On May 6, 2021 Aprea Therapeutics, Inc. (Nasdaq: APRE), a biopharmaceutical company focused on developing and commercializing novel cancer therapeutics that reactivate the mutant tumor suppressor protein, p53, reported financial results for the three months ended March 31, 2021 and provided a business update (Press release, Aprea, MAY 6, 2021, View Source [SID1234579431]).
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"During our recent R&D Day presentation, we reported an analysis of available data from its Phase 3 MDS trial. We identified an imbalance in dose modifications in the experimental arm which we believe negatively impacted efficacy, particularly the primary CR endpoint," said Christian S. Schade, Chairman and Chief Executive Officer of Aprea. "We remain confident that eprenetapopt and our next-generation oral agent, APR-548, represent important potential therapeutic options for cancer patients and are encouraged by emerging data from our ongoing clinical trials. We look forward to sharing data updates from these clinical trials as well as our continued progress in expanding the opportunity for our therapies in new indications."
Business Operations Update:
The Company is conducting, supporting, and planning multiple clinical trials of eprenetapopt (APR-246) and APR-548:
Phase 3 Frontline MDS Trial — In June 2020, the Company completed full enrollment of 154 patients in a pivotal Phase 3 trial of eprenetapopt with azacitidine for frontline treatment of patients with TP53 mutant MDS. The pivotal Phase 3 trial is supported by data from two Phase 1b/2 investigator-initiated trials, one in the U.S. and one in France, testing eprenetapopt with azacitidine as frontline treatment in TP53 mutant MDS and AML patients. The data from the U.S. and French Phase 1b/2 trials were published in The Journal of Clinical Oncology in January 2021 and February 2021, respectively. In December 2020, the Company announced that its pivotal Phase 3 trial failed to meet its predefined primary endpoint of complete remission (CR) rate. Analysis of the primary endpoint at this data cut demonstrated a higher CR rate (53% more patients achieving a CR) in the experimental arm receiving eprenetapopt with azacitidine versus the control arm receiving azacitidine alone but did not reach statistical significance. Based on a thorough analysis of the current Phase 3 trial data and comparisons to the U.S. and French Phase 1b/2 trials the Company believes that despite similar types and frequency of adverse events observed in the Phase 3 experimental arm and the Phase 1b/2 trials, patients in the Phase 3 experimental arm experienced substantially more study treatment dose modifications compared to the experience in the U.S. and French Phase 1b/2 trials. The Company believes that dose modifications of eprenetapopt and azacitidine led to undertreatment in the Phase 3 experimental arm that negatively impacted efficacy, particularly the primary endpoint of CR rate. The Company continues to follow patients who remain on-study and anticipates discussing with FDA the Phase 3 data and future possible regulatory pathways in the second half of 2021.
Phase 2 MDS/AML Post-Transplant Trial – The Company has completed enrollment of 33 patients in a single-arm, open-label Phase 2 clinical trial evaluating eprenetapopt with azacitidine as post-transplant maintenance therapy in TP53 mutant MDS and AML patients who have received an allogeneic stem cell transplant. The primary endpoint of the trial is the rate of relapse-free survival (RFS) at 12 months, with a published benchmark of ~30%. An interim analysis in April 2021 showed a 62% rate of RFS at 12 months, with a median RFS of 462 days. An interim analysis of overall survival (OS) showed a 77% OS at 1 year, with a median number of events not yet reached. The Company anticipates initial results from the primary endpoint of RFS at 12 months in the second quarter of 2021.
