On April 17, 2026 Antengene Corporation Limited ("Antengene", SEHK: 6996.HK) , a leading innovative, commercial-stage global biotech company dedicated to discovering, developing and commercializing first-in-class and/or best-in-class medicines for autoimmune disease, solid tumors and hematological malignancies indications, reported that it has released present results from three novel programs in poster presentations at the 2026 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (AACR 2026). The presentations will feature ATG-125 (B7-H3 x PD-L1 bispecific antibody-drug conjugate [ADC]), an IO + ADC dual-function molecule being developed for the treatment of solid tumors, as well as two investigational T cell engagers (TCEs) developed using the company’s proprietary AnTenGager TCE platform, including ATG-106 (CDH6 x CD3 TCE) for ovarian and kidney cancers, and ATG-112 (ALPPL2 x CD3 TCE) for gynecological tumors, digestive system malignancies, bladder cancer and NSCLC.

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Details of the Poster Presentation:
ATG-125 (B7-H3 x PD-L1 bispecific ADC)
Title: ATG-125, a novel B7H3 x PD-L1 bispecific antibody-drug conjugate, demonstrates potent antitumor efficacy by dual targeting of immune evasion and direct tumor killing
Abstract Number: 5599
Session Category: Immunology
Session Title: T Cell Engagers 2 / Antibody-Drug Conjugates 1
Date: April 21, 2026
Time: 02:00 PM – 05:00 PM (Pacific Time)
05:00 AM, April 22, 2026 – 08:00 AM, April 22, 2026 (Beijing Time)
Location: Poster Section 8

Introduction: B7-H3 and PD-L1 are immune checkpoint molecules broadly overexpressed across multiple solid tumors and are associated with immune evasion and poor prognosis. Although PD-1/PD-L1-directed therapies have demonstrated clinical benefit, treatment resistance remains a significant challenge. B7-H3 is also emerging as a promising ADC target due to its broad tumor expression and rapid internalization. ATG-125 is a novel B7-H3 x PD-L1 bispecific ADC designed to combine direct tumor killing with immune activation by co-targeting two complementary tumor-associated pathways in a single molecule.
Results: ATG-125 bound to both B7-H3 and PD-L1 with high specificity and nanomolar affinity and demonstrated robust antigen-dependent internalization in dual-positive tumor cells, enabling efficient intracellular payload release. The molecule induced tumor cell apoptosis, while its parental naked antibody blocked PD-1/PD-L1 interaction and elicited IL-2 and IFN-γ production in mixed lymphocyte reaction assays. ATG-125 also enhanced T-cell activation, as reflected by an increased ratio of CD69+/CD3+ T cells in co-cultures of tumor cells and human PBMCs. In vivo, ATG-125 demonstrated sustained antitumor activity in HCC827 xenograft models, increased tumor infiltration of CD4+ and CD8+ T cells in PBMC-humanized models, and inhibited tumor growth in a dose-dependent manner in MC38-hB7H3 syngeneic models, accompanied by elevated intratumoral CD8+ T-cell infiltration.
Conclusion: ATG-125 demonstrated synergistic IO+ADC antitumor activity through a differentiated mechanism combining enhanced internalization for payload delivery with the potential to restore anti-tumor immunity. Its compelling preclinical profile supports further development for patients with solid tumors.
ATG-106 (CDH6 x CD3 TCE)
Title: ATG-106, a novel "2+1" format CDH6-targeted T-cell Engager (TCE), shows potent T cell dependent cytotoxicity and in vivo anti-tumor efficacy
Abstract Number: 1621
Session Category: Immunology
Session Title: T Cell Engagers 1
Date: April 20, 2026
Time: 09:00 AM – 12:00 PM (Pacific Time)
00:00 AM, April 21, 2026 – 03:00 AM, April 21, 2026 (Beijing Time)
Location: Poster Section 10

