Core Insights - Xilio Therapeutics has reported promising clinical data for its investigational therapies, vilastobart and efarindodekin alfa, demonstrating significant potential in treating advanced solid tumors and microsatellite stable metastatic colorectal cancer [2][3][4] Pipeline and Business Updates - Vilastobart has shown a 40% objective response rate (ORR) in heavily pretreated patients with microsatellite stable metastatic colorectal cancer (mCRC) without liver metastases, particularly in those with high plasma tumor mutational burden (TMB) [4][3] - Efarindodekin alfa is being evaluated as a monotherapy in an ongoing Phase 1/2 clinical trial, with early data indicating a well-tolerated safety profile and promising anti-tumor activity [5][9] - XTX501, a bispecific PD-1/IL-2, is advancing towards an IND submission planned for mid-2026 [6][3] Financial Results - As of September 30, 2025, Xilio reported cash and cash equivalents of $103.8 million, a significant increase from $55.3 million at the end of 2024, primarily due to collaboration agreements and a public offering [11][12] - Collaboration and license revenue for Q3 2025 was $19.1 million, compared to $2.3 million in Q3 2024, reflecting growth from partnerships with AbbVie and Gilead [15] - The net loss for Q3 2025 was $16.3 million, an increase from $14.0 million in Q3 2024, driven by higher research and development expenses [15][24] Research and Development Highlights - Xilio's masked T cell engager programs are designed to enhance anti-tumor activity while minimizing systemic toxicity, with promising preclinical data supporting their best-in-class potential [10][8] - The company is actively seeking partnerships to further develop vilastobart in combination with PD-(L)1 or PD1-VEGF therapies for MSS CRC and other tumor types [4][3] Future Outlook - Xilio anticipates sufficient cash runway to fund operations into the first quarter of 2027, supported by recent financial milestones and ongoing collaborations [12][11] - The company plans to nominate development candidates for its CLDN18.2 and STEAP1 programs in late 2025 and early 2026, respectively, with IND applications expected in 2027 [14]

Summary of Xilio Therapeutics Conference Call Company Overview - **Company**: Xilio Therapeutics (NasdaqGS:XLO) - **Focus**: Development of novel masked biologics using proprietary protein engineering technology - **Key Products**: Velastigard (anti-CTLA-4), efarindodekin alfa (IL-12), XTX501 (PD-1/IL-2) Industry Context - **Industry**: Oncology, specifically focusing on immunotherapy for colorectal cancer - **Target Condition**: Microsatellite stable colorectal cancer (MSSCRC), which constitutes 95% of all colon cancers Key Data Updates - **SITC Conference**: Presented new clinical data for Velastigard in combination with Tislelizumab for MSSCRC - **Clinical Data**: - Velastigard demonstrated a **26% overall response rate** in late-line metastatic MSSCRC without liver metastases, compared to a **2% response rate** for Tislelizumab as monotherapy [8][9][10] - In a biomarker-defined population with high plasma tumor mutational burden (TMB), the overall response rate was **40%** [14][15] Biomarker Insights - **Plasma TMB**: - Approximately **55%** of MSSCRC patients have high plasma TMB (greater than 10 mutations per megabase) [12][15] - High plasma TMB correlates with better response rates to Velastigard and Tislelizumab combination therapy [12][14] - Plasma-based TMB assays are more sensitive and provide a comprehensive assessment compared to traditional tissue-based assays [11][19] Safety Profile - **Safety Data**: - Velastigard showed a **7% incidence of colitis**, significantly lower than traditional anti-CTLA-4 therapies [16][17] - Discontinuation rate for the combination therapy was only **5%**, indicating a favorable safety profile [17] Future Development Plans - **Partnerships**: Actively seeking partnerships to develop Velastigard in combination with PD-1, PD-L1, or newer PD-1 bispecifics [43][44] - **Regulatory Path**: Plans to assess the regulatory pathway for future development using plasma TMB as a predictive biomarker [43][44] - **Upcoming Milestones**: Additional phase two data for Velastigard expected in the first half of 2026 [47] Additional Clinical Programs - **Efarindodekin alfa**: Phase one data showed deep monotherapy responses and a well-tolerated safety profile [45] - **Masked T-cell Engagers**: Preclinical data demonstrated broad applicability and potential for reduced systemic toxicity [46] Conclusion - Xilio Therapeutics is positioned to leverage its innovative masking technology to address significant unmet medical needs in oncology, particularly in MSSCRC, with promising clinical data supporting the efficacy and safety of its lead product, Velastigard. The identification of plasma TMB as a predictive biomarker enhances the potential for targeted therapies in this patient population.

