SUZHOU, China, Aug. 25, 2022 /PRNewswire/ — CStone Pharmaceuticals (“CStone”, HKEX: 2616), a leading biopharmaceutical company focused on research, development, and commercialization of innovative immuno-oncology therapies and precision medicines, today reported 2022 interim financial results and recent business highlights, and leadership transition.
In the first of 2022, CStone continued to achieve breakthroughs with eye-catching performance. So far this year, we’ve obtained four NDA approvals for three of our innovative drugs. With the successful launch of potential best-in-class drug CEJEMLY® and first-in-class drug TIBSOVO®, we now have four commercial-stage products that position us as a leader in the biotech sector in China. We leveraged our well-established commercial operation system to rapidly advance commercialization through diverse paths. Thanks to our various initiatives and effective delivery, our product revenue grew steadily.
Innovation is the cornerstone for a biopharmaceutical company. This year, we’ve submitted two NDAs and presented clinical data at multiple international academic conferences. The clinical data from sugemalimab in stage III and stage IV NSCLC were published in the world-leading clinical oncology journal, The Lancet Oncology. Patient enrollment wrapped up in several phase 3 registrational studies. In addition, the first patient was enrolled in the pivotal study of lorlatinib, which we are co-developing with Pfizer, for the treatment of c-ros oncogene 1 (ROS1)-positive advanced NSCLC. With all these efforts, we are further diversifying our pipeline to meet patient needs and maximize the commercial value of our products.
Our Pipeline 2.0 strategy was in full swing as we secured breakthroughs in early-stage pipeline. The investigational new drug applications were approved in the U.S., Australia, and Mainland China for CS5001, a potential global best-in-class antibody-drug conjugate (ADC), targeting receptor tyrosine kinase-like orphan receptor 1 (ROR1), and the first patient has been dosed in a multi-regional clinical trial in the U.S. We’ve also been gearing up more than 10 early discovery and technology platform projects, with several of them achieving milestones.
We worked more closely with key global strategic partners to accelerate our commercialization agenda and further bolster our first-in-class/best-in-class early-stage pipeline. We officially launched CStone Global Industrialization Base, and are enabling technology transfer for several products in a bid to improve our long-term profitability.
CStone will continue to enhance its organic R&D and forge ahead with more than ten early discovery projects. It will expand strategic partnerships with its robust clinical development capabilities, accelerate commercialization to maximize product value and bolster financial performance to respond to market changes in an agile way.
The board (the “Board”) of directors of CStone Pharmaceuticals (the “Company”) also announced that Dr. Frank Ningjun Jiang, after leading CStone’s development for six years, had decided to retire from and will cease to serve as the CEO, the Executive Director, the Chairman of the Strategy Committee and an authorized representative of the Company, in effect from August 25, 2022. Dr. Jiang will serve as the Senior Advisor of the Company until the end of 2022 to ensure a smooth transition of the Company’s operations.
The Board announced that Dr. Jianxin Yang, the Senior Vice President and Chief Medical Officer of the Company, has been appointed as the CEO, the Executive Director, the Chairman of the Strategy Committee and an authorized representative of the Company, in effect from August 25, 2022.
Dr. Wei Li, Chairman of the Board, said, “Dr. Jiang joined CStone as the founding CEO at the beginning of CStone’s establishment. With more than 20 years of experience in pharmaceutical innovation and multinational enterprise management, Dr. Jiang pioneered CStone’s path of pharmaceutical innovation in China. Under his leadership, CStone has attracted outstanding management teams worldwide and established an innovative strategy with a global vision. As a result, CStone was successfully listed on the Stock Exchange in merely three years, obtained four NDAs (4 market drugs with 9 NDA) for FIC/BIC innovative immune-oncology drugs in six years, built a balanced oncology-focused pipeline of 15 innovative products, laying a solid foundation for its continuous climb to new heights. We are very fortunate to have had such an outstanding leader as Dr. Jiang during a critical period in the establishment and development of the Company. The Board would like to take this opportunity to express its sincere gratitude to Dr. Jiang for his valuable contribution to the Company during his tenure of office.”
The Board takes this opportunity to welcome Dr. Jianxin Yang to his new appointments. Dr. Yang, M.D., Ph.D., has been the Company’s Senior Vice President and Chief Medical Officer since December 2016. In this role, he was responsible for developing and implementing the overall clinical strategy. Dr. Yang has over 25 years of experience in biomedical research and clinical development of oncology drugs in the U.S. and China. Throughout his career, Dr. Yang has made significant contributions to the successful development of several anticancer drugs. He is also the author of over 50 publications and the inventor of 9 patents.
