PRT1419 / Prelude Therap - LARVOL DELTA

Interferon Synergizes with Inhibition of Pro-Apoptotic Proteins to Reduce Leukemia Burden in PDX Models of ML-DS (ASH 2024) - "Pegylated interferon alfa-2a (Pegasys, 24 μg/Kg, s.c.) dosing weekly for 6 weeks significantly prolonged survival of ML-DS PDX models in vivo...These data indicate that both Navitoclax and PRT1419 synergized with Pegasys to suppress leukemia burden in ML-DS PDX model. In summary, we showed that interferon signaling is suppressed in ML-DS blasts and interferon treatment reduced ML-DS cell viability in vitro and prolonged survival in vivo. Furthermore, interferon treatment in combination with Bcl-xL or MCL1 inhibition was superior in reducing leukemia burden compared to monotherapy."

Developmental Disorders • Genetic Disorders • Hematological Malignancies • Leukemia • Oncology • BCL2L1 • GATA1 • IFIH1 • PTPRC • STAG2 • STAT1

PBRM1 loss is associated with increased sensitivity to MCL1 and CDK9 inhibition in clear cell renal cancer. (PubMed, Front Oncol) - "Increased MCL1 activity has been described as a resistance mechanism to Sunitinib and Everolimus, two approved agents for ccRCC. PRT2527, a potent CDK9 inhibitor which depletes MCL1, was similarly efficacious in monotherapy and in combination with Sunitinib in PBRM1-loss cells. Taken together, these findings suggest PBRM1 loss is associated with MCL1i sensitivity in ccRCC and provide rationale for the evaluation of PRT1419 and PRT2527 for the treatment for PBRM1-deficient ccRCC."

IO biomarker • Journal • Clear Cell Renal Cell Carcinoma • Hematological Disorders • Hematological Malignancies • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • BCL2 • PBRM1

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 Therapeutics Announces Second Quarter 2023 Financial Results and Provides Corporate Update (GlobeNewswire) - "A Phase 1 multi-dose escalation clinical trial of PRT1419 in patients with hematologic malignancies is ongoing (NCT05107856). In this trial, PRT1419 is being evaluated as monotherapy for myeloid malignancies and in combination with azacitidine or venetoclax for patients with relapsed/refractory myeloid or B-cell malignancies....The Company will provide a clinical update on PRT1419 by year end."

P1 data • Acute Myelogenous Leukemia • Follicular Lymphoma • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Non-Hodgkin’s Lymphoma • Oncology

PHASE 1 STUDY OF PRT1419 (MCL1 INHIBITOR) AS MONOTHERAPY OR IN COMBINATION WITH AZACITIDINE OR VENETOCLAX IN PATIENTS WITH RELAPSED/REFRACTORY MYELOID OR B-CELL MALIGNANCIES (ICML 2023) - "As monotherapy, pts will receive escalating doses of intravenous PRT1419 once weekly in a 28-day cycle using a 3 + 3 dose escalation design until a maximum tolerated dose (MTD) or RP2D dose has been reached. The primary endpoints include safety, tolerability, dose-limiting toxicities (DLTs), and RP2D of PRT1419 as monotherapy. Secondary endpoints include safety, tolerability, DLTs, RP2D for PRT1419 in combination"

Clinical • Combination therapy • IO biomarker • Monotherapy • P1 data • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Oncology • BCL2 • MCL1

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

MCL1 inhibitor PRT1419 demonstrates anti-tumor activity in PBRM1-altered clear cell renal cancer and synergizes with standard of care agents (AACR 2023) - "PRT1419 synergized with both Sunitinib and Everolimus in inhibiting tumor growth in various models. Taken together, these findings suggest PBRM1 loss is associated with sensitivity to MCL1 inhibition in ccRCC and provide rationale for the evaluation of PRT1419 for the treatment for PBRM1-deficient ccRCC"

