XiYuan AnJian Advances Global Phase I Trial for BR01T in Chronic Low Back Pain, Targeting Three Major Chronic Pain Areas

New Progress in the Development of New Drugs for Chronic Pain

Just recently, on December 13, Vertex’s stock price surged by 13% in a single day, pushing its market capitalization above $100 billion. This sharp rise in Vertex’s market value was primarily driven by favorable clinical data for its chronic pain drug, VX-548.

Analgesics have long been a highly competitive sector, characterized by widespread demand and substantial market potential. According to data from the International Association for the Study of Pain, one in five people worldwide experiences chronic pain. The Blue Book on China’s Pain Prevention and Control and Health Promotion Strategy: Report on the Development of Pain Medicine in China indicates that over 300 million people in China are suffering from chronic pain, with the number growing rapidly by 10 to 20 million annually. Pain has thus become the third major public health issue, following cardiovascular and cerebrovascular diseases and cancer.

There is a large population of patients with chronic conditions, yet awareness rates, healthcare-seeking rates, and complete remission rates remain low. For a long time, pain management relied primarily on opioid analgesics. However, as numerous issues associated with opioid use have emerged, non-opioid analgesic targets are gradually gaining attention and undergoing development.

However, the mechanisms of action for chronic pain medications are complex, and drug development is highly challenging, resulting in few new drugs being approved for market launch. The positive results from VX-548 have brought a glimmer of hope to the field of novel analgesics.

Not only that, the development of innovative drugs in the field of chronic pain in China has also seen good news.

In October 2023, Brise Pharmaceuticals announced the initiation of its first global Phase I clinical trial, codenamed MBR01T-101, and successfully completed dosing of the first patient in the United States. This Phase I trial, targeting patients with chronic lower back pain, employs a double-blind, randomized, placebo-controlled, dose-escalation study design. The trial aims to evaluate the safety, tolerability, and efficacy of BR01T in the treatment of chronic lower back pain.

Brise Pharmaceuticals is an innovative drug development company focused on the field of pain, dedicated to the discovery, development, and commercialization of novel therapeutics for chronic pain. It aims to provide physicians with rational and effective pain management strategies, thereby alleviating patients’ suffering.

Brise Pharmaceuticals focuses on targets in the pain field with well-defined human genetic and pathological mechanisms, selects optimal pharmacotherapies and routes of administration, and builds a globally leading R&D pipeline for pain treatments through in-house development, collaborative partnerships, and mergers and acquisitions. The company also employs flexible clinical trial strategies to enhance drug accessibility and commercial value.

Looking back at the evolution of the pain management field, although there were several blockbuster products in the early stages, the limited understanding of disease mechanisms and the lack of safe drug delivery methods have meant that no new blockbuster pain medications have emerged on the international market for over two decades.

The primary reason lies in the complex etiology of diseases causing chronic pain, with varying pathogenic mechanisms across different conditions; therefore, monotherapy generally fails to meet the needs for long-term pain control. Furthermore, the efficacy of traditional treatment modalities is often unsatisfactory, and the widespread use of opioid analgesics further exacerbates the risks of drug tolerance and addiction.

According to Dr. Li Guochun, China has more than 20,000 physicians practicing in the field of pain management and over 2,000 pain clinics, with more than 70% of secondary and tertiary hospitals equipped with such departments. However, as most pain specialists are transitioned from anesthesiology, rehabilitation, geriatrics, or even orthopedics, the development of pain treatment devices in China has far outpaced that of pharmaceuticals.

"Furthermore, the general public’s limited understanding of pain and inability to distinguish between pain types have contributed to widespread medication misuse, leading to a growing number of patients with deep-seated chronic pain. 'Chronic pain medications are held to high safety standards, and there is substantial demand for such drugs in pain management departments; however, we are currently facing a shortage of both medical resources and pharmaceutical options,' said Dr. Li."

