Tianjun Yuansheng Files IPO Prospectus: Pioneering Blood-Based Early Detection of Alzheimer's Disease Up to 15–20 Years in Advance

During an exclusive interview with Li Juan, founder of Tianjun Yuansheng, we received the latest positive update from the company: Beijing Tiantan Hospital, Capital Medical University, has approved Tianjun Yuansheng’s “In Vitro Diagnostic (IVD) Project for Early Diagnosis/Blood Testing of Alzheimer’s Disease.” The expert review panel concluded that the project is significant and that the detection method represents a new technology.

In addition, Li Juan shared some good news: the “Chinese Expert Consensus on the Diagnosis and Treatment of Alzheimer’s Disease–Related Mild Cognitive Impairment (2021),” released in May 2022, has recommended plasma AD-related biomarkers such as p-tau181 and p-tau217 as diagnostic criteria for Alzheimer’s disease–related mild cognitive impairment.

In September 2021, more than ten Western research institutions jointly published a paper in *The Lancet Neurology*, concluding that blood-based detection of the biomarkers p-tau217 and p-tau181 can diagnose Alzheimer’s disease (AD) and differentiate it from other neurodegenerative disorders, such as frontotemporal lobar degeneration.

In the same month and year, a Chinese research team published a study on p-tau181 in the prestigious journal Frontiers in Neurology, titled “Plasma p-tau181 Level Predicts Neurodegeneration and Progression to Alzheimer’s Dementia: A Longitudinal Study.” The study concluded that plasma p-tau181, as a non-invasive biomarker, can be applied to the early detection of Alzheimer’s disease (AD). This finding is consistent with the results of collaborative research conducted by more than ten Western scientific institutions.

VCBeat has discovered that this domestic research team is the clinical research team of Tianjun Yuansheng, a high-tech enterprise specializing in the clinical translation of brain science technologies.

Li Juan, founder of Tianjun Yuansheng, stated, “Our teams in basic and clinical medicine have closely tracked international cutting-edge advancements since 1999 and conducted in-depth longitudinal research in the field of neuroimmunology. Today, our independently developed P-tau181 and P-tau217 assays are ready for clinical translation and are poised for industrialization.”

According to reports, Tianjun Yuansheng was established in November 2021. The company focuses on innovating early detection technologies for central nervous system (CNS) diseases and is committed to accelerating the widespread adoption in China of early diagnostic and companion diagnostic technologies for disease intervention in CNS disorders such as Alzheimer’s disease (AD), thereby championing indigenous Chinese innovation.

In 1907, Alois Alzheimer first presented the autopsy findings of a patient with Alzheimer’s disease at the Conference of Southwestern German Psychiatrists in Germany.

More than a century later, the global number of people with Alzheimer’s disease (AD) has exceeded 50 million, and this figure is projected to reach 152 million by 2050 (data source: Alzheimer’s Disease International).

In China, data from the "China Alzheimer's Disease Report 2022" shows that in 2019, the number of patients with Alzheimer's disease and related dementias in our country exceeded 13 million. In addition to the rapid increase in the number of cases, the harms of AD are gradually becoming apparent. In 2019, AD had become the fifth leading cause of death among the global population.

Although our understanding of Alzheimer’s disease (AD) is gradually deepening, the medical community has yet to achieve a breakthrough in AD. The etiology and pathogenesis remain elusive, there is a lack of objective, widely applicable diagnostic tools, and no curative treatment is currently available.

Li Juan stated, “Regarding the pathogenesis of Alzheimer’s disease, although there are five major pathogenic hypotheses, none of them can be verified at present. In addition, there are three major pain points in the treatment of Alzheimer’s disease.”

First, Alzheimer’s disease (AD) is highly insidious in its early stages, making it difficult for both patients and their families to detect. It is often only when memory or cognitive impairments begin to affect daily judgment that family members may start to recognize the presence of the disease. By this time, AD has generally progressed to the moderate stage, with varying degrees of cognitive decline already evident.

Second, to date, medications for Alzheimer’s disease (AD) are largely limited to symptomatic management and cannot reverse cognitive impairment or modify the disease course. Currently, no drug capable of improving cognition has successfully passed clinical trials, and it is unlikely that such products will receive regulatory approval in the near term.

