BARCELONA, Spain — An experimental drug that takes a novel approach to protecting injured brain cells has shown promising results in an early Phase 2 trial of patients with acute ischemic stroke (AIS).

Known as Scp776, the drug is based on insulin-like growth factor 1 (IGF-1), which plays a key role in brain health by protecting neurons from excitotoxicity, hypoglycemic damage, oxidative stress, inflammation, and apoptosis.

In the Phase 2a ARPEGGIO study, the drug showed preliminary signs of neurologic improvement compared with placebo in patients with large-vessel occlusion (LVO) stroke treated within the late time window (up to 24 hours after symptom onset).

Those treated with Scp776 showed a trend toward better National Institutes of Health Stroke Scale (NIHSS) scores, which measure stroke severity, at 7 days, and improved modified Rankin Scale (mRS) scores, which assess functional outcomes, at 90 days.

The drug also appeared to be safe and well tolerated with no serious adverse events compared with placebo.

“This is a unique and innovative drug, and these early results are very exciting” lead investigator of the ARPEGGIO trial, study investigator, Eva Mistry, MD, associate professor of neurology at the University of Cincinnati, Cincinnati, told Medscape Medical News.

“Attempts at finding a treatment that prevents the death of injured brain cells in stroke patients have so far not been successful. But we are hopeful that this could be different. This is a really exciting opportunity, and the implications are huge,” she added.

The study was presented on October 23 at 17th World Stroke Congress (WSC) 2025.

A ‘Designer Drug’

Mistry described Scp776 as a “designer drug.” She explained that IGF-1 receptors are abundant throughout the body, and IGF-1 signaling is thought to play a key role in halting or reversing cell death. However, the therapeutic use of IGF-1 has been limited for several reasons.

Natural IGF-1 has a short half-life of about 15 minutes, meaning it doesn’t remain in the body for long, and because its receptors are widely distributed, drugs targeting them can cause off-target effects.

Scp776 is designed to overcome these limitations by extending the half-life of IGF-1 and directing it to the site of injury. To achieve this, the drug incorporates a compound called annexin V, which binds to phosphatidylserine — a molecule exposed on the surface of critically injured cells — enabling selective delivery of IGF-1 to ischemic brain tissue.

The drug’s third component is an albumin scaffold, which extends its half-life to approximately 8 hours. It has previously been tested in phase 1 studies involving healthy volunteers, and this marks its first evaluation in patients.

The goal of the ARPEGGIO study was to identify the best dose of the drug and understand more about its safety profile and explore its effects on neurologic outcomes.

The placebo-controlled, dose-ranging study included 119 patients with LVO AIS who underwent endovascular thrombectomy. The drug was administered as two intravenous bolus doses given 24 hours apart, with an average treatment time of 11 hours after stroke onset.

Because IGF-1 can lower blood glucose, the study protocol included a glucose management plan using intravenous dextrose to maintain levels above 80 mg/dL.

Three dose levels of Scp776 were initially tested against placebo in 87 patients. A blinded independent safety committee selected the mid-dose — consisting of a first bolus of 2 mg/kg followed by a second bolus of 1.8 mg/kg 24 hours later — for evaluation in a dose-expansion phase involving an additional 32 patients.

A ‘Very Reasonable’ Safety Profile

Mistry reported that adverse events were equally distributed between Scp776 and placebo, suggesting the drug had a “very reasonable” safety profile.

Exploratory neurologic outcomes included three efficacy measures: stroke severity, infarct volume, and long-term functional outcome.

“Overall, the patients who were treated with the selected dose of the drug did better in terms of all three outcomes, with two showing particular benefit — stroke severity and 90 day functional outcome,” Mistry said.

In the intention-to-treat analysis, patients receiving the selected Scp776 dose had a mean NIHSS score of 10.0 at 7 days compared with 11.6 for those receiving placebo — an adjusted reduction of 1.63 points.

In the per-protocol analysis, NIHSS scores were 9.4 vs 11.7, an adjusted difference of 2.26 points. The 90-day functional outcome, measured by the mRS, also suggested potential benefit.

The shift analysis — evaluating the overall effect across all six categories of the mRS — showed a favorable shift toward lower scores with the selected dose, yielding an adjusted common odds ratio of 1.22.

Good functional outcomes (mRS, 0-2) were achieved in 62% of patients in the treatment group compared with 54% of those in the placebo group, an absolute difference of 8%.

Although the findings were not statistically significant, Mistry emphasized that the phase 2 study was small and not designed to demonstrate statistical significance.

“However, the overall directionality of the effect in both the NIHSS and mRS scores is exciting and suggests that this drug has the potential to improve outcomes in these patients,” she said.

A Promising, but Early, Approach

“Targeting IGF-1 is a very promising approach. Observational data that suggests that IGF-1 levels are associated with better outcomes in stroke patients, but it hasn’t been possible to safely and specifically develop this strategy before. But now with advanced bioengineering techniques, this is an option,” Mistry added.

The company developing the product, Silver Creek Pharmaceuticals, said that future development of the drug will focus on confirming efficacy in the ARPEGGIO patient population, and expanding into broader populations of patients with stroke, including those who are treated with thrombolytics.

The company is planning to initiate a Phase 2b/3 registrational study in the second half of 2026.

Beyond stroke, the company is also exploring use of the drug in proof-of-concept clinical studies in ST-elevation myocardial infarction, traumatic brain injury, and other high-impact medical emergencies.

Commenting on the study for Medscape Medical News, chair of the WSC plenary session where it was presented, Craig Anderson, MD, George Institute for Global Health, Sydney, Australia, said the results were “encouraging” but that it is too early to call the research a breakthrough.

The ARPEGGIO study was funded by Silver Creek Pharmaceuticals. Mistry reported receiving consulting/advisory board fees from Silver Creek, Takeda, and CSL Behring.