Q&A: Aprea Therapeutics' Oren Gilad on WEE1 Inhibitor Data and the Company's DNA Damage Response Strategy

Oren Gilad, PhD, president and chief executive officer of Aprea Therapeutics, Inc. sat with BioPharm International® at the 2026 BIO International Convention (BIO 2026), following a presentation of updated phase 1 data for the company's WEE1 inhibitor, APR-1051, at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting,¹ which was held on May 29–June 2 in Chicago. In the interview, Dr Gilad discusses APR-1051's clinical data, differentiation, Aprea's biomarker-driven patient selection, and its position in a competitive DNA damage response (DDR) landscape, along with the company's use of artificial intelligence (AI) and the status of its ataxia telangiectasia mutated and Rad3-related (ATR) inhibitor and legacy p53 programs.

BioPharm: What clinical data did Aprea Therapeutics present at ASCO 2026 for its WEE1 inhibitor APR-1051?

Dr Gilad (Aprea Therapeutics): At Aprea, we can’t wait to cure cancer. Aprea is a precision oncology company focused on targeted therapies for biomarker-defined populations, with an emphasis on the DDR pathway. APR-1051 can be used as a single agent or in combination with other therapies. We have seen a promising dose-response relationship, with stable disease at lower doses, including a confirmed partial response at a second imaging assessment, at higher doses.^1,2 We are now expanding enrollment to include at least 50 patients with uterine serous carcinoma and platinum-resistant, cyclin E-overexpressing ovarian cancer, with dose escalation and backfill expansion expected to complete in the second quarter of 2027.¹

How does APR-1051 differentiate itself from earlier WEE1 inhibitors, and what does that mean for Aprea's financial position?

The first WEE1 inhibitor studied clinically, MK-1775, later renamed AZD1775 and also known as adavosertib, showed activity but we believe was limited by off-target kinase inhibition affecting its therapeutic window. Zentalis Pharmaceuticals later modified that scaffold to create ZN-c3, or azenosertib, designed for improved selectivity.³ For APR-1051, we built a structurally distinct molecule intended to retain WEE1 potency while minimizing off-target liabilities, including PLK [Polo-like kinase] inhibition. The initial clinical profile supported our $30 million financing, which closed in March 2026.²

How competitive is the DDR therapeutics landscape today, and where do Aprea's ATR and p53 programs fit?

The synthetic lethality and DDR landscape is competitive but it remains highly attractive because the field is expanding beyond PARP [poly(ADP-ribose) polymerase] inhibition. Tango Therapeutics, for instance, is developing a PRMT5 [protein arginine methyltransferase 5] inhibitor for MTAP [methylthioadenosine phosphorylase]-deleted tumors and recently reported a 92% objective response rate in combination with Revolution Medicines' RAS(ON) inhibitor daraxonrasib in pancreatic cancer, a different mechanism from ours.⁴ Within WEE1 inhibition, we view Zentalis as our main competitor, while Debiopharm's Debio 0123 is being developed primarily as a combination agent rather than showing single-agent clinical activity.^5,6

Within ATR inhibition, several companies have advanced clinical candidates, but the class has historically been challenged by hematological toxicity. ATRN-119, our macrocyclic ATR inhibitor, belongs to a structural class we believe is unique among ATR inhibitors in clinical development, with a cleaner side-effect profile.⁷ The opportunity is not simply to be another ATR inhibitor, but to demonstrate that ATRN-119’s pharmaceutical properties can enable clinically meaningful exposures and combination strategies that may be difficult for less selective molecules. We are seeking a partner to advance it, since financing to date has focused on APR-1051.

Aprea’s p53 program occupies a different and potentially important position. Our legacy p53 asset, eprenetapopt (APR-246), had a successful phase 2 program but narrowly missed its primary endpoint in a pivotal phase 3 trial in TP53-mutant myelodysplastic syndrome. This suggests that any future development would need to focus on a more precisely defined molecular population in which the biological effect and benefit-risk profile can be demonstrated more clearly. We are in the process of identifying the subpopulations, including in high-risk myelodysplastic syndrome and acute myeloid leukemia, most likely to benefit.⁸

What key data would most increase confidence in Aprea's lead programs, and how is AI shaping that work?