Introduction: CDH6 plays an important role in embryonic kidney development but has negligible expression in adult kidney tissue. Its overexpression in ovarian and renal cancers, together with limited normal tissue expression, makes CDH6 an attractive therapeutic target. However, T cell engagers in solid tumors have often been limited by insufficient efficacy and the risk of cytokine release syndrome. To address these challenges, Antengene developed ATG-106, a novel "2+1", sterically masked CDH6 x CD3 bispecific TCE designed to deliver potent antitumor activity with the potential for a reduced CRS risk profile.
Results: ATG-106 exhibited reduced binding affinity to CD3+ cells before CDH6 crosslinking, while inducing approximately 100- to 400-fold more potent cytotoxicity against CDH6-positive tumor cells compared with a "1+1" CrossMab control TCE. The molecule demonstrated potent T cell-dependent cytotoxicity in ovarian and renal cancer models and showed low immunogenicity risk in vitro. In PBMC-humanized 786-O kidney cancer xenograft models, ATG-106 induced tumor shrinkage in all treated mice, with complete remissions observed in the 0.1 mg/kg and 0.3 mg/kg groups. ATG-106 also induced tumor shrinkage and complete remission in PBMC-humanized OVCAR-3 ovarian cancer models. Notably, pro-inflammatory cytokine levels remained very low in treated animals, suggesting low CRS risk. In non-human primate studies, the surrogate molecule ATG-106-RM was well tolerated at doses up to 10 mg/kg.
Conclusion: ATG-106 demonstrated limited T cell binding in the absence of target cells, potent cytotoxicity against tumor cells, and encouraging in vivo efficacy in ovarian and kidney cancer models. Favorable safety findings with the surrogate molecule in non-human primates further support continued clinical development of ATG-106 as a CDH6-targeted TCE candidate.
ATG-112 (ALPPL2 x CD3 TCE)
Title: ATG-112, a novel ALPP/G x CD3 bispecific T cell engager, for the treatment of ALPP/G+ solid tumors
Abstract Number: 1620
Session Category: Immunology
Session Title: T Cell Engagers 1
Date: April 20, 2026
Time: 09:00 AM – 12:00 PM (Pacific Time)
00:00 AM, April 21, 2026 – 03:00 AM, April 21, 2026 (Beijing Time)
Location: Poster Section 10

Introduction: Placental alkaline phosphatase and related placental-like/germ-cell isoforms, including ALPPL2 and ALPG, are aberrantly expressed in a range of solid tumors while being largely absent from normal adult tissues except the placenta, making them highly promising tumor-selective immunotherapy targets. Antengene developed ATG-112, an ALPP/G x CD3 bispecific TCE based on the AnTenGager platform in a "2+1" format, featuring bivalent antigen binding to improve low-antigen tumor recognition and a sterically masked CD3 binding arm designed to restrict T-cell activation to the tumor microenvironment.
Results: Tissue microarray IHC analysis showed that ALPP/G expression was restricted to placental tissue among normal organs and was not detected in other normal tissues, while frequent expression was observed in endometrial and ovarian cancers, with lower prevalence in bladder, gastric and pancreatic cancers. ATG-112 demonstrated high binding affinity to both ALPP/G-positive tumor cells and recombinant proteins, with EC50 and KD values in the sub-nanomolar range. It induced robust T cell-dependent cytotoxicity against target-positive cells with picomolar EC50 values, while in vitro cytokine-release assays showed minimal cytokine secretion from human PBMCs. In vitro studies also demonstrated that the spatial masking effect of ATG-112 is reversible. Immunogenicity assessment showed low immunogenic potential, and in vivo ATG-112 delivered potent tumor suppression across multiple dose levels in humanized mouse models, with low cytokine release and controllable CRS risk at efficacious doses. The program also demonstrated strong developability characteristics.
Conclusion: ATG-112 demonstrated a compelling preclinical profile, with potent in vitro and in vivo antitumor activity and minimal cytokine release. These findings support the continued advancement of ATG-112 toward clinical development for solid tumors.

(Press release, Antengene, APR 17, 2026, View Source [SID1234664488])

On April 17, 2026 Ultima Genomics, a developer of an innovative, ultra-high throughput sequencing architecture reported key milestones for its ppmSeq technology with a growing body of evidence from data presented across six abstracts, including an oral session and a plenary session at the 2026 AACR (Free AACR Whitepaper) Annual Meeting in San Diego, taking place April 17–22, 2026. Highlighting the program will be initial TRACERx MRD data showcasing the performance of ppmSeq relative to ultrasensitive bespoke panels. Data from collaborators, including LabCorp and DELFI Diagnostics, will also be presented at the conference. Collectively, these add to the growing body of evidence establishing ppmSeq as a new standard for ultrasensitive MRD, providing low single-digit parts-per-million sensitivity, with a simple, scalable, and distributable whole genome workflow that can be deployed globally.

