Established Pharmaceutical Company Makes a High-profile Entrance with "Unlimited" R&D Investment, Signaling an Imminent Explosion in This Emerging Field

Recently, Northeast Pharm announced its plan to acquire a 70% stock equity in Dingcheng Taiyuan for a total cash consideration of approximately RMB 187 million, thereby obtaining controlling stake in the company.

Dingcheng Taiyuan, founded in 2014, is a R&D enterprise focused on the development and transformation of solid tumor cell therapy products. According to available information, it has established a complete technical platform and product transformation system for TCR-T (T-cell receptor-engineered T-cell therapy) and CAR-T (chimeric antigen receptor T-cell therapy) cell therapy products.

Founded in 1946, Northeast Pharm is one of China's "four established pharmaceutical companies" and is renowned as the "cradle of the new China's national pharmaceutical industry". Starting from API, its current R&D pipeline has covered traditional pharmaceutical preparations. However, the company had no plans to venture into innovative drugs for many years. The purpose of this acquisition is to target TCR-T, and the company's responsible person stated that if the acquisition is successfully completed, sufficient funds will be allocated for scientific research and transformation, with "no upper limit". This represents a significant shift for Northeast Pharm, which has historically allocated less than 1% of its revenue to R&D.

So, what is the appeal of TCR-T?

R&D funds with "No Upper Limit": Established Pharmaceutical Company Seeks Opportunities for "Overtaking on the Curve"

Listed on the Shenzhen Stock Exchange in 1996, Northeast Pharm is a traditional pharmaceutical company whose main business is divided into pharmaceutical manufacturing and pharmaceutical commerce. In pharmaceutical manufacturing, the company focuses on API and preparations, producing a range of products including vitamins, anti-infectives, reproductive system medications, nervous system medications, digestive system medications, and biological diagnostic preparations.

In recent years, due to factors such as the in-depth advancement of national centralized procurement and the comprehensive implementation of generics consistency evaluations, competition in APIs and generics has intensified, prompting Northeast Pharm to undergo a transformation. The company aims to strengthen its R&D efforts in innovative drugs and high-tech generics.

In September 2022, Northeast Pharm announced an agreement with MedAbome in the United States, under which the latter will transfer its original antibody MAb11-22.1 to the former for the joint development of ADC and CAR-T cell therapy products. For this purpose, Northeast Pharm invested RMB 500 million of its self-owned funds to establish a wholly-owned subsidiary to advance the cooperation project for the introduced ADC drugs and CAR-T cell therapy technologies.

The acquisition of Dingcheng Taiyuan will give Northeast Pharm access to the latter's independently built core technical platform, enabling the development of TCR-T, TCR protein drugs, and CAR-T cell therapy products. It is reported that Dingcheng Taiyuan has developed 3 TCR-T cell therapy candidate drugs, DCTY1101, DCTY1102, and DCTY1103, targeting solid tumors such as pancreatic cancer and colorectal cancer.

In August of this year, DCTY1102 injection received a clinical trial implied permission from NMPA for the treatment of patients with advanced solid tumors positive for KRAS G12D mutation and the HLA-A*11:01 genotype.

Northeast Pharm stated that DCTY1102 has the potential to become the world's second and China's first TCR-T cell drug targeting KRAS-G12D to enter Phase I clinical research.

Furthermore, supported by Dingcheng Taiyuan's core technical platform, the TCR sequence discovery platform, the company has a reserve of over 30 sequence libraries, laying the foundation for future product transformation.

Whether Northeast Pharm's approach of taking a shortcut to introduce early TCR-T business will enable it to achieve overtaking on the curve in the field of cell therapy remains uncertain.

Targeting Solid Tumors: High Expectations for the TCR-T Race

TCR-T is an immunotherapy technology based on human T cells. It primarily uses gene editing technology to introduce T-cell receptor (TCR) genes that can specifically recognize tumor antigens into the patient's own T cells, enabling them to express exogenous TCRs and thus acquire the ability to specifically kill tumor cells.Currently, CAR-T, which has achieved great success in the field of hematologic tumors, has made slow progress in solid tumors due to the limitation of specific targets. In contrast, TCR-T recognizes polypeptide-MHC complexes, making it easier to infiltrate solid tumors and greatly broadening the targets for tumor immunotherapy. Additionally, TCR-T only mediates the release of a small amount of cytokines, resulting in superior safety.

In August of this year, with the FDA approval of Tecelra (Afamitresgene autoleucel, Afami-cel), a TCR-T therapy developed by Adaptimune Therapeutics, the TCR-T race witnessed a surge of enthusiasm.

Tecelra is the world's first TCR-T cell therapy approved for marketing. It is approved for second-line treatment of adult patients with unresectable or metastatic synovial sarcoma who have previously received chemotherapy and whose tumors express melanoma-associated antigen 4 (MAGEA4) and are positive for HLA-A02:01P, HLA-A02:02P, HLA-A02:03P, or HLA-A02:06P. This marks a significant milestone in the history of cellular immunotherapy.

Domestic TCR-T Therapy R&D Progress

Due to its unique advantages compared with CAR-T therapy, TCR-T therapy has attracted numerous pharmaceutical companies from both China and abroad to participate. In the Chinese market, TCR-T research ranks second only to the United States, making China the country/region with the second-highest number of TCR-T studies globally. Chinese companies such as XPH, TCRCure and UTC Therapeutics have all made layouts in this field.

XPH has garnered significant market attention with its TCR-T therapy TAEST16001. TAEST16001 is a self-developed TCR-T cell immunotherapy product by XPH that targets NY-ESO-1 with enhanced affinity. Its first clinical research indication is for patients with HLA-A*02:01-positive and NY-ESO-1 antigen-expressing advanced soft tissue sarcomas. TAEST16001 is the first TCR-T product in China to obtain an IND approval and the only TCR-T product in China to enter Phase II clinical research. 

TCRCure Biopharma Ltd. (hereinafter referred to as TCRCure) has developed multiple proprietary platforms such as TCR screening platform TRUST, cell transformation platform CHECK-T, cell transformation platform TURBO-T, virus transgenic vector production platform, and NK cell platform. Among its products, TC-N201 is an immunosuppressive molecule-modified TCR-T product developed for lung cancer and digestive tract tumors. TC-E202 is another TCR-T product by TCRCure, an engineered TCR-T cell that secretes anti-PD-1 monoclonal antibodies specific to HPV. It encodes both the HPV16 E6 TCR and the variable region fragment of the anti-PD-1 single-chain antibody. The modified T cells can also secrete PD-1 single-chain antibodies, effectively eliminating the inhibition of the tumor microenvironment, increasing T-cell infiltration, and enhancing the efficacy of TC-E202 against solid tumors.

UTC Therapeutics has developed the TCR-T product UTC-LS201, which integrates its own LACO-stim technology, with indications for NSCLC, ovarian cancer, and breast cancer.

Currently, TCR-T is still in the early clinical stages. However, since the approval of the first TCR-T therapy, the global cellular immunotherapy industry has been excited about its potential. In the next 3-5 years, TCR-T cell therapy is expected to experience explosive growth worldwide.

Primary references:

1. https://mp.weixin.qq.com/s/jjLeQJgp02vlhhgvD4eNcA

https://www.cde.org.cn/main/xxgk/listpage/da6efd086c099b7fc949121166f0130c.

2. Capital Games in Cell Therapy: The Highlight Moment and Market Reaction of TCR-T, Ouryao.

3. UTC Therapeutics: Seeking Up and Down, Only to Challenge the Difficulties of CAR-T Therapy in Solid Tumors, Yigu.

About  the Author    

Xiaobin

Xiaobin holds a Master's degree in Pharmacy and currently work as a public health control staff. Navigating through the intricate and complex data each day and feeling a sense of insignificance of herself. While being happy to witness the golden time of the development of Chinese bio-pharmaceutical industry. Hope to learn and improve together with everyone.