- GB491 (Lerociclib) and has got the official acceptance of the NDA in combination with Fluvestran as the treatment of HR+/HER2- locally advanced or metastatic breast cancer patients with disease progression following previous endocrine therapy. It has garnered international recognition for its superior efficacy and better safety tolerability.
- The low-medium dose group escalations of the phase I/II GB261(CD20/CD3, BsAb) clinical trial were completed, the high-dose groups are currently in dose escalation. Preliminary data shows promising efficacy and improved safety tolerability.
- The phase I/II clinical trial of GB263T (EGFR/cMET/cMET, TsAb) completed DLT (dose-limiting toxicity) observation in the low-medium dosed groups, and high-dose escalations are in progress currently. Encouraging preliminary clinical efficacy and safety data were observed, confirming the mechanism of action of GB263T to effectively inhibit the dual targets of EGFR and CMET.
- Nearly 10 tumor therapy projects with global differentiation are in the early discovery stage, and 1 potential FIC PCC molecule has entered the IND enabling stage.
- As of the end of June 2023, the cash balance of 1.36 billion RMB is enough to support the operation of the company in the next 3-4 years.
Shanghai, China, August 31, 2023 – Genor Biopharma (Stock code: 6998.HK) today announced its interim results for 2023, sharing the company's business progress, financial data, highlights during the period, and future development prospects.
Dr. GUO Feng, Chairman of the Board and Chief Executive Officer, Genor Biopharma, said: “With the continuous implementation of the 'Focus, Optimization, Acceleration, Expansion' strategy, Genor Biopharma successfully continued to rapidly promote the existing pipeline in the first half of 2023. One of our core products garnered international recognition at industry academic conferences. Furthermore, the results of the early research platform and the pressing on with commercial cooperation laid a solid foundation for the long-term sustainable development of the company.”
Core product garnered international recognition, clinical trials have advanced rapidly
GB491 (Lerociclib) – a differentiated oral CDK4/6 inhibitor which is 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 for use in combination with endocrine therapy in advanced breast cancer.
Patient enrolment of the Phase III trials for both first and second line has been completed quickly via adaptive and seamless experiment design, scientific reference and data bridging, seamless registration strategy, and excellent execution.
On 28 March 2023, the NMPA has officially accepted the NDA 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.
GB491 (Lerociclib) has garnered international recognition at the 2023 ASCO Annual Meeting, which was successfully held in Chicago from 2 June to 6 June 2023:
- The results of the LEONARDA-1 study were announced in the poster discussion session of the Metastatic Breast Cancer session with the title “Phase III randomized study of lerociclib plus fulvestrant in patients with HR+/HER2- locally advanced or metastatic breast cancer that has progressed on prior endocrine therapy”;
- The data from the Phase III clinical study of LEONARDA-1 were selected by ASCO for theASCO Daily Release, which was published in the ASCO Daily News Column on its website on 25 May 2023 (EST) with the title “Lerociclib/Fulvestrant May Reduce Risk of Disease Progression in Advanced HR-Positive/HER2-Negative Breast Cancer”;
- The LEONARDA-1 research report and article cited the views of the lead author Prof. Binghe Xu, MD, PhD, the academician of the Chinese Academy of Engineering, the Head of Medical Oncology at Cancer Hospital affiliated with Chinese Academy of Medical Sciences. According to Prof. Binghe XU.
- Based on the efficacy and safety data shown in the LEONARDA-1 study, GB491 (Lerociclib) has demonstrated superior efficacy, better safety and tolerability profile to patients with HR+/HER2- advanced breast cancer for whom prior endocrine therapy failed, providing a more reliable clinical option. It could become a preferred option among CDK4/6 inhibitors for refractory patients and patients with suboptimal recovery of myelosuppression after chemotherapy and suboptimal gastrointestinal/hepatic function or patients with poor tolerability.
GB491 (Lerociclib) will create a new landscape for the treatment of HR+/HER2-advanced breast cancer.
- HR+/HER2- is the most common subtype of advanced breast cancer, and its treatment has entered the era of targeted therapy. Combination therapy with CDK4/6 inhibitors has been recommended in multiple guidelines as the preferred regimen for patients with advanced breast cancer following previous failed endocrine therapy.
