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Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. (“Kelun-Biotech”, 6990.HK) announced that the new drug application (the “NDA”) for SKB264 (MK-2870, Brand name: 佳泰莱) in adult patients with unrespectable locally advanced, metastatic triple-negative breast cancer (TNBC) who have received at least two prior systemic therapies (at least one of them for advanced or metastatic setting) was accepted by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA). SKB264 (MK-2870) is expected to be the first domestic TROP2-ADC to be approved for marketing in China. This SKB264 New Drug Application is based on a multi-center, randomized, controlled phase 3 clinical study of SKB264 (MK-2870) monotherapy for second line or above locally advanced or metastatic

 SKB264 new drug application has been included in the priority review and approval process by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA). For drugs that included in the priority review, CDE will prioritize the review and verification procedures to effectively shorten the approval timeframe for launching clinical-valuable new drugs to the market. The Company plans to publish the Phase III clinical trial data at the Academic Conference 2024 and promote the early launch of SKB264, to enrich the clinical treatments for patients with second-line and above TNBC.

Breast cancer is the number one malignant tumor that seriously threatens women's health all over the world, and its incidence is increasing year by year. TNBC is a subtype of breast cancer with specific molecular expression characteristics, invasive behavior and metastatic patterns, and has a poorer prognosis than other subtypes of breast cancer, with higher rates of local recurrence and distant metastasis, and the 5-year survival rate is only 13% for advanced TNBC patients (National Cancer Institute 2022). Due to the lack of therapeutic targets such as endocrine and HER2, TNBC is insensitive to both hormonal and targeted therapies, and the current treatment is still based on chemotherapeutic agents. For patients with second-line and above TNBC, the progression-free survival of current clinically available chemotherapy regimens is less than 3 months, and overall survival is about 5-8 months (Kazmi et al. 2020, O'Shaughnessy et al. 2021), and there is a large and urgent unmet clinical need for more effective therapeutic agents

On December 2023, Kelun-Biotech updated efficacy and safety results from a phase II expansion cohort in patients with previously treated metastatic TNBC for SKB264 (MK-2870) have been presented at the 46th San Antonio Breast Cancer Symposium (SABCS). (SABCS 2023 news link here)

About SKB264 (MK-2870)

SKB264 is a representative innovative ADC targeting TROP2, developed by Kelun-Biotech 's internationally renowned ADC research and development platform—OptiDC. It consists of a humanized anti-TROP2 monoclonal antibody with high affinity and targeting, combined with the self-developed small toxin molecule T030 (a topoisomerase I inhibitor) through a stability-optimized CL2A linker. The drug-to-antibody ratio (DAR) averages as high as 7.4. The stability of SKB264 has been enhanced in two main ways, allowing more ADC to effectively reach tumor cells. Firstly, the antibody end of the linker uses a sulfonamide pyrimidine connector, which allows for irreversible coupling with the antibody. Secondly, T030 contains a methyl sulfone structure, which can securely bind with the toxin end of the linker. The linker of SKB264 is affected by both extracellular pH-sensitive cleavage and intracellular enzymatic cleavage within tumor cells, which leads to efficient release of the small toxin molecule to exert its anti-tumor effects. T030 activity is similar to that of DXd and also shows a “bystander effect”. In summary, SKB264 exerts its anti-tumor effect in three ways. Firstly, the pH-sensitive linker can cleave and release T030 in the acidic tumor microenvironment. Secondly, after being engulfed by tumor cells, SKB264 releases T030 via enzymatic cleavage. Thirdly, T030 can also penetrate the cell membrane to exert a "bystander effect" to kill surrounding tumor cells. With a high-affinity monoclonal antibody, highly active toxin molecule, good stability, and high DAR value, the overall design of SKB264 contributes to its robust anti-tumor activity which has been preliminarily demonstrated in clinical studies to date.

In May 2022, the Company licensed the exclusive rights to MSD (the tradename of Merck & Co., Inc, Rahway, NJ, USA) to develop, use, manufacture and commercialize SKB264 (MK-2870) in all territories outside of Greater China (includes Mainland China, Hong Kong, Macao, and Taiwan).

SKB264 has received 3 BTDs from the CDE of China’s NMPA for the treatment of locally advanced or metastatic TNBC, locally advanced or metastatic EGFR-mutated non-small cell lung cancer which has failed EGFR-TKI therapy, and locally advanced or metastatic hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer which has received at least second-line systemic therapy.

About Kelun-Biotech

Kelun-Biotech (6990.HK) is a holding subsidiary of Kelun Pharmaceutical (002422.SZ), which focuses on the R&D, manufacturing, commercialization and global collaboration of innovative biological drugs and small molecule drugs. The company focuses on major disease areas such as solid tumors, autoimmune, inflammatory, and metabolic diseases, and in establishing a globalized drug development and industrialization platform to address the unmet medical needs in China and the rest of world. The Company is committed to becoming a leading global enterprise in the field of innovative drugs.

At present, the Company has 33 ongoing innovative projects in major disease areas such as solid tumors, autoimmune, inflammatory, and metabolic diseases, including 14 projects in the clinical stage with several global trials being conducted simultaneously in multiple countries, including China, Europe, and the United States. The company has established one of the world’s leading proprietary ADC platforms, OptiDC, and has four ADC projects in the clinical stage (two of which are in the Phase III or NDA stage) and several projects in the preclinical stage. For more information, please visit https://kelun-biotech.com/.

