Spanish biotech firm aptaTargets is advancing a novel therapeutic approach for acute ischemic stroke with its lead candidate ApTOLL, an aptamer-based immune modulator designed to reduce brain damage following stroke events.
The company, which completed a Series B funding round in 2020 led by Inveready Asset Management and Spain's Centre for the Development of Industrial Technology (CDTI), is currently conducting a Phase Ib/IIa clinical trial to evaluate the therapy's efficacy in stroke patients.
Innovative Mechanism of Action
ApTOLL represents a departure from traditional stroke treatments by targeting the immune response that contributes to brain damage after stroke. The aptamer specifically antagonizes Toll-like receptor 4 (TLR4), a key mediator in the inflammatory cascade that occurs following cerebral ischemia.
By modulating this immune response, ApTOLL prevents the initial wave of inflammation that typically exacerbates neuronal damage after stroke onset. This approach addresses a critical unmet need in stroke care, where current treatment options are limited by narrow therapeutic windows and significant safety concerns.
Promising Preclinical Results
In experimental models of ischemic stroke, ApTOLL demonstrated remarkable neuroprotective effects, reducing brain damage by up to 65%. Particularly noteworthy is the drug's extended therapeutic window of 12 hours after stroke onset, significantly longer than the 4.5-hour window currently available for tissue plasminogen activator (tPA), the standard pharmacological treatment for ischemic stroke.
Clinical Development Progress
aptaTargets has made significant strides in bringing ApTOLL to patients since its founding in 2014 as a spin-out from Aptus Biotech. The company conducted its First-in-Human clinical trial (NCT04742062) in healthy volunteers during 2019 and 2020, confirming the therapy's safety profile.
Building on these positive results, aptaTargets initiated the APRIL study (NCT04734548), a Phase Ib/IIa trial in acute ischemic stroke patients. The Phase Ib portion of this study was completed in June 2021, with the Phase IIa component currently ongoing to establish clinical proof-of-concept.
Aptamer Technology Platform
ApTOLL leverages the unique properties of aptamers, which are synthetic oligonucleotides that fold into specific three-dimensional conformations. This structural complexity enables high affinity and selectivity for their targets, in this case, the TLR4 receptor.
Dr. María Pascual, Chief Scientific Officer at aptaTargets, explained, "Aptamers offer distinct advantages over antibodies, including greater stability, reduced immunogenicity, and more predictable pharmacokinetics. These properties make ApTOLL particularly well-suited for acute interventions like stroke treatment."
Addressing an Urgent Medical Need
Stroke remains a leading cause of death and disability worldwide, with ischemic strokes accounting for approximately 87% of all cases. Current treatment options are severely limited, with mechanical thrombectomy and tPA administration restricted to a small percentage of patients due to narrow time windows and contraindications.
"The development of ApTOLL represents a potential paradigm shift in acute stroke management," noted Dr. María Alonso de Leciñana, a neurologist at Ramón y Cajal Hospital and investigator in the APRIL study. "If clinical trials confirm the neuroprotective effects seen in preclinical models, we could significantly expand the number of patients who benefit from acute intervention after stroke."
Collaborative Development
aptaTargets' progress has been facilitated by strategic collaborations with academic and clinical partners. The company's drug development program began in partnership with Complutense University and Ramón y Cajal Hospital in Madrid, combining scientific expertise with clinical insights.
The 2020 Series B funding round has provided the financial resources necessary to advance ApTOLL through clinical development, with the potential to address a significant unmet need in stroke care.
Future Directions
While the current focus remains on establishing proof-of-concept in ischemic stroke patients, the TLR4-targeting mechanism of ApTOLL suggests potential applications in other conditions characterized by damaging inflammatory responses, including traumatic brain injury and certain neurodegenerative disorders.
As the APRIL study progresses, aptaTargets is positioned to potentially deliver a groundbreaking new therapy that could transform the treatment landscape for stroke patients, offering hope to millions affected by this devastating condition each year.
