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Sumitomo Pharma
Presents Encouraging New Data on
DSP-5336
Clinical Activity at the American Society of Hematology Annual Meeting
2023-12-11
·
BioSpace
临床结果
ASH会议
孤儿药
临床1期
–
DSP-5336
, an Investigational Menin and Mixed-lineage Leukemia Inhibitor, is Being Evaluated in Patients with Relapsed or Refractory Acute Leukemia, with Positive Preliminary Data Presented at ASH – CAMBRIDGE, Mass., Dec. 11, 2023 /PRNewswire/ --
Sumitomo Pharma America, Inc.
(SMPA) today announced new data from the ongoing Phase 1/2 first-in-human study of
DSP-5336
, in patients with relapsed or refractory acute leukemia, presented at the 65th American Society of Hematology (ASH) Annual Meeting & Exposition.
DSP-5336
is an investigational small molecule inhibitor of the
menin
and mixed-lineage leukemia (MLL) protein interaction, which plays key roles in biological pathways, including cell growth regulation, cell cycle control, genomic stability, bone development, and hematopoiesis.1,2,3 Data from the open-label, ongoing dose determination portion of the Phase 1/2 study enrolling patients with relapsed or refractory acute leukemia with relevant genomic alterations receiving oral
DSP-5336
up to 200 mg twice-daily were presented at the meeting. In the ongoing study, patients are continuing to dose escalate and are now at therapeutic levels. Preliminary results presented at ASH 2023 included four evaluable patients treated with
DSP-5336
200 mg twice-daily, three of whom showed objective responses. Clinical remission with partial hematologic recovery and clinical remission with incomplete count recovery (CRh/CRi) was achieved by one patient, CRi was achieved by one patient, and morphologic
leukemia
-free state (MLFS) was achieved by one patient. All patients cleared peripheral blasts. To date,
DSP-5336
has been well-tolerated, notably, with no treatment-related cardiac effects, including QT prolongation. Additionally,
differentiation syndrome
has not been observed at the 200 mg twice-daily dose. "While these data are early-stage, it is encouraging to see promising clinical activity from
DSP-5336
, particularly with limited safety signals and a clean tolerability pro date," said Navel Daver, M.D., Director, Department of
Leukemia
, Division of
Leukemia
Research Alliance Program, The
University of Texas MD Anderson Cancer Center
Cancer
Center and lead author on the
DSP-5336
poster at ASH. "
DSP-5336
is an investigational targeted therapy that inhibits
menin-MLL protein
interaction. Inhibition of the
menin-MLL protein
interaction may be able to reverse the leukemogenic activity of MLL fusion proteins and may be a future therapeutic option for
acute leukemia
."
Leukemia
is a type of
cancer
that forms in blood-forming tissue, characterized by the uncontrolled growth of blood cells, usually white blood cells in the bone marrow.4
Acute leukemia
, a form of
leukemia
, requires immediate treatment as blood cells multiply rapidly leading to a sudden onset of symptoms.4 "There is a high unmet need for new and innovative approaches in the treatment of relapsed or refractory acute leukemia, as many patients have limited options to treat the disease or do not respond to currently available
cancer
therapies," said Jatin Shah, M.D., Chief Oncology Development Officer, SMPA. "We believe we are close to determining the appropriate therapeutic dose of
DSP-5336
in our ongoing study and were encouraged by our discussions on these results with the leading hematological oncology community at ASH. We look forward to continuing the study of
DSP-5336
as a monotherapy and to exploring additional combination studies." Additional SMPA data presented at ASH included an oral presentation of encouraging preliminary results from the ongoing Phase 1/2 study of
TP-3654
monotherapy in patients with
relapsed or refractory myelofibrosis
who were previously treated with or ineligible for a
JAK inhibitor
JAK
inhibitor. About
DSP-5336
DSP-5336
is an investigational small molecule inhibitor of the
menin
and mixed-lineage leukemia (MLL) protein interaction.