References:

1. National Cancer Institute (2022) Cancer Stat Facts: Female Breast Cancer Subtypes.

2.[Kazmi S, Chatterjee D, Raju D, et al. (2020)] Overall survival analysis in patients with metastatic breast cancer and liver or lung metastases treated with eribulin, gemcitabine, or capecitabine. Breast Cancer Research and Treatment; 184(2):559-565.

3.[O'Shaughnessy J, Punie K, Oliveira M, et al. (2021)] Assessment of sacituzumab govitecan (SG) versus treatment of physician’s choice (TPC) cohort by agent in the phase 3 ASCENT study of patients (pts) with metastatic triple-negative breast cancer (mTNBC). (2021): 1077-1077. https://meetinglibrary.asco.org/record/198258/abstract

Forward-Looking Statements

This press release contains certain forward-looking statements. These statements are based on the beliefs of our management as well as assumptions made by and information currently available to our management. When used in this press release, the words “aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “going forward,” “intend,” “may,” “might,” “ought to,” “plan,” “potential,” “predict,” “project,” “seek,” “should,” “will,” “would” and the negative forms of these words and other similar expressions are intended to identify forward-looking statements. Such statements reflect the current views of our management with respect to future events, operations, liquidity and capital resources, some of which may not materialize or may change.

It is advised not to place any undue reliance on any forward-looking statements contained herein. The Company can give no assurance that these forward-looking statements will prove to have been correct. Expectations reflected in these forward-looking statements are subject to change and the Company undertakes no obligation to update or revise any forward-looking statements herein.

The 46th American San Antonio Breast Cancer Symposium (SABCS) will be held from December 5th to 9th, Central Standard Time (CST), and the latest clinical results evaluating Kelun-Biotech's TROP2 ADC SKB264 (also known as MK-2870) will be presented in the form of a poster spotlight presentationthe Phase II expansion study for patients with locally advanced or metastatic triple-negative breast cancer (TNBC).

Previously, Kelun-Biotech had presented efficacy and safety data of SKB264 from a Phase II expansion study in TNBC at 2022 SABCS, and this year we will present updated results including overall survival (OS) data.

The Phase II expansion study includes 59 patients with previously treated locally advanced or metastatic TNBC who received SKB264 monotherapy, with a median follow-up time of 22.8 months (data cutoff date: May 5, 2023).

Baseline characteristics:

Among the 59 enrolled patients, 89.8% (53 patients) had previously received three or more treatment regimens, 27.1% (16 patients) had previously received immunotherapy, about half had lung metastases, and one-third had liver metastases.

Efficacy:

Among the 59 treated patients with locally advanced or metastatic TNBC, the objective response rate (ORR) was 42.4%, with 3 patients achieving complete response (CR); the disease control rate (DCR) was 76.3%; the median duration of response (mDoR) was 11.5 months. In addition, median progression-free survival (mPFS) was 5.7 months, and the median overall survival (mOS) reached 16.8 months, with 12-month and 24-month OS rates of 65% and 39.5%, respectively. Nearly 40% of patients in the study treated with SKB264 were alive at two years.. In the subgroup of patients with high TROP2 expression (H-score>200, n=32), the ORR was 53.1%, mDoR was 11.1 months, mPFS was 5.8 months, mOS had not been reached, and the 12-month and 24-month OS rates were 65.3% and 57.3% respectively.

Safety:

Treatment-related adverse events (TRAEs) were mainly hematologic toxicity, which was clinically manageable. The most common treatment-related adverse events (TRAEs ≥10%) of Grade 3 or higher were neutrophil count decrease, white blood cell count decrease, anemia, and platelet count decrease. TRAEs led to dose reduction in 13.6% of patients. No interstitial lung disease (ILD) or diarrhea of Grade 3 or higher was observed. No deaths occurred due to TRAE.

 The updated clinical data indicated that patients with locally advanced or metastatic TNBC who have received multiple prior treatments may achieve sustained responses and extended overall survival (OS) trends with SKB264 treatment, and with manageable safety. Notably, a better response trend was observed in patients with locally advanced or metastatic TNBC with higher TROP2 expression.

Currently, the Phase III registrational clinical study of SKB264 monotherapy in at least second-line locally advanced or metastatic TNBC has reached the primary endpoint of improvement in PFS and has been included for priority review by the CDE. It is expected that a m product will be launched as soon as possible to benefit more patients.

