Multiple Chinese Biopharma Companies to Unveil Latest Hematologic Oncology Data at ASH 2021

The American Society of Hematology (ASH) Annual Meeting is the world's premier scientific forum in hematology, showcasing the latest and most cutting-edge research advancements in the field. The 63rd ASH Annual Meeting will be held from December 11 to 14 in the United States in a hybrid format combining in-person and virtual participation. According to publicly available information, numerous novel drugs developed or co-developed by Chinese companies will also be presented at this conference. This article provides a brief overview of select participating projects.

1. CStone Pharmaceuticals: Partner Servier to Announce Positive Global Phase III Results for Ivosidenib

Servier, a partner of Cstone Pharmaceuticals, will present data from the global Phase III, double-blind, placebo-controlled AGILE study evaluating the combination of ivosidenib and the chemotherapeutic agent azacitidine for previously untreated adult patients with IDH1-mutated acute myeloid leukemia (AML) as an oral presentation at the ASH Annual Meeting.

The results showed that, compared with azacitidine plus placebo, ivosidenib in combination with azacitidine significantly improved event-free survival (EFS) and key secondary endpoints, including complete remission (CR), overall survival (OS), and objective response rate (ORR).

It is reported that ivosidenib is a potent, highly selective oral "first-in-class" IDH1 inhibitor. The drug was originally developed by Agios Pharmaceuticals, and Servier acquired the rights to this product through its acquisition of Agios Pharmaceuticals' oncology business. CStone Pharmaceuticals holds the clinical development and commercialization rights for ivosidenib in Greater China and Singapore.

Ivosidenib has been approved in the United States as monotherapy for adult patients with IDH1-mutated relapsed or refractory acute myeloid leukemia (AML), as well as for newly diagnosed adult patients with IDH1-mutated AML who are ≥75 years of age or who have comorbidities that preclude the use of intensive induction chemotherapy. Recently, ivosidenib has been approved as the first and only targeted therapy for previously treated patients with IDH1-mutated cholangiocarcinoma.

Currently, the NMPA has accepted the New Drug Application (NDA) for ivosidenib for the treatment of adult patients with relapsed or refractory acute myeloid leukemia harboring IDH1 susceptible mutations, and the application has been granted priority review.

2. Boya Ji Yin: Announces Latest Research on New Surface Markers and Migration of Hematopoietic Stem Cells (HSC)

Boya Jiyin will present two studies on hematopoietic stem cells in poster format: a novel surface marker capable of supporting long-term hematopoietic stem cell reconstitution, and the enhancing effect of microtubule polymerization inhibition on hematopoietic stem cell homing and engraftment.

The first study reported by Boya Ji Yin demonstrates that CD66e is an effective functional hematopoietic stem cell biomarker, which can be utilized to support the efficient identification and reconstitution of long-term hematopoietic stem cells. Another study demonstrated that short-term inhibition of microtubule polymerization promotes the homing and engraftment of hematopoietic stem cells. These research findings are expected to be applied in the development of hematopoietic stem cell gene therapies and the clinical implementation of hematopoietic stem cell transplantation.

Currently, ET-01, BoyaJiyin's investigational gene-edited hematopoietic stem cell product for patients with transfusion-dependent β-thalassemia, is undergoing a Phase I clinical trial in China. ET-01 is an autologous CD34+ hematopoietic stem cell injection with CRISPR/Cas9-mediated modification of the BCL11A erythroid enhancer, which treats the disease by genetically modifying the patient's own hematopoietic stem cells and reinfusing them into the patient.

3. HUTCHMED: Announces Clinical Data for HMPL-523 and HMPL-306

HUTCHMED will present the latest analyses and updates from the ongoing clinical trials of HMPL-523 and HMPL-306 at this year's ASH Annual Meeting.

HMPL-523 is a novel, potent, and highly selective investigational oral small-molecule inhibitor targeting spleen tyrosine kinase ("Syk"). As a key protein in the B-cell signaling pathway, Syk is a well-established therapeutic target for various subtypes of B-cell lymphoma and autoimmune diseases.

Hutchmed currently holds all global rights to HMPL-523. The ESLIM-01 Phase 3 study is ongoing to evaluate the efficacy and safety of HMPL-523 in adult patients with primary immune thrombocytopenia (ITP), an autoimmune disease that increases the risk of bleeding. Additional details regarding this study can be found on ClinicalTrials.gov by searching registration number NCT05029635. HMPL-523 is also being investigated in China (NCT02857998), the United States, and Europe (NCT03779113) for the treatment of indolent non-Hodgkin lymphoma and various subtypes of B-cell malignancies. Additionally, clinical trials evaluating HMPL-523 for warm autoimmune hemolytic anemia (wAIHA), another autoimmune disease, are planned.

