A Multi-Center, Double-Blind, Randomized, Phase III Study to Investigate the Efficacy and Safety of Nofazinlimab (CS1003) in Combination With Lenvatinib Compared to Placebo in Combination With Lenvatinib as First-Line Therapy in Subjects With Advanced Hepatocellular Carcinoma (HCC)

This is a multi-center, double-blind, randomized, phase III study to investigate the efficacy and safety of Nofazinlimab (CS1003) in combination with lenvatinib and placebo in combination with lenvatinib in the treatment of subjects with no prior systemic treatment and with unresectable advanced hepatocellular carcinoma (HCC). Subjects cannot be eligible for locoregional therapy. In this study, Nofazinlimab (CS1003) (or placebo) and lenvatinib are both considered as the study treatment while Nofazinlimab (CS1003) (or placebo) is the investigational product of and lenvatinib is selected as the basic treatment for HCC.

Start Date13 Dec 2019

Sponsor / Collaborator

Cornerstone Pharmaceutical Co., Ltd

CTR20192524 / Active, not recruitingPhase 3

一项比较CS1003联合仑伐替尼方案与安慰剂联合仑伐替尼方案作为一线治疗晚期肝细胞癌（HCC）受试者的有效性与安全性的多中心、双盲、随机对照的III期临床研究

[Translation] A multicenter, double-blind, randomized, controlled phase III clinical study comparing the efficacy and safety of CS1003 combined with lenvatinib versus placebo combined with lenvatinib as first-line treatment for subjects with advanced hepatocellular carcinoma (HCC)

旨在评价CS1003联合仑伐替尼对比安慰剂联合仑伐替尼一线治疗晚期HCC患者的安全性和有效性。

[Translation]

The aim is to evaluate the safety and efficacy of CS1003 combined with lenvatinib versus placebo combined with lenvatinib as first-line treatment for patients with advanced HCC.

Start Date13 Dec 2019

Sponsor / Collaborator

Cstone Pharmaceutical (Shanghai) Co Ltd

[+1]

NCT03809767 / CompletedPhase 1

A Phase Ia/Ib, Open-Label, Multiple-Dose, Dose-Escalation and Expansion Study of the Anti-PD-1 Monoclonal Antibody CS1003 in Subjects With Advanced Solid Tumors or Lymphomas

This is a phase Ia/Ib, open-label, multiple-dose, dose-escalation and expansion study to evaluate the safety, tolerability, pharmacokinetics and anti-tumor activity of CS1003 in subjects with advanced solid tumors or lymphoma.

Start Date29 Oct 2018

Sponsor / Collaborator

Cornerstone Pharmaceutical Co., Ltd

100 Clinical Results associated with Nofazinlimab

100 Translational Medicine associated with Nofazinlimab

100 Patents (Medical) associated with Nofazinlimab

Literatures (Medical) associated with Nofazinlimab

01 Sep 2024·Targeted Oncology

A Phase 1a/1b Dose Escalation/Expansion Study of the Anti-PD-1 Monoclonal Antibody Nofazinlimab in Chinese Patients with Solid Tumors or Lymphoma

Article

Author: Huang, Gang ; Tse, Archie N ; Zhou, Caicun ; Guo, Ye ; Li, Wei ; Wang, Ziping ; Zhang, Wei ; Zhang, Yanqiao ; Ba, Yi ; Wu, Rachel ; Chen, Tong ; Yang, Haiyan ; Zhou, Yuhong ; Shen, Lin ; Gong, Jifang ; Wang, Mengzhao ; Li, Peiqi ; Dou, Jinzhou ; Cai, Qiqing ; Yue, Zenglian ; Cai, Zhongheng ; Tse, Archie N. ; Su, Rila

BACKGROUND:

Immune checkpoint blockade with anti-programmed cell death 1 (PD-1) antibodies has demonstrated efficacy in multiple tumor types. Nofazinlimab is a humanized rat antibody targeting PD-1. A first-in-human study of nofazinlimab conducted in Australia found no dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD) was not reached in the range of 1-10 mg/kg.

OBJECTIVE:

We evaluated nofazinlimab for multiple advanced malignancies in Chinese patients.