About SKB264 (MK-2870)

SKB264 is a representative innovative ADC targeting TROP2, developed by Kelun-Biotech 's internationally renowned ADC research and development platform—OptiDC. It consists of a humanized anti-TROP2 monoclonal antibody with high affinity and targeting, combined with the self-developed small toxin molecule T030 (a topoisomerase I inhibitor) through a stability-optimized CL2A linker. The drug-to-antibody ratio (DAR) averages as high as 7.4. The stability of SKB264 has been enhanced in two main ways, allowing more ADC to effectively reach tumor cells. Firstly, the antibody end of the linker uses a sulfonamide pyrimidine connector, which allows for irreversible coupling with the antibody. Secondly, T030 contains a methyl sulfone structure, which can securely bind with the toxin end of the linker. The linker of SKB264 is affected by both extracellular pH-sensitive cleavage and intracellular enzymatic cleavage within tumor cells, which leads to efficient release of the small toxin molecule to exert its anti-tumor effects. T030 activity is similar to that of DXd and also shows a “bystander effect”. In summary, SKB264 exerts its anti-tumor effect in three ways. Firstly, the pH-sensitive linker can cleave and release T030 in the acidic tumor microenvironment. Secondly, after being engulfed by tumor cells, SKB264 releases T030 via enzymatic cleavage. Thirdly, T030 can also penetrate the cell membrane to exert a "bystander effect" to kill surrounding tumor cells. With a high-affinity monoclonal antibody, highly active toxin molecule, good stability, and high DAR value, the overall design of SKB264 contributes to its robust anti-tumor activity which has been preliminarily demonstrated in clinical studies to date.

SKB264 has received 3 Breakthrough Therapy Designations (BTDs) from the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) for the treatment of locally advanced or metastatic triple-negative breast cancer (TNBC), locally advanced or metastatic EGFR-mutated non-small cell lung cancer which has failed EGFR-TKI therapy, and locally advanced or metastatic hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer which has received at least second-line systemic therapy.

Based on preliminary clinical data, SKB264 is currently being evaluated in Phase Ⅱ and Phase Ⅲ clinical trials as either a single agent or combination therapy in multiple solid tumors.

Domestic development:

· the Phase Ⅲ pivotal clinical study of SKB264 monotherapy in patients with advanced or metastatic TNBC who have failed at least second-line therapy has reached the primary endpoint and is expected to be the first domestic TROP2-ADC to be approved for marketing.

· Clinical trial registration of SKB264 monotherapy in patients with TKI-resistant EGFR-mutated NSCLC are rapidly advancing.

· Several Phase Ⅱ clinical studies in combination with pembrolizumab (KEYTRUDA?, MSD’s anti-PD-1 therapy) or KL-A167 (Kelun’s anti-PD-L1 monoclonal antibody) are advancing steadily.

Developments abroad:

Kelun-Biotech has granted MSD the exclusive right to develop, manufacture, and commercialize SKB264 (MK-2870) in all territories outside of Greater China (includes Mainland China, Hong Kong, Macao, and Taiwan). 

About Kelun-Biotech

Kelun-Biotech（6990.HK）is a holding subsidiary of Kelun Pharmaceutical (002422.SZ), which focuses on the R&D, manufacturing, commercialization and global collaboration of innovative biological drugs and small molecule drugs. The company focuses on major disease areas such as solid tumors, autoimmune, inflammatory, and metabolic diseases, and in establishing a globalized drug development and industrialization platform to address the unmet medical needs in China and the rest of world. The Company is committed to becoming a leading global enterprise in the field of innovative drugs.

At present, the Company has 33 ongoing innovative projects in major disease areas such as solid tumors, autoimmune, inflammatory, and metabolic diseases, including 14 projects in the clinical stage with several global trials being conducted simultaneously in multiple countries, including China, Europe, and the United States. The company has established one of the world’s leading proprietary ADC platforms, OptiDC, and has four ADC projects in the clinical stage (two of which are in the Phase III or NDA stage) and several projects in the preclinical stage. For more information, please visit https://kelun-biotech.com/.

Forward-Looking Statements

This press release contains certain forward-looking statements. These statements are based on the beliefs of our management as well as assumptions made by and information currently available to our management. When used in this press release, the words “aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “going forward,” “intend,” “may,” “might,” “ought to,” “plan,” “potential,” “predict,” “project,” “seek,” “should,” “will,” “would” and the negative forms of these words and other similar expressions are intended to identify forward-looking statements. Such statements reflect the current views of our management with respect to future events, operations, liquidity and capital resources, some of which may not materialize or may change.

It is advised not to place any undue reliance on any forward-looking statements contained herein. The Company can give no assurance that these forward-looking statements will prove to have been correct. Expectations reflected in these forward-looking statements are subject to change and the Company undertakes no obligation to update or revise any forward-looking statements herein.

Kelun-Biotech announces that KL590586 (EP0031) (small molecule RET kinase inhibitor, also named A400) program, licensed to global ex-China partner Ellipses Pharma, has been granted Orphan Drug Designation (ODD) by the US Food and Drug Administration (FDA) for the treatment of RET fusion-positive solid tumors.

Orphan drugs are drugs used for the prevention, treatment and diagnosis of rare diseases. The FDA grants ODD for investigational treatments for rare diseases, such as RET fusion-positive solid tumours, defined as affecting fewer than 200,000 people in the United States. The designation is an important milestone in the development of innovative drugs, it is expected to accelerate the progress of clinical trials in the United States. ODD qualifies the developer for certain incentives with the goal of accelerating drug development for patients, including tax credits and seven years of market exclusivity in the US upon approval by the FDA.

A400 (EP0031) is a next generation selective RET inhibitor (SRI) with broad activity against common RET fusions and mutations. Therefore, A400 (EP0031) may overcome resistance mechanisms to first generation SRIs. In preclinical studies, A400 (EP0031) demonstrated favourable inhibitory activity against key RET kinases in-vitro and in-vivo. A400 (EP0031) also demonstrated good penetration of the blood brain barrier in animal models. At present, Kelun-Biotech is conducting A400 (EP0031) pivotal clinical study in China for RET-positive non-small cell lung cancer.

