Pipeline Strategy and Progress

Our pipeline strategy is to build a risk-controlled clinical-stage pipeline with an exclusive focus on novel or highly differentiated biologics. To achieve a delicate balance between exclusive positioning of highly innovative therapeutics and the related development risk, we have built a globally competitive biologics pipeline comprising a risk-controlled and “fast-to-market” China Portfolio and a transformational “fast-to-PoC (proof of concept)” Global Portfolio.


China Portfolio

  • Novel or highly differentiated
  • Clinically advanced assets entering Phase 2/3
  • Addressing highly unmet medical needs
  • Controlled development risk
  • Aiming for product launches from 2021 and onwards

Global Portfolio

  • Novel or highly differentiated
  • Assets mostly discovered and developed in-house
  • Possessing full or shared global commercial rights
  • Aiming to conduct Phase 1/2 clinical trials in US
  • Multiple assets to enter clinical development in 2019

These two strategies and the resulting two portfolios complement each other. This enables us to achieve a balance among our ambition to develop novel or highly differentiated drugs, and our goal of efficiently advancing our pipeline assets towards commercialization while navigating the inherent development risks.

China Portfolio

The fast-to-market China portfolio is built around in-licensed investigational drugs that have demonstrated a favorable clinical safety profile and preliminary efficacy data in phase 1 or 2 trials in the US, Europe, or elsewhere. I-Mab only selects candidates with the potential to become novel or highly differentiated therapeutics for urgent unmet medical needs in China. Then, through in-house R&D and drawing on I-Mab’s deep knowledge and past experiences of the requirements for drug approval by the National Medical Products Administration (NMPA), the company builds additional data packages for late-stage clinical trials to support product registration. I-Mab’s direct access to Chinese clinical trial networks, combined with its insights into the Chinese regulatory environment, guides investigational drugs through this complex terrain.

The China portfolio today comprises five investigational drugs that are either in, or ready to enter, clinical trials in Greater China.

I-Mab plans to rapidly advance the China portfolio to NDA approval, and expects all the clinical assets in the China portfolio to undergo Phase 2, 3, or registrational trials in 2020, with NDAs to the NMPA being filed in sequence between 2021 and 2024. I-Mab will initially partner with a specialty pharmaceutical company with commercial experience and infrastructure in China to jointly market these products.

KEY

  • PRE-CLINICAL :
  • PHASE 1:
  • PHASE 2:
  • PHASE 3:
  • Marketed:
Drug Candidate
Novelty or
Key Differentiation
Indication
Therapeutic Area
Global Development
Phase
China Development
Phase
Candidate
Differentiation
Indication
  • TJ202 Differentiated CD38 mAb
    - Short infusion time (0.3 – 2 hrs), lower IRR (7%)
    - Potential for SLE by targeting pathogenic B cells
    Multiple myeloma /
    Autoimmune diseases

    TJ202:A Potential Highly Differentiated CD38 Antibody for Multiple Myeloma and Autoimmune Diseases

    TJ202 was originally developed by MorphoSys and showed favorable clinical safety and efficacy data from a clinical trial conducted in the European Union (EU). We own an exclusive license right to develop TJ202 in Greater China to address the current unmet needs and commercial opportunities in China for multiple myeloma and potentially autoimmune diseases, such as systemic lupus erythematosus (SLE). As shown in a Phase 1/2a study in adult patients with relapsed or refractory multiple myeloma (MM) in Austria and Germany, TJ202 is highly differentiated from the currently marketed CD38 antibody, with shorter infusion time (0.5–2 hours, compared with 3.5–6.5 hours) and lower infusion reaction rate (7% compared with 48%) under a similar pre-medication condition with dexamethasone, anti-pyretics and antihistamines. Unlike the currently marketed CD38 antibody, TJ202 does not down-regulate CD38 expression on the surface of bone marrow myeloma cells in vitro, maintaining sensitivity of myeloma cells to TJ202 for repeated treatments. 