- The innovative molecular structure with its unique PK/PD has allowed for continuous oral administration of Lerociclib without the need for treatment breaks. It achieves sustained target inhibition and anti-tumor effects while significantly reducing the common adverse effects of CDK4/6 inhibitors, such as severe myelosuppression and diarrhea.
- The LEONARDA-1 clinical study demonstrated that the combination therapy of Lerociclib with Fluvestran would significantly reduce the risk of disease progression and death as compared to using Fluvestran as a monotherapy. The investigator-assessed hazard ratio (HR) was 0.451 and the Blinded Independent Central Review (BICR) assessed HR was 0.353. The median progression free survival (mPFS) (months) assessed by the investigator and BICR were 11.07 vs. 5.49 and 11.93 vs. 5.75, respectively. Furthermore, the results of all predefined subgroups were consistent with the overall efficacy.
- The LEONARDA-1 clinical study showed that, in comparison with other marketed CDK4/6 inhibitors, Lerociclib had significant comprehensive advantages in terms of safety and tolerance profile. It recorded a low incidence rate of diarrhea at 19.7%, a relatively low percentage of grade III/IV myelosuppression, and only a 5.1% incidence rate of grade IV neutropenia.
- LEONARDA-1 enrolled a high proportion of refractory patients, including patients with liver metastasis, treated with primary resistance, with 4 or more metastatic organs, received first-line chemotherapy at an advanced stage. The use of Lerociclib substantially improved the PFS of the refractory patients, indicating a superior efficacy with advantages in terms of safety and tolerance profile and hence fully demonstrating the differentiation advantage of Lerociclib for clinical purposes.
Currently, the Company is pressing on with commercial cooperation in respect of GB491 (Lerociclib). As of 30 June 2023, Genor Biopharma has presented the phase III research data to various companies, among which several companies have commenced the process of data review. It plans to enter into cooperation agreements in 2023. The transfer of technology for local production of GB491 (Lerociclib) has also been initiated simultaneously.
GB261(CD20/CD3, BsAb)
GB261 (CD20/CD3, BsAb) is the first T-cell engager with low affinity to bind CD3 and has Fc functions (ADCC and CDC). GB261 (CD20/CD3, BsAb) significantly inhibits rituximabresistant 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 compound in the same class. Thus, GB261 (CD20/CD3, BsAb) is a highly potent bispecific 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.
More than a dozen of GB261 (CD20/CD3, BsAb) clinical centers has been established in Australia and China. We obtained the preliminary clinical Proof of Concept (POC) data in the firstin-human (FIH) clinical trial of GB261 in Australia in the process of a dose escalation up to 3mg, which were consistent with the molecular design mechanism of GB261 (CD20/CD3, BsAb), indicating a good safety, pharmacokinetic profile and clinical antitumor activities.
As of 30 June 2023, the low-medium dose group escalations of the phase I/II GB261 (CD20/CD3, BsAb) clinical trial were completed. The high-dose groups are currently in dose escalation.
Preliminary data showed that GB261 (CD20/CD3, BsAb) has demonstrated promising efficacy, while initial efficacy has also been seen in patients who have failed prior CD20/CD3 bi-specific antibodies (mosunetuzumab), CAR-T, and CD3/CD19 bi-specific antibodies therapies.
Preliminary clinical data showed favorable tolerability, which was favorable for combination therapy. Cytokine release syndrome (CRS) was mild, transient and less frequent compared with other CD20/CD3 bi-specific antibodies products (low incidence: 12.8% (Grade 1: 8.5%; Grade 2: 4.3%); no Grade 3; no anti-IL6 used; no interruption of treatment. No immune effector cell associated neurotoxicity syndrome (ICANS) was observed.
In respect of pharmacokinetics (PK), the half-life of GB261 (CD20/CD3, BsAb) was long and supported tri-weekly dosing.
GB261 (CD20/CD3, BsAb) is scheduled to complete dose escalations in the second half of 2023.
Currently, the Company is actively pushing forward the negotiation with global clinical development/commercialization partners in respect of GB261 (CD20/CD3, BsAb). As of 30 June 2023, it has primarily approached more than ten companies and engaged in multiple rounds of indepth exchanges with various companies. It plans to enter into cooperation agreements between 2023 to 2024.
