Chidamide

September 27, 2024 I Cereno Scientific (Nasdaq First North: CRNO B), a pioneering biotech developing innovative treatments for rare and common cardiovascular disease, today announced positive topline results from the Phase IIa trial of CS1 in Pulmonary Arterial Hypertension (PAH). The results demonstrate that CS1 is safe, well tolerated and has positive impact on clinically relevant parameters such as risk, functional class and hemodynamics. “ I am delighted to share the topline data from the Phase IIa trial of CS1 in PAH. Key results from the study demonstrate both that the primary endpoint was met with good safety and tolerability of CS1 in patients with PAH, and, in addition, we also show a positive impact already after 12 weeks on clinical parameters meaningful to patients and regulatory authorities. These results, together with our foundation of preclinical data, strengthen our conviction that CS1 is a disease-modifying therapy for PAH. We are excited to now move forward with the next development phase with CS1. Our mission is to deliver a drug addressing the pathological remodeling which is progressing the PAH disease and to provide a valuable addition to the PAH toolbox of therapeutics ”, said Sten R. Sörensen, CEO, Cereno Scientific. Pulmonary Arterial Hypertension PAH is a debilitating and fatal disease with no spontaneous improvement. Epigenetic mechanisms through histone deacetylase (HDAC) drive disease progression and continuous deterioration. The disease pathology is defined by endothelial dysfunction, inflammation, vasoconstriction, hypertrophy and remodeling of pulmonary small arteries, leading to poor lung function, right heart failure and ultimately death. Existing treatment alternatives are insufficient and do not address the root cause of the disease. The goal of PAH treatment is to improve risk score status (measured by amongst others REVEAL risk score), symptoms and physical capacity (measured by functional class) and hemodynamics (measured by mean Pulmonary Arterial Pressure, mPAP and Pulmonary Vascular Resistance, PVR), to ultimately improve both patients’ quality of life and extend survival. “ PAH is a rare and devastating disease for patients suffering from it. Despite advances in treatment options there is still a pronounced need for effective, safe and disease-modifying therapies for these patients. The results presented today with primary endpoints met regarding safety and tolerability and supporting signs of clinical efficacy including improvement in risk score, improvement of functional class and impact on mean pulmonary pressure are promising,” said Dr. Raymond Benza, Network Director of Pulmonary Hypertension at Mount Sinai Icahn School of Medicine, New York; and Principal Investigator of the Phase IIa trial of CS1 . CS1 and the CS1-003 Phase IIa trial CS1 is an HDAC inhibitor that works through epigenetic modulation, being developed as a safe, effective and disease modifying treatment for PAH. CS1 targets the root cause of the disease, aiming to reverse the pathological vascular remodeling of the small lung arteries. CS1-003 is a Phase IIa trial evaluating the safety, tolerability, pharmacokinetics, and exploratory efficacy of CS1 on top of standard-of-care in patients with PAH. The study initially had as an objective to recruit 30 patients. In June, recruitment was stopped after the Study Clinical Steering Committee concluded that there was sufficient data for evaluating the next steps in development. The study, which was performed at 10 clinical sites in the US, randomized 25 patients to CS1 treatment, out of which 21 patients completed the treatment without protocol deviations. CS1 – Phase IIa safety data – Primary endpoint of safety and tolerability met successfully The primary endpoint of safety and tolerability was met successfully: CS1 Phase IIa – Compelling positive impact on exploratory clinical efficacy parameters Efficacy data from the three doses were pooled together due to therapeutic drug exposure (i.e. plasma concentration) also in the low dose group. CS1 showed compelling positive impact on exploratory clinical parameters already over a 12-week treatment period: “ I am very pleased with the positive outcomes we are seeing in our patients following treatment with CS1. Their improvements in health and well-being are encouraging and reflect the potential effectiveness of the therapy. The majority of my patients have expressed interest in enrolling into the Expanded Access Program. This progress reaffirms my commitment to advancing treatments that can make a meaningful difference in patients’ lives with PAH ,” said Dr. Jason Guichard , Advanced Heart Failure and Transplant Cardiology, Department of Medicine, Division of Cardiology, Prisma Health-Upstate, Assistant