SCIB1 / Scancell - LARVOL DELTA

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 | "Clinical trial identification NCT04079166 Legal entity responsible for the study ScanCell Ltd Funding ScanCell Ltd 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

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 trial identification EudraCT: 2018-002844-10.Legal entity responsible for the study Scancell Ltd."

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

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

A DNA plasmid melanoma cancer vaccine, SCIB1, combined with nivolumab + ipilimumab in patients with advanced unresectable melanoma: Efficacy and safety results from the open-label Phase 2 SCOPE Trial (AACR 2025) - "SCIB1 in combination with nivolumab and ipilimumab as first line treatment for unresectable Stage 3/4 melanoma resulted in 80% 6-month PFS with strong vaccine specific T cell responses without an increase in clinically meaningful adverse events. These results, if confirmed, in a larger patient cohort provide confidence in initiating a randomized registration program in unresectable melanoma patients with our novel DNA plasmid technology."

Clinical • Late-breaking abstract • Metastases • P2 data • Melanoma • Oncology • Solid Tumor

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

Scancell to Present Clinical Data from the Ongoing Phase 2 SCOPE Trial of SCIB1 at 2025 AACR Annual Meeting (Scancell Press Release) - "Scancell Holdings plc...announce clinical data from the ongoing Phase 2 SCOPE trial will be presented at the American Association for Cancer Research (AACR) Annual Meeting....Scancell CMO Nermeen Varawalla will present the SCOPE clinical trial program, preliminary results of cohort 1 and their correlation with T cell responses."

P2 data • Melanoma

Scancell to present translational data from the Phase 2 ongoing SCOPE trial of SCIB1 at the 2025 AACR IO conference (Scancell Press Release) - "Scancell Holdings plc...announce translational data from the SCOPE trial demonstrating SCIB1 combined with nivolumab and ipilimumab will be presented during a poster session at the AACR IO conference....So far, 25 patients in cohort 1, receiving SCIB1 in combination with ipilimumab and nivolumab, have shown 84% disease control rate, 80% progression free and 20% complete response rate. The translational data that will be presented demonstrates functional vaccine specific T cell responses for patients enrolled in cohort 1 (SCIB1 plus ipilimumab and nivolumab)."

P2 data • Melanoma

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

Scancell announces further positive data from the ongoing SCOPE trial of SCIB1 with double CPIs for Advanced Melanoma (Scancell Press Release) - P2 | N=130 | SCOPE (NCT04079166) | Sponsor: Scancell Ltd | "Scancell Holdings...announces today that 25 patients in cohort 1, receiving SCIB1 in combination with ipilimumab and nivolumab, have reached the 25-week landmark point of the SCOPE trial. These patients are showing progression free survival (PFS) of 80% at 6 months, with 5 (20%) complete responders (CR). 21 of 25 patients (84%) have shown disease control (stable disease or tumour regression, DCR). 18 out of 25 patients have shown a clinical response which is an objective response rate (ORR) of 72%, with many patients continuing to show tumour shrinkage over time.....To date, cohort 1 of the SCOPE trial has recruited 42/43 patients, and it is anticipated that all of these patients will reach week 25 during H1 2025....It is anticipated that all cohort 3 patients will reach week 25 during H2 2025."

P2 data • Trial status • 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

TRP-2 / gp100 DNA vaccine and PD-1 checkpoint blockade combination for the treatment of intracranial tumors. (PubMed, Cancer Immunol Immunother) - "Here we show that SCIB1, a TRP-2 and gp100 directed ImmunoBody® DNA vaccine, generates a strong TRP-2 specific immune response, as demonstrated by the high number of TRP2-specific IFNγ spots produced and the detection of a significant number of pentamer positive T cells in the spleen of vaccinated mice...Time-to-death was significantly prolonged, and this correlated with increased CD4+ and CD8+ T cell infiltration in the tissue microenvironment (TME). However, in addition to PD-L1 and IDO, the GBM TME was found to contain a significant number of immunoregulatory T (Treg) cell-associated transcripts, and the presence of such cells is likely to significantly affect clinical outcome unless also tackled."