IO biomarker • Clear Cell Renal Cell Carcinoma • Kidney Cancer • Leukemia • Lymphoma • Oncology • Renal Cell Carcinoma • Solid Tumor • BCL2 • PBRM1

A phase 1, open-label, dose-escalation study of PRT1419, a selective induced myeloid leukemia cell differentiation protein (MCL-1) inhibitor, in patients (pts) with advanced/metastatic solid tumors (AACR 2023) - P1 | "PRT1419 demonstrated acceptable safety and tolerability in pts with advanced/metastatic solid tumors, with primary TRAEs of neutropenia, nausea, diarrhea, and vomiting. No cardiac toxicity was observed. BAX and caspase 3 activation was observed, suggesting potentially successful MCL-1 inhibition."

Clinical • Metastases • P1 data • Brain Cancer • Breast Cancer • CNS Tumor • Hematological Malignancies • Leukemia • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • Triple Negative Breast Cancer • CASP3

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

[VIRTUAL] Preclinical characterization of PRT1419, a potent, selective and orally available inhibitor of MCL1 (AACR 2021) - P1 | "Importantly, MCL1 has been implicated in mediating resistance to chemotherapy as well as targeted therapies, including the BCL2 inhibitor, venetoclax. Further, PRT1419 demonstrated synergistic activity with tyrosine kinase inhibitors to inhibit the proliferation of breast, melanoma, and non-small cell lung cancer cell lines. PRT1419 is currently under evaluation in a Phase I clinical trial in patients with relapsed/refractory hematologic malignancies (NCT04543305)."

IO biomarker • Preclinical • Acute Myelogenous Leukemia • Breast Cancer • Diffuse Large B Cell Lymphoma • Esophageal Cancer • Gastrointestinal Cancer • Hematological Malignancies • Leukemia • Lung Cancer • Lymphoma • Melanoma • Multiple Myeloma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • BCL2L1 • CASP3

PRMT5 Inhibition Alters Mitochondrial Dynamics in Mantle Cell Lymphoma Creating Vulnerability to BH3 Mimetic Compounds (ASH 2022) - "Selectively inhibiting PRMT5 has shown significant anti-tumor activity in preclinical MCL models, and a Phase 1 clinical trial with PRT543 (Prelude), a novel PRMT5 inhibitor, is underway...Combinatorial treatment was tested in vivo using the PDX.AA.MCL model of ibrutinib resistant MCL...Navitoclax and PRT808 single agent as well as PRT808+PRT1419 regimens significantly slowed disease progression...Of note, navitoclax dosing alone or in combination did not induce additional platelet loss. Our results provide rationale for combining BH3 mimetics and PRMT5 inhibition in clinical trials as a novel treatment strategy for MCL."

IO biomarker • Hematological Disorders • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Thrombocytopenia • BBC3 • BCL2 • BCL2L1 • BCL2L2 • E2F1 • PRMT5 • RELA

A Study of PRT1419 in Patients With Relapsed/Refractory Hematologic Malignancies (clinicaltrials.gov) - P1 | N=16 | Completed | Sponsor: Prelude Therapeutics | Active, not recruiting ➔ Completed | N=36 ➔ 16 | Trial completion date: Sep 2022 ➔ Mar 2022 | Trial primary completion date: Sep 2022 ➔ Mar 2022

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Myelodysplastic Syndrome • Non-Hodgkin’s Lymphoma • Oncology

Prelude Therapeutics Announces Third Quarter 2022 Financial Results and Provides Business Update (GlobeNewswire) - "The PRT2527 Phase 1 dose escalation study in solid tumors has enrolled 11 patients to date....The Company remains on track to select a recommended Phase 2 dose by year-end….Present solid tumor dose escalation data at a medical conference in 1H 2023. RP2D in hematological malignancies in 2H 2023. Present initial clinical results for hematological malignancies at a medical conference in 2H 2023.....MCL1 Inhibitor Program: To date, 26 patients have been enrolled in the PRT1419 Phase 1 solid tumor dose escalation and confirmation cohorts, including 15 patients at the recommended expansion dose of 80 mg/m2....Solid tumor data is expected to be presented at a medical conference 1H 2023. RP2D expected in hematological malignancies in 2H 2023. Hematological malignancy data expected to be presented in 2H 2023."

