8-K: Aprea Therapeutics Highlights Pipeline Progress at AACR Annual Meeting, Provides Clinical Trial Updates

Aprea Therapeutics announced details of four poster presentations at the AACR Annual Meeting, showcasing their next-generation WEE1 inhibitor, APR-1051, and a novel macrocyclic ATR inhibitor, ATRN-119.

Summary

• Aprea Therapeutics presented four posters at the American Association of Cancer Research (AACR) Annual Meeting, focusing on their WEE1 inhibitor, APR-1051, and ATR inhibitor, ATRN-119.
• Pre-clinical data for APR-1051 suggests it is a potent and selective WEE1 inhibitor with low off-target effects, particularly on the PLK family of kinases.
• APR-1051 has shown effectiveness in suppressing the growth of Cyclin E-overexpressing breast and ovarian cancer cell lines in mice, with minimal impact on red blood cell and platelet counts.
• The IND for APR-1051 has been cleared, and a Phase 1 clinical trial (ACESOT-1051) is planned to begin in June 2024, enrolling up to 79 patients with advanced solid tumors.
• ATRN-119, a macrocyclic ATR inhibitor, continues to show a good safety profile in an ongoing Phase 1/2a study, with no dose-limiting toxicities reported in 16 patients as of March 12, 2024.
• Preliminary signs of clinical benefit have been observed with ATRN-119, including stable disease in two patients, one of whom has been on treatment for 188 days.
• Aprea also presented pre-clinical data on ATRN-333, a next-generation macrocyclic ATR inhibitor, showing synergistic effects with lomustine in glioblastoma treatment using convection-enhanced delivery.
• The company has a strong intellectual property portfolio with four issued US patents protecting their lead molecules and analogs.
• Aprea had $21.6 million in cash and equivalents as of December 31, 2023, and closed a $16 million private placement in March 2024, with potential for an additional $18 million from warrant exercises.

Sentiment

Score: 8

Explanation: The document presents a positive outlook with promising pre-clinical and early clinical data, along with a clear path forward for their drug development programs. The company has also secured additional funding, which is a positive sign.

Positives

• APR-1051 shows high potency and selectivity for WEE1 inhibition with minimal off-target effects, suggesting a potentially safer profile.
• Pre-clinical data for APR-1051 indicates effectiveness against Cyclin E-overexpressing cancers and good tolerability in mice.
• The IND clearance for APR-1051 allows for the initiation of a Phase 1 clinical trial in June 2024.
• ATRN-119 has demonstrated a favorable safety profile with no dose-limiting toxicities in the ongoing Phase 1/2a study.
• Preliminary clinical benefit has been observed with ATRN-119, including stable disease in two patients.
• ATRN-333 shows promise as a chemosensitizer for glioblastoma when combined with lomustine and delivered via convection-enhanced delivery.
• The company has a strong intellectual property portfolio with multiple patents protecting their lead molecules.
• Aprea's recent private placement provides additional funding to support ongoing clinical trials.

Negatives

• The clinical trials for both APR-1051 and ATRN-119 are still in early stages, and efficacy data is preliminary.
• The company is dependent on additional financing to fund operations and complete the development and commercialization of their product candidates.
• The company has a limited history and the assets were acquired from Atrin Pharmaceuticals Inc.

Risks

• The success of clinical trials for APR-1051 and ATRN-119 is not guaranteed, and results may not meet expectations.
• The company's ability to secure additional funding may impact its ability to continue operations and development programs.
• There are risks associated with the interpretation of preclinical and early clinical results, which may not be indicative of final results.
• The company faces competition from other companies developing similar therapies.
• Regulatory and political developments could impact the company's ability to bring its products to market.

Future Outlook

Aprea anticipates several clinical milestones in 2024 and 2025, including completing dose escalation for ATRN-119, initiating the Phase 1 trial for APR-1051, and reporting efficacy data for both programs. The company is financed into 3Q 2025 and is evaluating strategic partnerships.

Management Comments

• Dr. Oren Gilad, President and CEO of Aprea, stated that the four poster presentations at AACR highlight the company's growing pipeline and commitment to helping cancer patients.
• Dr. Gilad also expressed pleasure in sharing the strong pre-clinical data and future clinical strategy for APR-1051 and excitement about the encouraging update on the ongoing clinical study of ATRN-119.
• Nadeem Mirza, MD, MPH, Senior Medical Advisor to Aprea, commented that enrollment continues in the dose escalation portion of the ATRN-119 trial and that they are encouraged by the preliminary signs of clinical benefit.

Industry Context

Aprea is operating in the competitive field of precision oncology, focusing on synthetic lethality through DDR inhibition. The company's focus on ATR and WEE1 inhibitors aligns with the industry's interest in targeting DNA damage response pathways for cancer treatment. The development of macrocyclic inhibitors and the emphasis on continuous dosing are differentiating factors in the ATR inhibitor space.

Comparison to Industry Standards

• Aprea's ATRN-119 is a macrocyclic ATR inhibitor, which is structurally different from first-generation acyclic ATR inhibitors like AstraZeneca's AZD6738 and Bayer's BAY1895344.
• Unlike some other ATR inhibitors that use intermittent dosing schedules, ATRN-119 is designed for continuous daily dosing, which Aprea believes may lead to better tumor control.
• Preclinical studies suggest that Aprea's APR-1051 has a higher selectivity for WEE1 and lower off-target inhibition of PLK kinases compared to Zentalis's Azenosertib (ZN-c3).
• Aprea's APR-1051 also shows a potentially favorable pharmacokinetic profile compared to other WEE1 inhibitors, with higher Cmax and AUC values in preclinical studies.
• Aprea's preclinical data suggests that APR-1051 has negligible inhibition of hERG channels, which is a potential advantage over some competitor WEE1 inhibitors that have reported QT prolongation AEs.
• The company's approach to glioblastoma treatment using convection-enhanced delivery of ATRN-333 is a novel approach compared to standard systemic drug delivery methods.

Stakeholder Impact

• Shareholders may view the positive clinical updates and financial news favorably.
• Employees may be encouraged by the progress of the company's pipeline.
• Patients with cancer may benefit from the development of new treatment options.
• Potential partners may be interested in the company's promising drug candidates.

Next Steps

• Aprea plans to initiate the Phase 1 clinical trial for APR-1051 in June 2024.
• The company will continue dose escalation in the Phase 1/2a trial for ATRN-119 throughout 2024.
• Aprea anticipates completing dose escalation for ATRN-119 in 4Q 2024 and reporting RP2D in 1Q 2025.
• The company plans to enroll the first patient in the Phase 1/2a monotherapy dose expansion for ATRN-119 in 1Q 2025.
• Aprea expects to report additional open-label efficacy data for ATRN-119 in 3Q 2025.
• The company will continue to evaluate strategic partnerships.

Key Dates

Keywords

WEE1 inhibitor, ATR inhibitor, APR-1051, ATRN-119, ATRN-333, cancer, clinical trial, synthetic lethality, precision oncology, DDR, AACR, glioblastoma, Cyclin E, biomarker, solid tumors