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"We built ppmSeq to find tumor-derived molecules in a sea of normal DNA, without the need to produce a customized assay for every patient," said Gilad Almogy, Founder and CEO of Ultima Genomics. "The data presented at AACR (Free AACR Whitepaper) this week demonstrate these capabilities and point toward a future where whole-genome MRD is the standard of care for patients globally."

Ultima showcases low single-digit parts-per-million accuracy across tumor types to be shown at AACR (Free AACR Whitepaper) 2026

Today, Ultima is showcasing low single-digit parts-per-million levels of accuracy across tumor types, which include samples from the TRACERx (TRAcking Cancer Evolution through therapy (Rx)) cancer program, one of the largest tumor evolution studies funded by Cancer Research UK to generate deep sequencing multi-region and multi-time-point genetic data from over 3,200 tumor samples from over 800 lung cancer patients.

Led by Professor Charles Swanton (UCL / Cancer Research UK / The Francis Crick Institute), an early validation pilot of ppmSeq across 50 plasma samples — using tumor-specific variants identified from prior whole genome sequencing — achieved high analytical sensitivity for ctDNA detection at low single-digit parts-per-million, without the complexity of bespoke panel approaches. Results will be presented at a plenary and a late-breaking oral session during the conference.

"TRACERx has always followed the science of cancer evolution wherever it leads," said Charles Swanton, Deputy Clinical Director at The Francis Crick Institute. "Improving the sensitivity of ctDNA detection is central to the wider ambition for MRD monitoring, and expanding studies across a broader patient population will give us the statistical power and clinical context to determine how whole genome MRD monitoring can be deployed at NHS scale and beyond."

"The ability to perform personalized, tumor-guided ctDNA detection at parts-per-million sensitivity — without bespoke panel design and production — fundamentally changes what is achievable in lung cancer MRD monitoring," said Dan A. Landau, MD, PhD, a core member at the New York Genome Center, and Professor of Medicine & Professor of Physiology and Biophysics at Weill Cornell Medicine.

Additional work will assess prognostic performance at scale, and with the created dataset, explore tumor-agnostic MRD approaches that require no prior knowledge of a patient’s tumor mutational profile. Follow-up data will be presented later in 2026.

Other collaborators, including Labcorp and DELFI Diagnostics, to present data addressing clinical implementation of ppmSeq and enablement of new applications at AACR (Free AACR Whitepaper) 2026

In addition to the TRACERx data, important collaborators will showcase the clinical implementation and real-world deployment of ppmSeq whole genome sequencing, including:

Labcorp: Analytical performance of an ultrasensitive whole genome sequencing assay for molecular residual disease detection – Poster No. 5307/2

Labcorp will present data from an independent analytical study of an assay developed in coordination with ppmSeq technology, including the performance across multiple solid tumor types in pre-surgical, treatment-naive plasma samples. This analysis of 120 non-cancerous donor samples showed specificity exceeding 99.9%, underscoring the ability of ppmSeq whole genome sequencing to accurately differentiate between cancerous and non-cancerous samples, minimizing false positives. Additional analysis across three commercially available cancer cell lines spanning 13 concentration levels from 0.5 to 500 parts per million showed a 95% limit of detection below 3 ppm, demonstrating the assay’s capacity to detect ultra-low levels of circulating tumor DNA (ctDNA). Collectively, these results represent a significant milestone in the transition from research-grade performance to clinical-grade reliability.

"The whole genome approach enabled by ppmSeq changes the operational efficiency for tumor-informed MRD testing in a reference laboratory setting," said Taylor Jensen, Ph.D., Vice President and Head of Oncology Science at Labcorp. "Eliminating the need for individualized design and physical production of a panel while maintaining low single-digit parts-per-million analytical sensitivity is the kind of advancement that makes broad clinical deployment feasible, and the analytical data we are presenting at AACR (Free AACR Whitepaper) support a compelling case for WGS-based MRD as a scalable solution."