In 2018, the World Health Organization (WHO) included chronic pain in the 11th Revision of the International Classification of Diseases (ICD-11) for the first time, classifying it as a distinct disease entity. The International Association for the Study of Pain (IASP) defines chronic pain as pain that persists or recurs for more than three months and has established subtypes of chronic pain, providing a crucial basis for developing corresponding diagnostic and therapeutic standards.

Meanwhile, new targets and pathways are entering the drug development pipeline, and opportunities in the field of chronic pain treatment are beginning to emerge. Taking migraine as an example, the role of calcitonin gene-related peptide (CGRP) in the pathophysiology of migraine has been elucidated. CGRP is a neurotransmitter with vasodilatory effects; its release levels increase significantly during migraine attacks, making it a key trigger for migraines. Clinical data on CGRP antibodies and small-molecule antagonists demonstrate that their clinical benefits in both preventive and acute treatment of migraine are significantly superior to existing therapies.

In May 2018, erenumab, the first CGRP-targeting drug co-developed by Amgen and Novartis, received approval from the U.S. FDA, thereby unlocking a blue-ocean market. Since then, multiple additional CGRP antibodies have gained FDA approval and achieved rapid sales growth. Reportedly, annual sales in this therapeutic area have already surpassed $4 billion and are projected to exceed $10 billion by 2027.

Li Guochun, Founder and CEO of Brise Pharmaceuticals, previously served as Chief Scientist at Yuheng Pharmaceutical and Principal Investigator at Novartis Pharmaceuticals in the United States. He possesses extensive expertise in the early-stage project initiation, antibody discovery, and engineering modification of biological macromolecule drugs. Later, he transitioned into the investment sector, becoming a Senior Partner at a leading domestic pharmaceutical venture capital fund, where he gained substantial experience in innovative drug-related investments and post-investment management. During his tenure at Yuheng Pharmaceutical, Dr. Li oversaw the entire process of innovative drug development. Within four years, he advanced the PD-1 antibody (zimberelimab) from preclinical IND filing to pivotal clinical studies, establishing it as the sixth domestically produced PD-1 inhibitor to reach the market. Additionally, in collaboration with WuXi Biologics, he successfully completed the overseas licensing deal for zimberelimab, valued at a total of $812 million.

Leveraging his extensive experience in both academia and industry, Dr. Li promptly recognized the therapeutic potential of CGRP-targeted therapies and the substantial unmet clinical needs behind them, deciding to launch a startup focused on this area. In 2021, Brise Pharmaceuticals was officially established and subsequently secured over RMB 100 million in financing, led by renowned investment institutions.

Focusing on unmet clinical needs in the field of chronic pain, Brise Pharmaceuticals has established a presence in three key segments: head and facial pain, musculoskeletal pain, and neuropathic pain. Based on the pathogenesis of different types of chronic pain, the company has developed multiple R&D pipelines targeting relevant therapeutic targets. These pipelines employ diverse molecular formats tailored to the characteristics of their respective targets, encompassing both large-molecule and small-molecule drugs.

According to Dr. Li Guochun, Brise Pharmaceuticals’ strategic rationale for focusing on three key therapeutic areas is primarily based on three factors: first, these markets offer substantial size and represent strong demand; second, there is a lack of innovative therapies and drugs; and third, although new drugs have been launched, they remain ineffective in over 50% of patients, indicating an area of unmet clinical need.

Meanwhile, the company’s pipeline strategy is guided by three key considerations. First, project selection is grounded in a solid scientific foundation, clear clinical needs, and viable commercialization prospects. Second, the pipeline is diversified, balancing early-stage certainty with long-term expansion potential. Third, the development pathway is well-defined, comprising assets ready for rapid commercialization as well as high-potential candidates that have attracted interest from multinational corporations (MNCs).

Brise Pharmaceuticals’ most advanced pipeline candidate, BR01T, is a breakthrough TrkA antibody. In October this year, the company announced that the first patient had been dosed in the U.S. as part of its global Phase I clinical trial.

