BAY2666605 / Bayer - LARVOL DELTA

The Role of PDE3A in Cancer. (PubMed, ACS Omega) - "PDE3A plays a pivotal role in tumorigenesis and cancer progression, with aberrant expression strongly associated with tumor proliferation, metastasis, and resistance to chemotherapy. As a therapeutic target, PDE3A holds significant potential. The development of PDE3A inhibitors or molecular adhesive agents may offer novel treatment strategies, particularly for chemotherapy-resistant tumor types."

Journal • Review • Breast Cancer • Gastrointestinal Stromal Tumor • Hepatocellular Cancer • Oncology • Sarcoma • Solid Tumor • Fascin • FSCN1 • METTL3 • MYBL2 • PDE3A

Preclinical profiling of CY002-243-1: A highly potent PDE3A-SLFN12 molecular glue for cancer therapy (AACR 2025) - "In the SK-MEL-3 Melanoma tumor xenograft model, administration of HP-001 (0.1 mpk, QD) promoted tumor regression (~95% tumor growth inhibition by 14 days), compared to ~90% tumor growth inhibition by 14 days in BAY2666605 (1 mpk, QD) group. CY002-243-1 is a highly potent, PDE3A-SLFN12 molecular glue, with marked anti-tumor activity as a single agent across diverse tumor cell."

Late-breaking abstract • Preclinical • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BCL2 • MAGEE1 • MCL1 • PDE3A

First-in-human dose escalation study of the first-in-class PDE3A-SLFN12 complex inducer BAY 2666605 in patients with advanced solid tumors co-expressing SLFN12 and PDE3A. (PubMed, Clin Cancer Res) - P1 | "Despite the decreased PDE3A enzymatic inhibition profile of BAY 2666605, the occurrence of thrombocytopenia in treated patients, an on-target effect of the compound, precluded the achievement of a therapeutic window, consequently leading to trial termination."

Journal • Metastases • P1 data • Hematological Disorders • Oncology • Solid Tumor • Thrombocytopenia • PDE3A

Discovery of BAY 2666605, a Molecular Glue for PDE3A and SLFN12. (PubMed, ACS Med Chem Lett) - "More analogs were prepared and tested with the goal of increasing metabolic stability and decreasing PDE3 inhibition while maintaining the cellular activity of BRD9500. This led to the discovery of BAY 2666605, a compound optimized for clinical testing."

Journal • Oncology • Targeted Protein Degradation • PDE3A

Velcrin molecular glues induce apoptosis in glioblastomas with high PDE3A and SLFN12 expression. (PubMed, Neurooncol Adv) - "We also determined that the velcrins BAY 2666605 and BRD3800 induce tumor regression in subcutaneous glioblastoma PDX models. Velcrins have antitumor activity in preclinical models of glioblastoma, warranting further investigation as potential therapeutic agents."

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • Targeted Protein Degradation • BRD3 • PDE3A

A Study to Learn How Safe BAY2666605 is, How it Affects the Body, How it Moves Into, Through and Out of the Body, the Maximum Amount That Can be Given and Its Action Against Tumors in Adult Participants With Skin Cancer That Has Spread to Other Parts of the Body and Other Types of Advanced Cancer (clinicaltrials.gov) - P1 | N=5 | Terminated | Sponsor: Bayer | Completed ➔ Terminated; Due to the high probability of not achieving a therapeutic window and lack of evidence of sufficient clinical benefit.

Metastases • Trial termination • Genetic Disorders • Glioblastoma • Melanoma • Oncology • Ovarian Cancer • Skin Cancer • Solid Tumor • PDE3A

Velcrin molecular glues induce cell death in glioblastomas with high PDE3A and SLFN12 expression. (SNO 2023) - "Lastly, we demonstrated that the velcrins BAY 2666605 and BAY 2501293 induce tumor regression in biomarker-positive subcutaneous glioblastoma patient-derived xenograft models. In summary, our data demonstrates that velcrins have anti-tumor activity in preclinical models of glioblastoma, warranting further investigation as potential therapeutic agents."

Brain Cancer • CNS Tumor • Glioblastoma • Inflammatory Arthritis • Oncology • Solid Tumor • Targeted Protein Degradation • PDE3A

A Study to Learn How Safe BAY2666605 is, How it Affects the Body, How it Moves Into, Through and Out of the Body, the Maximum Amount That Can be Given and Its Action Against Tumors in Adult Participants With Skin Cancer That Has Spread to Other Parts of the Body and Other Types of Advanced Cancer (clinicaltrials.gov) - P1 | N=5 | Completed | Sponsor: Bayer | Active, not recruiting ➔ Completed

Metastases • Trial completion • Genetic Disorders • Glioblastoma • Melanoma • Oncology • Ovarian Cancer • Skin Cancer • Solid Tumor • PDE3A

A Study to Learn How Safe BAY2666605 is, How it Affects the Body, How it Moves Into, Through and Out of the Body, the Maximum Amount That Can be Given and Its Action Against Tumors in Adult Participants With Skin Cancer That Has Spread to Other Parts of the Body and Other Types of Advanced Cancer (clinicaltrials.gov) - P1 | N=5 | Active, not recruiting | Sponsor: Bayer | Trial completion date: Jun 2024 ➔ Mar 2023 | Trial primary completion date: Mar 2024 ➔ Nov 2022

Metastases • Trial completion date • Trial primary completion date • Genetic Disorders • Glioblastoma • Melanoma • Oncology • Ovarian Cancer • Skin Cancer • Solid Tumor • PDE3A

A Study to Learn How Safe BAY2666605 is, How it Affects the Body, How it Moves Into, Through and Out of the Body, the Maximum Amount That Can be Given and Its Action Against Tumors in Adult Participants With Skin Cancer That Has Spread to Other Parts of the Body and Other Types of Advanced Cancer (clinicaltrials.gov) - P1 | N=5 | Active, not recruiting | Sponsor: Bayer | Recruiting ➔ Active, not recruiting | N=89 ➔ 5

Enrollment change • Enrollment closed • Metastases • Genetic Disorders • Glioblastoma • Melanoma • Oncology • Ovarian Cancer • Skin Cancer • Solid Tumor • PDE3A