AGM research and development update

14 October 2014

 

Scancell Holdings Plc

('Scancell')

 

AGM research and development update highlights progress in both SCIB1 clinical trial and

Moditope^® platform

 

Scancell Holdings Plc, (AIM:SCLP), the developer of novel immunotherapies for the treatment of cancer, will today provide a research and development update following the Company's AGM.  Dr Richard Goodfellow and Prof Lindy Durrant, Scancell's joint CEOs, will present an update on progress with the new ModitopeÒ platform as well as the ongoing SCIB1 Phase 1/2 clinical trial in malignant melanoma, the lead programme from the Company's ImmunoBodyÒ platform.  

 

Highlights

 

·      Encouraging survival and safety data from Phase 1/2 clinical trial suggests that SCIB1 has the potential to become the first effective stand-alone treatment for adjuvant melanoma.  All 16 patients with fully resected disease are still alive with a median survival of 26 months after starting treatment and only four have shown disease progression

·      Adjuvant melanoma represents a significant new market opportunity for SCIB1.

·      Combining SCIB1 and PD-1 blockade in animals enhances tumour destruction and extends survival times supporting the use of the combination for later stage disease

·      Modi-1 on schedule to be ready for clinical trials in 2016

·      Two new Moditope® protein targets identified

 

Dr Lindy Durrant, Joint CEO of Scancell, comments:  "Modi-1 remains on track for start of first-in man clinical trials in 2016.  The identification of new targets suggests that Moditope has significant potential as a  platform for generating multiple cancer immunotherapeutics.  In addition to the reported positive data from SCIB1, our Immunobody® platform continues to make good progress with a second vaccine target for lung cancer and the potential to take the platform into chronic infectious diseases."

 

Dr Richard Goodfellow, Joint CEO of Scancell, adds:  "Cancer immunotherapy is emerging as one of the most exciting areas of pharmaceutical research and development.  Scancell now has two innovative technology platforms in this emerging field, both of which are currently being evaluated by a number of pharmaceutical companies under a CDA.  The encouraging survival data on SCIB1, especially in patients with resected disease, offers an even greater market opportunity for SCIB1 and our pipeline of ImmunoBody® vaccines than was originally envisaged."

 

Research and Development Update

 

SCIB1

 

We are pleased to announce further encouraging data from the on-going Phase 1/2 clinical trial in patients with Stage III/IV melanoma treated with SCIB1.  To date, 32 patients have been treated with SCIB1, including seven at the higher 8mg dose.  Six patients are currently on long-term treatment and have received between 4 and 6 further doses of SCIB1 every 3-6 months.  Although recruitment of patients with advanced disease remains challenging it is expected that enrolment for the study will be completed during 2Q15.  A new clinical centre has been established at the Royal Surrey County Hospital in Guildford to accelerate recruitment.  SCIB1 continues to be a safe and well tolerated treatment with no withdrawals from the study due to adverse events.

 

Overall, only five of the 27 patients who have received at least three doses of 2-8mg SCIB1 since commencement of the study in 2010 have died.  Median survival time in Part 1 patients who received at least three treatments with the 2mg/4mg doses of SCIB1 is now 34 months since study entry.  This group of patients had 1-year, 2-year and 3-year survival rates of 100%, 67% and 50%, respectively.  For the Part 1 8mg cohort of patients, who were recruited later, the median survival time is currently 13 months since study entry.  The median survival time since initiating treatment with SCIB1 in Part 2 patients with resected disease (and receiving 4mg doses of SCIB1) is currently 25 months.

 

Importantly, all 16 patients (two in Part 1 and 14 in Part 2) with fully-resected metastatic disease (nine Stage III and seven Stage IV) are still alive with a median survival time of 26 months since study entry (range 20-39 months) and only four have shown evidence of disease progression.  The Stage III patients have a median survival time of 26 months since study entry and two (22%) have progressed.  This compares extremely favourably with results from a peptide vaccine trial (Slingluff et al., 2011) where 52% of fully-resected Stage III patients had progressed and 33% had died two years after the start of treatment.  The Stage IV patients treated with SCIB1 have a median survival time of 24 months since study entry and two of these patients (22%) have also progressed.  In the Slingluff study, 50% of the fully-resected Stage IV patients had progressed and 19% had died after two years of treatment. 

 

These results in patients with resected disease suggest that SCIB1 may have an important role to play as first line treatment in adjuvant melanoma.  These are patients who no longer have measurable disease (following surgery) and are often generally quite well.  However, they are at a high risk of recurrence and currently have very few, if any, effective treatment options.  This represents a significant and as yet untapped market opportunity, including some 360,000 patients in the US alone, of whom around 45% have the MHC antigen HLA-A2 and are therefore suitable for SCIB1 treatment.

 

Animal data supporting the synergistic effect of combining SCIB1 with PD-1 blockade was announced in August.  Any patients that progress following SCIB1 monotherapy, or indeed any patient with more advanced disease, may therefore benefit from the combination of SCIB1 with a checkpoint inhibitor.