Dr. Yang received a bachelor’s degree in medicine from Xianning Branch of Hubei Medical College, (currently known as Hubei Institute of Science and Technology) in Hubei, China in July 1985 and a master’s degree in pathophysiology from Nanjing Medical College, (currently known as Nanjing Medical University) in Nanjing, China in July 1989. He then received his Ph.D. training in molecular biology with Nobel Laureates Drs. Michael S. Brown and Joseph L. Goldstein at the University of Texas Southwestern Medical Center at Dallas, U.S. in June 1995. He conducted his postdoctoral training in chemical biology with Dr. Stuart L. Schreiber at Harvard University in the United States from 1995 to 1998.
The first half of 2022 has been fruitful for CStone with milestones across our maturing pipeline and business. Our commercial successes in the first half, including the launch of two First-in-Class (“FIC”)/Best-in-Class (“BIC”) therapies, put us in an elite tier of innovative biopharmaceutical companies from China as we now have four products in market and generating recurring revenue to provide financial strength and fund further growth initiatives. For the six months ended June 30, 2022 and as of the date of this announcement, significant progress has been made with respect to our product pipeline and business operations. A shortlist of our achievements over this period includes:
RMB261.8 million in total revenue, including RMB174.5 million of commercial revenue which is composed of RMB161.4 million in sales of our precision medicines and RMB13.1 million in royalty income of sugemalimab two new products launched: sugemalimab and ivosidenib, bringing us to a total of four products commercially launched and generating sales, several of which have no competitors and therefore at highly advantageous market positions four NDA approvals obtained for three products: sugemalimab for stage III NSCLC in mainland China, ivosidenib for IDH1-mutant relapsed/refractory acute myeloid leukemia (“R/ R AML”) in mainland China, pralsetinib for RET-mutant medullary thyroid cancer (“MTC”) & RET fusion-positive thyroid cancer (“TC”) in mainland China, and pralsetinib for RET fusion-positive non-small cell lung cancer (“NSCLC”) in Hong Kong, China two NDAs filed: pralsetinib for RET fusion-positive NSCLC and TC, RET-mutant MTC in Taiwan, China and pralsetinib for RET fusion-positive NSCLC in Hong Kong, China three positive topline data readouts for sugemalimab in various indications: relapsed or refractory extranodal natural killer/T-cell lymphoma (“R/R ENKTL”), first-line stage IV NSCLC and stage III NSCLC seven data presentations/publications at/on global academic conferences/top-tier medical journals two key clinical programs commenced: the first-in-human (“FIH”) global study of CS5001 (ROR1 ADC) and the pivotal study of lorlatinib for ROS1-positive advanced NSCLC in mainland China Over ten discovery projects in progress, including multi-specifics, antibody drug conjugates, and a proprietary platform for drugging intractable intracellular targets Further deepened our strategic partnerships with Pfizer, EQRx and Hengrui Successfully started pilot operations in our state-of-the-art manufacturing facility and achieved a technology transfer milestone for avapritinib
These achievements represent only a snapshot of what we have accomplished.
We have achieved healthy and steady growth in commercial capabilities, demonstrated again in our new product and indication launches, as well as increasing brand influence. We have remained focused on key innovative initiatives that will drive continuous growth: 1) enhancing clinical education and testing assistance to expand the pool of potential patients for our drugs; 2) further building-out scientific leadership by broadening the influence of guideline inclusions through academic activities; 3) optimizing our pricing strategy, improving hospital/direct-to-patient (“DTP”) pharmacy listing and entering into more insurance programs to expand accessibility and affordability; and 4) providing physician/patient education for better patient support and long-term medication. We have specifically focused our efforts on ensuring dedicated sales force coverage and enhancing sales productivity.
Our efforts to date have led to several successes. We have expanded our sales force coverage to approximately 700 hospitals as of the date of this announcement, up from 600 in 2021, accounting for approximately 70-80% of the relevant market for precision medicines. Currently, our in-market precision medicines have been included in 15 national guidelines, up from over ten at the time we released our 2021 annual results. In addition, they have been listed in 85 supplemental insurance plans, up from over 60 at the time we released our 2021 annual results.