Checkpoint block • Checkpoint inhibition • Journal • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • CD4 • CD8 • IDO1 • IFNG • PD-L1

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: Efficacy and safety results from the open-label phase 2 SCOPE trial. (ASCO 2024) - P2 | "SCIB1 given with nivolumab and ipilimumab, as 1 st line treatment in unresectable melanoma, improved the ORR to 85% without an increase in clinically meaningful adverse events. These results, if confirmed in the larger ongoing patient cohort, provide confidence in initiating a randomized registration program in unresectable melanoma patients with this novel DNA plasmid technology."

Clinical • Metastases • P2 data • Hematological Disorders • Melanoma • Neutropenia • Oncology • Pain • 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

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

Scancell announces multiple upcoming presentations at the 21st CIMT Annual Meeting (Scancell Press Release) - "Scancell Holdings plc...announces that multiple abstracts have been accepted for an oral and as poster presentations at the 21st Association for Cancer Immunotherapy CIMT Annual Meeting being, taking place in Mainz, Germany, on 15-17 May 2024. Impressive clinical data of SCIB1, supported by functional T cell responses to the TRP2 and gp100 peptides which can be detected in patients post vaccination, will be presented by Head of Translational Research, Dr Samantha Paston. The posters will show the isolation of specific TCRs that recognise post translationally modified peptides and the application of Anti-Sialyldi-Lewis-a as a CAR-T."

Clinical • P2 data • Gastrointestinal Cancer • Melanoma • Oncology • Skin Cancer • Solid Tumor

Clinical Update on the DC Targeting Melanoma Vaccine, SCIB1 and The Modi-1 Vaccine Targeting Citrullination (IO-SUMMIT EUROPE 2024) - "SCIB1 a DC targeting DNA vaccine gives at impressive 85% response rate in combination with ipilimumab and nivolumab in advanced melanoma. Citrullination occurs in stressed tumor cells and makes an excellent target for a universal cancer vaccine. Modi-1 targeting citrullination is currently in phase II clinical trial"

Clinical • Melanoma • Oncology • Solid Tumor

The first patient has been dosed with iSCIB1+ in the SCOPE trial (Scancell Press Release) - "Scancell Holdings plc...the developer of novel immunotherapies for the treatment of cancer and infectious disease, announces today that the first patient has been dosed with iSCIB1+ and doublet checkpoint inhibitor therapy, consisting of ipilimumab (Yervoy) plus nivolumab (Opdivo), in the SCOPE trial’s new cohort....Recruitment into the iSCIB1+ cohort is expected to be complete by the end of Q3 2024. Early data from this cohort is expected in Q4 2024."

Enrollment status • P2 data • Trial status • Melanoma

SCIB1 Plus Nivolumab/Ipilimumab Generates ORR of 85% in Advanced Unresectable Melanoma (OncLive) - P2 | N=87 | SCOPE (NCT03927456) | Sponsor: Scancell Ltd | "First-line treatment with the DNA vaccine SCIB1 in combination with nivolumab (Opdivo) and ipilimumab (Yervoy) elicited an overall response rate (ORR) of 85% in patients with advanced, unresectable melanoma (n = 13)....SCIB1 encodes a human IgG1 antibody with 3 epitopes from gp100 and 1 from TRP-2. Additionally, sequences encode 2 HLA-A*0201 restricted CD8 epitopes, which are present in 50% to 60% of the overall population. There are also 2 CD4 epitopes: HLA-DR4 restricted and HLA-DR7, -DR53, and -DQ6 restricted....The SCOPE trial is in its second stage, with 27 of 43 total patients now enrolled. Recruitment is expected to conclude in the second quarter of 2024, and additional data are expected in the fourth quarter of 2024.

P2 data • Melanoma