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

On October 23, 2025 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM:HCM; HKEX:13) reported preclinical data for HMPL-A251 at the AACR (Free AACR Whitepaper)‑NCI‑EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper), 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.

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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.

(Press release, Hutchison China MediTech, OCT 23, 2025, View Source [SID1234656946])

Blenrep approved by US FDA for use in treatment of relapsed/refractory multiple myeloma

On October 23, 2025 GSK plc (LSE/NYSE: GSK) reported the US Food and Drug Administration (FDA) has approved Blenrep (belantamab mafodotin-blmf) in combination with bortezomib and dexamethasone (BVd) for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least two prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory (IMID) agent.

The Blenrep approval is supported by data from the pivotal DREAMM-7 phase III trial. In patients who had two or more prior lines of therapy (3L+), including a PI and an IMID, Blenrep in combination demonstrated a clinically meaningful 51% reduction in the risk of death [HR 0.49, 95% confidence interval (CI): 0.32-0.76] and a tripled median progression-free survival (PFS) of 31.3 months [95% CI: 23.5-NR)] versus 10.4 months [95% CI: 7.0-13.4] for a daratumumab-based triplet (DVd) [HR 0.31, 95% CI: 0.21-0.47]. The safety and tolerability profiles of the Blenrep combination were broadly consistent with the known profiles of the individual agents.2

Tony Wood, Chief Scientific Officer, GSK, said: "Today’s FDA approval of Blenrep is another significant milestone, providing potential for superior efficacy, including overall survival, to US patients. There is an urgent need for new and novel therapies, as nearly all patients with multiple myeloma experience relapse and re-treating with the same mechanism of action often leads to suboptimal outcomes. As the only anti-BCMA agent that can be administered across healthcare settings, including in community centres where 70% of patients receive care, Blenrep fulfils a major patient need. We believe Blenrep can redefine treatment for patients with multiple myeloma in all parts of the world, and we are accelerating its development in earlier lines of therapy to support its use across all stages of this difficult-to-treat cancer."

Working closely with the FDA, Blenrep is available through a new, streamlined Risk Evaluation and Mitigation Strategy (REMS). The new REMS supports appropriate use and patient safety while reducing administrative burden through simplified patient forms, removal of duplicative checklists and efficient communication between HCPs and either optometrists or ophthalmologists monitoring eye care. GSK will also offer Together with GSK, an optional patient support programme available to all US patients prescribed Blenrep.

Data from the DREAMM (DRiving Excellence in Approaches to Multiple Myeloma) clinical trial programme will be submitted to the National Comprehensive Cancer Network (NCCN) guidelines this year. Recent results from the DREAMM studies, alongside emerging real-world evidence, provide a growing body of data for Blenrep.5,6

Sagar Lonial, MD, Chief Medical Officer, Winship Cancer Institute of Emory University in Atlanta, Georgia, Chair of Emory Department of Hematology and Medical Oncology, said: "With the approval of Blenrep, we now have a community-accessible BCMA-targeting agent with the potential to improve outcomes for patients following two or more prior lines of treatment, where options are limited. This approval marks an important advance in the US relapsed/refractory treatment landscape."

Michael Andreini, President and Chief Executive Officer of the Multiple Myeloma Research Foundation and the Multiple Myeloma Research Consortium, said: "The reality for most patients with multiple myeloma is a relentless cycle of remission and relapse, as their disease becomes refractory to treatments. Patients urgently need more effective treatment options that can offer more quality time with their loved ones. We see the potential for Blenrep in combination to help patients achieve this."

GSK is advancing the DREAMM clinical programme to demonstrate Blenrep’s potential benefit in earlier lines of treatment. Follow-up continues for overall survival (OS) in both DREAMM-7 and DREAMM-8 with data expected in early 2028, including in patients who have received only one prior line of therapy. DREAMM-10, a phase III trial in newly diagnosed transplant-ineligible patients, which represent over 70% of patients starting therapy, was initiated in Q4-2024.4 Interim efficacy and safety data for Blenrep as a first line treatment are expected in early 2028 with enrolment expanded to US sites to increase US patient representation in the study population. GSK continues to work with the FDA for US patients.

Approvals outside of the US
Blenrep combinations are approved in 2L+ relapsed or refractory multiple myeloma in the European Union7, UK8, Japan9, Canada, Switzerland and Brazil. Applications are currently under review in other markets globally, including China10 where the application is based on the results of DREAMM-7 and has been granted Breakthrough Therapy Designation and Priority Review.

