Cellmid (ASX:CDY) has entered into a research collaboration with a world leading research group at Complutense University in Spain to test its humanised and murine anti-midkine antibodies for the treatment of brain cancer.
The company's anti-MK antibodies were found to be highly effective at killing brain cancer cells and this will be further tested in vivo using state-of-the-art disease models.
The Complutense research group, headed by Associate Professor Guillermo Velsaco, are world leaders in the study of the molecular mechanisms that regulate brain cancer cell death, particularly via cannabinoid receptor signalling.
Midkine has been identified as the key signalling molecule promoting cancer stem cell growth and drug resistance in brain tumours.
A number of the company’s MK antibodies were highly effective at killing brain cancer cells including candidates with very high apparent potency.
Studies subject to the collaboration with Complutense University/IdISSC are expected to commence early in FY2016.
Previous work by Dr Velasco and his team identified MK as the key signalling molecule driving drug resistance in gliomas including its most deadly variant, glioblastoma multiforme (GBM).
Dr Velasco’s group also found that higher levels of MK in glioma and GBM patients were significantly correlated with more lethal disease variants.
Based on these discoveries, Cellmid and Dr Velasco’s group collaborated to investigate whether Cellmid’s murine anti-MK antibodies can prevent glioma/GBM cell growth in vitro.
“There is now strong scientific evidence to show that MK plays a key role in promoting the growth and proliferation of the most drug-resistant and refractory versions of these deadly brain tumours,” said Dr Velasco.
“The next logical step is to try to blockade MK using Cellmid’s anti-MK antibodies, and this is what we will now do using orthotopic xenotransplantation disease models.”
Cellmid head of product development Darren Jones said:
“Each antibody in this program has different features to the others. The collaboration will determine which antibody gives us our strongest shot at clinical efficacy.
“Preliminary experiments by Dr Velasco’s group have already given us some insights, but performance in these state-of-the-art disease models will be the definitive test.”
Cellmid and Complutense University are now expanding their collaboration to a full pre-clinical validation program.
The company will provide a number of its anti-MK antibodies to Complutense University for testing, including already humanised antibody CAB102, with the aim of selecting a lead molecule to advance specifically in a glioma/GBM clinical program.
Glioma, and its most deadly variant GBM, are the most common types of malignant brain tumours, making up approximately 40% of all primary brain tumours and around 70% of all primary malignant brain tumours.
Glioblastoma is the most lethal form of any cancer.
Prognosis is extremely poor; median survival for GBM patients is approximately 14 months, with 70% of patients dead within 2 years of diagnosis, and over 90% dead within 5 years.
Currently gliomas and GBM are incurable; the standard treatment is maximal safe resection (surgery) where possible, followed by concurrent radiation and chemotherapy with temolozomide (TMZ). However, the rate of recurrence is almost 100%.
“There remains an urgent need for new treatments to improve patients’ prospects in glioma and GBM,” Cellmid chief executive officer Maria Halasz said.
“We are cautiously optimistic that anti-MK therapy might help to address this need, not only because of MK’s promotion of drug resistance, but also because MK is a key driver of cancer stem cell replenishment.
“In addition, gliomas are the most highly vascularised tumours. Recent clinical strategies in gliomas include targeting blood vessel growth with antiangiogenic agents.”
Cellmid continues to progress the use of its anti-MK antibodies, working with Associate Professor Guillermo Velsaco and his world leading research group at Spain’s Complutense University to treat the most common types of malignant brain tumours.
Promisingly, Cellmid's anti-MK antibodies have shown strong anti-angiogenic activity in early studies.
Notably, Glioblastoma is an area of significant unmet need and committing to a combination therapy program means multiple collaboration opportunities in the future.
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