On March 4, 2026 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM:HCM; HKEX:13) reported that it has initiated a Phase I/IIa clinical trial of HMPL-A580, HUTCHMED’s second novel Antibody-Targeted Therapy Conjugate ("ATTC"), in patients with unresectable, advanced or metastatic solid tumors in China and the US. The first patient received the first dose on March 4, 2026.

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HMPL-A580 is a first-in-class ATTC comprising a highly selective and potent PI3K/PIKK small-molecule inhibitor payload linked to an anti-EGFR antibody via a cleavable linker, HUTCHMED’s second ATTC based on this highly novel PI3K/PIKK inhibitor payload. EGFR is highly expressed in multiple types of solid tumors and is well recognized as a driving force in tumorigenesis and disease progression. Preclinical data have shown that PAM pathway inhibition synergizes with anti-EGFR therapy to enhance anti-tumor activity, and will be presented at an upcoming scientific conference.

This first-in-human Phase I/IIa, multicenter, open-label study evaluates the safety, tolerability, pharmacokinetics, immunogenicity and preliminary efficacy of HMPL-A580. The study consists of two parts. In the Phase I dose escalation part, patients will receive HMPL-A580 intravenously at predefined dose levels to determine the maximum tolerated dose and recommended dose for expansion. The subsequent Phase IIa dose expansion/​optimization part is to further characterize the safety, tolerability and preliminary anti-tumor activity of HMPL-A580 in selected solid tumors, and to determine the recommended dose for the next phase. Additional details may be found at clinicaltrials.gov, using identifier NCT07396584.

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.

HUTCHMED has demonstrated how its partnerships leverage the expertise of multinational pharmaceutical companies to accelerate bringing novel medicines to address large unmet needs around the world, and plans to apply this strategy to its ATTC technology this year.

About the PAM Pathway and HMPL-A580

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.

By conjugating this highly novel payload to an anti-EGFR antibody, HMPL-A580 is designed to deliver targeted pathway inhibition directly into EGFR-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.

(Press release, Hutchison China MediTech, MAR 4, 2026, View Source [SID1234663246])

On March 4, 2026 Fapon Biopharma reported that Dr. Kaiqing Zhang, Ph.D., Associate Director of Business/Corporate Development, will deliver a company presentation at the 19th Annual European Life Sciences CEO Forum, taking place March 4–5 at the Hilton Zurich Airport Hotel.

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In a presentation titled "Unlocking the Next Generation of TCEs: Fapon’s Human/Cyno Cross-Reactive CD3/TCR VHH Platform", Fapon Biopharma will showcase its proprietary CD3/TCR VHH-based T-cell engager (TCE) platform, an innovative approach designed to overcome developability and flexibility challenges associated with traditional multi-specific antibodies.

Built on fully human/cynomolgus cross-reactive single-domain antibodies (VHH), the platform enables a modular "plug-and-play" design with optimized activation kinetics and therapeutic index. This technology is uniquely positioned to power the next wave of therapeutics across two high-growth pillars:

Oncology: Precision T-cell redirection to eradicate solid and hematological tumors, engineered for optimized activation kinetics and a wider therapeutic index to minimize cytokine risk.

Autoimmune Diseases: Potent T-cell engagers designed for deep B-cell depletion, offering a functional "immune reset" for patients with refractory conditions.

The cornerstone of our technology is a series of cross-species CD3/TCR VHHs with different affinity binding to both human and cynomolgus monkeys. This dual reactivity significantly de-risks preclinical safety and accelerates translational timelines. The platform has already successfully completed evaluation demonstrating superior efficacy and safety as well as predictable PK/PD in mouse and NHP studies.

With superior CMC profiles and flexibility for multi-valent formatting, Fapon Biopharma is seeking strategic partners for co-development and licensing. For partnership inquiries, please contact us at [email protected] (USA, Europe and other regions) or [email protected] (Asia-Pacific)

(Press release, Fapon Biopharma, MAR 4, 2026, View Source [SID1234663262])

On March 4, 2026, Xencor, Inc. (the "Company") reported to have received a notice of termination of an Amended and Restated Collaboration and License Agreement (the "Agreement"), effective as of June 1, 2024, with Genentech, Inc. ("GNE") and F. Hoffmann-La Roche Ltd ("Roche" and, GNE and Roche, collectively, "Genentech"), pursuant to which Genentech has elected to terminate the Agreement in its entirety for convenience. The effective date of the termination of the Agreement is September 4, 2026. Roche had previously announced, in connection with the reporting of its 2024 financial results in January 2025, that it removed efbalropendekin alfa, an engineered cytokine-Fc fusion protein and the sole active collaboration product under the Agreement, from its development pipeline, and the Company has expected Genentech’s administrative termination of the Agreement.