Our clinical team has demonstrated the ability to translate our advantages in innovation, speed, and quality into tangible results for patients and our business. We successfully obtained four NDA approvals covering three products, including two FIC precision medicines as well as our flagship immuno-oncology backbone drug. During the Reporting Period, sugemalimab received approval from the National Medical Products Administration (“NMPA”) for patients with stage III NSCLC without disease progression after concurrent or sequential chemoradiotherapy, making it the world’s only anti-PD-1/PD-L1 monoclonal antibody approved in this patient population, significantly strengthened its market positioning and adoption momentum. Ivosidenib, a first-in- class drug, was approved in mainland China for adult patients with R/R AML who have an IDH1 mutation. In addition, pralsetinib received approval for RET-mutant MTC and RET fusion-positive TC in mainland China, and received approval for RET fusion-positive NSCLC in Hong Kong, China.
The broader spectrum of our clinical development success is reflected in the fact that CStone had four data presentations at the 2022 American Society of Clinical Oncology Annual Meeting (ASCO 2022) and the 2022 World Conference on Lung Cancer (WCLC 2022), and three publications on The New England Journal of Medicine and The Lancet Oncology as of the date of this announcement. These presentations and publications covered study results of sugemalimab in stage III NSCLC, stage IV NSCLC and R/R ENKTL, nofazinlimab combined with lenvatinib in hepatocellular carcinoma (“HCC”) and ivosidenib in first-line acute myeloid leukemia (“AML”). In addition to the late-stage clinical development programs, meaningful progresses have also been made in our two early-stage programs since the last report including the progression into proof-of- concept (“PoC”) expansion cohorts in the global phase I study of CS2006 (NM21-1480; PD-L1/4- 1BB/HSA tri-specific) and robust enrolment of the FIH study of CS5001 (ROR1 ADC) in the U.S. and Australia.
Our research team has continued to make advances in our innovative early-stage programs, based on our “Gemstones on the Ring” research strategy. This strategy capitalizes on the modular “plug- and-play” nature of biologics. Following this research framework, we have in progress a total of over ten discovery projects and expect two potential FIC/BIC immune-oncology programs declaring pre-clinical candidates (“PCCs”) this year, including one tri-specific molecule against PD-L1, VEGF plus another immuno-oncology (“I/O” or “IO”) target, and one antibody-cytokine fusion molecule. Additionally, we have made great strides in our proprietary cell-penetrating therapeutic platform for targeting intractable intracellular proteins by achieving PoC in vitro for one of the treatment modalities using this platform.
Lastly, we launched pilot operations of our manufacturing facility as expected. We are steadily advancing our readiness for full-scale operations to produce our products for clinical trials as well as commercial sales. We are also in the process of technology transfer for multiple imported products which will reduce costs and improve long-term profitability of our products. Specifically, we have completed the technology transfer submission to Center for Drug Evaluation of NMPA (“CDE”) for avapritinib in July 2022.
I. Multiple Product Launches and Continued Robust Commercial Efforts
Since 2021, we have obtained a total of nine NDA approvals for four products, including four NDA approvals for three products as at the date of this announcement. Our commercial team continued its rapid execution of pre-launch and post-launch efforts to set the stage for market adoption of our products. TIBSOVO® (ivosidenib) received NDA approval in January 2022, achieved successful commercial launch in June 2022 (first prescriptions on June 8), and gained endorsement from all top KOLs in hematology.
Meanwhile, they have kept up robust efforts to engage the healthcare community, including healthcare providers, academic societies, patient groups, hospitals, pharmacies, payors, and other stakeholders, to provide education on our products and demonstrate our scientific leadership. In addition, they have expanded accessibility and affordability of our products through various patient identification programs and by working with payors to promote coverage of them in insurance programs.