Core Insights - Xilio Therapeutics announced a 40% objective response rate (ORR) in heavily pre-treated patients with microsatellite stable (MSS) metastatic colorectal cancer (mCRC) without liver metastases and with high plasma tumor mutational burden (TMB) [1][2][9] - Approximately 55% of patients with MSS CRC are estimated to have high plasma TMB, indicating a significant patient population with unmet medical needs [1][2][5] - The company will host a conference call on November 10, 2025, to discuss these findings with leading cancer experts [1][12] Clinical Data - The Phase 2 trial evaluated vilastobart, a tumor-activated anti-CTLA-4, in combination with atezolizumab (Tecentriq) [1][15] - A statistically significant correlation was found between plasma TMB status and response, with a p-value of 0.05 [9][13] - Among evaluable patients, 62.5% were classified as TMB-high, and all responders were TMB-high, demonstrating deep and durable responses with reductions in target lesions of up to 71% [13] Safety Profile - The combination of vilastobart and atezolizumab showed a differentiated and generally well-tolerated safety profile, with treatment-related adverse events primarily being Grade 1 or 2 [10] - Only 5% of patients discontinued treatment due to adverse events, and 7% experienced colitis of any grade [10] Biomarker Potential - Plasma-based TMB assays are more sensitive than traditional tissue-based assays and can provide a comprehensive assessment of mutational load, accounting for tumor heterogeneity [4][6] - The use of plasma TMB as a predictive biomarker could help identify MSS mCRC patients who may benefit from vilastobart treatment [2][3] Development Plans - Xilio is actively seeking a partner to further develop vilastobart in combination with PD-(L)1 or PD1-VEGF for MSS CRC and other tumor types [11]

Core Insights - Xilio Therapeutics, Inc. presented new data at the Society for Immunotherapy of Cancer (SITC) 40th Annual Meeting, showcasing the potential of its masked T cell engager programs and tumor-activated therapies, including efarindodekin alfa and vilastobart [1][2] Group 1: Masked T Cell Engager Programs - Xilio is advancing multiple preclinical programs for masked T cell engagers targeting tumor-associated antigens such as PSMA, CLDN18.2, and STEAP1, with a collaboration with AbbVie [3] - The company's masked T cell engager programs utilize advanced formats like ATACR and SEECR, designed to enhance T cell activation and durability [4] - Preclinical data indicate that Xilio's masking technology can significantly expand the therapeutic window for T cell engagers, demonstrating potent anti-tumor activity and reduced systemic toxicity in murine models [5] Group 2: Efarindodekin Alfa - Efarindodekin alfa is an investigational tumor-activated IL-12 being evaluated in a Phase 1/2 clinical trial for patients with advanced solid tumors, with promising Phase 1 data showing a generally well-tolerated safety profile and encouraging anti-tumor activity [7][11] - As of September 2, 2025, 62 patients had been treated, with a median age of 66 years, and most patients had received multiple prior lines of therapy [7] - The treatment demonstrated partial responses in patients with advanced solid tumors, including a 33% decrease in target lesions for HPV-negative head and neck squamous cell carcinoma and a 55% decrease for uveal melanoma [11] Group 3: Vilastobart - Vilastobart is an investigational tumor-activated, Fc-enhanced anti-CTLA-4 monoclonal antibody being evaluated in combination with atezolizumab for advanced solid tumors and MSS mCRC [9][19] - New data presented at SITC suggest that circulating tumor DNA (ctDNA) may serve as an early biomarker for response to vilastobart treatment, with significant reductions in ctDNA correlating with treatment response [10][18] - The combination therapy is currently in Phase 1C and Phase 2 trials, with ongoing evaluations of safety and efficacy [19] Group 4: Development Plans - Xilio plans to nominate development candidates for its CLDN18.2 and STEAP1 programs in late 2025 and early 2026, respectively, with expectations to advance at least two programs into IND enabling studies by 2027 [6] - The company has completed enrollment in the Phase 1A and Phase 1B portions of the clinical trial for efarindodekin alfa, with ongoing evaluations [8][13]