Professor of Medicine, University of South Carolina School of Medicine Greenville and investigator in the Phase IIa trial of CS1 in PAH. CS1 phase II a study clinical data, together with preclinical information, is consistent with reversing pathological remodeling An in-depth analysis made on a subgroup of patients with a remarkable response showed: The data from the CS1-003 trial, together with recently announced preclinical data from our HDAC inhibitor program, directly demonstrating our HDAC-inhibitor program’s dose-dependent positive impact on reverse vascular remodeling in small lung arteries, provide a basis for assuming that CS1 may act with a disease-modifying capacity in PAH. Clear path forward to develop a disease-modifying therapy for PAH​ Cereno will be initiating discussions with regulatory bodies based on these encouraging results and will progress pursuing a pivotal trial of CS1 in PAH. A comprehensive analysis of the complete CS1-003 data will be conducted, with the findings to be presented at upcoming medical conferences and published in a reputable medical journals. “ We are excited to take the next steps in our journey to make a meaningful impact for patients with PAH. Our plans include engaging with regulatory authorities to in pursuing a pivotal trial for CS1 and to continue enrolling patients in our Expanded Access Program . The CS1-003 trial demonstrated compelling signs of clinical efficacy already over a 12-week treatment period and we expect to see additional positive impact of CS1 with longer use of our drug in patients with PAH ” said Dr. Rahul Agrawal, CMO and Head of R&D, Cereno Scientific Webcast presentation on Monday, September 30 Cereno Scientific will host a webcast including a Q&A session where CEO Sten R. Sörensen, CMO and Head of R&D Dr. Rahul Agrawal, CSO Dr. Björn Dahlöf and Head of Preclinical Development, Nicholas Oakes, will present the CS1-003 topline results. Date and time: Monday, September 30, 2024, at 14:00 CET How to join: https://ir.financialhearings.com/cereno-scientific-2024 The webcast and presentation will be available on the Company’s website after the webinar at: https://cerenoscientific.com/events-presentations/ About the CS1-003 trial The CS1-003 trial titled “A Phase II, Prospective, Randomized, Open-label, Blinded Endpoint, Multicenter Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Exploratory Efficacy of 3 Doses of CS1 in Subjects With Pulmonary Arterial Hypertension ” (NCT05224531) randomized adult PAH patients with WHO Functional class II or III, stable on standard of care therapy for 90 days, to one of three total daily doses of CS1; 480 mg, 960 mg or 1920 mg. Subjects were enrolled for up to 22 weeks including a treatment period of 12 weeks. The trial was conducted at 10 specialist clinics in the US. 25 patients were randomized to CS1 treatment out of which 21 patients completed the treatment without protocol deviations. The study’s primary endpoint was to evaluate the safety and tolerability of CS1 treatment in patients with PAH. Other relevant standard endpoints used in previous studies of this patient group have been measured and evaluated in an exploratory fashion. A collaboration agreement with global healthcare company Abbott has allowed Cereno to use their cutting-edge technology CardioMEMS HF System in the trial, to measure mean Pulmonary Arterial Pressure (mPAP) and other hemodynamic parameters. CS1-003 is a Phase IIa trial that is not powered for statistically significant detection or exclusion of efficacy-related parameters. On June 28, 2024, Cereno announced the decision to close patient recruitment to the Phase IIa trial CS1-003 by July 1st, 2024, after the Study Clinical Steering Committee concluded that there was sufficient data for evaluating the next steps in development. About PAH Pulmonary Arterial Hypertension (PAH) is a rare disease and diagnosed with high blood pressure in the pulmonary circulation. Globally, the disease affects approximately 10 in 100,000 people. It is a severe, debilitating disease with no spontaneous improvement. The disease is characterized by a progressive narrowing of the pulmonary arterial vessels ultimately leading to right heart failure and death. Life expectancy is 2.5 years without therapy and 7.5 years on current standard of care. PAH has a major impact on quality of life and causes shortness of breath, fatigue, chest pains, reduced ability to work, unnatural swelling, fainting and heart palpitations. This has significant implications for a patient’s physical, mental, and social well-being. There is currently no cure available for PAH with the exception of lung transplantation, which patients are often too seriously ill to undergo. Current standard of care, mainly vasodilators, improves