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, 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 - Several small- and mid-cap biotech and medical stocks experienced significant after-hours trading activity on September 26, driven by clinical updates, investor presentations, and strategic announcements. Company Summaries - **Enanta Pharmaceuticals Inc. (ENTA)**: The stock surged 20% in after-hours trading to $9.48 after closing at $7.90, following the announcement of upcoming topline results from its Phase 2b study on zelicapavir for RSV treatment in high-risk adults [2][3]. - **Acumen Pharmaceuticals Inc. (ABOS)**: Shares rebounded 12.67% to $1.60 after closing at $1.42, driven by renewed interest in its Alzheimer's pipeline, particularly the Phase 2 candidate Sabirnetug (ACU193) [4]. - **Delcath Systems Inc. (DCTH)**: The stock gained 6.00% in after-hours trading to $11.39 after closing at $10.74, following renewed investor interest in its CHOPIN Phase 2 trial data presentation scheduled for ESMO 2025 Congress [5][6]. - **Vivos Therapeutics Inc. (VVOS)**: The stock climbed 4.81% to $3.27 after closing at $3.12, likely due to renewed interest following recent positive clinical trial results for its pediatric OSA treatment [7][8]. - **Xilio Therapeutics (XLO)**: Shares rose 4.28% to $0.83 after closing at $0.7959, driven by enthusiasm surrounding the initiation of a Phase 2 trial for its tumor-activated IL-12 candidate, which also triggered a $17.5 million payment from Gilead [9][10]. - **Nyxoah SA (NYXH)**: The stock increased 3.77% to $4.68 after closing at $4.51, supported by optimism regarding its international expansion and a recent patent infringement lawsuit against Inspire Medical Systems [11].