SUZHOU, China, August 15th, 2023 – 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 2023 interim results and recent business updates.
“In the first half of 2023, CStone delivered robust growth and positive results. Our three precision medicines achieved a 53% year-on-year increase in sales revenue with significant improvement of gross profit margin. Our cash reserves amount to RMB 1,005.4 million, and we significantly reduced our net losses.” said Dr. Jason Yang, CEO of CStone.
“We made remarkable progress in our global product pipeline. We expanded the First-in-Human (FIH) global study of CS5001, a key product of our CStone Pipeline 2.0 Strategy, to China from the United States and Australia, accelerating its development. The phase I clinical trial completed safety evaluation of several dose levels. CS5001, one of the most advanced ROR1 ADCs in global clinical development, showed promising safety, stability, and preliminary anti-tumor activity in hematological and solid malignancies.
We are awaiting the approval of sugemalimab (PD-L1) as first-line treatment of Stage IV NSCLC in the UK and the EU, with the GCP inspection notification from the EMA received recently. We expect the approval in the first half of 2024. We are also actively looking for partners to develop and commercialize sugemalimab and nofazinlimab (PD-1) outside of the Greater China, to advance the global commercialization of these assets.
Going forward, we will continue to strengthen our research and development capabilities for innovative products, optimize the commercial potential of existing products, and improve our global strategic positioning, to create more growth opportunities for the company and more value for investors, partners, and stakeholders.”
The first half of 2023 has been a fruitful period for CStone with milestones across our evolving pipeline and business. We have four products in market which generate recurring revenue to provide financial strength and fund further growth initiatives. For the six months ended June 30, 2023 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:
– RMB261.5 million in total revenue which is composed of RMB246.9 million in sales of our precision medicines and RMB14.6 million in royalty income of sugemalimab
– Two NDA approvals obtained for pralsetinib: first-line treatment of rearranged during transfection (“RET”) fusion-positive non-small cell lung cancer (“NSCLC”) in mainland China which leads to a broader coverage of pralsetinib in both first-line and second-line NSCLC; and RET fusion-positive NSCLC, RET-mutant medullary thyroid cancer (“MTC”) & RET fusion-positive thyroid cancer (“TC”) in Taiwan, China
– Five NDAs currently under review: sugemalimab for relapsed or refractory (“R/R”) extranodal natural killer/T-cell lymphoma (“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.”), sugemalimab for first-line gastric adenocarcinoma/gastroesophageal junction adenocarcinoma (“GC/GEJ”) in mainland China, sugemalimab for first-line esophageal squamous cell carcinoma (“ESCC”) in mainland China. The Good Clinical Practice (“GCP”) inspection notification from the European Medicines Agency (the “EMA”) for first-line stage IV NSCLC has been received
– Global multi-regional clinical trial of CS5001 making rapid progress: the first-in-human (“FIH”) global study of CS5001, a receptor tyrosine kinase-like orphan receptor 1 (“ROR1”) antibody-drug conjugate (“ADC”), being conducted in the United States of America (“U.S.”) and Australia, and has now expanded to include China, further accelerating the development of this product; dose finding phase I clinical trial has completed safety evaluation of several dose levels, with results indicating good safety and tolerability
– Other key clinical programs proceeding smoothly: patient recruitment completed in the pivotal study of lorlatinib for c-ros oncogene 1 (“ROS1”)-positive advanced NSCLC in mainland China and clinical trial progressing steadily for global phase III trial of nofazinlimab in combination with LENVIMA® (lenvatinib) in first-line advanced hepatocellular carcinoma (“HCC”)
– Six data presentations/publications at/on global academic conferences/top-tier medical journals, such as the ESMO World Congress on Gastrointestinal Cancer (“ESMO GI Congress”), Journal of Clinical Oncology, Nature Cancer, etc.