PATIENTS AND METHODS:

This was a phase 1a/1b, open-label, multicenter, dose-escalation/expansion trial. In phase 1a, patients received an abbreviated dose escalation of nofazinlimab at 60 mg and 200 mg every 3 weeks (Q3W) to determine DLTs and the recommended phase 2 dose (RP2D). In phase 1b, patients received the RP2D (monotherapy/combination) in six arms by tumor type; DLTs were evaluated for nofazinlimab plus lenvatinib in the unresectable hepatocellular carcinoma (uHCC) arm. Safety (continuously monitored in patients who received nofazinlimab) and efficacy (patients with measurable baseline disease) were assessed.

RESULTS:

Overall, 107 patients were eligible and received nofazinlimab. In phase 1a, no DLTs were observed; the RP2D was 200mg Q3W. In phase 1b, no DLTs were observed with nofazinlimab plus lenvatinib. The safety profile was consistent with that observed in the first-in-human study (NCT03475251). In phase 1b, 21/88 (23.9%) patients achieved confirmed objective responses, 26 (29.5%) had stable disease, and 9/20 (45.0%) patients with uHCC achieved confirmed objective responses to nofazinlimab plus lenvatinib.

CONCLUSIONS:

Nofazinlimab was well tolerated in Chinese patients. Preliminary efficacy was encouraging, particularly for nofazinlimab plus lenvatinib in uHCC, which is being studied in an ongoing phase 3 trial.

CLINICAL TRIAL REGISTRATION:

NCT03809767; registered 18 January 2019.

01 Jun 2024·Cancer

Dual CTLA‐4 and PD‐1 checkpoint blockade using CS1002 and CS1003 (nofazinlimab) in patients with advanced solid tumors: A first‐in‐human, dose‐escalation, and dose‐expansion study

Article

Author: Kotasek, Dusan ; Ma, Yiding ; Aghmesheh, Morteza ; Cosman, Rasha ; Chan, Stephen L ; Zielinski, Robert ; Mant, Andrew ; Bishnoi, Sarwan ; Moore, Maggie ; Li, Peiqi ; Pan, Zhaoxuan ; Tse, Archie N ; Yau, Thomas ; Prawira, Amy ; Su, Rila ; Eek, Richard ; Li, Fei

Abstract:

Background:

This study investigated the safety and efficacy of an anti–CTLA‐4 monoclonal antibody (CS1002) as monotherapy and in combination with an anti–PD‐1 monoclonal antibody (CS1003) in patients with advanced/metastatic solid tumors.

Methods:

The phase 1 study involved phase 1a monotherapy dose‐escalation (part 1) and phase 1b combination therapy dose escalation (part 2) and expansion (part 3). Various dosing schedules of CS1002 (0.3, 1, or 3 mg/kg every 3 weeks, or 3 mg/kg every 9 weeks) were evaluated with 200 mg CS1003 every 3 weeks in part 3.

Results:

Parts 1, 2, and 3 included a total of 13, 18, and 61 patients, respectively. No dose‐limiting toxicities or maximum tolerated doses were observed. Treatment‐related adverse events (TRAEs) were reported in 30.8%, 83.3%, and 75.0% of patients in parts 1, 2, and 3, respectively. Grade ≥3 TRAEs were experienced by 15.4%, 50.0%, and 18.3% of patients in each part. Of 61 patients evaluable for efficacy, 23 (37.7%) achieved objective responses in multiple tumor types. Higher objective response rates were observed with conventional and high‐dose CS1002 regimens (1 mg/kg every 3 weeks or 3 mg/kg every 9 weeks) compared to low‐dose CS1002 (0.3 mg/kg every 3 weeks) in microsatellite instability‐high/mismatch repair‐deficient tumors, melanoma, and hepatocellular carcinoma (50.0% vs. 58.8%, 14.3% vs. 42.9%, and 0% vs. 16.7%).

Conclusion:

CS1002, as monotherapy, and in combination with CS1003, had a manageable safety profile across a broad dosing range. Promising antitumor activities were observed in patients with immune oncology (IO)‐naive and IO‐refractory tumors across CS1002 dose levels when combined with CS1003, supporting further evaluation of this treatment combination for solid tumors.

