Abbreviations: r/r=relapsed or refractory; PTCL=peripheral T cell lymphoma; PMBCL=primary mediastinal B-cell lymphoma; ASPS=alveolar soft part sarcoma; HCC=hepatocellular carcinoma; mCRC=metastatic colorectal cancer; NSCLC=non-small cell lung cancer; mBC=metastatic breast cancer; eBC=early breast cancer; BC=breast cancer; RA=rheumatoid arthritis; DLBCL=diffuse large B-cell lymphoma; GCTB=giant-cell tumor of bone; PMO=postmenopausal osteoporosis; GBM=glioblastoma multiforme; nsNSCLC=non-squamous non-small cell lung cancer; NHL=non-Hodgkin lymphoma; 1L=the first line of treatment; 2L+=the second line and later lines of treatment; 3L+=the third line and later lines of treatment; JP=Japan; US=the United States; EU=Europe.
China or PRC represents for the People’s Republic of China, which for geographical reference only, excludes Hong Kong SAR, Macau SAR and Taiwan.
Greater China represents for PRC, Hong Kong SAR, Macau SAR and Taiwan.
* Denotes a core product.
** Progress bar denotes the most advanced ongoing clinical trial.
^ Denotes a key drug.
(1) The expected first NDA filling for key drugs.
(2) Clinical trials are sponsored by G1 Therapeutics, Inc., or G1 Therapeutics.
(3) Clinical trial is sponsored by ImmuneSensor Therapeutics, Inc., or ImmuneSensor Therapeutics.
GB491 (lerociclib) is a potent, selective, potentially best-in-class oral CDK4/6 for HR+/HER2-breast cancer in China, which accounts for 62.0% of all breast cancer patients in China, 2.8 times of the number of HER2+ breast cancer patients. GB491 has consistently demonstrated efficacy in several pre-clinical models and clinical trials in HR+/HER2-breast cancer. CDK4/6 inhibitors in combination with fulvestrant represent an established treatment for HR+/HER2- advanced or metastatic breast cancer and have demonstrated significant improvements in progression-free survival (PFS) and overall survival (OS). Preliminary results of clinical trials indicate that GB491 has a differentiated PK and tolerability profile from other CDK4/6 inhibitors, allowing for continuous dosing with fewer dose-limiting toxicities such as neutropenia and less complete blood count monitoring.
Clinical Trials: Lerociclib is currently undergoing a Phase 2a clinical trial conducted by our licensing partner, G1 Therapeutics, in the United States in combination with fulvestrant for patients with HR+/HER2-locally advanced or metastatic breast cancer after endocrine failure. We plan to evaluate GB491 in HR+/HER2-metastatic and early breast cancer in China.
GB221 is a potentially first-three-to-market Herceptin (trastuzumab) mAb for HER2+ mBC in China. We are dedicated to the HER2 pathway, which is an important driver in the development of targeted cancers, and anti-HER2 treatments have become the standard of care for HER2+ breast cancer of all stages. In addition, we believe that GB221 serves as a backbone to facilitate the development of combination therapies for solid tumors in various settings.
Clinical Trials: GB221 is currently under Phase 3 clinical trials in HER2+ metastatic and advanced breast cancer in China, with an NDA expected to be filed in the second half of 2020. GB221 has demonstrated a comparable safety and toxicity profile and efficacy to those of trastuzumab in pre-clinical studies and clinical trials.
We have adopted a differentiated combination therapy strategy with a broad and systematic clinical development plan for geptanolimab (GB226), an investigational, humanized, PD-1 mAb with the expectation that these combination therapies can lead to emerging market opportunities in commercialization.
Clinical Trial: We are developing GB226 as a monotherapy in various cancer indications, implementing a differentiated clinical strategy in terms of novel indications, and are currently advancing clinical trials in China, including:
a pivotal Phase 2 clinical trial as a monotherapy in r/r PMBCL,
a Phase 2 clinical trial in cervical cancer.
GB492 (IMSA101) is a STING agonist, potentially first-in-class in China, that we plan to develop in combination with GB226 for solid tumors. Multiple cancer immunotherapies including chimeric antigen receptor T-cell and immune checkpoint inhibitors (ICIs) have been successfully developed to treat various cancers by motivating adaptive antitumor immunity. However, many cancers have low clinical response rates to ICIs due to poor tumor immunogenicity. In tumor settings, STING is the major mediator of innate immune sensing of cancerous cells. Multiple studies show that STING agonist may be used in combination with ICIs as a new immune stimulatory therapy and enhance the efficacy of the cancer immunity cycle.
Clinical Trial: IMSA101 is currently undergoing a Phase 1 clinical trial conducted by our licensor, ImmuneSensor Therapeutics, in the United States alone or in combination with ICI for patients with solid tumors. We plan to evaluate GB492 in combination with GB226 in solid tumors in China.
We currently have multiple bi-specific antibody drug candidates, the highlights among which include candidates targeting on CD3×CD20, PD-L1×CD55 and EGFR×c-Met. We expect to file IND applications with the NMPA and advance these pre-clinical bi-specific antibody drug candidates into clinical stage within the next 12 to 18 months, and further explore global development opportunites.
The CD3×CD20 bi-specific antibody (GB261) is designed to possess strong T-cellactivation efficacy but relatively low binding affinity to CD3 to avoid cytokine GB261 is differentiated in that it maintains the ADCC/CDC function, which only kills cancer cells but not T-cells or other normal cells, enabling it to target cancer cells with better potency.
The PD-L1×CD55 bi-specific antibody has a novel mechanism of action, and we areexploring it in solid tumors, including pancreatic cancer. Simultaneous inhibition of the PD-L1 and CD55 signaling pathways is able to enhance the internalizing ability of the PD-L1×CD55 bi-specific antibody, thereby blocking PD-1/PD-L1 interaction to activate T-cell dependent immune response and decreasing CD55’s inhibition on complement-dependent cytotoxicity more powerfully.
The EGFR×c-Met bi-specific antibody is under development to target the hugeEGFR-TKI-relapsed NSCLC market. The activation of alternative pathways, including the c-Met signaling pathway, has been identified as a mechanism of resistance to EGFR-targeted therapies. Consequently, blocking one receptor tends to upregulate the other, leading to resistance to single-agent treatment. Because of the signaling crosstalk between EGFR and c-Met, inhibition of both receptors in combination may lead to improved outcomes for patients with c-Met- and EGFR-driven cancers.
GB242 is potentially one of the first three infliximab (Remicade) biosimilar products to the markets in China, and our clinical trial has the largest patient enrollment. Remicade has the most extensive indications approved in China among TNF--targeting drugs, including RA, AS, PsA, CD and UC, which gives GB242 a premium access to sizeable markets for autoimmune diseases in China.
Clinical Trials: We are currently conducting a Phase 3 clinical trial of GB242 in RA and plan to file an NDA with the NMPA by the second half of 2020. We also plan to extrapolate to other approved indications of Remicade, subject to NMPA approval.
GB223 is potentially one of the first three RANKL mAbs to markets in this drug class in China. We believe that RANKL inhibitors have huge market potential in China for the treatment of cancer and chronic diseases. We are developing GB223 in GCTB, which is mostly nonfatal disease but can lead to severe complications such as paraplegia and amputation and has high rates of recurrence after surgery. Meanwhile, we are initiating a clinical trial of GB223 in PMO. We also plan to explore potential therapeutic efficacy of GB223 in the broader osteoporosis indications.
Clinical Trials: GB223 is currently under a dose-escalating Phase 1 clinical trial in GCTB in China.