– Over ten discovery projects in progress, including multi-specifics, antibody drug conjugates, and a proprietary cell penetrating therapeutic (“CPT”) platform for drugging intractable intracellular targets; in vitro proof-of-concept (“PoC”) for CPT with three therapeutic modalities has been achieved
– The application of technology transfer for avapritinib is under review by the Center for Drug Evaluation (“CDE”) of the National Medical Products Administration (“NMPA”). The technology transfer for pralsetinib is proceeding smoothly, and a bio-equivalence (“BE”) study has been initiated
I. New Indication Launches and Continued Robust Commercial Efforts
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 RMB246.9 million in the first half of 2023 on the basis of steady growth in the total product sales of GAVRETO® (pralsetinib), AYVAKIT® (avapritinib) and TIBSOVO® (ivosidenib).
• Achieved successful launches of new indications
We expanded the indications for our in-market products and positioned them to become meaningful future contributors to our revenue.
– GAVRETO® (pralsetinib): The indication for the first-line treatment of patients with locally advanced or metastatic RET fusion-positive NSCLC was launched in mainland China.
– GAVRETO® (pralsetinib): The indications 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 were launched in Taiwan, China.
• 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 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.
• Formed a precision diagnostics ecosystem with key stakeholders to facilitate patient identification
– 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 isocitrate dehydrogenase 1 (“IDH1”) mutation in acute myeloid leukemia (“AML”). We also established Lung Cancer Precision Alliance (“LCPA”) with top pharmaceutical companies including BeiGene & Merck, which is the industry’s first alliance focusing on rare targets in the NSCLC field, in order to maximize the RET testing rate in broader market.
– We have strengthened partnership with National Pathology Quality Control Center (“PQCC”) to standardize testing process and improve testing accuracy, with number of participating hospitals continuously improving.
– We have continued to provide support to NSCLC/MTC patients for RET mutation testing and to AML patients for IDH1 mutation testing, covering approximately 1,200 patients since the program was launched.
• Established broad industry and academic awareness of our brand and scientific leadership
– GAVRETO® (pralsetinib), AYVAKIT® (avapritinib) and TIBSOVO® (ivosidenib) were included in 21 of China’s national guidelines for testing and treatment in multiple therapeutic areas, such as NSCLC, TC, GIST, SM, and AML, etc. In particular, the 2023 CSCO NSCLC guideline, the 2022 CSCO GIST Guidelines, the 2022 Chinese Guideline for Diagnosis and Treatment of Systemic Mastocytosis in Adults, and the 2022 China Anti Cancer Association (“CACA”) Hematological Oncology Guideline, etc.
– We are in close collaboration with several industry associations – Chinese Society of Clinical Oncology (“CSCO”), CACA, Chinese Medical Association, Chinese Medical Doctor Association, etc., – on diagnosis and treatment standardization projects for GIST, NSCLC, MTC and hematological malignancies, further strengthening our industry connections and demonstrating our expertise.
– We initiated or supported investigators in post-approval clinical projects, such as investigator-initiated trials (“IIT”) and real-world studies (“RWS”), to generate additional data in multiple cancer indications. For example, a multi-centered RWS evaluated the safety and efficacy of AYVAKIT® (avapritinib) in Chinese patients with GIST; another IIT aims to study the efficacy and safety profile of AYVAKIT® (avapritinib) for the treatment of R/R AML with KIT D816 or N822 mutations.
• 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 patient assistance program (“PAP”) scheme for GAVRETO® (pralsetinib) was updated to lower the barrier for some patients with low affordability and improve price competitiveness. We also launched a new PAP for AYVAKIT® (avapritinib) to support the long-term treatment for GIST patients. We adjusted the PAP scheme for TIBSOVO® (ivosidenib) to increase affordability and duration of treatment (“DOT”).
– We secured inclusion of AYVAKIT® (avapritinib), GAVRETO® (pralsetinib) and TIBSOVO® (ivosidenib) in 138 of the major commercial and government insurance programs in all major areas such as Beijing, Shanghai, Guangdong, Zhejiang, and Shandong, etc., covering a population of approximately 100 million.
– We continued strategic collaboration with Sinopharm Group Co., Ltd (“Sinopharm”) and formed a 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 300 hospitals and direct-to-patient pharmacies (“DTPs”), up from approximately 220 in 2022.
• Continued patient education and support to improve retention and DOT
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 8,000 subscribers and has published over 330 patient stories since launch. Moreover we have held approximately 200 patient education sessions, covering 20,000 potential patients.
