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

On December 17, 2025 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM:HCM; HKEX:13) reported 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.

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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.

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 (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). 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.

(Press release, Hutchison China MediTech, DEC 17, 2025, View Source [SID1234661460])

Tubulis to Present at the 44th Annual J.P. Morgan Healthcare Conference

On December 16, 2025 Tubulis reported that its CEO and Co-founder Dominik Schumacher will present a company overview and update at the 44th Annual J.P. Morgan Healthcare Conference in San Francisco.

The presentation will take place on Monday, January 12, 2026, at 3:00 pm PT in the Mission Bay Room (32nd Floor) at The Westin St. Francis.

(Press release, Tubulis, DEC 16, 2025, View Source [SID1234661475])

Vyriad Unveils Lead In Vivo CAR T Candidate VV169 and Data Supporting Future Clinical Development During ASH 2025

On December 16, 2025 Vyriad, Inc., a clinical-stage biotechnology company developing targeted genetic therapies for cancer and other serious diseases, reported detailed data on its lentiviral vector retargeting technologies and its lead therapeutic in vivo chimeric antigen receptor (CAR) T program, VV169, at the recently concluded 67th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.

The first poster detailed the company’s three in vivo T-cell-targeted delivery systems, the first of which will soon be tested clinically through the VV169 program in a U.S.-based clinical trial in patients with multiple myeloma. The second poster presented strong preclinical data for VV169 that supports its progression into clinical development. The therapy achieved a durable complete resolution of disease in mice with disseminated myeloma at all doses, including the lowest level.

"While we have recently seen remarkable proof-of-concept for in vivo CAR T in heavily pretreated multiple myeloma, the next hurdle is eliminating infusional toxicities, so that we can truly unlock the promise of this modality," said Stephen Russell, M.D., Ph.D., CEO of Vyriad. "Our singular focus is solving this technology challenge, and the data presented at ASH (Free ASH Whitepaper) demonstrate Vyriad’s strong and rapid progress. We are advancing our vectors’ targeting, transduction and safety capabilities to ensure this new generation of in vivo CAR T therapies carries the field’s momentum forward."

While recent breakthroughs have validated in vivo CAR T as a scalable alternative to complex ex vivo therapies, Vyriad sees an opportunity to optimize the modality for broad clinical use. Leveraging its deep expertise in virology and oncolytic viruses, the company has developed a proprietary platform anchored in advanced G protein engineering, yielding lentiviral vectors with high serum stability and enhanced transduction efficiency — key requirements for safe, precise, and low-dose in vivo gene delivery.

Evaluation of three in vivo targeting approaches

Vyriad has developed three distinct retargeting strategies to selectively transduce resting T cells in the lymphoid niche. This effort is part of the company’s ongoing pursuit of improving lentiviral vector targeting not only for precise and safe delivery, but also to streamline manufacturing and development even further. The three methods are:

Direct Covalent Display: This approach uses a chimeric VSV-G protein that displays a CD3-targeting ligand but is modified to blind its natural interaction with the low-density lipoprotein (LDL) receptor. This method was then applied to retarget the LV169 vector used in the VV169 program, enabling precise T-cell targeting for in vivo CAR T delivery.
Trimeric Adapter Proteins: A protein adapter is used to "cap" the unmodified VSV-G trimer and redirect it to CD3 while masking its ability to bind to natural receptors. This was achieved by mixing a conventional lentiviral vector with trimeric adapter proteins. The association between the G protein trimer and the trimeric cap remained highly stable during freeze-thaw cycles and at room temperature, underscoring its viability as an in vivo targeting platform.
Modular Covalent Display: SPY-tagged VSV-G proteins are covalently modified by mixing them with a SPY-catcher/CD3 ligand fusion protein at room temperature, which spontaneously binds SPY-tag, thereby redirecting entry to the SPY-catcher targeting ligand.
The direct covalent display method is currently undergoing clinical translation through VV169. Manufacturing studies for all three targeting approaches are currently underway.

Lead in vivo CAR T candidate VV169

VV169 is designed as a single intravenous administration of a B-cell maturation antigen (BCMA)-targeted CAR transgene, delivered by the LV-169 lentiviral vector. The second poster presented at ASH (Free ASH Whitepaper) 2025 details the complete elimination of disseminated multiple myeloma in humanized mouse models.

Key highlights of the data include:

100% of mice treated with a single intravenous injection of therapy cleared OPM-2 tumors completely within 28 days. This response held true for all dose levels, including the lowest dose tested. The mice remained tumor-free 84 days post-treatment and successfully resisted tumor re-challenge.
The treatment was well tolerated. Analysis of cytokines confirmed the absence of a severe cytokine storm. While IFNγ was elevated during T-cell expansion, inflammatory markers, such as IL-6, TNFα and GM-CSF, were barely detectable.
The use of a T-cell-specific promoter prevented CAR protein from being expressed on the virus particle itself, minimizing off-target gene delivery to myeloma cells
Vyriad is continuing preclinical work for the development of VV169 and plans to begin a clinical trial in the U.S. in 2026.

(Press release, Vyriad, DEC 16, 2025, View Source [SID1234661474])

I-SPY 2 Publication in Nature Communications Shows Signatera™ Can Predict Treatment Response and Recurrence Risk in Early-Stage Breast Cancer

On December 16, 2025 Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA and precision medicine, together with Quantum Leap Healthcare Collaborative, reported the publication of new findings from the I-SPY 2 trial in Nature Communications.