About multiple myeloma
Multiple myeloma is the third most common blood cancer globally and is generally considered treatable but not curable.11,12 There are approximately 180,000 new cases of multiple myeloma diagnosed globally each year. Research into new therapies is needed as multiple myeloma commonly becomes refractory to available treatments.13 Many patients with multiple myeloma, including approximately 70% in the US, are treated in a community cancer setting, leaving an urgent need for new, effective therapies with manageable side effects that can be administered outside of an academic centre.3,15,16

About Blenrep
Blenrep is a monoclonal ADC (antibody-drug conjugate) comprising a humanised BCMA (B-cell maturation antigen) conjugated to the cytotoxic agent auristatin F via a non-cleavable linker. The drug linker technology is licensed from Seagen Inc.; the monoclonal antibody is produced using POTELLIGENT Technology licensed from BioWa Inc., a member of the Kyowa Kirin Group.

Indication
In the US, Blenrep is indicated in combination with bortezomib and dexamethasone (BVd) for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least two prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent.

Please see accompanying US Prescribing Information which will soon be available here17.

About DREAMM-7
DREAMM-7 is a multicentre, open-label, randomised phase III clinical trial evaluating the efficacy and safety of belantamab mafodotin combined with bortezomib plus dexamethasone (BVd) compared to daratumumab combined with bortezomib plus dexamethasone (DVd) in patients with relapsed or refractory multiple myeloma who previously were treated with at least one prior line of multiple myeloma therapy, with documented disease progression during or after their most recent therapy. The trial enrolled 494 participants who were randomised 1:1 to receive either BVd or DVd. Belantamab mafodotin was administered at a dose of 2.5mg/kg intravenously every three weeks in combination for the first eight cycles and then continued as a single agent. The primary endpoint was PFS as per an independent review committee, with secondary endpoints including OS, duration of response (DOR), and minimal residual disease (MRD) negativity rate as assessed by next-generation sequencing. Other secondary endpoints include overall response rate (ORR), safety, and patient reported and quality of life outcomes.

PFS results17 were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Plenary Series in February 2024 and published in the New England Journal of Medicine. OS results18 were presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2024.

About DREAMM-10
DREAMM-10 is a multicentre, open-label, randomised phase III clinical trial in newly diagnosed transplant ineligible patients with multiple myeloma, evaluating belantamab mafodotin plus lenalidomide and dexamethasone (BRd) versus daratumumab plus lenalidomide and dexamethasone (DRd).

(Press release, GlaxoSmithKline, OCT 23, 2025, View Source [SID1234656945])

Genprex Announces Registered Direct Offering of up to $8.2 Million Priced At-The-Market Under Nasdaq Rules

On October 23, 2025 Genprex, Inc. ("Genprex" or the "Company") (NASDAQ: GNPX), a clinical-stage gene therapy company focused on developing life-changing therapies for patients with cancer and diabetes, reported that it has entered into definitive agreements for the issuance and sale of 243,622 shares of common stock at a purchase price of $11.21 per share in a registered direct offering priced at-the-market under Nasdaq rules. In a concurrent private placement, the Company will issue unregistered short-term warrants to purchase an aggregate of up to 487,244 shares of common stock at an exercise price of $11.00 per share that will be immediately exercisable upon issuance and will expire twenty-four months from the effective date of a registration statement registering for resale the shares of common stock underlying the warrants. The closing of the offering is expected to occur on or about October 24, 2025, subject to the satisfaction of customary closing conditions.

H.C. Wainwright & Co. is acting as the exclusive placement agent for the offering.

The gross proceeds to the Company from the offering are expected to be approximately $2.7 million before deducting placement agent fees and other offering expenses payable by the Company. The potential additional gross proceeds to the Company from the short-term warrants, if fully-exercised on a cash basis, will be approximately $5.5 million. No assurance can be given that any of such short-term warrants will be exercised for cash or at all. The Company intends to use the net proceeds from the offering for working capital and general corporate purposes.

