SUZHOU, China, March 15, 2023 /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 full-year financial results and recent business updates.
Dr. Jason Yang, CEO of CStone, commented, "In 2022, CStone achieved significant milestones in commercialization, with a substantial increase of 142% in commercial revenue and a near doubling of total revenue, and ended the year with a solid cash position. We have also made significant progress to develop our clinical pipeline towards regulatory approvals and commercial launches globally.
In 2022, we launched two new products, TIBSOVO® (ivosidenib) and CEJEMLY® (sugemalimab). Together with GAVRETO® (pralsetinib), AYVAKIT® (avapritinib) that were launched in 2021, we have four commercial products in the market that are expected to generate significant revenues in coming years.
We have continued to accelerate our clinical development and commercialization process. Since 2022, we have obtained five NDA approvals for three products, and five new NDAs currently under review, including sugemalimab for first-line stage IV NSCLC in the United Kingdom (U.K.) and the European Union (E.U.).
Global expansion is a critical part of our strategy to realize the full potential of our pipeline. To achieve this, we have made solid progress in our global strategic partnerships to facilitate drug development and commercialization. This highlights the global commercial value of our pipeline and international recognition of our innovative R&D capabilities.
We are conducting a phase I clinical trial for our potential best-in-class ROR1-targeting ADC, CS5001, in the U.S., Australia, and mainland China. We plan to release preliminary data by the end of the year and are exploring collaboration opportunities with overseas companies.
Over ten discovery projects are in progress, including multi-specifics, antibody-drug conjugates, and a proprietary platform for drugging intractable intracellular targets.
Moving forward, we will continue to leverage our industry-leading clinical development capabilities and utilizing multiple innovation sources to further build up our pipeline, accelerate drug development and bring innovative medicines to China and global markets, and at the same time realizing value for our various stakeholders."
BUSINESS HIGHLIGHTS
2022 has been a fruitful year for CStone with milestones across our evolving pipeline and business. Our commercial successes, 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 year ended December 31, 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:
– RMB481.4 million in total revenue, including RMB394.1 million in commercial revenue which is composed of RMB364.3 million in sales of our precision medicines and RMB29.8 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
– Five NDA approvals obtained for three products: sugemalimab for stage III non-small cell lung cancer ("NSCLC") in mainland China, ivosidenib for isocitrate dehydrogenase 1 ("IDH1")-mutant relapsed/refractory acute myeloid leukemia ("R/R AML") in mainland China, pralsetinib for rearranged during transfection ("RET")-mutant medullary thyroid cancer ("MTC") & RET fusion-positive thyroid cancer ("TC") in mainland China, pralsetinib for RET fusion-positive NSCLC in Hong Kong, China, and pralsetinib for RET fusionpositive NSCLC, RET-mutant MTC & RET fusion-positive TC in Taiwan, China
– Additional five NDAs currently under review: pralsetinib for first-line treatment of RET fusion-positive NSCLC in mainland China, sugemalimab for relapsed or refractory extranodal natural killer/T-cell lymphoma ("R/R ENKTL") in mainland China, sugemalimab for first-line stage IV NSCLC in the United Kingdom ("U.K."), sugemalimab for first-line stage IV NSCLC in the European Union ("E.U."), and sugemalimab for first-line gastric adenocarcinoma/gastroesophageal junction adenocarcinoma ("GC/GEJ") in mainland, China
– Five positive topline data readouts for sugemalimab in various indications: R/R ENKTL, first-line stage IV NSCLC, stage III NSCLC, first-line GC/GEJ and first-line esophageal squamous cell carcinoma ("ESCC")
– Eleven data presentations/publications at/on global academic conferences/top-tier medical journals
– Three key clinical programs commenced: the first-in-human ("FIH") global study of CS5001 (ROR1 ADC) in the United States of America ("U.S.") and Australia, first-patient-dosed in the pivotal study of lorlatinib for ROS1-positive advanced NSCLC in mainland China and enrolment completed for global phase III trial of nofazinlimab in combination with LENVIMA® (lenvatinib) in first-line advanced hepatocellular carcinoma ("HCC")
– Over ten discovery projects in progress, including multi-specifics, antibody drug conjugates,
and a proprietary platform for drugging intractable intracellular targets; one pre-clinical candidate ("PCC") declared for a potential FIC/BIC immuno-oncology tri-specific antibody against PD-L1, VEGF plus another immuno-oncology ("IO") target
– Further advanced our strategic partnerships with Pfizer, Hengrui and EQRx through clinical development, regulatory registrations and commercial launches
– Achieved the technology transfer submission to Center for Drug Evaluation ("CDE") of National Medical Products Administration ("NMPA") for avapritinib and the technology transfer for pralsetinib is in progress smoothly
I. Multiple Product Launches and Continued Robust Commercial Efforts
Highlights and details on our commercial activities as of the date of this announcement are as follows:
We generated overall net sales of RMB364.3 million in 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).
