SANSAN Pharma Files IPO Prospectus Highlighting Record $1.25B Upfront from Pfizer for PD-1/VEGF Bispecific Antibody SSGJ-707

On May 20, 3SBIOINC and its subsidiaries, 3SBio Group and Guojian Pharmaceutical, signed an agreement with Pfizer to exclusively grant Pfizer the rights to their self-developed...Breakthrough PD-1/VEGF Bispecific Antibody SSGJ-707Development, production, and commercialization rights globally (excluding mainland China).

3SBIOINC and 3SBio GroupRetain the development, production, and commercialization rights of SSGJ-707 in China.Based on the financial terms to be agreed upon, 3SBIOINC will grant Pfizer the option to commercialize SSGJ-707 in mainland China.

According to the agreement, 3SBIOINC will obtainA non-refundable and non-deductible upfront payment of $1.25 billion, andUp to $4.8 billion in development, regulatory approval, and sales milestone paymentsThe company will also charge a double-digit percentage of tiered sales royalties based on the product sales in the authorized regions. In addition, Pfizer will...Subscription3SBIOINC Value$100 million worth of common stock。

Since Akeso's 500 million USD upfront payment for Ivonescimab, Limelight Medicine's 588 million USD overseas upfront payment for LM-299, and Promab Biotechnologies' 800 million USD prepayment for PM8002,This time, 3SBIOINC's SSGJ-707 has set a new record for the upfront payment of domestically produced bispecific antibodies going overseas, with an upfront payment of 1.25 billion US dollars.

SSGJ-707 is a bispecific antibody targeting PD-1/VEGF developed by 3SBIOINC based on its CLF2 patent platform, which can simultaneously inhibit the dual targets of PD-1 and VEGF.

Phase II clinical interim analysis data show that SSGJ-707 has achieved excellent Objective Response Rate (ORR) and Disease Control Rate (DCR) in the treatment of Non-Small Cell Lung Cancer (NSCLC) patients. Whether used as a monotherapy or in combination with chemotherapy, it demonstrates significant anti-tumor activity and good safety, showing best-in-class potential.

In February this year, 3SBIOINC and Baili Tianheng reached a cooperation to jointly advance the combination therapy of SSGJ-707 and BL-B01D1 (a bispecific antibody ADC targeting EGFR×HER3) for the treatment of solid tumors.

In April this year, SSGJ-707 received the Breakthrough Therapy Designation from the National Medical Products Administration (NMPA) for the first-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) with positive PD-L1 expression. Previously, SSGJ-707 had obtained IND approval from the FDA.

Except for small cell lung cancer, the clinical research of SSGJ-707 for the treatment of colorectal cancer, endometrial cancer, ovarian cancer, and other fields is also underway.

The CLF2 patent platform is Guojian Pharmaceutical's Common Light Chain Linear Fab x2 bispecific antibody platform. A related paper was published in the mAb journal in 2022.

The CLF2 platform is built based on the unique properties of Guojian Pharmaceutical's anti-PD-1 monoclonal antibody 609A. It links the heavy chain of 609A Fab to the heavy chain of another monoclonal antibody and replaces the light chain of 609A Fab with the light chain of this monoclonal antibody, forming a tetravalent "2+2" symmetric bispecific antibody structure with a common light chain.

First, the anti-PD-1 antibody 609A it is based on possesses strong anti-tumor activity and unique properties. When 609A binds to the antigen PD-1, it primarily relies on the heavy chain; even when its light chain is replaced by the light chain of another antibody, the antibody still maintains a potent effect on PD-1. Moreover, compared to the two marketed anti-PD-1 antibodies, nivolumab and pembrolizumab, 609A binds to a different site on PD-1 and has demonstrated stronger tumor activity than these two antibodies in a humanized PD-1 mouse model.

