Cloverleaf Bio lands USD 33m seed with Lilly, AbbVie, and Boehringer backing

Connecticut-based Cloverleaf Bio has raised USD 33 million in an oversubscribed seed financing round to advance a platform of engineered transfer RNA (tRNA)-based therapeutics targeting cancer, with strategic backing from three major pharmaceutical companies at the preclinical stage.

The round was led by 4BIO Capital and includes participation from AbbVie Ventures, Eli Lilly and Company, and Boehringer Ingelheim Venture Fund alongside Draper Associates, Mission BioCapital, and American Cancer Society BrightEdge. The company said proceeds will support advancement of its lead inhibitory tRNA asset, CLB-001, toward early clinical testing in hepatocellular carcinoma (HCC), and preclinical development of an antibody-tRNA conjugate (ATC) targeting colorectal cancer. Cloverleaf also received prior non-dilutive support through a National Cancer Institute (NCI) Small Business Innovation Research (SBIR) grant and a USD 100,000 award from the Nucleate and Eli Lilly Genetic Medicine Grand Challenge — an early independent validation from a company that subsequently joined the seed round as a strategic investor.

Cloverleaf is a spinout from Yale University, founded by Austin Draycott (CEO), Cole Lewis (CSO), and Wendy Gilbert (SAB Chair), with Draycott and Lewis having conducted their doctoral research in Gilbert's Yale laboratory on RNA modifications and tRNA-modifying enzymes. Gilbert holds the Maxine F. Singer '57 PhD Professorship in Molecular Biophysics and Biochemistry at Yale.

The platform targets RNA-modifying enzymes that cancer cells become abnormally dependent on to sustain the high-throughput translation of oncogenic proteins — a vulnerability that normal cells do not share to the same degree. Cloverleaf's engineered tRNAs act as competitive substrate-mimic inhibitors, occupying enzyme active sites without being productively modified. The company said CLB-001 demonstrated greater potency and selectivity for cancerous cells over healthy tissue in preclinical studies, outperformed frontline standard of care in HCC models at lower doses and showed activity in lung adenocarcinoma models, and showed no markers of liver damage or systemic toxicity in animal tolerability studies. The ATC program retained activity in colorectal cancer cell lines resistant to both frontline chemotherapy and current-generation antibody-drug conjugate payloads, the company said.

The platform is described as tunable across more than 25 tRNA-modifying enzymes, with longer-term applicability the company said could extend to neurodegenerative and fibrotic diseases beyond oncology.

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