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 indications of advanced or metastatic RET-mutant MTC and RET fusion-positive TC were 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.
We have specifically focused our efforts on ensuring dedicated sales force coverage and successfully expanded our coverage to approximately 800 hospitals in over 180 cities as of the date of this announcement, up from 600 in 2021, accounting for approximately 75-80% of the relevant market for precision medicines where we believe we can maximize the return on our sales efforts.
– We have signed collaboration agreements with top gene sequencing companies to further improve the testing rate for RET mutation in NSCLC/TC, platelet-derived growth factor receptor alpha ("PDGFRA") exon 18 mutation in gastrointestinal stromal tumor ("GIST") and IDH1 mutation in AML, with education sessions covering over 5,000 pathologists and clinicians.
– We have strengthened partnership with National Pathology Quality Control Center ("PQCC") to standardize testing process and improve testing accuracy, with number of participating hospitals increasing by 60%.
– We expanded financial support programs to RET mutation testing in MTC patients and IDH1 mutation testing in AML patients from only RET mutation in NSCLC patients before, covering approximately 1,000 patients.
– GAVRETO® (pralsetinib), AYVAKIT® (avapritinib) and TIBSOVO® (ivosidenib) were included in 20 of China's national guidelines for testing and treatment in multiple therapeutic areas, such as NSCLC, TC, GIST and AML indication, etc. The newly included guidelines include 2022 CSCO Primary Lung Cancer Guideline, 2022 CSCO MTC Clinical Guideline, 2022 CSCO Hematologic Malignancy Guideline, 2022 China Anti Cancer Association ("CACA") Hematological Oncology Guideline, 2022 Chinese Guideline for Diagnosis and Treatment of Systemic Mastocytosis in adults, etc.
– We engaged in close collaboration with several industry associations – CSCO, CACA, Chinese Medical Association, Chinese Medical Doctor Association etc., – on diagnosis and treatment standardization projects for GIST, NSCLC and hematological malignancies, further strengthening our industry connections and demonstrating our expertise.
– We enhanced awareness and endorsement of our products among key opinion leaders ("KOLs") and healthcare professionals ("HCPs") via proactive engagement and constant education. As of the date of this announcement, we have held over 160 academic meetings and events reaching over 50,000 leading KOLs and HCPs, resulting in improved brand perception and product adoption within the healthcare community of our treatments.
– We initiated or 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 nine studies in collaboration with non-profit academic institutions. In particular, two real-world studies and one investigator-initiated trial have reached milestones, including the finalization and publication in 2022 CSCO of the clinical study report of pralsetinib for the treatment of NSCLC in Bo'ao with all patients benefiting from treatment and duration of therapy ("DOT") is more than 12 months, and the activation of thirteen sites for avapritinib study for the treatment of GIST and three top hematology hospitals for the treatment of R/R AML with KIT D816V mutation. In addition, we also observed the data from pool analysis of avapritinib in GIST with exon 17/18 mutations have obvious benefits compared with standard treatment.
– We have updated our pricing strategy for our in-market products. Specifically, the patient assistance program ("PAP") scheme of GAVRETO® (pralsetinib) was updated to support the long-term treatment of the patients. We adjusted the listing price of AYVAKIT® (avapritinib) and launched new PAP to improve affordability for GIST patients. We launched PAP for TIBSOVO® (ivosidenib) to increase affordability and DOT.
– We secured inclusion of AYVAKIT® (avapritinib), GAVRETO® (pralsetinib) and TIBSOVO® (ivosidenib) in 130 of the major commercial and government insurance programs covering more than 90 million population, up from over 60 million population as disclosed in our 2021 annual results announcement.
