PRT3645 / Prelude Therap - LARVOL DELTA

Discovery of PRT3645, a potent and brain-penetrant next-generation CDK4/6 inhibitor (ACS-Fall 2025) - "Preclinically, this compound demonstrated a modest bias for CDK4, efficacy in brain cancer models, and good combinability with other targeted therapies. PRT3645 was advanced to an open-label Phase 1 clinical trial where it was generally well tolerated and demonstrated exposures and target inhibition consistent with levels needed for efficacy in preclinical models."

Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Solid Tumor • ER • HER-2

A Study of PRT3645 in Participants With Select Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=22 | Completed | Sponsor: Prelude Therapeutics | Active, not recruiting ➔ Completed | Trial completion date: Dec 2024 ➔ Jun 2024 | Trial primary completion date: Dec 2024 ➔ Jun 2024

Metastases • Trial completion • Trial completion date • Trial primary completion date • Brain Cancer • Breast Cancer • CNS Tumor • Endometrial Cancer • Glioblastoma • Head and Neck Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CDKN2A • CDKN2B • ER • HER-2 • KRAS • TP53

The brain penetrant CDK4/6 inhibitor, PRT3645, is highly effective in combination with other targeted therapies in preclinical models of breast cancer, CRC and NSCLC (AACR 2024) - "In preclinical studies, PRT3645 was highly efficacious when combined with other targeted therapies, offering potential benefits across a wide spectrum of cancer types. In addition, the concept of dual inhibition of CDK4/6 and CDK2 presents a rational and promising approach to enhance the efficacy of cancer therapy."

Combination therapy • Preclinical • Breast Cancer • Colorectal Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF • CDKN2A • ER • HER-2

Prelude Highlights Continued Strength of Discovery Engine at 2024 AACR Annual Meeting (GlobeNewswire) - "Next generation CDK4/6 inhibitor, PRT3645, demonstrates preclinical synergy with SERDs, as well as MEK1/2 and CDK2 inhibition. PRT3645 has the potential to improve patient outcomes when used in combination with other targeted therapies."

Preclinical • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Prelude Announces Acceptance of Multiple Preclinical Abstracts at the 2024 AACR Annual Meeting (GlobeNewswire) - '"We look forward to sharing data on the preclinical characterization of our lead oral SMARCA2 degrader, PRT7732, which is on track to advance into Phase 1 clinical development in the second half of this year, and to presenting additional preclinical data for our highly selective and potent CDK9 inhibitor, PRT2527, that supports its potential therapeutic value in combination with BTK and BCL2 inhibitors in lymphoid malignancies. For our next generation CDK4/6 inhibitor, PRT3645, we will present preclinical data supporting its potential therapeutic value in combination with other targeted therapies for a range of tumor types in addition to breast cancer.'"

New P1 trial • Preclinical • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Hematological Malignancies • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Study of PRT3645 in Participants With Select Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=22 | Active, not recruiting | Sponsor: Prelude Therapeutics | Recruiting ➔ Active, not recruiting | N=61 ➔ 22

Enrollment change • Enrollment closed • Metastases • Brain Cancer • Breast Cancer • CNS Tumor • Endometrial Cancer • Glioblastoma • Head and Neck Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CDKN2A • CDKN2B • ER • HER-2 • KRAS • TP53

Prelude Announces Strategic Pipeline Progress and Updates, including its Partnership with AbCellera, and Reports Third Quarter Financial Results (GlobeNewswire) - "(i) MCL-1 inhibitor (PRT1419):...Given the overlap with the CDK9 program, Prelude does not plan to advance PRT1419 further at this time; (ii) CDK4/6 inhibitor (PRT3645):...Given the focus of the Company on SMARCA2 and CDK9, Prelude will not advance the program further and is actively pursuing further clinical development with external partners."

