Replies to post #217232 on Biotech Values

[masterlongevity]

amazing how much progress made in these back of the eye diseases over past 15 yrs.

[mcbio]

Re: Roche's RG7716/(ARPO)

I saw @JacobPlieth make reference generally to ARPO in connection with this news (wasn't clear to me if in positive, negative, or neutral context). Never heard of the company until his tweet today. Turns out this company was spun out of AKBA in 2011. Here's a link to the company presentation: http://ir.aerpio.com/phoenix.zhtml?c=254540&p=irol-presentations .

In short, they are developing a subcutaneous drug (AKB-9778) that they claim is the most potent activator of the Tie-2 pathway (the ultimate goal of RG7716 and similar drugs). AKB-9778 inhibits vascular endothelial protein tyrosine phosphatase (VE-PTP)(separate target in this similar pathway as Ang-2). ARPO claims that VE-PTP inhibition activates Tie2 more robustly than Ang-2 inhibition (seems to be supported by slide 9 of the company presentation).

If you look at slide 13 of the presentation, it shows the Phase 2a data in DME and it shows that AKB-9778 had no effect alone in change in retinal thickness over time versus the effect seen by Lucentis but then they claim the combo does better than Lucentis alone. Seems hard to believe there will be a true combo benefit given AKB-9778 has no effect on its own. They claim in the slide that DME is primarily a VEGF-driven disease so that's why no monotherapy effect. Still don't understand why we should believe there would be a combo benefit if it's primarily a VEGF-driven disease.

Slide 17 shows Phase 2a data in diabetic retinopathy which is the indication they seem to be focused on now. This shows the percentage of patients at 3 months with a 2-step or more improvement in diabetic retinopathy severity score. At 3 months, data showed just 11.4% of patients hit this with AKB-9778 vs. 4.2% in placebo. Seems very small but then they note they expect this benefit to grow over time (Lucentis showed 31-34% at month 12). But, they also note that Lucentis showed a 16-18% improvement at month 3 previously, which is much higher than AKB-9778 data.

So, I don't understand how this drug is supposed to compete in this landscape. There is no VEGF inhibitor associated with AKB-9778 so how will it compete with dual VEGF/Ang-2 drugs (even if VE-PTP is truly a better target than Ang-2). Also, the data doesn't stack up so far relative to VEGF inhibitors alone in either of these indications so not sure what I'm missing (if anything).