ISC 2026 | Results of two Phase II trials of LT3001 for the treatment of acute ischemic stroke

We were very excited today to present the results of these two international Phase II studies. LT3001 is a very interesting molecule. It’s a smart molecule based on a redesign of a three amino acid small molecule, which is known to have thrombolytic effects. But this was modified so that the compound actually has thrombolytic, antithrombotic, and free radical scavenger neuroprotection effects. This compound has been studied in a number of labs, including Dr Yang’s lab at Mass General Hospital. And it’s been compared to tPA. Like tPA, within the typical tPA window, it has much of the effects of tPA. It decreases stroke volume, it leads to decreased neurologic dysfunction, and it leads to increased cerebral perfusion. But in the late window, around three hours, four and a half hours, even 24 hours after stroke onset, this compound appears to perform in the preclinical studies that we have done, the various rat models and other animal models, to perform much better than tPA, which is why we’re excited specifically much better reperfusion, decreased cytotoxic edema, increased reperfusion, and a much safer essentially minimal or no hemorrhagic transformation rate. So it’s a very interesting molecule going into these Phase II studies.

Now we’ve compared today the Chinese study which was the 202 study, with the 205 study, which was more of a global study in the United States, in Taiwan, and many other countries around the world. What’s important to understand is that based on the positive results of the Chinese 202 study, we early terminated the 205 study because of those positive results. So let’s talk about the 202 study. We looked at patients that had a wide range of inclusion-exclusion criteria. In both of the studies, we enrolled patients that were not candidates for endovascular therapy or IV tPA. They had an NIH stroke scale score between 4 and 25, based on a CAT scan aspect score of between 6 and 10. Now, in the Chinese study, we based inclusion specifically on their history, their exam, and only a plain CT. In 40% of the studies in the 205 American global study, we required a perfusion mismatch.

When we looked at the 90-day results and the primary outcome measure of the study was safety, we saw no increased risk across all the doses that we studied of any symptomatic hemorrhage. In the Chinese study, we looked at two different doses, a low dose and a high dose of LT3001. And at 90 days, we saw essentially zero increased symptomatic intracranial hemorrhage, which was measured by increased NIH stroke scale score associated with bleeding on a CAT scan at 36 hours. So no symptomatic hemorrhage. So we met our primary endpoint there and across the 205 study as well in the States and more globally, we saw no increased risk of symptomatic hemorrhage. So we met our primary endpoint in as much as we saw that there was no safety concerns with this compound.

We then did a deep dive looking at various efficacy signals. We specifically looked at the modified Rankin scale scores of 0 to 1 and 0, 1, and 2 at 90 days with the different doses. And what we found was a very strong signal across both doses. It is important to mention that in the baseline characteristics in the 202 and the 205 studies, that both the treatment arms and the control arms were very well matched. These were well matched within each study. So our major efficacy finding was in the 202 study, looking at all patients, there was a 7% absolute improvement in MRS scale score 0, 1, or 2 at 90 days in the treatment group above the placebo group, which was, we think, a very strong signal.

We were very interested in the subgroup analysis, and we looked at patients particularly that had significant weakness, and that was defined by the NIH Stroke scale score of greater than two in item five and in item six. Specifically, in item five, referring to the arm, we looked at the patient population that either had an NIH score item five of greater than two or NIH item greater than two in item six. So either arm weakness or significant leg weakness or significant aphasia. And what we found was across the board in the 202 study, it didn’t matter if we looked at arm weakness, or leg weakness, or combined them, or aphasia, in any of those groups, there was a very, very strong signal suggesting the benefit of LT3001 over placebo in both the MRS0-1 and the MRS0-2 in both dose ranges. So we were very, very encouraged by that finding.

So looking at the overall study, what we have determined that going forward into Phase III, which is exactly what our plans are, there seems to be a target population. The target population is patients that have significant disability, that have moderate-sized strokes, and lastly, if there is large artery involvement, we also saw a significant improvement in the effect. Specifically, in the 202 Chinese study, we did an analysis based on whether or not there was large artery involvement or there was not large artery involvement. Similarly, we looked at patients in the 205 study that had perfusion mismatch performed or not perfusion mismatch performed. And what we found was across both studies, a much more dramatic effect of the drug in the patients that had large artery involvement in 202, or if they had mismatch, significant mismatch differences in the 205 study, those two populations seem to be correlated with the best and the strongest signals of efficacy of this compound.

So going forward in designing 303, as we design the inclusion-exclusion criteria, we’re going to keep in mind exactly where we saw the strongest signals coming out of these two Phase II studies. It’s clearly in patients that have at least moderate stroke that have some evidence of large artery involvement as opposed to subcortical strokes and thirdly have a pattern of disability that puts them in the category where they’ll have significant weakness or significant aphasia. So moderate-sized strokes, significant disability, cortical involvement or large artery involvement, that seems to be the patient population we’re going to want to target going into the initial Phase III design. So with these very positive results, we’re quite excited that we are well prepared now to finalize the design for a pivotal international Phase III study. And as we said at the presentation today, upward and onward to Phase III, very excited to move this very interesting compound forward.

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