In March 2021, Kelun-Biotech granted Ellipses an exclusive license for A400 (EP0031) in certain territories including the US and Europe, with Kelun-Biotech retaining certain rights in Greater China and parts of the Asia-Pacific region such as Korea, Singapore, Malaysia.

In June 2022, the FDA approved an investigational new drug application for A400 (EP0031), and a Phase 1/2 trial is ongoing in patients with malignant tumors with RET gene alteration.

About RET altered malignancies

RET fusions and mutations are present in a wide range of tumors, including non-small cell lung cancer, medullary thyroid cancer and other types of thyroid cancer, as well as colorectal cancer, so targeting RET gene changes is promising as a treatment for all types of cancer. However, for patients with RET gene alteration, the effect of traditional chemotherapy and immunotherapy is limited, especially for patients with drug resistance after first-generation SRI treatment, the acceptable treatment options are limited, and the prognosis is poor, and there are still unmet clinical needs.

About Kelun-Biotech

Kelun-Biotech（6990.HK）is a holding subsidiary of Kelun Pharmaceutical (002422.SZ), which focuses on the R&D, manufacturing, commercialization and global collaboration of innovative biological drugs and small molecule drugs. The company focuses on major disease areas such as solid tumors, autoimmune, inflammatory, and metabolic diseases, and establishing an globalized drug development and industrialization platform for the unmet medical needs in China and worldwide. The Company is committed to becoming an leading global enterprise in the field of innovation drugs.

At the present, the company has 33 ongoing innovative projects in major disease areas such as solid tumors, autoimmune, inflammatory, and metabolic diseases, including 14 projects in the clinical stage with multiple global trials conducted simultaneously in several regions including China, Europe, and the United States. The company has established one of the world’s leading in-house developed ADC platform, OptiDC, and has four ADC projects in the clinical stage (two of which are in the phase III or NDA stage, respectively) and several projects in the preclinical stage.

For more information, please visit https://kelun-biotech.com/.

About Ellipses Pharma Limited

Ellipses Pharma is a global drug development company based in London, focused on accelerating the development of cancer treatments through an innovative drug development model that combines unbiased vetting to de-risk initial asset selection with an uninterrupted funding flow to minimise the time it takes to advance lead products through clinical trials and reach patients. For more information, please visit www.ellipses.life

First Patient Completed Dose Administration in Phase III Registrational Clinical Study of Kelun-Biotech SKB264 for the Treatment of Second-line and Above HR+/HER2- Breast Cancer

Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. (otherwise known as Kelun-Biotech, stock code: 6990.HK) completed the first patient dose administration in China for its Phase III registrational study of the innovative TROP2 ADC product, SKB264 (also known as MK-2870) recently. This study, led by Professor Xu Binghe from the Cancer Hospital of Chinese Academy of Medical Sciences, is investigating the use of SKB264 for the treatment of second-line and above hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer.

SKB264 (MK-2870), which is jointly developed with MSD (the tradename of Merck & Co., Inc., Rahway, NJ, USA), is one of the core products of Kelun-Biotech and possesses independent intellectual property rights, is the first domestically produced TROP2-ADC to secure Breakthrough Therapy Designation (BTD) from the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) for the treatment of HR+/HER2- breast cancer and has subsequently entered into Phase III registrational studies. Accordingly, Kelun-Biotech has carefully designed a comprehensive development plan for this core asset in China. Currently, SKB264 monotherapy is being investigated in Phase III registrational clinical studies for HR+/HER2- breast cancer patients in the second-line setting and beyond. Additionally, SKB264 in combination or uncombination with A167 (anti-PD-L1 monoclonal antibody) is undergoing Phase II investigational studies in first-line patients. In addition, SKB264 for patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) who have received at least 2 prior systemic therapies, with at least 1 of those therapies targeting an advanced or metastatic stage, has been approved for in Priority Review by the CDE.

According to the latest data of the International Agency for Research on Cancer (IARC), 2.3 million new cases of breast cancer occurred worldwide in 2020, accounting for about 25% of female malignancies. Surpassing lung cancer for the first time, it is becoming the most common malignant tumor and poses a serious threat to the health of women worldwide. The annual number of new cases of female breast cancer in China (416,000) is far higher than that in other countries, ranking first in the world. Approximately 60% of breast cancer patients in China have tumors that express HR+/HER2-, and about 70%[1-2] with a higher proportion abroad. As SKB264 (MK-2870) progressively advances into the Phase III registrational clinical study for second-line and above HR+/HER2- breast cancer, and successfully administered the initial patient dosage, this provides an encouraging indication that SKB264 (MK-2870) is poised to benefit a larger population of HR+/HER2- breast cancer patients in the near future.

About SKB264 (MK-2870)

SKB264 is an innovative TROP2-directed ADC which was developed by OptiDC, a well-known international ADC R&D platform of Kelun-Biotech, using a proprietary payload-linker strategy (Kthiol design strategy) that achieves an optimized balance of ADC safety and efficacy by combining novel irreversible antibody conjugation chemistry, pH-sensitive payload release mechanisms, and site-specific moderately potent toxin molecules with a DAR of 7.4 (novel topoisomerase I inhibitors) ^[3].