DELFI: Enhanced cfDNA fragmentation-based treatment monitoring on the Ultima Genomics platform – Abstract No. 3863/24

This study examined the performance of DELFI-TF, a cfDNA fragmentation-based tool for monitoring cancer treatment response, across Ultima vs Illumina platforms. Fragmentation profiles were consistent across platforms, and Ultima-based DELFI-TF values strongly tracked tumor burden and longitudinal treatment response. Notably, combining DELFI-TF with Ultima’s ppmSeq enabled distinction of tumor- from normal-derived DNA fragments, opening a path toward improved ctDNA detection sensitivity.

Labcorp: Utility of TAPS+: a positive-readout methylation sequencing approach for high-fidelity epigenetic profiling – Poster No. 3213/23

This study evaluated the TAPS+ workflow from Watchmaker Genomics on a 24-sample cohort of invasive breast carcinoma patients and healthy donors. TAPS+ demonstrated higher library yields, shorter turnaround times, and enabled the identification of more potentially relevant differentially methylated regions, in addition to a higher rate of DNA methylation observed in fully methylated control samples (88.8% vs. 76.8%). Importantly, TAPS+ libraries sequenced on the Ultima Genomics UG 100 platform showed equivalent methylation patterns, conversion efficiency, and transcription sites (TSS) profiles to those generated on an alternative sequencing platform, validating cross-platform reproducibility. Together, these results position TAPS+ with Ultima WGS as a robust, platform-agnostic epigenetic profiling method suitable for clinical assay development and early cancer detection.

Ultima announces inaugural global MRD Symposium focused on the current and future state of minimal residual disease detection technologies and utility in clinical practice

Prior to AACR (Free AACR Whitepaper), Ultima Genomics will co-host its inaugural global MRD symposium alongside Dan Landau and Charles Swanton. This exclusive event will bring together leaders in oncology research to discuss clinical adoption of MRD globally, and novel sequencing approaches that provide ultra-sensitive detection, and will feature a short series of selected presentations from key experts in the pharmaceutical, translational, and research fields.

Registration and details are available at: www.ultimagenomics.com/mrd-symposium

Summary of selected presentations at AACR (Free AACR Whitepaper):

Session

Presenters

Location/Time

Presentation Title

Discovery Science Plenary

Dan Landau

Weill Cornell Medicine

PLENARY

Sat. April 18

The Next Frontier in Minimal Residual Disease: Solid Tumors

Late-Breaking Poster Session: Clinical Research (LBPO.CL02)

Jonathan Wan
Francis Crick Institute

Section 52 LB116/3

Mon. April 20

Error-corrected plasma whole-genome sequencing for personalised and tumour-agnostic minimal residual disease detection in NSCLC

Poster – Liquid Biopsies: Circulating Nucleic Acids 4 (PO.CL01.10)

Andrew Georgiadis Labcorp

Section 45 5307/2

Tues. April 21

Analytical performance of an ultrasensitive whole genome sequencing assay for molecular residual disease detection

Mini Symposium – AACR (Free AACR Whitepaper) Project GENIE Use Cases (MS.MD01.01)

Elizabeth E. Martin
Broad Institute of MIT and Harvard

Room 14 Mezzanine Level Mon. April 20

Leveraging Ultima Genomics ppmSeq WGS-cfDNA to accurately detect clonal evolution over sequential blood biopsies

Poster – Liquid Biopsies: Circulating Nucleic Acids 3 (PO.CL01.09)

Laurel K. Millberg
DELFI Diagnostics

Section 45 3863/24

Mon. April 20

Enhanced cfDNA fragmentation-based treatment monitoring on the Ultima Genomics platform

Poster – Epigenetic Changes as Molecular Markers of Cancer (PO.MCB06.03)

Kimberly A. Holden Labcorp

Section 20 3213/23

Mon. April 20

Utility of TAPS+: a positive-readout methylation sequencing approach for high-fidelity epigenetic profiling

Poster – Network Biology and Precision Medicine (PO.BCS01.14)

Orly Alter

University of Utah and Prism AI Therapeutics, Inc

Section 3 6884/28

Wed. April 22

Quantum mechanics-based multi-tensor AI/ML correctly predicts glioblastoma patients’ overall survival, gene targets, and treatment response from whole genomes

(Press release, Ultima Genomics, APR 17, 2026, View Source [SID1234664487])

On April 17, 2026 Marengo Therapeutics, Inc., a clinical-stage biotechnology company pioneering precision immunotherapies for oncology and inflammation and immunology (I&I), reported multiple presentations that highlight clear progress for key assets at the 2026 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting taking place April 17-22, 2026 in San Diego, CA.

