SUZHOU, China, May 31, 2022 – 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 2021 full-year financial results and recent business highlights.
Dr. Frank Jiang, CEO of CStone, commented,
“As a full-fledged biopharmaceutical company, we achieved significant milestones in 2021. As of today, our four innovative drugs --- first-in-class precision medicines GAVRETO, AYVAKIT and TIBSOVO and potential best-in-class immuno-oncology therapy sugemalimab --- have been granted the NDA approvals in the Greater China region.
We accelerated our commercialization agenda that enabled us to post impressive sales performance. With a well-established commercial operation system, we’ve successfully reached and partnered with a wider range of hospitals across major cities.
We further demonstrated strong R&D capabilities. In 2021, we submitted six new drug applications and had seven oral presentations of our clinical data at global academic conferences. The clinical data from the registrational study of sugemalimab in stage III/IV non-small cell lung cancer were published on The Lancet Oncology, respectively. The registrational study of sugemalimab in the treatment of extranodal natural killer/T-cell lymphoma met the primary endpoint. Multiple phase 3 registrational clinical trials have completed the enrollment of all subjects, including the registrational clinical trial of sugemalimab plus chemotherapy as the first-line treatment of gastric adenocarcinoma/gastro-esophageal junction adenocarcinoma, and esophageal squamous cell carcinoma, and the international multi-center registrational study of nofazinlimab (CS1003) in combination with lenvatinib for the first-line treatment of advanced hepatocellular carcinoma (HCC). With all these efforts, we are now well-positioned to further meet the needs of patients and maximize the commercial value of our products.
Our Pipeline 2.0 strategy was in full swing with breakthroughs made in our early-stage pipeline. We received the IND approvals of CS5001, a potential global best-in-class ROR1-targeting ADC, in the U.S., Australia, and mainland China, and the first patient was enrolled in the U.S. In addition, we obtained the IND approval of CS2006, a PD-L1/4-1BB/HSA tri-specific antibody, in mainland China. We also initiated and moved forward more than 10 early discovery and technology platform projects.
We leveraged global strategic partnerships to foster commercialization and drug development. CStone Global R&D Headquarters and Manufacturing Base was inaugurated to bolster our in-house R&D capabilities.
In 2022, we will strive to maximize commercial potential with new product and indication launches and continued efforts in market penetration and expansion including further improving diagnostic rate, building scientific leadership and strengthening the accessibility and affordability of our drugs. We have a diverse and balanced pipeline and will continue to focus on cancers with high incidence rates. We will gear up our Pipeline 2.0 strategy, and unleash the global potential of our portfolio. We will make every effort to provide innovative immuno-oncology therapies and precision medicines, and deliver on our commitment to addressing the unmet needs of cancer patients.”
2021 was a breakout year in CStone’s history marked by the launch of two first-in-class precision medicines and multiple additional milestones across our pipeline and business. For the year ended December 31, 2021 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:
These achievements represent only a snapshot of what we have accomplished.
We have fully developed our commercial capabilities, making rapid and significant progress in building the team, infrastructure, and industry network over the past year. Our commercial team has executed a clearly defined strategy and achieved successful launches of three products. We have shaped the treatment paradigm for the target diseases of our precision medicines with broad physician education, collaboration with industry associations on diagnostic and treatment standardization, and collaboration with diagnostics companies. As a result, we have seen continuous improvement in diagnostic rates for the approved indications for avapritinib and pralsetinib since their launch. Currently, our precision medicines have been included in over 10 national guidelines, up from 7 at the time we released our 2021 interim results announcement. In addition, they have been listed in over 60 supplemental insurance plans, up from 20, covering an urban population of approximately 60 million people, up from 40 million at the time we released our 2021 interim 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 approval of four products within 12 months, including three first-in-class precision medicines as well as our flagship immuno-oncology backbone drug. We have also advanced a number of trials through significant clinical milestones. For one, sugemalimab met the primary endpoint in a study of patients with stage III NSCLC without disease progression after concurrent or sequential chemoradiotherapy in our one-of-a-kind GEMSTONE-301 trial, making it the world’s only anti-PD-1/PD-L1 monoclonal antibody to achieve this outcome. The broader spectrum of our clinical development success is reflected in the fact that CStone was invited to present data via seven (7) oral presentations at global academic conferences, a rare accomplishment among Chinese biotech companies. These presentations covered study results of sugemalimab in stage III NSCLC and stage IV NSCLC patients, pralsetinib in first-line NSCLC and MTC patients in China and ivosedinib in R/R AML patients in China as well as first-line AML patients in a global trial. In the latter, the global phase III AGILE trial was halted for further enrolment due to overwhelmingly compelling efficacy and the results were published in The New England Journal of Medicine . Moreover, the results of the unique sugemalimab trials for both stage III NSCLC and stage IV NSCLC have been published in the oncology journal The Lancet Oncology .
