Leade Bio Advances Phase II Candidate Tairilafeng to Address High Unmet Need in Stroke Treatment

Globally, stroke is the second leading cause of death among individuals aged 60 and older, as well as a major cause of disability.

Intravenous thrombolysis is currently one of the most primary measures for restoring blood flow; however, statistics show that only 2.4% of patients receive thrombolytic therapy, as most patients fail to seek hospital care and undergo thrombolysis in a timely manner. Neuroprotective therapy is currently the predominant treatment modality for stroke patients. Nevertheless, there are few clinically approved neuroprotective agents, even fewer with high efficacy, and the required treatment duration is prolonged. Even with treatment, it is estimated that more than 35% of patients will inevitably suffer from disability. Therefore, there is an urgent clinical need for neuroprotective therapies with breakthrough efficacy to reduce the risk of patient disability.

To address this clinical treatment gap, many domestic biotech companies are accelerating new drug development, aiming to break through the limitations in stroke therapeutics.Laide Biotechnology, a rising star enterprise, is one of them.

Laide Biomedical, established in 2022, specializes in the development of therapeutics for major diseases such as neurological disorders. Its core product, Tirilazad, is a best-in-class novel drug for the treatment of stroke that has currently entered Phase II clinical trials. Previous study results have confirmed that Tirilazad possesses potent oxygen free radical scavenging activity and a more favorable safety profile.

Recently, VCBeat interviewed Mr. Zhang Jian, Founder and General Manager of Laide Biomedical, who discussed the company’s founding vision, the current state of the stroke market, and the core competitiveness of Tirilazad.

Acute stroke is defined as neurological deficits resulting from acute focal injury to the central nervous system due to vascular causes. Ischemic stroke accounts for approximately 87% of all strokes, hemorrhagic stroke for 10%, and subarachnoid hemorrhage for 3%. Globally, there are 15 million stroke patients annually, and in the United States, someone experiences a stroke on average every 40 seconds.

In China, according to the "China Stroke Report 2020," there are approximately 28.76 million stroke patients in the country, with about 3.94 million new cases and around 2.19 million deaths annually. Additionally, as many as 77.7% of patients will experience lifelong sequelae.

Despite the large number of stroke patients, there are few approved therapeutic drugs available, failing to meet the current treatment gap.

“There are relatively few drugs for the treatment of stroke, primarily because there are limited mechanisms available for drug development, unlike oncology drugs, which have numerous targetable pathways,” mentioned Zhang Jian.It is reported that there are currently only about 85 stroke drugs approved or under development globally, with very few innovative drugs already on the market. In contrast, during the same period, there were as many as 720 drugs for solid tumor treatment that were either approved or in development.

However, Zhang Jian, who once worked at Simcere Pharmaceutical, saw a new opportunity in the potential of tirilazad for treating stroke.

In 2017, Zhang Jian discovered tirilazad and recognized its therapeutic potential. At that time, the drug was a Class 1 new drug invented by Nanjing Zhongrui Pharmaceutical Co., Ltd., and research data indicated that,Tirilazad possesses potent oxygen free radical scavenging capacity, significantly protecting neural cells from injury caused by cerebral infarction. It has the potential to further improve clinical outcomes in ischemic stroke and exhibits a favorable safety profile across a wide dosage range.More importantly,Preclinical study data indicate that the efficacy of terilavone is twice that of edaravone, the conventional first-line emergency medication for stroke patients.

This means that if terilafon is approved for marketing, it will have strong market potential.

At that time, China’s biopharmaceutical industry, particularly the research and development of innovative oncology drugs, was experiencing a surge in activity. However, Zhang Jian and Professor Su Guoqiang, the inventor of tirilazad and then-General Manager of Nanjing Zhongrui Pharmaceutical Co., Ltd., did not agree with the approach of blindly chasing hot trends. Instead, they aimed to promote genuine source innovation. In their view, tirilazad was an independently developed domestic product with potential therapeutic efficacy and broad market prospects. It focused on stroke, a field that was not currently trending but had long suffered from unmet clinical needs. Therefore, they believed that collaborating to bring tirilazad to market would provide more treatment options and hope for stroke patients.

Fueled by confidence in tirilazad, Laide Biomedical was established in 2022 after extensive preparations.

Currently, the drug classes for treating stroke include thrombolytic and anticoagulant agents, neuroprotective agents, anticoagulant factor inhibitors, and anti-cerebral edema drugs. Among these, edaravone, aspirin, and apixaban are the mainstays of current stroke treatment.

Among these drug classes, neuroprotective agents play an indispensable role. Oxygen free radical-mediated chain reactions are a significant cause of neural injury in acute cerebral infarction, particularly delayed neuronal injury. Therefore, the early administration of anti-free radical drugs to scavenge cerebral oxygen free radicals can mitigate ischemic injury from cerebral infarction and improve neurological function.

The most representative neuroprotective agent is edaravone, developed by Mitsubishi Pharma in Japan. Approved for market launch in 2001, this drug primarily works by scavenging oxygen free radicals and inhibiting lipid peroxidation, thereby preventing damage to brain cells.

“Tireravone was developed through structural modification of edaravone,” said Zhang Jian, “ButTirilazad has undergone a structural leap, resulting in physicochemical properties that are entirely distinct from those of edaravone, including differences in the mechanism of oxygen free radical scavenging, efficacy, and safety profile. Despite retaining the "-razad" suffix in its name, it is essentially a compound with fundamentally different characteristics.”

