Artios' AACR Data Success: What It Means for Aprea Therapeutics' ATRN-119 Program

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Game-Changing Results Validate ATR Inhibition Strategy

Artios Pharma recently presented breakthrough data from its STELLA Phase 1/2a trial at the American Association for Cancer Research (AACR) Annual Meeting 2025, demonstrating remarkable success with its ATR inhibitor ART0380 in combination with low-dose irinotecan. These impressive results not only validate Artios' approach but also cast a promising light on Aprea Therapeutics' (APRE) development of ATRN-119, its own ATR inhibitor.

Breaking Down Artios' Impressive Data

The STELLA trial results revealed compelling evidence for the efficacy of ATR inhibition in patients with ATM-deficient tumors:

• 50% confirmed overall response rate (cORR) in ATM-negative solid tumors at the recommended Phase 2 dose
• 37% cORR in patients with ATM-deficient (ATM-low or ATM-negative) solid tumors
• Two confirmed complete responses in heavily pretreated pancreatic cancer patients
• Partial responses across multiple tumor types including pancreatic and colorectal cancer
• Favorable safety profile suitable for long-term dosing

These results represent an unprecedented level of clinical activity for the ATR inhibitor class. The data particularly stands out considering the responses came in patients with difficult-to-treat cancers who had exhausted standard treatment options.

The Science Behind ATR Inhibition

To understand the significance of these results, it's important to grasp the underlying biology. ATR (Ataxia telangiectasia and Rad3-related) plays a crucial role in how cells respond to DNA damage and replication stress. Cancer cells often have defects in DNA repair pathways, such as ATM loss of function, making them more dependent on ATR to survive.

Artios' strategy exploits this vulnerability through what they call "triple targeting":

1. Selecting cancers with high replication stress (ATM-deficient tumors)
2. Inducing further replication stress with low-dose irinotecan
3. Preventing cellular rescue by inhibiting ATR with ART0380

This approach creates a synthetic lethality scenario where cancer cells, but not normal cells, are selectively killed.

What This Means for Aprea Therapeutics' ATRN-119

Aprea Therapeutics is developing ATRN-119, described as "a potent and highly selective first-in-class macrocyclic ATR inhibitor," targeting the same biological pathway and patient population as Artios' ART0380.

The Artios data serves as strong validation for Aprea's therapeutic strategy. Here's why investors should take note:

1. Market Validation

Artios' success effectively creates a proof-of-concept for the class, demonstrating that ATR inhibition can deliver meaningful clinical benefits in ATM-deficient tumors. This de-risks Aprea's program by validating the biological target.

2. Early Signs of Efficacy

In Aprea's ongoing ABOYA-119 trial, ATRN-119 is already showing promising early signs of single-agent activity. Three patients in the 550 mg twice daily cohort demonstrated tumor shrinkage of 7%, 14%, and 21%, respectively, even before reaching the recommended Phase 2 dose.

Most notably, these tumor reductions were achieved with ATRN-119 as a monotherapy, whereas Artios' impressive results came from combination therapy with irinotecan. If ATRN-119 continues to demonstrate single-agent activity, it could potentially offer a simpler treatment regimen with fewer side effects.

3. Differentiated Product Profile

ATRN-119 is the first macrocyclic ATR inhibitor in the clinic, which may offer advantages in terms of selectivity, pharmacokinetics, and safety profile. Aprea highlights that ATRN-119 is "designed to provide a clean safety profile and is optimized for precision-focused development."

4. Potential for Combination Strategies

Artios' success with low-dose irinotecan points to a clear development path for ATRN-119 as well. Based on Artios' data, Aprea could explore similar combination strategies to potentially achieve even greater efficacy than what's already being observed with monotherapy.

The Market Opportunity

ATM deficiency is present in up to 24% of solid tumors with high unmet medical need, according to Artios' presentation. This represents a substantial addressable market for targeted therapies like ATRN-119.

The particularly strong responses seen in pancreatic and colorectal cancer patients with Artios' ATR inhibitor are especially noteworthy. Pancreatic cancer remains one of the most challenging cancers to treat, with dismal five-year survival rates. Any therapy showing meaningful activity in this indication has significant market potential.

Current Status of ATRN-119 Development

Aprea's ABOYA-119, a Phase 1/2a trial evaluating ATRN-119 as monotherapy in patients with advanced solid tumors harboring at least one mutation in DNA damage response (DDR) genes, continues to progress:

• Six patients have demonstrated stable disease to date
• Three patients in the current dose cohort (550 mg twice daily) showed tumor shrinkage:
  • A female patient with leiomyosarcoma harboring RB1/ATM mutations achieved 21% tumor reduction
  • A male patient with acinar cell carcinoma of the pancreas harboring ATM mutation experienced 14% tumor reduction
  • A female patient with ovarian cancer harboring BRIP1 mutation showed 7% tumor reduction

Importantly, Aprea notes these results were observed at a dose level below the anticipated recommended Phase 2 dose, suggesting the potential for even greater efficacy as dose escalation continues.

Looking Ahead

Aprea expects to report preliminary safety and efficacy data from the ABOYA-119 trial in the second half of 2025, with the recommended Phase 2 dose expected to be identified in the first half of 2026.

The company reported $19.3 million in cash and cash equivalents as of March 31, 2025, providing runway into early Q2 2026 - sufficient resources to reach these important clinical milestones.

Investment Takeaway

Artios' impressive clinical data at AACR provides strong validation for the therapeutic approach that Aprea is pursuing with ATRN-119. With early signs of efficacy already observed as a monotherapy, ATRN-119 represents a potential best-in-class opportunity in the emerging field of ATR inhibition.

For investors considering Aprea Therapeutics, the Artios data serves as a significant positive catalyst and risk-reduction event, even though it comes from a competitor. It demonstrates that the biological target is valid and that patients with ATM-deficient tumors can achieve meaningful clinical responses through this approach.

If ATRN-119 continues to show efficacy as a monotherapy and proves to have a favorable safety profile, Aprea could be well-positioned to capture significant value in this emerging therapeutic space.

Disclaimer: This article is for informational purposes only and does not constitute investment advice. Consult with a financial professional before making investment decisions.

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