On April 20, 2026 Monte Rosa Therapeutics, Inc. (Nasdaq: GLUE), a clinical-stage biotechnology company developing novel molecular glue degrader (MGD)-based medicines, reported the company will present preclinical data highlighting the potential of its highly selective, first-in-class cyclin E1 (CCNE1)-directed MGD, MRT-55811, to treat CCNE1-amplified solid tumors at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2026, being held April 17-22 in San Diego, CA.

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"CCNE1 MGDs represent a first-in-class opportunity to directly target a frequently amplified driver oncogene in several solid tumor cancer populations with high unmet medical need. In CCNE1-amplified in vivo models of ovarian, gastric, and breast cancer, MRT-55811 demonstrated compelling monotherapy anti-tumor activity," said Sharon Townson, Ph.D., Chief Scientific Officer of Monte Rosa Therapeutics. "MRT-55811 also exhibited superior selectivity when compared to clinical-stage CDK2 inhibitors, suggesting that our CCNE1-directed MGDs could avoid the dose-limiting toxicities reported for these less selective agents. We believe that our oral CCNE1 degrader has the potential to provide clinical benefit across multiple cancer types where CCNE1 is amplified. These data also reinforce the power of our QuEEN discovery engine, as cyclin E1 represents yet another previously undruggable target we’ve successfully targeted. We anticipate submitting an IND for this program later this year."

The presentation, "Selective targeting of CCNE1 using molecular glue degraders for the treatment of CCNE1 amplified cancers" (Abstract Presentation Number 6778), will be presented by Ralph Tiedt, Ph.D., Vice President, Biology, Monte Rosa Therapeutics, at the Minisymposium, "Targeted Protein Degradation and Non-canonical Oncogenic Signaling," on April 21, 2026, from 2:30 p.m. to 4:30 p.m. PT.

Summary of results:

MRT-55811 exhibited potent degradation and high selectivity for CCNE1, with no detectable degradation of closely related cyclins or cyclin-dependent kinases (CDKs), and favorable drug-like properties.
MRT-55811 induced deep cyclin E1 degradation and downstream pathway suppression, as well as co-degradation of CDK2 within the cyclin E1/CDK2 holoenzyme complex in CCNE1-amplified cell lines.
MRT-55811 demonstrated superior selectivity compared with clinical-stage CDK2 inhibitors, which exhibited significant off-target activity, as evidenced by kinome profiling and genetic modeling.
In CCNE1-amplified cancer cell lines, MRT-55811 selectively inhibited cellular proliferation, while sparing cell lines without amplification.
In vivo, MRT-55811 monotherapy resulted in tumor regression and pathway suppression in multiple CCNE1-amplified models.
MRT-55811 downmodulated retinoblastoma (RB) protein phosphorylation and E2F-driven gene expression, demonstrating on-target effects in tumors grown in vivo.

About CCNE1 MGDs
Cyclin E1 (CCNE1) is a well-recognized human oncogene and critical driver of cell cycle progression and cell proliferation and was historically considered an undruggable target. It acts as the regulatory subunit of the CCNE1-CDK2 holoenzyme, which coordinates G1-S cell cycle progression and drives cell proliferation through RB phosphorylation and repression. CCNE1 is frequently amplified or overexpressed across multiple cancer types, including ovarian, endometrial, gastric, breast, and others. Leveraging a cryptic pocket, Monte Rosa’s CCNE1-directed MGDs selectively degrade the cyclin E1/CDK2 holoenzyme complex, while sparing other proteins such as other closely related cyclins or CDKs. As a result of this exquisite selectivity, CCNE1-directed MGDs represent an opportunity to directly and selectively target a frequently amplified driver oncogene across multiple cancers.

(Press release, Monte Rosa Therapeutics, APR 20, 2026, View Source [SID1234664587])