The study results de-risks midkine as a therapeutic target and paves the way for its antibody program to proceed towards clinical studies.
In May 2014, CAB102 was selected as the company's lead humanised anti-midkine antibody. It has demonstrated the greatest efficacy in reducing mean tumour volumes at 21 days post treatment by 50% when combined with carboplatin, the standard therapy in lung cancer.
"The lack of dose limiting toxicities in these studies is heartening for our CAB102 clinical plans," head of product development Darren Jones said.
"These studies are the first ever to formally show that a well-designed MK-specific molecule has no deleterious side effects."
Chief executive officer Maria Halasz added:
"There has been much discussion about the safety of targeting midkine for therapeutic purposes.
"A clean toxicology result for CAB102 not only increases our confidence in CAB102 itself being a safe molecule, but also suggests that MK as a target is druggable without triggering significant side-effects."
As a final step towards gaining regulatory approval for clinical studies, further toxicology and safety studies will now be performed using multiple doses of CAB102 in rats and cynomolgus macaques.
Cellmid engaged a leading US pre-clinical contract research organisation to conduct two studies using its humanized lead anti-MK antibody, CAB102.
The studies were performed in rats and non-human primates (cynomolgus macaques).
Importantly, the endogenous MK of both species has identical CAB102-binding properties as human MK.
As such, doses of CAB102 given to these species should recognise and interact with any MK in a way that is analogous to human dosing.
Single doses of CAB102 were administered by intravenous infusion at 3 dose levels, 10, 50 or 100mg/kg.
Animals were monitored for 14 days post-dose for clinical observations, morbidities, weight changes, clinical chemistries and blood cell counts.
At study end necropsies were performed with all major organs examined for gross abnormalities.
Histological specimens were also collected for further investigation in case of any irregularities.
CAB102 was well tolerated at all dose levels in both species. The only notable observation was a slight and transient decrease in red blood cells and increases in bilirubin in the cynomolgus macaques.
No such effect was seen in the rats.
Necropsies confirmed that there have been no CAB102-induced abnormalities or changes to organs of the treated animals.
Even at a very high dose of 100 mg/kg, which is up to 10 times higher than the anticipated maximum dose for humans, there have been no adverse effects seen.
This is significant as Cellmid purposely designed CAB102 to interact identically with the MK of other species as it does to human MK.
Therefore, when CAB102 is given to rats and cynomolgus macaques, it should recognise and neutralise these species' own MK in a similar manner to that in humans.
Cellmid is now making good progress towards clinical studies for its anti-midkine antibody CAB102 after successful formal safety and toxicology studies.
While further studies are required to gain regulatory approval, the latest results are promising given that even at a dose 10 times higher than anticipated for humans, the antibody had no adverse effects on the tested animals.
It is also notable for being the first studies ever to formally show that a well-designed MK-specific molecule has no deleterious side effects.
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