Our research team has made transformational changes to its capacity for early-stage innovation and efficiency. In 2021, we refined our research strategy to harness the modular nature of biologics to accelerate internal drug discovery around new modalities. Additionally, we established a new global R&D center, expanding our capacities in critical areas such as antibody discovery and development, systems pharmacology, and bioinformatics. These initiatives bolster our immuno-oncology and precision medicine franchises and enhance our capacity to meet our long-term target of filing 1-2 INDs per year.
Our latest business development partnerships will maximize the commercial value of our CTLA-4 antibody and bring access to proprietary technology to generate new pre-clinical assets with BIC/FIC potential.
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 products which will reduce costs and improve long-term profitability of our products.
These achievements give us the potential to finish 2022 with the launch of ivosidenib, additional launches for in-market products across a range of indications and geographies, new IND filings, new preclinical development programs, and further the maturation of our business into a full-fledged biopharmaceutical company with end-to-end capabilities.
For the year ended December 31, 2021 and as of the date of this announcement, significant progress has been made with respect to our product pipeline and business operations:
1. Multiple Product Launches and Continued Robust Commercial Efforts
We have maintained a significantly accelerated level of commercial activity with the launch of two first-in-class precision medicines, AYVAKIT® (avapritinib) and GAVRETO® (pralsetinib), which we brought to market over the course of May and June 2021. We continued our success into the beginning of 2022 with the commercial launch of CEJEMLY® (sugemalimab), in partnership with Pfizer. Most recently, we have received NDA approval for another first-in-class product, TIBSOVO® (ivosidenib), and expect to launch soon in mainland China.
Our growing commercial team continued its rapid execution of pre-launch and post-launch efforts to set the stage for market adoption of our products. 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 access and affordability of our products through various patient identification programs and by working with payors to promote coverage of them in insurance programs.
Lastly, they are supporting the broader pipeline of late-stage assets by mapping out commercialization plans for those coming to market in the near-term, including in close collaboration with our commercial partners.
Highlights and details on our 2021 commercial activity follow below：
We achieved a rapid sales ramp up of AYVAKIT® (avapritinib) and GAVRETO® (pralsetinib), our first two drugs to market, generating combined net sales of RMB 162.8 million within the first eight months following their launch.
Our comprehensive commercial efforts resulted in successful launches of our approved products.
2. 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. In total, we secured seven NDA approvals and submitted six 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 four key dimensions:
Details follow below：
3. Research Efforts Harness Biologics Modular Potential and Reinforce Core IO Franchise
In 2021, we made significant progress developing two high-potential pre-clinical assets and advancing them toward clinical development. We received IND approval for our ROR1 antibody drug conjugate (“ADC”) (CS5001) in the U.S., Australia and mainland China, and announced the commencement of the first-in-human (“FIH”) clinical trial in the U.S.. Our PD-L1/4-1BB/HSA tri-specific molecule, CS2006, also received approval of its IND application and is proceeding toward first-in-human study in China in the near-term.
Beside these two molecules, we are developing additional Pipeline 2.0 assets. Precision medicine and immuno-oncology combinations remain our strategic focus. In the near-term, we will pursue developments in these areas using two emerging therapeutic modalities: ADCs which deliver cytotoxic agents to tumor with precision, and multi-specific biologics which are combinations of themselves. Additionally, we have systemically revised our research strategy to take advantage of the modular nature of biologics that allows “plug-and-play” of various modules into an antibody backbone to provide different specificity and functionality. This research strategy offers an efficient and streamlined approach to create a suite of FIC/BIC/FW molecules via collective efforts of in-house research and platform partner collaborations. In support of this effort, we recently recruited new talent with expertise in protein engineering, structural biology, and quantitative systems pharmacology.
Following this modular research framework, which we have fully implemented, we initiated and have in progress a total of over 10 discovery projects in 2021 that are currently in progress, including multi-specifics, ADCs, antibody-cytokine fusion molecules, and a proprietary platform for targeting otherwise undruggable intracellular proteins. Additionally, we are working with our new strategic partner, Singapore-based DotBio, to harness the company’s proprietary technology platform to co-develop preclinical multi-specific assets. CStone will lead the design of the target combination based on the intended mechanism of action while DotBio will be responsible for engineering the molecules.
To further strengthen our in-house discovery research capability, we are establishing the CStone Global R&D Center, a brand-new research facility located adjacent to the manufacturing plant in Suzhou. The Center will be a cutting-edge discovery and translational research institute where state-of-the-art technical and functional platforms such as antibody discovery and development, systems pharmacology, and bioinformatics drive CStone’s Pipeline 2.0 forward.