    We have initiated a Phase 2 registrational trial as a third-line monotherapy, and a Phase 3 trial in combination with lenalidomide as a second-line therapy, both in patients with MM in Greater China. We aim to submit an NDA for TJ202 as a monotherapy in 2021, followed by another NDA submission for TJ202 as a combination therapy. An IND application for a trial in SLE is expected to be submitted in the fourth quarter of 2019.

    Clinical Trials:

    TJ202 Combined With Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma

    NCT03860038

    TJ202, Lenalidomide and Dexamethasone vs. Lenalidomide and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma

    NCT03952091

  • TJ101 Long-acting growth hormone
    - Convenient weekly dosing, better compliance
    - Potential better safety over pegylated hGH
    Pediatric growth
    hormone deficiency

    TJ101:A Potential Highly Differentiated Long-Acting Growth Hormone for Growth Hormone Deficiency

    Originally developed by Genexine, TJ101 (INN: eftansomatropin) is a long-acting recombinant human growth hormone (rhGH) with a novel molecular format of the hyFc-fusion technology. We own the Greater China rights to develop TJ101 as a weekly treatment for pediatric growth hormone (rhGH) deficiency. TJ101 is superior to the existing daily injection of rhGH for convenience of usage and patient compliance, and has potentially better safety as a pegylated formulation. 


    Currently, only 3.7% of pediatric patients with growth hormone deficiency receive growth hormone therapies, mostly on daily regimen. The advantages of TJ101 have significant clinical relevance to address an important clinical need and to cover a significant market gap.


    TJ101 has demonstrated safety and preliminary efficacy in three multi-regional clinical trials conducted by Genexine in Europe and Asia. In a previous Phase 2 trial conducted by Genexine, both weekly and bi-weekly administration of TJ101 demonstrated similar efficacy to daily injection of Genotropin, a short-acting rhGH. TJ101 has a good safety profile with no study drug-related serious adverse events, and its tolerability is consistent with known properties of marketed rhGH products. We expect to submit an IND for a Phase 3 registrational trial in China by in 2020.


    Clinical Trials:

    A Clinical Study in AGHD to Assess Safety, Tolerability and Efficacy of GX-H9

    NCT02946606

    Dose Finding Study of GX-H9 in Paeditaric Patients With Growth Hormone Deficiency

    NCT03309891

  • TJ301 Differentiated soluble gp130 IL-6 inhibitor
    - Novel MoA through trans-signaling pathway
    - Better safety profile with highly differentiated potential
    Ulcerative colitis /
    Auto-immune disease

    TJ301:A Potential Highly Differentiated IL-6 Blocker for Ulcerative Colitis and other Autoimmune Diseases

    In-licensed from Ferring, TJ301 (INN: olamkicept) is the only clinical-stage selective and highly differentiated interleukin-6 (IL-6) inhibitor, owing to its novel mechanism of action on the trans-signaling pathway. Compared with the approved antibody drugs that directly block IL-6 or IL-6 receptor, TJ301 is expected to provide a better safety profile for the treatment of IL-6-mediated inflammation without affecting some of the normal physiological functions of IL-6, such as acute immune response against infection and metabolic regulation.


    TJ301 was well-tolerated in three clinical trials conducted in Germany involving 128 subjects, including two Phase 1 trials and one Phase 2a biomarker study (FUTURE study). No apparent dose-related AEs were observed. Promising interim treatment effects of TJ301 were observed in both ulcerative colitis (UC) and Crohn’s disease patients in the FUTURE study.


    TJ301 is expected to have applications in a broad spectrum of autoimmune disease indications. We have initiated a multi-regional Phase 2 clinical trial in Taiwan, South Korea, and China. We expect to obtain interim data from this Phase 2 clinical trial by in 2020. After clinical efficacy and differentiation are validated for UC, we plan to develop TJ301 in other inflammation indications in which the pathogenic role of IL-6 is implicated.