Menin
is a scaffold nuclear protein that plays various key roles in biological pathways, including cell growth regulation, cell cycle control, genomic stability, bone development, and hematopoiesis.1,2 In preclinical studies,
DSP-5336
has shown selective growth inhibition in human
acute leukemia
cell lines with KMT2A (MLL) rearrangements or
NPM1
mutations.1,3
DSP-5336
showed induced reduction of gene expression of
HOXA9
and
MEIS1
, which are highly expressing
leukemia
associate genes, and increased expression of differentiation marker gene
CD11b
in the human
acute leukemia
cell lines with
MLL
rearrangements.5,6
DSP-5336
also showed growth inhibition and changes of gene expression levels of
HOXA9
,
MEIS1
and
CD11b
on human
acute leukemia
patient samples with
MLL
rearrangements or
NPM1
mutations.5,6 The safety and efficacy of
DSP-5336
is currently being clinically evaluated in a Phase 1/2 dose escalation/dose expansion study in patients with relapsed or refractory acute leukemia (NCT04988555). The FDA granted Orphan Drug Designation for
DSP-5336
for the indication of
acute myeloid leukemia
in June 2022. About
TP-3654
TP-3654
is an oral investigational inhibitor of
PIM1 kinase
, which has shown potential antitumor and antifibrotic activity through multiple pathways, including induction of apoptosis in preclinical models.7,8
TP-3654
was observed to inhibit proliferation and induce apoptosis in murine and human hematopoietic cells expressing the clinically relevant JAK2V617F mutation.7
TP-3654
alone and in combination with
ruxolitinib
showed white blood cell and neutrophil count normalization, and also reduced spleen size and
bone marrow fibrosis
in JAK2V617F and MPLW515L murine models of
myelofibrosis.8
The safety and efficacy of
TP-3654
is currently being clinically evaluated in a Phase 1/2 study in patients with intermediate and high-risk
myelofibrosis
(NCT04176198). The
U.S. Food and Drug Administration (FDA)
granted Orphan Drug Designation for
TP-3654
for the indication of
myelofibrosis
in May 2022. About
Sumitomo Pharma
Sumitomo Pharma Co., Ltd.
is a global pharmaceutical company based in Japan with key operations in the U.S. (
Sumitomo Pharma America, Inc.
), Canada (Sumitomo Pharma Canada, Inc.) and Europe (Sumitomo Pharma Switzerland GmbH) focused on addressing patient needs in psychiatry & neurology, oncology, urology, women's health, rare disease, and cell & gene therapies. With several marketed products in the U.S., Canada, and Europe, a diverse pipeline of early- to late-stage assets, and in-house advanced technology capabilities, we aim to accelerate discovery, research, and development to bring novel therapies to patients sooner. For more information, please visit and LinkedIn to follow us. The
Sumitomo Pharma
icon is a trademark of
Sumitomo Pharma Co., Ltd.
, used under license. SUMITOMO PHARMA is a trademark of
Sumitomo Pharma Co., Ltd.
, used under license. SUMITOMO is a registered trademark of
Sumitomo Chemical Co., Ltd.
, used under license.
Sumitomo Pharma America, Inc.
is a U.S. subsidiary of
Sumitomo Pharma Co., Ltd.
© 2023
Sumitomo Pharma America, Inc.
All rights reserved. For a copy of this release, visit
Sumitomo Pharma America
's website at . References Cierpicki T, Grembecka J. Challenges and opportunities in targeting the
menin-MLL
Interaction. Future Med Chem. 2014; 6(4):447-462. doi:10.4155/fmc.13.214. Matkar S, Thiel A, Hua X.
Menin
: a scaffold protein that controls gene expression and cell signaling. Trends Biochem Sci. 2013; 38(8):394-402. doi:10.1016/j.tibs.2013.05.005. Kuhn MWM, Song E, Feng Z, et al. Targeting chromatin regulators inhibits leukemogenic gene expression in
NPM1 mutant leukemia
NPM1
mutant leukemia.
Cancer
Discov. 2016; 6(10):1166-1181. doi:10.1158/2159-8290.CD-16-0237. Chennamadhavuni A, Lyengar V, Mukkamalla SKR, et al.
Leukemia
. [Updated 2023 Jan 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: . Eguchi K, Shimizu T, Kato D, et al. Preclinical Evaluation of a Novel Orally Bioavailable
Menin-MLL Interaction Inhibitor
,
DSP-5336
, for the Treatment of
Acute Leukemia
Patients with
MLL-Rearrangement
or
NPM1
Mutation. Blood (2021) 138 (Supplement 1): 3339. . Daver N, Zeidner JF, Yuda J, et al. 2911 Phase 1/2 First-in-Human Study of the
Menin-MLL Inhibitor
Menin-MLL
Inhibitor
DSP-5336
in Patients with Relapsed or Refractory Acute Leukemia. American Society of Hematology 2023. Available at: Foulks JM, Carpenter KJ, Luo B, et al. A small-molecule inhibitor of
PIM kinases
as a potential treatment for
urothelial carcinomas
. Neoplasia. 2014;16(5):403-412. Dutta A., Nath D, Yang Y, et al. Genetic ablation of
Pim1
or pharmacologic inhibition with
TP-3654
ameliorates
myelofibrosis
in murine models.
Leukemia
. 2022; 36 (3): 746-759. doi: 10.1038/s41375-021-01464-2.
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机构
Sumitomo Pharma Co., Ltd.
Sumitomo Pharma America, Inc.
The University of Texas MD Anderson Cancer Center
[+2]
适应症
白血病
性发育障碍
肿瘤
[+5]
靶点
menin
septin-9
JAK
[+7]
药物
DSP-5336
TP-3654
Inhaled JAK inhibitor(Theravance, Inc.)
[+2]
标准版
¥
16800
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