CStone Announces Abstract Release of CS5001 (ROR1 ADC) First-in-Human Clinical Data on ASCO Website

• CS5001 is the first known ROR1 antibody-drug conjugate (ADC) to demonstrate clinical anti-tumor activity in both solid tumors and lymphomas, and among the top two globally in clinical development.
• First-in-human study data show that CS5001 is well tolerated with promising anti-tumor activity at various dose levels in heavily pretreated, advanced solid tumors and lymphomas.
• Dose escalation in the global, multi-center, phase 1 trial of CS5001 is ongoing in the United States, Australia, and China, with plans to initiate dose-expansion studies in multiple tumor types soon and registrational trials in 2024.
• CStone will present additional up-to-date clinical data at the upcoming ASCO meeting.

SUZHOU, China, May 24, 2024 /PRNewswire/ -- CStone Pharmaceuticals ("CStone", HKEX: 2616), an innovation-driven biopharmaceutical company focused on the research and development of anti-cancer therapies, today announced that the abstract containing the preliminary data from the first-in-human, global, multi-regional, phase 1a/1b study of CS5001 (ROR1 ADC) in patients with advanced solid tumors and lymphomas has been published on the website of the American Society of Clinical Oncology (ASCO) 2024 Annual Meeting. Additional up-to-date clinical data will be presented in a poster session during the ASCO Meeting.

• Abstract Title: A phase 1a/1b, multi-regional, first-in-human study of CS5001, a novel anti-ROR1 ADC, in patients with advanced solid tumors and lymphomas.
• Session date and time: June 1, 2024, from 9:00 a.m. to 12:00 p.m. (Central Daylight Time)
• Abstract number for publication: 3023

CS5001, one of the key assets in CStone Pipeline 2.0, is a novel ROR1-targeted ADC designed with a unique pyrrolobenzodiazepine (PBD) prodrug. This study aims to evaluate the safety, pharmacokinetics (PK), and anti-tumor activity of CS5001 in patients with advanced solid tumors and B-cell lymphomas. As of the data cut-off date in the abstract, dose-limiting toxicity (DLT) assessments for the first eight dose levels (7 to 125 μg/kg) in phase 1a have been completed without observing any DLTs and the maximum tolerated dose (MTD) has not been reached. CS5001 appears to be well tolerated, with expected PK characteristics and preliminary anti-tumor activity observed in various solid tumors and hematologic malignancies, including diffuse large B-cell lymphoma (DLBCL), Hodgkin lymphoma, non-small cell lung cancer (NSCLC), pancreatic cancer, etc.

As the study proceeds, the upcoming ASCO poster will for the first time disclose additional efficacy and safety data of CS5001:

• As of the data cut-off date in poster, the dose has been escalated to dose level 9 (156 μg/kg) with no DLTs observed, and MTD has not been reached.
• Most treatment-related adverse events observed were Grade 1 or 2 (per NCI-CTCAE v5.0), indicating that CS5001 was well tolerated by heavily pretreated patients with advanced solid tumors and lymphomas.
• PK data suggested dose-proportional exposure of CS5001, with similar exposure for ADC and total antibody, demonstrating excellent stability of CS5001 ADC in circulation.
• Encouraging anti-tumor activity has been observed in various solid tumors (per RECIST v1.1) and hematologic malignancies (per Lugano 2014):
  • Hodgkin Lymphoma: Objective responses were observed from dose level 5 (50 μg/kg) and above, including 1 complete response (CR) and 4 partial responses (PR) among 9 evaluable patients at dose levels 5-9, achieving an objective response rate (ORR) of 55.6%.
  • DLBCL: Objective responses were observed from dose level 7 (100 μg/kg) and above, including 1 CR and 2 PRs among 6 evaluable patients at dose levels 7-9, achieving an ORR of 50.0%.
  • In solid tumors, multiple PRs and stable diseases (SDs) with reduced tumor burden were emerging from dose level 7 (100 μg/kg) and above, notably in NSCLC (1 PR and 3 SDs), pancreatic cancer (1 PR), triple-negative breast cancer (TNBC; 1 SD), and ovarian cancer (1 SD). Based on the efficacy trends observed, more potent anti-tumor activity is expected in solid tumors as the dose increases.

To date, the phase 1a dose escalation in the reported study remains ongoing, with parallel backfilling of additional patients at selected higher doses to determine preliminary phase 2 recommended dose (RP2D) and to evaluate the relationship between ROR1 expression and efficacy. Updated data will be promptly disclosed at upcoming investor meetings and academic conferences (e.g. ESMO and ASH). Phase 1b will be initiated in the near term in multiple indications for dose optimization, followed by initiation of pivotal trials by the end of 2024.

About CS5001 (ROR1 ADC)

CS5001 is a clinical-stage antibody-drug conjugate ("ADC") targeting ROR1 (receptor tyrosine kinase-like orphan receptor 1). CS5001 has been uniquely designed with proprietary tumor-cleavable linker and pyrrolobenzodiazepine ("PBD") prodrug. Only after reaching the tumor, the linker and prodrug are cleaved to release the PBD toxin, resulting in lethal DNA cross-links in cancer cells. The use of the linker plus PBD prodrug effectively helps addressing the toxicity problem associated with traditional PBD payloads, leading to a better safety profile. CS5001 has demonstrated complete tumor suppression in several preclinical cancer models and demonstrated favorable serum half-life and pharmacokinetic characteristics. CS5001 is a promising candidate drug with precision treatment potential in both hematologic tumors and malignant solid tumors. Additionally, CS5001 utilizes site-specific conjugation for a precise drug antibody ratio of which enables homogeneous production and large-scale manufacturing.

In October 2020, CStone signed a licensing agreement with LigaChem Biosciences, Inc. (LCB) for the development and commercialization of CS5001 which was originally generated by collaboration of LCB and ABL Bio, both South Korea-based leading biotech companies. Under the agreement, CStone obtains the exclusive global right to develop and commercialize CS5001 outside the Republic of Korea.

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 patient's unmet medical needs in China and globally, the company has made significant strides since its inception. To date, the company has successfully launched four innovative drugs and secured approvals for 14 new drug applications (NDAs) covering 9 indications. The company's pipeline is balanced by 12 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 www.cstonepharma.com.

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source: CStone