ABM Therapeutics Files IPO Prospectus: Advancing Systemic BRAF Inhibitor ABM-1310 to Overcome the Blood-Brain Barrier in Metastatic Brain Tumors
Over the past century, continuous advancements in diagnostic and therapeutic technologies have improved survival outcomes for cancer patients in many scenarios. However, brain metastases remain a major challenge in modern oncology treatment. Due to the presence of the blood-brain barrier, most anticancer drugs exhibit poor brain penetration, failing to reach therapeutic concentrations. Statistics show that nearly 300,000 new cases of brain metastases occur annually in the United States alone, with a median overall survival of only 13–15 months and a five-year survival rate of less than 5%.
Clinically, the standard of care for patients with brain metastases under current conditions is radiation therapy. Conventional radiotherapy is associated with significant side effects, leading to a sharp decline in patients’ quality of life post-treatment, while chemotherapy options are limited to temozolomide or its analogs.
In late November, ABM Therapeutics, a domestic biopharmaceutical innovator focused on small-molecule drug development, announced that its self-developed next-generation BRAF inhibitor, ABM-1310, for the treatment of various malignant tumors and brain metastases, has received Investigational New Drug (IND) clearance from the U.S. Food and Drug Administration (FDA), paving the way for Phase I clinical trials. This announcement has drawn significant attention within China’s new drug R&D sector. VCBeat promptly contacted Dr. Chen Chen, founder of ABM Therapeutics, who shared insights into the company’s unique technological advantages and R&D strategies that have enabled the development of brain-penetrant targeted therapies.
Dr. Chen Chen, Founder of Bichen Pharmaceuticals
Bichen Pharmaceuticals, established in 2015, has set up operational centers in both the United States and China. Since its inception, Bichen Pharmaceuticals has built a robust R&D pipeline focused on brain-penetrant drugs capable of crossing the blood-brain barrier, through independent research and development as well as in-depth collaborations with CRO companies. Dr. Chen Chen told VCBeat that Bichen Pharmaceuticals will recruit patients with BRAF V600E/K gene mutations and launch a newly approved clinical trial at renowned cancer centers in the United States. “This is our first clinical project filed in the U.S.,” said Dr. Chen. He indicated that the company is evolving into a development platform for anticancer drugs and other small-molecule therapeutics capable of penetrating the brain, while actively seeking multi-level, multi-dimensional collaborations in both preclinical and clinical stages.
Brain tumors are classified into two types: primary and metastatic, with a patient ratio of approximately 1:20. Dr. Chen Chen pointed out that brain metastases are highly common in the later stages among patients with major organ cancers, such as lung and breast cancer. “Taking lung cancer as an example, most cases in China are induced by smoking, and the tumor cells are highly aggressive, making them prone to metastasizing to the brain.”
With advancements in imaging, primary brain tumors can be treated surgically, whereas metastatic brain tumors are often disseminated and typically do not meet the criteria for surgical intervention. Furthermore, the unique physiological conditions of the brain, including its oxygen- and glucose-rich environment and the presence of the blood-brain barrier, pose significant challenges to the pharmacological treatment of metastatic brain tumors.
On the one hand, although the human brain accounts for only about 3% of total body mass, it consumes more than 20% of the body’s oxygen and glucose during operation; this oxygen- and glucose-rich environment facilitates the rapid growth of brain tumor cells. On the other hand, the endothelial cells lining the cerebral blood vessels are tightly packed, with high expression of P-glycoprotein transporters. Abundant proteins fill the intercellular spaces, thereby blocking substances other than oxygen and glucose from entering the brain. Due to the strong self-maintenance capacity of neurons and other cells in the brain, most drugs fail to reach therapeutic concentrations. Only small-molecule drugs that utilize glucose transporters or possess characteristics such as small size, structural stability, and good water solubility can potentially penetrate the blood-brain barrier and enter the brain.
“For the past 50 years, the FDA has not approved any new drugs for brain metastases from cancer, and pharmacological therapy has yielded unsatisfactory results in prolonging survival among patients with brain metastases.” It was not until the 2018 ASCO Annual Meeting that the ALK inhibitor alectinib, in a head-to-head clinical trial against the first-generation ALK inhibitor crizotinib, demonstrated an extension of median progression-free survival (PFS) in lung cancer patients with brain metastases from 7.4 months to 27.7 months. This marked the first clinical validation that brain-penetrant anticancer agents can achieve nearly a 400% improvement in efficacy.
Dr. Chen Chen told VCBeat that the technical team at Bichen Pharmaceuticals, during the development of ABM-1310, used the efficacy of alectinib in treating brain metastases as a benchmark, aiming to achieve comparable or even superior therapeutic effects by targeting BRAF. In animal studies, the free concentration of ABM-1310 in the brain reached 100%. “Furthermore, preclinical animal data showed that, at equivalent doses, ABM-1310 more than doubled the survival time of experimental mice compared with vemurafenib, the first BRAF inhibitor approved by the U.S. FDA in 2011.”
It is understood that ABM-1310 has completed its Phase Ia clinical trial in the United States and will conduct a Phase Ib umbrella clinical trial in China, enrolling patients with various types of cancer to run concurrently. Dr. Chen Chen predicts that, given the current lack of approved therapies for brain metastases from tumors, if ABM-1310 yields favorable data in subsequent Phase II clinical trials, it may be eligible to directly submit a New Drug Application (NDA) for marketing approval.
