Aprea Therapeutics, Inc. (NASDAQ:APRE) is a clinical-stage biopharmaceutical company focused on precision oncology through synthetic lethality. The company's lead product candidate, ATRN-119, is a macrocyclic ATR inhibitor currently in a Phase 1/2a clinical trial for solid tumor indications. Aprea's pipeline also includes APR-1051, a WEE1 inhibitor, which recently received IND clearance and is expected to enter a Phase 1 dose-escalation study in the second quarter of 2024.

Business Overview

Aprea Therapeutics was originally incorporated in 2002 and commenced principal operations in 2006. Prior to the acquisition of Atrin Pharmaceuticals Inc. in May 2022, the company was engaged in the clinical development of cancer therapeutics that reactivate the mutant p53 tumor suppressor protein. However, following the failure of its pivotal Phase 3 myelodysplastic syndromes trial for eprenetapopt in December 2020, the company shifted its focus to the discovery and development of molecules targeting DNA damage response (DDR) pathways in oncology through synthetic lethality.

The company's lead product candidate, ATRN-119, is a macrocyclic ATR inhibitor currently in a Phase 1/2a clinical trial (ABOYA-119) for solid tumor indications. The primary endpoint of the Phase 1 part of the trial is to evaluate the tolerability and pharmacokinetics of ATRN-119 when administered orally on a continuous, once-daily schedule. Aprea anticipates reporting Phase 1 readout data in the first quarter of 2025.

In addition to ATRN-119, Aprea's pipeline includes APR-1051, a WEE1 inhibitor, for which the company recently received IND clearance from the FDA. Aprea plans to initiate a Phase 1 dose-escalation study (ACESOT-1051) for APR-1051 in the second quarter of 2024 and expects to report open-label safety/efficacy data in the second quarter of 2025 and the recommended Phase 2 dose in the second half of 2025.

Financials

For the full year 2023, Aprea reported total revenue of $583,231, which was primarily derived from grant funding. The company's net loss for the year was $14,286,756, with an operating cash outflow of $12,177,608 and free cash outflow of $12,270,701.

In the first quarter of 2024, Aprea reported grant revenue of $380,569, with a net loss of $2,810,091, an operating cash outflow of $3,935,891, and a free cash outflow of $3,943,869. The company's cash and cash equivalents as of March 31, 2024, stood at $32.4 million, which management believes will be sufficient to fund operations into the third quarter of 2025.

Liquidity

As of March 31, 2024, Aprea had cash and cash equivalents of $32.4 million, which the company believes will enable it to fund its operating expenses and capital expenditure requirements into the third quarter of 2025. The company's net losses were $2.8 million and $14.3 million for the three months ended March 31, 2024, and the year ended December 31, 2023, respectively.

Aprea has financed its operations primarily through the net proceeds received from the initial public offering of its common stock and subsequent sales of common stock through public and private offerings. In March 2024, the company raised approximately $14.7 million, net of underwriting discounts and offering expenses, through the sale of common stock, pre-funded warrants, and common stock purchase warrants in a private placement.

Risks and Challenges

Aprea faces several risks and challenges common to clinical-stage biopharmaceutical companies, including the uncertainty of clinical trial outcomes, regulatory approvals, and commercialization of its product candidates. The company's lead product candidate, ATRN-119, is in the early stages of clinical development, and there is no guarantee that it will successfully complete clinical trials or receive marketing approval.

Additionally, the company's pipeline is currently focused on synthetic lethality, which is an emerging therapeutic approach in oncology. While the company believes this approach has the potential to impact a wide range of cancer types, the success of this strategy is not yet proven, and there may be challenges in demonstrating the clinical benefit of its product candidates.

Aprea also faces competition from other companies developing products that target similar pathways, as well as potential challenges in manufacturing, scaling its operations, and securing adequate funding to support its ongoing research and development activities.

Outlook

Aprea has not provided specific financial guidance for the full year 2024. However, the company has stated that its existing cash and cash equivalents as of March 31, 2024, will enable it to fund its operating expenses and capital expenditure requirements into the third quarter of 2025.

The company's primary focus in 2024 will be on the continued clinical development of ATRN-119 and the initiation of the Phase 1 dose-escalation study for APR-1051. Aprea expects to report Phase 1 readout data for ATRN-119 in the first quarter of 2025 and open-label safety/efficacy data for APR-1051 in the second quarter of 2025, with the recommended Phase 2 dose expected in the second half of 2025.

Conclusion

Aprea Therapeutics is a clinical-stage biopharmaceutical company with a focus on developing novel synthetic lethality-based cancer therapies. The company's lead product candidate, ATRN-119, is currently in a Phase 1/2a clinical trial for solid tumor indications, and its pipeline also includes APR-1051, a WEE1 inhibitor, which recently received IND clearance and is expected to enter a Phase 1 study in the second quarter of 2024.

While Aprea faces the typical risks and challenges associated with clinical-stage biopharmaceutical companies, the company's focus on synthetic lethality and its promising pipeline of product candidates position it well to potentially make significant contributions to the field of precision oncology. Investors will be closely watching the company's progress in the coming years as it continues to advance its clinical programs and navigate the regulatory landscape.