On May 8, 2023 Prelude Therapeutics Incorporated (Nasdaq: PRLD), a clinical-stage precision oncology company, reported financial results for the first quarter ended March 31, 2023, and provided an update on recent clinical and development pipeline progress (Press release, Prelude Therapeutics, MAY 8, 2023, View Source [SID1234631173]).
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"Our recent presentations at the 2023 AACR (Free AACR Whitepaper) Annual Meeting highlight the meaningful progress we made across our clinical and preclinical pipeline programs. In addition to our clinical presentations on PRT2527 (CDK9 inhibitor) and PRT1419 (MCL-1 Inhibitor) that demonstrated differentiated and potential best-in-class PK/PD profiles of these molecules, our preclinical research demonstrated the promise of our pipeline in addressing unmet patient needs in cancer through combination approaches. Patient enrollment in the phase 1 dose escalation of PRT3789 (first-in-class SMARCA2 selective degrader) is now underway. Our teams are focused on advancing our pipeline to key milestones and we look forward to reporting further updates in the coming months," said Kris Vaddi, Ph.D., Chief Executive Officer of Prelude.
Recent Highlights
2023 AACR (Free AACR Whitepaper) Annual Meeting: Prelude participated in the 2023 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, presenting two clinical and six preclinical poster presentations. Initial safety, pharmacokinetic and pharmacodynamic profiles in solid tumors for both PRT2527 and PRT1419 were presented. Preclinical data for both the Company’s next generation CDK4/6 inhibitor, PRT3645, and the SMARCA2 degrader, PRT3789, in combination with other targeted therapies, demonstrated the combinability of these compounds with standard of care medicines and inform potential clinical development.
Program Updates and Upcoming Milestones
PRT2527- CDK9 Inhibitor Program
PRT2527, Prelude’s potentially best in class CDK9 inhibitor, is completing a solid tumor dose escalation study. In adults with advanced solid tumors, PRT2527 was generally well-tolerated with manageable neutropenia and absence of significant gastrointestinal events or hepatotoxicity. The short half-life of PRT2527 enables acute CDK9 inhibition over a defined period making it potentially suitable for weekly administration without inducing significant toxicity. The observed dose-dependent downregulation of CDK9 transcriptional targets – MYC and MCL-1 mRNA expression in PBMCs isolated from patients treated with PRT2527 –was consistent with the degree of target engagement required for preclinical efficacy. The 15 m/mg2 QW dose of PRT2527 was selected for further evaluation in dose-confirmation cohort.
The overall safety profile observed in this study supports further development of PRT2527 in combination with other targeted therapies, including in hematologic malignancies. The Company is on track to establish a RP2D in hematological malignancies in 2H 2023.
PRT1419- MCL1 Inhibitor Program
PRT1419 demonstrated an acceptable safety and tolerability profile in patients with advanced and metastatic solid tumors, with the most common TRAEs of nausea, vomiting, and diarrhea. Neutropenia was deemed to be dose related. No cardiac toxicity was observed. Pharmacokinetics/pharmacodynamics and safety data in the 80 mg/m2 QW PRT1419 dose cohort support further evaluation of this dose in future studies. Induction of activated-BAX and cleaved caspase-3 was observed at 80 and 120 mg/m2 QW PRT1419, suggesting successful MCL-1 inhibition. No tumor reductions met response criteria. Further investigation of PRT1419 in patients with hematologic malignancy is ongoing. The Company is on track to determine the RP2D in hematological RP2D and will provide a clinical update at year end.
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.
PRT3789 SMARCA2 Targeted Protein Degrader Program
Phase 1 dose escalation of PRT3789 (first-in-class selective SMARCA2 degrader) is ongoing. The Company recently presented preclinical data, showing that SMARCA2 selective degraders demonstrate anti-proliferation activity and promote cell differentiation in a wide range of indications demonstrating activity as monotherapy, as well as in combination with KRAS G12C inhibitors, chemotherapy and other targeted agents. Consistent with the Company’s plans to nominate an orally bioavailable candidate in early 2024, preclinical data at AACR (Free AACR Whitepaper) showed that oral administration of multiple internally developed compounds results in significant tumor growth inhibition of SMARCA4-deficient lung cancer xenografts at well-tolerated doses.
First Quarter 2023 Financial Results
Cash, Cash Equivalents and Marketable Securities: Cash, cash equivalents, and marketable securities as of March 31, 2023, were $172.3 million. Prelude anticipates that its existing cash, cash equivalents and marketable securities will fund the Company’s operations into the fourth quarter of 2024.
Research and Development (R&D) Expenses: For the first quarter of 2023, R&D expense decreased to $21.8 million from $22.8 million for the prior year period. Research and development expenses decreased primarily due to the timing of our clinical research programs. We expect our R&D expenses to vary from quarter to quarter, primarily due to the timing of our clinical development activities.
General and Administrative (G&A) Expenses: For the first quarter of 2023, G&A expenses were relatively unchanged as compared to the three months ended March 31, 2022.
Net Loss: For the three months ended March 31, 2023, net loss was $27.7 million, or $0.58 per share compared to $29.5 million, or $0.63 per share, for the prior year period. Included in the net loss for the quarter ended March 31, 2023, was $6.3 million of non-cash expense related to the impact of expensing share-based payments, including employee stock options, as compared to $6.8 million for the same period in 2022.