    Clinical Trials:

    Safety and Efficacy of TJ301 IV in Participants With Active Ulcerative Colitis
    NCT03235752

  • Enoblituzumab Most advanced B7-H3 mAb
    - T cell activation combined with tumor killing
    - MoA with broader tumor indications
    Head and neck
    cancer / Oncology

    Enoblituzumab :The Most Advanced Clinical Stage Humanized B7-H3 Antibody as a Potential Immuno-oncology Treatment

    Originally developed by MacroGenics, enoblituzumab is a humanized antibody directed at B7-H3, a member of the B7 family of T-cell checkpoint regulators. B7-H3 is widely expressed across multiple tumor types and plays a key role in the regulation of immune response against cancers. We recently acquired the development and commercial rights of enoblituzumab from MacroGenics for Greater China.


    As the only conventional B7-H3 antibody in clinical development worldwide, enoblituzumab is the most advanced clinical-stage anti-cancer immunotherapy for a variety of solid tumors that overexpress B7-H3. In multiple clinical trials conducted by MacroGenics, enoblituzumab has shown a well-tolerated safety profile and preliminary clinical efficacy. It increased CD8 T-cell infiltration in tumors with more focused T-cell repertoires in patients treated with enoblituzumab as a monotherapy. A combination therapy with enoblituzumab and pembrolizumab correlates with preliminary efficacy signals in recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) and non-small cell lung cancer (NSCLC).


    We plan to submit an IND for a Phase 2 or registrational trial in China if approved by the NMPA in patients with recurrent or metastatic SCCHN. Further clinical development is being planned together with MacroGenics to extend to other cancer indications in China and globally.

    Clinical Trials:

    Safety Study of Enoblituzumab (MGA271) in Combination With Pembrolizumab or MGA012 in Refractory Cancer
    NCT02475213


    Neoadjuvant Enoblituzumab (MGA271) in Men With Localized Intermediate and High-Risk Prostate Cancer
    NCT02923180


    Safety Study of Enoblituzumab (MGA271) in Combination With Ipilimumab in Refractory Cancer
    NCT02381314


    Enoblituzumab (MGA271) in Children With B7-H3-expressing Solid Tumors
    NCT02982941

  • TJ107 Novel long-acting IL-7
    - Novel agent to treat cancers with lymphopenia
    - Potential combo therapy with PD-1/PD-L1
    Oncology-related
    lymphopenia

    TJ107:The First Long-acting Recombinant Human IL-7 with the Potential for Cancer Treatment-related Lymphopenia and Cancer Immunotherapy 

    TJ107 (INN: efineptakin) is the world’s first and only long-acting recombinant human interleukin-7 (rhIL-7) known to boost cancer-fighting T lymphocytes by increasing their number and functions. We have acquired exclusive rights from Genexine to develop and commercialize TJ107 in Greater China. We have positioned TJ107 to address a huge unmet medical need in oncology. First, TJ107 can be an oncology-care agent to treat cancer treatment-related lymphopenia (low blood lymphocyte levels), a common condition that occurs in cancer patients who have received chemotherapy or radiation therapy, and for which there is no approved treatment. This condition causes further damage to patients’ already compromised immune system and weakens its ability to fight cancers. Second, TJ107 has been shown to synergize with a PD-1 antibody in a tumor animal model potentially through increased T-lymphocyte activation and proliferation.


    The clinical safety and effect of TJ107 on T cells have been investigated in multiple previous and ongoing clinical trials in South Korea and the United States. TJ107 was well-tolerated without serious adverse events, and TJ107 treatment resulted in a substantial increase in the number of CD4 and CD8 T cells, natural killer T cells, naive T cells, central memory, effector memory, and terminally differentiated effector memory T cells, without affecting the number of B cells, natural killer cells, monocytes or Tregs.


    By leveraging the results of Genexine’s ongoing clinical trials in South Korea and the United States in advanced solid tumors, we aim to rapidly advance the clinical development of TJ107 for approval in Greater China. We are conducting a Phase 1b trial in China to determine a suitable dose range for subsequent trials. We plan to submit a clinical trial application for a Phase 2 trial in cancer patients in 2020. 