The BRAF (V-raf murine sarcoma viral oncogene homolog B1) target selected for ABM-1310 is a member of the Raf kinase family and serves as the most potent activator in the downstream MAPK signaling pathway. BRAF mutations represent a major tumor driver, accounting for approximately 8% of all cancers, and are prevalent in melanoma, colorectal cancer, lung cancer, gliomas, and other malignancies, making it a well-established target in drug development.
Since the first-generation BRAF inhibitor vemurafenib was approved by the U.S. Food and Drug Administration (FDA) in 2011 for the treatment of melanoma, dabrafenib (2013) and encorafenib (2018) have also been successively approved. Currently, there are nine BRAF inhibitors in clinical development, three of which involve Chinese pharmaceutical companies, including BeiGene, Chia Tai Tianqing, Salubris, and Zeltis Biosciences.
According to Dr. Chen Chen, after repeated validation through scientific research and clinical practice, accurately grasping the biological principles of drug targets is an important foundation for drug development and innovation. “For some successfully launched innovative drugs, preliminary basic research centered on the target may have lasted up to 20 years. Meanwhile, there have been cases of clinical trial failures where certain candidates entered the drug development process without being fully validated scientifically.”
New drug development is a highly complex discipline that requires substantial investment of time and capital. Every decision made from the project initiation stage onward will ultimately determine the success or failure of a new drug. A technical team with comprehensive experience across the entire drug development lifecycle can proactively anticipate potential challenges during the R&D process, formulate mitigation strategies in advance, and maintain a steady momentum in the development pipeline.
At this stage, the overall level of new drug research and development (R&D) in China remains focused on improvement and differentiation. Dr. Chen Chen believes that this model aligns with the current characteristics of China’s new drug R&D ecosystem. “The development of entirely novel targets involves substantial capital investment, and there is significant uncertainty in translating basic research into pharmaceutical products. The high risks associated with early-stage investments place a considerable burden on the entire innovative drug ecosystem.”
Typically, drugs in early development based on novel targets can only address a portion of patients’ needs, leaving unmet clinical demands to gradually emerge. Compound optimization grounded in biologically relevant, comprehensive scientific understanding offers a solution to this challenge. Such optimization involves numerous critical decisions; given the considerable complexity of drug mechanisms of action, an incomplete understanding of biological mechanisms can compromise the accuracy of these decisions, ultimately affecting toxicity profiles, tolerable human doses, and final therapeutic efficacy associated with different molecular structures.
“New drug development relies on scientific advancements and a deepening understanding of therapeutic targets to enhance efficacy while reducing side effects,” emphasized Dr. Chen Chen. “The market return for such drugs will undoubtedly be substantial.” Bichen Pharmaceuticals has assembled a team of experts in the biopharmaceutical field, each bringing over two decades of experience in nervous system drug development, clinical trials for oncology drugs, and many years of corporate management expertise. By engaging in deep collaboration with Contract Research Organizations (CROs), the company is achieving innovative R&D breakthroughs in small-molecule drugs capable of crossing the blood-brain barrier.
Dr. Chen Chen earned his bachelor’s degree from the Department of Chemistry at Xiamen University and subsequently obtained his Ph.D. from the Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences. He has nearly 20 years of experience in the U.S. pharmaceutical industry, specializing in the research and development of small-molecule drugs for the central nervous system.
Prior to returning to China to launch his own venture, Dr. Chen Chen was employed at Neurocrine Biosciences, a NASDAQ-listed company specializing in the research and development of neurological drugs. He has published more than 110 research papers and holds 25 U.S. patents. Furthermore, Dr. Chen has developed multiple drug candidates that advanced through Phase I–III clinical trials, including elagolix, a treatment for endometriosis and uterine leiomyomas, which received FDA marketing approval in July 2018. According to forecasts by consulting firms, elagolix is projected to become a blockbuster drug with annual sales exceeding $1 billion.
In 2009, Dr. Chen Chen returned to China and served as the CEO of Sandia Pharmaceutical Technology (Shanghai) Co., Ltd. During his involvement in establishing Sandia’s new drug R&D department and managing its chemistry division, Dr. Chen observed significant limitations in existing oncology drugs for treating brain cancer or brain metastases from primary tumors elsewhere. He believed that optimizing the structure of oncology drugs based on design principles for central nervous system (CNS) small-molecule therapeutics could provide a strategic entry point into the field of brain tumor pharmacotherapy.
Since 2015, Dr. Chen Chen has led the team at Biopharm (Bichen Medicine) to modify tumor-targeted drug molecules that have proven clinically effective but fail to penetrate the brain, redesigning them into forms capable of effectively entering the central nervous system. Dr. Chen stated that the team’s practices over the past few years have preliminarily validated Biopharm’s methodology. “Moving forward, we will leverage our company’s technology platform to optimize a broader range of tumor-targeted drug molecules, aiming to overcome the blood-brain barrier.”
It is reported that Bichen Pharma has initiated a new round of financing, with the proceeds to be primarily allocated to the research and development and clinical trial advancement of ABM-1310 and other pipeline candidates in development.