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.

Vilastobart (anti-CTLA-4) in MSS mCRC Patients with High Plasma TMB November 10, 2025 1 Forward-Looking Statements and Disclaimers This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding plans, timing and expectations related to: development timelines and anticipated milestones for Xilio's programs; the timing and receipt of future payments under Xilio's collaboration or ...

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]

Pipeline and Programs - Vilastobart (tumor-activated anti-CTLA-4) reported a preliminary Objective Response Rate (ORR) of 26% in Phase 2 for heavily pre-treated patients with microsatellite stable colorectal cancer (MSS CRC) without liver metastases[35, 41] - XTX301 (tumor-activated IL-12) is advancing in partnership with Gilead, with a potential $75 million option fee at Phase 1/2 data package[67, 69] - XTX501 (tumor-activated PD-1/IL-2 bispecific) IND submission is anticipated in mid-2026[74] - The company plans to nominate development candidates for PSMA, CLDN182, and STEAP1 masked T cell engager programs in Q3 2025, Q4 2025, and 1H 2026, respectively[24, 101] Financials and Partnerships - The company had $89.1 million in cash and cash equivalents as of March 31, 2025[120] - The company received approximately $47.2 million in estimated net proceeds from equity financing in June 2025[120] - The company anticipates a cash runway through the end of Q3 2026[21, 120] - The company is eligible to receive up to $100 million in additional gross proceeds from equity financing by 2H 2026[21, 120] - The company has a collaboration, license, and option agreement with AbbVie for tumor-activated immunotherapies, including masked T cell engagers, with up to ~$2.1 billion in total contingent payments[20, 113] Technology and Approach - The company's platform exploits dysregulated matrix metalloprotease (MMP) activity in tumors to activate molecules[12] - The company's masked T cell engagers are designed to optimize the therapeutic index by maximizing tumor exposure and minimizing peripheral activity and off-tumor cytotoxicity[98]

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]