HUTCHMED Launches Phase I Study of BTK Inhibitor HMPL-760 in Previously Treated Non-Hodgkin B-Cell Lymphoma Patients in China


– HMPL-760 is the eleventh innovative oncology drug candidate discovered internally by HUTCHMED –

– HMPL-760 is HUTCHMED’s fifth candidate in clinical development for hematologic malignancies, including amdizalisib and HMPL-523 which also target the B cell receptor (“BCR”) signaling pathway, as well as tazemetostat and HMPL-306 –

HONG KONG and SHANGHAI and FLORHAM PARK, NJ, January 10, 2022 (GLOBE NEWSWIRE) – HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq / AIM: HCM; HKEX: 13) has initiated a phase I study in China of HMPL-760, a very potent, selective and reversible inhibitor with a long-lasting commitment against Bruton’s tyrosine kinase (“ BTK ‘), including wild type and C481S mutated BTK. The first patient received their first dose on January 4, 2022.

The clinical study is an open-label, multicenter study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary efficacy profile of HMPL-760. The study is recruiting patients with previously treated chronic lymphocytic leukemia / chronic lymphocytic lymphoma (CLL / SLL) or other types of non-Hodgkin lymphoma (“NHL”), including patients treated with a previous regimen containing an inhibitor. BTK, the disease of which carries either wild-type BTK or acquired resistance to first generation BTK inhibitors due to additional BTK mutations.

An initial dose escalation step to determine the maximum tolerated dose (MTD) and / or recommended phase II dose (“RP2D”) is planned, followed by a dose extension phase in which patients will receive HMPL-760 to further assess the safety, tolerability and clinical activity of RP2D. About 100 patients should be included.

HMPL-760 is HUTCHMED’s fifth investigational drug candidate targeting hematologic malignancies in clinical development. Amdizalisib (HMPL-689, targeting the delta isoform of phosphoinositide 3-kinase or PI3K delta) and HMPL-523 (targeting spleen tyrosine kinase or Syk) are also being studied in several phase II trials against B-dominant malignant tumors. Phase II registration studies are underway in China for amdizalisib in patients with follicular lymphoma (FL), for which it has achieved breakthrough therapy designation in China, and marginal zone lymphoma (MZL).

In addition to the three BCR inhibitors, for hematologic malignancies, HUTCHMED is also developing its internally discovered drug candidate HMPL-306, a dual mutant isocitrate dehydrogenase inhibitor 1 and 2, and tazemetostat, a methyltransferase inhibitor. ‘EZH2 (under development in Greater China by HUTCHMED as part of a strategic collaboration with Epizyme).

About BTK and non-Hodgkin lymphoma

BTK is a key component of the B cell receptor signaling pathway and is an important regulator of cell proliferation and cell survival in various lymphomas. Abnormal activation of B-cell receptor signaling is closely linked to the development of hematologic B-cell-type cancers, which account for approximately 85% of all cases of NHL.1 BTK is considered to be a validated target for drugs to treat certain hematologic cancers, however the C481S mutation of BTK is a known resistance mechanism for first and second generation BTK inhibitors. In 2020, it is estimated that around 93,000 new cases of NHL were diagnosed in China.2

About HMPL-760

HMPL-760 is an experimental, highly selective, non-covalent, third-generation inhibitor of BTK, both wild-type and C481S mutant enzymes, with preclinical data suggesting high target specificity and higher potency compared to first generation BTK inhibitors. The BTK C481S mutation plays an important role in resistance to certain BTK inhibitors.3,4

HMPL-760 is HUTCHMED’s eleventh potential innovative oncology drug candidate to enter clinical development. HUTCHMED currently retains all rights to HMPL-760 worldwide.

About HUTCHMED

HUTCHMED (Nasdaq / AIM: HCM; HKEX: 13) is an innovative, commercial-stage biopharmaceutical company. She is engaged in the discovery, development and global commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has more than 4,500 employees in all of its companies, at the center of which is a team of more than 1,400 people in oncology / immunology. Since its inception, 11 cancer drug candidates have moved from in-house discovery to clinical studies around the world, with its first three oncology drugs now approved and marketed in China. For more information, please visit: www.hutch-med.com or follow us on LinkedIn.

Forward-looking statements

This press release contains forward-looking statements within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect HUTCHMED’s current expectations regarding future events, including its expectations regarding the future. therapeutic potential of HMPL-760, amdizalisib, HMPL-523, HMPL-306 and tazemetostat for patients, his expectations as to whether studies of HMPL-760, amdizalisib, HMPL-523, HMPL-306 and tazemetostat would meet their criteria for primary or secondary evaluation, and their expectations for when to complete and publish the results of those studies. Forward-looking statements involve risks and uncertainties. These risks and uncertainties include, among others, assumptions regarding enrollment rates and the timing and availability of subjects meeting the inclusion and exclusion criteria for a study; changes to clinical protocols or regulatory requirements; unexpected adverse events or safety issues; the ability of HMPL-760, amdizalisib, HMPL-523, HMPL-306 and tazemetostat, including as combination therapy, to meet the primary or secondary endpoint of a study, obtain regulatory approval in different jurisdictions and obtain commercial acceptance after obtaining regulatory approval; the potential market for HMPL-760, amdizalisib, HMPL-523, HMPL-306 and tazemetostat for a targeted indication; the adequacy of funding; and the impact of the COVID-19 pandemic on economic, regulatory and general political conditions. Existing and potential investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For more information on these and other risks, see the documents filed by HUTCHMED with the United States Securities and Exchange Commission, the Hong Kong Stock Exchange Limited, and AIM. HUTCHMED assumes no obligation to update or revise any information contained in this press release, whether as a result of new information, future events or circumstances or otherwise.

CONTACTS

Investor surveys

Mark Lee, Senior Vice President

+852 2121 8200

Annie Cheng, vice-president

+1 (973) 567 3786

Media inquiries

Americas – Brad Miles,
Solebury Trout

+1 (917) 570 7340 (Mobile)
[email protected]

Europe – Ben Atwell / Alex Shaw,
FTI Council

+44 20 3727 1030 / +44 7771 913 902 (Mobile) / +44 7779 545 055 (Mobile)
[email protected]

Asia – Zhou Yi,
Brunswick

+852 9783 6894 (mobile)
[email protected]

Appointed advisor

Atholl Tweedie / Freddy Crossley,
Panmure Gordon (UK) Limited

+44 (20) 7886 2500

______________________________

1 American Cancer Society (2019, January 29). Types of B cell lymphoma https://www.cancer.org/cancer/non-hodgkin-lymphoma/about/b-cell-lymphoma.html. Accessed January 5, 2022.
2 Information sheet from the World Cancer Observatory, China. https://gco.iarc.fr/today/data/factsheets/populations/160-china-fact-sheets.pdf. Accessed November 17, 2021.
3 Woyach JA, Ruppert AS, Guinn D, et al. BTKC481S-Ibrutinib-mediated resistance in chronic lymphoid leukemia. J Clin Oncol. 2017; 35 (13): 1437-1443. do I:10.1200 / JCO.2016.70.2282.
4 Woyach JA, Huang Y, Rogers K, et al. Resistance to acalabrutinib in CLL is mediated primarily by BTK mutations. Blood. 2019; 134 (Supplement_1): 504. doi:10.1182 / sang-2019-127674.

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