iSCIB1+ / Scancell - LARVOL DELTA

SCOPE Plus: iSCIB1+ in Combination With Ipilimumab and Nivolumab as First-Line Treatment for Advanced Unresectable Melanoma (clinicaltrials.gov) - P3 | N=550 | Not yet recruiting | Sponsor: Scancell Ltd

New P3 trial • Genetic Disorders • Melanoma • Oncology • Skin Cancer • Solid Tumor • BRAF

The Medicines and Healthcare products Regulatory Agency (MHRA) has granted a clinical trial authorisation for the phase III registrational study of iSCIB1+. (Proactiveinvestors) - "The trial will enrol 550 patients with stage III or IV melanoma across about 90 sites in the US, EU, UK, Canada and Australia....The trial is expected to start by the end of 2026, with initial survival data targeted for the second half of 2028."

New P3 trial • P3 data • Melanoma

SCOPE, A phase 2 clinical trial with off-the-shelf DNA plasmid vaccine in first line advanced melanoma combined with check point blockade, shows good T cell responses which correlate with long progression free survival (AACR 2026) - "SCIB1 induced T cell responses in 88% patients, 75% RFS at 39 months cut off (n=16) versus 63% for Pembrolizumab (Keynote 054). iSCIB1+ in combination with nivolumab and ipilimumab as first line treatment for unresectable melanoma showed improved PFS of 74% at 16 months without an increase in clinically meaningful adverse events. Clinical benefit was correlated with strong iSCIB1+ induced T cell responses. These data support a registrational, randomized, controlled trial of iSCIB1 + with potential to redefine frontline therapy for unresectable advanced melanoma."

Checkpoint block • Clinical • Metastases • P2 data • Melanoma • Oncology • Solid Tumor • CD4 • CD8 • IFNG

Scancell receives FDA Fast Track Designation for iSCIB1+ in advanced melanoma and provides data update from its SCOPE Phase 2 study (Scancell Press Release) - "Potent and durable efficacy with iSCIB1+ of 77% progression free survival (PFS) at 20 months, in combination with ipilimumab and nivolumab, demonstrated in the Phase 2 SCOPE trial; more PFS and additional early overall survival (OS) data expected in H1 2027; Initiation of the registrational Phase 3 trial with iSCIB1+ in advanced melanoma anticipated in H2 2026."

Fast track • New P3 trial • P2 data • Melanoma

Scancell announces FDA clearance of IND application for global Phase 3 trial of iSCIB1+ in advanced melanoma (The Manila Times) - "Unlocks path towards registrational Phase 3 trial planned to start in 2026."

IND • New P3 trial • Melanoma

SCIB1 and iSCIB1+ in Melanoma Patients Receiving Nivolumab With Ipilimumab or SCIB1 With Pembrolizumab (The SCOPE Study) (clinicaltrials.gov) - P2 | N=173 | Active, not recruiting | Sponsor: Scancell Ltd | Recruiting ➔ Active, not recruiting

Enrollment closed • Melanoma • Oncology • Solid Tumor • BRAF

A DNA plasmid melanoma cancer vaccine, SCIB1 and iSCIB1+ combined with nivolumab and ipilimumab in advanced unresectable melanoma induces potent clinically meaningful CD8 T cell responses in 80% of the patient population (ESMO-IO 2025) - P2 | "Patients with permissive alleles demonstrated a higher mean ORR rate of 70% (range 64-75%), compared to 45% (range 33-50) in the non-permissive group which is consistent with the ORR reported for CPIs.Conclusions These data support that SCIB1 and iSCIB1+ induces potent T cell responses, resulting in positive clinical responses in 80% of the patient population. Significant T cell responses were induced to peptides included in iSCIB1+."

Clinical • IO biomarker • Metastases • Melanoma • Oncology • Solid Tumor • CD4 • CD8 • IFNG

SCOPE, phase II clinical trial with off-the-shelf DNA plasmid vaccine in first line advanced melanoma combined with check point blockade (ESMO-IO 2025) - P2 | "Background SCIB1 and iSCIB1+ are off-the-shelf DNA plasmid vaccines encoding TRP-2 and gp100...Eligible patients received standard-of-care (SOC) nivolumab and ipilimumab plus up to 10 intramuscular vaccine doses over 24 months with RECIST 1.1 imaging...By comparison the median PFS has not been reached in these cohorts, iSCIB1+ shows 74% PFS at 12 months suggesting a 20% clinical benefit without increasing toxicity. These data support a registrational, randomised, controlled trial of iSCIB1+ with potential to redefine frontline therapy for unresectable advanced melanoma."

