| PROGRAM | MOA | INDICATION | PRECLINICAL | IND | PHASE I | PHASE II |
|---|---|---|---|---|---|---|
| KPG-818 (Epaldeudomide) | CRL4-CRBN MODULATOR | Cutaneous Manifestation of Systemic Lupus Erythematosus (SLE-CM) | ||||
| Systemic Lupus Erythematosus (SLE) | ||||||
| Inflammatory Bowel Disease (lBD) | ||||||
| Multiple Myeloma (MM) | ||||||
| Non-Hodgkin Lymphoma (NHL) | ||||||
| Immune Thrombocytopenia (ITP) | ||||||
| KPG-121 | CRL4-CRBN MODULATOR | Metastatic Castration-Resistant Prostate Cancer (mCRPc) | ||||
| KP-09S | CRL4-CRBN MODULATOR | Hematological Malignancies | ||||
| gDAC-S | Degrader-Antibody Conjugate |
Solid Tumors | ||||
| gDAC-H | Degrader-Antibody Conjugate |
Hematological Malignancies | ||||
| gDAC-A | Degrader-Antibody Conjugate |
Auto-immune Diseases | ||||
KPG-818 is a novel oral molecular glue modulator of the E3 ubiquitin ligase complex CRL4-CRBN. It demonstrated high binding affinity to CRBN and potent degradation of zinc-finger transcription factors Aiolos (IKZF3) and Ikaros (IKZF1). KPG-818 effectively regulates immune cells (B cells, T cells, and pDC cells) and the release of multiple cytokines, possessing broad immunomodulatory, anti-angiogenic and anti-tumor effects. In the Phase IIa clinical study in systemic lupus erythematosus (SLE) patients completed in the US, KPG-818 was well tolerated and demonstrated promising preliminary efficacy. KPG-818 was well tolerated in healthy subjects in a Phase I clinical study completed in China. The Center for Drug Evaluation (CDE) of China's National Medical Products Administration (NMPA) has approved Phase IIb clinical trial of KPG-818 capsule for the treatment of moderate to severe cutaneous manifestations of SLE.
KPG-121 is a modulator of the Cereblon (CRBN) E3 ubiquitin ligase complex CRL4-CRBN targeting rapid ubiquitination and degradation of casein kinase 1A1 (CK1α). It promotes anti-proliferation and anti-angiogenesis activities and enhances immunomodulatory properties. KPG-121 significantly improves anti-tumor efficacy when combined with androgen-receptor antagonists including enzalutamide, abiraterone acetate, apalutamide, or darolutamide in xenograft models when compared to the androgen-receptor antagonist therapy alone. A Phase I study to evaluate the safety, pharmacokinetics, and efficacy of KPG-121 when combined with enzalutamide, abiraterone, or apalutamide for the treatment of patients with metastatic or non-metastatic castration-resistant prostate cancer was completed in the US. KPG-121 was well tolerated and demonstrated a favorable pharmacokinetic profile as well as promising efficacy. The U.S. Food and Drug Administration ( FDA ) has approved a Phase II/III clinical trial of KPG-121 in combination with Abiraterone as a first-line treatment of metastatic castration resistant prostate cancer ( mCRPC ).
KP-09S belongs to a novel class of molecular glues targeting the CRBN E3 ubiquitin ligase complex CRL4-CRBN with great potential for the treatment of relapsed/refractory hematological malignancies.