P1 data • P1/2 data • Acute Lymphocytic Leukemia • Adult T-Cell Leukemia-Lymphoma • B Acute Lymphoblastic Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor

NA1-115-7, from Zygogynum pancheri, is a new selective MCL-1 inhibitor inducing the apoptosis of hematological cancer cells but non-toxic to normal blood cells or cardiomyocytes. (PubMed, Biomed Pharmacother) - "Synthetic inhibitors targeting these proteins have been developed, and some hematological malignancies are now widely treated with a BCL-2 inhibitor (venetoclax)...Six MCL-1 inhibitors (S64315, AZD-5991, AMG-176, AMG-397, ABBV-467 and PRT1419) have been evaluated in clinical trials since 2016, but some were affected by safety issues and none are currently used clinically...Importantly, a similar treatment with NA1-115-7 was not toxic to erythrocytes, peripheral blood mononuclear cells, platelets, or cardiomyocytes. These results highlight the potential of natural products for use as specific BH3 mimetics non-toxic to normal cells, and they suggest that NA1-115-7 may be a promising tool for use in cancer treatment."

IO biomarker • Journal • Hematological Disorders • Hematological Malignancies • Lymphoma • Oncology • BCL2L1

Prelude Therapeutics Announces Second Quarter 2022 Financial Results and Business Update (GlobeNewswire) - "MCL1 Inhibitor Program: Prelude remains on track to begin evaluating combinations with PRT1419 and report early findings by the end of 2022. MCL1 inhibition has potential in hematologic indications such as acute myeloid leukemia, mantle cell lymphoma and chronic lymphocytic leukemia. CDK9 Inhibitor Program: Prelude remains on track to complete dose escalation and identify a recommended Phase 2 dose for PRT2527 in the upcoming months."

Clinical data • New trial • Trial status • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

Combination of the MCL1 inhibitor PRT1419 and SMARCA2 degrader PRT3789 shows combinatorial benefit in SMARCA4 deleted lung cancer (AACR 2022) - "In a broader lung cancer cell line viability screen conducted with PRT1419, we observed that the presence of multiple, co-occurring alterations in SWI/SNF family members such as SMARCA4, ARID1A/B mutations and loss of SMARCA2 protein were associated with sensitivity to PRT1419. Based on these findings, preclinical evaluation of PRT1419 in other tumor types with recurrent SWI/SNF mutations is ongoing."

IO biomarker • Hematological Malignancies • Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • ARID1A • ARID1B • ARID2 • BCL2 • SMARCA2 • SMARCA4

Prelude Therapeutics Reports Full Year 2021 Financial Results (GlobeNewswire) - "Prelude intends to complete the data analyses of the ongoing expansion cohorts for PRT543, including adenoid cystic carcinoma (ACC). Prelude expects to report data for the PRMT5 program in 2H/2022; PRT1419...Prelude plans to initiate a combination trial with venetoclax by mid-year and report data by year-end 2022; CKD9: Prelude intends to complete enrollment in the Phase 1 dose escalation study and identify a recommended Phase 2 dose by 2H/2022; CDK4/6: Prelude intends to file an Investigational New Drug (IND) application mid-year and initiate a Phase 1 trial in 2H/2022; SMARCA2/BRM: Prelude plans to complete IND-enabling studies and submit an IND application by year-end 2022."