 

ImmunoBody® platform

 

Scancell's Immunobody® immunotherapy platform enhances the uptake and presentation of cancer antigens to harness the high avidity T cell responses that destroy tumours.  The platform has been validated both in animals and in the clinic with SCIB1 but many opportunities also exist for the development of a pipeline of ImmunoBody® vaccines, both for cancer and chronic infectious diseases.

 

A second ImmunoBody® vaccine targeting the lung cancer antigen NY-ESO-1 (SCIB2) has been developed to the point at which the product is fully defined and ready for further preclinical development as a potential immunotherapy for any tumour that expresses the NY-ESO-1 antigen such as lung, oesophageal, gastric, ovarian and bladder cancers.  During the past 12 months research on other ImmunoBody® vaccines for prostate, liver and colorectal cancer have also been further advanced.

 

In addition, Scancell has conducted proof of concept studies with ImmunoBody® constructs expressing antigens from influenza and Epstein Barr virus and is in early discussions with potential partners for the co-development of ImmunoBody® vaccines for the treatment or prophylaxis of infectious diseases.

 

Modi-1

 

Scancell's Moditope® immunotherapy platform is based on exploiting the normal immune response to stressed cells, which is largely mediated by CD4+ T cells, and harnessing this mechanism to eradicate cancer cells.  Scancell's first target for Moditope® is vimentin - a major cytoskeletal protein found in mesenchymal cells.  Many epithelial tumours switch from expression of cytokeratin to vimentin during metastasis in a process known as epithelial mesenchymal transition (EMT); this change in phenotype enables the cell to become mobile and metastasize to new locations in the body.

 

Scancell has now selected two modified vimentin peptides in which the arginine residues have been substituted by citrulline to form the basis of its first Moditope® development candidate, Modi-1.  The inclusion of additional modified peptides from other Moditope® target proteins into Modi-1 is currently under review. Animal studies have shown that the two vimentin peptides stimulate potent anti-tumour responses and leads to significant improvements in survival, suggesting that the Modi-1 product could have outstanding potential as a novel immunotherapy.  Immune response studies with cells isolated from cancer patients have confirmed that T cell responses were stimulated by both modified vimentin peptides.  

 

Optimisation studies have identified the adjuvant, dose and administration route for testing Modi-1 in the First in Man study.  In animal studies, an aggressive tumour cell line confirmed that the two vimentin peptides eradicate tumour cells in a therapeutic, and therefore clinically relevant, setting.  Remarkably, these responses were evident when tumours had reached a late stage of development.

 

Moditope vaccines  have the potential to treat a wide variety of cancers.  Scancell is currently further evaluating  the initial indications for the first clinical trial with Modi-1 in terms of  clinical need and market opportunity and based upon the possible addition of other peptide targets into the product.

 

Scancell is considering options for conducting the initial Modi-1 study in both Europe and the US and is designing the development and regulatory strategy to allow for either approach.  The development programme will include manufacture plus toxicology and stability testing of the final formulated product.  This data will form the basis of a clinical trial application, which is anticipated to be ready for submission in the first half of 2016.

 

Moditope® platform

 

Having exemplified the Moditope® platform with modified vimentin peptides, Scancell has been expanding the platform to other citrullinated tumour proteins that could be incorporated into Modi-1 or developed into a pipeline of other multiple-cancer immunotherapeutics.  We are therefore pleased to announce today the identification of two further Moditope® protein targets, alpha-enolase and ING4.

 

Human alpha-enolase is a glycolytic enzyme that is overexpressed by lung, liver and other cancers.  We have identified a citrullinated peptide within human alpha-enolase that induces a powerful and specific immune response and that elicits both increased survival and decreased tumour volume compared to control groups in animal models.  Analysis of blood samples from donors has indicated that humans have a T cell repertoire that is able to recognise citrullinated alpha-enolase.

 

The tumour suppressor protein encoded by the ING4 gene plays a role in many cancer related processes.  Two citrullinated peptides from human ING4 have been shown to induce specific T cell responses.  Further studies are ongoing to evaluate the effect of these citrullinated peptides on tumour volume and survival.  Both alpha-enolase and ING4 are believed to offer excellent prospects for future Moditope® immunotherapies.

 

 

-ENDS-

 

For Further Information:

 

Dr Richard Goodfellow, Joint CEO Professor Lindy Durrant, Joint CEO	Scancell Holdings Plc Scancell Holdings Plc	+ 44 (0) 20 3727 1000
Christopher Golden/Stephen Keys	Cenkos Securities	+ 44 (0) 20 7397 8900
Mo Noonan/Simon Conway	FTI Consulting	+ 44 (0) 20 3727 1000

 

 

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 being evaluated in a Phase 1/2 clinical trial.  Data from the trial demonstrate that SCIB1, when used as monotherapy, has a marked effect on tumour load, produces a melanoma-specific immune response and highly encouraging survival trend without serious side effects.

 

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.

 

Pre-clinical data on a combination of SCIB1 and checkpoint inhibition (blockade of the PD-1 immune checkpoint pathway), has shown enhanced tumour destruction and significantly longer survival times than when either treatment was used alone.

 

Scancell has also identified and patented a series of modified epitopes that stimulate the production of killer CD4+ T cells 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.