Aprea Therapeutics, Inc. (NASDAQ:APRE) is a clinical-stage biopharmaceutical company at the forefront of the precision oncology landscape, pioneering innovative treatments that capitalize on cancer cells' unique vulnerabilities while minimizing damage to healthy cells. The company's strategic focus on synthetic lethality, an emerging approach in cancer therapeutics, has positioned it as a trailblazer in this promising field.
Business Overview and Chronology Aprea Therapeutics was originally incorporated in 2002 and commenced principal operations in 2006. Initially, the company focused on developing cancer therapeutics that reactivate the mutant p53 tumor suppressor protein. However, in December 2020, Aprea announced that its pivotal Phase 3 myelodysplastic syndromes trial failed to meet its predefined primary endpoint of complete remission rate. This setback, combined with FDA feedback and the costs associated with continuing the APR-246 development program, led to a significant shift in the company's focus.
In May 2022, Aprea acquired Atrin Pharmaceuticals Inc., marking a transformative moment for the company. This acquisition redirected Aprea's efforts towards the discovery and development of molecules targeting DNA Damage Response (DDR) pathways in oncology through synthetic lethality. The company has since discontinued significant ongoing preclinical studies and clinical trials involving APR-246, concentrating instead on its newly acquired assets.
Today, Aprea's two clinical programs - the novel oral macrocyclic ATR inhibitor, ATRN-119, and the next-generation oral inhibitor of the WEE1 kinase, APR-1051 - form the cornerstone of the company's pipeline of synthetic lethality-based cancer therapeutics. Both programs were internally discovered, developed, and evaluated by Aprea's dedicated team of scientists and clinicians.
To support its mission of developing novel synthetic lethality-based cancer therapeutics, Aprea has assembled a team with extensive experience in the discovery, development, and commercialization of oncology drugs. The company has devoted substantially all of its resources to developing its product candidates, building its intellectual property portfolio, business planning, raising capital, and providing general and administrative support for these operations.
Financial Overview As of September 30, 2024, Aprea reported $26.2 million in cash and cash equivalents, which the company believes will enable it to fund its operating expenses and capital expenditure requirements through at least the next twelve months. During the third quarter of 2024, the company reported grant revenue of $354,620 and a net loss of $3.78 million, or $0.64 per share. This compares to a net loss of $3.20 million, or $0.86 per share, in the same period of the prior year.
For the nine months ended September 30, 2024, Aprea reported grant revenue of $1.30 million and a net loss of $10.06 million, or $1.88 per share. This represents a slight improvement compared to the net loss of $10.84 million, or $3.03 per share, recorded in the same period of 2023.
Aprea has not generated any commercial revenues to date, as the company's lead product candidates, ATRN-119 and APR-1051, are still in clinical development. The company's primary sources of funding have been from the public sales of its common stock, including a recent private placement in March 2024 that raised approximately $16.0 million in gross proceeds.
For the fiscal year 2023, Aprea reported no revenue and a net loss of $14.29 million. The company's annual operating cash flow for 2023 was negative $12.18 million, with a free cash flow of negative $12.27 million. The year-over-year quarterly revenue growth was 11%, primarily due to higher grant revenue from the National Cancer Institute.
Liquidity As of September 30, 2024, Aprea reported $26.2 million in cash and cash equivalents. The company believes this will fund its operating expenses and capital expenditure requirements for at least the next twelve months. Aprea's primary sources of funding have been from public sales of common stock, including a recent private placement in March 2024 that raised approximately $16.0 million in gross proceeds.
The company's financial position as of September 30, 2024, shows a debt-to-equity ratio of 0.00, indicating no long-term debt. The current ratio and quick ratio both stand at 7.28, suggesting strong short-term liquidity. Aprea does not have any disclosed available credit lines.
Pipeline and Clinical Progress Aprea's lead product candidate, ATRN-119, is a clinical-stage oral small molecule inhibitor of the ATR kinase, a master regulator of the DNA damage response. The company is currently enrolling patients into the ABOYA-119 Phase 1/2a clinical trial to evaluate ATRN-119's safety, tolerability, and pharmacokinetics when administered on a continuous, once-daily schedule. In November 2024, Aprea announced that it had amended the study protocol to add additional patient cohorts, including a twice-daily (BID) dosing regimen, to potentially optimize the clinical outcomes for patients. Preliminary data has shown ATRN-119 to be safe and well-tolerated, with no dose-limiting toxicities and no significant hematological toxicity reported. Aprea expects potential efficacy data readout from the ATRN-119 trial in the second half of 2025.
The company's second clinical program, APR-1051, is a WEE1 inhibitor that has demonstrated in vivo anti-proliferative activity in multiple cancer cell lines. In March 2024, Aprea's IND application for APR-1051 was cleared by the FDA, and the company subsequently enrolled the first patient into the ACESOT-1051 Phase 1 dose-escalation study. Preliminary results from this trial, presented at the EORTC-NCI-AACR International Conference in October 2024, indicated that APR-1051 was safe and well-tolerated, with no unexpected toxicities observed. The ACESOT-1051 trial is evaluating doses of 10 mg to 150 mg once daily, and as of November 2024, Aprea is enrolling the fourth cohort at a 50 mg once daily dose. Aprea expects to report open-label safety and efficacy data from the APR-1051 trial in the first half of 2025.
In addition to these two clinical programs, Aprea also has an early preclinical research program focused on an undisclosed DDR target. The company is also evaluating potential combination opportunities for its product candidates, including studying the combination of ATRN-119 and APR-1051.
Intellectual Property and Exclusivity Aprea's intellectual property portfolio is a key strategic asset, providing comprehensive protection for its product candidates and technologies. The company's ATR inhibitor program is covered by a strong patent estate, including four granted U.S. patents, one pending U.S. application, and one pending provisional application. Internationally, Aprea has 19 granted non-U.S. patents and 16 pending non-U.S. patent applications. The granted patents will expire between 2035 and 2037, and the pending applications, if granted, could extend exclusivity into 2044. Additional regulatory exclusivities of up to five years may also be available.
Risks and Challenges As a clinical-stage biopharmaceutical company, Aprea faces several risks and challenges inherent to the industry. These include the inherent uncertainty of clinical development, the potential for delays or failures in clinical trials, the need for regulatory approvals, and the competition from other therapies targeting similar cancer vulnerabilities. Additionally, the company's reliance on third-party manufacturers and the potential for supply chain disruptions could impact its ability to advance its product candidates.
Aprea also faces the risk of not being able to generate sufficient revenue to achieve profitability, as the company has not yet commercialized any of its product candidates. The company's future success will depend on its ability to successfully develop, obtain regulatory approval for, and commercialize its pipeline of synthetic lethality-based cancer therapeutics.
Conclusion Aprea Therapeutics is a pioneering clinical-stage biopharmaceutical company that has positioned itself at the forefront of the precision oncology landscape. By focusing on the emerging field of synthetic lethality, the company is developing innovative treatments that target specific cancer cell vulnerabilities while minimizing damage to healthy cells. With a robust pipeline, including the promising ATRN-119 and APR-1051 programs, and a strong intellectual property portfolio, Aprea is well-positioned to continue its trailblazing efforts in this rapidly evolving oncology space. As the company navigates the challenges inherent to clinical development, its dedication to advancing its synthetic lethality-based approach may unlock new possibilities in the fight against cancer.