Pipeline
Our lead candidate THE001 (DPPG2-TSL-DOX) is a thermosensitive liposomal formulation of doxorubicin (DOX). We are building a pipeline around THE001 for the treatment of DOX-sensitive tumors with locally advanced soft tissue sarcoma (LA-STS) as the lead indication. An open label, Phase I dose escalation study of THE001 in STS in combination with regional hyperthermia was initiated in April 2023.
Advantages
We aim to replace the established gold standard for the treatment of LA-STS (conventional DOX) with THE001, which has several advantages:
- Significantly improved tumor treatment efficacy
- Enabling life-saving surgery for previously unresectable tumors
- Additive immune induction through regional hyperthermia and doxorubicin-induced immunogenic cell death with the goal of preventing tumor recurrence – an added benefit in case of locally advanced solid tumors
Our vision is to offer a curative treatment option to patients with a very high unmet medical need.
Rationale
THE001 was compared to DOX in a Phase 1-equivalent animal study in cats with histologically confirmed, locally advanced feline fibrosarcomas. These naturally occurring tumors grow invasively and share clinical and biological similarities with human sarcomas. Cats treated with THE001 showed a durable anti-tumor response while animals treated with DOX showed early tumor progression (read publication).
THE001 has also been successfully tested in other settings, including bladder cancer.
Background
Soft tissue sarcomas (STS) are a heterogeneous group of tumors with more than 50 histologic subtypes that can develop at almost any anatomic site. Locally advanced STS (LA-STS) are large invasive tumors that are difficult or impossible to resect. Neoadjuvant therapy is used to shrink the tumor preoperatively and allow tumor surgery with curative intent. The current standard of care for all chemosensitive LA-STS is DOX in combination with ifosfamide or dacarbazine.
Guidelines also recommend combining DOX-based therapy with regional hyperthermia. Nevertheless, there is a very high unmet medical need in patients: response rate <30%, often unresectable tumors or extensive/function-restricting surgery, high recurrence rate, and high risk of distant metastases.