Phase 1/2 AML Trial – The Company is currently enrolling a Phase 1/2 clinical trial evaluating the safety, tolerability, and preliminary efficacy of eprenetapopt therapy in TP53 mutant AML patients. The lead-in portion of the trial evaluated the tolerability of eprenetapopt with venetoclax, with or without azacitidine, and no dose-limiting toxicities were observed in 12 patients receiving either regimen. Based on these results, the Company has expanded the trial to treat 33 additional frontline TP53 mutant AML patients with the combination of eprenetapopt, venetoclax and azacitidine. In the 19 frontline AML patients who are evaluable for efficacy with the triplet regimen, the Company has observed a 63% CR + CRi composite response rate and a 31% CR rate. The Company anticipates completion of enrollment in the triplet regimen expansion cohort during the second quarter of 2021 and availability of preliminary response rate data from the cohort also in the second quarter of 2021.
Phase 1 NHL Trial – The Company is currently enrolling a Phase 1 clinical trial in relapsed/refractory TP53 mutant chronic lymphoid leukemia (CLL) assessing eprenetapopt with venetoclax and rituximab and eprenetapopt with ibrutinib in order to further assess eprenetapopt in hematological malignancies. The first patient was enrolled in the first quarter of 2021. The Company is also planning to evaluate the combination of eprenetapopt with venetoclax in relapsed/refractory mantle cell lymphoma.
Phase 1/2 Solid Tumor Trial – The Company is currently enrolling a Phase 1/2 clinical trial in relapsed/refractory gastric, bladder and non-small cell lung cancers assessing eprenetapopt with anti-PD-1 therapy. The dose-escalation phase of the trial enrolled 6 patients with advanced solid tumors and no dose-limiting toxicities were observed. Based on these results, the Company is enrolling expansion cohorts for patients with advanced gastric, bladder and non-small cell lung cancers and has currently enrolled 15 patients across these expansion arms. A poster presentation for this trial has been accepted for presentation at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting (abstract TPS3161).
APR-548 Phase 1 Trial — The Company’s second product candidate, APR-548, is a next-generation p53 reactivator that is being developed in an oral dosage form. The Company has planned a Phase 1 dose-escalation clinical trial evaluating the safety, tolerability, and preliminary efficacy of APR-548 with azacitidine in frontline and relapsed/refractory MDS patients. The Company anticipates the first patient to be enrolled in the second quarter of 2021.
First Quarter Financial Results
Cash and cash equivalents: As of March 31, 2021, the Company had $77.6 million of cash and cash equivalents compared to $89.0 million of cash and cash equivalents as of December 31, 2020. The Company expects cash burn for the full year 2021 to be between $30.0 million $35.0 million. The Company believes its cash and cash equivalents as of March 31, 2021 will be sufficient to meet its current projected operating requirements into 2023.
Research and Development (R&D) expenses: R&D expenses were $6.8 million for the quarter ended March 31, 2021, compared to $9.1 million for the comparable period in 2020. The decrease in R&D expenses was primarily due to decreases in clinical trial costs for (i) our pivotal Phase 3 clinical trial of eprenetapopt with azacitidine for the frontline treatment of TP53 mutant MDS which completed enrollment in Q2 2020 and (ii) our Phase 2 post-transplant MDS/AML clinical trial. These decreases were partially offset by increases in clinical trial costs for our Phase 1/2 clinical trial for the treatment of TP53 mutant AML with venetoclax and azacitidine, our Phase 1/2 clinical trial in relapsed/refractory gastric, bladder and non-small cell lung cancers assessing eprenetapopt with anti-PD-1 therapy, and our Phase 1 clinical trial in relapsed/refractory TP53 mutant chronic lymphoid leukemia (CLL) assessing eprenetapopt with venetoclax and rituximab, and eprenetapopt with ibrutinib.
General and Administrative (G&A) expenses: G&A expenses were $3.4 million for the quarter ended March 31, 2021, compared to $2.8 million for the comparable period in 2020. The increase in G&A expenses was primarily due to increases in non-cash stock-based compensation and insurance expense.
Net loss: Net loss was $9.7 million, or $0.46 per share for the quarter ended March 31, 2021, compared to a net loss of $9.4 million, or $0.45 per share for the quarter ended March 31, 2020. The Company had 21,186,827 shares of common stock outstanding as of March 31, 2021.