Nature Publication for Cellmid’s Midkine in Cancer

• Findings that midkine plays an essential role in the metastatic spread of malignant melanomas were published in the prestigious journal NATURE
• Cellmid holds the most significant global IP portfolio around midkine globally
• This high quality independent study provides strong validation of Cellmid’s cancer therapeutic and diagnostic programs targeting midkine

Cellmid Limited (ASX: CDY) is pleased to advise that the highest ranked paper Nature has published the results of a significant study showing for the first time that midkine, around which the Company holds extensive intellectual property rights, is a crucial agent in the promotion of melanoma metastasis.  

The paper, entitled "Whole-body imaging of lymphovascular niches identifies pre-metastatic roles of midkine", by Professor Marisol Soengas and her group based in CNIO in Madrid, describes how midkine drives the often-fatal metastatic spread of melanoma cells from the primary tumour in the skin to distant organs such as liver, lung, bone and brain. This independent study published in Nature is highly significant for Cellmid for four key reasons:

• It provides strong validation for Cellmid’s cancer therapeutic and diagnostic programs, which use the Company’s proprietary midkine antibodies;
• It adds to the considerable data on the prognostic value of detecting midkine in different cancer types, where elevated midkine levels in various tissues correspond with poor therapeutic outcomes;
• It significantly increases visibility and credibility of Cellmid’s cancer therapeutic programs targeting midkine; and
• As the holder of the most significant intellectual property and antibody assets around midkine globally the publication places the Company in a unique position for partnerships.

The Company’s antibodies against midkine have already shown considerable promise in reducing tumour growth and restricting new blood supply to different solid tumours (some of these results have been released in the ASX announcements on 3 October 2013 and 5 October 2016). Together with these new discoveries around metastasis, inhibiting midkine for better treatment of melanoma becomes a compelling drug development program for Cellmid.

While most conventional anti-cancer treatments aim to kill rapidly dividing tumour cells, the ability to stop the spread of metastatic tumour cells would be of immense benefit for many advanced cancer patients with diverse tumour types.

It is widely accepted that lymphatic vessels are often the escape route for cancer cells to spread initially to nearby lymph nodes, followed by metastasis to more distant vital organs. The sprouting of new lymphatic vessels from the tumour into surrounding lymph nodes was thought to facilitate this step-wise metastatic spread via a process called lymphangiogenesis.

However, the group at CNIO in Madrid used a sophisticated mouse model to demonstrate that the primary tumour induces aberrant lymphangiogenesis in lymph nodes and organs located at considerable distances from the tumour, creating a pre-metastatic niche for tumour cells to lodge in. Importantly, midkine release from the tumour was found to stimulate distant lymphangiogenesis, creating a route for cancer cells to colonize sites throughout the body independent of local spread into lymph nodes adjacent to the primary tumour.

Midkine also enhanced the ability of tumour cells to adhere to lymphatic vessels. Therefore, midkine not only promotes lymphangiogenesis, but also tumour cell colonization in newly formed lymphatic vessels. These actions of midkine extend Cellmid’s current knowledge about midkine’s role in tumours as well as in blood vessel formation and cellular interactions throughout the body. Together with previous studies, the current findings provide strong rationale for Cellmid’s oncology program targeting midkine with therapeutic antibodies.

In their Nature News and Views commentary on the study, Hoshino and Lyden from Weill Cornell Medicine in New York describe how "…MDK (midkine) downregulation in an aggressive melanoma led to drastic inhibition of lymphangiogenesis, and reduced number of metastases", concluding that this work "…might open a door to diagnostic and therapeutic strategies that aim to deal with metastases before they arise".  David Olmeda, lead author on the Nature paper, lends further support for Cellmid’s midkine program in oncology "…we focussed on… MIDKINE, because it was new and could represent an alternative therapeutic target".