TIDMHCM
Hutchison China Meditech Limited
29 March 2021
Press Release
HUTCHMED Initiates International Phase I Trials of IDH1/2 Dual
Inhibitor in Patients with Advanced Solid Tumors or Hematological
Malignancies
- HMPL-306 is the sixth innovative oncology drug candidate
discovered in house by HUTCHMED to enter into global development
-
Hong Kong, Shanghai & Florham Park, NJ - Monday, March 29,
2021: Hutchison China MediTech Limited ("HUTCHMED") (Nasdaq/AIM:
HCM) has initiated two international Phase I studies of HMPL-306,
its novel selective small molecule dual inhibitor of isocitrate
dehydrogenase ("IDH") 1 and 2 mutations. One trial is in patients
with advanced solid tumors and one trial is in patients with
hematological malignancies. Both trials have sites in the US and
Europe. The first international patient was dosed on March 25,
2021, following a Phase I trial that was initiated in China in the
second half of 2020. This new program is a demonstration of
HUTCHMED's accelerating and expanding global clinical development
presence.
These two trials are multi-center studies to evaluate the
safety, tolerability pharmacokinetics, pharmacodynamics and
preliminary efficacy of HMPL--306. The first trial is in solid
tumors (including but not limited to gliomas, chondrosarcomas, or
cholangiocarcinomas), while a second trial is in advanced relapsed,
refractory or resistant hematological malignancies that harbor IDH1
or IDH2 mutations. The first stage of each study is a dose
escalation phase where cohorts of patients will receive ascending
oral doses of HMPL--306 to determine the maximum tolerated dose
and/or the recommended Phase II dose ("RP2D"). The second stage is
a dose expansion phase where patients will receive HMPL--306 to
further evaluate the safety, tolerability, and clinical activity at
the RP2D. Additional details may be found at clinicaltrials.gov,
using identifiers NCT04762602 and NCT04764474, respectively.
The MD Anderson Cancer Center ("MDACC") is the lead institution
on both studies. The lead investigator for the hematological
malignancies study is Dr. Farhad Ravandi, the Janiece and Stephen
A. Lasher Professor of Medicine and Chief of Section of
Developmental Therapeutics in the Department of Leukemia at The
University of Texas MDACC. The lead investigator for the solid
tumor study is Dr. Filip Janku, Associate Professor, Department of
Investigational Cancer Therapeutics at The University of Texas
MDACC.
A Phase I study of HMPL-306 is underway in China, with the first
patient dosed in July 2020. Additional details of that study may be
found at clinicaltrials.gov, using identifier NCT04272957.
HMPL-306 is HUTCHMED's ninth innovative oncology drug candidate
that it has discovered that has entered clinical development and
the sixth to enter global clinical development. Cytoplasmic mutant
IDH1 and mitochondrial mutant IDH2 have been known to switch to the
other form when targeted by an inhibitor of IDH1 mutant alone or
IDH2 mutant alone. By targeting both IDH1 and IDH2 mutations,
HMPL-306 could potentially provide therapeutic benefits in cancer
patients harboring either IDH mutation, and may address acquired
resistance to IDH inhibition through isoform switching.
About IDH and Malignancies
IDHs are critical metabolic enzymes that help to break down
nutrients and generate energy for cells. When mutated, IDH creates
a molecule that alters the cell's genetic programming and prevents
cells from maturing, 2-hydroxyglutarate ("2-HG"). Reduction in 2-HG
levels can be used as a marker of target engagement by an IDH
inhibitor. IDH1 or IDH2 mutations are common genetic alterations in
various types of blood and solid tumors, including acute myeloid
leukemia ("AML") with approximately 20% of patients having mutant
IDH genes, myelodysplastic syndrome (MDS), myeloproliferative
neoplasms (MPNs), low-grade glioma and intrahepatic
cholangiocarcinoma ("IHCC"). Mutant IDH isoform switching, either
from cytoplasmic mutant IDH1 to mitochondrial mutant IDH2, or vice
versa, is a mechanism of acquired resistance to IDH inhibition in
AML and cholangiocarcinoma. [1](, [2] , [3]) Currently, the U.S.
Food and Drug Administration (FDA) has approved one drug for IDH1
mutation and one drug for IDH2 mutation, but no dual inhibitor
targeting both IDH1 and IDH2 mutants has been approved.
In the US, it is estimated that there were approximately 20,000
new cases of AML in 2020 and the five-year relative survival rate
is 28.7%. [4]
IDH mutations are present in a number of solid tumors, including
malignant glioma and IHCC. In the US, the annual incidence of
malignant glioma is estimated to be 20,000, 50-70% of which are
glioblastoma. [5](, [6]) Approximately 60-80% of Grade 2 or 3
glioma and secondary glioblastoma harbor IDH mutations. [7] IHCC
accounts for 10-20% of primary liver cancer, which was estimated to
be diagnosed in 42,810 US patients in 2020. [8](, [9])
Approximately 20-30% of IHCC harbors IDH mutations. [10]
About HUTCHMED
HUTCHMED (Nasdaq/AIM: HCM) is an innovative, commercial-stage,
biopharmaceutical company committed, over the past twenty years, to
the discovery and global development of targeted therapies and
immunotherapies for the treatment of cancer and immunological
diseases. It has advanced ten cancer drug candidates from discovery
into clinical studies around the world and has extensive commercial
infrastructure in its home market of China. For more information,
please visit: www.hutch-med.com.
