My 2 cents on CHF pathway to approval:I have previously stated...

My 2 cents on CHF pathway to approval:

I have previously stated I believe there is a chance for an Accelerated Approval pathway. Now after doing some further research I believe that this pathway will be the most likely way forward. The sources of my research primarily include material for a course I am completing put together by HarvardX (Prescription Drug Regulation, Cost, and Access) as well as FDA sources and journal sources as well as my own opinion.

Rex-L ticks the key requirements of:

· Serious condition with unmet medical need

· Approvable surrogate endpoint 3-Point MACE as a predictor of time to a MACE of any kind

· And it may be considered unethical to deny current/future target patients in need of this treatment (based on the large risk reductions in MACE – effect size of 54% p= 0.003 – clinically meaningful on top of current SOC and highly significant) to wait for the outcome of an additional phase III trial.

The gist of granting accelerated approval is to allow a drug that shows substantial early promise for a serious condition to be made widely available to patients as soon as possible. Early approval also greatly benefits manufacturers which can start earning revenue sooner and may have more time on the market in which to earn those revenues before their patent expires and generic drugs are approved.

We also know the FDA is able to further evaluate efficacy, safety, clinical benefit to risk profile via Phase IV studies. Phase IV studies to confirm a drug’s benefits are statutorily required if a drug is approved under the FDA’s accelerated approval pathway, and are also expected of other fast-track pathway drugs.

The FDA will likely take the full 60 days – or more if snowed under – IMO because experience has shown that post-approval requirements on manufacturers may not be completed in a timely fashion; and when they are completed and show negative outcomes, it can be hard for them to pull back on their approval decision.

Other considerations IMO supporting an accelerated approval:

· Rex-L is an innovative therapy (this is what was intended for the accelerated approval pathway – however accelerated approvals have become plagued with non-innovative drugs).

· The surrogate 3-Point MACE is well established and accepted by the FDA. This compares favourably to a potential candidate that shows a small change in a biomarker level that is not well established to be a valid predictor of a real world benefit.

· There was evidence of a treatment effect on 3-Point MACE reduction across all 537 patients (30% p=0.027); a treatment effect in 206 NYHA Class II patients (55% p=0.009); a treatment effect for ischemics and/or diabetics (37% p=0.019); and our likely target population ischemiscs and/or diabetics with hsCRP > or = 2mg/L (54% p=0.003 – highly significant and clinically meaningful).

· Rex-L has shown statistically significant unparalleled reduction in 3-Point MACE outcomes with an outstanding safety profile for the target CHF population. In fact, this alone could warrant a full approval, but I’ll stick with accelerated approval being more likely for now.

Some of my personal views for entertainment purposes:

· Rem-L results on top of Standard of Care – so more probable that the benefits (and risks) of treatment outside the clinical trial setting will carry over into the real world non-clinical trial setting.

· I think because Rex-L is an ‘add-on’ to current SOC, we are less likely to be seen as direct competition to their existing therapies in the CHF space. In fact, if we show to keep patients alive longer – then we may be good for their business. So I think we will have less behind the scenes resistance on this front.

· Dr Perin; CEO Itescu; Dr Rose; and Dr Krause. Plausible MOA – not targeting fluid overload, targeting instead smouldering inflammation and preserving viable heart tissue to prevent/slow disease progression.

· I honestly think the FDA want a win in today’s continuing COVID environment, and I don’t think they have it in for off the shelf MSC products. They pride themselves as being the first country to approve a lot of new drugs. What an uplifting story to approve Rex-L for the public in need (especially in these COVID and long COVID times).

Before I forget, in the 2016 21^st Century Cures Act, legislators created a breakthrough pathway for regenerative medicine products, drugs based on engineered human cells, based on the breakthrough therapy designation, even though these regenerative medicine products would have qualified for one of the five existing pathways already (some reading still to do …)

In summary, I hate to put myself out there but here goes: my best guess 80% chance of Accelerated Approval; 15% chance of full approval; 5% chance Breakthrough Therapy designation. If accelerated approval or full approval granted for CHF, then MSB SP over $20 in following 18 months to 24 months. You heard it here first folks!

PS: If Rex-L approved for heart, would SurgeCentre or others consider using it off-label for CLBP???

Not to be consideredfinancial advice. DYOR.