Ann: Trading Halt, page-64

Hi All,

I have just been reading through the slides & looking at them in depth. Our numbers were not as good as in previous trials validating the test as indicated purely for DKD this morning & yes, that’s a bit disappointing. Please keep reading b4 you become stressed.

However, this is a novel test in predicting CKD/DKD up to 4 years prior to the event & I have posted the Conclusion above. I think that investors should read all the slides on the website. This was co-presented with Janssen for the CANVAS study CKD/CVD, so they would have to be in agreeance with what is presented in the poster, including comments on the prognostic validation of PromarkerD.

This was from CANVAS, their Canafliglozin cardiac trial for Type2 DM. 2976 patient samples were analysed. 31.1% of patients developed CKD over a four year period, 926/2976 patients. 32.7% on Canafliglozin 652/1994 and 27.9% on placebo 274/982.

Looking at the baseline eGFR, all patients had an eGFR >60ml/min/1.73m with a mean of 82.3, so in the normal range for kidney function at recruitment.

For test scores for the risk of CKD utilising PromarkerD

2099 patients were low risk (70.5%)
405 patients were moderate risk (13.6%)
472 patients were high risk (15.9%)

So if you look at these numbers 877/2976 patients were identified by PromarkerD test as being moderate to high risk for developing kidney disease, hence a warning for their Physician to increase the incidence of screening including standard blood tests, not just PromarkerD. 926/2976 in fact did develop kidney disease defined as a drop in eGFR to less than 60ml/min/1.73m.

The CANVAS trial was for diabetic cardiac patients who were on an ARB or ACE Inhibitor & are more likely to also be on diuretic drugs also & this has been identified as a factor in an acute drop in eGFR for patients being treated with Canafliglozin from recent research.

All the more reason to keep a close eye on these patient’s renal function & from the study, the higher the risk score, the more prognostic.

You can’t sugarcoat the fact that our numbers weren’t as good as previously in this massive trial, however as stated there may be a demographic reasons for this. There was a mean age of 61.9 years +/- 7.7 years. The mean time of a diabetes diagnosis was 12 years.

It was in cardiac patients with Type2 DM also, so you really need to take into account other treatments such as diuretics, Lasix (Frusemide) for heart failure, in particular that can slam the kidneys hard in HF patients in a very short space of time.

I was under the impression from ANNs that we would be looking at the CREEDENCE study, but obviously Janssen decided to do CANVAS with the harder basket of DKD + CVD patients & you can clearly see that in trial baseline patients, the demographic is older with a significant comorbidity.

So I’m taking this into consideration when looking at results also. That makes sense in the demographic. My interpretation is that it is CLINICALLY SIGNIFICANT & backs up the claim of validation of the test in CKD/CVD patients in a large clinical trial.

If we were purely just looking at a demographic of Type 2 DM, over that represents the real world incidence in adults, 18+ the numbers could be different again.

It’s good we went the hard yards first for patients in DKD/CVD, though. It’s the latest indication for Canafliglozin (Invokana) in the USA, Canada & has just been given the heads up in the EU/UK for that indication.

So you can understand the reasoning there, & the most high risk for cardiovascular events for patients with Type 2 DM.

GLTAH