Forward-Looking Statements
This press release contains forward-looking statements within
the meaning of the "safe harbor" provisions of the U.S. Private
Securities Litigation Reform Act of 1995. These forward-looking
statements reflect HUTCHMED's current expectations regarding future
events, including its expectations for the initiation of clinical
development of HMPL-306 and the potential benefits of HMPL-306 in
patients harboring IDH mutations. Forward-looking statements
involve risks and uncertainties. Such risks and uncertainties
include, among other things, assumptions regarding clinical trial
enrollment rates, timing and availability of subjects meeting a
study's inclusion and exclusion criteria, changes to clinical
protocols or regulatory requirements, unexpected adverse events or
safety issues, the ability of drug candidate HMPL-306 as a
monotherapy or in combinations to meet the primary or secondary
endpoint of a study, to obtain regulatory approval in different
jurisdictions and to gain commercial acceptance after obtaining
regulatory approval, the potential market of HMPL-306 for a
targeted indication, the sufficiency of funding, and the impact of
the COVID-19 pandemic on general economic, regulatory and political
conditions. Existing and prospective investors are cautioned not to
place undue reliance on these forward-looking statements, which
speak only as of the date hereof. For further discussion of these
and other risks, see HUTCHMED's filings with the U.S. Securities
and Exchange Commission and on AIM. HUTCHMED undertakes no
obligation to update or revise the information contained in this
press release, whether as a result of new information, future
events or circumstances or otherwise.
CONTACTS
Investor Enquiries
Mark Lee, Senior Vice President +852 2121 8200
Annie Cheng, Vice President +1 (973) 567 3786
Media Enquiries
Americas - Brad Miles, +1 (917) 570 7340 (Mobile)
Solebury Trout bmiles@troutgroup.com
Europe - Ben Atwell / Alex Shaw, +44 20 3727 1030 / +44 7771 913 902 (Mobile) / +44 7779 545 055 (Mobile)
FTI Consulting HUTCHMED@fticonsulting.com
Asia - Joseph Chi Lo / Zhou Yi, +852 9850 5033 (Mobile) / +852 97 83 6894 (Mobile)
Brunswick HUTCHMED@brunswickgroup.com
Nominated Advisor
Freddy Crossley / Atholl Tweedie,
Panmure Gordon (UK) Limited +44 (20) 7886 2500
[1] Choe S et al. Blood 2019;134(Supplement_1):545.
doi:10.1182/blood-2019-122671.
[2] Harding JJ et al. Isoform Switching as a Mechanism of
Acquired Resistance to Mutant Isocitrate Dehydrogenase Inhibition.
Cancer Discov. 2018;8(12):1540-1547.
doi:10.1158/2159-8290.CD-18-0877.
[3] Delahousse J et al. Circulating oncometabolite
D-2-hydroxyglutarate enantiomer is a surrogate marker of isocitrate
dehydrogenase-mutated intrahepatic cholangiocarcinomas. Eur J
Cancer 2018;90:83-91. doi:10.1016/j.ejca.2017.11.024.
[4] National Cancer Institute -
seer.cancer.gov/statfacts/html/amyl.html.
[5] Ostrom QT, Patil N et al. CBTRUS Statistical Report: Primary
Brain and Other Central Nervous System Tumors Diagnosed in the
United States in 2013-2017. Neuro Oncol. 2020;22(12 Suppl
2):iv1-iv96. doi:10.1093/neuonc/noaa200.
[6] Wen P, Kesari S. Malignant Gliomas in Adults. N Engl J Med
2008;359:492-507. doi: 10.1056/NEJMra0708126.
[7] Yan H, Parsons W et al. IDH1 and IDH2 Mutations in Gliomas.
N Engl J Med 2009;360:765-73. doi: 10.1056/NEJMoa0808710.
[8] Massarweh NN, El-Serag HB. Epidemiology of Hepatocellular
Carcinoma and Intrahepatic Cholangiocarcinoma. Cancer Control
September 2017. doi: 10.1177/1073274817729245.
[9] SEER Cancer Stat Facts: Liver and Intrahepatic Bile Duct
Cancer. National Cancer Institute.
seer.cancer.gov/statfacts/html/livibd.html
[10] Lowery MA, Ptashkin R et al. Comprehensive Molecular
Profiling of Intrahepatic and Extrahepatic Cholangiocarcinomas:
Potential Targets for Intervention. Clin Cancer Res.
2018;24(17):4154-4161. doi: 10.1158/1078-0432.CCR-18-0078.
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