More responders, particularly within prospectively defined biomarker populations, would increase confidence the most. We expect to treat between 80 and 100 patients in the ACESOT-1051 phase 1 portion. As of the ASCO presentation, approximately 24 patients had been dosed, with dose escalation expected to complete in the first half of 2027.^2,3 In this heavily pretreated population, I would put the bar for meaningful activity at an objective response rate of 30% to 40% with responses lasting around six months.

Identifying the right biomarker and synthetic lethal interaction is the difference between success and failure, which is why we invest heavily in translational research. We use AI to screen published clinical and preclinical data, identify patterns to help prioritize the patient populations most likely to respond, alone or in combination. AI helps but every hypothesis must be validated experimentally and ultimately in patients.

What would success look like for the company over the next 5 years?

Over the next 5 years, success would mean translating our science into meaningful and durable benefits for patients. Success means helping as many patients as we can and demonstrating they receive real benefit while experiencing fewer side effects than with chemotherapy; that mission is personal to me, since my mother ultimately stopped chemotherapy because she could not tolerate another round. On the investor side, success means a good return for the confidence our investors have shown us.

We plan to continue sharing data at upcoming medical conferences.

BIO 2026 occurred June 22–25 in San Diego. Watch a video interview with Dr Gilad here.

Explore more of our conference coverage here.

References

1. Aprea Therapeutics. Aprea Therapeutics presents updated phase 1 data on WEE1 inhibitor APR-1051 at ASCO 2026, demonstrating early monotherapy activity and manageable tolerability in advanced solid tumors. Published June 1, 2026. Accessed July 13, 2026. https://ir.aprea.com/news-releases/news-release-details/aprea-therapeutics-presents-updated-phase-1-data-wee1-inhibitor
2. Aprea Therapeutics. Aprea Therapeutics reports first quarter 2026 financial results and provides a corporate update. Published May 13, 2026. Accessed July 13, 2026. https://ir.aprea.com/news-releases/news-release-details/aprea-therapeutics-reports-first-quarter-2026-financial-results
3. ClinicalTrials.gov. Study of APR-1051 in Patients With Advanced Solid Tumors (ACESOT-1051). NCT06260514. Updated April 23, 2026. Accessed July 13, 2026. https://clinicaltrials.gov/study/NCT06260514
4. Tango Therapeutics. Tango Therapeutics announces combination of vopimetostat and daraxonrasib demonstrated 92% objective response rate in pancreatic cancer. Published June 8, 2026. Accessed July 13, 2026. https://ir.tangotx.com/news-releases/news-release-details/tango-therapeutics-announces-combination-vopimetostat-and/
5. Nelen J, Sarkar B, Jiménez-Bernad J, et al. Wee1-targeting inhibitors: from virtual screening to lead discovery. Bioorg Med Chem. 2026;138:118645. doi:10.1016/j.bmc.2026.118645
6. Debiopharm. Debiopharm advances into the clinical phase for their potent WEE1 inhibitor. Published March 5, 2020. Accessed July 13, 2026. https://www.debiopharm.com/drug-development/press-releases/debiopharm-advances-into-the-highly-anticipated-clinical-phase-for-their-potent-wee1-inhibitor/
7. Aprea Therapeutics. Aprea Therapeutics Establishes Recommended Phase 2 Dose (RP2D) for ATRN-119, Considering Combination Therapies. Published October 15, 2025. Accessed July 13, 2026. https://www.globenewswire.com/news-release/2025/10/15/3167027/0/en/Aprea-Therapeutics-Establishes-Recommended-Phase-2-Dose-RP2D-for-ATRN-119-Considering-Combination-Therapies.html
8. Aprea Therapeutics. Aprea Therapeutics announces results of primary endpoint from phase 3 trial of eprenetapopt in TP53 mutant myelodysplastic syndromes (MDS). Published December 28, 2020. Accessed July 13, 2026. https://ir.aprea.com/news-releases/news-release-details/aprea-therapeutics-announces-results-primary-endpoint-phase-3