Tasly Biopharma signed license agreement with Sutro to introduce new ADC drug STRO-002

Tasly Biopharma signed license agreement with Sutro to introduce new ADC drug STRO-002

On December 24, Tasly Pharmaceutical Group Co., Ltd. (600535. SH) announced that its holding subsidiary Shanghai Tasly Biopharmaceuticals Co., Ltd. (hereinafter referred to as “Tasly Biopharma”) has obtained the exclusive license of the US Sutro Biopharma (hereinafter referred to as “Sutro”) to exclusively develop, register and commercialize an antibody-drug conjugate targeting folate receptor α (FRα) (hereinafter referred to as “STRO-002”) in the region (i.e., mainland China, Hong Kong and Macao Special Administrative Regions, Taiwan region), a kind of drug currently used in clinical studies for ovarian and endometrial cancer in Europe and the United States. Under the license agreement, Tasly Biopharma shall make an initial payment of $40 million and up to $345 million potential development and commercialization milestone payments, as well as an agreed percentage of sales.

As the leading innovative biopharmaceutical company in China, Tasly Biopharma with an aim to provide first-in-class/best-in-class biopharmaceuticals with reasonable prices for patients at home and abroad, is committed to meeting the growing clinical needs in the treatment of cardiovascular and cerebrovascular diseases, tumors, autoimmunity, digestion and metabolism diseases. At present, we have 16 biological drug pipeline products. The introduction of STRO-002 will form differentiation advantages, further broaden the Tasly biological cancer therapeutic drug product pipeline, improve the product portfolio and solve major unmet clinical needs.

01

ADC products are in the exclusive growth period with broad market prospects

In recent decades, tumor treatment models have been evolving rapidly, from the earliest chemotherapeutic drugs to small-molecule targeted drugs, a monoclonal antibody targeted drugs, tumor immunotherapy, etc.; meanwhile, the expectations of industry, supervision and patients for the clinical benefits of innovative therapies are also rising. ADC (Antibody-Drug Conjugate), as an innovative therapeutic method combining the advantages of targeted therapy and chemotherapy, can site-directed remove cancer cells and reduce the damage to normal cells, with high technical barriers. Recently, it has received significant attention from the pharmaceutical industry and has been approved for the market continuously. With increased enthusiasm for R&D and investment financing, the number of product transactions in the ADC field reached 34 in 2020, nearly twice as many as in 2019, and is expected to play an important role in the upgrading of tumor therapy in the future.

ADC is an innovative drug composed of antibodies, toxins, and linkers. Its concept was first proposed by Paul Ehrlich in the early 1910s and described as a “magic bullet”. However, due to the development bottlenecks of an antibody preparation, payload conjugation, and other technologies, the first ADC drug was not approved by FDA for marketing (Mylotarg) until 2000. Subsequently, ADC has entered into slow R&D progress, and the first solid tumor ADC was not available until 2013. In recent years, with the rapid development of monoclonal antibody drugs and the progress and breakthroughs in ADC key technologies, including cleavable linker, more effective and safer small molecule loading, and site-directed conjugation, ADC has been iterated to the third generation, and the pace of listing has been accelerated. Up to now, 14 ADC drugs have been listed worldwide, and more than 100 ADCs have been applied in clinical research, presenting an exclusive growth period for ADC. According to Clarivate’s estimate, global sales of currently marketed ADCs will exceed $16.4 billion by 2026.

02

With high product technical barriers and significant iterative advantages

STRO-002 is a third-generation ADC developed by Sutro with global intellectual property rights, wherein both cell-free protein synthesis technology used for antibody part of the product and ADC site-directed conjugation technology through unnatural amino acids have high technical barriers, and it is expected to solve the pharmaceutical quality and pharmacological problems of the product caused by traditional ADC non-site-directed conjugation. Reportedly, the conjugation methods of ADC mainly include non-site-directed conjugation and site-directed conjugation. Non-site-directed conjugation was the method used in early ADC development. Overall, the final products of non-site-directed conjugated ADCs are mixtures, including different DAR values (drug-antibody ratio) and different conjugation sites, performing poor stability, and they are prone to aggregation, besides, the cytotoxins are easy to fall off and produce non-therapeutic toxic side effects, with a narrow therapeutic window. Moreover, there also exist technical problems in the analysis, identification, and control of differences between production batches.