It is understood that this Phase I trial, targeting patients with chronic lower back pain, employed a double-blind, randomized, placebo-controlled, dose-escalation study design. The trial aims to evaluate the safety, tolerability, and efficacy of BR01T in treating chronic lower back pain. By inhibiting TrkA in both acute and chronic pain states, BR01T selectively modulates key pain signaling pathways, providing optimal pain relief for patients while avoiding potential bone-related side effects. Consequently, BR01T introduces a novel mechanism of action and clinical option distinct from traditional opioids or nonsteroidal anti-inflammatory drugs (NSAIDs).

Another potential blockbuster candidate in Brise Pharmaceuticals’ pipeline is BR005, a next-generation small-molecule CGRP receptor antagonist. Compared with existing drugs, BR005 offers superior pharmacological and pharmacokinetic advantages and holds promise as an integrated therapy for both acute treatment and preventive management of migraine. An Investigational New Drug (IND) application has been submitted in China, with Phase I clinical trials expected to commence in the first half of next year.

Furthermore, BR007 is a bone-targeting small molecule conjugate drug that specifically inhibits TGF-β receptors in bone tissue cells. TGF-β receptors are widely expressed in the human body, participate in multiple signal transduction pathways, and perform diverse functions. By avoiding non-specific systemic inhibition of TGF-β, BR007 mitigates various severe side effects. Additionally, studies have shown that excessive activation of the TGF-β pathway is closely associated with a variety of bone-related diseases. Research on BR007 for the indication of progressive diaphyseal dysplasia will facilitate its expansion to a broader range of bone-related disease indications.

Notably, there are currently no approved drugs domestically or internationally for the treatment of various hyperostosis-related conditions, particularly osteoarthritis. In September 2022, BR007 was granted Orphan Drug Designation by the U.S. FDA. This designation marks the first orphan drug status awarded by the FDA to any Brise Pharmaceuticals project, representing a significant milestone for the company.

According to Dr. Li, the company expects to maintain a pace of launching blockbuster products into clinical trials annually over the next 2–4 years, thereby efficiently bringing its pain management pipeline to market.

Overall, Brise Pharmaceuticals’ product R&D strategy is primarily divided into three pillars: first, focusing on targets with well-defined human genetic and pain pathophysiology mechanisms; second, selecting the optimal therapeutic modalities and routes of administration; and third, building a globally leading pain treatment R&D pipeline through in-house development, collaborative partnerships, and mergers and acquisitions, while gradually establishing commercialization channels and systems in China.

It is understood that, in addition to new drug development, the company leverages its strengths in pharmaceutical R&D and clinical practice to actively collaborate with other pain management device manufacturers and digital health companies. By capitalizing on their respective advantages and achieving complementary synergies, these partners aim to address current shortcomings in pain management and provide patients with safer, more effective, and sustainable comprehensive management solutions.

The company’s product portfolio strategy is rooted in a unique operational approach. Unlike traditional innovative pharmaceutical companies that build their pipelines around specific technology platforms, Brise Pharmaceuticals adopts the U.S. “Hub & Spoke” model. It clearly defines milestone nodes and evaluation models for input-output analysis on a per-new-drug-project basis, enabling dynamic allocation of personnel and funding as needed.

This innovative model enables more convenient and flexible asset disposal and enhances liquidity, creating multiple exit pathways for shareholders to maximize returns. Meanwhile, the project-centric approach delivers its greatest benefit to enterprises by improving the “success rate” of new drug development and reducing associated risks.

In the future, Brise Pharmaceuticals will leverage its foundational research and medical insights in the field of pain disorders, along with its long-term accumulation of relevant clinical resources, to select product pipelines and clinical development pathways that best align with clinical use scenarios and offer the most viable commercialization routes. This strategy aims to develop more novel clinical drugs for chronic pain, ultimately benefiting patients.

“The pain management sector represents a large market, yet few players have strategically positioned themselves within it. While many perceive it as highly challenging, it is precisely during breakthroughs that opportunities arise,” said Dr. Li Guochun, founder of Brise Pharmaceuticals.