the patient’s symptoms and involves, at best, a moderate slowing of the disease progression. There is therefore a great need for safer therapies with disease-modifying capacity that address the root causes of PAH and that can give patients an increased opportunity for an improved quality of life and a longer life. About CS1 Drug candidate CS1 is an HDAC inhibitor that works through epigenetic modulation, being developed as a treatment for the rare disease PAH. CS1 holds the potential to be an effective, safe and disease-modifying drug, targeting the root cause of the disease by reverse remodeling. In preclinical cardiovascular disease models, HDAC inhibitors have shown disease-modifying potential through reverse pathological remodeling, as well as anti-fibrotic, anti-inflammatory, pulmonary pressure-reducing, and anti-thrombotic effects. CS1’s unique efficacy profile aligns well with the underlying mechanisms of PAH, positioning it to address the critical unmet need for more effective treatment options. The goal of CS1’s development is to improve quality of life and extend survival for patients with PAH. CS1 is part of Cereno’s HDACi portfolio, untapping the potential of epigenetic modulation in CVD. CS1 has been granted orphan drug status in both the US and EU. Since January 30, 2024, CS1 is approved by the FDA for Expanded Access, as an extension of the ongoing Phase IIa trial CS1-003 evaluating CS1 in PAH. The EAP gives patients that have completed the Phase IIa trial the opportunity to, after being judged suitable and to benefit from CS1 treatment by investigators, continue CS1 treatment of PAH when no comparable or satisfactory alternative therapy options are available. The EAP allows Cereno to, under a formal FDA-approved protocol, collect safety and efficacy data from long-term exposure to CS1 in patients with PAH. As such, this initiative not only supports the treatment of PAH patients but also enables Cereno to gather additional CS1 usage documentation for regulatory discussions and Phase IIb/III pivotal study design planning. On August 30, 2024, the Company announced that the first patient had been dosed under the EAP. About Cereno Scientific AB Cereno Scientific develops innovative treatments for rare and common cardiovascular disease. The lead drug candidate, CS1, is an HDAC (histone deacetylase) inhibitor that acts as an epigenetic modulator with pressure-reducing, reverse-remodeling, anti-inflammatory, anti-fibrotic and anti-thrombotic properties. A Phase IIa trial evaluating CS1’s safety, tolerability, and exploratory efficacy in patients with the rare disease pulmonary arterial hypertension (PAH) demonstrated that CS1 was safe, well-tolerated and showed a positive impact on exploratory clinical efficacy parameters. CS1 study data, together with preclinical information, is consistent with reversing pathological remodeling. A collaboration agreement with global healthcare company Abbott allowed Cereno to use their cutting-edge technology CardioMEMS HF System in the trial. Since January 2024, we are delighted that the FDA´s Expanded Access Program will enable patients with PAH, a serious life-threatening disease condition, to gain access to CS1 where no comparable alternative therapy options are available. Cereno’s pipeline comprises two additional programs in development through research collaborations with the University of Michigan CS014 is a new chemical entity with a multi-fold mechanism of action as an epigenetic modulator – regulating platelet activity, fibrinolysis, and clot stability for the prevention of thrombosis without an increased risk of bleeding as documented in preclinical trials. The drug candidate has also demonstrated a favorable profile in preclinical models of other cardiovascular diseases, such as PAH, with reverse remodeling of pulmonary arterial vessels and effects on vascular fibrosis. On 28th of June, 2024, Cereno initiated a first-in-human Phase I trial of CS014. Preclinical candidate CS585 is an oral, highly potent and selective prostacyclin (IP) receptor agonist that has demonstrated the potential to significantly improve disease mechanisms relevant to cardiovascular disease. While CS585 has not yet been assigned a specific indication for clinical development, preclinical data indicates that it could potentially be used in indications like Pulmonary Hypertension and thrombosis prevention without increased risk of bleeding. CS585 was in-licensed from the University of Michigan in 2023. The Company is headquartered in GoCo Health Innovation City, in Gothenburg, Sweden, and has a US subsidiary; Cereno Scientific Inc. Based in Kendall Square, Boston, Massachusetts, US. Cereno is listed on the Nasdaq First North (CRNO B). The Certified Adviser is Carnegie Investment Bank AB, certifiedadviser@carnegie.se. More information is on www.cerenoscientific.com. SOURCE: Cereno Scientific

