Prelude Therapeutics Incorporated is at the forefront of precision oncology, focusing on the development of innovative therapies that target the underlying mechanisms of cancer. The company has established a diverse pipeline of drug candidates, including first-in-class SMARCA2 degraders and a potentially best-in-class CDK9 inhibitor. These therapies are designed to selectively target cancer-promoting pathways, with the aim of improving clinical outcomes while minimizing off-target effects. Prelude's approach includes leveraging targeted protein degradation technologies to create next-generation antibody-drug conjugates (Precision ADCs), which enhance the therapeutic potential of existing cancer treatments.

The company's research emphasizes a bold, scientific methodology that is not limited by specific platforms or target classes. Prelude Therapeutics is committed to addressing high unmet needs in oncology, particularly for hard-to-treat solid tumors and hematologic malignancies. Their innovative drug candidates, such as PRT3789 (a SMARCA2 degrader) and PRT2527 (a CDK9 inhibitor), are currently in various stages of clinical trials, showcasing the company's dedication to transforming cancer treatment through precision medicine. By focusing on the unique biological characteristics of tumors, Prelude aims to deliver safe and effective therapies that can significantly improve the lives of cancer patients.

United States

Prelude Therapeutics Incorporated, a clinical-stage biopharmaceutical company, focuses on the discovery and development of small molecule therapies optimized to target the key driver mechanisms in cancers. It is developing PRT543 that is in Phase 1 clinical trials in select solid tumors and myeloid malignancies in patients who are refractory to or intolerant of established therapies; and PRT811, which is in Phase 1 clinical trials in solid tumors, including glioblastoma multiforme and primary central nervous system lymphomas. The company is also developing PRT1419, a potent and selective inhibitor of the anti-apoptotic protein; PRT2527, a potent inhibitor of CDK9 that exhibits high kinome selectivity; PRT-SCA2 for multiple genomically selected cancers; and PRT-K4 for solid tumors. Prelude Therapeutics Incorporated was founded in 2016 and is based in Wilmington, Delaware.

Cancer

Hematologic Diseases

Lung Diseases

Prelude Therapeutics Incorporated

PRT3645 is a highly selective and differentiated CDK4/6 inhibitor. PRT3645 is a CDK4 biased compound with tissue and brain penetration qualities, and has potential in multiple indications including gliomas, head and neck cancers and non-small cell lung cancer, in addition to HR+/HER2- and HR+/HER2+ breast cancers.

PRT3645 (CDK4/6 inhibitor) + KEYTRUDA®

Myelodysplastic syndrome

Myelofibrosis

Solid tumor/s

Protein Arginine Methyl Transferase 5 &nbsp;(PRMT5) is a member of a family of enzymes involved in the methylation &nbsp;of arginine residues on histones and other cytosolic and nuclear &nbsp;proteins. Through arginine methylation of histones, transcription &nbsp;factors and the spliceosome complex, PRMT5 regulates the expression of &nbsp;genes involved in promoting cancer cell growth and survival. These &nbsp;include cell cycle genes, tumor suppressors, oncogenes, and genes &nbsp;involved in proliferation and signaling. Overexpression and increased &nbsp;enzymatic activity of PRMT5 are associated with poor outcome and &nbsp;decreased survival in multiple human cancer settings. Consistent with &nbsp;its role in promoting cancer, PRMT5 inhibition has been shown to &nbsp;decrease tumor growth in preclinical models. Therefore, PRMT5 is &nbsp;believed to serve as an important mediator of cancer progression and can &nbsp;be targeted to treat a range of solid tumors and hematological &nbsp;malignancies.
<a href="https://preludetx.com/prmt5/">Source</a>

PRT543 (PRMT5 inhibitor)

Acute myeloid leukemia

Hematologic malignancies

Prelude is developing PRT2527, which is designed to be a potent and selective CDK9 inhibitor. PRT2527 was shown to reduce MCL1 and MYC protein levels and was highly active in preclinical models at well-tolerated doses. PRT2527 has demonstrated high potency and kinase selectivity which may offer improved efficacy and safety compared to less selective CDK9 inhibitors.

PRT2527 (CDK9 inhibitor)

Breast cancer

Glioblastoma

Head and neck cancer

Non-small cell lung carcinoma

PRT3645 (CDK4/6 inhibitor)  

Esophageal cancer

Gastric cancer

PRT3789 is a first-in-class highly selective degrader of SMARCA2 protein, which along with SMARCA4 controls gene regulation through chromatin remodeling. Cancer cells with SMARCA4 mutations are dependent on SMARCA2 for their growth and survival and selectively degrading SMARCA2 induces cell death in cancer cells while sparing normal cells. PRT3789 is efficacious and well tolerated in preclinical models of SMARCA4 deleted/mutated cancers as monotherapy and in combination with standards of care. The Company believes a selective SMARCA2 degrader has the potential to be of benefit in up to 70,000 US/EU cancer patients with the SMARCA4 mutation.
Patients with SMARCA4 mutations or deletions may have poor clinical outcomes and limited treatment options. Therefore, mutated, or deleted SMARCA4 cancers provides a potential biomarker to select those patients most likely to respond to treatment with a highly selective SMARCA2 degrader.

PRT3789 [SMARCA2 degrader]

PRT7732, Oral SMARCA2 degrader, is structurally distinct from PRT3789 and may provide clinically meaningful differences, including potential utility in earlier lines of therapy.

PRT7732 [SMARCA2 degrader]

primary central nervous system lymphomas

PRT811 (PRMT5 inhibitor) 

B-cell malignancies

Relapsed/refractory acute myeloid leukemia

PRT1419 is designed to be a potent and selective inhibitor of the &nbsp;anti-apoptotic protein, MCL1. MCL1 has been shown to have a critical &nbsp;role in promoting cancer cell survival and is frequently found to be &nbsp;amplified or overexpressed in both solid tumors and hematologic cancers. &nbsp;Inhibition of MCL1 expression and/or function is therefore of &nbsp;considerable therapeutic interest in cancer. Small molecule MCL1 &nbsp;inhibitors have been shown to be efficacious as monotherapy in &nbsp;preclinical models of multiple myeloma, acute myeloid leukemia and &nbsp;lymphoma. PRT1419 demonstrated potent and selective inhibition of MCL1 in vitro and in vivo that resulted in tumor regressions in preclinical models of hematologic malignancies following once weekly oral dosing.
<a href="https://preludetx.com/other-programs/">Source</a>

Prelude Therapeutics Incorporated

Company Details