Plain Language Summary:

CS1002 is a human immunoglobulin (Ig) G1 monoclonal antibody that blocks the interaction of CTLA‐4 with its ligands and increases T‐cell activation/proliferation. CS1003, now named nofazinlimab, is a humanized, recombinant IgG4 monoclonal antibody that blocks the interaction between human PD‐1 and its ligands.In this original article, we determined the safety profile of CS1002 as monotherapy and in combination with CS1003. Furthermore, we explored the antitumor activity of the combination in anti–programmed cell death protein (ligand)‐1 (PD‐[L]1)‐naive microsatellite instability‐high/mismatch repair‐deficient (MSI‐H/dMMR) pan tumors, and anti–PD‐(L)1‐refractory melanoma and hepatocellular carcinoma (HCC).CS1002 in combination with CS1003 had manageable safety profile across a broad dosing range and showed promising antitumor activities across CS1002 dose levels when combined with CS1003. This supports further assessment of CS1002 in combination with CS1003 for the treatment of solid tumors.

09 Nov 2023·British journal of cancer

A first-in-human phase 1 study of nofazinlimab, an anti-PD-1 antibody, in advanced solid tumors and in combination with regorafenib in metastatic colorectal cancer

Article

Author: Ma, Yiding ; Hu, Hui-Han ; Yue, Zenglian ; Kotasek, Dusan ; Coward, Jermaine ; Cosman, Rasha ; Park, John J ; Lemech, Charlotte ; Day, Daphne ; Kuo, James C ; Wu, Rachel ; Markman, Ben ; Li, Peiqi ; Brown, Michael P ; Prawira, Amy ; Tse, Archie N ; Bishnoi, Sarwan ; Su, Rila ; Strother, R Matthew

Abstract:

Background:

We assessed nofazinlimab, an anti-PD-1 antibody, in solid tumors and combined with regorafenib in metastatic colorectal cancer (mCRC).

Methods:

This phase 1 study comprised nofazinlimab dose escalation (phase 1a) and expansion (phase 1b), and regorafenib dose escalation (80 or 120 mg QD, days 1–21 of 28-day cycles) combined with 300-mg nofazinlimab Q4W (part 2a) to determine safety, efficacy, and RP2D.

Results:

In phase 1a (N = 21), no dose-limiting toxicity occurred from 1 to 10 mg/kg Q3W, with 200 mg Q3W determined as the monotherapy RP2D. In phase 1b (N = 87), 400-mg Q6W and 200-mg Q3W regimens were found comparable. In part 2a (N = 14), both regimens were deemed plausible RP2Ds. Fatigue was the most frequent treatment-emergent adverse event (AE) in this study. Any-grade and grade 3/4 nofazinlimab-related AEs were 71.4% and 14.3%, 56.3% and 5.7%, and 57.1% and 21.4% in phases 1a, 1b, and part 2a, respectively. ORRs were 14.3% and 25.3% in phases 1a and 1b, respectively. In part 2a, no patients had radiological responses.

Conclusions:

Nofazinlimab monotherapy was well tolerated and demonstrated preliminary anti-tumor activity in multiple tumor types. Regorafenib plus nofazinlimab had a manageable safety profile but was not associated with any response in mCRC.

Clinical trial registr ation:

Clinicaltrials.gov (NCT03475251).

News (Medical) associated with Nofazinlimab

29 Sep 2024

·pipelinereview.com

Cereno Scientific announces positive topline results of Phase IIa trial with lead candidate CS1 in Pulmonary Arterial Hypertension