Pipeline update • Hematological Malignancies • Solid Tumor

Prelude Announces Multiple Clinical and Preclinical Poster Presentations at AACR-NCI-EORTC International Conference (GlobeNewswire) - P1 | N=61 | NCT05538572 | Sponsor: Prelude Therapeutics | "Prelude Therapeutics Incorporated...announces multiple clinical and preclinical posters at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics....Initial clinical data from first three dose escalation cohorts (20, 40 and 80 mg QD) were reported. Treatment with PRT3645 was associated with a substantial decrease in pRb and Ki67 expression, indicating a high level of target engagement at the doses evaluated. PRT3645 exhibited tolerable dose escalation in the initial three dose cohorts of patients with no significant gastrointestinal, hematologic or neurological events reported to date, leveraging its enhanced selectivity profile."

P1 data • Solid Tumor

A phase 1 open-label, dose-escalation study of central nervous system–penetrant cyclindependent kinase (CDK)4/6 inhibitor PRT3645 in patients with select advanced or metastatic solid tumors. (AACR-NCI-EORTC 2023) - No abstract available

Clinical • Metastases • P1 data • Oncology • Solid Tumor

Prelude Therapeutics Announces Second Quarter 2023 Financial Results and Provides Corporate Update (GlobeNewswire) - "The Company’s objective is to establish a biologically active confirmation dose by Q1 2024....The Company intends to provide a program update by year end on the CDK9 inhibitor program and present initial results at a future scientific meeting....A Phase 1 multi-dose escalation clinical trial of PRT3645 (NCT05538572) is underway and the Company expects to reach a biologically active dose confirmation in Q4 2023....The Company intends to provide a program update by year end and present initial results at a future scientific meeting....A Phase 1 multi-dose escalation clinical trial of PRT3789 is ongoing (NCT05639751) in biomarker selected SMARCA4 mutated cancers. The Company intends to evaluate PRT3789 as monotherapy as well as in combination....The Company intends to provide a program update by year end and expects to reach confirmation dose in the first half of 2024."

P1 data • Brain Cancer • Breast Cancer • Chronic Lymphocytic Leukemia • CNS Tumor • Glioblastoma • Head and Neck Cancer • Hematological Malignancies • Leukemia • Lung Cancer • Lymphoma • Malignant Pleural Mesothelioma • Mantle Cell Lymphoma • Mesothelioma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • Solid Tumor

Prelude Therapeutics Announces Launch of Proposed Public Offering (GlobeNewswire) - "Prelude Therapeutics Incorporated...today announced that it has commenced an underwritten public offering of $100.0 million of shares of common stock and, in lieu of common stock to investors that so choose, pre-funded warrants to purchase shares of common stock. All of the shares of common stock and pre-funded warrants are being offered by Prelude. In addition, Prelude has granted the underwriter a 30-day option to purchase additional shares of its common stock in an amount equal to 15% of the securities offered in the public offering....Prelude intends to use the net proceeds from the offering, together with its existing cash and cash equivalents, to advance its current clinical pipeline, including PRT2527, PRT1419, PRT3645 and PRT3789; advance its research and discovery efforts including its efforts for a new SMARCA2 oral molecule; and support organizational growth and for working capital and other general corporate purposes."

Financing • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • B Acute Lymphoblastic Leukemia • Brain Cancer • Breast Cancer • Chronic Lymphocytic Leukemia • CNS Tumor • Ewing Sarcoma • Genito-urinary Cancer • Glioblastoma • Glioma • Head and Neck Cancer • Hematological Malignancies • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Leukemia • Liposarcoma • Lung Cancer • Lymphoma • Malignant Pleural Mesothelioma • Mantle Cell Lymphoma • Mesothelioma • Multiple Myeloma • Myelodysplastic Syndrome • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Prostate Cancer • Sarcoma • Small Lymphocytic Lymphoma • Soft Tissue Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Synovial Sarcoma • T Acute Lymphoblastic Leukemia • Thoracic Cancer • Triple Negative Breast Cancer

Prelude Therapeutics Announces First Quarter 2023 Financial Results and Operations Update (GlobeNewswire) - "PRT3645-Next Generation CDK4/6 Inhibitor Program: Prelude showed that PRT3645 is highly efficacious when combined with KRAS/MEK inhibitors, and with a brain penetrant HER2 receptor kinase inhibitor in in vivo preclinical models. Additionally, oral administration of PRT3645 induces tumor regression in palbociclib-resistant preclinical models. Dose escalation phase of PRT3645 is progressing per plan and the Company expects to provide an update by year end."