Checkpoint block • Clinical • Late-breaking abstract • Metastases • P2 data • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • BRAF • CD8

Scancell Holdings…announces updated positive data from the SCOPE Phase 2 trial of iSCIB1+ in combination with ipilimumab and nivolumab, current standard of care (SoC) (GlobeNewswire) - "A late-breaking abstract on the data has been released, and an additional poster presentation will be made during an oral session at the ESMO Immuno-Oncology Congress 2025....Updated data in this cohort show progression free survival (PFS) was 74% at 16 months in the target population. This compares favourably to PFS reported with ipilimumab plus nivolumab alone of 50% at 11.5 months. The favourable PFS remains consistent across key subgroups analysed including PD-L1 low, BRAF Wildtype and prior checkpoint inhibitor exposure, who might be expected to have worse outcomes....Overall response rate for the target population in Cohort 3 was 56%, with a disease control rate of 79%."

Late-breaking abstract • P2 data • Melanoma

SCOPE, an open label phase 2 parallel multi cohort clinical trial evaluating an off-the-shelf DNA plasmid vaccine in first line advanced melanoma combined with check point blockade - interim read-out (SITC 2025) - "iSCIB1+ has additional epitopes applicable to more HLA haplotypes, A2, A3, A31, Bw4, B35 & B44 that represent 80% of the population (figure 1).Methods This phase 2 open label single arm parallel multi-cohort clinical program evaluates the immune response, safety and efficacy of SCIB1/iSCIB1+ in 140 advanced first line melanoma patients at 16 clinical sites in the United Kingdom.Cohort 1 has 43 patients all with HLA A2 receiving ipilimumab and nivolumab with 10 doses of intra-muscular SCIB1 over 24-months...Cohort 2 has 10 HLA A2 patients who received SCIB 1 with pembrolizumab and was stopped due to slow enrolment.Results ELISpot assays demonstrated that 19/31 (61.2%) patients made a T-cell response to iSCIB1+ which increased to 79% (15/19) amongst clinical responders...SCIB1 & iSCIB1+ encoding two clusters of CD8 epitopes, TRP-2 and gp100, with ELISpot T cell responses to all epitopes in HLA matched patientsAbstract 1325 Figure 2Request permissionsRECIST 1.1 best..."

Checkpoint block • Clinical • Late-breaking abstract • Metastases • P2 data • Melanoma • Oncology • Solid Tumor • CD4 • CD8 • GZMB • IFNG • PRF1

SCOPE, an open label phase 2 parallel multi cohort clinical trial evaluating an off-the-shelf DNA plasmid vaccine in first line advanced melanoma combined with check point blockade - interim read-out (SITC 2025) - "iSCIB1+ has additional epitopes applicable to more HLA haplotypes, A2, A3, A31, Bw4, B35 & B44 that represent 80% of the population (figure 1).Methods This phase 2 open label single arm parallel multi-cohort clinical program evaluates the immune response, safety and efficacy of SCIB1/iSCIB1+ in 140 advanced first line melanoma patients at 16 clinical sites in the United Kingdom.Cohort 1 has 43 patients all with HLA A2 receiving ipilimumab and nivolumab with 10 doses of intra-muscular SCIB1 over 24-months...Cohort 2 has 10 HLA A2 patients who received SCIB 1 with pembrolizumab and was stopped due to slow enrolment.Results ELISpot assays demonstrated that 19/31 (61.2%) patients made a T-cell response to iSCIB1+ which increased to 79% (15/19) amongst clinical responders...SCIB1 & iSCIB1+ encoding two clusters of CD8 epitopes, TRP-2 and gp100, with ELISpot T cell responses to all epitopes in HLA matched patientsAbstract 1325 Figure 2Request permissionsRECIST 1.1 best..."

Checkpoint block • Clinical • Late-breaking abstract • Metastases • P2 data • Melanoma • Oncology • Solid Tumor • CD4 • CD8 • GZMB • IFNG • PRF1

SCOPE phase II clinical trial program evaluating off-the-shelf DNA plasmid vaccines, SCIB1 and iSCIB1+ administered in combination with checkpoint inhibitors in advanced unresectable melanoma (ESMO 2025) - P2 | "In Cohort 2 only,10 such patients, received pembrolizumab...Trial design The SCOPE phase 2 open label single arm clinical program evaluates within defined cohorts the safety and efficacy of SCIB1 and iSCIB1+ in over 140 patients with unresectable melanoma receiving immunotherapy with ipilimumab and nivolumab at 16 UK trial sites...In Cohort 2 only,10 such patients, received pembrolizumab...Legal entity responsible for the study Scancell Ltd. Funding Scancell Ltd."