HMPL-306 is a novel, selective small-molecule inhibitor dual-targeting isocitrate dehydrogenase (“IDH”) 1 and 2 mutations, and is the sixth innovative oncology drug from HUTCHMED to enter global clinical development. IDH1 or IDH2 mutations are common genetic alterations across various hematological malignancies, gliomas, and solid tumors, particularly in acute myeloid leukemia (AML). Existing clinical data indicate that when using inhibitors targeting either IDH1 or IDH2 mutations alone, cytoplasmic IDH1 mutations and mitochondrial IDH2 mutations can interconvert. By simultaneously inhibiting both IDH1 and IDH2 mutations, the therapy is expected to provide therapeutic benefits for cancer patients harboring either type of IDH mutation, and may potentially overcome acquired resistance to IDH inhibition driven by subtype switching.

Hutchmed currently holds all global rights to HMPL-306. Phase I clinical trials of HMPL-306 are currently being conducted in patients with hematologic malignancies in China (NCT04272957), the United States, and Europe (NCT04764474), as well as in patients with solid tumors in the United States and Europe (NCT04762602).

4. I-Mab Biopharma: Announces Latest Clinical Data on Anti-CD47 Antibody for the Treatment of Non-Hodgkin Lymphoma

At this year's ASH Annual Meeting, I-Mab will present preliminary safety and positive efficacy data from a U.S. clinical study of lemzoparlimab in combination with rituximab (Rituxan) for the treatment of relapsed or refractory non-Hodgkin lymphoma (NHL).

Lemzoparlimab (also known as TJC4) is a differentiated anti-CD47 antibody independently developed by I-Mab. It effectively targets tumor cells while minimizing adverse effects on red blood cells, thereby preventing severe anemia. Currently, I-Mab and AbbVie are jointly developing this drug globally.

This announcement will cover an international multicenter trial currently being conducted in both China and the United States. Patient recruitment in the U.S. for the clinical study evaluating lazolimab in combination with rituximab for the treatment of non-Hodgkin lymphoma is progressing smoothly. The study has recently been expanded to China, where it has been initiated and the first patient has already been dosed. According to the study plan, this investigational drug is expected to enter the registration clinical trial phase in China in 2022.

5. BeiGene: Announces Clinical Data on Zanubrutinib for the Treatment of Chronic Lymphocytic Leukemia

BeiGene will present clinical results and real-world data from over a dozen hematologic malignancy research programs at this year's ASH Annual Meeting, including two oral presentations on the Phase 3 SEQUOIA trial. This marks the first time BeiGene has reported results from the SEQUOIA study, which compared the BTK inhibitor zanubrutinib with bendamustine plus rituximab (B+R) in patients with treatment-naïve chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

The study results demonstrate that zanubrutinib is superior to the B+R regimen as a first-line treatment for patients with chronic lymphocytic leukemia (CLL). Specifically, in the interim analysis, data from the randomized Cohort 1 of the SEQUOIA trial met the primary endpoint, with zanubrutinib achieving a highly statistically significant improvement in progression-free survival (PFS) compared to the B+R regimen; the hazard ratio (HR) was 0.42, and this benefit was consistently observed across patients with diverse characteristics. Overall response rate (ORR) data also indicated superior efficacy. Zanubrutinib demonstrated favorable overall tolerability in CLL patients, with a low incidence of atrial fibrillation, a key safety endpoint. Additionally, in the ongoing Cohort 3 (Group D) study, the combination of zanubrutinib and venetoclax (a Bcl-2 inhibitor) for CLL patients harboring del(17p), a high-risk feature, also showed favorable tolerability.

BeiGene stated, "Additional data presented at the ASH meeting demonstrate that zanubrutinib holds promise as an alternative for patients intolerant to other BTK inhibitors." Currently, BeiGene is conducting a Phase 2 trial enrolling patients with relapsed or refractory B-cell malignancies who were previously treated with ibrutinib and/or acalabrutinib but developed intolerance. According to the press release, the study results showed: durable disease control or improved responses were observed in patients treated with zanubrutinib; and the majority of patients receiving zanubrutinib (73%) did not experience recurrence of the adverse events that had previously led to the discontinuation of ibrutinib and/or acalabrutinib.

6. Legend Biotech: Releases Latest Data on BCMA CAR-T and Trispecific CAR-T

Legend Biotech will present trial results from 12 clinical programs at the 2021 ASH Annual Meeting, including two oral presentations and 10 poster presentations.

