Scancell Holdings Regulatory News (SCLP)

9 December 2013

Scancell Holdings Plc

Compelling new immune response data and promising survival trend suggest potential for SCIB1 as an effective novel therapy in metastatic melanoma

Scancell Holdings plc ('Scancell' or the 'Company'), the developer of novel immunotherapies for the treatment of cancer, is pleased to announce encouraging results from Part 2 of its on-going Phase 1/2 clinical trial in patients with Stage III/IV melanoma treated with the SCIB1 ImmunoBodyÒ as well as an update from patients in Part 1 of the study.

Highlights

Part 2 study results

· All 14 study patients produced a melanoma-specific T-cell response to treatment

· All patients are still alive; only three patients have any evidence of disease progression

· Median survival time of Part 2 patients since initiating treatment is currently 15 months; 21 months since diagnosis of metastatic disease

· Six patients are continuing on extended, long-term treatment with SCIB1

· SCIB1 therapy was well tolerated with no reports of serious drug-related side effects in line with results reported from Part 1 of the study

Part 1 study update

· The four patients who were alive at the time of the initial Part 1 report (December 2012) remain alive

· Median survival time in Part 1 patients who received at least three treatments with the 2mg/4mg doses of SCIB1 is now 25 months

These results confirm that Scancell's SCIB1 ImmunoBodyÒ therapy is producing a melanoma-specific immune response in patients with Stage III/IV melanoma. This is particularly evident in patients with resected disease. Together with the immunological and clinical data from Part 1 of the study, the results suggest that these induced immune responses might also be contributing to the control of tumour in these patients.

Prof Lindy Durrant, Joint CEO of Scancell Holdings and Professor of Cancer Immunotherapy at Nottingham University, commented: "These results exceeded our highest expectations confirming that SCIB1 induces a consistent melanoma-specific immune response in Stage III/IV melanoma patients, especially in those with resected disease. Whilst the numbers are still small, it suggests that SCIB1 may be contributing to prolonged survival by controlling tumour growth and supports our belief that the highly targeted ImmunoBody® approach generates potent and specific T cells that can control malignant disease."

Prof Poulam Patel, the principal investigator in the trial and Prof of Clinical Oncology at the University of Nottingham, added: "This promising new data further supports our hypothesis that SCIB1 can harness the body's own immune system to control metastatic melanoma in a safe and effective way. More generally it also adds to the growing belief that training T cells to target and control tumour growth is one of the most promising new ways of treating cancer. In patients with more extensive metastases, it is feasible that combining SCIB1 with the latest checkpoint inhibitor drugs, which allow T cells to work better within the tumour environment, may offer further patient benefit."

Study Design

The first part of this single arm, open label, Phase 1/2 clinical trial was conducted in five UK centres in 11 patients, ten with Stage IV and one with Stage III malignant melanoma.  Patients were to be given five doses of 0.4mg, 2mg or 4mg of SCIB1, delivered by Ichor Medical Systems' TriGrid™ electroporation delivery device, over a period of sixmonths.  One patient in the 0.4mg dose group and one in the 4mg dose group who received only a single dose of SCIB1 were withdrawn from the study due to progressive disease shortly after study entry and were replaced to ensure that at least three patients in each dose cohort could be fully evaluated for immune response.  During the course of the study, regulatory approval was granted to increase the SCIB1 dose from 2mg to 4mg in patients in the 2mg cohort, if the treatment was well tolerated.  Two patients in this group received two 4mg doses of SCIB1 and onepatient received a single 4mg dose. Regulatory approval was subsequently obtained for treating a cohort of patients with 8mg of drug. Dosing of these patients is currently on-going.

In Part 2 of the study, 14 patients with resected Stage III/IV melanoma (eight with Stage III and six with Stage IV) entered the study. One patient was only able to tolerate three doses of 2mg and withdrew from the study. Of the remaining patients, 12 received a full 4mg dose of SCIB1 on five occasions over a period of 6 months and one received four doses of 4mg and one dose of 2mg.

During the course of the study, regulatory approval was granted to continue treating eligible patients for a period of up to 5 years from the formal end of the study. During this period patients can receive a 4mg dose of SCIB1 every 3-6 months.

Clinical response

Part 1

Four out of the six patients in the 2mg/4mg cohorts who received at least three doses of SCIB1 are still alive and one remains disease-free more than 2 years after starting treatment. All of the patients in the 0.4mg dose group have died from melanoma progression. The median survival time for the six evaluable patients in the 2mg/4mg cohorts is currently 25 months.

One patient in the 4mg dose group with multiple tumour lesions present at the start of treatment showed a "differential response" pattern in which all of her lung lesions decreased in size or disappeared completely following six months of treatment with SCIB1 whereas one abdominal wall tumour nodule grew and was resected. Staining of tissue taken from the resected nodule showed it had lost expression of one of the target melanoma antigens, gp100, but had high levels of PD-1 protein, which is known to attenuate high avidity T cell responses; this suggests that combining SCIB1 treatment with anti-PD-1 monoclonal antibodies may be an effective therapeutic approach. The patient continued on extended treatment with SCIB1 until she was subsequently found to have recurrent melanoma in her intestines; this tumour was also excised and treatment was discontinued.

Part 2

All of the resected Stage III/IV patients treated with SCIB1 in Part 2 remain alive and only three have had progressive disease to date. One patient had their lesion excised in January 2013 and has no further disease progression to date. The other two patients have progressed within the last month. The median survival time for Part 2 patients is currently 15 months from study entry and 21 months from diagnosis of metastatic disease.

Immune response

Immune response was measured by peptide-specific proliferation. A positive response required at least twice the background control at each time point and at least twice the pre-treatment control value on two or more of the six time points measured. In addition, responses were assessed using an enzyme-linked immunosorbent (ELISPOT) assay after T cell expansion in vitro, where a positive response was more than three standard deviations above the pre-treatment control value on two or more of the six time points measured. Fresh samples were analysed in both assays, except for one patient where the controls for the fresh proliferation assay were not validated and the assay was repeated using frozen samples.

Part 1

One patient in the 0.4mg cohort, all three patients in the 2mg/4mg dose cohort and two patients in the 4mg dose cohort mounted a measurable proliferation response to the melanoma-specific epitopes in SCIB1. In addition, the patient with the differential clinical response was assessed using the ELISPOT assay and made a strong response to the melanoma TRP-2 antigen.

Part 2

All 14 patients responded to treatment in either the proliferation or ELISPOT assay. Twelve patients were immune responders in the proliferation assay, 13 patients responded in the ELISPOT assay and 11 patients responded in both assays, including the patient who only received three doses of 2mg of SCIB1. Broad, high frequency responses were seen against both the two CD8+ T cell epitopes and against the two CD4+ T cell epitopes. Six patients responded to all four epitopes, five patients responded to three epitopes and three patients responded to two epitopes. Statistically significant responses (p>0.0001) were seen after three, four or five immunisations but not after two, indicating that at least three doses are required for a strong immune response to develop.

Due to these encouraging results six patients are continuing on extended, long-term treatment with SCIB1.

Tolerability and Safety

The SCIB1 immunotherapy produced very few side effects, none of which were serious, with no new or unexpected issues found over those reported with the results from Part 1 of the study where no systemic dose-limiting toxicities were observed. The most commonly reported adverse events were injection site reactions and cold- and flu-like symptoms. The electroporation procedure itself was less well-tolerated in some patients and, in certain cases, required pre-treatment sedation. However, only one patient has withdrawn from the study for this reason and seven chose to continue treatment in Part 2 of the study (one has since discontinued).

For Further Information:

About Scancell

Scancell is developing novel immunotherapies for the treatment of cancer based on its ImmunoBody® and Moditope® technology platforms. Scancell's first ImmunoBody®, SCIB1 is being developed for the treatment of melanoma and is in Phase 1/2 clinical trials. Preliminary evidence from Part 1 of the study showing that SCIB1 produced an immune response which might be associated with clinical benefit in patients with malignant melanoma was released in December 2012.

Scancell's ImmunoBody® vaccines target dendritic cells and stimulate both parts of the cellular immune system; the helper cell system where inflammation is stimulated at the tumour site; and the cytotoxic T-lymphocyte or CTL response where immune system cells are primed to recognise and kill specific cells.

Scancell has also identified and patented a series of modified epitopes that stimulate the production of killer CD4 that destroy tumours without toxicity. The Directors believe that the Moditope® platform could play a major role in the development of safe and effective cancer immunotherapies in the future.