    Clinical Trials:

    Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of TJ107 in Chinese Patients With Advanced Solid Tumors

    NCT04001075


    Abstract

Global Portfolio

Whereas the goal of the China portfolio is to bring in-licensed products to the Chinese market as quickly as possible, the global portfolio focuses on demonstrating proof of concept, safety, and preliminary efficacy of I-Mab’s internally developed innovative biologic drug candidates. Our fast-to-PoC global approach is illustrated by our Global Portfolio, in which the strategy is to clinically validate these candidates under the US FDA’s streamlined regulatory system for innovative drugs, and to use the validated clinical data to pursue further development in China. 


Our Global Portfolio focuses on two molecular classes: monoclonal antibodies and bi-specific antibodies.


Monoclonal antibodies. Among the five monoclonal antibody drug candidates, TJM2, TJC4 and TJD5 are undergoing Phase 1 clinical trials in the US. TJ210 and TJX7 are at the CMC stage and are expected to be ready for IND submissions and subsequent Phase 1 clinical trials in 2020 in the US.


Our CD47 and CD73 antibodies are globally competitive and have huge potential to become the next generation of immuno-oncology agents. TJC4 and TJD5 in our Global Portfolio have attracted a high level of interest from global pharmaceutical companies and KOLs due to their clinical differentiation from competitor antibodies. This is a strong testament to our discovery capability in target biology, antibody engineering, translational medicine and antibody CMC. 


Bi-specific antibody panel. Despite the recent success of checkpoint inhibitors, it is estimated that more than 60% of cancer patients do not respond to PD-1/PD-L1 monotherapies. In addition, some patients develop resistance after initial treatment with these therapies. As a result, the standard of care today leaves many cancer patients underserved. There is consensus among cancer immunologists that tumors that do not respond to PD-1/PD-L1 treatment have poor immunologic features, such as an absence or paucity of tumor-fighting immune cells, or the presence of dysfunctional immune cells within the tumors, collectively known as “cold tumors.”  


We believe that PD-1/PD-L1 non-responders can be better treated with novel bi-specific antibodies with a second targeting component attached to the anti-PD-L1 moiety. This elicits a sufficient immune response to convert a “cold tumor” to an immune-active “hot tumor.” Such unique properties of our bi-specific antibodies cannot be substituted by a combination of the PD-L1 antibody with a selected second component (either cytokine or antibody) in a free form. The underlying mechanism is such that the second component must be structurally integrated with the tumor-engaging PD-L1 antibody in order to concentrate and function inside the tumor, which cannot be readily achieved by the two free agents used in combination.


We have successfully generated a panel of five bi-specific antibodies in which our proprietary PD-L1 antibody acts as the backbone (the first signal) and is linked with various second components (the second signal). These include a 4-1BB agonist antibody (TJ-L14B), an IL-7 cytokine (TJ-L1I7) and a B7-H3 antibody (TJ-L1H3), a CD73 antibody (TJ-L1D5) and a CD47 antibody (TJ-L1C4), which work synergistically with the PD-L1 backbone in various assays and cancer animal models. This unique panel of bi-specific antibodies is only made possible by our proprietary and partnered antibody-engineering technologies and the availability of our proprietary monoclonal antibodies. 


In addition, we have generated two other bi-specific antibodies that are tailor-made to function as novel ‘fortified’ antibodies by linking TJC4 with granulocyte-macrophage colony-stimulating factor (GM-CSF) for the treatment of solid tumors, or by linking one of our tumor-associated antigen antibodies with a 4-1BB antibody as a novel cancer treatment agent that only activates T cells after tumor engagement. 


All bi-specific antibodies have been validated in a series of robust in vitro and in vivo studies for biological proof-of-concept, providing a solid basis for clinical validation in cancer patients.