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Findings to be shared include late-breaking interim Phase 2a clinical results from Marengo’s ongoing STARt-002 Phase 1b/2a trial of invikafusp alfa plus TRODELVY as part of a collaboration with Gilead Sciences and the first public disclosure of its second precision T cell activator from the STAR program, IPN01203/STAR0501, being advanced in partnership with Ipsen in the prestigious New Drugs on the Horizon session.

"Combining invikafusp alfa with ADC-mediated immunogenic tumor killing is a scientifically compelling approach, and it is exciting to see this translate into meaningful clinical responses in patients with metastatic breast cancer," said Kevin Chin, M.D., Chief Medical Officer of Marengo Therapeutics. "The observation of confirmed complete responses in heavily pretreated breast cancer patients that did not respond to any prior therapy further reinforces our confidence in this novel combination. As enrollment progresses rapidly, we look forward to reporting additional data that both validate our platform and potentially offer a critical new treatment option in a disease with high unmet need."

The initial Phase 2a data build on results presented at the 2025 San Antonio Breast Cancer Symposium, demonstrating encouraging clinical activity with invikafusp alfa plus TRODELVY (sacituzumab govitecan-hziy) in heavily pretreated metastatic breast cancer patients, including confirmed complete responses, across both metastatic triple-negative breast cancer (TNBC) and HR+/HER2- breast cancer.

To date, invikafusp alfa with TRODELVY has shown a safety profile consistent with the known profiles of the individual agents. Pharmacodynamic analyses further confirmed that invikafusp alfa maintains its mechanism of action in a combination regimen, driving robust and selective expansion of Vβ6/Vβ10 T cells. The STARt-002 Phase 1b/2a trial is actively enrolling patients at select cancer centers across North America, with enrollment expected to be completed later this year.

"In a heavily pretreated metastatic breast cancer population, the observation of confirmed complete responses is notable and warrants attention," said Erika Hamilton, M.D., Chief Development Officer, Late Phase and Director of Breast Cancer Research. "While these are early data, the activity observed across both TNBC and HR+/HER2− subtypes, along with a safety profile consistent with the individual agents, supports further clinical evaluation of this combination."

In parallel, Marengo will highlight the continued advancement of the STAR platform through its collaboration with Ipsen. The next clinical candidate, IPN01203/STAR0501, has been selected for an oral presentation during the New Drugs on the Horizon session.

"Together with Marengo, we are advancing a novel precision T cell activation approach with the potential to transform treatment paradigms in solid tumors," said David Jenkins, Senior Vice President, Head of Research and External Innovation at Ipsen. "The rapid progression of this program into the clinic underscores the strength of our collaboration and the quality of scientific execution, and we look forward to exploring its clinical potential."

"We are excited to see the second STAR program advance into the clinic with Ipsen and to share these important data with the scientific community," said Zhen Su, M.D., MBA, Chief Executive Officer of Marengo Therapeutics. "This milestone reflects both the strength of our platform and the productivity of our collaboration as we work together to bring novel immunotherapies to patients with solid tumors."

Additional presentation details are as follows:

Presentation: Initial clinical and translational results and selection of recommended phase 2 dose (RP2D) from START-002: A Phase 1b/2 study of invikafusp alfa, a first-in-class dual T-cell agonist, in combination with sacituzumab govitecan in metastatic triple-negative or HR+/HER2- breast cancer
Abstract Number: LBA045 / 5

Session: First-in-Human Phase I Clinical Trials

Date/Time: Monday April 20, 9:00 AM – 12:00 PM PT

Presentation: Development of IPN01203, a dual T cell agonist activating Vβ6/Vβ10 TCR-expressing T cells
Abstract Number: ND12

Session: New Drugs on the Horizon: Part 3

Date/Time: Monday, April 20, 10:15 AM – 11:45 AM PT

(Press release, Marengo Therapeutics, APR 17, 2026, View Source [SID1234664486])

On April 17, 2026 CREATE Medicines, Inc. ("CREATE"), a clinical-stage biotechnology company pioneering in vivo immune cell programming, reported it will present two posters at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2026, taking place April 17–22, 2026 in San Diego.

