliable way to move their discoveries forward. Researchers can access the full range of genome engineering services through Synthego, as well as downstream services including small molecule screening, cell-based assays, high content imaging, iPSC differentiation, and multi-omics through partners. The result is a streamlined drug discovery process that can help accelerate the development of life-saving treatments.
Synthego's CRISPR Discovery Partners include
Arctoris, a tech-enabled drug discovery service company, combines wet lab automation and machine learning with a world-class team of experienced drug discovery researchers to enable the accelerated development of small molecule, biologics, and cell therapy assets.
BrainXell provides differentiation services to generate high-purity, iPSC-derived human neurons, astrocytes, and microglia for research use with a focus on drug discovery. BrainXell also offers fibroblast reprogramming and select downstream assay services.
Curia, a global contract research, development and manufacturing organization (CDMO), offers products and services from discovery through manufacturing to help customers transform R&D results into real-world impact.
PhenoVista, a San Diego-based CRO, specializes in modern, human, cell-based in vitro assay development and analysis. Internationally recognized for developing and implementing both fully bespoke projects and pre-validated Ready-2-Go assay services, this award-winning research partner leverages high-content imaging to enable life scientists to accelerate their discovery of novel therapeutics and improve global health.
Pluristyx offers expertise and tools to support and accelerate the development and commercialization of revolutionary therapeutics to treat serious human diseases by providing unique products, consulting, and contract services, including cell line expansion and banking.
Synthego is a genome engineering company that enables the acceleration of life science research and development in the pursuit of improved human health. The company leverages machine learning, automation, and gene editing to build platforms and products for science at scale. With its foundations in engineering disciplines, the company's platform technologies vertically integrate proprietary hardware, software, bioinformatics, chemistries, and molecular biology to advance basic research, target validation, and clinical trials. With its technologies cited in hundreds of peer-reviewed publications and utilized by thousands of commercial and academic researchers and therapeutic drug developers, Synthego is at the forefront of innovation enabling the next generation of medicines by delivering genome editing at an unprecedented scale.
prnewswire | May 08, 2023
Frost & Sullivan announced that it has awarded Genomenon with the 2023 Global Technology Innovation Leadership Award. Each year, Frost & Sullivan presents this award to the company that has developed a product with innovative features and functionality that is gaining rapid acceptance in the market. The award recognizes the quality of the solution and the customer value enhancements it enables. Frost & Sullivan market analysts determined that Genomenon excels in many of the criteria and best practices identified as critical for the global pharma and clinical diagnostics genomics markets.
Genomenon is a genomic intelligence software company that combines AI-powered Genomic Language Processing (GLP) with expert review by genetic scientists to deliver the most comprehensive knowledgebase of genomic evidence available. Their fit-for-purpose combinatorial approach to identifying and indexing published genomic evidence gives them a unique advantage over other open access and commercial genomic data resources in this space.
Clinical diagnostic labs rely on Genomenon's Mastermind Genomic Search Engine to find critical information needed to diagnose rare genetic diseases and identify the most appropriate patient treatment options. Pharmaceutical companies engaged in the development of rare disease therapeutics partner with Genomenon to gain deep insights into the genetic drivers of disease. The Genomenon scientific team leverages information in the Mastermind knowledgebase to provide the genomic intelligence pharmaceutical companies need to better understand disease mechanisms, more accurately estimate disease prevalence, design clinical trials, and prepare documentation for regulatory approvals.
Pavel Zhebrouski, a best practices research analyst at Frost & Sullivan, observed, "Genomenon differentiates itself in the space by providing a unique combination of AI technology and human expertise. Genomenon empowers rare disease pharmaceutical and biotechnology companies to make informed decisions about promising candidates in their pipeline and help propel novel therapeutics to market. Its commitment to innovation and creativity, scientific rigor, and accuracy, while achieving commercial success, differentiates it from competitors," added Tejashri Khadilkar, Frost & Sullivan industry analyst.
Frost & Sullivan Best Practices awards recognize companies in various regional and global markets for demonstrating outstanding achievement and superior performance in leadership, technological innovation, customer service, and strategic product development. Industry analysts compare market participants and measure performance through in-depth interviews, analyses, and extensive secondary research to identify best practices in the industry.
Genomenon is an AI-driven genomics company focused on making genomic information actionable for patients with rare genetic diseases and cancer. Keeping pace with the ever-evolving body of knowledge within genomics, Genomenon connects current research with patient DNA to accelerate clinical decision-making and pharmaceutical drug discovery and development.