Highlights and details on our commercial activities as of the date of this announcement are as follows:
Steady and Continued Ramp Up in Product Sales
We generated overall net sales of RMB161.4 million in the first half of 2022 on the basis of a steady growth in the total product sales of GAVRETO® (pralsetinib) and AYVAKIT® (avapritinib), as well as a successful launch of TIBSOVO® (ivosidenib). Achieved Successful Launches of New Products and Indications
We expanded the number of in-market products and indications they cover with effective launches that position them to become meaningful future contributors to revenue. TIBSOVO® (ivosidenib): Launched in mainland China, with 100% channel availability in major target hospitals and pharmacies. GAVRETO® (pralsetinib): The indication of advanced or metastatic RET-mutant MTC and RET fusion-positive TC was launched in mainland China. Also, the indication of RET fusion-positive metastatic NSCLC was launched in Hong Kong, China. CEJEMLY® (sugemalimab): A new indication was successfully launched in mainland China for the treatment of patients with unresectable stage III NSCLC whose disease has not progressed following concurrent or sequential platinum- based chemoradiotherapy. Expansion of sales force coverage in key markets for prescriptions of precision drugs
We have specifically focused our efforts on ensuring dedicated sales force coverage and successfully expanded our coverage to approximately 700 hospitals as of the date of this announcement, up from 600 in 2021, accounting for approximately 70-80% of the relevant market for precision medicines where we believe we can maximize the return on our sales efforts. Launched anchor projects to facilitate patient identification and support prescriptions We have signed collaboration agreements with top gene sequencing companies to further improve the testing rate for RET alterations in NSCLC/TC and isocitrate dehydrogenase 1 (“IDH1”) mutation in hematologic cancers. We provided support programs for RET alterations testing in MTC patients, and expanded test assistance programs to IDH1 mutation patients. Besides pathologists, we strengthened clinicians’ participation in test-related academic activities to further improve test awareness. Established broad industry and academic awareness of our brand and scientific leadership We included GAVRETO®(pralsetinib), AYVAKIT®(avapritinib) and TIBSOVO® (ivosidenib) in 15 of China’s national guidelines, i.e. Chinese Society of Clinical Oncology (“CSCO”) NSCLC/gastrointestinal stromal tumors (“GIST”) Guidelines, Chinese Medical Association Guidelines, and Guidelines on Clinical Practice of Molecular Tests in NSCLC, for treatment paradigms for multiple therapeutic areas (NSCLC, TC, GIST and AML). We engaged in close collaboration with several industry associations – Chinese Society of Clinical Oncology, China Anti-Cancer Association, and Chinese Medical Doctor Association – on diagnostic and treatment standardization projects for GIST, NSCLC and hematological malignancies, further strengthening our industry connections and demonstrating our expertise. We enhanced awareness of our products among physicians and key opinion leaders (“KOLs”) via proactive engagement and constant education. As of the date of this announcement, we have held over 80 academic meetings and events reaching over 80,000 leading KOLs and healthcare professionals (“HCPs”), resulting in an enhanced awareness within the healthcare community of our treatments. We sponsored leading KOLs in post-approval clinical projects such as investigator-initiated trials and real-world studies to generate additional data in multiple cancer indications which may support the adoption of our drugs. We funded research in collaboration with non-profit academic institutions. In particular, two real-world studies have reached milestones, including the finalization of the clinical study report of pralsetinib for the treatment of NSCLC in Bo’ao and the activation of two sites for avapritinib for the treatment of GIST. Developing a range of approaches to promote accessibility and affordability of our drugs We have updated our pricing strategy for our in-market products. Specifically, the listing price of AYVAKIT® (avapritinib) was adjusted to increase affordability of the first treatment cycle. The patient assistance program (“PAP”) scheme of GAVRETO® (pralsetinib) was updated to support the long-term treatment of the patients. We secured inclusion of AYVAKIT® (avapritinib) and GAVRETO® (pralsetinib) in 85 of the major commercial and government insurance programs, up from over 60 as disclosed in our 2021 annual results announcement. We continued strategic collaboration with Sinopharm Group Co., Ltd (“Sinopharm”) to broaden hospital and pharmacy distribution coverage for both GAVRETO® (pralsetinib) and AYVAKIT® (avapritinib). As of the date of this announcement, AYVAKIT® (avapritinib), GAVRETO® (pralsetinib) and TIBSOVO® (ivosidenib) have been listed in approximately 150 hospitals and DTPs, up from approximately 100 in 2021. We continued strategic collaboration with three of the largest integrated innovative healthcare service platforms in mainland China – Shanghai Meditrust Health Co., Ltd., Beijing Yuanxin Technology Group Co., Ltd., and Medbanks Health Technology Co., Ltd. – to improve distribution and affordability of GAVRETO® (pralsetinib), AYVAKIT® (avapritinib) and TIBSOVO® (ivosidenib) by facilitating enrolment in city insurance programs. Continued physician/patient education and support, for retention and long-term medication
We kept operating disease management programs through online platforms, to provide education on long term treatment for HCPs, and to provide education sessions and follow-up service for patients, to support retention ratio. Collaborating with global strategic partners to support global launches of IO backbone drugs We are closely collaborating with our partners Pfizer and EQRx on the development and commercialization of sugemalimab in mainland China and outside of Greater China, respectively. With EQRx, we are working closely on global development and regulatory strategies for sugemalimab, including the U.S., the U.K. and the European Union (“EU”), as well as territories beyond these such as the Middle East, Turkey and Africa. The global market size of PD-(L)1 for the treatment of NSCLC, gastric and esophageal cancers is forecasted to be approximately US$30 billion in 2026.