• Collaborating with Pfizer on the commercialization of sugemalimab in China
– We are closely collaborating with our partner Pfizer on the commercialization of sugemalimab in mainland China.
– In 2023, sugemalimab as a treatment of stage III NSCLC has been upgraded to a Level 1 recommendation in the 2023 CSCO NSCLC guideline and the 2023 CSCO Immunotherapy guideline. In addition, sugemalimab has been included in the 2023 clinical practice guideline for stage IV primary lung cancer in China.
II. Innovation, High Quality and Rapid Execution Lead to Advances across an Evolving Pipeline
Details are as follows:
• Sugemalimab (CS1001, PD-L1 antibody), new indications under review and expanding to Europe and the U.K.
– Stage IV NSCLC:
• For the markets outside of Greater China, the marketing authorization application (“MAA”) for stage IV NSCLC indication is under review by the regulatory agencies in multiple countries and regions. In February 2023 and December 2022, the MAA filing for sugemalimab in combination with chemotherapy as the first-line treatment for patients with metastatic NSCLC was accepted by the EMA in the E.U. and the Medicines and Healthcare products Regulatory Agency (“MHRA”) in the U.K. respectively. Currently, this indication is under review by both parties. In July 2023, we received the GCP inspection notification from EMA for this indication in the E.U.
• In June 2023, we announced that the results of Overall Survival (“OS”) interim analysis in the registrational GEMSTONE-302 study in patients with stage IV NSCLC were published in a world-renowned oncology journal – Nature Cancer.
• 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 April 2023, we received the NDA acceptance from the NMPA for the first-line treatment of patients with unresectable locally advanced, recurrent, or metastatic ESCC.
• In January 2023, we announced that the GEMSTONE-304 study for the 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 progression-free survival (“PFS”) and OS compared with placebo in combination with chemotherapy. We presented the detailed results at the ESMO GI Congress in June 2023.
– R/R ENKTL:
• In March 2023, we announced that the results of the registrational GEMSTONE-201 study in patients with R/R ENKTL were published in a top-tier oncology journal – Journal of Clinical Oncology.
• Pralsetinib (CS3009, RET inhibitor)
– 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 June 2023, we received the NDA approval 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 June 2023, we published updated results from the phase I/II ARROW trial in Chinese patients with RET fusion-positive NSCLC in Cancer.
• CS5001 (LCB71, ROR1 ADC)
– The global FIH study of this potential best-in-class (“BIC”) ROR1 ADC has shown swift recruitment to the dose-escalation part in the U.S. and Australia with good safety and tolerability demonstrated. This multi-regional clinical trial has now expanded to include China, further accelerating the development of this product. As one of the most advanced ROR1 ADCs in clinical development, CS5001 has therapeutic potential for various hematological and solid malignancies.
– CS5001 has many distinctive features, including proprietary site-specific conjugation, tumor-cleavable linker, and prodrug technology. CS5001 demonstrated a BIC potential in mantle cell lymphoma and triple negative breast cancer xenograft models compared to a benchmark ROR1 ADC. In addition, CS5001 demonstrated a bystander effect in in vitro co-culture systems, suggesting that solid tumors with heterogeneous/low expression of ROR1 may also benefit. In March 2023, we presented the translational data of CS5001 in an oral session at the 13th world ADC London conference (“World ADC London”).
– In addition, we have identified a promising candidate ROR1 antibody clone for immuno-histochemistry (“IHC”) to enable biomarker-driven patient selection based on tumor ROR1 expression, supporting precision medicine efforts in the future.
• Ivosidenib (CS3010, IDH1 inhibitor)
– In January 2023, we completed the China bridging study of ivosidenib in R/R AML patients.
– In May 2023, we reached alignment with CDE on the regulatory pathway toward full approval of ivosidenib as a treatment for R/R AML, and application dossiers are currently under preparation.
• Avapritinib (CS3007, KIT/PDGFRA inhibitor)
– In May 2023, our partner, Blueprint Medicines, received NDA approval from the U.S. Food and Drug Administration (“FDA”) for the treatment of adults with indolent systemic mastocytosis.
– In June 2023, we presented new data of avapritinib in patients with advanced GIST at the American Society of Clinical Oncology (“ASCO”) Annual Meeting 2023.
