Ascendis Pharma Shares New Data and Updates from Phase 1/2 IL-Believe Trial at ASCO 2024

COPENHAGEN, Denmark, June 03, 2024 — Ascendis Pharma, Inc. has shared significant findings from its ongoing Phase 1/2 IL-Believe Trial at the American Society of Clinical Oncology (ASCO) 2024 annual meeting. The data showcases new outcomes from the trial assessing TransCon IL-2 β/γ, either as a standalone treatment or in combination with other agents, for patients with advanced or metastatic solid tumors.

Key Findings from the IL-Believe Trial

1. Combination Therapy Success: In the Phase 2 dose expansion Cohort 4, which involved treating anti-PD-1 refractory melanoma with a combination of TransCon IL-2 β/γ and TransCon TLR7/8 Agonist, 40% of efficacy-evaluable patients (2 out of 5) exhibited confirmed clinical responses. This indicates a potential synergistic effect of the combination therapy with no new safety concerns emerging.

2. Monotherapy and Combination Efficacy: Among patients who experienced disease progression on checkpoint inhibitors, 45% (5 out of 11) demonstrated confirmed clinical responses to TransCon IL-2 β/γ, whether used alone or in combination therapy. Specifically:
- Monotherapy: Out of 4 patients, one displayed a partial response in colorectal cancer.
- Combination with Pembrolizumab: In 2 patients, one achieved a complete response and another a partial response in cases of small-cell lung cancer.
- Combination with TransCon TLR7/8 Agonist: Among 5 patients, 2 showed partial responses in melanoma.

3. Biomarker Analysis: The biomarker studies revealed consistent cytotoxic immune cell expansion in both monotherapy and combination therapy with pembrolizumab. Administration of TransCon IL-2 β/γ was linked to an upsurge in cytotoxic lymphocytes and elevated cytokine and chemokine levels in the blood, without an increase in Tregs or eosinophils, which are markers of toxicity. A significant correlation was noted between clinical benefits and the expansion and activation of CD8+ T cells.

4. Safety and Tolerability: The trial indicated that TransCon IL-2 β/γ, whether administered alone or with pembrolizumab or TransCon TLR7/8 Agonist, was generally well tolerated, and no new safety signals were identified.

Dr. Stina Singel, Executive Vice President and Head of Clinical Development, Oncology at Ascendis Pharma, expressed optimism about the clinical response and safety profile of TransCon IL-2 β/γ. She highlighted the therapy's ability to recruit and amplify the body’s immune response while maintaining safety. These findings support TransCon IL-2 β/γ as a pioneering IL-2 cytokine therapy that not only shows efficacy as a monotherapy in a convenient outpatient setting every three weeks but also demonstrates a direct link between clinical benefit and CD8+ T cell expansion. Additional data from larger, indication-specific cohorts are anticipated later this year.

Overview of TransCon IL-2 β/γ

TransCon IL-2 β/γ is an investigational long-acting prodrug designed for sustained release of an IL-2Rβ/γ-selective analog. It aims to overcome the limitations of traditional interleukin-2 (IL-2) cancer immunotherapy by ensuring prolonged activation of IL-2Rβ/γ with a low peak concentration (Cmax). The IL-Believe Trial is assessing the safety and tolerability of this therapy alone or in combination with pembrolizumab, chemotherapy, or TransCon TLR7/8 Agonist in patients with locally advanced or metastatic solid tumors. The recommended Phase 2 dose (RP2D) for TransCon IL-2 β/γ is 120 µg/kg, administered intravenously every three weeks in an outpatient setting.

About Ascendis Pharma

Ascendis Pharma is a biopharmaceutical company that utilizes its proprietary TransCon technology platform to develop innovative therapies aimed at improving patients' lives. The company is headquartered in Copenhagen, Denmark, and operates additional facilities in Europe and the United States.

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