Thermosome, a clinical-stage drug development company focused on targeted tumor therapies, announced today that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to its lead compound THE001 for the treatment of soft tissue sarcomas (STS). This designation complements the ODD previously granted by the European Medicines Agency (EMA).
The FDA's decision provides Thermosome with significant benefits, including tax credits for qualified clinical trials, exemption from user fees, and seven years of market exclusivity following approval. Notably, the FDA recognized that THE001 may be clinically superior to currently approved non-liposomal forms of doxorubicin due to its potential for increased efficacy.
"We see the U.S. Orphan Drug Designation as a strong regulatory validation of the potential of our innovative approach in soft tissue sarcoma," said Dr. Pascal Schweizer, co-founder and CEO/CFO of Thermosome. "This recognition, based on preclinical and early clinical data from our Phase 1 study, marks an important milestone and is a further step into the U.S. market – the world's most important market for patent-protected drugs."
Novel Technology Platform
THE001 represents a significant advancement in targeted cancer therapy. It is a thermosensitive liposomal formulation of doxorubicin (DPPG2-TSL-DOX) with a distinct mechanism of action compared to conventional liposomal formulations.
The technology enables intravascular drug release triggered by mild heat using clinically established hyperthermia devices. This approach can achieve up to 15-fold higher local drug concentrations in tumors, potentially improving clinical efficacy by creating a concentrated therapeutic effect at the desired site of action.
These elevated local concentrations reach even poorly perfused tumor areas, potentially overcoming drug resistance mechanisms. Such targeted delivery cannot be achieved with conventional doxorubicin administration due to systemic toxicity limitations.
Thermosome aims to further enhance treatment efficacy through an additive immune response induced by regional hyperthermia. Beyond soft tissue sarcoma, THE001 shows potential for development in other anthracycline-sensitive solid tumors, including breast, bladder, and ovarian cancers.
Phase I Clinical Progress
The company is currently conducting a Phase I, open-label, interventional dose-escalation trial (NCT05858710) at two German clinical sites. The study is enrolling patients with locally advanced unresectable or metastatic STS, testing THE001 at various dose levels for up to 6 cycles every 3 weeks, with an option to extend to 12 cycles in patients showing at least disease control.
Both completed dose levels (20 mg/m² and 40 mg/m²) have been well tolerated and declared safe by the independent data safety monitoring board (DSMB). The primary endpoints of the study are safety and tolerability of THE001 and determination of the maximum tolerated dose, with a secondary objective of evaluating anti-tumor activity.
Initial clinical data were presented at the CTOS 2024 Annual Meeting, showing promising preliminary results.
Strengthened Patent Portfolio
Concurrent with the regulatory milestone, Thermosome announced a significant expansion of its intellectual property portfolio with four new PCT patent applications:
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PCT/EP2024/076239: Covers the synthetic phospholipid excipient DPPG2 incorporated into THE001, potentially providing composition of matter protection by claiming a single stereoisomer form.
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PCT/EP2024/076242: Describes a novel lipid excipient toolbox for independent adjustment of liposomal surface charge, offering enhanced control over protein corona and liposomal fate.
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PCT/EP2024/076287: Protects new lipid excipients for lipid-based nanoparticles designed for RNA/DNA delivery.
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PCT/EP2024/076319: Covers a new LNP morphology with improved dispersion stability for delivery of small molecules and genetic material.
These additions bring Thermosome's total patent families to seven, including key protections for DPPG2 composition of matter (granted in 33 countries), the specific liposomal formulation of THE001, and its dosing regimen in combination with hyperthermia.
Addressing Unmet Needs in Soft Tissue Sarcoma
Soft tissue sarcoma represents a significant unmet medical need. These rare tumors disproportionately affect younger patients and present unique treatment challenges. Locally advanced STS (LA-STS) are large invasive tumors that are difficult or impossible to surgically remove.
Current standard treatment involves neoadjuvant therapy to shrink tumors preoperatively, allowing for potentially curative surgical intervention. Free doxorubicin in combination with ifosfamide or dacarbazine has been the gold standard for neoadjuvant therapy of chemo-sensitive LA-STS for decades, often combined with regional hyperthermia as recommended by treatment guidelines.
However, with response rates below 30%, there remains a significant need for improved treatment options. The challenge is compounded by STS occurring in more than 50 different subtypes that do not share common driver mutations, making biologic targeting approaches difficult.
Thermosome's physically controlled targeting approach with THE001 potentially offers a solution that could work across multiple STS subtypes, addressing a critical gap in current treatment paradigms.
Dr. Schweizer added, "In parallel with our clinical development, we are evaluating strategic partnerships to advance THE001 and fully realize its therapeutic potential across multiple indications."