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The presentations at AACR (Free AACR Whitepaper) highlight the CREATE platform in action, showcasing new data across CREATE’s multi-immune in vivo CAR portfolio and introducing the first in vivo data for RetroT, the company’s all-RNA genome integration platform designed to enable stable, durable cell engineering without viral components.

The data demonstrates simultaneous engineering of myeloid cells, NK cells, and T cells with tailored CAR mRNAs driving tumor regression and remodeling of the tumor microenvironment in a colorectal cancer model. First-in-vivo evidence for RetroT demonstrates that CAR T cells engineered without double-strand breaks or viral vectors significantly reduced tumor burden in a leukemia model, validating the platform’s potential as a path to stable, durable CAR expression.

"CREATE was built to rapidly iterate directly from our clinical data and unlock the clear advantages of in vivo cell therapy," said Robert Hofmeister, Ph.D., Chief Scientific Officer of CREATE. "The work we are presenting at AACR (Free AACR Whitepaper) underscores this unique capability of our platform, leveraging our experience in over 50 patients to develop the next generation multi-immune CARs or stably integrated mRNA in vivo therapies. These advances position the platform for near-term development of novel scalable therapies across autoimmune and oncology."

CREATE is advancing the broadest portfolio of in vivo CAR therapies, supporting the largest human clinical dataset in the field, built through the application of its integrated mRNA, lipid nanoparticle, and CAR engineering platform. This dataset enables rapid translation from clinical insight to pipeline innovation, informing both current programs and the design of next-generation in vivo CAR therapies.

AACR Poster Presentation Details:

Title: In Vivo CAR mRNA Engineering of T Cells and Myeloid Cells Enables Potent Anti-Tumor Control of Solid Cancers
Date & Time: Sunday, April 19, 2026, 2–5 PM PT
Location: Poster Section 7
Session Category: Immunology
Session Title: Alternative Cell Type and In Situ Cell Therapies
Poster Board #: 18
Abstract #: 144

Title: Stepwise In Vivo CAR T Cell Engineering via Transient RNA Programming and RetroT All-RNA Genome Integration
Date & Time: Monday, April 20, 2026, 9 AM–12 PM PT
Location: Poster Section 53
Session Title: Late-Breaking Research: Immunology 2
Poster Board #: 20
Abstract #: LB155

More information is available on the AACR (Free AACR Whitepaper) Annual Meeting website.

(Press release, Create Medicines, APR 17, 2026, View Source [SID1234664485])

On April 17, 2026 Nested Therapeutics, a clinical-stage oncology company developing transformative therapies for RAS/MAPK-driven disorders, reported initial clinical results from its ongoing Phase 1 study evaluating NST-628, a brain-penetrant non-degrading pan-RAF/MEK molecular glue, in patients with advanced solid tumors. Data presented at the AACR (Free AACR Whitepaper) Annual Meeting 2026 demonstrate encouraging single-agent anti-tumor activity and a favorable tolerability profile in a range of RAF and RAS-mutant tumors, including a 38% response rate and 85% disease control rate at the recommended dose in heavily pretreated NRAS and BRAF Class II/III melanoma, a population that represents approximately 33% of cutaneous melanoma patients, for whom no approved targeted therapies are available.

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"These initial data support our hypothesis that targeting RAF/MEK signaling with a single-agent, fully brain-penetrant pan-RAF/MEK molecular glue can deliver meaningful clinical benefit with a tolerability profile that supports sustained dosing even in comparison to what may be expected from combination regimens," said Darrin Miles, Chief Executive Officer of Nested Therapeutics. "We are particularly encouraged by the durable responses in NRAS and BRAF Class II/III melanoma – large patient populations with historically poorer outcomes and for whom there are no approved targeted therapy options – as well as early signals of clinical activity beyond melanoma, including in KRAS-mutant solid tumors and evidence of brain penetrance. Together, these clinical findings, in addition to robust preclinical evidence and favorable drug properties, support the potential for NST-628 to address significant unmet need across RAS/MAPK-driven cancers and to serve as a foundational therapy in both monotherapy and combination settings."