• Lorlatinib (ALK/ROS-1 inhibitor)
– We are working with Pfizer to jointly develop lorlatinib in Greater China and conducting a pivotal study in patients with ROS1-positive advanced NSCLC. In June 2023, we completed the patient enrollment for this study.
III. Building out Research Pipeline Leveraging Multiple Sources of Innovation
Precision medicines and immuno-oncology combinations remain our strategic focus. ADCs which deliver cytotoxic agents to tumors with precision, and multi-specific biologics which can create new biology and combinations represent two near-term modalities for early development.
We have made significant progress in the first half of 2023 with several initiatives:
• First-in-Class (“FIC”) ADCs: Two FIC ADC programs are progressing toward preclinical candidate (“PCC”) nomination, including one where a novel tumor-associated antigen which is expressed in multiple large tumor indications was identified using an in-house machine-learning bioinformatic algorithm. Candidate antibodies have been selected, and the conjugated lead molecules have demonstrated encouraging in vitro potency and in vivo efficacy. Investigational new drug applications (“INDs”) are expected to be filed in 2024 or 2025.
• I/O multi-specifics: CS2009, which is a tri-specific molecule against PD-1, VEGF plus another I/O target, is under cell line development. IND is expected to be filed in 2024. Additionally, two other I/O multi-specific programs are progressing through IND-enabling and PCC selection phases, respectively.
• Cell penetrating therapeutic platform: Numerous well-known oncology targets are intracellular proteins deemed undruggable by current therapeutic approaches. We are developing a proprietary CPT 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 have obtained in vitro PoC using this platform for three treatment modalities thus far and observed drug-like in vivo pharmacokinetics as well as tumor bio-distribution.
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.
On February 22, 2023, Blueprint Medicines announced that they will regain global commercialization and development rights to pralsetinib from Roche, excluding Greater China. The transition is scheduled to be completed in February 2024, and Blueprint Medicines has initiated a process to re-partner pralsetinib outside of Greater China. We are currently working together with Roche and Blueprint Medicines to take necessary steps to ensure continuity of supply of pralsetinib for patients in Greater China.
Under our partnership with Jiangsu Hengrui Pharmaceuticals Co., Ltd. (“Hengrui”) for anti-CTLA-4 mAb (CS1002), a phase Ib/II trial of CS1002 combination therapy for the treatment of advanced solid tumors including HCC and NSCLC is being conducted by Hengrui.
We regained rights for the development and commercialization of sugemalimab and nofazinlimab outside of Greater China, with the termination of the License Agreement for sugemalimab and nofazinlimab between CStone and EQRx on May 9, 2023. The transition has been completed in August 2023. Currently, we are leading the regulatory process for sugemalimab MAA reviews by the EMA and the U.K. MHRA. The termination of this License Agreement will not affect the upfront and milestone payments previously received from EQRx. We are currently exploring potential partnership opportunities for both sugemalimab and nofazinlimab outside of Greater China.
V. Other Business Updates
Manufacturing. We are also in the process of technology transfer for multiple imported products which is expected to reduce costs and improve long-term profitability of our products. Specifically, the application relating to technology transfer for avapritinib is under review by the CDE. At the same time, the technology transfer for pralsetinib is proceeding smoothly, and a BE study has been initiated.
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 next twelve months.
A detailed breakdown of expected developments for the next twelve months is set forth as below.
