But what is the difference between the, quite often people see on their reports when they access their own records, T2 lesions or gadolinium enhancing lesions, Also, they hear that black holes, T1 lesions, so what is that?

Yeah, so these are a little bit more technical descriptions of what lesions look like.

And so one of the sequences, and so MRI, I think of the different sequences as different staining.

So if you think about, perhaps if you're thinking about wood, you can use different staining on wood and it will bring out different things.

And those different sequences are similar in MRI.

We use a T2 sequence, which is very sensitive at picking up lesions.

And all that means is that lesion, T2 lesion, means it's a lesion that's there.

How often MS people should have MRI scans? And should they all have with a contrast or non-contrast? How does that work in service? Yeah, so I think

What was sort of the process to actually come up with this rationale for doing trials in this way?

Yeah, so I think the idea of applying these trials is something that in neurology we've learned from different fields.

So this has been something that has been used now in several different fields of medicine.

And the reality is when you have a significant unmet need, you want to accelerate clinical trial development.

That is, you want to try to get trials working in as quickly as possible and also make them as financially viable as possible.

And I think that's where the rationale for these multi-arm, multi-stage studies exist.

The traditional way of doing clinical trials is where one starts with a phase two trial, one completes a phase two trial, and then does a completely different phase three trial.

And then, as said, if agents do pass the interim, of course, there's no guarantee there will be phase three success, but at least we've had a first look, as it were, and we have more confidence that there will be phase three if they pass the interim outcome.

So before we jump into any of the actual findings specifically, just give a little bit of background for our audience on just kind of the goals and the intentions behind this study in general.

Yeah, so you might be familiar, Marco, about and your audience is likely familiar with the 2024 revisions to the McDonald's criteria.

And those were published last year and they included several changes and principle among them and probably the largest philosophical change is that we can now make a diagnosis of multiple sclerosis in individuals who are asymptomatic and have incidentally been found to have lesions on MRIs of the brain, and also in individuals who have what we call are symptoms not specific for MS.

And these could be symptoms of either short duration or might not get to the bar of what we call a typical clinical attack or progression of neurological symptoms.

And as a reminder, the 2017 criteria, so the previous iteration, required you to have either a typical attack or progression from onset in order to be in the diagnostic criteria.

So really a big departure from that.

And so what we were hoping to do with this study, we made use of our data set, which is the CABS-MS study.

So, you know, just talk a little bit about some of that application when you do have a patient who might be kind of sitting in that 50-50 gray zone per se.

Like, what are the pearls that we need to have in our mind?

Yeah.

I think when we think about starting the disease-modifying therapy in an individual who has a, an active form of, of multiple sclerosis, I think, you know, one of the cornerstones, I would say, of making that decision is shared decision-making.

I think we tend to sit down with the patient and analyze the data that we have at hand, what we know about their multiple sclerosis, and we use several factors to inform how likely we think their disease is gonna be active or potentially might not respond to the initial treatment you give.

And we look, uh, heavily at the MRI.

The MRI is really a useful marker because it shows us, one, how many lesions a person might have, both, you know, where those lesions are and also kind of the amount of lesions.

Lesions certainly that are in the spinal cord, a very large burden of diseases.

Dan, any other thoughts?