 SKB264 has received 3 Breakthrough Therapy Designations (BTDs) from the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) for the treatment of locally advanced or metastatic triple-negative breast cancer (TNBC), locally advanced or metastatic EGFR-mutated non-small cell lung cancer which has failed EGFR-TKI therapy, and locally advanced or metastatic hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer which has received at least second-line systemic therapy.

Based on preliminary clinical data, SKB264 is currently being evaluated in Phase Ⅱ and Phase Ⅲ clinical trials as either a single agent or combination therapy in multiple solid tumors.

Domestic development:

• the Phase Ⅲ registrational clinical study of SKB264 monotherapy in patients with advanced or metastatic TNBC who have failed at least second-line therapy has arrived the primary endpoint and is expected to be the first domestic TROP2-ADC to be approved for marketing.

• Phase III clinical studies of SKB264 monotherapy in patients with TKI-resistant EGFR-mutated NSCLC are rapidly advancing.

• Several Phase Ⅱ clinical studies in combination with pembrolizumab (KEYTRUDA?, MSD’s anti-PD-1 therapy) or KL-A167 (Kelun’s anti-PD-L1 monoclonal antibody) are conducting smoothly.

Developments abroad:

Kelun-Biotech has granted MSD the exclusive rights to develop, manufacture, and commercialize SKB264 (MK-2870) in all territories outside of Greater China (includes Mainland China, Hong Kong, Macao, and Taiwan). Currently, MSD has initiated a clinical study of MK-2870 EGFR-mutant NSCLC, and several other global multicenter registrational clinical studies are under preparation.

About Kelun-Biotech

Kelun-Biotech（6990.HK）is a subsidiary of Kelun Pharmaceutical Holdings, which focuses on the R&D, manufacture, commercialization and international cooperation of biotechnology-derived pharmaceuticals and innovative small molecule drugs. The company focuses on major disease areas such as solid tumors, autoimmune, inflammatory, and metabolic disease. Building an international drug development and industrialization platform around the unmet clinical needs of the world and China, the Company is committed to becoming an internationally leading enterprise in the field of innovation. Significant progress has been made in the field of biotechnological drugs, including ADCs, monoclonal antibodies, bispecific antibodies, and sought-after technologies for innovative small molecule drugs. OptiDC, an internationally renowned ADC research and development platform, has been successfully constructed, and 4 ADCs are in clinical trials (including 2 in the registrational Phase III or NDA filing stage), along with several projects in preclinical development. At present, the company has 33 innovative projects for the treatment of major diseases such as solid tumors, autoimmune, inflammatory, and metabolic disease, and 14 projects are advancing in clinical studies, including multiple global multicenter clinical trials which are being conducted simultaneously in several countries including China, Europe, and the United States. To learn more, please visit https://kelun-biotech.com/ .

References:

[1] 郑莹, 等. 中国癌症杂志, 2013(08):10-18.

[2] DeSantis CE, et al. CA Cancer J Clin, 2016, 66(1):31-42.

[3] Cheng Yezhe, et al. Preclinical profiles of SKB264, a novel anti-TROP2 antibody conjugated to topoisomerase inhibitor, demonstrated promising antitumor efficacy compared to IMMU-132. Frontiers in Oncology, Vol 12, 2022.

Forward-Looking Statements

This press release contains certain forward-looking statements. These statements are based on the beliefs of our management as well as assumptions made by and information currently available to our management. When used in this press release, the words “aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “going forward,” “intend,” “may,” “might,” “ought to,” “plan,” “potential,” “predict,” “project,” “seek,” “should,” “will,” “would” and the negative forms of these words and other similar expressions are intended to identify forward-looking statements. Such statements reflect the current views of our management with respect to future events, operations, liquidity and capital resources, some of which may not materialize or may change.

It is advised not to place any undue reliance on any forward-looking statements contained herein. The Company can give no assurance that these forward-looking statements will prove to have been correct. Expectations reflected in these forward-looking statements are subject to change and the Company undertakes no obligation to update or revise any forward-looking statements herein.

On October 20, 2023, the European Society for Medical Oncology (ESMO) Conference grandly commenced in Madrid, Spain. The ESMO Conference is the most esteemed and influential oncology conference in Europe, and this annual event garners the participation of top-tier experts and scholars from around the globe. By disseminating the latest findings in cancer clinical research, the ESMO Conference provides a high-quality platform for dialogue and learning for oncologists and other relevant stakeholders, thereby significantly influencing the practice of oncology.

During the ESMO Conference, Kelun-Biotech and MSD had a cordial meeting in Madrid on the afternoon of October 21st, local time. The leadership team and clinical team from both parties were present at ‘this meeting.

During the meeting, the management and project teams of Kelun-Biotech and MSD deliberated on the research and development progress of the multi-ongoing clinical collaboration projects and the preclinical projects that will soon enter into clinical stage. They engaged in extensive discussions regarding the potential synergy and upcoming plans for Ｅxecution of global clinical studies for the collaboration projects. Both teams are expected to work closely together to accelerate the development of projects in the clinical stage, including the rapid expansion of indications, exploration of monotherapy and combination therapy activities, and therapeutic benefit in the early-stage setting of certain cancers. This amicable meeting has significantly bolstered the foundation of collaboration between Kelun-Biotech and MSD and considerably advanced the subsequent clinical development of the ongoing collaboration projects. In addition, there is a possibility for Kelun and MSD to explore other collaboration opportunities on new target ADC assets.

