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 - Exelixis, Inc. announced detailed results from the STELLAR-303 trial, which evaluated zanzalintinib in combination with atezolizumab against regorafenib in patients with previously treated non-MSI-high metastatic colorectal cancer [1] Group 1 - The study met one of its dual primary endpoints, showing a 20% reduction in the risk of death with the combination treatment [1]

Core Insights - Natera, Inc. announced results from the phase 3 IMvigor011 clinical trial in muscle-invasive bladder cancer (MIBC) [1] - The findings indicate that Signatera can enhance the adjuvant treatment window and optimize the use of adjuvant atezolizumab (Tecentriq®) in MIBC [1] - The trial results show improvements in disease-free survival (DFS) and overall survival (OS) [1] Company Summary - Natera, Inc. is recognized as a global leader in cell-free DNA and precision medicine [1] - The company is actively involved in advancing treatment options for muscle-invasive bladder cancer through innovative clinical trials [1] Industry Summary - The results from the IMvigor011 trial may influence the treatment landscape for muscle-invasive bladder cancer, particularly in the use of adjuvant therapies [1] - The findings could lead to broader applications of precision medicine in oncology, enhancing patient outcomes [1]

Core Insights - Sonnet BioTherapeutics is expanding its clinical study of SON-1010 in combination with atezolizumab for patients with advanced platinum-resistant ovarian cancer, showing promising early results with a 66% tumor response rate at the highest dose [1][2] - The company is also exploring a higher maintenance dose of SON-1010 to assess its safety and efficacy before moving to a randomized Phase 2a trial [1][2] - SON-1010 is designed to enhance immune response in tumors by delivering IL-12 directly to the tumor microenvironment, potentially improving treatment outcomes for various cancers [3][4] Company Overview - Sonnet BioTherapeutics focuses on developing targeted biologic drugs using its Fully Human Albumin-Binding (FHAB) platform, which aims to optimize the safety and efficacy of immune-modulating therapies [6][7] - The company is currently evaluating SON-1210, another candidate using the FHAB platform, for the treatment of pancreatic cancer in collaboration with the Sarcoma Oncology Center [7] Clinical Trial Details - The SB221 trial is a Phase 1b/2a multicenter study assessing the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of SON-1010, both alone and in combination with atezolizumab [5] - The trial aims to establish the maximum tolerated dose (MTD) and evaluate the potential for improved efficacy in patients with platinum-resistant ovarian cancer [5]

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]

Core Insights - Sonnet BioTherapeutics Holdings, Inc. is set to present at the 6th Annual Cytokine-Based Drug Development Summit on May 15-16, 2025, focusing on managing toxicity related to cytokine overexpression to enhance therapeutic windows [1][2]. Company Overview - Sonnet is an oncology-focused biotechnology company that utilizes a proprietary platform called FHAB (Fully Human Albumin-Binding) for developing targeted biologic drugs [3]. - The FHAB technology employs a fully human single chain antibody fragment that binds to human serum albumin for targeted transport to tumor and lymphatic tissues, aiming to improve the safety and efficacy of immune-modulating biologic drugs [3]. Lead Programs - The lead program, SON-1010 (IL-12-FHAB), is in development for treating solid tumors, certain sarcomas, and ovarian cancer, currently undergoing a Phase 1/2a study in collaboration with Roche [4]. - A second program, SON-1210 (IL12-FHAB-IL15), is being evaluated for solid tumors, with plans for an investigator-initiated Phase 1/2a study for pancreatic cancer in collaboration with the Sarcoma Oncology Center [4]. Presentation Details - Dr. Richard Kenney, Chief Medical Officer, will discuss strategies for managing cytokine toxicity and optimizing therapeutic indices during the presentation [1][7]. - Key topics include receptor bias to reduce toxicity, optimizing cytokine potency, and examining factors influencing the therapeutic window [7].

Core Insights - Sonnet BioTherapeutics Holdings, Inc. announced positive safety results for SON-1010 in a Phase 1b/2a clinical trial for advanced solid tumors and platinum-resistant ovarian cancer [2][5] - The management team, including Interim CEO Raghu Rao and Chief Medical Officer Dr. Richard Kenney, discussed the implications of these results in a Virtual Investor segment [1][2] Company Overview - Sonnet is a clinical-stage biotechnology company focused on developing immunotherapeutic drugs targeting the tumor microenvironment (TME) [1][4] - The company utilizes a proprietary FHAB (Fully Human Albumin-Binding) platform for creating targeted biologic drugs, enhancing safety and efficacy [4] Product Development - SON-1010 (IL-12-FHAB) is the lead program aimed at treating solid tumors, certain sarcomas, and ovarian cancer, currently in a Phase 1/2a study in collaboration with Roche [5] - The company is also developing SON-1210 (IL12-FHAB-IL15) for solid tumors, with plans for an investigator-initiated Phase 1/2a study for pancreatic cancer [5]