The linker employed by STRO-002 is a protease-cleavable Val-Cit-PABA, and its small molecule load is a derivative of the marine extract Hemiasterlin, specifically, a novel microtubule inhibitor and a weak substrate of the P-glycoprotein pump with the potential of anti-drug resistance.

With the assistance of Sutro, Tasly Biopharma will realize the technical landing production in the cooperative area, containing a series of leading technologies such as cell-free protein synthesis and site-directed coupling of unnatural amino acids.

03

Targeting folate receptors avoids competition for homogenization

The target of STRO-002, FRα, is tumor cell-specific, highly expressed in tumor tissues such as ovarian cancer, endometrial cancer, breast cancer, and non-small cell lung cancer, but not expressed or very lowly expressed in normal tissues, so targeted FRα is expected to specifically treat a variety of solid tumors including ovarian cancer, NSCLC, breast cancer, and endometrial cancer. Worth saying, FRα is an ADC target with less competition but a clear possibility of finished drugs, and it is available to avoid homogenization competition and form differentiation advantages. Currently, no ADC product targeting FRα has won the listing approval worldwide, and there are a total of 3 ADC products in the clinical stage. STRO-002 is the only product able to distinguish the expression level of FRα in patients in clinical trials at present, and it has the potential to become the best “best-in-class” of its kind.

04

The preferred development of ovarian cancer indications is expected to fill the clinical gap and enrich the treatment landscape

Indicating in the GLOBOCAN project statistics of the WHO International Agency for Research on Cancer (IARC), China found 55,300 new ovarian cancers, and 37500 died in 2020. The incidence of ovarian cancer is insidious. Due to the lack of effective screening and early diagnostic measures, 70% of patients are diagnosed at an advanced stage. Most patients with advanced ovarian cancer experience disease recurrence after platinum-based chemotherapy. Almost all patients with recurrent ovarian cancer will eventually develop platinum resistance.

According to the Guidelines for the Diagnosis and Treatment of Ovarian Malignant Tumors (2021 Edition), non-platinum chemotherapy or combination chemotherapy combined with anti-angiogenic targeted drugs is preferred for patients with platinum-resistant or refractory recurrent ovarian cancer. As shown in the guidelines and literature search, different studies had objective response rate (ORR) of about 10% ~ 25% and progression-free survival (PFS) of about 3-6.5 months after chemotherapy, but in limited benefit. Adding anti-angiogenic drugs could improve PFS, but the overall survival (OS) is not significantly improved. Overall, treatment options for advanced ovarian cancer are limited, and there exist significant unmet clinical needs.

Accordingly, STRO-002 is currently carrying out a phase I clinical study for recurrent ovarian cancer and endometrial cancer in Europe and the United States. The dose-escalation study for recurrent ovarian cancer was completed in August 2020. The relevant clinical data were published at the ASCO meeting in 2021. As revealed in data statistics, STRO-002 performs positive preliminary efficacy against platinum-resistant/recurrent ovarian cancer recurred after multiple lines of therapy with well safe tolerance. In this regard, Sutro intends to communicate with FDA to accelerate the approval and marketing of phase 2 single-arm study as a registered clinical application.

Furthermore, Sutro also plans to initiate a clinical study of STRO-002 later combined with Bevazimab for the treatment of recurrent ovarian cancer in the United States. What’s more, there is potential for STRO-002 to expand to other tumor indications such as triple-negative breast cancer and NSCLC with positive folate receptor α expression, and now, preclinical studies for NSCLC are undergoing.