Dear Doc, The evidence is all around you…You are falling into...

Dear Doc,

The evidence is all around you…

You are falling into the trap of comparing apples with pears with bananas….or put another way treatment naive, steroid refractory or biologic refractory UC patients.

The key word in this instance is “medically refractory” patients.

Lets leave to one side , the fact that a Prof of IBD at the Cleveland Clinic has just presented at the world’s largest IBD forum and told participants that MSCs are a treatment for Ulcerative Colitis…


At least you might have listened to Silviu give some very clear guidance at the last results conference call of the 31st March 2022, where he made the following observations about the current Investigator Lead Phase 1/2a Clinical Trials in response to a question in the Q&A section .

Silviu Itescu -- Chief Executive Officer

So let me address several of those questions. So first of all, remember that these patients are effectively no-option patients. They've already cycled through biologics and have failed and continue to have very active disease. So from that point of view, the control arm here is going to do really badly, right? So I don't think that the size of a pivotal trial will be anywhere near the size of trial that the biologics are targeting.

Remember that the first-line biologics have a very high responder rate within the control population. So they need large numbers. We expect very few responders, a very low response rate in the control. And as you can see in the first 12 patients, the control patients had no response and in fact, got worse during the three-month period of follow-up.

So I think in terms of a design of a study going forward, I think the numbers are going to be much more than you might anticipate. Secondly, I think while this study was set up to evaluate for up to 48 patients, it was not powered as such. And so, the objective for us was to see whether we have a signal of efficacy and safety by this local delivery method in both a sufficient number of ulcerative colitis patients and Crohn's patients to have a view as to how to potentially structure a randomized controlled study, that would be an in-house study with or without partners. And I think the objective of that is we're a good way through this.

And whether we stop after we've had all patients or whether we stop somewhere short of the 48 patients, I think, is still up to the data sets to tell us, right? The science will tell us that. But I think we're very excited by the data we've seen already. And I think this is an opportunity to address an unmet need that otherwise is not addressable today. So we're very excited about this.

So why does Silviu think the responder rate will be so low ?

Well lets start by looking at a very large Phase 3 RCT for Ustekinumab. This was the first IL23
inhibitor approved by the FDA, sold under the brand name Stelara by Jansen Pharma (J&J) . As you can see from the poster abstract below, the placebo or control arm performed woefully at a 5.3% response. This is particularly relevant because the placebo was evaluated against Stelara only after all treatment options , including TNF alpha inhibitors, such as Infliximab and anti integrins like Vedolizumab had been exhausted.
This is where it gets interesting, but you will need to go to page 36 out of 111 to the Supplementary Appendix of this published study in the NEJM to find out why . As most people are too lazy to do the work , i provided you with the key information below: (see reference link on poster). The sub population referred to in this study is precisely the subset we have been asked to treat in our Phase 3 RCT at the Cleveland Clinic . In other words, because this is effectively a salvage treatment, the placebo arm achieved only 0-2% remission for Stelara compared to the 100% (with only 4 patients) at 6 weeks for Remestemcel in comparison . When I have more time , i will explain more about how Prof Lightner has designed this trial using escalating doses . The first 4 treated received only 150m cells whereas the dose is likely to be escalated to 300m in the next cohort. All this can be validated by searching the Clinical trials Registry .

As the proverb goes Doc….”a little knowledge is a dangerous thing” . Anyone with a specialist knowledge of IBD can see that the first 6 weeks endoscopic remission data for Remestemcel is amazing. I suspect higher dosing and a second booster shot (part of the trial protocol ) at 3 months will further strengthen the patient outcome …but we will have to wait and see !

Oh, by the way Doc, if your not familiar with Stelara you should be . Its forecast to do $US 10bn of sales in 2022. OP

“Patients who were biologic failures to both anti-TNF and vedolizumab represented the mostrefractory patient population enrolled in UC studies so far. These patients comprised 16.6% ofpatients randomized in this study (160 of 961 patients) and 32.6% of patients (160 of 491patients) who had a history of biologic failure. In this subpopulation, the proportions of patientswho achieved clinical remission (including aCR) at week 8 were greater in the 130 mg (10.9%and 9.1% [aCR]) and 6 mg/kg (10.3% and 10.3% [aCR]) groups compared with patients in theplacebo group (0% and 2.1% [aCR]).”


Please do not rely on the facts or opinions given in the above post when making an investment decision. DYOR.