We expect to advance the three monoclonal antibodies currently in US Phase 1 trials into Phase 2, and to initiate new US clinical trials for TJ210 and TJX7 and the first few bispecific antibodies by the end of 2020 or early 2021. As part of this effort, I-Mab is expanding its clinical team based in Maryland, US, and is also setting up a translational medicine group with a biomarker laboratory in the US.

KEY

  • PRE-CLINICAL :
  • PHASE 1:
  • PHASE 2:
  • PHASE 3:
  • Marketed:
Drug Candidate
Target
Molecular Format
Indication
Therapeutic Area
Development
Phase
Drug Candidate
Target
Indication
  • TJM2
    GM-CSF
    Monoclonal antibody
    Autoimmune diseases / Cytokine release syndrome

    TJM2:A GM-CSF monoclonal antibody for autoimmune diseases and CAR-T-related therapies

    TJM2 is an internally discovered neutralizing antibody against human granulocyte-macrophage colony stimulating factor (GM-CSF), an important cytokine that plays a critical role in chronic inflammation and destruction in autoimmune diseases such as rheumatoid arthritis (RA). GM-CSF can polarize macrophages into a pro-inflammatory M1 phenotype and is known to induce an inflammatory cascade involving other pro-inflammatory cytokines such as tumor-necrosis factor (TNF), interleukin-1 (IL-1), IL-6, IL-12, and IL-23. It is evident that GM-CSF plays a crucial role in the pathogenesis and disease progression of multiple autoimmune conditions.


    TJM2 is a humanized IgG1 that displays high-affinity binding to GM-CSF and blocks its signaling and downstream effects. We initiated a first-in-human study in healthy volunteers in the US. We have enrolled and completed dosing of four planned cohorts, with each cohort consisting of eight subjects. Data from this clinical trial has facilitated IND submission in China in August 2019 for a multiple-dose Phase 1b study in patients with RA, before expanding to other autoimmune and inflammatory conditions in which GM-CSF is known as a pathogenic cytokine in disease activity and progression, and which have a high unmet medical need. TJM2 is expected to be the first antibody of its class to enter clinic trials in China in 2020. If approved, it is expected to provide an effective treatment option as a disease-modifying anti-rheumatic drug therapy. We also intend to investigate the efficacy of TJM2 in reducing or preventing cytokine release syndrome (CRS) and neurotoxicity associated with CAR-T therapy through collaborations.

    Clinical Trials:


    Study of TJ003234 (Anti-GM-CSF Monoclonal Antibody) in Healthy Adult Subjects

    NCT03794180

  • TJC4
    CD47
    Monoclonal antibody
    Multiple cancer indications

    TJC4:A potential highly differentiated CD47 antibody for immuno-oncology

    As a fully human monoclonal antibody targeting CD47, TJC4 is a prime example of I-Mab’s in-house innovation. CD47 has emerged as one of the most promising immuno-oncology targets. Blockade of the CD47-SIRPα pathway involved in tumor progression represents one of the most effective tumor-killing mechanisms. However, the first wave of clinical-stage CD47 antibodies were found to bind to red blood cells (RBCs) and cause significant hematologic adverse effects, such as severe anemia.


    TJC4 has the potential to stand out from other clinical-stage CD47 antibodies. Unlike competitor molecules, we developed TJC4 by design to uniquely minimize the binding to RBCs while retaining anti-tumor activities in line with other antibodies of the same class. This key differentiation is achieved through additional RBC counter-screening to select rare antibody clones that bind to CD47 with high affinity but do not bind to, or bind minimally, to RBCs. The differentiation of TJC4 has been extensively validated in a series of robust in vitro assays and primate studies. In a GLP toxicology study involving 40 monkeys, no hematologic side-effects were seen even with repeated injections of high doses of TJC4 (up to 100 mg/kg). This unique property may enable TJC4 to be used safely at higher doses to explore its treatment potential in cancers, differentiating it from other clinical-stage CD47 antibodies. 