The shares of common stock offered in the registered direct offering (but not the unregistered short-term warrants issued in the concurrent private placement nor the shares of common stock underlying the unregistered short-term warrants) described above are being offered by the Company pursuant to a "shelf" registration statement on Form S-3 (File No. 333-271386) that was declared effective by the Securities and Exchange Commission (the "SEC") on June 9, 2023. The offering of the shares of common stock in the registered direct offering is being made only by means of a prospectus, including a prospectus supplement, forming a part of the effective registration statement. A final prospectus supplement and accompanying prospectus relating to the registered direct offering will be filed with the SEC. Electronic copies of the final prospectus supplement and accompanying prospectus may be obtained, when available, on the SEC’s website at View Source or by contacting H.C. Wainwright & Co., LLC at 430 Park Avenue, 3rd Floor, New York, New York 10022, by phone at (212) 856-5711 or e-mail at [email protected].

The unregistered warrants described above and the shares of common stock issuable upon exercise of such warrants are being offered in a private placement under Section 4(a)(2) of the Securities Act of 1933, as amended (the "Securities Act"), and/or Regulation D promulgated thereunder and have not been registered under the Securities Act, or applicable state securities laws. Accordingly, the unregistered warrants and underlying shares of common stock may not be offered or sold in the United States except pursuant to an effective registration statement or an applicable exemption from the registration requirements of the Securities Act and such applicable state securities laws.

This press release does not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or jurisdiction.

(Press release, Genprex, OCT 23, 2025, View Source [SID1234656944])

Genprex Collaborators to Present Positive Preclinical Data on the Use of Reqorsa® Gene Therapy for the Treatment of Lung Cancer at the 2025 AACR-NCI-EROTC International Conference on Molecular Targets and Cancer Therapeutics

On October 23, 2025 Genprex, Inc. ("Genprex" or the "Company") (NASDAQ: GNPX), a clinical-stage gene therapy company focused on developing life-changing therapies for patients with cancer and diabetes, reported that its research collaborators will present positive preclinical data at the upcoming 2025 AACR (Free AACR Whitepaper)-NCI-EROTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) taking place October 22-26, 2025 at the Hynes Convention Center in Boston. The collaborators will present positive preclinical data from a study of Genprex’s lead drug candidate, Reqorsa Gene Therapy (quaratusugene ozeplasmid), for the treatment of ALK-EML4 positive non-small cell lung cancer (NSCLC).

"We are delighted to have our academic partners present this compelling preclinical evidence that supports the therapeutic use of REQORSA in ALK Positive NSCLC," said Ryan Confer, President and Chief Executive Officer at Genprex. "Our researchers found that REQORSA alone or in combination with alectinib was able to shrink tumors by 79 percent, suggesting that REQORSA may be active as a single agent and may also be an ideal companion drug for patients with advanced disease. These data support a pathway for a potential future clinical trial for REQORSA."

The featured Genprex-supported poster to be presented at the 2025 EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics:

Title: "Quaratusugene ozeplasmid mediated TUSC2 upregulation in EML4-ALK bearing non-small cell lung carcinoma induces apoptosis and is highly effective in preclinical studies"

Collaborator: The University of Michigan Rogel Cancer Center

Session: Poster Session C

Session Date and Time: Saturday, October 25, 2025 from 12:30 – 4:00 p.m. ET

The featured Genprex-supported abstract to be presented at the 2025 EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics:

NSCLC bearing the EML4-ALK fusion (Echinoderm microtubule-associated protein-like 4- Anaplastic Lymphoma Kinase) occurs in approximately 5% of NSCLC. Tumors bearing the fusion are sensitive to ALK Tyrosine Kinase Inhibitors (TKIs), that form the first and second line of treatment for these patients. However, ALK+ lung cancers invariably develop resistance to ALK inhibitors, creating the need for newer treatment strategies.

Tumor Suppressor Candidate 2 (TUSC2) is a tumor suppressor gene that is known to have low endogenous expression in NSCLC. REQORSA Gene Therapy, referred to as quaratusugene ozeplasmid (QO) in the abstract and developed by Genprex, is a gene therapy (TUSC2 plasmid encapsulated in non-viral lipid nanoparticles) that upregulates TUSC2 expression in cancer cells by delivering the functional TUSC2 gene.