It is reported that, structurally, unlike edaravone'sProne to dissociation and electron loss,Tirzepatide has a rigid structure and does not dissociate; this characteristicIt addresses the limitations of existing drugs, including weak oxygen free radical scavenging capacity, molecular instability, and the need for high doses.

Current research data indicate that, in rat models, tirilazad can maintain high blood and intracranial concentrations at lower doses. Preclinical studies have shown that tirilazad is 2.4 times more potent than edaravone in scavenging oxygen free radicals. Multiple in vivo pharmacodynamic models have demonstrated that tirilazad significantly improves neurological deficits caused by ischemic brain injury and reduces the area of cerebral infarction. In terms of safety, tirilazad exhibited a favorable safety profile in Phase Ia clinical trials, with single doses escalated up to 480 mg. Zhang Jian stated that tirilazad even has the potential to surpass edaravone in both efficacy and safety.

Tirilazad has demonstrated significant therapeutic potential and development value in the treatment of stroke.

In addition to molecular innovation, Laide Biomedical has also innovated the administration route of terrelavone.

Currently, the treatment duration for existing neuroprotective agents is typically 14 days, with some regimens extending up to 90 days. Despite the prolonged treatment periods, clinical efficacy rates remain to be significantly improved. According to published literature, the clinical efficacy rate of most currently available neuroprotective agents is below 67%, whereas the efficacy rate of placebo is generally around 55%.

However, new scientific research indicates that there is still room for improvement in current dosing regimens. “Updated studies on the mechanisms of inflammation-induced injury and repair in stroke suggest that continuing free radical scavenging for more than 7 days during acute stroke treatment may be detrimental to neuroregeneration and functional recovery,” mentioned Zhang Jian. “Therefore, based on the potent efficacy of Tirilazad,Laide proposed a treatment regimen of “continuous administration for 72 hours within 24 hours of disease onset.””

Laide Biomedical proposed this plan based on three points of scientific rigor:

1. The blood-brain barrier in patients typically opens within 16–48 hours; administering medication within 24 hours of onset can fully leverage this time window, allowing more drug to enter the intracranial space over a longer duration.

2. Free radicals are primarily generated in an early explosive manner, and the harmful inflammatory state also mainly occurs in the early phase after stroke.Continuous administration to maintain stable and effective plasma drug concentrations can more effectively eliminate free radicals generated during the early burst phase;

3. The drug was administered for 72 hours rather than 14 days because the generation of oxygen free radicals in the brain occurs in two phases: those produced in the early phase exert detrimental effects on the brain, whereas those generated in the later phase can promote neural repair. Indiscriminate scavenging of these radicals may therefore hinder brain recovery.

“In fact, this dosing regimen is not applicable to all drugs. Its feasibility hinges on the ability to achieve substantial drug exposure; however, if a drug lacks high potency, it would require large doses to achieve therapeutic effects, inevitably posing safety risks. Tirilazad, by contrast, is highly potent and can deliver robust efficacy at lower doses, thereby eliminating concerns about the safety risks associated with the high doses required for such a regimen. Therefore, continuous administration over 72 hours to maintain stable drug concentrations demonstrates a favorable safety profile and is well-suited for molecules like tirilazad, which combine high potency with a strong safety margin,” said Zhang Jian.

Building on innovations in molecular structure and dosing regimens, Laide Biomedical has established multi-dimensional core competencies for Telitacicept:

First, since the mechanism of scavenging oxygen free radicals for ischemia-reperfusion injury has been proven effective, the clinical research risk of tirilazad is relatively low;

Secondly, tirilazad demonstrates a favorable safety profile. Currently, its Phase I clinical trials have been completed, and studies have shown that tirilazad for injection exhibits good safety in healthy subjects even at high doses and exposure levels.

Furthermore, tirilazad features a simple synthesis method, stable manufacturing process, and low production cost, thereby posing no concerns for industrial-scale production; if approved for market launch in the future, its price will be more controllable and affordable.

Meanwhile, Laide Biomedical has discovered that tirilazad not only holds therapeutic potential for stroke but also offers broader applicability across a wider range of disease areas, thereby generating greater long-term development value.

Currently, terilavon has entered Phase II clinical trials. Zhang Jian stated that the most urgent task for Laide Biomedical is to advance the clinical research progress of this product.

Meanwhile, Laide Biomedical has already begun expanding the indications for tirilazad. Its planned pipeline aims to provide comprehensive coverage across the entire spectrum of stroke care, ranging from early thrombolysis and acute-phase neuroprotection to recovery-phase neuroregeneration and thrombosis prevention in the recurrence phase. The company is also exploring innovative therapeutic approaches for other neurological disorders, including intracerebral hemorrhage, cerebral edema, and Alzheimer’s disease.

The emergence of any new drug is invariably accompanied by iteration and improvement. Jiangsu Laide Biomedical Co., Ltd. has already embarked on the development of a next-generation tirilazad, designed to enhance blood-brain barrier penetration and focus on hyperacute treatment of ischemic stroke.

However, Jiangsu Laide Biomedical Co., Ltd. is not solely focused on brain diseases or small-molecule drug development. In the future, it will also exert efforts in fields such as gene therapy and even bacterial therapy, expanding its product pipeline to ensure the company’s comprehensive development.