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

Phase 2Phase 1Clinical ResultOrphan Drug

23 Aug 2024

·www.prnewswire.com

CStone Reports 2024 Interim Results and Recent Corporate Updates

Total revenue of RMB 254.2 million for 2024 H1; achieving first-time profitability with cash reserve at RMB 814 million as of June 30, 2024. NDA approval of sugemalimab (PD-L1) for Stage IV NSCLC in EU, marking the first successful international approval of a China domestic anti-PD-L1 mAb. Partnered with Ewopharma for sugemalimab commercialization in Central and Eastern Europe, expecting more global partnerships for sugemalimab in the rest of 2024. To launch sugemalimab in Europe and other ex-China markets in early 2025 and to support the company to achieve sustained profitability. Key Pipeline 2.0 asset – CS5001, the first ROR1 ADC with clinical anti-tumor activity in both solid tumors and lymphomas; initiation of a phase 1b study in lymphomas with registrational potential expected in 2024. Key Pipeline 2.0 asset – CS2009, a trispecific antibody targeting PD-1, CTLA4, and VEGFa; aiming for IND submissions in 2024 / 2025. Partnered with Hengrui Pharmaceuticals to commercialize AYVAKIT® (avapritinib) in mainland China. AYVAKIT®'s manufacturing localization application approved by China NMPA; GAVRETO®'s (pralsetinib) application under review. Domestic manufacturing of both precision medicines will significantly reduce costs and improve long-term profitability. New NDA approval of sugemalimab (PD-L1) for first-line gastric cancer in China; NDA for Stage IV NSCLC currently under review by UK MHRA. The Company to host an interim results investor conference call in Chinese on August 26th at 10:00-11:00 am HKT. SUZHOU, China, Aug. 23, 2024 /PRNewswire/ -- CStone Pharmaceuticals (HKEX: 2616), an innovation-driven biopharmaceutical company focused on the research and development of anti-cancer therapies, today reported interim financial results for 2024 and recent business highlights. Dr. Jason Yang, CEO, President of R&D, and Executive Director of Board at CStone, said, "The first half of 2024 marks an important turning point for CStone's growth, achieving several critical milestones and outstanding financial performance. With diversified revenue streams and ongoing cost control, we achieved profitability for the first time and laid a solid foundation for company's future growth. The EU approval of sugemalimab for first-line Stage IV NSCLC represents a significant breakthrough in our global strategy. In addition to the commercial agreement reached this year with Ewopharma for Central and Eastern Europe, we anticipate expanding sugemalimab partnerships across Western Europe and other regions in the rest of 2024, with global sales to commence from early 2025. We are confident that sugemalimab – a potential best-in-class anti-PD-L1 antibody – will deliver significant revenue to support the company to achieve sustained profitability. Pipeline 2.0 is the "new growth engine" for CStone. We will initiate a phase 1b study of CS5001 (ROR1 ADC) with registrational potential for lymphoma in 2024, and plan to present updated clinical data at the American Society of Hematology (ASH) annual meeting later this year. CS2009 (a trispecific antibody targeting PD-1, CTLA4, and VEGFa) is expected to enter an FIH clinical trial in 2024/2025. Meanwhile, we are advancing more innovative assets for oncology and autoimmune diseases with global rights towards clinical stage. Following the commercialization agreement with and successful transition to Allist to commercialize GAVRETO® (pralsetinib) in China last year, we entered a partnership with Hengrui Pharmaceuticals to commercialize AYVAKIT® (avapritinib) in China to leverage its large and strong sale force. Earlier this year, we received the approval for AYVAKIT®'s manufacturing localization application and filed an application for GAVRETO®. With reduced costs of goods from local supply and the strong commercial capability from our partners, we expect rapid sales growth for these two precision medicines to contribute sustainable profit to the Company in coming years. In terms of regulatory progress, sugemalimab received approval in mainland China for first-line gastric cancer, further broadening its coverage in the domestic market. In ex-China market, the UK Medicines and Healthcare products Regulatory Agency (MHRA) is currently reviewing sugemalimab marketing authorization application (MAA) for first-line Stage IV NSCLC that has recently been approved by the European Commission (EC). We plan to submit additional MAAs to the European Medicines Agency (EMA) for other indications of sugemalimab, including Stage III NSCLC, first-line gastric cancer, first-line esophageal squamous cell carcinoma (ESCC), and relapsed/refractory extranodal NK/T-cell lymphoma. Looking ahead, CStone will work closely with our commercial partners to drive the commercial performance of AYVAKIT® and GAVRETO® in China and sugemalimab globally, continue to advance the innovative assets in Pipeline 2.0 to the clinic, and expand our global business to achieve sustained profitability." Financial Highlights International Financial Reporting Standards (IFRS) Measures: Revenue was RMB254.2 million for the six months ended June 30, 2024, composed of RMB118.3 million in sales of pharmaceutical products (avapritinib and pralsetinib), RMB122.6 million in license fee income and RMB13.3 million in royalty income of sugemalimab, representing an increase of RMB122.6 million in license fee income which largely offset a decrease of RMB128.6 million in revenue from sales of pharmaceutical products, such that total revenue decreased by RMB7.3 million, or 2.8%, period-on-period. Research