– We continued strategic collaboration with Sinopharm Group Co., Ltd ("Sinopharm") and formed new partnership with Shanghai Pharmaceuticals Holding Co., Ltd ("SPH") to broaden hospital and pharmacy distribution coverage for GAVRETO® (pralsetinib), AYVAKIT® (avapritinib) and TIBSOVO® (ivosidenib). As of the date of this announcement, AYVAKIT® (avapritinib), GAVRETO® (pralsetinib) and TIBSOVO® (ivosidenib) have been listed in approximately 220 hospitals and direct-to-patient pharmacies ("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.
We made continuous efforts in patient support via online patient communities and offline education sessions to improve patient retention and DOT. As of the date of this announcement, our online platform has over 5,000 subscribers and published over 200 patient stories and information. We held 130 patient education sessions, covering 15,000 potential patients.
– We are closely collaborating with our partners Pfizer on the commercialization of sugemalimab in mainland China.
– For the launch readiness in China, we worked together with Pfizer to sign off all commercial agreements and set up ordering process and commercial/PAP goods supply. In addition, we have opened distributor accounts and supported bidding progress to ensure patient accessibility upon the NDA approval.
– In 2022, sugemalimab has been recommended in the 2022 Chinese Society of Clinical Oncology ("CSCO") Non-Small Cell Lung Cancer guideline and 2022 CSCO Immunotherapy guideline for the treatment of stage III and stage IV NSCLC patients. In addition, sugemalimab has also been included in Ctong Stage III NSCLC Diagnosis and Therapy Expert Consensus and 2022 Chinese Medical Association guideline for clinical diagnosis and treatment of lung cancer.
– With EQRx, we are working closely on development and regulatory strategies for sugemalimab outside of greater China, including the U.K. and the E.U., as well as additional regions. 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 an Evolving 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 five NDA approvals and submitted seven NDA filings as we rounded out our diverse and evolving 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 evidenced by the facts that it took only six months for ivosidenib from NDA acceptance to NDA approval, and we had eleven data presentations/publications at/on global academic conferences/top-tier medical journals.
Details are as follows:
– 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 progression-free survival ("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 World Conference on Lung Cancer ("WCLC") 2022.
– In September 2022, we received the NDA acceptance from the NMPA for the treatment of patients with R/R ENKTL with priority review granted.
– In January 2022, we announced that the registrational GEMSTONE-201 study 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 American Society of Clinical Oncology ("ASCO") 2022.
– In February 2023, we received the NDA acceptance from the NMPA for the first-line treatment of patients with locally advanced or metastatic GC/GEJ.
– In November 2022, we announced that the GEMSTONE-303 study for first-line treatment of patients with unresectable locally advanced or metastatic GC/GEJ has met its PFS primary endpoint. Sugemalimab in combination with chemotherapy demonstrated statistically significant and clinically meaningful improvement in PFS, compared with placebo plus chemotherapy.
– In January 2022, we completed enrolment for two key phase III registrational clinical trials, one for the first-line treatment of unresectable locally advanced or metastatic GC/GEJ, and the other for the first-line treatment of unresectable locally advanced, recurrent, or metastatic ESCC.
– In January 2022, we announced that the pre-specified overall survival ("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 global fillings.
– In January 2023, we announced that the GEMSTONE-304 study for first-line treatment of unresectable locally advanced, recurrent, or metastatic ESCC, has met its primary endpoints. Sugemalimab in combination with chemotherapy demonstrated a statistically significant and clinically meaningful improvement in PFS and OS compared with placebo in combination with chemotherapy.
– For the markets outside of Greater China, we are working closely with EQRx on discussions for regulatory submissions for indications in stage IV NSCLC and other indications in multiple countries and regions.
– 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.
– 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 January 2023, we received the NDA approval from the Taiwan Food and Drug Administration ("TFDA") for the treatment of patients with RET fusion-positive locally advanced or metastatic NSCLC, and advanced or metastatic RET-mutant MTC and RET fusion-positive TC.
– In October 2022, we received the NDA acceptance from the NMPA for the first-line treatment of patients with RET fusion-positive locally advanced or metastatic NSCLC who have not been previously treated with systemic therapy.