GB263T (EGFR/cMET/cMET, TsAb)
GB263T (EGFR/cMET/cMET, TsAb) was the first tri-specific antibody of EGFR/cMET/cMET in the world, targeting EGFR and two different cMET epitopes, so designed to enhance its safety and efficacy. With highly differentiated design, GB263T (EGFR/cMET/cMET, TsAb) exhibits multiple mechanisms of action to inhibit primary and secondary EGFR mutations and cMET signaling pathway simultaneously.
In pre-clinical studies, GB263T (EGFR/cMET/cMET, TsAb) effectively thwarted ligand-induced phosphorylation of EGFR and c-MET compared to its Amivantamab (JNJ-372) analogue, and demonstrated better dual inhibition of EGFR and cMET signaling pathways. Meanwhile, GB263T (EGFR/cMET/cMET, TsAb) effectively induced the endocytosis of EGFR and cMET, and significantly reduced the protein expression levels of EGFR and cMET. GB263T (EGFR/cMET/ cMET, TsAb) played a significant dosage-dependent role in tumor suppression in several different tumor models including EGFR exon 20 insertions, EGFR exon 19 deletions, C797S mutations and various cMET expression abnormalities. In toxicology studies in cynomolgus monkeys, no significant toxic side effects were observed after 4 weeks of observation, even in the highly-dosed group.
As of 30 June 2023, the phase I/II clinical trial of GB263T (EGFR/cMET/cMET, TsAb) completed DLT (dose-limiting toxicity) observation in the low-medium dosed groups, and high-dose escalations are in progress currently.
preliminary clinical efficacy has been observed, which validated that the mechanism of action of GB263T (EGFR/cMET/cMET, TsAb) effectively inhibited the dual targets of EGFR and CMET. Patients with EGFR-sensitive mutated NSCLC who failed multi-line therapies including the third generation TKI and platinum-based chemotherapy responded to GB263T; and the PR exceeded 24 weeks.
Preliminary clinical data demonstrated that GB263T (EGFR/cMET/cMET, TsAb) is safe and well tolerated, with an infusion reaction rate (IRR) of 35.7%, significantly lower than that of competitor (66%), and both were mildly graded 1/2. No MET target-related peripheral edema toxicity was observed.
The Company is expecting the validation of the clinical POC data to be completed in 2023.
Focus on highly differentiated products, deepen cooperation and enhance value
Focusing on the potential global first-in-class (FIC)/best-in-class (BIC) innovation pipeline, the Company’s R&D team has been actively exploring cooperative development 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.
In the area of efficient and high-quality innovation, Genor Biopharma has launched multi-dimensional highly differentiated R&D projects in addition to bi-specific/ multi-specific antibodies. The company 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 30 June 2023, five global FIC/BIC bi-specific/multi-specific antibody projects were carried out; around ten differentiated innovation projects involving different molecular forms were in the early stage of research and development. And currently, 1 potential FIC PCC molecule has entered the IND enabling 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.
Efficient operation, continuous promotion and winning in 2023
"Focus and Optimization", Genor Biopharma will continue to implement the development strategy, promote the key projects in 2023 with higher operational efficiency, achieve strategic goals, and achieve "Acceleration and Expansion".
In terms of early stage research and development, 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, and further promote global innovation based on the in-depth understanding of target molecular biology, cell biology and immunological mechanisms.
With regards to acceleration of clinical advancement and diversification of market expansion. The company plans to submit the NDA to the NMPA in the next 12 months depending on the results of the phase III clinical trial of GB491 (Lerociclib) in the first line HR+/HER2-breast cancer and to achieve the approval of 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. We remain committed to addressing the large market of breast cancer in China and around the world with a safe, effective and well tolerated novel therapy.
As for bi-specific and tri-specific antibody drug candidates, the Company 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 6-12 months. 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 6 months. On the basis of the global POC data for GB261 (CD20/CD3, BsAb) and GB263T (EGFR/cMET/ cMET, TsAb), the Company will actively expand external partnership in our clinical programs.
FINANCIAL HIGHLIGHTS
- Total comprehensive loss was approximately RMB276.4 million for the Reporting Period, as compared with approximately RMB407.5 million for the six months ended 30 June 2022. The decrease was primarily due to (i) decrease in expenses and (ii) total revenue generated for the Reporting Period.
- As of the end of June 2023, the cash balance of 1.36 billion RMB is enough to support the operation of the company in the next 3-4 years.