and development expenses were RMB66.2 million for the six months ended June 30, 2024, representing a decrease of RMB120.6 million from RMB186.8 million for the six months ended June 30, 2023, primarily due to a decrease in milestone fee and third party contracting costs and a decrease in employee costs. Administrative expenses were RMB46.7 million for the six months ended June 30, 2024, representing a decrease of RMB42.5 million from RMB89.2 million for the six months ended June 30, 2023, primarily due to a decrease in employee costs. Selling and marketing expenses were RMB62.8 million for the six months ended June 30, 2024, representing a decrease of RMB68.6 million from RMB131.4 million for the six months ended June 30, 2023, primarily attributable to a decrease in employee costs. Profit for the period was RMB15.7 million for the six months ended June 30, 2024, representing a turnaround from a loss of RMB209.2 million for the six months ended June 30, 2023, primarily attributable to a substantial decrease in operating expenses and an increase in gross profit. Non-International Financial Reporting Standards (Non-IFRS) Measures: Research and development expenses excluding the share-based payment expenses were RMB71.0 million for the six months ended June 30, 2024, representing a decrease of RMB127.1 million from RMB198.1 million for the six months ended June 30, 2023, primarily due to a decrease in milestone fee and third party contracting costs and a decrease in employee costs. Administrative and selling and marketing expenses excluding the share-based payment expenses were RMB109.6 million for the six months ended June 30, 2024, representing a decrease of RMB73.5 million from RMB183.1 million for the six months ended June 30, 2023, primarily attributable to a decrease in employee costs. Profit for the period excluding the share-based payment expenses was RMB10.8 million for the six months ended June 30, 2024, representing a turnaround from the loss of RMB183.0 million for the six months ended June 30, 2023, primarily attributable to a substantial decrease in operating expenses and an increase in gross profit. Business Highlights For the six months ended June 30, 2024 and as of the date of this announcement, tremendous progress has been made with respect to our product pipeline and business operations. Key achievements over this period include: Key Pipeline Highlights: Immunotherapy Sugemalimab (anti-PD-L1 antibody) EU Approval: In July 2024, the European Commission (EC) approved sugemalimab (Brand name: Cejemly®) in combination with platinum-based chemotherapy for the first-line treatment of adults with metastatic NSCLC with no sensitizing EGFR mutations, or ALK, ROS1 or RET genomic tumor aberrations. This marks the first successful international approval of a China domestic anti-PD-L1 monoclonal antibody. Sugemalimab's MAA for first-line Stage IV NSCLC is currently under review by the UK MHRA. Strategic Partnership: In May 2024, we entered a strategic collaboration with Ewopharma to commercialize sugemalimab in Switzerland and 18 CEE countries. CStone will receive up to $51.3 million consisting of an upfront payment and additional payables upon regulatory and sales milestones. Fifth Indication Approved in China: In March 2024, sugemalimab was approved in China for its fifth indication – sugemalimab in combination with fluoropyrimidine- and platinum-containing chemotherapy as a first-line treatment for unresectable locally advanced or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma with a PD-L1 expression (Combined Positive Score [CPS] ≥5). Publication in Nature Medicine: In February 2024, the progression-free survival (PFS) final analysis and overall survival (OS) interim analysis of the GEMSTONE-304 study (first-line ESCC) were published in a top-tier medical journal – Nature Medicine. Long-Term OS Data at ESMO: In July 2024, the long-term OS analysis of the GEMSTONE-302 study (first-line Stage IV NSCLC) was accepted for poster presentation at the 2024 Congress of European Society for Medical Oncology (ESMO). Guideline Inclusion: In 2024, Cejemly® (sugemalimab) is recommended as a Tier-1 treatment based on Class-1A evidence in multiple Chinese clinical guidelines, including the CSCO guidelines for gastric cancer, esophageal cancer, and immune checkpoint inhibitors, and included in the Chinese Expert Consensus on Immunotherapy for Lymphoma. Nofazinlimab (PD-1) Global Phase III Study: In March 2024, we completed a prespecified interim analysis for the global phase III trial of nofazinlimab in combination with LENVIMA® (lenvatinib) for the first-line treatment of patients with unresectable or metastatic hepatocellular carcinoma (HCC). No new or unexpected safety signals were observed, and the independent Data Monitoring Committee (iDMC) recommended continuing the trial without protocol modifications until the final OS analysis. Pipeline 2.0 CS5001, a receptor tyrosine kinase-like orphan receptor 1 (ROR1) antibody-drug conjugate (ADC) First-in-Human Study: The global first-in-human (FIH) is ongoing in the US, Australia and China. As of the date of this announcement, the dose has been escalated to the 10th level without observing any dose-limiting toxicities (DLTs) or reaching the maximum tolerated dose (MTD). Promising Antitumor Activity: CS5001 has been well tolerated and safe and has exhibited encouraging anti-tumor activities in various solid tumors and hematologic malignancies. CS5001 is so far the first ROR1 ADC known to demonstrate clinical anti-tumor activity in both solid tumors and lymphomas. ASCO 2024 Presentation: On June 1, 2024, we presented the latest FIH data at the 2024 ASCO annual meeting in a poster session. We also plan to