FDA Fast-Tracks AUTX-703 in Relapsed/Refractory AML

• The FDA granted fast track designation to AUTX-703 for the treatment of patients with relapsed/refractory acute myelogenous leukemia (R/R AML).
• Preclinical studies demonstrated dose-dependent survival benefits and potent KAT2A/B degradation in AML xenograft models, with significant survival advantages and increased myeloid differentiation.
• The FDA cleared the investigational new drug (IND) application for AUTX-703, with clinical trials in hematological malignancies set to begin in 2025.

The FDA has granted FTD to AUTX-703, a novel, first-in-class oral degrader of KAT2A/B, for the treatment of patients with R/R AML.¹

Auron Therapeutics, the developer of AUTX-703, plans to initiate clinical trials in patients with hematological malignancies, including AML, in the first quarter of 2025.¹ This trial plans to evaluate the safety, tolerability, and initial efficacy of AUTX-703.¹

“We are pleased that the FDA has recognized AUTX-703 as a potentially transformative treatment option for patients with relapsed or refractory AML, a group in urgent need of novel therapies. The fast track designation highlights the critical demand for innovative treatments, and we are excited to advance AUTX-703 into clinical trials, as well as to explore the broader potential of KAT2A/B modulation,” said Kate Yen, PhD, founder and chief executive officer of Auron Therapeutics, in a press release.

On February 4, 2025, the FDA also cleared the IND application for AUTX-703, enabling its clinical development.²

Acute myeloid leukemia (AML) cells: © LASZLO - stock.adobe.com

Preclinical Data of AUTX-703

Preclinically, findings presented at the 2024 American Society of Hematology (ASH) Annual Meeting demonstrated the therapeutic potential of AUTX-703 in AML.^2,3 In a primary patient AML xenograft model, NSG mice were engrafted and treated with various dosing regimens of AUTX-703 after peripheral blast levels reached approximately 3%. A vehicle control group was also included.

After 4 weeks of treatment, vehicle-treated mice showed a significant increase in peripheral blast cell levels and began to die from the disease. In contrast, mice treated with AUTX-703 demonstrated dose-dependent survival benefits. At 8 weeks, significant survival advantages were observed in 2 of the 3 dosing groups (P <.005).⁴ Notably, AUTX-703 was well-tolerated across all doses.

These findings also showed that AUTX-703 selectively degraded KAT2A/B, inducing monocytic differentiation and inhibiting cell proliferation in both AML cell lines and ex vivo patient samples. AUTX-703 exhibited dose-dependent degradation of KAT2A/B in bone marrow and spleen, accompanied by reductions in hCD45-positive/hCD34-positive blasts and increased myeloid differentiation in peripheral blood, bone marrow, and spleen.⁴

In addition to being studied in AML, the Company plans to examine AUTX-703 for the treatment of patients with solid tumors such as neuroendocrine prostate and small-cell lung cancer.²

“These preclinical data represent the first demonstration of AUTX-703’s potent KAT2A/B degradation, which promotes cellular differentiation and leads to significant survival advantages in AML models,” added Yen, in the press release.¹ “These findings further validate the capabilities of our AURIGIN platform, which is designed to identify promising oncology targets with potential across multiple cancer types.”

REFERENCES:

1. Auron Therapeutics announces AUTX-703 granted fast track designation by the FDA for relapsed or refractory acute myelogenous leukemia. News Release. Auron Therapeutics. February 24, 2025. Accessed February 24, 2025. https://tinyurl.com/mv8cnthf

2. Auron Therapeutics announces FDA clearance to initiate clinical development of AUTX-703 and completion of series B financing. News Release. Auron Therapeutics. February 4, 2025. Accessed February 24, 2025. https://tinyurl.com/afbt83kc

3. Duparc H, Neef J, Kandiah J, et al. AUTX-703, a novel and potent KAT2A and KAT2B protein degrader, induces differentiation and offers survival advantage in a primary human AML xenograft model. Blood. 2024;144(suppl 1):3585. doi:10.1182/blood-2024-208179

4. Auron presents new preclinical data for AUTX-703 in AML at ASH Annual Meeting. News Release. Auron Therapeutics. December 9, 2024. Accessed February 24, 2025. https://tinyurl.com/k855ssh3