Key Data Highlights

As of the data cutoff date of February 1, 2026, NST-628 has been administered to 69 patients: 64 patients in dose-escalation and 5 patients in the expansion phase. Key findings are summarized below.

Monotherapy Clinical Activity in evaluable patients (with at least one tumor assessment or who discontinued the study) at Recommended Dose for Expansion (RDE)

NST-628 monotherapy demonstrated a 38% response rate in BRAF Class II/III and NRAS-mutant melanoma (N=13) and 33% response rate overall (N=18); response rates include one unconfirmed partial response
Disease control rate was 85% in the melanoma subgroup and 72% overall
With a median follow-up of 6.4 months, the median duration of response in melanoma was not yet reached
Anti-Tumor Activity Beyond Melanoma

Responses to NST-628 were observed across multiple tumor types and genotypes, including KRAS-mutant ovarian and cervical cancers – highlighted by an ongoing partial response in a KRAS G12V-mutant cervical cancer patient with a treatment duration exceeding one year – as well as NRAS/BRAF Class III-mutant colorectal cancer and BRAF Class II-mutant thymic cancer
A patient with high-grade astrocytoma (BRAF V600E), previously treated with multiple lines of RAF/MEK-targeted therapy, demonstrated 70% tumor shrinkage on NST-628 monotherapy, consistent with NST-628’s preclinical brain penetration profile
Reductions in ctDNA correlated with radiographic response
Safety and Tolerability

Adverse events were consistent with the mechanism of action and predominantly Grade 1-2
Most common treatment-related adverse events included dermatologic, gastrointestinal, CK elevation, constitutional, and ocular events
Grade ≥3 TRAEs were infrequent; most common was CK elevation
No Grade 5 events reported
At the RDE:
Discontinuation rate: 9%
Dose intensity (actual dose delivered vs. intended): 82%
"The anti-tumor activity observed with NST-628 monotherapy is encouraging," said Philip Komarnitsky, MD, PhD, Chief Medical Officer of Nested Therapeutics. "A safety profile that supports continuous dosing at 82% dose intensity with a 9% discontinuation rate, combined with the response rate of 38% and disease control rate of 85% in NRAS and BRAF Class II/III melanoma patients at the recommended dose, is promising for this patient population with no approved targeted therapies. The clinical evidence of activity in malignancies with BRAF class III mutations, an emerging resistance mechanism to RAS inhibitors, and of brain penetrance consistent with preclinical findings is particularly noteworthy. These data support the continued development of NST-628 as monotherapy and its evaluation in rational combinations."

Nested plans to continue enrollment in the ongoing Phase 1 expansion cohort and evaluate NST-628 in additional malignant and non-malignant MAPK-driven diseases and combination settings, including mutant-selective RAS and other inhibitors.

Poster Presentation Details

Title: Preliminary results from a Phase 1a/b dose-escalation and expansion trial of the pan-RAF-MEK molecular glue NST-628 in patients (pts) with advanced or refractory RAF, KRAS, and NRAS-mutant solid tumors

Presenter: Ahmad A. Tarhini, MD, PhD, Moffitt Cancer Center

Presentation Date and Time: Monday, April 20, 2026, 2:00 PM-5:00 PM PT

Session: PO.CT01.01 – Phase 0 and First-in-Human Phase I Clinical Trials

Location: Section 51

About the Phase 1 Study of NST-628, NST-628-001

The ongoing Phase 1 open-label, single-arm, two-part study (NCT06326411) is investigating the safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of single-agent NST-628 in adult patients with RAS-MAPK pathway mutated/dependent advanced solid tumors, especially diverse KRAS, NRAS, and BRAF alterations, who have exhausted standard treatment options. The study includes two parts: dose escalation (Part A), which enrolled 64 patients across seven dose regimens, followed by dose expansion (Part B) at the recommended dose for expansion. Part B is currently enrolling. For more information, visit clinicaltrials.gov.

About NST-628

NST-628 is a brain-penetrant, non-degrading molecular glue designed to inhibit RAF and MEK signaling by stabilizing RAF-MEK complexes in a catalytically inactive form. This mechanism is intended to prevent pathway reactivation, a common liability of existing RAS/MAPK-targeted therapies, and enable more durable pathway suppression across RAS/MAPK-driven cancers.

(Press release, Nested Therapeutics, APR 17, 2026, View Source [SID1234664484])