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 by maximizing deployment effectiveness and leveraging digital platform
• Improving diagnosis rate and accuracy via deep collaboration with diagnostic companies, industry associations (e.g. PQCC), patient platforms and big data companies
• Strengthening branding and scientific leadership by leveraging the inclusion of guidelines, holding academic activities, and conducting post-approval clinical projects with focus on differentiation in clinical and safety profile
• Strengthening accessibility with continued efforts in hospitals and DTPs listing
• Improving affordability through pricing strategy optimization and commercial insurance/ innovative payment plans
• Enhancing patient education and support through patient community engagement, education sessions and follow-ups leveraging digital platform
Research & Development
NDA approvals expected:
• Sugemalimab: NDA approval for R/R ENKTL in mainland China by the end of 2023
• Sugemalimab: MAA approval for the first-line treatment in stage IV NSCLC in the E.U. in the first half of 2024
• Sugemalimab: MAA approval for the first-line treatment in stage IV NSCLC in the U.K. in the first half of 2024
• Sugemalimab: NDA approval for the first-line treatment in advanced GC/GEJ in mainland China in late 2023 or the first half of 2024
• Sugemalimab: NDA approval for the first-line treatment in advanced ESCC in mainland China in late 2023 or the first half of 2024
NDA filing expected:
• Lorlatinib: supplemental NDA filing in mainland China for ROS1-positive advanced NSCLC in 2024
Topline readouts expected:
• Sugemalimab: topline readout of the pre-specified OS final analysis in the GEMSTONE-303 study of sugemalimab in combination with chemotherapy for the first-line treatment of patients with advanced GC/GEJ in the third quarter of 2023
• Nofazinlimab: topline readout of the global phase III trial of nofazinlimab in combination with LENVIMA® (lenvatinib) for the first-line treatment of patients with advanced HCC in the first quarter of 2024
Early clinical programs:
• CS5001: update on clinical safety and efficacy by the end of 2023 and conference presentation in the first half of 2024
International Financial Reporting Standards (“IFRS”) Measures:
• Revenue was RMB 261.5 million for the six months ended June 30, 2023, composed of RMB 246.9 million in sales of pharmaceutical products (avapritinib, pralsetinib and ivosidenib) and RMB14.6 million in royalty income of sugemalimab, representing an increase of pharmaceutical products sales of RMB85.5 million, or 53%, from RMB161.4 million for the six months ended June 30, 2022 and an increase of royalty income of RMB1.5 million, or 11%, from RMB13.1 million for the six months ended June 30, 2022.
• Research and development expenses were RMB186.8 million for the six months ended June 30, 2023, representing a decrease of RMB79.8 million from RMB266.6 million for the six months ended June 30, 2022, primarily due to the decrease in milestone fee and third party contracting costs and the decrease in employee costs.
• Administrative expenses were RMB89.2 million for the six months ended June 30, 2023, representing a decrease of RMB 45.6 million from RMB134.8 million for the six months ended June 30, 2022, primarily due to the decrease in employee costs.
• Selling and marketing expenses were RMB131.4 million for the six months ended June 30, 2023, representing a decrease of RMB15.0 million from RMB146.4 million for the six months ended June 30, 2022, primarily attributable to the decrease in employee costs and professional fees.
• Loss for the period was RMB 209.2 million for the six months ended June 30, 2023, representing a decrease of RMB152.4 million, or 42%, from RMB361.6 million for the six months ended June 30, 2022, primarily attributable to the decrease in research and development expenses and decrease in employee costs.
Non-International Financial Reporting Standards (“Non-IFRS”) Measures:
• Research and development expenses excluding the share-based payment expenses were RMB198.1 million for the six months ended June 30, 2023, representing a decrease of RMB20.8 million from RMB218.9 million for the six months ended June 30, 2022, primarily due to the decrease in milestone fee and third party contracting costs and the decrease in employee costs.
• Administrative and selling and marketing expenses excluding the share-based payment expenses were RMB183.1 million for the six months ended June 30, 2023, representing a decrease of RMB41.3 million from RMB224.4 million for the six months ended June 30, 2022, primarily attributable to the decrease in employee costs and professional fees.
• Loss for the period excluding the share-based payment expenses was RMB183.0 million for the six months ended June 30, 2023, representing a decrease of RMB74.1 million, or 29%, from RMB257.1 million for the six months ended June 30, 2022, primarily attributable to the decrease in research and development expenses and the decrease in employee costs.
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 management team with extensive experience in innovative drug development, clinical research, and commercialization. The company has built an oncology-focused pipeline of 14 drug candidates with a strategic emphasis on immuno-oncology combination therapies. Currently, CStone has received eleven NDA approvals for its four drugs. Multiple late-stage drug candidates are now under pivotal clinical trials or registration. CStone’s vision is to bring innovative oncology therapies to cancer patients worldwide.
For more information about CStone, please visit www.cstonepharma.com.
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.