TLC178


Soft Tissue Sarcoma (STS)
There are more than 50 histological subtypes of STS, which are associated with unique clinical, prognostic and therapeutic features. The rarity and heterogeneity of the disease render STS difficult to study and to treat. In the United States, the incidence of diagnosed STS is approximately 12,310 new cases per year, leading to approximately 5,000 deaths annually. The heterogeneity of STS poses a challenge to a standard chemotherapy approach. For most patients with unresectable or metastatic disease, chemotherapy is primarily palliative. Ifosfamide and doxorubicin are routinely used for these patients, with response rates of 50 to 60%. However, it is unclear if the treatment improves overall survival, which remains at approximately 12 to 18 months for these patients. Other treatment options for second-line therapeutic regimens remain very limited and are only recommended for palliative therapy.

Rhabdomyosarcoma (RMS)
RMS is a tumor that develops from skeletal muscle precursors. It often affects children in the first decade of their lives and results in tumors that are located at various sites in the body such as the head, neck, arms, legs, trunk and urinary and reproductive organs. RMS is a rare disease with 350 new cases diagnosed in the United States each year. Surgical excision of the tumor, when possible, is the primary treatment for RMS. However, for patients with advanced disease, prognosis is poor. Current recommendations include multidrug chemotherapy, often containing vincristine, dactinomycin and cyclophosphamide. Less than 20% of patients with metastatic RMS respond to aggressive multimodality treatment, and up to 30% of RMS patients relapse within three years of diagnosis. Most patients with recurrent RMS will die within one year of relapse (a median survival time of 0.82 years), and, with a five-year survival rate of less than 20%, there are currently no established guidelines for chemotherapy in the relapse setting. Little meaningful improvement in the treatment of this disease has been observed over the last 30 years. 


Non Small Cell Lung Carcinoma (NSCLC)
According to a 2017 American Cancer Society analysis, lung cancer is the leading cancer death in the United States with 155,870 deaths every year. Lung cancer is also the second most common cancer in the United States with 222,500 new cases annually. NSCLC constitutes 80% of all types of lung cancer. Adenocarcinoma and squamous cell carcinoma are major histological subtypes of NSCLC. Most patients are diagnosed with advanced disease and cannot be cured. Immunotherapy, several targeted therapies and platinum-based doublet chemotherapy are first-line treatment options for advanced disease.

For those NSCLC patients without driver mutations and with low PD-L1 expression, combination cytotoxic chemotherapies are recommended as first-line treatment according to the 2017 American Society of Clinical Oncology Clinical Practice Guideline. For patients who progressed after first line combination cytotoxic chemotherapy who are not responsive to first-line immunotherapy or contraindicated to second line immunotherapy, there exists a need to identify a better salvage regimen to decrease the risk of cross-resistance and also reduce toxicity.

TLC178 is our proprietary NanoX formulation of the anticancer drug vinorelbine, developed for the treatment of rhabdomyosarcoma (RMS), a rare form of soft tissue sarcoma that most frequently occurs in children.

Vinorelbine is a vinca alkaloid chemotherapy agent commonly used off-label to treat RMS and other sarcomas. TLC178 is a formulation of vinorelbine loaded into liposomes, designed to reduce toxicity and improve efficacy with fewer administrations.

We are initially developing TLC178 for pediatric RMS. The increased specificity of TLC178 for tumor versus non tumor tissue through the use of our NanoX technology, which utilizes enhanced permeability and retention effects, will enable greater dose intensity, with attendant benefits in antitumor response without impairing the safety profile. TLC178 will have significantly lower myelosuppression, resulting in a lower rate of severe neutropenia. 

In parallel with the pediatric RMS study, we plan to conduct a series of trials evaluating TLC178 in STS and indications for which vinorelbine has been approved, such as non-small cell lung carcinoma.

TLC178

API

Vinorelbine 

DDS Platform

NanoX

Potential Indications

Soft tissue sarcoma / rhabdomyosarcoma /  non-small cell lung carcinoma

Advantages

  • Improved selective delivery to tumor vs non-tumor tissue
  • Higher drug concentration at tumor confers higher activity
  • Less drug to non-tumor sites to reduce myelosuppression, enabling higher dose frequency
  • Efficacy imrpovement in treatment response rate and duration of response

Development Status

Phase I/II