SHENZHEN, China, April 30, 2024 /PRNewswire/ -- Shenzhen Chipscreen Biosciences Co., Ltd. (Chipscreen Biosciences, Stock Symbol: 688321.SH) announced that the company's lead innovative product Chidamide (Epidaza®) , an oral subtype-selective histone deacetylase (HDAC) inhibitor, combined with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), has been officially approved by the National Medical Products Administration (NMPA) for treatment of previously untreated diffuse large B-cell lymphoma (DLBCL) with positive MYC and BCL2 expression. Up to now, Chidamide has been approved for multiple indications globally. (For more information, please review the global commercialization situation). Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma, with approximately 30000 new cases occurring annually in China. Clinical diagnosis and treatment guidelines and consensus both domestically and internationally recommend the R-CHOP regimen as the standard first-line treatment for DLBCL. However, about one-third or more of patients in the overall population still experience ineffective or early recurrence of first-line R-CHOP treatment. Meanwhile, approximately 30% of patients with DLBCL exhibit simultaneous overexpression of MYC/BCL2 protein (referred to as "double expression" lymphoma, DEL), and their efficacy and prognosis after R-CHOP treatment are significantly lower than those of non double expression patients. Therefore, how to combine new drugs based on R-CHOP regimen to provide a more effective and safer treatment to our patients is a significant unmet medical need. The approval of this new indication is based on a randomized, double-blind, placebo-controlled, multicenter Phase III clinical trial DEB trial (NCT04231448). The DEB trial is the first Phase III registered clinical study in the world as first line treatment of MYC/BCL2 dual expression diffuse large B-cell lymphoma. This trial is to evaluate the efficacy and safety of Chidamide combined with R-CHOP compared to R-CHOP in primary treatment and MYC/BCL2 dual expression DLBCL subjects. Based on the interim analysis conducted by the Independent Data Monitoring Committee (iDMC), the efficacy and safety indicators set by the protocol were achieved. Compared with the R-CHOP regimen, the Chidamide combination regimen significantly improved the complete response rate (CRR) of the study's key secondary endpoint, and the study's primary endpoint, event free survival (EFS), also showed a clear trend of benefit. The experimental safety profile is consistent with known risks, and no new significant safety signals were found. The results of the interim analysis of the DEB Phase III study were selected as the Late breaking Abstract (LBA) for the American Society of Clinical Oncology (ASCO) Annual Meeting on April 24, 2024. Dr. Xianping Lu, Chairman and General Manager of Chipscreen Biosciences, stated, "The classic R-CHOP regimen has been used as a first-line treatment for diffuse large B-cell lymphoma (DLBCL) for nearly 20 years, but its therapeutic effect is not satisfactory in populations with dual expression of BCL2 and MYC proteins. The combination of Chidamide and R-CHOP is the world's first phase 3 registered clinical study that focuses on first line therapy of dual expressed DLBCL, and also the world's first R-CHOP improvement study with significant benefits in complete remission rate. We believe that the approval of the new indication will bring new hope and better survival benefits to patients." About Chidamide (Epidaza®) Chidamide (Tucidinostat, Trade name: Epidaza®), a Class 1.1 innovative drug, is a novel molecular entity with global patent protection and the first marketed product developed independently by Chipscreen Biosciences. The first original chemical new drug approved in China, Chidamide is also the first oral subtype-selective histone deacetylase (HDAC) inhibitor in the world, Since its approval in China in December 2014 for the treatment of peripheral T-cell lymphoma, Chidamide has achieved significant commercialization worldwide and continuously explored new indications. Global commercialization situation: In December 2014, Chidamide was approved for use in patients with recurrent or refractory peripheral T-cell lymphoma (PTCL) in China; In November 2019, Chidamide was approved to combine aromatase inhibitors to treat locally advanced or metastatic breast cancer patients with estrogen receptor positive, human epidermal growth factor receptor-2 negative, postmenopausal, and endocrine therapy relapse or progress in China; In June 2021, Chidamide was approved for monotherapy in the treatment of recurrent or refractory (R/R) adult T-cell leukemia (ATL) in Japan; In December 2021, Chidamide was approved for monotherapy for recurrent or refractory (R/R) peripheral T-cell lymphoma (PTCL) in Japan; In March 2023, Chidamide was approved to be used for postmenopausal women with locally advanced or metastatic breast cancer who are hormone receptor positive, type II human epidermal growth factor receptor (HER2) negative, and relapse or worsen after endocrine therapy (in combination with exemestane) in Taiwan, China; In April 30, 2024, Chidamide was approved to use in combination with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) for previously untreated diffuse large B-cell lymphoma (DLBCL) patients with positive MYC and BCL2 expression in China. Global exploration of other indications: In addition to ongoing global multicenter phase III clinical trial for the first-line treatment of melanoma in comniation with Opdivo, Chidamide is also conducting multiple clinical trials in China and internationally in combination with different anti-tumor immunotherapies. In November 2023, the Phase II clinical trial of the first-line treatment of non-small cell lung cancer with Chidamide combined with Tislelizumab was completed and enrolled. On March 4, 2024, Professor Ruihua Xu and Professor Feng Wang from the Cancer Prevention and Treatment Center of Sun Yat sen University led the research on CAPAbility-01, which was published on the world's top academic journal Nature Medicine (IF=82.9). As one of the most valuable sub journals under Nature, the publication of Nature Medicine reflects the academic authority's recognition of CAPAbility-01 research. This study indicates that for patients with microsatellite stable/mismatched repair function intact (MSS/pMMR) type metastatic colorectal cancer (mCRC), a three drug regimen led by Chidamide (Chidamide+sintilimab antibody+bevacizumab) for third line and above treatment, with an 18 week PFS rate of 64.0%, an ORR of 44.0%, and a median PFS of 7.3 months, is considered a promising treatment option for MSS/pMMR advanced CRC patients. On April 24, 2024, an abstract entitled "Tucidinostat plus R-CHOP in previously untreated diffuse large B-cell lymphoma with double expression of MYC and BCL2: An interim analysis from the phase III DEB study" was selected the American Society of Clinical Oncology (ASCO) LBA list for the 2024 ASCO, which submitted by Professor Weili Zhao's team from Ruijin Hospital affiliated with Shanghai Jiao Tong University School of Medicine About Chipscreen Chipscreen Biosciences is an innovative drug company driven by core technologies with globally competitive pipelines. As a pioneer in drug innovation & development in China, adhering to the concept of "Constant Innovation for Life", we focus on developing revolutionary innovative drugs with new mechanisms of action, to address patients' pressing clinical needs. Our complete industry chain that covers early exploratory discovery through commercialization allows us to provide innovative Chinese drugs for patients worldwide. With a global development strategy based on early-stage research in China, Chipscreen Biosciences has leveraged the top scientists and teams with extensive experience in related fields from the Shenzhen Small Molecule Early R&D Center and Chengdu Small Molecule Early R&D Center to create an integrated technology platform based on AI-driven design and chemical genomics, which spanned the whole process from basic science to clinical translation. We have successfully developed first-in-class and best-in-class innovative drugs. Currently, we have marketed two drugs for threeindications in Mainland China, two indications in Japan, and one indication in Taiwan, China. In addition, we have launched a number of R&D projects with differentiated advantages and global competitiveness in the five major areas, including malignant tumors, metabolic diseases, autoimmune diseases, central nervous system diseases, and antivirals. Chipscreen Biosciences has formed a global industrial layout consisting of Shenzhen Head Office/R&D Center/GMP production base, Chengdu Regional Head Office/R&D Center/GMP production base, Beijing Branch, Shanghai Branch, and Chipscreen Biosciences (USA) Co., Ltd. Meanwhile, as one of the first batches of national "innovative drug incubation bases" and national high-tech enterprises, Chipscreen Biosciences has independently undertaken many national "863" plans and national major science and technology projects, such as "10th five-year plan", "11th five-year plan", "12th five-year plan" and "13th five-year plan", and National Science and Technology primary Project for Innovative Drug Development. We have filed over 660 invention patents in China and worldwide, with over 180 granted. SOURCE Shenzhen Chipscreen Biosciences Co., Ltd.