Core Insights - Scancell Holdings plc has received FDA clearance for its Investigational New Drug application for a Phase 3 trial of iSCIB1+ Immunobody® in advanced melanoma, with progression-free survival as the primary endpoint [1][3] - The Phase 2 SCOPE trial demonstrated a 24% improvement in progression-free survival (PFS) for iSCIB1+ compared to the standard of care and historical controls [1][4] - The SCOPE trial involved 140 patients and evaluated the efficacy of iSCIB1+ in combination with nivolumab and ipilimumab for previously untreated unresectable stage IIIB/IV melanoma [2][5] Company Developments - Scancell has identified a selection marker to enrich the Phase 3 trial for responders, focusing on patients with specific human leukocyte antigen (HLA) alleles, which represent 80% of melanoma patients [3] - Updated data from the SCOPE trial show that PFS for the target population was 74% at 16 months, significantly higher than the 50% PFS reported for the current standard of care (ipilimumab plus nivolumab) at 11.5 months [4] - The company is exploring various financing options, including potential partnerships, to support the Phase 3 trial [3] Product Pipeline - iSCIB1+ is part of Scancell's DNA ImmunoBody® platform, which aims to generate safe and long-lasting tumor-specific immunity [6] - The company is also developing Modi-1, a peptide immunotherapy from its Moditope® platform, currently in a Phase 2 study for a range of solid tumors [6] - Scancell's subsidiary, GlyMab Therapeutics Ltd., is focused on developing high-affinity GlyMab® antibodies targeting tumor-specific glycans [6]

Core Insights - Scancell Holdings plc has announced positive data from the SCOPE Phase 2 trial of iSCIB1+ in combination with ipilimumab and nivolumab, showing a significant improvement in progression-free survival (PFS) and overall survival (OS) compared to standard of care [2][4][6]. Group 1: Trial Results - The PFS for the target population was reported at 74% at 16 months, compared to 50% at 11.5 months for the standard of care [4][6]. - The overall response rate for the target population in Cohort 3 was 56%, with a disease control rate of 79% [5]. - Early OS data indicates a 14% improvement at 26 months over standard of care [4][5]. Group 2: Regulatory and Development Plans - The company is in advanced planning for registrational trials, having received positive scientific advice from regulators [1][6]. - Discussions with the U.S. Food and Drug Administration (FDA) and other regulatory agencies have been positive, supporting plans to move to Phase 3 registrational development [6][8]. - The company has decided not to continue with Cohort 4, focusing instead on the optimal method of administration for late-stage development [8]. Group 3: Target Population and Biomarkers - iSCIB1+ is selected for further development in patients with specific human leukocyte antigen (HLA) alleles, representing 80% of melanoma patients [3][12]. - The trial data supports the use of HLA as a biomarker for registrational trials, with a PFS of 20% at 14 months in the non-target population [4][12]. - The selected HLA alleles include A2, A3, A31, Bw4, B35, and B44, which are crucial for identifying potential responders in future clinical development [12].

Core Insights - Scancell Holdings plc presented positive Phase 2 data for its iSCIB1+ Immunobody in late-stage melanoma, indicating a potential new benchmark in treatment efficacy, durability, immune responses, and safety [2][3][4] Efficacy and Safety - The SCOPE trial results show a progression-free survival (PFS) rate of 78% at 11 months for iSCIB1+, significantly higher than the historic 12-month PFS of 46% for the combination of ipilimumab and nivolumab [3][4] - Combined data for the defined HLA target population across Cohorts 1 and 3 indicate a 22-month PFS of 69%, representing a meaningful improvement over historic doublet checkpoint therapy [4][5] - The overall response rate (ORR) and disease control rate (DCR) for iSCIB1+ demonstrate superiority when combined with either doublet or single checkpoint therapy, with a favorable safety profile observed in over 100 patients [4][5] Development Plans - Development plans for iSCIB1+ have been accelerated, including regulatory and partnering discussions, with randomized studies expected to begin in 2026 [5][6] - The company aims to expand the addressable patient population to approximately 80% of late-stage melanoma patients, indicating a longer patent life for iSCIB1+ [5][8] Clinical Trial Details - The SCOPE trial is an open-label Phase 2 study evaluating SCIB1/iSCIB1+ in combination with checkpoint inhibitors in late-stage melanoma, enrolling over 140 patients across four cohorts [6][7] - The trial aims to assess the efficacy, safety, and durability of SCIB1 or iSCIB1+ DNA Immunobody therapies in combination with standard of care checkpoint inhibitors [6][7]

