HBW-3220 / Hyperway Pharma - LARVOL DELTA

A Phase III, Open-Label, Randomized Study of HBW-3220 Capsules Compared to Investigator's Choice in Participants With Relapsed/​Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Previously Exposed to Bruton Tyrosine Kinase (BTK) Inhibitors (ChiCTR) - P3 | N=216 | Not yet recruiting | Sponsor: Chinese Academy of Medical Sciences Hospital of Hematology; Hyperway Pharmaceutical Co.,Ltd.

New P3 trial • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

Fourth-generation BTK inhibitor HBW-3220 in the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma (Sohu.com) - P1/2a | N=120 | CTR20221130 | "Results showed that 38 patients underwent at least one efficacy assessment. The objective response rates (ORRs) for CLL/SLL, marginal zone lymphoma (MZL), and mantle cell lymphoma (MCL) were 63% (n=19), 75% (n=4), and 43% (n=7), respectively. All CLL/SLL patients had received at least one irreversible BTK inhibitor, of which 53% had TP53 mutations and 37% had BTK C481S mutations. The ORR for CLL/SLL patients taking both irreversible BTK inhibitors and BCL2 inhibitors was 82% (n=11), while it was 72% in the Pirtobrutinib treatment group. The ORR for CLL/SLL patients with BTK C481S mutations was 71% (n=7)."

P1/2 data • Chronic Lymphocytic Leukemia • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Small Lymphocytic Lymphoma

Phase I/IIa clinical study of 4th generation BTK inhibitor HBW-3220 capsules in patients with B-cell malignancies. (ASCO 2025) - P | "The rates of Grade 3 or higher AEs for neutropenia, decreased hemoglobin, decreased platelets, and bleeding were all lower than those for Pirtobrutinib. HBW-3220 capsules show good safety, tolerability, and outstanding efficacy in CLL/SLL patients, with significant potential to surpass existing treatments."

Clinical • IO biomarker • P1/2 data • Anemia • B Cell Non-Hodgkin Lymphoma • Chronic Lymphocytic Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Pain • Pneumonia • Respiratory Diseases • Small Lymphocytic Lymphoma • CRP • TP53

A Multi-Center Phase I/II Study to Investigate the Safety, Tolerability, Efficacy and Pharmacokinetic of HBW-3210 Capsules in Chinese patients with mature B cell lymphoma (ChiCTR) - P1/2 | N=80 | Recruiting | Sponsor: Beijing Tiantan Hospital, Capital Medical University; Hyperway Pharmaceutical Co.,Ltd.

New P1/2 trial • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A phase IIA clinical trial to evaluate a reversible Bruton's tyrosine kinase inhibitor (BTKi) HBW-3220 capsules in patients with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL). (ASCO 2024) - "Background: This clinical study is to evaluate HBW-3220, a novel BTKi with an improved in vitro profile than the existing non-covalent drugs pirtobrutinib (approved) and nemtabrutinib (Phase III). The current data show that HBW-3220 is well tolerated with no DLT occurred at daily doses up to 150 mg, displaying most promising efficacy in patients with CLL/SLL, MZL, and MCL. Clinical trial information: ChiCTR2200062537."

Clinical • IO biomarker • P2a data • Anemia • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pain • Pneumonia • Respiratory Diseases • Small Lymphocytic Lymphoma • Waldenstrom Macroglobulinemia • HCK

Phase I clinical study of Bruton's tyrosine kinase inhibitor (BTKi) HBW-3220 capsules in patients with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL) (AACR 2024) - "Purpose: This clinical study is to evaluate HBW-3220, a novel reversible BTK inhibitor (BTKi) with an improved in vitro profile than the existing non-covalent drugs pirtobrutinib (LOXO-305, approved) and MK-1026 (Phase III). HBW-3220 shows superior inhibition against BTK wild-type and several common mutants, such as C481S, C481R, T474I, T316A, and L528W (the one predominantly enriched in patients resistant to the newer-generation BTKis), and hematopoietic cell kinase (HCK), a key contributor to the development of ibrutinib resistance associated with kinase-defective BTK. This phase I clinical study was conducted in R/R B-NHL patients who had received two or more prior lines of treatments... The current data show that HBW-3220 is well tolerated, showing no DLT occurred at daily doses up to 150 mg, and has good efficacy in patients with CLL/SLL, MZL, and MCL."

Clinical • IO biomarker • P1 data • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • HCK

Phase I clinical study of orally-dosed HBW-3220 in patients with relapsed/refractory B-cell lymphoma. (ASCO 2023) - "The current data show that HBW-3220 is well tolerated and of efficacy in patients with B-cell lymphoma. Its clinical PK characteristics support once-a-day administration. Clinical trial information: ChiCTR20221130."

Clinical • P1 data • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Respiratory Diseases • Small Lymphocytic Lymphoma • Waldenstrom Macroglobulinemia

[VIRTUAL] DISCOVERY OF HBW-3-10: A POTENT, ORALLY ACTIVE, REVERSIBLE BRUTON’S TYROSINE KINASE (BTK) INHIBITOR WITH ANTITUMOR ACTIVITIES IN MICE (EHA 2021) - "LOXO-305 and ARQ-531 are two examples of the second generation reversible BTK inhibitors in advanced clinical trials for ibrutinib-resistant CLL. compound BTK IC50 (nM) BTKc481s IC50 (nM) TMD8 IC50 (nM) hERG (uM) Cmax (ng/mL) AUC 0-∞(ng·hr/mL) T1/2 (hr) ARQ-531 4.1 2.2 82.2 3.53 2414 12963 4.0 HBW-3-10 2.8 1.6 13.9 9.88 25721 211031 3.4 Conclusion We have discovered a novel second generation reversible BTK inhibitor HBW-3-10, that has a superior preclinical profile, efficacy and safety than other known ones. HBW-3-10 provides a valuable clinical candidate for treating Ibrutinib resistant CLL and beyond!"

Preclinical • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

"Live at #EHA2021 Hyperway's reversible BTK inhibitors HBW-3-20 and HBW-3-10 show superior PK and antitumor effects to comparator compounds in mouse models" (@Cortellis)

Preclinical • Oncology

[VIRTUAL] Discovery of HBW-3-10: A potent, orally active, reversible Bruton’s tyrosine kinase (BTK) inhibitor with antitumor activity in mice. (ASCO 2021) - "LOXO-305 and ARQ-531 are two examples of the second generation reversible BTK inhibitors in advanced clinical trials for ibrutinib-resistant CLL . We have discovered a novel second generation reversible BTK inhibitors HBW-3-10, that has a superior preclinical profile, efficacy and safety than other known ones . HBW-3-10 provides a valuable clinical candidate for treating Ibrutinib resistant CLL and beyond!"

Preclinical • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology