Aprea Therapeutics Presents Results From French Phase Ib/II Clinical Trial of APR-246 (Eprenetapopt) and Azacitidine in Patients with TP53 Mutant Myelodysplastic Syndromes and Acute Myeloid Leukemia at the 25th European Hematology Association Annual Meetin

Rhea-AI Summary

Aprea Therapeutics (Nasdaq: APRE) presented updated data from its Phase 1b/2 clinical trial of APR-246 combined with azacitidine for TP53 mutant myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) at the EHA Annual Meeting. The trial showed a 75% overall response rate (ORR) and a 57% complete remission (CR) rate in evaluable MDS patients. The median overall survival (OS) was 12.1 months across all patients and improved to 13.7 months for those receiving 3 or more cycles. The results indicate significant therapeutic potential for high-risk MDS and AML patients.

Positive

• 75% overall response rate (ORR) in evaluable MDS patients
• 57% complete remission (CR) rate by IWG criteria
• 12.1 months median overall survival (OS) in all enrolled patients
• 13.7 months median OS in patients receiving 3 or more cycles of therapy
• Majority of responding patients showed decreased mutant TP53 variant allele frequency

Negative

• None.

• 57% CR and 75% ORR rate by IWG criteria in all evaluable MDS patients

• 12.1 months median OS in intention-to-treat MDS patients with 9.7 months median duration of follow-up

• 13.7 months median OS in patients receiving 3 or more cycles of therapy with 9.7 months duration of follow-up

BOSTON, June 12, 2020 (GLOBE NEWSWIRE) -- Aprea Therapeutics, Inc. (Nasdaq: APRE), a biopharmaceutical company focused on developing and commercializing novel cancer therapeutics that reactivate mutant tumor suppressor protein, p53, today announced the oral presentation of updated data from its French Phase 1b/2 clinical trial at the 25th European Hematology Association Annual Meeting (EHA). The trial is evaluating the safety and efficacy of APR-246 (eprenetapopt) in combination with azacitidine (AZA) for the treatment of TP53 mutant myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). The clinical trial is sponsored by the Groupe Francophone des Myélodysplasies (GFM).

As of the April 1, 2020 data cutoff, the overall response rate (ORR) in 28 evaluable MDS patients was 75%, with a 57% complete remission (CR) rate, by International Working Group (IWG) criteria. With a median duration of follow-up of 9.7 months, the median overall survival (OS) for all enrolled patients (n=52) was 12.1 months and in MDS patients (n=34) was 12.1 months. For patients who remained on treatment for 3 or more cycles of treatment the median OS was higher at 13.7 months versus 2.8 months for patients who were on treatment for fewer than 3 cycles. Relative to baseline, mutant TP53 variant allele frequency (VAF) was decreased in responding patients by 3 cycles of treatment, including 20 (51%) patients who achieved mutant TP53 negativity by next-generation sequencing (NGS).

“The data from this ongoing trial of eprenetapopt with azacitidine continue to be very encouraging in these most difficult-to-treat TP53 mutant MDS and AML patients, who not only have at least one TP53 mutation but the majority of whom also have high risk cytogenetic abnormalities,” said Thomas Cluzeau, M.D., co-lead investigator for the GFM trial. “We continue to observe ORR and CR rates in these patients that are substantially higher than the GFM’s experience with azacitidine monotherapy. Furthermore, with increased duration of follow-up, we now also see the emergence of highly encouraging overall survival that appears to be better than azacitidine alone or in combination with others agents in this very high-risk molecular group of patients with a TP53 mutation.”

Details of the on-demand oral presentation are as follows:

Title: APR-246 Combined with Azacitidine in TP53 Mutated Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia. A Phase 2 Study by the Groupe Francophone des Myélodysplasies (GFM)

Oral Abstract Session: Novel treatments for MDS I

Abstract: S181

About the Clinical Trial

Eligible patients in the Phase Ib/II clinical trial include hypomethylating agent (HMA) naïve, TP53 mutated MDS and AML. All enrolled patients were to receive APR-246 as a 4,500 mg fixed dose IV daily for 4 days and AZA over 7 days in 28-day cycles. The primary endpoint of the trial is CR rate.

About Aprea Therapeutics, Inc.

Aprea Therapeutics, Inc. is a biopharmaceutical company headquartered in Boston, Massachusetts with research facilities in Stockholm, Sweden, focused on developing and commercializing novel cancer therapeutics that reactivate mutant tumor suppressor protein, p53. The Company’s lead product candidate is APR-246 (eprenetapopt), a small molecule in clinical development for hematologic malignancies, including myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). APR-246 has received Breakthrough Therapy, Orphan Drug and Fast Track designations from the FDA for MDS, and Orphan Drug designation from the European Commission for MDS, AML and ovarian cancer. For more information, please visit the company website at www.aprea.com.

The Company may use, and intends to use, its investor relations website at https://ir.aprea.com/ as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation FD.

About Myelodysplastic Syndromes

Myelodysplastic syndromes (MDS) represents a spectrum of hematopoietic stem cell malignancies in which bone marrow fails to produce sufficient numbers of healthy blood cells. Approximately 30-40% of MDS patients progress to acute myeloid leukemia (AML) and mutation of the p53 tumor suppressor protein is thought to contribute to disease progression. Mutations in p53 are found in up to 20% of MDS and AML patients and are associated with poor overall prognosis.

About p53 and APR-246 (eprenetapopt)

The p53 tumor suppressor gene is the most frequently mutated gene in human cancer, occurring in approximately 50% of all human tumors. These mutations are often associated with resistance to anti-cancer drugs and poor overall survival, representing a major unmet medical need in the treatment of cancer.

APR-246 (eprenetapopt) is a small molecule that has demonstrated reactivation of mutant and inactivated p53 protein – by restoring wild-type p53 conformation and function – and thereby induce programmed cell death in human cancer cells. Pre-clinical anti-tumor activity has been observed with APR-246 in a wide variety of solid and hematological cancers, including MDS, AML, and ovarian cancer, among others. Additionally, strong synergy has been seen with both traditional anti-cancer agents, such as chemotherapy, as well as newer mechanism-based anti-cancer drugs and immuno-oncology checkpoint inhibitors. In addition to pre-clinical testing, a Phase 1/2 clinical program with APR-246 has been completed, demonstrating a favorable safety profile and both biological and confirmed clinical responses in hematological malignancies and solid tumors with mutations in the TP53 gene.

Forward-Looking Statement
Certain information contained in this press release includes “forward-looking statements”, within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, related to our clinical trials, regulatory submissions and projected cash position. We may, in some cases use terms such as “predicts,” “believes,” “potential,” “continue,” “anticipates,” “estimates,” “expects,” “plans,” “intends,” “targeting,” “confidence,” “may,” “could,” “might,” “likely,” “will,” “should” or other words that convey uncertainty of the future events or outcomes to identify these forward-looking statements. Our forward-looking statements are based on current beliefs and expectations of our management team that involve risks, potential changes in circumstances, assumptions, and uncertainties. Any or all of the forward-looking statements may turn out to be wrong or be affected by inaccurate assumptions we might make or by known or unknown risks and uncertainties. These forward looking statements are subject to risks and uncertainties including risks related to the success and timing of our clinical trials or other studies, risks associated with the coronavirus pandemic and the other risks set forth in our filings with the U.S. Securities and Exchange Commission. For all these reasons, actual results and developments could be materially different from those expressed in or implied by our forward-looking statements. You are cautioned not to place undue reliance on these forward-looking statements, which are made only as of the date of this press release. We undertake no obligation to publicly update such forward-looking statements to reflect subsequent events or circumstances.

Source:  Aprea Therapeutics, Inc.

Corporate Contacts:

Scott M. Coiante
Sr. Vice President and Chief Financial Officer
617-463-9385

Gregory A. Korbel
Vice President of Business Development
617-463-9385

FAQ

What were the results of Aprea Therapeutics' Phase 1b/2 clinical trial for APR-246?

The trial reported a 75% overall response rate and a 57% complete remission rate in evaluable MDS patients, with a median overall survival of 12.1 months.

What does the median overall survival (OS) indicate for patients in the trial?

The median OS of 12.1 months for all patients and 13.7 months for those on treatment for 3 or more cycles suggests improved outcomes for high-risk MDS and AML patients.

What is the significance of the trial's findings for TP53 mutant patients?

The trial findings indicate that APR-246 combined with azacitidine may offer a considerable therapeutic advantage for difficult-to-treat TP53 mutant MDS and AML patients.

What further steps will Aprea Therapeutics take after the trial results?

Aprea Therapeutics is likely to continue its clinical development efforts and may explore regulatory submissions based on the encouraging trial outcomes.