Core Viewpoint - Scancell Holdings plc has made significant progress in developing its active immunotherapies, particularly the DNA ImmunoBody iSCIB1+ and Moditope Modi-1, showing promising clinical results in treating advanced melanoma and head and neck cancer, respectively. The company is accelerating its development plans and preparing for future regulatory studies and partnerships [10][16][21]. Clinical Development - Positive data from the Phase 2 SCOPE trial indicates that iSCIB1+ in combination with checkpoint inhibitors can potentially set a new standard for advanced melanoma treatment, with an 11-month progression-free survival (PFS) of 78% compared to 46% for standard doublet therapy [5][23][34]. - The overall response rate (ORR) for iSCIB1+ is 64%, exceeding the 48%-50% reported for existing checkpoint therapies [22][23]. - Early results from the Phase 2 ModiFY trial show that Modi-1 combined with a single checkpoint inhibitor yields an ORR of 43% in head and neck cancer, significantly higher than historical rates [43][45]. Manufacturing and Regulatory Plans - A commercial-scale GMP manufacturing process for iSCIB1+ has been developed, ensuring high-quality formulation and long-term stability, which reduces costs and improves accessibility [24][39]. - The company plans to initiate randomized studies for iSCIB1+ in 2026, with ongoing discussions with regulatory bodies in the US, UK, and Europe [25][40]. Financial Overview - For the year ending April 30, 2025, Scancell reported an operating loss of £15.0 million, a decrease from £18.3 million in 2024, with a cash balance of £16.9 million [13][62]. - The company raised £11.3 million in late 2024, contributing to a cash runway extending into the second half of 2026 [11][59]. Corporate Developments - Scancell has strengthened its leadership team with key appointments, including Phillip L'Huillier as CEO, enhancing its capabilities for late-stage development [20][57]. - The establishment of GlyMab Therapeutics Limited as a wholly owned subsidiary aims to focus on antibody assets and platforms, with a second commercial license agreement with Genmab valued at $6 million and potential milestones of up to $630 million [11][27][49].

Core Insights - Scancell Holdings plc has reported significant clinical progress and financial results for the year ending April 30, 2025, highlighting advancements in its immunotherapy products, particularly iSCIB1+ and Modi-1, which show promising efficacy in treating advanced melanoma and head and neck cancers respectively [1][10][11]. Clinical Developments - Positive data from the Phase 2 SCOPE trial indicates that iSCIB1+ in combination with checkpoint inhibitors has a progression-free survival (PFS) of 78% at 11 months, significantly higher than the historical 12-month PFS of 46% for standard doublet therapy [5][10][22]. - The overall response rate (ORR) for iSCIB1+ is reported at 64%, exceeding the 48-50% range for existing checkpoint inhibition treatments [22][23]. - Early results from the Phase 2 ModiFY trial show that Modi-1 combined with a single checkpoint inhibitor yields an ORR of 43% in head and neck cancer, surpassing historical rates for single-agent therapies [11][44][45]. Manufacturing and Development Plans - A commercial-scale GMP manufacturing process for iSCIB1+ has been developed, ensuring high-quality formulation and long-term stability, which enhances global accessibility and reduces costs [24][40]. - The company plans to initiate randomized studies for iSCIB1+ in 2026, with ongoing discussions with potential partners for future development [10][25][41]. Financial Performance - Scancell reported an operating loss of £15.0 million for the year, a decrease from £18.3 million in the previous year, with a cash balance of £16.9 million as of April 30, 2025 [13][61]. - The company secured a second commercial license with Genmab for SC2811, which includes $6 million in upfront payments and potential milestones totaling $630 million [11][27]. Corporate Developments - The leadership team has been strengthened with key appointments, including Phillip L'Huillier as CEO, enhancing the company's capabilities for late-stage development [20][56]. - The establishment of GlyMab Therapeutics Limited as a wholly owned subsidiary aims to focus on antibody assets and platforms, providing strategic optionality for further development [11][49].

Core Insights - The SCOPE trial of SCIB1/iSCIB1+ shows promising results in treating advanced unresectable melanoma, indicating a potential new benchmark for efficacy, durability, immune responses, and safety [2][3][5] Efficacy and Safety - The overall response rate (ORR) for iSCIB1+ in target HLA type patients was 69%, significantly higher than the 48-50% ORR for standard care [1][4] - The 12-month progression-free survival (PFS) for Cohort 1 was 64.6%, and for Cohort 3, it was 80.8%, compared to 43.9% for the standard treatment [4][5] - The safety profile of SCIB1/iSCIB1+ combinations was consistent with that of ipilimumab and nivolumab alone, indicating no additional safety concerns [4][6] Future Development Plans - iSCIB1+ has been selected for further development, with plans for a registrational Phase 2b/3 global study being accelerated [1][7] - The study aims to enroll over 140 patients and evaluate the efficacy, safety, and durability of SCIB1/iSCIB1+ in combination with standard checkpoint inhibitors [7][9] Biomarker Potential - The data suggests the possibility of a patient selection biomarker based on HLA class I alleles, which could enhance participant selection for future studies [5][6] Market Context - The combination of ipilimumab and nivolumab currently holds a market share of 65-70% among metastatic melanoma patients in the US, highlighting the competitive landscape [7]