Secondly, due to the symmetric design using a common light chain and an antibody structure similar to IgG, bispecific antibodies produced through CLF2 can effectively avoid mispairing issues between different chains. They can be directly expressed in CHO cells, with fewer impurities for easier purification, offering significant advantages in production efficiency and cost. Among the two designed bispecific antibodies, the monomeric fraction content after one Protein A purification was over 99%, and they remained stable at room temperature.

Third, the bispecific antibody designed on the CLF2 platform demonstrated stronger biological activity both in vivo and in vitro compared to its corresponding two monoclonal antibodies. For instance, the bispecific antibody targeting PD-1×PD-L1 showed EC50 values for binding to PD-1 and PD-L1 that were very close to those of 609A and the PD-L1 monoclonal antibody used with their respective targets. However, beyond this, the bispecific antibody can also bridge PD-1 and PD-L1, mediating the formation of PD-1 clusters, thereby exhibiting a stronger ability to stimulate IL-2 and IFN-γ secretion than monoclonal antibodies—a function that a mixture of two monoclonal antibodies lacks.

3SBIOINC's 2024 annual report disclosed that its revenue reached 9.11 billion yuan, increasing by 16.5% year-on-year; gross profit reached 7.83 billion yuan, rising by 17.9% year-on-year; net profit attributable to shareholders reached 2.09 billion yuan, up by 34.9% year-on-year, maintaining a stable and continuous growth trend.

On one hand, as one of the first biopharmaceutical companies in China to enter the recombinant protein market, 3SBIOINC has already established a key market in its early stages — its products in the two major blood-related fields of erythropoiesis-stimulating agents and thrombopoietic agents continue to hold the leading position in their respective categories, forming a stable and continuously revenue-generating cash flow business. Additionally, Guojian Pharmaceutical's TNF-α inhibitor Yisaipu and anti-HER2 monoclonal antibody Saiputing maintain steady growth in an increasingly competitive market.

On the other hand, as one of the early players in China's biopharmaceutical industry, 3SBIOINC has also been an early mover in the field of advanced macromolecular drugs. For instance, the CLF2 patent platform dates back to 2021 or earlier. SSGJ-705 (HER2/PD-1 bispecific antibody) and SSGJ-706 (PD-1×PD-L1 bispecific antibody) both received IND approval in both China and the U.S. in 2021.

Meanwhile, since 2023, 3SBIOINC and its subsidiaries have been actively engaged in BD-related activities: In November, they reached a strategic cooperation and exclusive licensing agreement with CStone Pharmaceuticals for nofazinlimab (anti-PD-1 monoclonal antibody) in mainland China; In December, they entered into a licensing agreement with SiAn Medical Technology to obtain exclusive rights for the development, registration, production, and commercialization of its self-developed CS1/BCMA dual-target CAR-T (SA102) in Greater China; In the same month, they collaborated with Zenith Pharmaceutical on technical development, commercialization, and other aspects regarding its self-developed Eltrombopag Olamine for Oral Suspension (oral small molecule TPO receptor agonist/TPO-RA).

It is not difficult to see,Whether it is out-licensing or pipeline acquisition, 3SBIOINC's commercialization layout in the pipeline shows a trend of focusing on Greater China.Reflected in this transaction with Pfizer, 3SBIOINC has temporarily retained the commercial rights of SSGJ-707 in mainland China.

In terms of independent research and development, multiple pipelines are gradually entering the NDA harvest period, which will form a multi-level and multi-field innovative drug revenue stream in the future. The layout of monoclonal antibodies in the autoimmune field is rich, and the next BD target may emerge from this, including early pipelines with dual filings in China and the US — the highly sought-after target IL33, the star target TL1A, and the promising target BDCA2 for lupus erythematosus.

When the starting gun fires and multiple mature Chinese pharmaceutical companies join the BD battle, will the criteria for crossing the finish line change?

References:

Guojian Pharmaceutical "The Results of CLF2, a Bispecific Antibody Platform Independently Developed by Guojian Pharmaceutical, Published in the International Academic Journal mAbs"

Deep Blue View: "Established Pharmaceutical Companies, New Stars in Bispecific Antibodies"