Core Insights - Xilio Therapeutics, Inc. is set to present late-breaking data on vilastobart, a tumor-activated anti-CTLA-4 therapy, at the SITC 40th Annual Meeting from November 5-9, 2025 [1] - The Phase 2 data will focus on the response rate of vilastobart in combination with atezolizumab for patients with microsatellite stable metastatic colorectal cancer and high plasma tumor mutational burden [1] Presentation Details - The abstract title for the presentation is "Plasma Tumor Mutational Burden (pTMB) Enriched for Response to Vilastobart in Combination with Atezolizumab in Patients with Microsatellite Stable (MSS) Metastatic Colorectal Cancer" [2] - The late-breaking abstract number is 1315, and the presentation is scheduled for November 7, 2025, from 9:00 a.m. to 7:00 p.m. EST at the Gaylord National Resort and Convention Center [2] Company Overview - Xilio Therapeutics is a clinical-stage biotechnology company focused on developing tumor-activated immuno-oncology therapies aimed at improving cancer treatment outcomes while minimizing systemic side effects [3] - The company utilizes a proprietary platform to advance a pipeline of novel tumor-activated immuno-oncology molecules designed to enhance therapeutic efficacy within the tumor microenvironment [3]

Core Insights - Xilio Therapeutics, Inc. announced a late-breaking poster presentation for vilastobart, a tumor-activated anti-CTLA-4 therapy, at the Society for Immunotherapy of Cancer (SITC) 40th Annual Meeting [1] - The Phase 2 data will focus on the response rate of vilastobart in combination with atezolizumab for patients with microsatellite stable metastatic colorectal cancer and high plasma tumor mutational burden [1] Presentation Details - Abstract Title: Plasma Tumor Mutational Burden (pTMB) Enriched for Response to Vilastobart in Combination with Atezolizumab in Patients with Microsatellite Stable (MSS) Metastatic Colorectal Cancer [2] - Late-Breaking Abstract Number: 1315 [2] - Presentation Date: November 7, 2025 [2] - Location: Prince George ABC Exhibit Halls, Gaylord National Resort and Convention Center [2] - The poster will be available on the Xilio Therapeutics website on the same day [2] Company Overview - Xilio Therapeutics is a clinical-stage biotechnology company focused on developing tumor-activated immuno-oncology therapies aimed at improving cancer treatment outcomes while minimizing systemic side effects [3] - The company utilizes a proprietary platform to advance a pipeline of novel tumor-activated immuno-oncology molecules designed to enhance therapeutic efficacy within the tumor microenvironment [3]

Core Insights - Xilio Therapeutics, Inc. is set to present multiple clinical and preclinical data at the Society for Immunotherapy of Cancer (SITC) 40th Annual Meeting from November 6-9, 2025, focusing on tumor-activated immuno-oncology therapies for cancer patients [1][2]. Company Overview - Xilio Therapeutics is a clinical-stage biotechnology company dedicated to discovering and developing tumor-activated immuno-oncology therapies aimed at improving patient outcomes while minimizing systemic side effects associated with current treatments [2]. Upcoming Presentations - The company will present clinical data for vilastobart, an anti-CTLA-4 therapy, and efarindodekin alfa (XTX301), an IL-12 therapy, along with preclinical data on masked T cell engager programs [2]. - Specific poster presentations include: - "ctDNA as a Potential Surrogate Biomarker for Response to Combination Vilastobart and Atezolizumab in Heavily Pretreated Microsatellite Stable (MSS) Metastatic Colorectal Cancer (mCRC)" on November 7, 2025 [4]. - "XTX301, a Tumor-Activated Interleukin-12 (IL-12), Demonstrated IL-12 Pharmacology in Patients with Advanced Solid Tumors: Pharmacodynamic Data from First-in-Human Phase 1 Study" on November 7, 2025 [4]. - "Masked T Cell Engagers Designed to Drive Potent Synthetic Anti-Tumor Immunity with Favorable Tolerability" on November 8, 2025 [4].