The study examined how Signatera can refine risk assessment in patients with early-stage breast cancer whose tumors resist neoadjuvant therapy (NAT). These cancers often leave behind substantial residual disease and carry a higher risk of metastasis, though only about 15–30% recur within three years1-3. Distinguishing which NAT-resistant tumors are more likely to recur could guide treatment decisions to potentially prevent or delay metastatic recurrence.

Researchers used Signatera to measure personalized circulating tumor DNA (ctDNA) in 723 women with high-risk, early-stage breast cancer receiving NAT at four time points: 1) before treatment; 2) after three weeks of paclitaxel with or without an investigational agent; 3) between paclitaxel- and anthracycline-based regimens; and 4) after completing neoadjuvant therapy. Key findings include:

Signatera ctDNA testing improved prognostic precision beyond residual cancer burden (RCB) alone in patients with high RCB (RCB-II/III) following neoadjuvant therapy (NAT).
Signatera-negative patients, at either pretreatment or post-NAT, had a much lower risk of metastasis:
RCB-II: Post-NAT, pre-surgery (T3) 3-year DRFS = 88% (ctDNA–) vs. 57% (ctDNA+), adj HR = 0.29, p = 0.001
RCB-III: Post-NAT, pre-surgery (T3) 3-year DRFS = 83% (ctDNA–) vs. 22% (ctDNA+), adj HR = 0.14, p < 0.001
Persistent Signatera positivity post-NAT (T3) was a strong independent predictor of metastatic recurrence (adj HR = 5.20, p < 0.001).
Early Signatera ctDNA clearance at week 3 (T1) was strongly associated with favorable response to NAT, including regimens containing immune checkpoint inhibitors and HER2-targeted therapies, supporting its potential as an early, dynamic biomarker of treatment sensitivity.
Personalized Signatera assay variants remained highly stable despite tumor evolution, with median conservation rates of 94–97% between pretreatment and post-NAT tumor samples.
"These findings show that ctDNA provided critical insight into which therapy-resistant tumors were most likely to recur and, importantly, which were not," said Laura Esserman, M.D., MBA, and Laura van ‘t Veer, Ph.D., professors at the UCSF and principal investigators of the I-SPY study. "That distinction is vital because it can help us identify who remains at higher risk for recurrence and who may not need more aggressive treatment. Our next step is to integrate these findings and examine how ctDNA, pathology and imaging can complement each other. The I-SPY trial provides a framework to optimize all of the information for the benefit of patients."

"The I-SPY 2 publication adds to a growing body of evidence supporting Signatera’s role in early breast cancer," said Minetta Liu, M.D., chief medical officer of oncology and early cancer detection at Natera. "Building on our previous studies, this work provides further validation that Signatera can improve risk assessment for therapy-resistant disease. We are grateful for our ongoing collaboration with the I-SPY investigators on research that brings us closer to more personalized and effective care for patients."

(Press release, Natera, DEC 16, 2025, View Source [SID1234661473])

Iambic Therapeutics to Present at the 44th Annual J.P. Morgan Healthcare Conference

On December 16, 2025 Iambic, a clinical-stage life sciences and technology company advancing novel medicines through its AI-driven discovery and development platform, reported that Tom Miller, Ph.D. (Co-Founder and Chief Executive Officer) and Fred Manby, Ph.D. (Co-Founder and Chief Technology Officer) will present at the 44th Annual J.P. Morgan Healthcare Conference. Iambic’s presentation will take place on Tuesday, January 13, 2026, at 4:30 p.m. PT at the Westin St. Francis Hotel in San Francisco.

Iambic will highlight strategic progress over the past year, which has laid the groundwork for significant upcoming milestones. Highlights include:

Presentation of Phase 1/1b data for IAM1363, Iambic’s lead AI-designed drug candidate, demonstrating anti-tumor activity across HER2-wild-type and HER2-mutated cancers and a favorable safety profile
Research collaboration and drug supply agreement with Jazz Pharmaceuticals to evaluate IAM1363 in combination with zanidatamab in HER2-positive breast cancer
Presentation of IAM1363 pre-clinical NSCLC data at the World Conference on Lung Cancer showing potent anti-tumor activity and significant tumor regression across HER2-amplified and HER2-mutant NSCLC models, including greater anti-tumor activity compared to zongertinib
Technology-enablement collaboration with Revolution Medicines, leveraging Iambic’s NeuralPLexer protein-ligand prediction model to accelerate oncology target discovery
Continued development and validation of Enchant, Iambic’s multimodal model for predicting clinical and preclinical endpoints, with industry-leading performance benchmarks
Raising an oversubscribed financing exceeding $100 million to support clinical expansion and continued platform growth
The company will also preview key activities anticipated in the near-term, including:

Upcoming clinical data readouts, further defining IAM1363’s best-in-class potential and combination opportunities across HER2-driven cancers
Initiation of additional clinical trials for its potential first- and best-in-class programs, underscoring continued progress in advancing multiple pipeline candidates
Additional discovery and technology collaborations with biopharmaceutical partners, reflecting strong industry demand for Iambic’s platform capabilities
Advancement of new internal programs, broadening the company’s AI-driven discovery pipeline
Release of next-generation NeuralPLexer and Enchant models, featuring increased prediction breadth, expanded property coverage, and broader modality applicability
Iambic will also be at the conference to meet with investors and potential biopharmaceutical and technology partners.

(Press release, Iambic Therapeutics, DEC 16, 2025, View Source [SID1234661472])