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Cellmid selects lead anti-midkine antibody for oncology clinical trials

Published: 16:00 07 May 2014 AEST

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Cellmid (ASX:CDY) shares are expected to lift today after selecting its lead humanised anti-midkine antibody, which has demonstrated a significant reduction in chemotherapy resistance.
    
This is a significant step in advancing towards clinical studies and on track with the development program outlined to the market earlier in 2014.

The lead antibody, designated CAB102, has been shown to significantly reduce chemotherapy resistance in a preclinical model of lung cancer in combination with carboplatin. 

In addition to its functional activity in vivo, it has produced strong in vitro results in specifically designed midkine migration assays. 

Initial cell expression and stability data confirmed that it can be manufactured commercially, making it an economically feasible drug product.

Cellmid CEO Maria Halasz added:

“With the completion of lead selection, and after a well-planned and extensive testing program, our preparations for clinical trials are well on track.” 

CAB102 anti-midkine antibody

Selection of CAB102 is the result of a pre-clinical program in which dozens of Cellmid’s proprietary and patent-protected murine anti-midkine antibodies were assessed for efficacy and mechanism of action both in vivo and in vitro. 

The two most promising murine antibodies identified by this process were humanised by Cellmid’s collaborators, Biotecnol Ltd.

Of the 78 humanised antibody variants generated by Biotecnol, the six most promising candidates were then assessed further for mechanism of action, in vivo antitumor efficacy, and ‘manufacturability’.

Notably, all six candidates demonstrated similar or improved affinity when compared to their murine precursors.

Specificity for midkine has been retained, with no evidence of binding to other proteins. 

A preliminary assessment showed all six candidates were secreted at commercially viable concentrations during cell culture, all six were readily purified and have been confirmed as structurally stable and aggregate free.

The candidates were then tested for functional activity using an in vitro cell migration inhibition assay and an in vivo tumor xenograft model in combination with carboplatin. 

Carboplatin was selected as the chemotherapy of choice as it is standard therapy in lung cancer. 

As expected, and consistent with clinical experience, carboplatin did not significantly reduce tumor volume or mass when used alone compared to untreated controls in the NCI-H460 model. 

However, three candidates significantly reduced tumor growth when combined with carboplatin.

Head of Product Development Darren Jones commented:

“Strong preclinical performance by reducing chemotherapy resistance is important to progress our “first in class” anti-MK antibody program to the clinic.

The results are consistent with the independent findings by other research groups confirming midkine’s role in chemotherapy resistance in glioblastoma, and provide a strong commercial rational for our product development program in multiple cancer
types.” 

Other Progress

In April, Cellmid achieved serum-stable, drug-like midkine (MK) manufacture achieved at large scale for clinical use by one of its commercial partners.

This set the stage for commercial production of anti-MK antibodies once clinical studies are proven.

The manufacturing milestone is one of the key findings that was presented at the company’s third Midkine Symposium held in Kyoto, Japan.

Other key findings included pre-clinical efficacy studies conducted by Dr Guillermo Velasco from the Complutense University in Madrid showing that its anti-MK antibodies could overcome drug-resistance in the deadly brain cancer glioma.

Animal studies by Dr Astrid Liedert at the University of Ulm, Germany, have also shown its anti-MK antibodies enhancing bone fracture healing in vivo.

The symposium, which was co-hosted by MK discoverers Emeritus Professor Takashi Muramatsu and Professor Kenji Kadomatsu built on the success of the first two MK conferences held in Sydney (2010) and Istanbul (2012).

It attracted scientists from eleven countries while some of the company’s commercial collaboration partners also attended for the first time.


Analysis

Cellmid's anti-midkine program has been shown to significantly reduce chemotherapy resistance in a preclinical model of lung cancer in combination with carboplatin. 

In addition to its functional activity in vivo, it has produced strong in vitro results in specifically designed midkine migration assays. 

This is especially important given that these antibodies are expected to become clinic-ready by the end of 2014.

In combination with Cellmid's other products, the company's building a strong base for the generation of increasing revenues and adding significant value to its midkine program today and in achieving serum-stable, drug-like midkine (MK) manufacture at large scale for clinical use by one of its commercial partners.

We have estimated a valuation for Cellmid that equates to a share price target of $0.041 to $0.068 based on its rising cash flows and progress towards clinical trials.

 

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