GB226 is an investigational, humanized, IgG4 mAb targeting the programmed cell death-1 receptor (PD-1) on immune cells. It selectively blocks dual ligands (PD-L1 and PD-L2), and restores the ability of the immune system to recognize and kill tumor cells.

 

As the world's first PD-1 for peripheral T-cell lymphoma (PTCL), Aibining (GB226, Geptanolimab) has been granted priority review by the National Medical Products Administration (NMPA) for its marketing application (NDA). Approval is expected in the second half of 2021.

 

Relapse and refractory peripheral T-cell lymphoma (r/r PTCL) presents highly unmet medical needs with a median overall survival (OS) of less than one year for patients who failed first line therapy. Novel combination therapies have been extensively explored to enhance clinical benefit for r/r PTCL patients.

 

Comparing to existing therapies approved for PTCL, highlights of GB226 are listed below:

 

  • Demonstrated promising efficacy with an Independent Review Committee (IRC) - assessed ORR of 39.4%, which is highly competitive to the other approved drugs in r/r PTCL

 

  • The clinical benefit is very sustainable. As of 30 April 2021, according to IRC assessment, the median DOR is over 18 months among those patients with confirmed response, nearly twice of existing therapies.

 

  • The clinical benefit has been shown in the major PTCL subtypes including the very aggressive subtypes (ALCL ALK-ORR: 53.8%, ENKTL ORR: 64.7%).

 

  • Relapsed or refractory patients who failed Chidamide also obtained the benefit, and the ORR reached 37.5%.

 

  • As a drug with new MOA, GB226 has a good safety profile with a much lower hematological and gastrointestinal toxicities compared with other approved r/r PTCL regimens.

 

  • GB226 is the only drug which has the low overlapped toxicities with the potential combination therapies. Together with the unique Immuno-Oncology (I/O) MOA and the promising clinical activity, GB226 can provide r/r PTCL patients better treatment results via potential combination therapy.

 

We will continue to explore approval for geptanolimab (GB226) in other indications as well as novel combination therapy potential, including combination therapy with our STING agonist (GB492), to benefit more patients in China with unmet medical needs

GB491 (lerociclib), is a novel, potent, selective oral bioavailable CDK4/6 inhibitor co-developed by the Company and G1 Therapeutics, a US based company, for use in combination with endocrine therapy/targeted therapies in breast cancer. Based on the data published at European Society for Medical Oncology 2020 conference, GB491, comparing to the currently approved CDK4/6 inhibitor in China, palbociclib, has demonstrated a better safety profile and could be a potentially best-in-class CDK4/6 drug candidate.

 

In addition to China, the company is also actively expanding GB491 market development in Asia Pacific (excluding Japan) countries and regions, equivalent to 1.5 times the market shares of China.

 

  • In March 2021, we obtained investigational new drug (“IND”) and Ethic Committee (“EC”) approvals for the Phase 1b bridging studies: (1) GB491 and Letrozole in first line HR+/ HER2- advanced breast cancer; and (2) GB491 and Fulvestrant in second line HR+/HER2- advanced breast cancer.

 

  • In May 2021, we submitted IND applications for the two Phase 3 clinical studies.

 

  • In June 2021, we received EC approval for the Phase 3 clinical trial of GB491 and Fulvestrant in second line HR+/HER2- advanced breast cancer.

 

  • In July 2021, the Company has received IND approvals from the NMPA for the two Phase 3 clinical studies: (1) GB491 and Letrozole in first line HR+/HER2- advanced breast cancer; and (2) GB491 and Fulvestrant in second line HR+/HER2- advanced breast cancer.

 

  • In August 2021, the Ethic Committee Approval for the phase 3 clinical trial in first line HR+/HER2- advanced breast cancer has been obtained.

 

  • On August 26, 2021, the clinical trial of GB491 combined with flurvestrine in the treatment of second-line HR+/HER2- advanced breast cancer was approved by the Office of Genetics.

 

  • On September 8, 2021, the company achieved the first patient dose of the (CDK4/6) Phase 1b bridging study: GB491 and Letrozole in first-line HR+/HER2- advanced breast cancer.

 

  • On October 28, 2021, the company achieved the first patient dose for GB491 and Fulvestrant in second-line HR+/HER2- advanced breast cancer.

 

  • It is planned to reach the second-line interim analysis node in the second quarter of 2023.

GB492 (IMSA101, STimulator of interferon genes, STING) is the major mediator of innate immune sensing of cancerous cells, which the Group exclusively licensed from ImmuneSensor Therapeutic in June 2020.

 

STING agonist, as an immune stimulatory therapy, may further increase the response of immune checkpoint inhibitors for patients. Multiple studies have shown that STING agonists can activate the cGAS-STING signaling and significantly enhance the efficacy of cancer immunity cycle when using in combo with other immune checkpoint inhibitors (ICI), which may become a potential first-in-class therapy.

 

  • In March 2021, we submitted the IND application for the Phase 1/2 clinical trial of GB492 mono or in combination with GB226 in patients with advanced/treatment-refractory malignancies to the NMPA.

 

  • In May 2021, the IND of GB492 was approved by NMPA, in which an innovative FIH trial design was employed to combine the dose escalations when GB492 is administered alone and when it is administered with GB226 in ONE FIH study.

 

  • In July 2021, the Ethic Committee approval for the Phase 1/2 clinical trial of GB492 in patients with advanced/treatment-refractory malignancies was received in July 2021.

 

  • 16 September 2021, the first patient was dosed in the Phase I/IIa clinical trial of GB492 in China.

GB261 is a highly differentiated CD20/CD3 bi-specific antibody developed in-house. GB261 is the first T-cell engager with very low CD3 binding affinity and maintaining Fc effector functions (ADCC and CDC). With similar binding affinity to CD20 as rituximab, GB261 significantly inhibits rituximab-resistant cancer cell proliferation by in vitro assays and in vivo models.

 

More importantly, GB261 induces low levels of cytokine production by hPBMC and in monkeys, indicating low occurrences of CRS. Thus, GB261 is a highly promising bispecific therapeutic antibody for B cell malignancies. It may ultimately provide a concept shift to better and safer T-cell engager antibody drugs for various cancers.

 

  • In March 2021, we submitted the first-in-human clinical trial application for GB261 in Australia.

 

  • In June 2021, EC approval and clinical trial notification (“CTN”) were obtained in Australia.

 

  • With CMC fully compliant with NMPA and US FDA standard, we plan to conduct global multi-center clinical trials across Australia, China and the US. Dual IND fillings with the NMPA in China and FDA in the US are in progress.

 

  • The Genor team has got both EC and CTN approvals for the GB261’s FIH trial in Australia, in which an optimized trial design was employed to achieve a good balance of patient safety and trial acceleration. We anticipate Australian patient efficacy and safety data to become available in 1H 2022.

 

  • The pre-IND application for the first in human clinical trial of GB261 has been submitted to CDE in August 2021.

 

  • 19 October 2021, the first patient was dosed in the First in Human (FIH) clinical trial of GB261 (CD20/CD3, BsAb) for the treatment of B-cell non-Hodgkin Lymphoma (B-NHL) in Australia Peninsula & South Eastern Haematology & Oncology Group Center.

 

  • We expect to file IND for GB261 (CD20/CD3) in China and the US in the near-term.

GB263T has been designed as a tri-specific antibody targeting EGFR and two different cMet epitopes. The tri-specific antibody has two Fabs to bind EGFR. Its Fc fragment has been mutated to enhance Fc functions. Thus, GB263T with highly differentiated design, exhibits multiple mechanisms of action to inhibit primary and secondary EGFR mutations and cMet signaling pathway simultaneously. The significant anti-tumor activities have been demonstrated by in vitro studies and in vivo animal models.

 

  • GB263T potently blocked ligand-induced phosphorylation of EGFR and c-Met, and demonstrated better dual inhibition of EGFR and cMet signaling pathways compared to JNJ analogue (Fig. 1).

 

  • GB263T effectively induced internalization of EGFR and cMet, and downregulated the expression levels of both EGFR and cMet (Fig. 1).

 

  • GB263T strongly inhibited cell growth of Ba/F3 cells harboring EGFRexon20ins (Fig. 2), and resulted in dose-dependent inhibition of tumor growth by in vivo studies (Fig. 3).

  • GB263T showed remarkable ADCC effects to kill cancer cells harboring resistance mutations in EGFR with c-Met expression or amplification.

 

  • In addition, GB263T did not show any major toxicities in monkeys, even at a high dose of 100mg/kg given weekly for 4 weeks in a pre-tox study.

 

  • We plan to quickly move GB263T (EGFR/cMet/cMet) into clinical stage and file IND early next year.

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.

 

  • In November 2020, the NMPA accepted our NDA submission for GB242.

 

  • In April-May 2021, the On-Site Inspection for the Drug Registration (注册现场核查) were successfully completed, including:

 

    • Manufacturing Inspection (生产核查) & GMP Compliance Inspection (GMP 符合性检 查) in our Yuxi site, Yunan province;

 

    • Development Site Inspection (研制现场核查) in Shanghai;

 

    • Clinical Trial Data Inspection (临床试验数据核查) for Phase 1 & Phase 3 studies.

 

  • we expect to launch infliximab biosimilar (GB242) in the next 6 to 12 months, upon approval of NDAs that are currently under review.