Xilio Therapeutics(XLO)2023-03-02 21:18Immuno-Oncology Therapies Development - The company is developing tumor-activated immuno-oncology therapies aimed at improving cancer treatment outcomes while minimizing systemic side effects [30]. - The company’s goal is to transform cancer treatment by developing highly potent, tumor-selective therapies that provide effective and durable options for patients [41]. - The company aims to explore combination therapies using XTX202 and XTX301 to increase the potential for curative regimens in oncology [40]. - The company intends to explore XTX202 in additional solid tumor indications, including non-small cell lung cancer (NSCLC) and head and neck squamous cell cancer [119]. - The company has a clinical-stage cytokine pipeline that includes tumor-activated product candidates XTX202 (IL-2) and XTX301 (IL-12) [186]. XTX202 Clinical Trials and Data - XTX202, an engineered IL-2 therapy, is currently in a Phase 1 clinical trial with a recommended Phase 2 dose expected to be established; no signs of vascular leak syndrome have been observed to date [31]. - The company plans to report preliminary anti-tumor activity, safety, pharmacokinetic, and pharmacodynamic data from the Phase 1/2 trial of XTX202 in Q3 2023, involving approximately 15-20 patients [44]. - Preliminary data from the Phase 1 trial of XTX202 shows increased numbers of tumor-infiltrating lymphocytes and CD8+ effector T cells, indicating tumor-selective activation [62]. - The ongoing Phase 1 clinical trial for XTX202 has treated 16 patients at dose levels ranging from 0.27 mg/kg to 1.4 mg/kg, with no signs of vascular leak syndrome observed [108]. - The company plans to initiate a Phase 2 trial for XTX202 in patients with unresectable or metastatic melanoma and metastatic renal cell carcinoma (RCC) in April 2023 [105]. XTX301 Clinical Trials and Data - XTX301, an engineered IL-12 therapy, has received FDA clearance for clinical evaluation, with preliminary safety data anticipated by Q4 2023 [32]. - XTX301, a tumor-activated IL-12 product candidate, has received FDA clearance for evaluation in patients with advanced solid tumors, with a starting dose of 5.0 µg/kg [122]. - Preliminary safety data from the Phase 1 clinical trial is expected to be reported in Q4 2023, focusing on monotherapy dose-escalation [140]. - XTX301 demonstrated potent anti-tumor activity in preclinical studies without inducing significant systemic toxicity, indicating effective masking design [129]. - XTX301 was tolerated in non-human primates (NHPs) at doses up to 2 mg/kg once weekly, with a circulating half-life of approximately 4 days [132]. XTX101 Clinical Trials and Data - XTX101, an anti-CTLA-4 monoclonal antibody, is in a Phase 1 trial, with a recommended Phase 2 dose of 150 mg every six weeks established; preliminary data is expected in Q2 2023 [33][35]. - XTX101 aims to achieve a three-fold increase in therapeutic index, potentially transforming treatment outcomes for patients [145]. - XTX101 demonstrated 67% overall activation in a study of 82 tumor biopsies across various solid tumors [29]. - The combination of XTX101 with an anti-PD-1/PD-L1 antibody resulted in robust tumor growth inhibition of 82%, with minimal toxicity observed [159]. - As of March 1, 2023, 24 patients have been treated with XTX101 in a Phase 1 trial, with enrollment in monotherapy dose-expansion ongoing [162]. GPS Platform and Technology - The GPS platform is designed to create tumor-activated molecules that minimize systemic toxicity, enhancing the therapeutic index of immuno-oncology therapies [39]. - The GPS platform has shown preclinical validation for developing tumor-activated cytokines and antibodies, with promising early clinical evidence [62]. - The proprietary GPS platform aims to develop additional product candidates for tumor-selective activation and improved therapeutic index [165]. - The company aims to develop novel immuno-oncology (I-O) therapies using its GPS platform, focusing on overcoming the limitations of cytokines, such as short half-life and significant toxicity [48]. - XTX202 was engineered to be activated preferentially within the tumor microenvironment, enhancing its therapeutic index [78]. Financial and Regulatory Considerations - The company has paid AskGene an upfront payment of 13.0 million upon achieving specified regulatory milestones for licensed IL-2 products [202]. - The company must secure FDA approval for new drug or biological products, which involves multiple regulatory steps and compliance with good clinical practices [218][224]. - The company is obligated to pay up to $10.3 million for the first three licensed products or services achieving specified milestones [208]. - The company must pay tiered royalties in the low single digits on aggregate annual net sales of licensed products on a country-by-country basis until the expiration of the last-to-expire patent [208]. - The company has entered into a cross-license agreement with AskGene, granting exclusive licenses for AskGene patent rights related to non-antigen binding IL-2 products in oncology [201]. Patent and Intellectual Property - The company has 16 patent application families related to its business, with statutory expiration dates ranging between 2037 and 2043 [180]. - The company owns, co-owns, or exclusively in-licenses three patent families related to masked anti-CTLA-4 antibody constructs, including XTX101, with statutory expiration dates ranging between 2037 and 2042 [187]. - The company owns two patent families relating to masked IL-2 cytokines, including XTX202, with six pending U.S. applications and one issued U.S. patent [188]. - The company has a statutory expiration date for its IL-12 patent family in 2041, without considering any possible patent term adjustments or extensions [188]. - The company intends to apply for patent term extensions on issued patents covering product candidates once they receive FDA approval [197].