II. Innovation, High Quality and Rapid Execution Lead to Advances across a Maturing Pipeline
CStone followed through on an aggressive clinical agenda with further developments across its pipeline. As of the date of this announcement, we have secured four NDA approvals and submitted two NDA filings as we rounded out our diverse and maturing pipeline of in-market and near-commercial ready drugs. In doing so, our clinical engine once again distinguished itself in terms of innovation, speed, and quality, as evidence by the facts that it took only six months for ivosidenib from NDA acceptance to NDA approval, and we had seven data presentations/publications at/on global academic conferences/top-tier medical journals.
Details are as follows:
Sugemalimab (CS1001, PD-L1 antibody), became the only anti-PD-1/PD-L1 monoclonal antibody approved for both stage III and stage IV NSCLC. In May 2022, we received the NDA approval from the NMPA for the treatment of patients with unresectable stage III NSCLC whose disease has not progressed following concurrent or sequential platinum-based chemoradiotherapy. Sugemalimab became the first anti-PD-1/PD-L1 monoclonal antibody approved in this patient population. In May 2022, we announced that the final PFS analysis of the registrational GEMSTONE-301 study further demonstrates sugemalimab’s robust efficacy and significant clinical benefits shown in interim analysis in stage III NSCLC patients. In August 2022, we presented the detailed results at WCLC 2022. In January 2022, we announced that the pre-specified OS interim analysis showed sugemalimab in combination with chemotherapy significantly and clinical meaningfully improved the overall survival in stage IV NSCLC patients, and the data has been presented at ASCO 2022. The positive OS data will be used for ex- China filling. In January 2022, we announced that the registrational trial for R/R ENKTL met the primary endpoint and demonstrated a complete response (“CR”) rate significantly exceeding that of the currently available targeted monotherapy for these patients. We presented the topline results in an oral abstract session at ASCO 2022. In January 2022, we completed enrolment for two key phase III registrational clinical trials, one for the first-line treatment of metastatic gastric adenocarcinoma/ gastro-esophageal junction adenocarcinoma, and the other for the first-line treatment of metastatic esophageal squamous cell carcinoma. For the markets outside of Greater China, we are working closely with EQRx on regulatory discussions for regulatory submissions for indications in stage III NSCLC, stage IV NSCLC, and R/R ENKTL in multiple countries and regions. For stage IV NSCLC, we expect the first filing outside of the U.S. in the next six months. Meanwhile, constructive conversations with the U.S. FDA are ongoing to gain greater clarity on the regulatory path. For R/R ENKTL, sugemalimab has received Breakthrough Therapy Designation (“BTD”) from the U.S. FDA and we expect the Biologics License Application (“BLA”) filing in 2023. Nofazinlimab (CS1003, PD-1 antibody) In March 2022, we completed enrolment for the global phase III trial of nofazinlimab in combination with LENVIMA® (lenvatinib) in first-line treatment of patients with advanced HCC. In June 2022, we presented the results from the phase Ib study of nofazinlimab combined with lenvatinib as first-line treatment in Chinese HCC patients at ASCO 2022. Pralsetinib (CS3009, RET inhibitor) – We have secured two NDA approvals and have one NDA filing currently under review. In March 2022, we received the NDA approval from the NMPA for the treatment of patients with advanced or metastatic RET-mutant MTC and RET fusion-positive TC. In July 2022, we received the NDA approval from the Hong Kong Department of Health (“HK DoH”) for the treatment of patients with RET fusion-positive locally advanced or metastatic NSCLC. In February 2022, we received the NDA acceptance from the Taiwan Food and Drug Administration (“TFDA”) for the treatment of patients with RET fusion- positive locally advanced or metastatic NSCLC, RET-mutant MTC and RET fusion-positive TC. Ivosidenib (CS3010, IDH1 inhibitor) – We have secured our first NDA approval for this product. In January 2022, we received an NDA approval from the NMPA for the treatment of adults with R/R AML with an IDH1 mutation. Lorlatinib (ROS-1 inhibitor) We are working with Pfizer to jointly develop lorlatinib for c-ros oncogene 1 (“ROS1”)-positive advanced NSCLC in Greater China. In May 2022, we enrolled the first patient in the pivotal study of lorlatinib for the treatment of ROS1- positive advanced NSCLC. Enrolment continues at a steady pace. CS5001 (LCB71, ROR1 ADC) After obtaining an approval of the IND application from the U.S. FDA and approval from the Australia Ethics Committee (“EC”), the FIH study of this potential best-in-class ROR1 ADC has shown swift recruitment to the dose- escalation part in both countries. Additionally, we submitted an IND application to the NMPA in March 2022 and received the approval in May 2022. To enable biomarker-driven patient selection based on tumor ROR1 expression, we have identified candidate ROR1 antibody clones for immuno-histochemistry (“IHC”) to support such precision medicine effort in the future. CS2006 (NM21-1480, PD-L1/4-1BB/HSA tri-specific molecule) The FIH study is ongoing and includes sites in the U.S. and Taiwan. The dose- escalation part of the study has been completed and the study has proceeded to PoC stage to further explore the safety and efficacy of CS2006 in selected tumor indications. Data from the dose escalation part is planned to be submitted to the Society for Immunotherapy of Cancer (“SITC“) this year. We received the IND approval from the NMPA in September 2021. We presented the preclinical data at AACR 2022.
