AACR 2026 | Abbisko Therapeutics Showcases Six Research Advances Highlighting pan-KRAS, 4th Generation EGFR, and Synthetic Lethality Approaches

The presentations span multiple key innovation areas, including the pan-KRAS inhibitor ABSK211, the 4^th generation EGFR inhibitor ABK-EGFR-1, the CDK4 selective inhibitor ABK-CDK4, the MTA-cooperative PRMT5 inhibitor ABSK131, as well as a ctDNA-based study investigating resistance mechanisms to the FGFR2/3 inhibitor ABSK061.

pan-KRAS Inhibitor ABSK211

ABSK211 is a potent, highly selective, and orally bioavailable small-molecule pan-KRAS inhibitor developed by Abbisko Therapeutics. It demonstrates broad inhibitory activity against multiple KRAS mutations, addressing significant unmet medical needs in KRAS-driven cancers. At AACR 2026, Abbisko presented preclinical data for both monotherapy and combination strategies of ABSK211.

Monotherapy: Broad and Potent Inhibition Across KRAS Mutations

KRAS mutations are highly prevalent across multiple cancers, including pancreatic (~90%), colorectal (~35%), and lung cancer (~25%). While several pan-KRAS inhibitors have entered clinical development, there remains a critical need for enhanced potency.

In preclinical studies, ABSK211 demonstrated:

• Robust in vitro activity: ABSK211 significantly reduced cell viability across multiple KRAS alterations (including G12, G13, Q61, and WT amplification) at sub-nanomolar to nanomolar concentrations. Meanwhile ABSK211 displayed marginal inhibition in KRAS wild-type cell line with normal copy.

• Strong in vivo efficacy: Oral administration induced deep tumor regression in multiple KRAS G12V xenograft models, with robust target engagement.

• Broad mutation coverage: Consistent and significant antitumor activity was observed in models harboring KRAS G12D/C/S and G13D mutations.

These findings support the clinical advancement of ABSK211, which is currently undergoing IND-enabling studies.

Poster Information

• Title: Preclinical characterization of ABSK211: A highly potent, orally bioavailable and selective pan-KRAS inhibitor with broad and robust activity in KRAS-driven tumors
• Time: April 22, 2026, 9:00 AM – 12:00 PM (PT)
• Location: Poster Section 13, Board #10
• Abstract #: 7090

Combination Therapy: Multi-Mechanistic Synergy Enhances Antitumor Activity

Combination therapy is widely considered a key strategy to improve treatment outcomes in KRAS-mutant cancers. ABSK211 demonstrated synergistic antitumor activity with multiple therapeutic agents:

• In vitro synergy: Significant anti-proliferative synergy with PRMT5 inhibitors across KRAS mutations; strong synergy observed with EGFR monoclonal antibodies and chemotherapy in KRAS G12D/G12V models.

• Enhanced in vivo efficacy: Combination regimens with PRMT5 inhibitors, cetuximab, immunotherapies, and chemotherapy showed superior tumor growth inhibition and improved durability compared to monotherapy.

These results demonstrate that ABSK211 can significantly enhance antitumor efficacy through multi-mechanistic synergy, supporting its further development in combination strategies.

Poster Information

• Title: ABSK211, a highly potent and orally available pan-KRAS inhibitor, demonstrates robust antitumor efficacy in combination with multiple agents
• Time: April 22, 2026, 9:00 AM – 12:00 PM (PT)
• Location: Poster Section 13, Board #3
• Abstract #: 7083

4^th Generation EGFR Inhibitor ABK-EGFR-1

ABK-EGFR-1 is a novel 4^th generation EGFR inhibitor developed by Abbisko Therapeutics, specifically designed to target the EGFR C797S resistance mutation. It combines high selectivity with central nervous system (CNS) penetration to address key clinical challenges following resistance to 3^rd generation EGFR TKIs.

Targeting C797S-Mediated Resistance

The EGFR C797S mutation is a clinically validated mechanism of resistance to third-generation EGFR TKIs, with an estimated 51,000–146,000 cases annually worldwide. Currently, no approved therapies specifically target this mutation, representing a significant unmet clinical need. Preclinical studies showed that ABK-EGFR-1:

• Exhibits high selectivity over wild-type EGFR and other kinases.

• Demonstrates significant in vivo antitumor activity in multiple EGFR C797S-driven xenograft models, effectively inhibiting tumor growth.

• Possesses excellent blood-brain barrier penetration and favorable drug-like properties.

These findings support further development of ABK-EGFR-1 as a next-generation targeted therapy for EGFR-resistant cancers, particularly for patients with brain metastases.

Poster Information

• Title: Discovery and characterization of ABK-EGFR-1, a 4^th generation EGFR C797S Inhibitor with excellent selectivity and brain penetration
• Time: April 21, 2026, 2:00 PM – 5:00 PM (PT)
• Location: Poster Section 53, Board #7
• Abstract #: LB350

CDK4 Selective Inhibitor ABK-CDK4

ABK-CDK4 is a highly selective, brain-penetrant small-molecule CDK4 inhibitor developed by Abbisko Therapeutics. It is designed to selectively target CDK4, reduce CDK6-related toxicity, and expand treatment potential for patients with brain metastases.