This new R&D facility will occupy approximately 16,000 square-meters of research and office space, an approximately six-fold increase from our current facilities. We have completed the design, begun construction and expect to commence operations by the fourth quarter of 2022.
In a further effort to spur innovation, we will dedicate space within this facility to house an incubator to foster the growth of biotech startups developing promising molecules and technological platforms to which we can have early access. We will broadly select candidates for the incubator based on their potential to contribute molecules for discovery platforms that would be highly complementary to our Pipeline 2.0 efforts. We are currently in active discussions with several incubator candidates, with DotBio slated to be the first among them, and expect to announce additional candidates soon.
Details of our progress are below：
4. Strategic Relationships Advance Commercialization Activities and Pipeline Development
We continue to grow and deepen relationships with key global strategic partners and to forge new partnerships to expand commercialization of our in-market and late-stage drugs, bolster our early-stage pipeline of potential First-in-Class (FIC)/Best-in-Class (BIC) molecules, and access technologies that complement our research and development efforts.
In November 2021, we formed a strategic collaboration agreement with Singapore-based DotBio to pursue joint design and engineering of up to three pre-clinical assets with BIC/ FIC potential, harnessing DotBio’s proprietary technology platform for prefabricating antibody modules. This collaboration, which includes CStone making an equity investment in DotBio, represents the first project to be settled at CStone Global R&D Headquarters and Industrialization Base in Suzhou. CStone will lead the design of target combination based on the intended mechanism of action and DotBio will lead the molecular design and engineering. It will become a source of innovative preclinical candidates to support CStone’s Pipeline 2.0 strategy, further accelerating drug discovery with de novo design.
In November 2021, we established a new strategic partnership with Jiangsu Hengrui Pharmaceuticals Co., Ltd. (“Hengrui”). This strategic partnership marks another milestone in CStone’s mission to introduce innovative oncology therapies in China after the commercial launch of two first-in-class drugs this year. CStone granted the exclusive rights to Hengrui for research, development, registration, manufacturing and commercialization of anti-CTLA-4 mAb (CS1002), a backbone immuno-oncology asset, in Greater China. CStone will retain the rights to develop and commercialize CS1002 outside of Greater China. CStone and Hengrui will partner respective R&D and commercial expertise to accelerate the development and commercialization of CS1002 to fully unleash its commercial value.
In addition, we broadened our relationship with Pfizer in 2021 with the agreement to co-develop Pfizer’s late-stage oncology asset lorlatinib in second line ROS1-positive NSCLC in Greater China. This type of collaboration was envisioned in the original partnership that we announced in 2020. It is a significant advancement which not only expands our partnership with Pfizer, but also provides validation of our clinical and research strength. The plan for lorlatinib is to assess if this agent can provide benefits to the patients with relapsed ROS1-positive advanced NSCLC, which if positive would add a new therapeutic approach to our lung cancer pipeline. This program also bolsters the foundation of our relationship with a global biopharmaceutical leader and sets us up for future collaboration with them.
With EQRx, we are advancing discussions with regulatory bodies 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 hepatocellular carcinoma (“HCC”) in the U.S. and major EU markets.
5. Other Business Updates
Capital Markets Access. Due to the strong performance in our shares during the 12 months by the end of 2021, our stock has been included in the Hang Seng Composite Index and the Hong Kong Stock Connect. This development is significant as it makes our shares accessible to investors in mainland China, and can foster greater trading in our shares, more efficient price discovery and additional liquidity for investors.
Manufacturing. Additionally, 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 products which will reduce costs and improve long-term profitability of our products.
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 2022. Additionally, to further strengthen CStone’s in-house research capability, we anticipate the grand opening of the new global R&D center in the second half of 2022.
A detailed breakdown of expected developments for the remainder of 2022 is 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:
Research & Development
NDA approvals expected:
NDA filings expected:
Topline readouts expected:
First-in-human study initiation:
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 2022, 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 with demonstrable efficiency 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 proof-of-concept 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.
We believe that focusing on these aspects of our business will give us significant and powerful levers for unlocking the full potential of our portfolio and realizing sustainable, long-term value creation. We are moving closer to producing a steady volume of commercially viable and clinically differentiated candidate molecules that can generate diverse and recurring revenue streams. As a result, we are actively shortening the pathway to achieving our ultimate vision of clinical success--to provide breakthrough therapies for cancer patients to help them live longer and healthier lives--while realizing the full commercial value of our innovative capacity and distinctive operating model.
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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 seven 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.
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.