disclose more lymphoma data at the 2024 ASH annual meeting. Phase 1b with Registrational Potential: We plan to initiate phase Ib dose-expansion studies with registrational potential in multiple indications for dose optimization by the end of 2024. ROR1 Antibody Development: We have identified a promising candidate ROR1 antibody clone for immunohistochemistry (IHC) and plan to evaluate the relationship between ROR1 expression and efficacy in phase 1b. CS2009 (PD-1, CTLA4 and VEGFa Trispecific Antibody) Potential FIC/BIC: CS2009 is potentially FIC/BIC next-generation I/O backbone that targets three critical immune suppressive pathways in tumor microenvironment and has the potential to enhance the efficacy of PD-(L)1 therapies in high-prevalence cancers, including NSCLC and HCC. IND Submission: Currently under IND-enabling process; IND submissions expected in 2024/2025. FIC/BIC ADCs CS5006 (Novel Target) & CS5005 (SSTR2): Two FIC ADC programs are advancing toward PCC nomination. CS5006, targeting high-prevalence tumors with a novel tumor-associated antigen identified using in-house machine-learning bioinformatic algorithm, is expected to submit IND in 2025. CS5005 (SSTR2 ADC) has demonstrated encouraging in vitro and in vivo efficacy with its conjugated lead molecules; IND submission expected in 2025. CS5007 (EGFRxHER3 Bispecific ADC) & CS2011 (EGFRxHER3 Bispecific Antibody) are progressing towards PCC nomination. CS5007 (CS2011) targets EGFR and HER3, and both are well-validated targets with proven syngeneic antitumor activity. IND submissions are expected in 2025. Autoimmune Multispecific Antibody CS2013, which is a bispecific molecule targeting two key pathways critical for B-cell development, is in discovery stage, with selection of lead molecule expected by the end of 2024. CS2013 is designed to address unmet needs in treating systemic lupus erythematosus (SLE), IgA nephropathy (IgAN), and other B-cell mediated autoimmune diseases. Precision Medicine GAVRETO® (pralsetinib) Manufacturing Localization in Process: In April 2024, the application of manufacturing localization for GAVRETO® has been accepted by CDE of China NMPA and is currently under review. Commercial Transition: Following the exclusive commercialization agreement for GAVRETO® in November 2023, we transitioned commercial activities to Allist in 2024 H1 and are in close collaboration. AYVAKIT® (avapritinib) Manufacturing Localization Approved: The manufacturing localization applications of AYVAKIT® (300mg and 100mg) were approved by China NMPA in June and August 2024. Partnership with Hengrui Medicine: In July 2024, we entered an exclusive partnership with Hengrui to commercialize AYVAKIT® in mainland China. CStone received an upfront payment of RMB 35 million and will continue to book sales revenue from AYVAKIT® in mainland China in our financial reports, with service fees payable to Hengrui. Inclusion in National Reimbursement Drug List (NRDL): AYVAKIT® was included to the 2023 NRDL in China for the treatment of adults with unresectable or metastatic GIST harboring the PDGFRA exon 18 mutation, including PDGFRA D842V mutations. The updated NRDL has been implemented since January 1, 2024. Guideline Inclusions: GAVRETO® and AYVAKIT® were included in 15 national guidelines in China, covering multiple therapeutic areas such as NSCLC, thyroid cancer (TC), GIST, systemic mastocytosis (SM), etc. Future and Outlook Looking forward, we remain committed to advancing our innovative pipeline and maximizing commercial value of our marketed products. Anticipated near-term catalysts include Sugemalimab: MAA approval for the first-line treatment of Stage IV NSCLC in the U.K. expected in 2024 H2, and more global partnerships expected in 2024. CS5001: Presentation of the latest clinical safety and efficacy data at international academic conferences (e.g. ASH in 2024 H2), initiation of phase 1b trial with registrational potential in 2024, and global business development (BD) partnerships expected in 2024 or 2025. CS2009: IND submissions expected in 2024/2025. CS5006: IND submission expected in 2025. CS5005: IND submission expected in 2025. CS2011/CS5007: IND submission expected in 2025. GAVRETO® (pralsetinib): Approval for manufacturing localization expected in 2025 H1. Nofazinlimab: Final OS analysis expected in 2025 H1; seeking ex-China partnership opportunities. Interim Results Investor Call The Company will host a 2024 interim results conference call at 10:00 a.m. to 11:00 a.m. (Hong Kong time) on Monday, August 26, 2024. Please attend the conference call through the link: (Password:564723). About CStone CStone (HKEX: 2616), established in late 2015, is an innovation-driven biopharmaceutical company focused on the research and development of anti-cancer therapies. Dedicated to addressing patients' unmet medical needs in China and globally, the Company has made significant strides since its inception. To date, the Company has successfully launched 4 innovative drugs and secured approvals for 14 new drug applications (NDAs) covering 9 indications. The company's pipeline is balanced by 16 promising candidates, featuring potentially first-in-class or best-in-class antibody-drug conjugates (ADCs), multispecific antibodies, immunotherapies and precision medicines. CStone also prides itself on a management team with comprehensive experiences and capabilities that span the entire drug development spectrum, from preclinical and translational research to clinical development, drug manufacturing, business development, and commercialization. For more information about CStone, please visit . IR contact: [email protected] PR contact: [email protected] 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. SOURCE CStone