Differentiation Through Selectivity and CNS Penetration

1^st generation CDK4/6 inhibitors (e.g., palbociclib, ribociclib, and abemaciclib) have demonstrated clinical benefit in breast cancer, but CDK6 inhibition is associated with dose-limiting hematologic toxicities. In addition, 20–40% of breast cancer patients develop brain metastases, while current therapies have limited CNS exposure.

Preclinical studies showed that ABK-CDK4:

• High selectivity: Over 50-fold selectivity for CDK4 versus CDK6, potentially reducing CDK6-related toxicity.

• CNS penetration: Favorable CNS exposure (Kpuu > 0.5) and drug-like properties.

• Antitumor activity: Effective inhibition of Rb phosphorylation and tumor growth in HR+/HER2− breast cancer models

These results suggest that ABK-CDK4 may overcome key limitations of current CDK4/6 inhibitors and provide a differentiated therapeutic option.

Poster Information

• Title: Discovery of ABK-CDK4, a selective and brain-penetrant CDK4 inhibitor
• Time: April 20, 2026, 9:00 AM - 12:00 PM (PT)
• Location: Poster Section 20, Board #13
• Abstract #: 1905

MTA-cooperative PRMT5 inhibitor ABSK131

ABSK131 is a potent and selective small-molecule MTA-cooperative PRMT5 inhibitor developed by Abbisko Therapeutics, targeting MTAP-deleted tumors, and is currently in clinical development.

Broad Synergy Across Multiple Therapeutic Modalities

MTAP homozygous deletion occurs in approximately 10–15% of solid tumors and frequently co-exists with oncogenic drivers such as KRAS and EGFR. In addition, MTAP abnormities are associated with poor prognosis following standard-of-care therapies across multiple cancer types. Therefore, there remains a significant unmet need for novel and effective combination therapies centered on MTA-cooperative PRMT5 inhibitor for MTAP-deleted tumors, with the potential to enable precision patient stratification and deliver synergistic therapeutic benefits.

Preclinical studies demonstrated that ABSK131 exhibits strong synergistic activity with multiple therapies:

• KRAS inhibitors: Enhanced tumor growth inhibition in KRAS-mutant, MTAP-deleted models when combined with AMG 510 or ABSK141.

• EGFR inhibitors: Improved anti-proliferative and in vivo antitumor activity in EGFR-mutant, MTAP-deleted NSCLC models when combined with osimertinib.

• MAT2A inhibitors: Consistent synergistic effects across multiple tumor models when combined with IDE397.

• Chemotherapy: Synergistic activity observed both in vitro and in vivo when combined with carboplatin in NSCLC models.

These findings support ABSK131 as a potential backbone therapy for combination strategies in MTAP-deleted tumors.

Poster Information

• Title: Synergistic antitumor activity of the MTA-cooperative PRMT5 inhibitor ABSK131 in combination with multiple therapeutic agents in diverse cancer models
• Time: April 21, 2026, 9:00 AM - 12:00 PM (PT)
• Location: Poster Section 14, Board #23
• Abstract #: 4504

FGFR2/3 Inhibitor ABSK061

ABSK061 is a highly potent and selective small-molecule FGFR2/3 inhibitor developed by Abbisko Therapeutics. It has demonstrated encouraging efficacy and safety in Phase I studies and is currently being evaluated in a Phase II trial for gastric cancer.

ctDNA Analysis Reveals Resistance Mechanisms

Acquired resistance remains a major challenge limiting the long-term benefit of targeted therapies. Using ctDNA-based next-generation sequencing (NGS), Abbisko conducted longitudinal genomic analyses comparing baseline and progression samples to elucidate resistance mechanisms to ABSK061:

On-target resistance: Polyclonal acquired FGFR2 mutations in the FGFR2 kinase domain were commonly observed in gastric cancer and cholangiocarcinoma.

Off-target resistance: FGFR2-Atered NSCLC was prone to develop acquired alterations in genes involved in RTK/RAS pathways.

These findings provide important molecular insights into resistance mechanisms and inform the design of future combination and sequential treatment strategies.

Poster Information

• Title: Circulating tumor DNA (ctDNA)-based profiling of acquired resistance to the fibroblast growth factor receptor (FGFR)2/3 inhibitor lavengratinib(ABSK061) in patient(pt)s with advanced solid tumors
• Time: April 21, 2026, 9:00 AM - 12:00 PM (PT)
• Location: Poster Section 45, Board #14
• Abstract #: 5319

At AACR 2026, Abbisko Therapeutics showcased the latest preclinical and translational research advances across multiple pipeline programs, demonstrating its strong capabilities in drug discovery and development. As these programs continue to advance into clinical stages, the company is further strengthening its globally competitive R&D platform.

Looking ahead, Abbisko Therapeutics will continue to focus on addressing unmet medical needs and accelerating the translation of innovative discoveries into clinical applications, with the goal of delivering more first-in-class and best-in-class therapies to patients worldwide.

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SOURCE Abbisko Therapeutics