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During the first half of 2024, the Company ceased all cost-sharing development activities by electing to opt-out of co-development under the Agreement. Genentech assumed sole responsibility for all clinical, regulatory and commercial activities for certain collaboration products, including efbalropendekin alfa.

(Filing, Xencor, MAR 4, 2026, View Source [SID1234663374])

On March 4, 2026 INOVIO (NASDAQ: INO), and Akeso, Inc. (9926.HK) ("Akeso") reported that they have entered into a clinical trial collaboration and supply agreement to evaluate INO-5412, INOVIO’s DNA immunotherapy candidate, in combination with cadonilimab, Akeso’s first-in-class PD-1/CTLA-4 bispecific antibody, for the potential treatment of GBM. The combination therapy will be studied as a part of INSIGhT, the innovative Phase 2 adaptive platform trial sponsored by the Dana-Farber Cancer Institute and conducted with Mass General Brigham Cancer Care, Inc., which is designed to quickly and efficiently find new treatments for GBM. Dosing in the combination therapy trial is expected to begin in the second half of 2026.

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INO-5412 is composed of INO-5401 and T cell immune activator INO-9012. When combined with a checkpoint blockade, targeted DNA immunotherapy has the potential to overcome the challenges of immune checkpoint therapy alone by stimulating an immune response against tumor antigens and driving T cell infiltration into the glioblastoma tumor microenvironment. In an ongoing Phase 2 trial in newly diagnosed GBM patients, INO-5401 plus INO-9012 in combination with a PD-1 checkpoint inhibitor elicited robust immune responses that potentially correlate with enhanced survival. The novel combination of INO-5412 with cadonilimab to treat GBM builds on this promising data and could potentially benefit patients by providing additional checkpoint inhibition through CTLA-4 binding.

Cadonilimab has received marketing approval in China for several indications, including first-line gastric cancer, first-line cervical cancer, and second/third-line cervical cancer, demonstrating effectiveness irrespective of PD-L1 expression status. As the world’s first approved bispecific antibody for cancer immunotherapy developed in China, its clinical value is well-established through real-world application and validation across multiple Phase 3 trials. The drug is currently involved in over 11 Phase 3/registration clinical studies. Among these are two international multicenter trials: a Phase 3 registrational trial for the first-line treatment of gastric cancer, and a Phase 2 registrational trial for the second-line treatment of liver cancer in patients who exhibit resistance to immune checkpoint inhibitors (IO).

Dr. David Reardon, Director of the Center for Neuro-Oncology at the Dana-Farber Cancer Institute and a professor at Harvard Medical School said, "The INSIGhT trial was designed to help quickly advance cutting-edge treatments for GBM, the most common and aggressive form of brain cancer for which there are few effective treatments currently available or in development. We are excited to include INOVIO and Akeso’s novel combination immunotherapy in the trial and welcome their efforts to help improve potential outcomes for patients."

Dr. Michael Sumner, INOVIO’s Chief Medical Officer, said, "This collaboration is an important step forward for our cancer immunotherapy research and we are delighted to partner with two trailblazing organizations to advance this promising candidate in our late-stage clinical pipeline. Combining INO-5412 with Akeso’s novel checkpoint modality represents an important evolution of our research in GBM, builds on our previous data showing the potential to improve patient outcomes and highlights our ongoing commitment to advancing innovative treatments for diseases with significant unmet need."

Yu (Michelle) Xia, PhD, founder, chairwoman, president, and Chief Executive Officer of Akeso, said, "We are truly excited to collaborate with INOVIO for the treatment of GBM. We are advancing cadonilimab worldwide through Akeso’s ‘in-house innovation + global partnership’ strategy to realize its breakthrough clinical benefits for patients all around the world across multiple cancer types. By collaborating with INOVIO, we aim to harness the benefit of combining INOVIO’s DNA medicine with cadonilimab’s dual checkpoint inhibition for the treatment of GBM, a particularly challenging central nervous system malignancy. We also look forward to working with one of the world’s leading cancer centers in the clinical development of the new cadonilimab and INO-5412 combination treatment for GBM."

Under the terms of the agreement, INOVIO and Akeso will provide support for the INSIGhT study, including supplying their respective therapeutic products, while the investigative sponsors will oversee the day-to-day clinical operations.

About INSIGhT
The INdividualized Screening trial of Innovative Glioblastoma Therapy (INSIGhT) is investigating novel treatments in patients with newly diagnosed GBM. INSIGhT uses a shared control arm to test multiple investigational therapies at one time, with each arm independently compared only to the control. The arm of the trial that involves the collaboration between INOVIO and Akeso will investigate the safety and efficacy of INO-5412 in combination with cadonilimab in patients with histologically confirmed intracranial glioblastoma or gliosarcoma. Dosing is expected to begin in the second half of 2026. For more information about the clinical study, see www.clinicaltrials.gov, identifier NCT02977780.