III. Research Efforts Harness Biologics Modular Potential and Reinforce Core IO Franchise
Precision medicines and immuno-oncology combinations remain our strategic focus. Antibody-drug conjugates which deliver cytotoxic agents to tumor with precision, and multi- specific biologics which can create new biology and are combinations of themselves represent two near-term modalities for early-development.
Our research team has continued to make momentous progress in advancing the early-stage innovative programs, predicated on our “Gemstones on the Ring” research strategy which capitalizes on the modular “plug-and-play” nature of biologics. Following this research framework, we have in progress a total of over ten discovery projects and expect two potentially FIC/BIC immune-oncology programs declaring PCCs this year. Additionally, we have made great strides in our proprietary cell-penetrating therapeutic platform for targeting intractable intracellular proteins by achieving PoC in vitro for one of the treatment modalities using this platform. We have established a sustainable innovative research engine that utilizes clinical insights and translational knowledge to drive discovery, and will continue to strengthen our model of innovation sourcing through organic research at our new global R&D Center in Suzhou, China, as well as collaboration with our business partners. These initiatives bolster our immuno-oncology and precision medicine franchises and enhance our capacity to meet our long-term target of filing one-two INDs per year.
We have made significant progress year-to-date with several initiatives:
Two FIC/BIC I/O programs are on-track for pre-clinical candidate (“PCC”) declaration this year, including one tri-specific molecule against PD-L1, VEGF plus another I/O target, and one antibody-cytokine fusion molecule. Cell-penetrating therapeutic platform. Many well-known oncology targets are intracellular proteins that are considered undruggable by current therapeutic approaches. We are developing a proprietary cell-penetrating therapeutic platform against these otherwise intractable targets. Significant progress has been made in the development of this platform with broad therapeutic potential for oncology and beyond. We obtained in vitro PoC using this platform with one of the treatment modalities and expect additional in vitro/in vivo PoCs with multiple treatment modalities by the end of this year.
IV. Strategic Relationships Advance Commercialization Activities and Pipeline Development
We continue to grow and deepen relationships with key global strategic partners to expand commercialization of our in-market and late-stage drugs, bolster our early-stage pipeline of potential FIC/BIC molecules, and access technologies that complement our research and development efforts.
To begin with, we made significant progress on our relationship with Pfizer this year. In May 2022, we received the second indication approval of sugemalimab as a consolidation therapy to improve progression-free survival in patients with stage III NSCLC, after concurrent or sequential platinum-based chemoradiotherapy. Moreover, for the co-development program of lorlatinib for the treatment of ROS1-positive advanced NSCLC, the first patient was enrolled in the pivotal study in May 2022 under the joint efforts of CStone and Pfizer.
With EQRx, we are advancing regulatory submission in multiple countries and jurisdictions all around the world – the U.S., the U.K., and the EU – regarding the registration of sugemalimab for NSCLC and ENKTL indications. We are collaborating with EQRx to explore the feasibility of extending indications for this drug in the global market including gastric cancer and esophageal cancer. In addition, we are working with EQRx on a global phase III study of nofazinlimab in HCC in the U.S. and major EU markets.
