Dedicated to providing a prognostic test for early AJCC Stage I and Stage II melanoma to better identify a patient’s true risk of disease progression

Melanoma is the leading cause of
cancer-related death in 20-35 year olds.

Melanoma, the most deadly of skin cancers has an increasing worldwide incidence with currently 17,000 patients diagnosed annually in the UK alone.

Presently, disease staging and risk of spread (metastasis) is based on the microscopic appearance/depth of the original tumour (American Joint Committee on Cancer (AJCC) staging criteria), in which patients classified with early stage I tumours are treated by surgical excision, defined as low risk, and subsequently followed up clinically for up to 5 years post-diagnosis. However, approximately 10% of patients with AJCC stage I melanomas will go on to develop metastasis, resulting in poor prognosis and a 5 year survival rate of <10%.

Worldwide, around 232,000 people were estimated to have been diagnosed with malignant melanoma in 2012, with incidence rates varying across the world (Based on a graphic created by Cancer Research UK)

AMLo Biosciences has identified two proteins (AMBLor™) in the skin overlying the primary tumour that are lost in high-risk melanoma

AMBLor™ is a new test in development based on two protein markers, AMBRA1 and loricrin (AMLo) that are normally present in the upper layer of the skin (epidermis). However loss of these markers in early-AJCC stage 1 stage is associated with high-risk tumour subsets while they are retained in the epidermis overlying genuinely low-risk tumours.

The AMBLor™ biomarkers have now been validated in three independent powered cohorts of over 400 patients with AJCC stage I melanoma with known clinical outcomes demonstrating their clinical accuracy and prognostic utility.

Representative photomicrographs of AJCC stage I cutaneous melanomas following AMBLor staining

DAB counterstain used throughout.
i. Maintenance of epidermal Ambra1 expression overlying primary melanoma (t)
ii. Maintenance of epidermal loricrin expression overlying the same primary melanoma depicted in image i).

iii. Loss of epidermal Ambra1 expression in the peri-tumoural epidermis overlying a primary melanoma
iv. Loss of epidermal loricrin expression in the peri-tumoural epidermis overlying the same tumour as iii).

AMBLor™ is a simple prognostic test that fits seamlessly into current diagnostic protocols and is based on the use of 2 antibodies on formalin fixed paraffin embedded tissue sections and automated immunohistochemistry routinely performed in diagnostic pathology laboratories worldwide.

Digital analysis of the AMBLor™ test is simple and easy to interpret, with a quick turn around time such that it can be performed and analyzed concurrently with other diagnostic tests within a short enough timeframe to help guide further investigations such as sentinel lymph node biopsy.

Validation of AMBLor™ in two combined independent AJCC I Cohorts

ABOVE Kaplan-Meir survival curve representing disease free survival (DFS) in the combined data from two cohorts, totaling of 379 AJCC stage I melanomas with up to 12-years follow up. Univariate analysis of AMBLor™ reveals a significantly increased risk of metastasis in patients with “high-risk” AMBLor™ expression compared to “low-risk” patients. (DFS = 97.9% “low-risk” versus 86.1% “high-risk” at 96-months (Log-rank (Mantel-Cox) P = <0.0001, HR 6.2 (95% CI 2.7 – 14.5)).

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Sensitivity

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Specificity
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Positive Predictive Value

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Negative Predictive Value (absolute risk of metastasis in low risk sub set)

ABOVE Table indicating sensitivity and specificity of AMBLor as a prognostic biomarker; an NPV of 97.9% (and 2.1% risk of metastasis in low risk subset) indicates the robustness of the assay, enabling patient reassurance and potentially earlier discharge from secondary of such patient sub groups; significantly reducing healthcare costs and resources.

The AMBLor test offers personalised, prognostic information for clinicians and patients over and above AJCC staging alone

Our prognostic test for melanoma: making it available to those in need

AMLo Biosciences is registering in several global territories, making our prognostic test for melanoma available to those in need

AMLo Biosciences aims to deliver our prognostic biomarker test (AMBLor™) to the American Joint Committee on Cancer (AJCC) Stage I and II cutaneous melanomas which represent approximately 91% of all cases at initial presentation.

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AJCC Stage I & II cutaneous melanomas

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Low-risk tumours that develop metastatic disease

Risk of disease progression is currently determined based on pathological features of the surgically removed melanoma but using this methodology, 10% of seemingly low risk tumours will go on to develop metastatic disease, at which point treatment options are limited.

By identifying disease risk at an early stage, we aim to reduce the physiological burden and increase reassurance for those individuals with low risk early stage melanomas while enabling earlier therapeutic interventions for those potentially at high risk.

We put patients at the heart of everything we do

AMLo Biosciences is committed to:

 

  • reducing mortality from malignant melanoma by accurately identifying the risk of metastatic disease in early-stage melanoma patients using our simple and cost effective immunohistochemical test – AMBLor™.
  • providing peace of mind for melanoma patients who are truly low-risk of disease progression by providing them with an accurate determination of their true risk of progression.
  • informing clinicians to help them plan further investigations and early treatment for those predicted to be at risk of metastasis.
  • improving patient outcomes and reducing the financial burden of melanoma on global healthcare economies.

Active patient involvement from the very start

AMLo Biosciences’ aim of putting patients at the centre of everything we do is not only aimed at the implementation of our test. We have actively encouraged involvement of melanoma patients, their carers and their families in the development of our company.

In the past few years, projects associated with the development of AMBLor™ have attracted nearly £2 million in research funding. All of these projects have been actively developed with patient involvement, with our latest studies having at least three patients sitting on the steering committee of each project.

We actively disseminate research findings through our associated melanoma patient support group (over 50 members at South Tees Hospitals, United Kingdom). In return, we are able to receive feedback on our work and future project planning from the public, who ultimately will benefit most from our discoveries.

A future of accurate melanoma diagnosis and better patient outcomes

AMLo Biosciences plans to launch its technology globally and make a positive impact on patients’ lives.

AMLo Biosciences Limited is a company registered in England and Wales. Company # 11004534

Trading address: Newcastle University, The Medical School, Framlington Place, Newcastle upon Tyne, NE2 4HH, United Kingdom

Registered address: c/o RMT Accountants & Business Advisors Ltd, Gosforth Park Avenue, Newcastle upon Tyne, NE12 8EG, United Kingdom

VAT # 285288950

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