Drug ApprovalPhase 1ImmunotherapyPhase 3License out/in

08 May 2023

·www.fiercebiotech.com

EQRx abandons low cost drug plan, slashes programs down to 1 and cuts staff in 'reset'

EQRx has dubbed its pipeline, partnership and staff cuts a “reset." EQRx is abandoning its plan to provide drugs that are typically expensive at lower prices. The biotech is also cutting ties with two of its partners, letting go of 170 staff members and slashing all assets from its pipeline except one. The restructuring has been dubbed a “reset” of EQRx’s business and clinical focuses, according to a May 8 earnings call and an accompanying release. The Massachusetts-based biotech initially set out to radically reduce drug prices via a “global buyers club” made up of insurers and hospital systems worldwide. However, the dream lost traction at the end of last year when the biotech chose not to seek FDA approval of cancer drug sugemalimab because officials wouldn’t accept clinical data from China. Shortly after, the immuno-inflammatory company trimmed its team by 18%, leaving around 300 staff members at the end of March of this year. The move was made in hopes of streamlining expenses and was projected to save $18 million annually. Now, EQRX has reduced its workforce again, eliminating 170 roles, or about 57% of its team. Alongside the workforce culls, the company won’t be filling positions of prior departures. The company is also ditching all of its programs except lerociclib, a CDK 4/6 inhibitor that was licensed from G1 Therapeutics in 2020. The therapy is currently being tested in a phase 3 trial in combo with approved drug letrozole in patients with first-line advanced endometrial cancer, as well as a phase 2 trial in patients with first- and second-line advanced breast cancer alongside letrozole or faslodex. As for the rest of its (former) pipeline, EQRx has dedicated $25 million to rolling out all its early-stage, immuno-inflammatory cancer programs into a new wholly owned subsidiary. The biotech is also looking for a partner to commercialize its third-generation EGFR inhibitor, dubbed aumolertinib, outside of China. The asset is currently being studied in a three-arm phase 3b clinical trial as a monotherapy or combo treatment with chemotherapy compared to approved drug Tagrisso as a first-line treatment of EGFR-mutated non-small cell lung cancer. Part of the reset includes ending deals with CStone Pharmaceuticals and Lynk Pharmaceuticals, both China-based biotechs. EQRx inked a deal with CStone back in 2020, paying out $150 million cash and with up to $1.15 billion possible in milestone payments for a pair of PD-1/PD-L1 meds. The biotech is now returning the rights to nofazinlimab, an anti-PD-1 antibody in development for various tumors, and the aforementioned sugemalimab, a PD-L1 inhibitor that’s being studied in several types of cancer. The Lynk deal, also penned in 2020, gave EQRx exclusive licensing rights for the research, development and commercialization of LNK-207, a JAK-1 inhibitor also known as EQ121. The U.S. biotech gained global rights to the asset except in mainland China, Hong Kong, Macau and Taiwan, paying an undisclosed upfront fee giving Lynk the chance to make up to $172 million in milestone payments in return. When it’s all said and done, EQRx estimates total restructuring costs for the year could top out at $55 million. The reset is expected to save at least $125 million annually, EQRx President and CEO Melanie Nallicheri said on the May 8 call. The company had $1.3 billion in cash, cash equivalents and short-term investments at the end of quarter one to funnel toward lerociclib’s development. “We're bringing our cash burn way down—this is a time when this scale of capital is extremely valuable,” Nallicheri said. “Capital has become expensive and there are a lot of people out there that are trimming their portfolios; there are a lot of companies that are trading below cash.” The CEO said the $1.3 billion puts the company “in an interesting position” to put together “an interesting portfolio.”