The highlight of the report is the presentation of updated data from the CARTITUDE program (ciltacabtagene autoleucel—a BCMA-targeted CAR-T therapy for the treatment of patients with relapsed or refractory multiple myeloma). The report will detail long-term follow-up data and new subgroup analysis results from the Phase 1b/2 CARTITUDE-1 study, as well as results from a patient prognosis-adjusted indirect comparison of the CARTITUDE-1 study versus real-world standard of care from the LocoMMotion study. Additionally, initial data for Cohort B and long-term follow-up data for Cohort A from the CARTITUDE-2 study, which explores earlier-line populations, will also be presented.

Additionally, Legend Biotech will present preclinical in vivo data for its novel tri-specific single-domain antibody (VHH) CAR-T (LCAR-AIO) for the first time. LCAR-AIO targets three antigens: CD19, CD20, and CD22, and has the potential to be developed for the treatment of patients with relapsed B-cell lymphoma and those who have previously received CD19 CAR-T therapy.

7. InnoCare: Announces Latest Data on Orelabrutinib

InnoCare Pharma will present data on orelabrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, at this year's ASH Annual Meeting. Research results on Waldenström’s macroglobulinemia led by Professor Zhou Daobin have been selected for an oral presentation, while research results on chronic lymphocytic leukemia/small lymphocytic lymphoma led by Professor Li Jianyong and on primary immune thrombocytopenia conducted by Professor Hou Ming have been selected for poster presentations.

Orelabrutinib is a Class 1 innovative drug independently developed by InnoCare Pharma. It is a novel highly selective BTK inhibitor indicated for the treatment of lymphoma and autoimmune diseases. On December 25, 2020, orelabrutinib was approved in China for two indications: relapsed/refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), and relapsed/refractory mantle cell lymphoma (MCL). Additionally, clinical trials of orelabrutinib are currently underway in China for the treatment of various B-cell lymphomas, including marginal zone lymphoma (MZL), central nervous system lymphoma (CNSL), Waldenström's macroglobulinemia (WM), and diffuse large B-cell lymphoma (DLBCL).

Orelabrutinib has been granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration (FDA) for the treatment of relapsed/refractory mantle cell lymphoma (R/R MCL).

8. Ascentage Pharma: Announces Six Studies on Three Investigational New Drugs

Six research updates on three investigational new drugs from Ascentage Pharma (olverembatinib, APG-2575, and APG-1252) have been selected for oral and poster presentations at this year's ASH Annual Meeting. Among them, olverembatinib (HQP1351), an innovative Class 1 investigational new drug, is a novel third-generation BCR-ABL tyrosine kinase inhibitor (TKI) indicated for the treatment of chronic myeloid leukemia (CML) resistant to first- and second-generation TKIs. Currently, the New Drug Application (NDA) for this drug has been submitted in China and has been granted priority review. Lisaftoclax (APG-2575) is a selective Bcl-2 inhibitor currently undergoing multiple clinical trials globally, including in the United States, China, and Europe. Pelcitoclax (APG-1252) is a novel dual Bcl-2/Bcl-xL inhibitor that restores apoptosis by selectively inhibiting the Bcl-2 and Bcl-xL proteins.

Among them, the latest safety and efficacy results from a Phase I study of olverembatinib in TKI-resistant CML subjects were selected for oral presentation. Data showed that among evaluable subjects who had not achieved a response at baseline, the complete hematologic response (CHR) rate was 97.0%, the complete cytogenetic response (CCyR) rate was 62.1%, and the major molecular response (MMR) rate was 51.0%. At month 36, the progression-free survival (PFS) rates for subjects with chronic-phase (CML-CP) and accelerated-phase (CML-AP) CML were 96.3% and 71.4%, respectively. The responses to olverembatinib were durable and independent of baseline BCR-ABL1 mutation status. Most treatment-related adverse events in the study were Grade 1 or 2.

Other studies to be presented as posters include: ① latest results from the pivotal Phase 2 trial of olverembatinib in patients with TKI-resistant, BCR-ABL T315I-mutated CML-CP and CML-AP; ② a Phase 1b bridging study evaluating the pharmacokinetics (PK), safety, and efficacy of olverembatinib in refractory CML and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL); ③ a Phase 1 clinical study assessing the safety, PK, and pharmacodynamics (PD) of lisaftoclax in hematologic malignancies; ④ a Phase 1b clinical study of lisaftoclax as monotherapy or in combination for relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL); and ⑤ the anti-natural killer/T-cell lymphoma activity of pelcitoclax.

Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, stated that the clinical data for olverembatinib to be presented at the 2021 ASH Annual Meeting demonstrated favorable efficacy and tolerability. This marks the fourth consecutive year that research progress on this drug has been selected for an oral presentation at ASH. Additionally, this meeting marks the debut of Ascentage Pharma's key apoptosis-targeting candidates, APG-2575 and APG-1252, at the ASH Annual Meeting.

