Bencao Bada Announces First-in-Class LAT1-Targeting Drug NBQ72S Completes First Patient Dosing in Global Phase I Trial for Brain Tumors

Brain tumors are considered the most challenging hurdle in oncology, as their unique location hinders conventional anticancer drugs from reaching the brain to exert therapeutic effects, which is one of the reasons why brain cancer remains difficult to cure.

Brain tumors are classified into primary brain tumors (originating from intracranial brain tissue) and metastatic brain tumors (resulting from the spread of malignant tumors from other parts of the body) based on their site of origin. Statistics indicate that approximately 10% of patients diagnosed with malignant tumors will develop brain metastases during disease progression. The likelihood of brain metastasis varies among different primary tumors, with lung cancer, breast cancer, and melanoma being the most common primary malignancies associated with brain metastases.

According to JAMA Oncology 2019（doi:10.1001/jamaoncol.2019.2996）Studies show that there are approximately 400,000 new cases of primary brain tumors globally each year, with over 240,000 deaths. China and the United States have the highest incidence rates worldwide. Moreover, the incidence of metastatic brain tumors is ten times that of primary brain tumors, and the number of patients is twenty times higher, indicating a significant unmet clinical need.

For instance, the current first-line treatment for glioblastoma multiforme (GBM), the most common primary brain tumor, primarily involves surgical resection combined with radiotherapy and chemotherapy. However, this therapeutic approach has significant limitations, with the vast majority of patients experiencing recurrence and encountering certain side effects. Furthermore, in the realm of brain cancer drug development, no innovative drugs have been approved for market entry as first-line treatments for brain cancer over the past several decades.

The presence of the blood-brain barrier prevents most anticancer drugs from entering the brain or significantly reduces their brain penetration, making it difficult to achieve effective drug concentrations in the brain and at brain tumor sites. Furthermore, the unique physiological conditions of the brain, such as its high oxygen and glucose levels, greatly increase the difficulty of treatment. There is an urgent market need for an innovative drug capable of crossing the blood-brain barrier, delivering precise anticancer effects, and demonstrating significant therapeutic efficacy.

How can high brain penetration of drugs be ensured while precisely killing brain tumor cells? This has become an insurmountable hurdle in the development of new drugs for brain cancer.

Recently, VCBeat (WeChat ID: vcbeat) learned that Nantong Bencao Bada Pharmaceutical Technology Co., Ltd. (hereinafter referred to as "Bencao Bada") announced itsGlobal First-in-Class Novel Drug NBQ72S for Brain Tumor Treatment Successfully Administered to First Patient, a Phase I clinical trial for the treatment of advanced malignant tumors is underway。

What is Bencao Bada’s strategy for overcoming the blood-brain barrier? In the race to develop new brain cancer drugs, what competitive advantages does Bencao Bada’s technology pipeline offer? To address these questions, VCBeat conducted an exclusive interview with Dr. Yan Shixiang, CEO of Bencao Bada and partner at Bencao Capital, who provides readers with insights into the most cutting-edge anti-brain cancer strategies.

To understand Bencao Bada’s strategy against brain cancer, it is essential first to grasp the fundamental reasons why the blood-brain barrier is difficult to overcome. The blood-brain barrier (BBB) is a selective “barrier” existing between the blood vessels and the brain that prevents certain substances (mostly harmful ones) from entering the brain from the bloodstream. This barrier typically allows only a very small fraction of low-molecular-weight substances to penetrate into the brain via passive diffusion, while essential nutrients required by the brain (such as glucose, amino acids, and nucleotides) are actively transported into the brain through carrier-mediated systems. Most drugs are blocked from entering the brain by the BBB; furthermore, the BBB expresses abundant efflux transporters and various drug-metabolizing enzymes, which further actively limit the efficiency of drug entry into the brain.

So, what kind of drugs can efficiently cross the blood-brain barrier and be delivered to brain tumor regions?Currently, the most advanced pipeline candidate under Bencao Bada, NBQ72S, is a first-in-class novel bifunctional small-molecule drug targeting human L-type amino acid transporter 1 (LAT1). LAT1 is a member of the solute carrier (SLC) superfamily and is typically highly expressed at the blood-brain barrier. It also exhibits markedly elevated expression in most aggressive malignant tumor cells, such as those found in glioblastoma multiforme, breast cancer, lung cancer, and melanoma.

Bencao Bada’s strategy adopts a small-molecule “ADC-like” drug design approach, combining a substrate structure capable of active transport across the blood-brain barrier via LAT1 with a cytotoxic moiety that kills tumor cells.

NBQ72S is efficiently and actively transported across the blood-brain barrier into the brain via LAT1, and selectively enters tumor cells with high LAT1 expression, thereby sparing normal tissues that typically do not express LAT1 from damage.Within tumor cells, NBQ72S acts throughInterfering with DNA replication in rapidly dividing tumor cellsExert its cytotoxic activity to kill tumors.

via transportersActive Transport Across the Blood-Brain Barrier, andPrecise Targeting of Tumor Cells for Specific Killing, which is why NBQ72S is referred to as a "dual-function" small-molecule drug.

Dr. Yan Shixiang also responded, “If we set aside the unique brain-penetrating capability of NBQ72S, its dual functionality can independently achieve precise killing of rapidly dividing tumor cells, which is similar to the mechanism of action of conventional targeted small-molecule anticancer drugs. At Nantong Bencao Bada Pharmaceutical Technology Co., Ltd., we are also exploring the clinical efficacy of NBQ72S in other cancer types, particularly in tumors with a high probability of brain metastasis. So far, the preclinical results of NBQ72S for brain metastases in triple-negative breast cancer have been very encouraging.”

It is reported that Nantong Bencao Bada Pharmaceutical Technology Co., Ltd. is conducting a Phase I dose-escalation clinical trial of NBQ72S, with a planned enrollment of 30 patients. The company intends to expand the drug’s indications to various central nervous system tumors in subsequent studies, including glioblastoma multiforme, brain metastases from lung cancer, and brain metastases from breast cancer.

In addition to serving as the CEO of Nantong Bencao Bada Pharmaceutical Technology Co., Ltd., Dr. Yan Shixiang is a partner at Bencao Capital and oversees its incubation and operations platform. With over 17 years of experience in drug R&D, management, and operations, Dr. Yan possesses profound expertise and extensive experience across all stages of new drug development and various therapeutic areas.

Bencao Bada was, more precisely, incubated by Bencao Capital. Established in 2015, Bencao Capital is a specialized fund dedicated to investing in globally leading life sciences and healthcare companies. It focuses on two key investment areas: innovative pharmaceuticals, and cross-disciplinary innovative medical devices and diagnostic technologies. The firm has extensive investment experience and resource accumulation across multiple fields, including new drug development, medical devices, clinical diagnostics, mobile health, and healthcare services.

Bencao Capital’s incubation and operational platform is centered on “empowering portfolio companies and translating cutting-edge science.” Leveraging Bencao Capital’s own industry talent resources, it fully harnesses the synergies between China’s and overseas advantages to more efficiently enhance asset and portfolio company value. Committed to improving the translation efficiency of top-tier biomedical sciences, the platform aims to incubate industry-leading companies.

“Not only do we invest in projects, but we also engage deeply and collaborate closely when the opportunity arises,” stated Dr. Yan Shixiang. “Nantong Bencao Bada Pharmaceutical Technology Co., Ltd. is actually the first enterprise we have incubated using this model. Based on our current operational experience, this innovative approach enables maximized resource utilization by fully leveraging the synergies between Chinese and international advantages. For instance, China offers high-quality, cost-effective, and efficient preclinical CRO services, along with a large patient population that facilitates rapid enrollment in clinical trials. Meanwhile, overseas partners bring extensive experience in medical translation and deep expertise in specialized niche fields. This integration of resources achieves high efficiency, which is highly beneficial for both capital investors and portfolio companies.”