On the morning of October 22nd (local time), the ESMO Conference published the results from a Phase I/II basket study in the form of a mini-oral presentation. This study investigated the innovative TROP2-ADC (SKB264, also known as MK-2870), which is under joint development by both Kelun-Biotech and MSD, for the treatment of patients with hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC). This oral presentation is based on an abstract that was published on the ESMO official website on October 16th.

About Kelun-Biotech

Kelun-Biotech is a subsidiary of Kelun Pharmaceutical Holdings, which focuses on the R&D, manufacture, commercialization and international cooperation of biotechnology-derived pharmaceuticals and innovative small molecule drugs. The company focuses on major disease areas such as solid tumors, autoimmune, inflammatory, and metabolic disease. Building an international drug development and industrialization platform around the unmet clinical needs of the world and China, the Company is committed to becoming an internationally leading enterprise in the field of innovation. Significant progress has been made in the field of biotechnological drugs, including ADCs, monoclonal antibodies, bispecific antibodies, and sought-after technologies for innovative small molecule drugs. OptiDC, an internationally renowned ADC research and development platform, has been successfully constructed, and 4 ADCs are in clinical trials (including 2 in the registrational Phase III or NDA filing stage), along with several projects in preclinical development. At present, the company has 33 innovative projects for the treatment of major diseases such as solid tumors, autoimmune, inflammatory, and metabolic disease, and 14 projects are advancing in clinical studies, including multiple global multicenter clinical trials which are being conducted simultaneously in several countries including China, Europe, and the United States. To learn more, please visit https://kelun-biotech.com/ .

On September 14, Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. reached an exclusive license agreement with the Affiliated Hospital of Southwest Medical University on the bone-targeting radiolabeled drug TBM-001. Kelun-Biotech will obtain the global exclusive rights to the TBM-001 project, including worldwide research, development, production, and commercial promotion, and global sublicensing rights. Kelun-Biotech will pay the Affiliated Hospital of Southwest Medical University a total of 38.5 million yuan for the initial contract payment and development milestones, as well as royalties from foreign re-licensing and net sales after product launch.

The signing ceremony was held at Nanyuan Hotel in Luzhou City, Sichuan Province. The Deputy Mayor of Luzhou City Suping Luo, the Vice President of Southwest Medical University Minhai Nie, the Party Secretary of the Affiliated Hospital of Southwest Medical University Yong Xu, the Dean Yong Jiang, the Chairman of Kelun-Biotech Gexin Liu, and the General Manager of Kelun-Biotech Junyou Ge, etc. attended the signing ceremony.

The radionuclide-drug conjugate (RDC) drug is an emerging tumor precision diagnostic and therapeutic drug developed based on radionuclide-targeting ligand molecular coupling technology. RDC uses tumor target-specific molecules as carriers to guide radionuclides to accurately target tumors and achieve brachytherapy, which has unique advantages in early diagnosis of tumors and therapeutic evaluation.TBM-001 is an innovative RDC drug independently developed by Professor CY's team from the Department of Nuclear Medicine of the Affiliated Hospital of Southwest Medical University, and intended to be used for early diagnosis of bone tumor metastasis and precision targeted therapy. According to data from clinical researches initiated by the investigators, TBM-001 has shown effectiveness and safety superior to existing radioactive drug for bone metastasis in imaging diagnosis and treatment of late-stage prostate cancer, breast cancer, lung cancer and other bone metastases of malignant tumor, and significantly improved the quality of life of patients.

Regarding this cooperation, Gexin Liu, the chairman of Kelun-Biotech, stated that radioactive drug is an industry that require high investment with a high barrier of entry. The strong alliance between a regional leading university and high-level technology company is an important measure to break through key technologies and resource links in the industry, and an effective way to promote independent innovation and achievement transformation in the field of nuclear medicine in our country. Both parties are leaders in their respective fields. We all boasts distinct advantages in nuclear medicine discovery, clinical transformation, and conjugated drugs represented by ADC, and we all have industry-leading innovative achievements. This signing marks a new stage in the strategic cooperation between the two parties, highlighting our pragmatic development philosophy and our will and belief in working together for a win-win outcome and benefiting patients in the field of targeting radionuclide-drug conjugate.

Regarding this cooperation, Junyou Ge, the general manager of Kelun-Biotech, stated that RDC has become a new hot topic for anti-tumor drug research and development following Antibody-Drug Conjugates (ADC) at present. TBM-001 is a bone-targeting RDC with differentiated advantages. The innovative technology of Affiliated Hospital of Southwest Medical University and its philosophy are very consistent with Kelun-Biotech's strategy to strengthen the innovative advantages in the field of targeted drug conjugates, so we are pleased to cooperate with the Affiliated Hospital of Southwest Medical University. The Department of Nuclear Medicine has mature platform resources in the discovery of radioactive drugs and the clinical transformation of diagnosis and treatment. Combined with Kelun-Biotech's technical advantages in the ADC field and a complete new drug research and development system, both parties shall be benefited to jointly enter the RDC frontier field with high resource and technical barriers.