Checkpoint inhibition • Clinical • Combination therapy • Metastases • P2 data • Melanoma • Oncology • Solid Tumor • CD8

Scancell reports Phase 2 data showing strongly improved outcomes in Late-Stage Melanoma with its Immunobody iSCIB1+ (Scancell Press Release) - P2 | N=173 | SCOPE (NCT04079166) | Sponsor: Scancell Ltd | "Patients in Cohorts 1 and 3 received SCIB1 or iSCIB1+, respectively, in combination with ipilimumab and nivolumab, the current standard of care ('SoC'). The combined overall response rate ('ORR') for evaluable patients in Cohorts 1 and 3 was 68.6% (46 out of 67 patients), with a disease control rate ('DCR') of 88.0% and complete response rate ('CR') of 17.9% (12 out of 67 patients). Cohort 2 evaluating SCIB1 in combination with pembrolizumab showed comparable results in the 9 target patients after the cohort was stopped due to the change in SoC in the UK....Cohort 1 achieved 12-month progression-free survival ('PFS') of 64.6%, and Cohort 3 demonstrated 11-month PFS of 80.8%. These compare favorably to previously reported PFS of 43.9% for ipilimumab plus nivolumab at 12 months."

P2 data • Melanoma

Scancell initiates new arm (Cohort 4) in SCOPE Phase 2 study to evaluate intradermal administration and an accelerated dosing regimen for iSCIB1+ (Scancell Press Release) - "Scancell Holdings plc...announces today that dosing of patients has commenced in Cohort 4 of its Phase 2 clinical SCOPE study. This cohort will evaluate iSCIB1+ Immunobody through intradermal administration and accelerated dosing in patients with advanced unresectable melanoma. The initial 8 patients have now been safely dosed in the fourth cohort with iSCIB1+, including patients recruited through the NHS Cancer Vaccine Launch Pad. No significant adverse events have been observed with intradermal dosing. The trial remains on track, with data from Cohorts 1 through 3 expected in July 2025. With ongoing strong recruitment continuing in the iSCIB1+ Cohort 4, initial data in this cohort is expected around the end of 2025."

P2 data • Trial status • Melanoma

Partnership with NHS Cancer Vaccine Launch Pad Enabling Fast-Tracked Access for Melanoma Patients (Scancell Press Release) - "Scancell Holdings plc...announces a partnership with the NHS Cancer Vaccine Launch Pad (CVLP) to fast-track access for NHS patients into the fourth cohort of the Company’s Phase 2 clinical SCOPE study. This cohort will evaluate intradermal administration of Scancell’s iSCIB1+, potent, targeted 'off-the-shelf' Immunobody second generation DNA cancer vaccine, in patients with advanced unresectable melanoma receiving standard of care immunotherapy treatments....NHS Hospitals across the country will be able to take part in this transformational study, with eligible patients from around the UK being referred to a participating NHS site. The partnership is being coordinated and run by the Southampton Clinical Trials Unit, with the first patients expected to be referred from May....Clinical data from SCIB1 in cohort 1 and iSCIB1+ in cohort 3 is expected around mid-2025, while clinical data from iSCIB1+ in cohort 4, following the partnership with CVLP, is expected late 2025."

Licensing / partnership • P2 data • Melanoma

SCIB1 and iSCIB1+ in Melanoma Patients Receiving Nivolumab With Ipilimumab or SCIB1 With Pembrolizumab (The SCOPE Study) (clinicaltrials.gov) - P2 | N=173 | Recruiting | Sponsor: Scancell Ltd | N=130 ➔ 173 | Trial completion date: Jan 2026 ➔ Jan 2027 | Trial primary completion date: Jan 2026 ➔ Jan 2027

Enrollment change • Trial completion date • Trial primary completion date • Melanoma • Oncology • Solid Tumor • BRAF

Interim Results for the six months ended 31 October 2024 (Scancell Press Release) - "SCIB1/ iSCIB1+ (SCOPE trial):...SCIB1 in...first cohort now fully recruited with 43 patients and 25-week ORR data expected mid 2025; iSCIB1+, a next generation vaccine, continues strong recruitment with 25-week ORR data expected H2 2025; Intradermal cohort with iSCIB1+ added to the study to provide delivery route comparison. Early data from this additional cohort expected H2 2025."