    We are evaluating TJC4 in a Phase 1 clinical trial with cancer patients in the US. We have also obtained IND approval by NMPA and plan to begin a Phase 1 clinical trial of TJC4 in patients with hematologic malignancies in China.


    Clinical Trials:


    Study of TJ011133 Subjects With Relapsed/Refractory Advanced Solid Tumors and Lymphoma

    NCT03934814


    Abstract

  • TJD5
    CD73
    Monoclonal antibody
    Multiple cancer indications

    TJD5:A potential highly differentiated CD73 antibody for cancer treatment

    TJD5 is an internally developed, humanized inhibitory antibody against human CD73. CD73 is expressed in tumors and is the rate-limiting enzyme that converts extracellular AMP to adenosine, a potent immunosuppressive molecule in the tumor micro-environment. TJD5 allosterically inhibits CD73 in a substrate non-competitive manner. This results in a decrease in adenosine production and an increase of T cell anti-tumor activity. 

    TJD5 is differentiated from clinical-stage antibodies of the same class by its novel epitope, which works through a unique intra-dimer binding mode, resulting in a complete inhibition of the enzymatic activity and avoiding the aberrant pharmacological property known as the “hook effect.” TJD5 displays sub-nanomolar binding affinity to CD73. In vitro, TJD5 completely reverses adenosine monophosphate (AMP) or tumor-cell-mediated suppression of T cells in a concentration-dependent manner; in vivo, TJD5 combined with a PD-L1 antibody exhibits a superior or synergistic inhibitory effect on tumor growth.


    We have initiated a Phase 1 clinical trial in the US in patients with advanced solid tumors in collaboration with TRACON Pharmaceuticals. Safety data on TJD5 is expected in 2020. In China, we plan to begin a clinical trial to evaluate the safety, tolerability, pharmacodynamics/pharmacokinetics, and potential efficacy primarily in patients with lung cancer. 

    Clinical Trials:


    Study of TJ004309 in Combination With Atezolizumab (Tecentriq®) in Patients With Advanced or Metastatic Cancer

    NCT03835949

  • TJ210
    C5aR
    Monoclonal antibody
    Oncology / Autoimmune disease

    TJ210:A Potential Highly Differentiated Antibody Targeting Myeloid Derived Suppressor Cells in Cancers and Autoimmune Diseases

    TJ210 is a fully human, high-affinity antibody directed against complement factor C5a receptor 1 (C5aR1) for the treatment of cancers and potentially autoimmune diseases. Tumors produce large amounts of C5a to attract C5aR1-expressing myeloid-derived suppressor cells (MDSCs), M2 macrophages and neutrophils. These myeloid cells critically contribute to an immunosuppressive microenvironment as part of the evading mechanism of tumors, and are associated with poor prognosis and resistance to PD-1/PD-L1 therapies in many cancers. Inhibition of C5a or its receptor in mice leads to markedly reduced MDSCs and has an inhibitory effect on tumor growth in various tumor-bearing animal models. TJ210 has been shown to have a synergistic anti-tumor effect when combined with PD-1 therapies in PD-1-resistant tumor models. TJ210 exerts strong anti-tumor activity by blocking the activation and migration of C5aR1-expressing myeloid cells. 


    TJ210 is highly differentiated as it binds to a novel epitope and possesses superior functional properties. Compared with a competitor antibody, TJ210 shows higher in vitro potency, especially when C5a concentrations are high. TJ210 binds to C5a receptors in both humans and monkeys, making preclinical safety assessment possible. In addition, TJ210 has therapeutic potential in multiple inflammatory and autoimmune indications in which the role of the C5a/C5aR axis has been implicated. We partnered with the original developer of TJ210, MorphoSys, for Greater China rights and shared global rights. TJ210 is progressing towards IND submission in the US in 2020.