Enrollment status • IND • New P1 trial • New trial • Adenoid Cystic Carcinoma • Breast Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Sarcoma • Solid Tumor

Prelude Therapeutics Provides Clinical Update and Announces Presentation of New Preclinical Data at the Upcoming 2022 AACR Annual Meeting (GlobeNewswire) - "SMARCA2/BRM Protein Degrader...During 2022, Prelude intends to....Complete IND-enabling studies and submit an IND application by year-end 2022; The abstract highlights new preclinical data demonstrating synergistic benefit when PRT1419 was combined with the Company’s novel and selective SMARCA2 degrader, PRT3789, in SMARCA4 deleted lung cancer models. Potent synergistic interaction in SMARCA4 deleted cell lines was observed in vitro, whereas no additive benefit was seen in SMARCA4 WT lines."

IND • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Study of PRT1419 in Patients With Relapsed/Refractory Hematologic Malignancies (clinicaltrials.gov) - P1 | N=36 | Active, not recruiting | Sponsor: Prelude Therapeutics | Recruiting ➔ Active, not recruiting

Enrollment closed • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Myelodysplastic Syndrome • Non-Hodgkin’s Lymphoma • Oncology

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

Prelude Therapeutics Announces Second Quarter 2021 Financial Results and Operations Update (GlobeNewswire) - "Research and Development (R&D) Expenses: For the second quarter of 2021, R&D expense increased by $12.6 million to $22.4 million for the three months ended June 30, 2021 from $9.8 million for the three months ended June 30, 2020. The increase was mainly due to increased clinical research costs for the PRT543, PRT811 and PRT1419 (Oral and IV) programs, and increased chemistry, manufacturing and other costs for those trials."

Commercial • Oncology

Prelude Therapeutics Announces Second Quarter 2021 Financial Results and Operations Update (GlobeNewswire) - “PRT543…The Company expects to present data from the expansion cohorts at medical meetings throughout 2022…PRT811; Dose Expansion Portion of Phase 1 Trial Expected to Commence in 3Q21; Data from Dose Escalation Portion to be Presented at the AACR-NCI-EORTC Annual Meeting…PRT1419…The Company expects to add dose expansion and combination cohorts to the Phase 1 clinical trial in the second half of 2021…The Company remains on track to submit an Investigational New Drug (IND) application in 2021 for PRT2527, which is designed to be a potent and selective CDK9 inhibitor. In addition, the Company continues to expect to initiate IND-enabling studies for PRT-SCA2, which is designed to be a SMARCA2 protein degrader, by the end of the year.”

IND • P1 data • Trial status • Acute Myelogenous Leukemia • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • Solid Tumor

A Study of PRT1419 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=30; Not yet recruiting; Sponsor: Prelude Therapeutics

New P1 trial • Breast Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Sarcoma • Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer

Prelude Therapeutics Announces Fourth Quarter and Full Year 2020 Financial Results and Provides Operational Update (GlobeNewswire) - “Data on Preclinical Characterization to be Featured at the 2021 AACR Annual Meeting. Data on the preclinical characterization of PRT1419 will be featured during a poster session at the 2021 AACR Annual Meeting. A copy of the poster, titled ‘Preclinical characterization of PRT1419, a potent, selective and orally available inhibitor of MCL1’ (abstract 983), will be available in the Publication section of the Prelude Therapeutics website following the conclusion of the meeting.”

Preclinical • Oncology

Prelude Therapeutics Announces Fourth Quarter and Full Year 2020 Financial Results and Provides Operational Update (GlobeNewswire) - “PRT1419: Oral Formulation: Dose Expansion and Combination Cohorts Expected to be Added to Ongoing Phase 1 Trial in the Second Half of 2021. The dose escalation portion of the Company’s first-in-human Phase 1 open-label, multicenter, dose-escalation study of oral PRT1419 in patients with relapsed/refractory hematologic malignancies, including acute myeloid leukemia and high-risk myelodysplastic syndromes, remains ongoing…The Company expects to add dose expansion and combination cohorts to the Phase 1 clinical trial in the second half of 2021.”

Trial status • Acute Myelogenous Leukemia • Hematological Malignancies • Myelodysplastic Syndrome • Oncology