RCS - Hutchmed China Ltd - HUTCHMED Initiates Development of ATTC Candidate

HUTCHMED (China)Announcement

Wed 07:00

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RNS Number : 8252L  Hutchmed (China) Limited  17 December 2025

Press Release

 

HUTCHMED Initiates Global Clinical Development of ATTC Candidate HMPL-A251 in Patients with Solid Tumors

 

- First-in-human trial of candidate from the next-generation ATTC platform -

- Simultaneous China and global clinical development strategy to expedite
development process -

Hong Kong, Shanghai & Florham Park, NJ -   Wednesday, December 17,
2025: HUTCHMED (China) Limited ("HUTCHMED (https://www.hutch-med.com/) ")
(Nasdaq/AIM:HCM; HKEX:13) today announces the initiation of its global Phase I
clinical development program for HMPL-A251, a first-in-class PI3K/PIKK-HER2
Antibody-Targeted Therapy Conjugate ("ATTC") comprising a highly selective and
potent PI3K/PIKK inhibitor payload conjugated to a humanized anti-HER2 IgG1
antibody via a cleavable linker. Study sites are in the US and China. The
first patient received the first dose on December 16, 2025, in China.

 

This first-in-human Phase I/IIa, open-label, multicenter clinical study
evaluates HMPL-A251 monotherapy in adult patients with unresectable, advanced
or metastatic HER2-expressing solid tumors. The study is divided into two
parts, a Phase I dose escalation part and a Phase IIa dose expansion and
optimization part. The primary outcome measures are to evaluate the safety and
tolerability of HMPL-A251 and to determine the maximum tolerated dose (MTD)
and/or recommended dose(s) for expansion ("RDE") in the Phase I part, and to
further evaluate safety and preliminary efficacy at RDEs and to determine the
recommended dose for Phase II (RP2D) or Phase III (RP3D) in the Phase IIa
part. Secondary outcome measures include preliminary antitumor activity,
pharmacokinetic profile, and the immunogenicity of HMPL-A251. Additional
details may be found at clinicaltrials.gov, using identifier NCT07228247
(https://clinicaltrials.gov/study/NCT07228247) .

 

HMPL-A251 is the first clinical-stage candidate derived from HUTCHMED's
next-generation ATTC platform. The first family of programs are based on a
highly potent and selective PI3K/PIKK inhibitor payload. By conjugating this
highly novel payload to an anti-HER2 antibody, the molecule is designed to
deliver targeted pathway inhibition directly into HER2-expressing tumor cells,
thereby potentially overcoming the systemic toxicity and narrow therapeutic
index historically associated with PI3K/PIKK inhibitors. This approach aims to
achieve deeper and more durable target inhibition while improving the overall
tolerability profile.

 

Preclinical data for HMPL-A251 were presented at the 2025 AACR-NCI-EORTC
International Conference on Molecular Targets and Cancer Therapeutics. This
body of evidence supports the translational potential of the ATTC platform,
the ongoing global clinical evaluation of HMPL-A251, and the broad potential
of HUTCHMED's PI3K/PIKK inhibitor linker-payload to underpin a family of
future ATTC drug candidates.

 

About the ATTC Platform

HUTCHMED's ATTC platform represents a next-generation approach to precision
oncology, combining monoclonal antibodies with proprietary small-molecule
inhibitor payloads to deliver dual mechanisms of action. Unlike traditional
cytotoxin-based Antibody Drug Conjugates, ATTCs combine targeted therapies to
achieve synergistic anti-tumor activity and durable responses in preclinical
models, outperforming standalone antibody or small-molecule inhibitor
components in efficacy and safety.

 

Built on over 20 years of targeted therapy expertise, the platform enables
development of drug candidates for diverse cancer types. By leveraging
antibody-guided delivery and tumor-specific payload release, ATTCs improve the
accessibility to tumors and reduce off-tumor toxicity. This overcomes
challenges of traditional small-molecule inhibitors, ensures safer long-term
use, and supports combinations with chemotherapy and immunotherapy, unlocking
potential for early-line treatments.