P1 data • Preclinical • Oncology • Solid Tumor

The brain penetrant CDK4/6 Inhibitor, PRT3645, is highly effective in combination with other targeted therapies in preclinical models of NSCLC, CRC, and HER2-positive breast cancer (AACR 2023) - P1 | "In preclinical studies, PRT3645 was highly efficacious when combined with KRAS/MEK inhibitors, and with a brain penetrant HER2 receptor TKI, both in-vitro and in-vivo. PRT3645 has advanced into Phase 1 clinical trials (NCT05538572)."

Combination therapy • Preclinical • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CDK1 • CDK6 • CDK9 • CDKN2A • ER • HER-2 • KRAS • RB1

Prelude Therapeutics to Present at American Association for Cancer Research 2023 Conference (GlobeNewswire) - "Prelude Therapeutics...announced details relating to eight abstracts being presented at the American Association for Cancer Research (AACR) Annual Meeting 2023, taking place April 14-19 in Orlando, Florida. 'Prelude's six preclinical and two clinical abstracts being presented at the AACR Annual Meeting highlight the important progress we are making across our pipeline. Initial safety, pharmacokinetic and pharmacodynamic profiles in solid tumors for both PRT2527 and PRT1419 support continued development of both compounds in hematological cancers'...'Additionally, we will be presenting preclinical data on our orally bioavailable SMARCA2 degrader program for the first time'...'We are also presenting preclinical data for both our next generation CDK4/6 inhibitor, PRT3645, and our SMARCA2 degrader, PRT3789, in combination with other targeted therapies."

Clinical data • Preclinical • Hematological Malignancies • Oncology • Solid Tumor

Prelude Therapeutics Reports Full Year 2022 Financial Results and Provides Corporate Update (GlobeNewswire) - "PRT3645-Next Generation CDK4/6 Inhibitor Program:...Key 2023 objective includes: Present initial Phase 1 clinical results at a medical conference in 2H 2023."

P1 data • Oncology • Solid Tumor

A Study of PRT3645 in Participants With Select Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=51 | Recruiting | Sponsor: Prelude Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open • Brain Cancer • Breast Cancer • CNS Tumor • Glioblastoma • Head and Neck Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Lung Cancer • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CDKN2A • CDKN2B • HER-2 • KRAS

Prelude Therapeutics Announces Third Quarter 2022 Financial Results and Provides Business Update (GlobeNewswire) - “Brain Penetrant CDK4/6: Phase 1 clinical trial is being initiated for PRT3645 in biomarker enriched patients with select tumor types including sarcomas, mesothelioma, gliomas, head and neck cancers and non-small cell lung cancer, in addition to breast cancer with or without brain metastases. Present initial clinical results at a medical conference in 2H 2023. RP2D in solid tumors in 2H 2024...SMARCA2/BRM Protein Degrader Program: Prelude received IND clearance in October for PRT3879. Prelude plans to dose the first patient in Q1 2023. SMARCA2 inhibition has the greatest potential in patients with SMARCA4 deficient cancers, including up to 10% of all non-small cell lung cancers. Provide Clinical update 2H 2023....In the Phase 1 trials for PRT543 and PRT811, both molecules were generally well tolerated....Full results from the two clinical trials will be shared in the first half of 2023."

P1 data • Trial status • Breast Cancer • CNS Tumor • Glioblastoma • Glioma • Head and Neck Cancer • Lung Cancer • Mesothelioma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Sarcoma • Solid Tumor

A Phase 1 Study of PRT3645 in Participants With Select Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=51 | Not yet recruiting | Sponsor: Prelude Therapeutics

New P1 trial • Brain Cancer • Breast Cancer • Glioblastoma • Head and Neck Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Lung Cancer • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CDKN2A • CDKN2B • HER-2 • KRAS

Prelude Therapeutics Announces Second Quarter 2022 Financial Results and Business Update (GlobeNewswire) - "Today, Prelude is pleased to announce the acceptance of our latest IND for PRT3645, a differentiated and highly brain penetrant CDK4/6 inhibitor....Phase 1 clinical trial, to begin in Q4, will include select cancer types including sarcomas, P16 mutated mesothelioma, gliomas, HPV negative head and neck cancers and CDK pathway-altered non-small cell lung cancer, in addition to HR+/HER2+ and HR+/HER2- breast cancer with or without brain metastases."

IND • New P1 trial • Brain Cancer • Breast Cancer • CNS Tumor • Glioblastoma • Glioma • Head and Neck Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

Prelude Therapeutics Announces First Quarter 2022 Financial Results and Operations Update (GlobeNewswire) - "As previously announced, Prelude has prioritized PRT811 for clinical development in select expansion cohorts. Prelude intends to complete the data analyses of the ongoing expansion cohorts and expects to announce next steps for the PRMT5 program in 2H2022; Prelude continues to expect to file an IND application mid-year, with the initiation of a Phase 1 trial of PRT3645 to follow in 2H2022."

Clinical • IND • New P1 trial • Oncology

Brain penetrant CDK4/6 inhibitor PRT3645 demonstrates anti-tumor activity and enhances survival in glioblastoma and breast cancer brain metastasis models (AACR 2022) - "Furthermore, PRT3645 demonstrated additive in vitro activity with fulvestrant or tucatinib in ER+ and HER2+ breast cancer lines.PRT3645 exhibits favorable in vitro safety pharmacology and ADME profiles, including brain exposure in rodents at steady state, and demonstrates oral bioavailability across rodents, dog and nonhuman primates. In a HER2+ BT474-luc orthotopic model, similarly efficacious single agent activity of PRT3645 was achieved, as well as a significant combinatorial benefit on tumor growth and median survival when administered with the brain penetrant HER2 kinase inhibitor, tucatinib. PRT3645 was highly efficacious in a U87-luc GBM orthotopic model and demonstrated enhanced median survival benefit when combined with an orally active brain penetrant PRMT5 inhibitor.In summary, PRT3645 demonstrates an excellent balance of potency, selectivity, PK parameters across species, brain penetrance and favorable tissue distribution relative to brain exposure, and..."

Breast Cancer • Estrogen Receptor Positive Breast Cancer • Glioblastoma • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Melanoma • Oncology • Solid Tumor • CDK1 • CDK2 • CDK9 • ER • HER-2 • PRMT5

Prelude Therapeutics Provides Clinical Update and Announces Presentation of New Preclinical Data at the Upcoming 2022 AACR Annual Meeting (GlobeNewswire) - "'For the PRMT5 program, which includes PRT543 and PRT811, we are concentrating our efforts on PRT811 because of its superior safety profile, higher level of target engagement, and unique brain penetrant properties. Our development efforts for PRT811 are focused on specific indications, including splicing mutated myeloid malignancies and solid tumors, including uveal melanoma, and IDH1 mutated high grade glioma. We anticipate reporting data from the ongoing dose expansion cohorts in 2H/2022'...'we believe PRT1419 has the potential to be a best-in-class MCL1 inhibitor. We look forward to reporting data from the combination study in 2H/2022.'....'An IND submission for PRT3645 is planned for mid-year, with a second IND submission for our SMARCA2/BRM candidate by year-end 2022.'"

IND • New trial • CNS Lymphoma • Glioma • Hematological Malignancies • Melanoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor