On March 31, 2023 Genor Biopharma (Stock code: 6998.HK) reported its 2022 annual financial results, business progress and other highlights in the past year (Press release, Genor Biopharma, MAR 31, 2023, View Source [SID1234629910]).
Dr. GUO Feng, Chairman of the Board and Chief Executive Officer, Genor Biopharma, said: "2022 was a year full of changes and challenges. It was also a year for the positive development of Genor Biopharma and the firm implementation of the strategy of ‘Focus, Optimization, Acceleration and Enrich’. The company has achieved a number of important milestones at a speed better than the industry average, and lays a solid foundation for steady growth in 2023."
Focus and Optimization, Acceleration 2022
GB491 (Lerociclib) – a CDK4/6 inhibitor was developed for breast cancer patients with better safety and excellent efficacy
GB491 (Lerociclib) is a novel, potent, selective oral bioavailable CDK4/6 inhibitor co-developed by the Group and G1 Therapeutics, a US-based company, for use in combination with endocrine therapy in advanced breast cancer. Patient enrollment in Phase III trials for both the first line and the second line was completed quickly via adaptive and seamless experiment design, scientific reference and data bridging, a seamless registration strategy, and excellent execution.
At present, NMPA has officially accepted the new drug application for GB491 (Lerociclib) in combination with Fluvestran as the treatment of HR+/HER2- locally advanced or metastatic breast cancer patients with disease progression following previous endocrine therapy. And GB491 (Lerociclib) has completed patient enrolment for the first line Phase III clinical trial.
Based on data from the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2020 Conference, GB491 (Lerociclib) has demonstrated excellent safety and tolerability profile, enabling uninterrupted daily dosing and better long-term benefits, and could potentially be a BIC CDK4/6 drug candidate.
GB261 (CD20/CD3, BsAb) – potential best-in-class (BIC) CD20/CD3
GB261 (CD20/CD3, BsAb) is the first T-cell engager with ultra-low affinity to bind CD3 and has Fc-enabled functions (ADCC and CDC). GB261 (CD20/CD3, BsAb) significantly inhibits rituximab-resistant cancer cell proliferation in both in vitro assays and in vivo models; meanwhile with T-cell activation, GB261 (CD20/CD3, BsAb) induces less cytokine release compared with compounds in the same class. Thus, GB261 (CD20/CD3, BsAb) is a highly potent bi-specific therapeutic antibody for B-cell malignancies. It has potential to be a better and safer T-cell engager with competitive advantages over other CD3/CD20 agents.
GB261 (CD20/CD3, BsAb) has opened more than a dozen clinical centres in Australia and China. Efficacy has been observed in the first-in-human (FIH) clinical trial in Australia in the dose-climbing low-dose group with preliminary clinical Proof of Concept (POC) data, which was consistent with the molecular design mechanism of GB261 (CD20/CD3, BsAb), indicating a good safety, pharmacokinetic profile and clinical antitumor activities. The high-dose group currently is in dose escalation.
In China, GB261 (CD20/CD3, BsAb) obtained an implied license for Phase I/II clinical trials from the NMPA on May 23, 2023 for the treatment of patients with recurrent or refractory B-cell non-Hodgkin lymphoma (B-NHL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). On September 8, 2022, GB261 (CD20/CD3, BsAb) Phase I/II clinical trials achieved the first patient dosing in China.
GB263T (EGFR/cMET/cMETT, TsAb) – the world’s first EGFR/cMET/cMET tri-specific antibody
GB263T (EGFR/cMET/cMET, TsAb) is targeting EGFR and two different epitopes of cMET, and has been designed with the goal of improving safety and efficacy. Thus, GB263T is a highly differentiated tri-specific antibody that exhibits multiple mechanisms of action to inhibit primary and secondary EGFR mutations and cMET signaling pathway simultaneously.
Preclinical studies showed that GB263T (EGFR/cMET/cMET, TsAb) potently blocked ligand-induced phosphorylation of EGFR and cMET, and demonstrated better dual inhibition of EGFR and cMET signaling pathways compared to the JNJ-372 analogue. GB263T (EGFR/cMET/cMET, TsAb) effectively induced enhanced internalization of EGFR and cMET, and downregulated the expression levels of both EGFR and cMet proteins. The in vivo anti-cancer efficacy of GB263T (EGFR/cMET/cMET, TsAb) was demonstrated in several different tumor models, such as those with EGFR exon 20 insertion, EGFR exon 19 deletion, including C797S mutation, and various cMET alteration models. In all models studied, GB263T (EGFR/cMET/cMET, TsAb) demonstrated significant and dose-dependent tumor inhibition. In addition, GB263T (EGFR/cMET/cMET, TsAb) did not show any major toxicities in monkeys, even at a high dose given for four weeks in a GLP tox study.
Bellberry HREC approval for the FIH clinical trial of GB263T (EGFR/cMET/cMET, TsAb) was obtained in Australia on March 28, 2022 for the treatment of patients with advanced non-small cell lung cancer (NSCLC), with the first patient dosed on May 18.
In China, the Phase I/II clinical trials application for GB263T (EGFR/cMET/cMET, TsAb) was approved by the National Medical Products Administration (NMPA) on June 2, 2022, with the first patient dosed on October 14, 2022 in China for the treatment of patients with advanced NSCLC. The high-dose group currently is in dose escalation.
GB492 (IMSA101) – potential best-in-class STING agonist
GB492 (IMSA101) 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 cGAS-STING signaling and significantly enhance the efficacy of the cancer immunity cycle when used in combination with other immune checkpoint inhibitors (ICI). It may become a potential FIC therapy.
In Phase I/II clinical trials of GB492 (IMSA101) as a monotherapy or in combination with GB226 (Aibining艾比寧, Geptanolimab) in patients with advanced/treatment-refractory malignancies, monotherapy clinical trials were finished and a dose escalation up to 400ug was completed in January 2022
In January 2022, approval was obtained from the CDE to directly conduct a dose-escalating study of GB492 (IMSA101) in combination with PD-1 in patients with advanced malignancy, based on the available data on the 400ug dose group in the monotherapy study in China and all data of the monotherapy dose-escalation study in the United States. In this clinical trial, an innovative FIH trial design was employed to combine the dose escalations when GB492 (IMSA101) was administered alone and when it was administered with GB226 (Aibining艾比寧, Geptanolimab). It is the first STING agonist combination therapy that has obtained clinical trial approval in China.
Deep cultivation and cooperation, value enrichment
Focusing on the potential global first-in-class (FIC)/best-in-class (BIC) innovation pipeline, Genor Biopharma has developed and is executing a comprehensive strategy to optimize and enrich the existing product portfolio and conduct molecular research with the greatest potential to produce clinical and commercially viable drugs. It aims to address unmet medical needs in China and around the world. As of December 31, 2022, five FIC/BIC bi-specific/multi-specific antibody projects were carried out and nearly 10 differentiated innovation projects involving different molecular forms were in the early stage of research and development.
Independent innovation and strategic cooperation have developed simultaneously. In May 2022, Genor Biopharma entered into a cooperative development agreement with Abogen Biosciences Co., Ltd. ("Abogen") to jointly develop globally innovative mRNA products and related pharmaceuticals. GH Biopharma’s antibody development platform will be integrated with Abogen’s mRNA technology platform to enable them to jointly research and develop mRNA drugs for tumor treatment. It is progressing smoothly. One of the collaborative projects is in the pre-pcc stage. Currently, the Group is exploring opportunities to conduct cooperative development projects with various innovative technology platforms. It is actively expanding external cooperation in early research and development, commercialization and other levels, in order to continuously expand global innovation.
On February 23, 2022, the NMPA granted marketing approval for Jiayoujian 佳佑健 (GB242, Infliximab) which is used for the treatment of rheumatoid arthritis, ankylosing spondylitis, psoriasis, adult ulcerative colitis, adult and pediatric (aged above 6 years old) Crohn’s disease and fistulizing Crohn’s disease. Genor Biopharma commercialized its first product. Up to now, Jiayoujian 佳佑健 (GB242, Infliximab) is available for online procurement in 22 provinces and cities across the country, and has achieved sales of approximately RMB 11.9 million.
Efficient operation, win in 2023
In the face of the complex international situation and uncertainties brought about by the COVID-19 pandemic, Genor Biopharma has clarified its development priorities and adopted a variety of effective measures to continuously optimize its organizational structure, operation management and daily business. In 2023, it will promote key projects with higher operational efficiency to achieve its strategic goals.
Specifically, Genor Biopharma will continue to focus on promoting key projects and exploration of FIC potential in multi-dimensions to achieve an effective balance between efficiency and cost based on the in-depth understanding of target molecular biology, cell biology and immunological mechanisms. Cooperative R&D and open innovation, Genor Biopharma is actively exploring cooperation projects between its platform for early discovery of highly differential T-cell Engager / bi-specific/multi-specific antibodies in immune-oncology / BsADC and different innovative technology platforms to further promote global innovation through cooperation.
In terms of clinical pipeline advancement, Genor Biopharma expects to achieve the approval of the new drug application for GB491 (Lerociclib cyclin-dependent kinase 4/6 inhibitor) in combination with Fluvestran as the treatment of HR+/HER2- locally advanced or metastatic breast cancer patients with disease progression following previous endocrine therapy; and to submit an NDA application to the NMPA depending on the results of the Phase III clinical trials of GB491 (Lerociclib) in 1L HR+/HER2- breast cancer. It remains committed to addressing the large group of breast cancer patients in China and around the world with a safe, effective and well-tolerated novel therapy in the next 18 months.
As for bi-specific and tri-specific antibody drug candidates, Genor Biopharma will continue to accelerate the development of clinical trials in Australia and China. GB261 (CD20/CD3, BsAb) is scheduled to complete its phase I/II clinical trials within the next 12 to 18 months and proceed to the pivotal registration trial. The clinical trial of GB263T (EGFR/cMET/cMET, TsAb) will continue to progress rapidly, with preliminary clinical data to validate POC planned within the next 12 months. Meanwhile, Genor Biopharma will actively expand external partnerships in its clinical programs.
Total revenue was RMB15.9 million for the Reporting Period, primarily generated by (i) drug sales of Jiayoujian 佳佑健 (GB242, Infliximab Biosimilar), and (ii) providing research and manufacturing services to our customers under fee-for-service contracts.
Research and development expenses were RMB583.9 million for the Reporting Period, as compared with RMB612.7 million for the year ended 31 December 2021. The spending was mainly attributable to (i) our new drugs development fee and ongoing clinical trials expenses and (ii) our employee salary and related benefit costs. The decrease was mainly due to the decrease in employee benefits expenses.
Total comprehensive loss was RMB731.8 million for the Reporting Period, as compared with RMB865.8 million for the year ended 31 December 2021. The decrease was primarily due to (i) decrease in expenses and (ii) total revenue generated for the Reporting Period.
By the end of December 2022, the cash balance was RMB1.59 billion. Enough to support the company’s stable operation in the next 4-5 years.