 

About the PAM Pathway and HMPL-A251

The PI3K/AKT/mTOR ("PAM") pathway is a critical intracellular network involved
in cell growth, survival, and division. Alterations in the PAM pathway are
frequently associated with poor prognosis and resistance to treatment across
various cancers. However, existing PAM-targeted drugs face significant
challenges, including on-target toxicities that restrict dosing, feedback
loops that enable pathway reactivation, and insufficient tumor-specific
delivery. HUTCHMED has designed a highly novel PI3K/PIKK inhibitor
linker-payload to overcome these challenges with broad potential to lead to a
family of antibody conjugate drug candidates.

 

HMPL-A251 is a first-in-class ATTC comprising of this highly selective and
potent PI3K/PIKK inhibitor payload conjugated to a humanized anti-HER2 IgG1
antibody via a cleavable linker, designed to address challenges by enhancing
targeted delivery directly to tumor cells, maximizing therapeutic benefit
while minimizing systemic exposure. In preclinical studies, the HMPL-A251
payload exhibited high selectivity, potency, and robust anti-tumor activity.
HMPL-A251 exhibited superior anti-tumor efficacy and tolerability compared to
co-administration of the naked antibody and payload.

 

About HUTCHMED

HUTCHMED (Nasdaq/AIM:HCM; HKEX:13) is an innovative, commercial-stage,
biopharmaceutical company. It is committed to the discovery and global
development and commercialization of targeted therapies and immunotherapies
for the treatment of cancer and immunological diseases. Since inception it has
focused on bringing drug candidates from in-house discovery to patients around
the world, with its first three medicines marketed in China, the first of
which is also approved around the world including in the US, Europe and Japan.
For more information, please visit: www.hutch‑med.com
(https://www.hutch-med.com/) or follow us on LinkedIn
(https://www.linkedin.com/company/hutchmed/) .

 

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 regarding the
therapeutic potential of HMPL‑A251 and other drug candidates from the ATTC
platform and the further development of HMPL‑A251 and other drug candidates
from the ATTC platform in this and other indications. Forward-looking
statements involve risks and uncertainties. Such risks and uncertainties
include, among other things, assumptions regarding the timing and outcome of
clinical studies and the sufficiency of clinical data to support an new drug
application submission of HMPL‑A251 and other drug candidates from the ATTC
platform in China or other jurisdictions, its potential to gain approvals from
regulatory authorities on an expedited basis or at all, the efficacy and
safety profile of HMPL‑A251 and other drug candidates from the ATTC
platform, HUTCHMED's ability to fund, implement and complete its further
clinical development and commercialization plans for HMPL‑A251 and other
drug candidates from the ATTC platform and the timing of these events.
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 US Securities and Exchange Commission, The Stock Exchange of Hong Kong
Limited 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                                  +852 2121 8200 / ir@hutch-med.com (mailto:ir@hutch-med.com)

 Media Enquiries
 FTI Consulting -                                    +44 20 3727 1030 / HUTCHMED@fticonsulting.com
                                                     (mailto:HUTCHMED@fticonsulting.com)
    Ben Atwell / Tim Stamper                            +44 7771 913 902 (Mobile) / +44 7421 898 348 (Mobile)
 Brunswick - Zhou Yi                                 +852 9783 6894 (Mobile) / HUTCHMED@brunswickgroup.com
                                                     (mailto:HUTCHMED@brunswickgroup.com)

 Panmure Liberum                                     Nominated Advisor and Joint Broker
 Atholl Tweedie / Emma Earl / Rupert Dearden         +44 20 7886 2500

 Cavendish                                           Joint Broker
 Geoff Nash / Nigel Birks                            +44 20 7220 0500

 Deutsche Numis                                      Joint Broker
 Freddie Barnfield / Jeffrey Wong / Duncan Monteith  +44 20 7260 1000

 

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