Third, the social burden caused by Alzheimer’s disease (AD) is becoming increasingly severe, with a significant proportion of caregivers suffering from anxiety or depression. Regarding the social burden, the study “Reassessment of the Disease Burden of Alzheimer’s Disease in China and Worldwide” pointed out that in 2015, the annual per capita cost for Alzheimer’s disease patients in China was $19,144.36, and the total socioeconomic burden attributable to Alzheimer’s disease in the country reached $167.74 billion.

Regarding caregivers, a study in Europe and the United States showed that patients with Alzheimer’s disease and mild cognitive impairment require one dedicated caregiver, those with moderate impairment need two to three caregivers, and those with severe impairment require six to seven caregivers. This places an excessively heavy burden on families.

Additionally, statistical data from Professor Jia Jianping’s team at Xuanwu Hospital in 2018 showed that 30% of caregivers developed anxiety disorders and 30% developed depression. The first domestic “Survey Report on the Family Living Conditions of Patients with Alzheimer’s Disease,” released in 2020, indicated that 65.43% of caregivers saw no hope for treatment and experienced significant psychological stress; 68.69% reported adverse effects on their health; and 78.39% experienced disruptions to their social lives.

To address the aforementioned challenges, the most effective strategy is “early detection, early diagnosis, and early treatment.” Clinical experts in China have stated: “If patients with Alzheimer’s disease (AD) can be identified at an early or ultra-early stage, it will not only prevent delayed treatment and create opportunities for future pharmacological and non-pharmacological interventions, but also postpone AD onset by five years through early intervention, alleviate 35%–40% of sequelae and/or complications in AD patients, and reduce the number of AD patients by 57% and medical costs by 45% by 2050.”

Therefore, early detection and diagnosis have become new hopes for addressing the issue of AD.. However, at the current stage, the diagnosis of Alzheimer's disease primarily relies on medical history collection, physical examination, and cognitive scale assessment, lacking objective diagnostic tools.

Currently, the only objective tool is cerebrospinal fluid (CSF) testing; however, this method requires sample collection via lumbar puncture. Lumbar puncture not only necessitates performance under local anesthesia but also causes certain harm to patients, resulting in poor patient compliance and high procedural risk. Consequently, it is difficult to implement clinically as a diagnostic tool for Alzheimer’s disease (AD).

Recognizing these pain points, the core team founded Tianjun Yuansheng, aiming to provide a precise early diagnostic tool for Alzheimer’s disease (AD) patients worldwide. This tool facilitates earlier disease detection and timely clinical intervention and treatment, thereby slowing disease progression and reducing complications and sequelae.

Li Juan stated, “Since 1999, our team has continuously tracked cutting-edge international technologies and intensified research efforts. In 2012, we ultimately designated protein sites 217 and 181 as the targets for development, given that these two sites exhibit a linear relationship with the specific pathology of Alzheimer’s disease (AD), and their biomarkers can indicate AD.”

Following this, after a decade of exploration, the clinical research team finally obtained high-quality antibody pairs, providing the prerequisite for the translation of scientific achievements.

Based on the laboratory achievements of Beijing Tianjun Yuansheng Biotechnology Co., Ltd,In the future, screening for Alzheimer's disease will be diagnosable simply through peripheral blood testing, similar to routine biochemical assays.Laboratory data show that the results of peripheral blood testing are linearly correlated with those of cerebrospinal fluid testing.

So, what is the principle behind peripheral blood testing for Alzheimer's disease (AD), and what is its value?

To understand the principle of peripheral blood testing for Alzheimer’s disease (AD), it is necessary to first comprehend the two mainstream pathological hypotheses of AD: the β-amyloid (Aβ) cascade hypothesis and the hypothesis of abnormal tau protein phosphorylation.

Currently, the medical community has clearly established that abnormal substance deposition occurs in the brains of patients with Alzheimer's disease (AD), with the primary components being amyloid-beta (Aβ) and Tau proteins.

The amyloid-beta cascade hypothesis posits that the pathological process of Alzheimer’s disease (AD) is influenced by the interaction between amyloid precursor protein and Aβ. Aβ peptides accumulate in the brain, and once a certain threshold is reached, they cause the deposition of abnormal substances, ultimately leading to neuronal damage or death. This hypothesis is supported by experimental evidence.

The Hypothesis of Abnormal Tau Protein Phosphorylation posits that, under normal physiological conditions, tau protein is soluble and binds to tubulin to promote microtubule stability. In the brains of patients with Alzheimer’s disease (AD), tau protein undergoes phosphorylation, causing it to transition from a soluble to an insoluble state and become highly aggregated. This process leads to synaptic dysfunction and neurodegeneration, resulting in the formation of neurofibrillary tangles. Furthermore, tau protein phosphorylation is closely correlated with cognitive impairment throughout the course of AD.

On the other hand, after long-term research, the team at Beijing Tianjun Yuansheng Biotechnology Co., Ltd. found that blood p-tau181 is closely associated with Aβ deposition, while blood p-tau217 shows a strong positive correlation with both Aβ and Tau deposition.

Meanwhile, longitudinal data from the large prospective elderly cohort in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) estimate that plasma p-tau181 reaches abnormal levels 6.5 years and 5.7 years before cerebrospinal fluid (CSF) and PET detection of Aβ abnormalities, respectively, indicating that p-tau181 can predict AD approximately 6 years in advance. Another study showed that p-tau217 can predict AD 15–20 years in advance.

Based on the aforementioned hypothesis and its scientific findings, the scientist team at Tianjun Yuansheng believes that Alzheimer’s disease (AD) can be predicted 15–20 years in advance through testing reagents for peripheral blood-related biomarkers.This not only provides clinicians with an objective, user-friendly, and easily scalable tool for disease diagnosis, but also secures the golden window of opportunity for early intervention in patients. Early or ultra-early intervention can effectively slow disease progression, improve prognosis, and significantly reduce the disease burden.

It is worth noting that the concentrations of p-tau181 and p-tau217 in peripheral blood are extremely low, at the picogram level (1 picogram = one trillionth of a gram). Previous detection technologies were unable to measure concentrations at this level. In 2021, the U.S. FDA approved a device based on single-molecule array technology for clinical use in diagnosing neurological disorders using peripheral blood biomarkers. This technology enhances measurement sensitivity to the picogram level, making it particularly suitable for detecting central nervous system mediators with ultra-low concentrations in peripheral blood. The device also lays the foundation for peripheral blood testing for Alzheimer’s disease (AD).

In addition to U.S. companies developing single-molecule immunoarray technology devices, four domestic enterprises are also engaged in the research and development of related products, with two of them having entered the stage of clinical trial application approval. In March 2022, Beijing Tianjun Yuansheng Biotechnology Co., Ltd. signed a strategic partnership agreement with one of the companies that had applied for clinical registration, aiming to jointly promote the widespread adoption of peripheral blood-based central nervous system biomarker testing in China.

Currently, Tianjun Yuansheng’s peripheral blood testing reagents have entered the type testing phase and are poised to commence clinical trials.

In our interview, we found that Tianjun Yuansheng differs from other teams in that its core members all come from medical backgrounds. For instance, Li Juan has ten years of clinical practice experience in neurology; co-founder Zhao Yuqian was formerly a physician at the PLA 306 Hospital, where he served as Director of the Department of Scientific Training and later as Director of the Medical Affairs Office; Professor Li and Professor Xu are basic science and clinical science experts in the field of brain science, respectively, and both remain active on the front lines of research and clinical practice.

Unlike other startup teams, the core team of Tianjun Yuansheng is composed entirely of physicians who have been deeply engaged in the field of brain science for many years, possessing abundant clinical resources and extensive accumulation of research expertise in this domain.

It would be incorrect to assume that these physician-turned-entrepreneurs lack business experience. According to reports, founder Li Juan previously held administrative management roles at a mega state-owned enterprise directly under the State-owned Assets Supervision and Administration Commission (SASAC), which is listed on both the A-share and H-share markets, and served as the Director of Administration and Human Resources at a leading private hospital in China. Co-founder Zhao Yuqian has successfully launched startups three times, facilitating the clinical translation of four laboratory research achievements. He built a marketing team through acquisitions, achieving annual sales of RMB 600 million for a single product, and entered the in vitro diagnostics (IVD) industry in 2015.

It is evident that the team at Beijing Tianjun Yuansheng Biotechnology Co., Ltd. possesses not only extensive clinical resources and medical expertise but also rich experience in corporate operations and management.

We are confident that, with the efforts of the team at Beijing Tianjun Yuansheng Biotechnology Co., Ltd., its peripheral blood testing reagent products will successfully obtain regulatory approval and be widely applied in the early diagnosis of Alzheimer’s disease (AD) patients.

At the end of the interview, Li Juan stated, “Tianjun Yuansheng is currently undertaking a new round of financing, and the funds raised will be primarily used for the clinical trials of its peripheral blood testing reagent products.”