9、CARsgen Therapeutics: Announces Latest Data for Two BCMA-Targeted CAR-T Products

CARsgen Therapeutics will present the latest research data on CT053 as a poster at the 2021 ASH Annual Meeting. CT053 (zevorcabtagene autoleucel, abbreviated as Zevo-cel) is a fully human anti-BCMA autologous CAR-T cell candidate product independently developed by CARsgen Therapeutics, intended for the treatment of relapsed/refractory multiple myeloma. According to the press release, CT053 incorporates an upgraded CAR construct designed by CARsgen Therapeutics, featuring a fully human anti-BCMA specific single-chain antibody with lower immunogenicity and higher stability, which can reduce the auto-activation of CAR-T cells in the absence of tumor-associated targets.

Two studies on CT053 will be presented at this conference. One is a Phase 1/2 study conducted in Chinese patients with relapsed and/or refractory multiple myeloma. The results showed: In Phase 1 of the LUMMICAR-1 study, a total of 14 subjects with relapsed/refractory multiple myeloma received CT053 treatment. As of July 8, 2021, the median follow-up duration was 13.6 months. Overall tolerability was favorable, with no dose-limiting toxicities (DLTs) or deaths reported, and no Grade ≥3 cytokine release syndrome (CRS) or neurotoxicity observed. The overall response rate (ORR) among the 14 subjects reached 100%, with 78.6% achieving stringent complete response (sCR) with minimal residual disease (MRD) negativity (10^-5). The 12-month progression-free survival (PFS) rate was 85.7%. Among the 12 subjects without extramedullary disease (EMD), the complete response (CR) rate reached 91.7%, and the 12-month PFS rate reached 100%.

Another analysis focused on high-risk factor stratification for CT053 in subjects with relapsed and refractory multiple myeloma. The results indicated that a total of 38 subjects received CT053 treatment across the LUMMICAR-1 study and an investigator-initiated trial (IIT), with a median follow-up duration of 13.9 months. The overall response rate (ORR) was 92.1%, the complete response (CR) rate was 78.9%, the median duration of response (mDOR) was 24.0 months, and the median progression-free survival (mPFS) was 22.7 months. Compared with subjects with extramedullary disease (EMD), those without EMD demonstrated a higher CR rate (88.5% vs. 58.3%), as well as longer mDOR (24.0 months vs. 9.2 months) and mPFS (25.0 months vs. 9.3 months). Furthermore, subjects with high-risk cytogenetics and ISS stage III at baseline demonstrated substantial clinical benefit, while those without these two high-risk factors exhibited even more pronounced therapeutic efficacy.

10. Gracell Biotechnologies: Announces Preclinical Study Results of Dual-Targeting CD19/CD7 CAR-T Candidate Product

Gracell Biotechnologies will present preclinical data on its CAR-T cell therapy candidate, GC502, for the treatment of B-cell malignancies in the form of an e-poster at the conference. GC502 is an off-the-shelf, allogeneic, dual-targeting CD19/CD7 CAR-T cell monotherapy. According to the press release, the innovative dual-targeting CAR design is intended to enable the CD19 CAR on the cell therapy product to specifically target malignant cells, while the CD7 CAR is designed to suppress host-versus-graft (HvG) rejection. This unique design endows GC502 with the potential to be developed as a monotherapy.

The recently disclosed preclinical study results demonstrate that GC502 exhibits significant in vivo anti-tumor activity and effectively inhibits HvG without the need for additional immunosuppressive therapy. Currently, this candidate product is in the exploratory preclinical research stage, primarily targeting the treatment of B-cell malignancies, including: B-cell acute lymphoblastic leukemia (B-ALL) and B-cell non-Hodgkin lymphoma (B-NHL).

11. Adagene: First Disclosure of Preclinical Data for Two Antibody Programs

According to the press release, by targeting neoantigen epitopes and incorporating precision masking technology, Alphamab Oncology aims to tailor antibody candidates that combine both safety and efficacy. When developing potent therapeutic antibody drugs, such as bispecific T-cell engagers or antibody-drug conjugates, Alphamab Oncology aims to surpass the efficacy of conventional monoclonal antibodies while ensuring patient safety. These innovative technologies are respectively referred to as NEObody™, SAFEbody™, and POWERbody™.

Adagene will present preclinical data for two novel antibody drug candidates, ADG153 and ADG152, at this conference. ADG153 is an anti-CD47 SAFEbody™ antibody, while ADG152 is a CD20xCD3 POWERbody™ antibody. Preclinical data demonstrate that ADG153 and ADG152 exhibit significantly differentiated profiles. According to the press release, Adagene continues to expand and advance its innovative preclinical pipeline. Including ADG152 and ADG153, five programs are currently in the preclinical research stage for new drug applications.

Source: Corporate announcements of respective companies.

Executive Editor: Liuli

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