  • TJX7
    CXCL13
    Monoclonal antibody
    Autoimmune disease

    TJX7:A novel CXCL13 antibody for autoimmune diseases

    TJX7 is an internally discovered, humanized neutralizing antibody targeting the CXCL13 chemokine. CXCL13, through its receptor CXCR5, plays a key role in forming germinal centers, which are critical for immune response. One of the key pathogenic features in autoimmune diseases is related to the aberrant formation of ectopic germinal centers formed in affected organs, contributing to chronic inflammation and tissue destruction. Elevated serum CXCL13 levels, CXCR5-expressing T cells and pathogenic germinal center B cells, and even ectopic germinal center formation are found in multiple autoimmune diseases, including Sjögren’s syndrome, RA, multiple sclerosis, and SLE. 

    TJX7 is being developed for the treatment of autoimmune disorders and has been shown to bind to CXCL13 with sub-nanomolar affinity, effectively blocking the interaction between CXCL13 and CXCR5 and downstream signaling. TJX7 has been shown to completely inhibit the migration of primary human tonsil B cells. Pharmacodynamic studies in mice and cynomolgus monkeys have confirmed TJX7’s inhibitory effects on germinal center formation and antibody production. Results generated so far indicate that TJX7 may provide a new therapeutic angle in the treatment of autoimmune diseases as it acts uniquely at the core of tissue pathologies. TJX7 is currently under CMC and preclinical development. 

  • PD-L1 based BsAbs
    Multiple
    Bi-specific antibody
    Multiple cancer indications

    PD-L1-based Bi-specific Antibodies: 

    PD-L1-based bi-specific antibodies are designed according to the scientific rationale that a PD-L1 antibody, when engineered with a selected second immune component such as a cytokine or another antibody, is able to convert “cold tumors,” which typically do not respond to PD-1/PD-L1 inhibitors, into “hot tumors,” which are more sensitive to PD-1/PD-L1 therapies. Such PD-L1-based bi-specific antibodies are expected to increase the probability of treatment success in patients who do not respond to PD-1/PD-L1 treatment. 

    Based on this concept, we have generated a panel of bi-specific antibodies using our proprietary PD-L1 antibody sequence as the backbone (the first signal), linked to a second component (the second signal) of selected immune properties. The second signal for this panel of bi-specific antibodies includes IL-7 cytokine (expanding T effector cells), 4-1BB and B7-H3 antibodies (activating T cells synergistically with PD-L1), CD47 antibody (adding the macrophage-killing mechanism) and CD73 antibody (altering tumor microenvironment). We strive to validate all bi-specific antibodies through a series of robust in vitro and in vivo studies for proof-of-concept, providing a solid basis for further development.


    Abstract

  • Fortified BsAbs
    Multiple
    Bi-specific antibody
    Specific cancer therapeutic purposes

    “Fortified” Bi-specific Antibodies for Specific Cancer Therapeutic Purposes: 

    TJ-C4GM is a novel molecule composed of our CD47 antibody linked to an engineered GM-CSF moiety fused at the C-terminus of the antibody heavy chain, creating a “fortified” version of the CD47 antibody that is specifically designed for the treatment of solid tumors through the CD47-mediated macrophage-activating mechanism. The unique functional properties of TJ-C4GM have been confirmed in a series of in vitro and in vivo tumor animal models, in which TJ-C4GM showed superior anti-tumor activity than TJC4 or GM-CSF used either alone or in combination. TJ-C4GM is currently at the CMC and preclinical development stage.

    TJ-CLDN4B is a bi-specific antibody targeting both a tumor-associated antigen and 4-1BB, a co-stimulatory molecule on T cells. In collaboration with ABL Bio, we developed TJ-CLDN4B with two key advantages over antibodies in clinical development. First, it is capable of binding to tumor cells even with low expression levels of tumor-associated antigen, making it more suitable for a broader patient population. Second, T cells are only activated after tumor cell engagement by TJ-CLDN4B, which avoids the liver toxicity associated with pan-activating 4-1BB antibodies in clinical studies. TJ-CLDN4B is currently at the CMC and preclinical development stage.


    Abstract

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