Data monitoring committee

The primary endpoint was a composite endpoint of stroke, systemic embolism, major bleeding, and cardiovascular death.

The original trial included all-cause mortality, but the DSMB noted that most of the deaths, in fact, all the deaths that were occurring were non-cardiovascular.

And so they appropriately, I think, changed it to cardiovascular mortality.

So what did the study show? And I should say also that the follow-up was two years, so 24 months.

If you're talking about a very large pharmaceutical company, they'll have resources to draw on.

If you're talking about a startup company, They're not going to have those resources and they're going to depend very heavily on having external vendors helping to support them versus a large pharmaceutical company who may do a lot of their DMC management internally.

Yeah.

And what does that look like, Robin, in terms of what does that process look like and having that independent oversight look like?

So the thing that I've noticed, and I actually have partnered with a couple of GCP auditors, is that the GCP auditors do a really good job at looking at the overall structure of how the GCP requirements and study review.

They go out and they do their audits.

They know if there's a DMC in place, ask for the charter, ask for evidence the meetings have happened.

But if they look at a meeting report, would they know it was correct? Would they know that the fundamental things that need to be there are there? The nice thing about an independent auditor such as myself that can come in and look at the entire project and help set up governance is I'm not acting as it's not punitive, it's proactive.

How did you tell us a bit about your journey and how you got here?

I had a background in technology communications and I was at a business show and ran into a woman who had started the first commercial DMC service and ended up going to work for her and becoming vice president of the company and then spent more than 20 years working with her and her company was acquired and And after the transition, it was a good time for me to take all that knowledge and kind of move on and figure out ways to give back.

Amazing.

I love it.

So you referenced the changes that kind of started in 2024, but let's get into some of those specifics.

So what's changed as far as the guidelines, the regulations?

Specifically with ICH E6 Release 3, the ultimate responsibility falls on the sponsor, not the CRO, not the vendor, not the DMC, Data Safety Monitoring Committee administrators.

The complete guidance put out, including the FDA, now says that the sponsor is responsible for basically independently making sure that they're providing evidence.

So this is positioned to be the first standard of care for that treatment and if successful could be approved at least into Indonesia and into that region as early as early next year.

Now data from 75 patients has now gone to the Independent Data Monitoring Committee or DMC.

Can you talk us through what the DMC does and why this is such an important milestone?

It's very significant.

Most of them were even on infusion prostacyclines.

This is the first, to my knowledge, the first and only study that was stopped early by the DSMB because of overwhelming efficacy at a pre-specified interim analysis, which I think is very impressive.

And I think the other really important thing to point out here is that these are really hard endpoints.

Like there's no disease progression or worsening hall walk.

We have up to three doses.

As you may be aware in gene therapy, you do a, the way the design works, you treat patient one, you wait 30 days, you have a DSMB, drug safety monitoring board, and then you get clearance to move on.

And so we're working through that process of study.

And as I mentioned, we expect to have, stay tuned for, we should be sharing some of the early data on the first three glaucoma patients at the lowest dose level.

So we've enrolled over 850 patients so far across our sites to the heparin domain.

So far, the DSMB has met.

It, it appears to be safe in terms of the intervention, and we hope to answer the heparin question soon in community-acquired pneumonia.

And we also have got some funding to do dexamethasone.