• The independent Data Safety Monitoring Board deemed dose level 2 safe and recommended proceeding to the final dose level 3.

Munich, Germany – December 4, 2024 – Thermosome, a pharmaceutical company specializing in targeted cancer therapies, announced today that its ongoing Phase I trial has advanced to dose level 3 (DL3). This follows the independent Data Safety Monitoring Board’s (DSMB) confirmation of dose level 2 (DL2) safety and recommendation for escalation to the final dose level (DL3). The trial assesses the company’s lead compound, THE001, in patients with heavily pretreated, locally advanced unresectable, or metastatic soft tissue sarcoma (STS) in conjunction with regional hyperthermia. To date, the safety profile remains positive, with no dose-limiting toxicities or suspected unexpected serious adverse events (SUSARs) observed at DL1 and DL2, respectively. The majority of adverse events were mild (CTCAE ≤ grade 2), reversible, and consistent with the anticipated effects of the active pharmaceutical ingredient, doxorubicin.

“Following early indications of efficacy in our ongoing trial, this marks another significant achievement for our company, demonstrating the safe administration of THE001,” stated Dr. Frank Hermann, CMO of Thermosome. “Importantly, there were no signs of renal or cardiac impairment, nor any formulation-related adverse events such as infusion reactions, thanks to the innovative liposomal formulation. No participant discontinued treatment due to adverse events. Combined with previously reported pharmacokinetic and anti-tumor activity data, the overall trial data are very promising. They highlight THE001’s potential, alongside regional hyperthermia, as a well-tolerated, innovative treatment option in STS, significantly enhancing local clinical activity with comparable systemic exposure to doxorubicin but a superior pharmacokinetic profile.”

“Having overseen various past, present, and future local treatment modality programs, the preliminary clinical data for THE001 plus regional hyperthermia are extremely encouraging – not only regarding clinical activity in a heavily pretreated soft tissue sarcoma patient population but also from pharmacokinetic and safety perspectives,” commented Prof. Alexander Eggermont, Professor of Clinical and Translational Immunotherapy at the University Medical Center Utrecht (The Netherlands) and a member of Thermosome’s Clinical Advisory Board. “For such innovative approaches, initial safety confirmation from the independent Data Safety Monitoring Board is crucial, which we now have for both DL1 and DL2. I eagerly anticipate further progress in DL3 and beyond. In my opinion, THE001 plus regional hyperthermia holds significant promise as a targeted tumor therapy in STS and beyond.”

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About Thermosome

Thermosome is a clinical-stage drug development company focused on targeted tumor therapy combined with immune stimulation for improved cancer treatment. Its core technology is a novel, proprietary tumor-targeting approach that substantially increases local drug concentrations and improves tumor penetration for enhanced clinical efficacy.

The primary clinical indication for its lead drug candidate THE001 is soft tissue sarcoma, where the company aims to improve upon the current standard of care (free doxorubicin). Thermosome’s approach enables targeted tumor treatment regardless of specific molecular targets, encompassing patient populations across all tumor subtypes. More information:

About THE001

Thermosome’s clinical-stage lead drug candidate THE001 is a thermosensitive liposomal formulation of the chemotherapeutic drug doxorubicin (DPPG2-TSL-DOX). It operates differently from conventional liposomes. Thermosome’s technology facilitates intravascular drug release triggered by mild heat using established clinical hyperthermia devices. This results in up to 15 times higher local drug concentrations within the tumor, aiming to improve clinical efficacy through a localized boost at the target site. These high local concentrations, even in poorly perfused areas, are intended to overcome drug resistance—an effect unattainable with conventional doxorubicin due to systemic toxicity. Thermosome intends to further enhance treatment efficacy through an additive immune response induced by regional hyperthermia. THE001 has potential for future development in other anthracycline-sensitive solid tumors, such as breast, bladder, and ovarian cancers.

About the Phase I Study

The Phase I, open-label, interventional dose-escalation trial, enrolling patients with locally advanced unresectable or metastatic STS, is being conducted at two German clinical sites, testing THE001 at 3 different dose levels in up to 6 cycles every 3 weeks. The initial dose level of 20 mg/m² (DL1) was well-tolerated and progressed to 40 mg/m² (DL2) in February 2024. At the final dose level, patients will receive 50 mg/m² (DL3). The study’s primary endpoints are the safety and tolerability of THE001 and the determination of the maximum tolerated dose. A secondary objective is the assessment of anti-tumor activity. Initial clinical data were presented at the CTOS 2024 Annual Meeting.

About Soft Tissue Sarcomas (STS)

STS is an atypical tumor affecting a population that includes many young patients. Locally advanced STS (LA-STS) are large invasive tumors that are difficult or impossible to surgically remove. Neoadjuvant therapy is used to shrink these tumors before surgery to enable curative-intent tumor resection. Free doxorubicin combined with ifosfamide or dacarbazine has been the standard neoadjuvant treatment for all chemosensitive LA-STS for decades. Guidelines also recommend combining DOX-based therapy with regional hyperthermia. However, with response rates below 30%, there’s a significant need for better treatment options.

Soft tissue sarcomas encompass over 50 subtypes lacking a common driver mutation, making biological targeting more challenging than physically controlled targeting with the most active agent. THE001 has received European Orphan Drug Designation for STS.

Company Contact
Thermosome GmbH
Am Klopferspitz 19
82152 Planegg/Martinsried
phone +49 89 7167760 31
media@thermosome.com

Media Inquiries
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Dr. Ludger Wess / Ines-Regina Buth
Managing Partners
info@akampion.com
Tel. +49 40 88 16 59 64 / +49 30 23 63 27 68

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