Minhai Nie, the Vice President of Southwest Medical University, stated that the Department of Nuclear Medicine has deep technical experience in clinical diagnosis, treatment, research and development of radiopharmaceuticals and clinical transformation. It possesses a Class IV "Radiopharmaceuticals Use Permit" and obtained National Drug Clinical Trial Accreditation. We look forward to our cooperation based on complementary advantages and efficient collaboration to realize the commercial value of TBM-001 as soon as possible, allowing patients with bone metastases from tumors to use more effective drugs at an earlier date.

Suping Luo, the Deputy Mayor of Luzhou City, congratulates both parties on reaching a cooperation on the TBM-001 project. She mentioned that the municipal party committee and the municipal government will fully support our cooperation, and they will provide corresponding services to support the strong alliance between Kelun-Biotech and the Affiliated Hospital of Southwest Medical University to help them grow and develop. She hopes that both parties will leverage their own advantages to achieve a perfect combination of conjugate and nuclear medicine, provide new treatment techniques to ensure the health of the people, and promote the high-quality development of the bio-nuclear medicine industry in Luzhou, Sichuan, and even the whole country.

In December 2022, the Affiliated Hospital of Southwest Medical University reached an cooperation with the "National Engineering Research Center for Bio-targeted Drugs" of Kelun-Biotech. The cooperation have started in the field of radioactive drugs. In addition to TBM-001, the Company and the Affiliated Hospital of Southwest Medical University have also initiated the co-development of other RDC drugs targeting unmet clinical needs. Kelun-Biotech will work together with partners in the industry to integrate superior resources, fully utilize the technical advantages of the OptiDC platform, and accelerate the pace in tapping into the new filed of RDC.

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About the Affiliated Hospital of Southwest Medical University

The affiliated hospital of Southwest Medical University was established in August 1950, located in Luzhou City, Sichuan Province. It is a tertiary general hospital directly under the Health Commission of Sichuan Provincial. It serves nearly 60 million people in the combined region of Sichuan, Chongqing, Yunnan, and Guizhou provinces. The hospital currently has two campuses, Zhongshan and Kangjian Center, and is a comprehensive clinical teaching hospital integrating medical treatment, teaching, and scientific research.

About the Nuclear Medicine Department of the Affiliated Hospital of Southwest Medical University

The Department of Nuclear Medicine at the Affiliated Hospital of Southwest Medical University is a top-tier nuclear medicine department in China. According to the big data analysis of SCI papers of nuclear medicine published worldwide in 2022 released by the authoritative organization Healsan Consulting LLC, the Affiliated Hospital of Southwest Medical University ranks third in the world and first in China in terms of the impact of its SCI papers of nuclear medicine.

About Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.

Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. (6990.HK) (hereinafter referred to as "Kelun-Biotech") is a holding subsidiary of Kelun Pharmaceutical. It is committed to the R&D, manufacturing, commercialization, and international cooperation of biotechnological drugs and innovative small molecule drugs. Kelun-Biotech has been committed to addressing medical needs in China and globally. With a key focus on major disease areas such as cancer, autoimmunity, inflammation, and metabolism, it aims to build an international drug R&D and industrialization platform, striving to become a leading innovative enterprise. Kelun-Biotech has made significant progress in the field of biotechnological drugs, including ADCs, monoclonal antibodies, bispecific antibodies, and innovative small molecule drugs with new targets. Kelun-Biotech has successfully established the internationally renowned ADC R&D platform OptiDC, with 4 ADCs investigated in clinical studies (2 of which are in the registration Phase III or NDA stage, respectively), and several ADCs in preclinical studies. Kelun-Biotech currently has 33 innovative projects for the treatment of major diseases such as cancer, autoimmunity, inflammation, and metabolism, including 14 in clinical stage. Several clinical trials are multi-center studies conducted simultaneously in multiple countries including China, Europe and America.

On September 11, 2023, Kelun-Biotech announced that the major product A140 solution for infusion (Cetuximab Solution for Infusion, trade name: Datalai?) was recently accepted for marketing application by the Center for Drug Evaluation of the National Medical Products Administration (acceptance number: CXSS2300075).

A140 solution for infusion is the first cetuximab solution for infusion that filed an application for marketing in China. It is intended for the treatment of metastatic colorectal cancer with wild-type RAS genes: used in combination with FOLFOX or FOLFIRI regimens for first-line treatment; and in combination with irinotecan for patients who have failed treatment containing irinotecan. At the same time, it is also intended for the treatment of head and neck squamous cell carcinoma (HNSCC): used in combination with platinum and fluorouracil chemotherapy for first-line treatment of recurrent and/or metastatic diseases; and in combination with radiotherapy for the treatment of locally advanced diseases.