License out/inPhase 3Phase 2Clinical Trial TerminationPhase 1

100 Deals associated with Nofazinlimab

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced Hepatocellular Carcinoma	Phase 3	US	Cornerstone Pharmaceutical Co., Ltd	13 Dec 2019
Advanced Hepatocellular Carcinoma	Phase 3	CN	Cornerstone Pharmaceutical Co., Ltd	13 Dec 2019
Advanced Hepatocellular Carcinoma	Phase 3	IT	Cornerstone Pharmaceutical Co., Ltd	13 Dec 2019
Advanced Hepatocellular Carcinoma	Phase 3	PL	Cornerstone Pharmaceutical Co., Ltd	13 Dec 2019
Advanced Hepatocellular Carcinoma	Phase 3	ES	Cornerstone Pharmaceutical Co., Ltd	13 Dec 2019
Advanced Hepatocellular Carcinoma	Phase 3	TW	Cornerstone Pharmaceutical Co., Ltd	13 Dec 2019
Liver Cancer	Phase 3	-	EQRx International, Inc.	-
Lymphoma	Phase 1	CN	Cornerstone Pharmaceutical Co., Ltd	29 Oct 2018
Advanced cancer	Phase 1	AU	Cornerstone Pharmaceutical Co., Ltd	09 May 2018
Advanced Malignant Solid Neoplasm	Phase 1	AU	Cornerstone Pharmaceutical Co., Ltd	26 Apr 2018

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03809767 (Pubmed \| Target Oncol) Manual	Phase 1	Solid tumor \| Lymphoma	107	Nofazinlimab (Phase 1a)	tajedubrzt(wgkduktkrl) = none ldxxucvyfv (rnqgtwbred ) View more	Positive	04 Sep 2024
NCT03809767 (Pubmed \| Target Oncol) Manual	Phase 1	Solid tumor \| Lymphoma	107	Nofazinlimab (Phase 1b)		Positive	04 Sep 2024
NCT03475251 (phase 1 study of nofazinlimab, Pubmed \| Br J Cancer)	Phase 1	Advanced Malignant Solid Neoplasm \| Metastatic Colorectal Carcinoma PD-1 antibody	-	Nofazinlimab monotherapy	amgchlcuws(cyjzibudjh) = Fatigue was the most frequent treatment-emergent adverse event (AE) in this study vbpbzngnib (nifvveefii ) View more	Positive	09 Nov 2023
NCT03809767 (ASCO2022) Manual	Phase 1	Unresectable Hepatocellular Carcinoma First line	20	Lenvatinib+CS1003	getiaewujl(wzsdifdhju) = Confirmed ORR was changed from 30.0% to 45.0% (95% CI: 23.06%, 68.47%) with 9 pts achieving partial response. vpjqchjzxk (kuqafyuyvp ) View more	Positive	02 Jun 2022
NCT03523819 (ESMO_IO2021) Manual	Phase 1	HR-positive/HER2-low Solid Tumors	36	CS1002+CS1003 (MSI-H/dMMR tumors or MEL + arm A)	sbmnfpndyp(oepbrxpein) = 5 (9.3%) pts had AEs leading to discontinuation of CS1002 and CS1003. vygedvfnnj (kyukuiohxr ) View more	Positive	09 Dec 2021
NCT03523819 (ESMO_IO2021) Manual	Phase 1	HR-positive/HER2-low Solid Tumors	36	CS1002+CS1003 (MSI-H/dMMR tumors or MEL + arm B)		Positive	09 Dec 2021
NCT03809767 (ESMO2020) Manual	Phase 1	Unresectable Hepatocellular Carcinoma First line	19	CS1003+lenvatinib	qffbtfmviz(akbzeuebrn) = lwejlvwbkh wjlnryubtk (jqxlwutobn ) View more	Positive	17 Sep 2020

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