P2 data • Melanoma

Results for the Year Ended 30 April 2024 (Scancell Press Release) - "SCIB1/ iSCIB1+ (SCOPE trial): Full cohort data with SCIB1 and iSCIB1+ expected in Q4 2024 and H1 2025 respectively. Phase 2/3 registration study in advanced melanoma planned to begin in 2025 supported by strategic guidance from international key opinion leaders. Modi-1 (ModiFY trial): Modi-1 completed dose escalation and safety cohorts of the Phase 1/2 ModiFY trial and continues in the expansion cohorts....RCC cohort dosing has commenced with early clinical read-out expected in H1 2025."

New P2/3 trial • P2 data • Trial status • Genito-urinary Cancer • Kidney Cancer • Melanoma • Oncology • Renal Cell Carcinoma • Skin Cancer • Solid Tumor

PharmaJet and Scancell Sign Strategic Partnership Agreement for Development and Commercialization of a Needle-free DNA Vaccine for Advanced Melanoma (Businesswire) - "PharmaJet...announced that it has entered into a long-term license and supply agreement with Scancell Holdings plc (LSE – SCLP.L) to use the US FDA 510(k)-cleared / CE-marked PharmaJet Stratis Intramuscular (IM) Needle-free System for the delivery of its advanced melanoma DNA vaccine (Immunobody SCIB1/iSCIB1+)....Under the terms of the agreement, Scancell will use Stratis for the clinical development and commercialization of their advanced melanoma DNA vaccine. PharmaJet will receive development and regulatory milestone payments, and upon commercialization, will also receive royalties on net sales. Scancell will be responsible for the clinical and regulatory development as well as commercialization of the combined product."

Licensing / partnership • Melanoma • Oncology • Skin Cancer • Solid Tumor

Scancell Provides Update from iSCIB1+ Clinical Advisory Meeting to Strengthen Plans for Phase 2/3 Registration Clinical Trial (Scancell Press Release) - "Scancell Holdings plc...announces that a group of leading medical oncologists in the field of melanoma treatment reviewed and strengthened Scancell’s plan for a Phase 2/3 registration study following completion of the ongoing SCOPE study. Scancell’s plans to conduct an adaptive randomised controlled Phase 2/3 SCOPE-2 trial is supported by a panel of experts....Scancell continues to recruit to the SCOPE study, which includes patients treated with SCIB1 as well as iSCIB1+. 32/43 patients have been recruited into the SCIB1 cohort and 22/43 into the iSCIB1+ cohort, with clinical results expected in Q4 2024 and Q1 2025, respectively."

New P2/3 trial • P2 data • Trial status • Melanoma • Oncology • Skin Cancer • Solid Tumor

SCIB1 and iSCIB1+ in Melanoma Patients Receiving Nivolumab With Ipilimumab or SCIB1 With Pembrolizumab (The SCOPE Study) (clinicaltrials.gov) - P2 | N=130 | Recruiting | Sponsor: Scancell Ltd | N=87 ➔ 130

Enrollment change • Metastases • Melanoma • Oncology • Solid Tumor • BRAF

A DNA plasmid melanoma cancer vaccine, SCIB1, combined with nivolumab + ipilimumab in patients with advanced unresectable melanoma (CIMT 2024) - "SCIB1 in combination with nivolumab and ipilimumab as first line treatment for unresectable melanoma resulted in an ORR of 82% without an increase in clinically meaningful adverse events. The addition of the iSCIB1+ vaccine cohort should increase the number of patients that can benefit from this vaccine."

Clinical • Metastases • Melanoma • Oncology • Solid Tumor

A DNA plasmid melanoma cancer vaccine, SCIB1, combined with nivolumab + ipilimumab in patients with advanced unresectable melanoma (CIMT 2024) - "SCIB1 in combination with nivolumab and ipilimumab as first line treatment for unresectable melanoma resulted in an ORR of 82% without an increase in clinically meaningful adverse events. The addition of the iSCIB1+ vaccine cohort should increase the number of patients that can benefit from this vaccine."

Clinical • Metastases • Melanoma • Oncology • Solid Tumor