Core Insights - Xilio Therapeutics announced updated Phase 2 data for vilastobart, showing deep and durable responses with a differentiated safety profile for anti-CTLA-4 combination therapy [1][5] - The company is on track to nominate its first development candidates for masked T cell engager programs in the second half of 2025 [1][12] - As of June 30, 2025, Xilio reported $121.6 million in cash and cash equivalents, providing a cash runway through the end of the third quarter of 2026 [1][13] Pipeline and Business Updates - Vilastobart is a tumor-activated, Fc-enhanced anti-CTLA-4 monoclonal antibody currently evaluated in combination with atezolizumab for advanced solid tumors and metastatic microsatellite stable colorectal cancer [3][14] - XTX301, a tumor-activated IL-12, is designed to stimulate anti-tumor immunity and is being evaluated as a monotherapy in a Phase 1 clinical trial [4][15] - Xilio's masked T cell engager programs include bispecific and tri-specific molecules designed to enhance T cell activation and are advancing through IND-enabling studies [7][9] Financial Results - Collaboration and license revenue for the quarter ended June 30, 2025, was $8.1 million, up from $2.4 million in the same quarter of 2024 [17] - Research and development expenses increased to $15.3 million in Q2 2025 from $11.2 million in Q2 2024, driven by clinical development activities [17] - The net loss for the quarter ended June 30, 2025, was $15.8 million, compared to a net loss of $13.9 million for the same period in 2024 [17][23]

Company Overview - Xilio Therapeutics, Inc. is a clinical-stage biotechnology company focused on discovering and developing tumor-activated immuno-oncology therapies aimed at improving outcomes for cancer patients while minimizing systemic side effects [4] Leadership Appointment - Akintunde (Tunde) Bello, Ph.D., has been appointed to the board of directors of Xilio Therapeutics, bringing over 25 years of experience in oncology research and development [1][2] - Dr. Bello has a strong track record in developing novel therapies, including significant contributions to cancer immunotherapies such as anti-CTLA-4 and PD-1 [2][3] Expertise and Background - Dr. Bello previously served as senior vice president at Bristol Myers Squibb, overseeing clinical pharmacology and pharmacometrics across multiple therapeutic areas [3] - His academic credentials include a B.Sc. in biomedical sciences, an M.Sc. in instrumentation and analytical science, and a Ph.D. in pharmaceutical sciences [3] Strategic Goals - The company aims to leverage Dr. Bello's expertise to advance its pipeline, including XTX501, a masked PD-1/IL-2 bi-specific therapy, and other bi-specific and tri-specific T cell engager programs [2][3] - Xilio's innovative approach focuses on optimizing the therapeutic index by localizing anti-tumor activity within the tumor microenvironment [4]

Core Insights - Xilio Therapeutics announced a preliminary objective response rate (ORR) of 26% in heavily pre-treated patients with metastatic microsatellite stable colorectal cancer (MSS CRC) without liver metastases, demonstrating deep and durable responses lasting up to 37 weeks [1][4][10] - The combination therapy of vilastobart and atezolizumab showed a differentiated safety profile with a low incidence of immune-related adverse events, particularly colitis [2][7][11] - The ongoing Phase 2 trial is evaluating vilastobart in combination with atezolizumab, with plans to expand the study to include a higher dose level [9][13] Patient Data - As of May 12, 2025, 44 patients with metastatic MSS CRC were treated with vilastobart at 100 mg every six weeks and atezolizumab at 1200 mg every three weeks, with a median age of 55 years [3][5] - 80% of patients had previously received three or more lines of anti-cancer therapy, indicating a heavily pre-treated population [3] Anti-Tumor Activity - The preliminary ORR of 26% included seven partial responses, with six confirmed responses, and substantial decreases in tumor biomarkers such as circulating tumor DNA [4][10] - In patients without liver metastases, responses were deep and durable, with reductions in target lesions of up to 71% from baseline [10] Safety Profile - The combination therapy exhibited a low incidence of immune-mediated adverse events, with only 7% of patients experiencing colitis [7][11] - Common treatment-related adverse events included fatigue (30%), infusion-related reactions (23%), and diarrhea (18%) [11] Future Development Plans - Xilio is enrolling a cohort of patients at a higher dose level of 150 mg Q6W for vilastobart in the ongoing Phase 2 trial, with additional data expected in the first half of 2026 [9][12] - The company is seeking partnership opportunities to accelerate the development of the vilastobart program [12]