This product is a recombinant epidermal growth factor receptor (EGFR) human-mouse chimeric monoclonal antibody (mAb), which inhibits the growth and survival of tumor cells expressing EGFR. The A140 solution for infusion is firstly developed in China to be filed for production in accordance with the “Guidelines for Design of Clinical Trials of Injectable Cetuximab Biosimilar (for Trial Implementation)” using the original cetuximab as a reference drug. The reference drug ctuximab (trade name: Erbitux?) was approved for import into China in 2007. The approved indications in China include metastatic colorectal cancer and HNSCC. As of 2022, the global market size of cetuximab has reached 1.73 billion US dollars, and the sales in China have reached 2.253 billion yuan. Due to reasons such as drug accessibility, the clinical demand for cetuximab has not been met. A140 solution for infusion has the same amino acid sequence and mechanism of action as cetuximab, and its proposed indications are consistent with Erbitux?. The A140 solution for infusion will provide significantly increased accessibility once the Application is approved, and will bring compliant, safe, and effective treatment options to more patients.

In recent years, due to factors such as population aging and unhealthy lifestyles caused by improved living standards (such as sedentary lifestyle, high-fat and high-protein diets, etc.), the incidence of colorectal cancer in China has been on the rise. According to the epidemiological data of cancer released by the National Cancer Center of China in 2022, there were 408,000 new cases of colorectal cancer and 196,000 deaths in China. The incidence and mortality rates of colorectal cancer ranked second and fourth among all malignant tumors, respectively. Currently, cetuximab is one of the main treatment options for metastatic colorectal cancer with the primary tumor located in the left half of the colon and expressing wild-type RAS EGFR.

Head and neck squamous cell carcinoma (HNSCC) is the most common malignant tumor in the head and neck area. In 2022, there were about 78,000 new cases of HNSCC and over 40,000 deaths in China. The incidence and mortality rates of HNSCC ranks seventh and sixth among all malignant tumors in Chinese men, respectively. Since cetuximab was approved globally for first-line treatment of recurrent or metastatic HNSCC and used in combination with radiotherapy for locally advanced HNSCC, it has allowed many HNSCC patients worldwide to receive treatment plans containing cetuximab, which improved their quality of life and extended their life expectancy.

The application for registration of A140 solution for infusion is based on information from a series of studies, including pharmacologic comparative study, non-clinical comparative study, and clinical comparative study. The Phase III clinical safety and efficacy study of A140 is a randomized, double-blinded, parallel-controlled, multi-centered Phase III clinical study comparing the efficacy, safety and immunogenicity of A140 and the original cetuximab combination chemotherapy regimen (mFOLFOX6 regimen) for first-line treatment of RAS wild-type metastatic colorectal cancer.

About Kelun-Biotech

Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. (6990.HK) (hereinafter referred to as "Kelun-Biotech") is a holding subsidiary of Kelun Pharmaceutical. It is committed to the R&D, manufacturing, commercialization, and international cooperation of biotechnological drugs and innovative small molecule drugs. Kelun-Biotech has been committed to addressing medical needs in China and globally. With a key focus on major disease areas such as cancer, autoimmunity, inflammation, and metabolism, it aims to build an international drug R&D and industrialization platform, striving to become a leading innovative enterprise. Kelun-Biotech has made significant progress in the field of biotechnological drugs, including ADCs, monoclonal antibodies, bispecific antibodies, and innovative small molecule drugs with new targets. Kelun-Biotech has successfully established the internationally renowned ADC R&D platform OptiDC, with 4 ADCs investigated in clinical studies (2 of which are in the registration Phase III or NDA stage, respectively), and several ADCs in preclinical studies. Kelun-Biotech currently has 33 innovative projects for the treatment of major diseases such as cancer, autoimmunity, inflammation, and metabolism, including 14 in clinical stage. Several clinical trials are multi-center studies conducted simultaneously in multiple countries including China, Europe and America. For more information, please visit https://kelun-biotech.com/.

To enrich the leisure life of employees, improve their physical fitness, and enhance team cohesion, the labor union of Kelun-Biotech held the seventh badminton match on September 2, 2023. There were 7 participating teams, with nearly 90 employees, at this match. Regular team matches and fun games (juggling, serving, and drawing) were arranged. The participating players fought hard on the court, showcasing the charm of sports competition. The entire event was full of exciting moments.

The match was conducted under the following principle, i.e., " It’s not winning that matters, but friendship and safety". Before the competition, each team took their spare time for serious training to continuously improving their skills in order to get prepared to achieve excellent results. During the competition, they strove hard and sweat on the court. Off the court, each team communicated with one another and made progress together. Meanwhile, the members of the organizing committee and the chief referee took their responsibilities and made fair judgments. Their heart-devoted contrition ensured the smooth running of this badminton match.

Intense battles have unfolded between the teams since the beginning of the match. The players fought for every point with full vigor and vitality, and participated in the competition with full passion, high morale, and a spirit of unity. Although the team members were randomly grouped without good rapport, this does not affect their performance on the field. During the break, the team leaders timely arranged tactics and mobilized their team members to ensure that they sprint on the court in the best condition.

After intense competition, the first, second, and third places were finally determined, and the Excellent Team Award was bestowed. Each team received rewards such as sports backpacks, fascia guns, and badminton strings.

The badminton match is not just a competitive event, but also an opportunity to promote employee communication and cooperation. Through the match, employees not only exercised their bodies and improved their technical skills, but also enhanced friendship and cooperation between departments. Meanwhile, this match fully demonstrates the spirit of our employees who unite as one to make positive and striving efforts, and further highlights the cultural charm of "health, happiness, and confidence" in the company.