In addition, we further strengthened the strategic partnership with Jiangsu Hengrui Pharmaceuticals Co., Ltd. (“Hengrui”). Last year, CStone and Hengrui established a strategic partnership by leveraging respective R&D and commercial expertise to accelerate the development and commercialization of our anti-CTLA-4 mAb (CS1002) to fully unleash its commercial value. In the first half of 2022, Hengrui received the IND clearance from NMPA for a phase Ib/II trial of CS1002 combination therapy for the treatment of advanced solid tumors.
V. Other Business Updates
Manufacturing. We have completed construction of our state-of-the-art manufacturing facility and began running pilot operations at the end of 2021 as projected. The manufacturing facility has a capacity of 26,000 liters for biologics and 1 billion tablets/capsules for small molecule drugs. We are also in the process of technology transfer for multiple imported products which will reduce costs and improve long-term profitability of our products. Specifically, we have completed the technology transfer submission to CDE for avapritinib in July 2022.
Future and outlook
The Next Twelve Months
Our commercial team is working rapidly to expand the addressable market for our products and maximize their commercial potential with a focus on the following:
Improving market coverage organically by maximizing deployment effectiveness and leveraging digital platform. Improving diagnosis rate and accuracy via collaboration with next generation sequencing companies and National Pathology Quality Control Center. Strengthening physician education with focus on differentiation in clinical and safety profile, and improve quality and influence on academic meetings. Strengthening accessibility with continued efforts in hospitals and DTPs listing. Improving affordability through pricing strategy optimization and commercial insurance/ innovative payment plans. Enhancing patient management through digital platform.
Research & Development
NDA approvals expected:
Pralsetinib: NDA approval in Taiwan, China for the treatment of patients with RET fusion- positive locally advanced or metastatic NSCLC, RET-mutant MTC and RET fusion-positive TC in the fourth quarter of 2022 or the first quarter of 2023. Pralsetinib: NDA approval in mainland China for the first-line treatment of RET fusion- positive locally advanced or metastatic NSCLC in 2023. Sugemalimab: NDA approval for R/R ENKTL in mainland China in the first half of 2023.
NDA filings expected:
Pralsetinib: NDA filing in mainland China for the first-line treatment of RET fusion-positive locally advanced or metastatic NSCLC in the second half of 2022. Sugemalimab: NDA filing for R/R ENKTL in mainland China in the second half of 2022. Sugemalimab: The first filing for stage IV NSCLC outside of the U.S. in the next six months. Sugemalimab: BLA filing for R/R ENKTL in the U.S. in 2023. Sugemalimab: NDA filing in mainland China for the first-line treatment of metastatic gastric adenocarcinoma/gastro-esophageal in the first half of 2023. Sugemalimab: NDA filing in mainland China for the first-line treatment of metastatic esophageal squamous cell carcinoma in the first half of 2023.
Topline readouts expected:
Sugemalimab: topline readout of the phase III trial for the first-line treatment of metastatic gastric adenocarcinoma/gastro-esophageal junction adenocarcinoma in the fourth quarter of 2022 or the first quarter of 2023. Sugemalimab: topline readout of the phase III trial for the first-line treatment of metastatic esophageal squamous cell carcinoma in the fourth quarter of 2022 or the first quarter of 2023. Sugemalimab: topline readout of the phase III trial for stage III NSCLC OS interim analysis in the first half of 2023. Nofazinlimab: topline readout of the global phase III trial of nofazinlimab in combination with LENVIMA® (lenvatinib) in first-line treatment of patients with advanced HCC in the first half of 2023.
CS2006: Initiation of PoC expansion cohorts of CS2006 monotherapy in selected solid tumor indications and data presentation from dose-escalation at SITC.
Advancing one-two FIC/BIC immune-oncology (I/O) programs in our discovery projects into preclinical development. Obtaining in vitro/in vivo PoC of the proprietary cell-penetrating therapeutic platform with one or more additional treatment modalities.
Having launched pilot operations, in the current year we are progressing with the preparations for commercial-scale operations that will give us the ability to control the supply of our own products, whether for use in clinical trials or for commercial sales. The facility will have a production capacity of 26,000 litres for biologics and 1 billion tablets for small molecules. For the next 12 months, we will continue the technology transfer for multiple products which will reduce costs and improve long-term profitability of our products.