Researchers evaluated TUSC2 expression in several ALK+ cell lines and patient derived organoids (PDOs), both before and after exposure to QO. The studies indicate that QO mediated overexpression of TUSC2 significantly induced apoptosis in ALK+ cell lines and PDOs, as demonstrated by increase in caspase 3/7 activity of the cells, increased protein expression of pro-apoptotic markers, reduced colony formation ability of the cells, and increased DNA fragmentation. Furthermore, researchers have observed a robust pro-apoptotic response in ALK+ NSCLC cell lines with acquired resistance to the ALK inhibitor, alectinib, resulting in reduced cell viability when treated with QO and alectinib in combination. To better understand how QO and alectinib work in combination, researcher subcutaneously injected NCI-H2228 ALK+ cells into nude mice and when the tumors developed to approximately 100mm3, mice were randomized into 4 groups. Mice from group 1 were treated with vehicle control, group 2 were treated with QO (25ug/mouse, i.v., every three days), group 3 were treated with alectinib (0.5mg/kg/mouse, oral gavage, every day) and group 4 were treated with QO and alectinib in combination at the same concentration and frequency of dosing for up to a month.

The results showed that alectinib shrunk tumors by 60% (group 3). However, QO alone (group 2) and in combination with alectinib (group 4) were able to shrink the tumors by 79%. This finding showed that QO has a 23% improved outcome than alectinib, leading to the hypothesis that QO may be an ideal companion drug for patients with advanced disease or a treatment for patients who cannot tolerate alectinib. Researchers are also currently monitoring the mice for survival, and tumor measurements recorded at 2 weeks after the end of treatment indicate that tumors in mice that received single drug treatment are regrowing faster than tumors in mice that received combined treatment of QO and alectinib, further emphasizing the clinical relevance of this novel combination in ALK+ NSCLC.

Taken together, the in vitro and in vivo data suggest that QO mediated overexpression of TUSC2 in ALK+ NSCLC is effective in decreasing growth and proliferation through the activation of apoptotic pathways, thereby paving the way for a potential clinical trial.

About Reqorsa Gene Therapy

REQORSA (quaratusugene ozeplasmid) consists of a plasmid containing the TUSC2 gene encapsulated in non-viral lipid-based nanoparticles in a lipoplex form (the Company’s Oncoprex Delivery System), which has a positive charge. REQORSA is injected intravenously and specifically targets cancer cells. REQORSA is designed to deliver the functioning TUSC2 gene to negatively charged cancer cells while minimizing uptake by normal tissue. Laboratory studies conducted at MD Anderson show that the uptake of TUSC2 in tumor cells in vitro after REQORSA treatment was 10 to 33 times the uptake in normal cells.

(Press release, Genprex, OCT 23, 2025, View Source [SID1234656943])

Defence To Present New Scientific Data On Its Adc-Enhancing Accum Technology At The World Adc Conference In San Diego, Usa, November 4-5, 2025

On October 23, 2025 Defence Therapeutics Inc. ("Defence" or the "Company"), a leading biotechnology company specialized in drug delivery technologies, reported that it will present new scientific data highlighting the performance of its Accum technology in enhancing the efficacy of antibody-drug conjugates (ADCs) at the 16th World ADC Conference in San Diego, CA, USA.

Defence’s proprietary Accum platform is engineered to improve intracellular delivery and endosomal escape of therapeutic payloads, addressing a critical limitation of current ADCs and enabling higher potency with reduced off-target toxicity. The new results to be presented build on a growing body of evidence demonstrating Accum’s ability to significantly improve the therapeutic index of ADCs.

"These findings further demonstrate how Accum can unlock the full potential of ADCs by enabling more efficient delivery of their toxic payloads directly into cancer cells," said Maxime Parisotto, Chief Scientific Officer of Defence Therapeutics. "We are excited to share this data with the scientific community and continue advancing our research toward next-generation targeted therapies."

Interested attendees are invited to visit the Defence Therapeutics poster presentation at the Conference Exhibition Hall Town & Country Resort in San Diego, CA, USA on Tuesday and Wednesday November 4-5, 2025, to meet with Defence’s CSO Maxime Parisotto, PhD, MBA, and Head of Quality & Operation Mark Lambermon, Phd, to learn more about the company’s ongoing research and development efforts.

(Press release, Defence Therapeutics, OCT 23, 2025, View Source;utm_medium=rss&utm_campaign=defence-to-present-new-scientific-data-on-its-adc-enhancing-accum-technology-at-the-world-adc-conference-in-san-diego-usa-november-4-5-2025 [SID1234656942])