Targeted protein degradation (TPD) is an alternative to conventional protein inhibition that is gaining attention due to advantages such as ensuring complete elimination of the target protein, reduced off-target effects or the potential to target previously inaccessible or “undruggable” proteins. Proteolysis targeting chimeras (PROTACs) are agents used for TPD that have proven effective for degradation of histone deacetylase (HDAC), among other different proteins.
Photys Therapeutics Inc. has signed a license agreement with Hangzhou Polymed Biopharmaceuticals Inc. for HPB-143, a phase I-ready IRAK-4 degrader. IRAK-4 degradation offers potential to treat various autoimmune indications, including atopic dermatitis and hidradenitis suppurativa.
Right open reading frame kinase 2 (RIOK2) plays an essential role in ribosome assembly and cell growth, survival and stress responses. Research has linked RIOK2 to tumor progression and poor prognosis in several types of cancer such as breast, lung, prostate or hematological tumors.
Lycia Therapeutics Inc. has reported progress in its immunology pipeline that comprises lysosomal targeting chimera (LYTAC)-based protein degradation therapies. The company is advancing its two lead programs toward the clinic: LCA-0061, a Catalytac degrader that catalytically degrades IgE, and LCA-0321, a Lytac degrader designed to specifically bind and rapidly deplete anti-thyroid-stimulating hormone receptor (TSHR) autoantibodies.
Auron Therapeutics Inc. has received FDA clearance of its IND application for its oral KAT2A/B degrader AUTX-703 in hematological malignancies. A phase I proof-of-concept trial in acute myeloid leukemia (AML) will open enrollment this quarter, supported by a recently completed $27 million series B financing.
Seed Therapeutics Inc.’s ST-01156 has been awarded orphan drug designation for the treatment of Ewing sarcoma as well as rare pediatric disease designation by the FDA.
Son of sevenless homolog 1 (SOS1) is an essential guanine nucleotide exchange factor (GEF) in KRAS-driven tumors, and it also functions as a downstream node protein of BCR-ABL, suggesting its critical role in the pathogenesis of chronic myeloid leukemia (CML). Investigators at Shanghaitech University have reported the discovery and preclinical characterization of a novel potent SOS1 proteolysis targeting chimera (PROTAC) – SIAIS-562055 – being developed as an anticancer agent.
In the preclinical setting, inhibitors of histone deacetylase 6 (HDAC6) have proven effective at reducing liver inflammation through modulation of the immune response.
Immune checkpoint blockade is one of the major advances in cancer treatment in recent years. However, the majority of immune checkpoints are embedded in the cell membrane and this fact represents a limitation for targeted degradation using proteolysis-targeting chimeras (PROTACs).
Aromatase inhibitors (AI) are among the most widely used therapies in the treatment of breast tumors expressing estrogen receptor α (ERα). Alone or in combination with other agents, they are the standard of care for hormone receptor-positive tumors.
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