– In January 2022, we received an NDA approval from the NMPA for the treatment of adults with R/R AML with an IDH1 mutation.
– In October 2022, we received Pediatric and Minority Serious Disease Designation from TFDA for IDH1-mutated R/R AML in adults.
– 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. The enrolment continues at a steady pace.
– 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 receptor tyrosine kinase-like orphan receptor 1 ("ROR1") antibody-drug conjugate ("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.
– The FIH study is ongoing and includes sites in the U.S. and Taiwan. The dose-scalation part of the study has been completed, and the maximum tolerated dose ("MTD") was not reached; preliminary data from the dose escalation part was presented at the Society of Immunotherapy Cancer ("SITC") 2022, which indicated a benign and differentiated safety profile with no notable liver toxicities; an unconfirmed Partial Response was observed in a colorectal cancer subject; meanwhile, full 4-1BB agonism was observed across a broad dose range providing complete inhibition of PD-L1, thus, clinically validating the concept of affinity-balancing built into the design of the molecule. The study has proceeded to proof of-concept ("PoC") stage to further explore the safety and efficacy of CS2006 in selected tumor indications in U.S., E.U. and Taiwan. We received the IND approval from the NMPA in September 2021. We presented the preclinical data at American Association for Cancer Research ("AACR") 2022.
III. Building out Research Pipeline Leveraging Multiple Sources of Innovation
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.
We have made significant progress in 2022 with several initiatives:
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 several treatment modalities in 2022 and expect additional in vitro/in vivo PoCs with multiple additional treatment modalities in 2023.
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 continued to make significant and smooth progress on our relationship with Pfizer to explore China markets for sugemalimab. In addition, we are working with EQRx on exploring global markets for sugemalimab and a global phase III study of nofazinlimab in HCC.
In 2022, we entered into a new partnership with Roche Pharmaceuticals Co., Ltd ("Roche") who became the global marketing authorization holder ("MAH") for pralsetinib. As part of this agreement, we acquired full manufacturing right to pralsetinib. Locally manufactured supply is expected to provide significant cost saving and as a result improve CStone's overall profitability. In the meantime, Roche will be responsible for the manufacturing and supply of pralsetinib for China before our successful technology transfer. On February 22, 2023, Roche announced that Blueprint Medicines will regain global commercialization and development rights to pralsetinib in the future, excluding Greater China. Under the terms of the agreement, the termination will be effective within 12 months from the notification date of February 22, 2023. CStone is currently working together with Roche and Blueprint to take necessary step to maintain the marketing authorization for Pralsetinib and ensure continuity of supply of Pralsetinib for patients in China.
We further strengthened the strategic partnership with Jiangsu Hengrui Pharmaceuticals Co., Ltd. ("Hengrui"). In 2021, 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 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, and has initiated two studies in HCC and NSCLC respectively.
V. Other Business Updates
Manufacturing. 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 and bio-equivalence ("BE") has been demonstrated to support technology transfer. At the same time, the technology transfer for pralsetinib is in progress smoothly.
FUTURE AND OUTLOOK
We are working to bring a number of significant clinical and commercial developments to fruition that will be catalysts for our growth in the rest of 2023. A detailed breakdown of expected developments for the remainder of 2023 is below.
Commercial Developments
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:
Research & Development
NDA approvals expected:
NDA filing expected:
Topline readouts expected:
Early clinical programs:
FINANCIAL HIGHLIGHTS
International Financial Reporting Standards ("IFRS") Measures:
Non-International Financial Reporting Standards ("Non-IFRS") Measures:
About CStone
CStone (HKEX: 2616) is a biopharmaceutical company focused on research, development, and commercialization of 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 ten NDA approvals for its 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.
Forward-looking statements
The forward-looking statements made in this article only relate to events or information as of the date when the statements are made in this article. Except as required by law, we undertake no obligation to update or publicly revise any forward-looking statements, whether as a result of new information, future events or otherwise, after the date on which the statements are made or to reflect the occurrence of unanticipated events. You should read this article completely and with the understanding that our actual future results or performance may be materially different from what we expect. All statements in this article are made on the date of publication of this article and may change due to future developments.