Looking Beyond 2022
Our commercial, clinical, research and business development capabilities provide a solid basis for CStone to maximize shareholder value as we pursue ground-breaking science with a portfolio of in- market products, some of which secure approval and commercial distribution in global markets. To begin, we are further strengthening our commercial team and presence in the healthcare community that will facilitate the launch and uptake of our drugs in mainland China. We are continuing to expand and deepen our coverage of markets where prescriptions of precision medicines are concentrated.
Our clinical team is working efficiently to expand our portfolio of commercially available drugs and their total addressable market through a combination of indication expansions and geographic coverage. As a result, we are poised to establish a competitive presence in some of the most prevalent cancers.
At the research stage, we are carving out a competitive position in emerging modalities with potential FIC/BIC candidates that will reinforce our core IO and precision medicine franchise. Our improved pre-clinical innovation and development capabilities are on track to generate a greater and more sustainable volume of discovery programs and IND candidates that reach the post-PoC stage.
Our business development efforts will seek to unlock the full value of CStone’s business through strategic partnership and deal making. With its leadership and search and evaluation team situated in the U.S., they have a clear line of sight into the most promising innovations in oncology as well as more direct access to assets and partners for strategic collaboration. Our strategy will remain centered on pipeline building transactions with a focus on FIC or BIC assets with global rights. Equally significant, they will prioritize multi-dimensional collaborations and portfolio deals over single asset in-licensing, while remaining flexible for assets of high clinical and commercial value. In addition, business development will also play a critical role and maximizing asset value through global development and commercial partnerships for CStone assets.
International Financial Reporting Standards (“IFRS”) Measures:
Revenue was RMB261.8 million for the six months ended June 30, 2022, composed of RMB161.4 million in sales of pharmaceutical products, representing sales of the Company’s pharmaceutical products (avapritinib, pralsetinib, newly launched ivosidenib), RMB87.3 million in license fee income, and RMB13.1 million in royalty income of sugemalimab, representing an increase of RMB182.4 million from RMB79.4 million for the six months ended June 30, 2021, primarily attributable to the increase in the total product sales of avapritinib and pralsetinib, and the revenue generated from newly launched ivosidenib and sugemalimab. Research and development expenses were RMB266.6 million for the six months ended June 30, 2022, representing a decrease of RMB246.2 million from RMB512.8 million for the six months ended June 30, 2021, primarily due to lower spending on approved products. Administrative expenses were RMB134.8 million for the six months ended June 30, 2022, representing a decrease of RMB19.3 million from RMB154.1 million for the six months ended June 30, 2021, primarily due to the decrease in share-based payment expenses. Selling and marketing expenses were RMB146.4 million for the six months ended June 30, 2022, representing an increase of RMB12.8 million from RMB133.6 million for the six months ended June 30, 2021, primarily attributable to sales force coverage expansion. Loss for the period was RMB361.6 million for the six months ended June 30, 2022, representing a decrease of RMB412.3 million from RMB773.9 million for the six months ended June 30, 2021, primarily attributable to the increase in revenue and decrease in research and development expenses.
Non-International Financial Reporting Standards (“Non-IFRS”) Measures:
Research and development expenses excluding the share-based payment expenses were RMB218.9 million for the six months ended June 30, 2022, representing a decrease of RMB225.9 million from RMB444.8 million for the six months ended June 30, 2021, primarily due to lower spending on approved products. Administrative and selling and marketing expenses excluding the share-based payment expenses were RMB224.4 million for the six months ended June 30, 2022, representing an increase of RMB10.1 million from RMB214.3 million for the six months ended June 30, 2021, primarily attributable to sales force coverage expansion. Loss for the period excluding the share-based payment expenses was RMB257.1 million, representing a decrease of RMB375.4 million from RMB632.5 million for the six months ended June 30, 2021, primarily attributable to the increase in revenue and decrease in research and development expenses.
CStone (HKEX: 2616) is a biopharmaceutical company focused on researching, developing, and commercializing innovative immuno-oncology and precision medicines to address the unmet medical needs of cancer patients in China and worldwide. Established in 2015, CStone has assembled a world-class management team with extensive experience in innovative drug development, clinical research, and commercialization. The company has built an oncology-focused pipeline of 15 drug candidates with a strategic emphasis on immuno-oncology combination therapies. Currently, CStone has received nine NDA approvals for four drugs. Multiple late-stage drug candidates are now under pivotal clinical trials or registration. CStone’s vision is to become globally recognized as a world-renowned biopharmaceutical company by bringing innovative oncology therapies to cancer patients worldwide.
For more information about CStone, please visit www.cstonepharma.com.
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