About GBM
Glioblastoma (GBM) is the most common and aggressive type of brain cancer and remains a devastating disease for both patients and caregivers. Its prognosis is extremely poor, with few therapies approved over the last 10 years. The median overall survival for patients receiving standard of care therapy is approximately 15 months in patients with an unmethylated MGMT (O-6-methylguanine-DNA methyltransferase) promoter and the median progression-free survival is approximately 4 to 6 months. The estimated annual incidence of GBM in the U.S. is 11,362 cases or 3.21 cases per 100,000 persons and the median age at diagnosis is 65 years.

About INO-5412
INO-5412 is an investigational DNA medicine that combines INO-5401 and INO-9012 into a single vial as a potentially powerful cancer immunotherapy particularly when given in combination with checkpoint inhibitors. INO-5401 plus INO-9012 has been previously investigated as a potential therapeutic treatment targeting a number of cancers, including GBM and cancers exhibiting BRCA1 and BRCA2 mutations. Data from an ongoing Phase 2 trial in newly diagnosed GBM patients, highlighted in a 2022 oral presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), demonstrated that INO-5401 plus INO-9012 in combination with a PD-1 checkpoint inhibitor elicited robust immune responses that potentially correlated with enhanced survival. (Reardon D. et al, ASCO (Free ASCO Whitepaper) 2022).

INO-5401 encodes for INOVIO’s SynCon antigens for hTERT, WT1, and PSMA, which are antigens The National Cancer Institute has highlighted as important targets and designated as high priorities for cancer immunotherapy development. These three antigens have been reported to be over-expressed and often mutated in a variety of human cancers, including GBM. INO-9012 encodes for IL-12, which is a T cell immune activator.

About Cadonilimab
Cadonilimab, independently developed by Akeso, is the world’s first PD-1/CTLA-4 bispecific immuno-oncology therapy. It has been approved and reimbursed in China for three indications: recurrent/metastatic cervical cancer after platinum-based chemotherapy failure, first-line gastric cancer, and first-line cervical cancer. The drug has also been investigated in over 30 clinical trials spanning more than 20 tumor types. Currently, 11 Phase III or registrational trials are ongoing, with three already having met primary endpoints. With a novel dual-targeting mechanism against PD-1 and CTLA-4, cadonilimab demonstrates superior efficacy and a favorable safety profile compared to combination therapies. It has shown strong anti-tumor activity regardless of PD-L1 status and holds breakthrough potential in IO-resistant and immunologically "cold" tumors.

(Press release, Inovio, MAR 4, 2026, View Source [SID1234663247])

On March 4, 2026 Creatv Bio, a Division of Creatv MicroTech, Inc. ("Creatv") reported the initiation of a collaboration with CytoDyn Inc. of Vancouver, Washington ("CytoDyn") to provide its’ LifeTracDx liquid biopsy test to support a Phase 2 study evaluating CytoDyn’s leronlimab in combination with TAS-102 and Bevacizumab in previously treated patients with relapsed/refractory metastatic Colorectal Cancer (mCRC).

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CytoDyn’s Phase 2 study in mCRC (NCT06699836), now underway, is enrolling 60 participants who will be tested with the LifeTracDx blood test at multiple-time points over the course of the trial. Collected under the study protocol as an exploratory biomarker, Creatv Bio’s LifeTracDx Blood Test will be used to evaluate numeric increases in PD-L1 expression across the patient population. The study’s primary endpoint is objective response rate (ORR), defined as the proportion of patients achieving a confirmed complete or partial response per RECIST v1.1, evaluating the efficacy of leronlimab in combination with trifluridine and tipiracil plus bevacizumab in patients with CCR5-positive, refractory, microsatellite-stable metastatic colorectal cancer (mCRC) over a 12-month treatment period.

LifeTracDx uses both circulating tumor cells (CTCs) and Cancer Associated Macrophage-Like (CAML) cells, which are macrophages that engulf tumor cells, as sensitive and accurate markers for real-time monitoring of tumor response to all forms of treatment and provides pharmacokinetic changes of both CCR5 and PD-L1 from the tumor microenvironment.

In prior studies, leronlimab induced PD-L1 expression on CTCs and CAMLS in 88% of metastatic breast cancer patients treated at doses above 525 mg/week, reinforcing the proposed ability of CCR5 blockade to convert "cold" tumors into "hot," PD-L1–positive tumors. In addition, changes observed in circulating atypical CAMLs further support leronlimab’s role in remodeling the tumor immune microenvironment and enhancing responsiveness to checkpoint blockade.

Creatv Bio has demonstrated that monitoring the expressions of PD-L1 using the LifeTracDx blood test at baseline, followed by sequential sampling after induction of therapy, may identify patients who have upregulated PD-L1 expression in their tumors.

(Press release, CytoDyn, MAR 4, 2026, View Source [SID1234663263])