RCS - Hutchmed China Ltd - HUTCHMED Presents Data at AACR NCI EORTC

HUTCHMED (China)Announcement

Thu 07:00

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RNS Number : 4427E  Hutchmed (China) Limited  23 October 2025

Press Release

 

HUTCHMED Highlights HMPL-A251 Data Presented at the AACR‑NCI‑EORTC International Conference on Molecular Targets and Cancer Therapeutics

 

- First investigational drug candidate using the HUTCHMED ATTC technology
platform to create potent targeted therapy payloads while mitigating related
toxicities -

- Unique, highly potent PI3K/PIKK inhibitor payload optimized to exploit
antibody-conjugate advantages, with directed delivery and low plasma exposure
of free payload -

- Preclinical data shows robust antitumor activity with synergistic and
bystander killing effects -

Hong Kong, Shanghai & Florham Park, NJ - Thursday, October 23, 2025:
HUTCHMED (China) Limited ("HUTCHMED (https://www.hutch-med.com/) ")
(Nasdaq/AIM:HCM; HKEX:13) today announces preclinical data for HMPL-A251 at
the AACR‑NCI‑EORTC International Conference on Molecular Targets and
Cancer Therapeutics, held October 22-26, 2025, in Boston, USA. HMPL-A251 is a
first-in-class PI3K/AKT/mTOR ("PAM")-HER2 Antibody-Targeted Therapy Conjugate
("ATTC") comprising of a highly selective and potent PI3K/PIKK inhibitor
payload linked to a humanized anti-HER2 IgG1 antibody, via a cleavable linker.

 

HER2 is a well-established therapeutic target. HER2 overexpression is found in
a variety of cancer types and often associated with poor prognosis. As a key
downstream signaling pathway of HER2, the PAM pathway contributes
significantly to the resistance against HER2-targeting treatments when
altered. HMPL-A251 is innovatively designed to leverage the synergy between
HER2 targeting and PAM pathway inhibition to address limitations of
traditional toxin-based antibody-drug conjugates ("ADCs") and standalone PAM
inhibitors.

 

In vitro, the PI3K/PIKK inhibitor payload exhibited high potency, selectivity,
and broad anti-tumor activity across a panel of 130 tumor cell lines. By
conjugating this potent payload with an anti-HER2 antibody via a hydrophilic
linker, the ATTC compound HMPL-A251, upon binding to the HER2-positive target
cells, undergoes rapid internalization, lysosomal trafficking, payload
release, and inhibition of PAM and PIKK signaling, inducing tumor cell
apoptosis. HMPL-A251 demonstrated HER2-dependent antitumor activity in vitro,
potently inhibiting HER2-positive tumor cell growth regardless of PAM pathway
alterations, with moderately reduced activity in HER2-low, PAM-altered cell
lines. HMPL-A251 also demonstrated a bystander effect on HER2-null cells when
co-cultured with HER2-positive cells.

 

Unlike toxin-based ADCs, which often face challenges with toxicity related to
their cytotoxic payloads, ATTCs are designed to prioritize tumor-specific
delivery of a pathway-modulating payload, enhancing safety for long‑term use
and enabling potential frontline combinations with chemotherapy. In vivo,
HMPL-A251 demonstrated superior anti-tumor efficacy and tolerability as
compared to the naked antibody and payload administered together. A single
intravenous dose of HMPL-A251 induced tumor regression across multiple models
including HER2-positive and HER2-low models with or without PAM alteration.
Efficacy correlated strongly with payload concentration and target inhibition
in tumor tissue. Notably, when benchmarked against T-DXd (trastuzumab
deruxtecan, a HER2‑directed ADC), HMPL-A251 achieved superior or comparable
efficacy at equivalent doses in most tested models. Moreover, payload-based
toxicities are expected to be low, as the plasma exposure of free payload was
much lower than for HMPL-251, with a mass ratio of less than 1:500,000.

 

"We are excited to share the progress of HMPL-A251, the first candidate from
our ATTC platform. It represents a potentially significant leap forward in
addressing the limitations of toxin-based ADCs and narrow therapeutic window
of systemic PAM inhibitors. By combining selective PI3K/PIKK inhibition with
precise HER2 targeting, HMPL-A251 achieves potent antitumor effects while
maintaining a favorable safety profile," said Dr Michael Shi, Head of R&D
and Chief Medical Officer of HUTCHMED. "The compelling preclinical data
presented underscore its potential to redefine treatment for a wide spectrum
of cancers, and we are excited to advance HMPL-A251 as well as more ATTC drug
candidates toward clinical trials."

 

HUTCHMED plans to initiate global clinical trials for HMPL-A251 around the end
of 2025, followed by multiple global Investigational New Drug (IND) filings
for more ATTC candidates in 2026.

 

About the ATTC platform

HUTCHMED's Antibody-Targeted Therapy Conjugate 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 ADCs, 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 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 US Private Securities Litigation Reform
Act of 1995. These forward-looking statements reflect HUTCHMED's current
expectations regarding future events, including but not limited to its
expectations regarding the therapeutic potential of HMPL‑A251 and other drug
candidates from the ATTC platform, the further clinical development for
HMPL‑A251 and other drug candidates from the ATTC platform, its expectations
as to whether any studies on HMPL‑A251 and other drug candidates from the
ATTC platform would meet their primary or secondary endpoints, and its
expectations as to the timing of the completion and the release of results
from such studies. Such risks and uncertainties include, among other things,
assumptions regarding enrollment rates and the 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 HMPL‑A251 and other drug candidates from the
ATTC platform, including as combination therapies, 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 markets of HMPL‑A251 other drug candidates from the
ATTC platform for a targeted indication, and the sufficiency of funding.
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 / Alex Shaw                              +44 7771 913 902 (Mobile) / +44 7779 545 055 (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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