Personalized Cancer Therapy 

PIPELINE

Proof of principal studies for other indications has begun as indicated in the following figure. These indications have been selected based on interviews with clinical oncologists, key opinion leaders, and literature findings. For consideration in selection, the cancer must present as a solid tumor that can be safely resected.

 pipelinefigure

Metaclipse has identified breast cancer, melanoma, lymphoma, prostate cancer, and renal cancer as being the initial disease targets for the clinical development and commercialization of its proprietary patient- and tumor-specific immunotherapy.

Breast Cancer
Based on preclinical studies in murine tumor models and its analysis of unmet need and commercial viability, Metaclipse anticipates that patients with breast cancer are most suited to being responsive to its patient-specific immunotherapy. While breast cancers have recently been classified into 10 different types, current diagnoses and treatments fall into three broad classes, of which patients with so-called ‘triple-negative’ breast cancer (TNBC) are those most suited to the Metaclipse approach. Women without breast cancer metastases have a 5-year survival rate of 96%, while those with metastatic breast cancer have a 5-year survival rate of 21% (U.S. National Cancer Institute’s Surveillance Epidemiology and End Results (SEER) Database).

Metaclipse anticipates its MembrexTM immunotherapy will be suitable for treating both patients with so-called triple-negative breast cancers (TNBC) i.e., those not expressing estrogen receptor (ER-), progesterone receptor (PR-), and human epidermal growth factor receptor 2 (HER-2).

Patients presenting with TNBC are generally in their early 40s. Their prognosis is very poor compared to other types of breast cancers and customarily they develop metastatic tumors in their lungs, brain and distant lymph nodes.  As nodal status does not correlate with tumor size, it is difficult to predict metastasis from tumor size. Current drugs for treating patients with TNBC have limited use due to their toxicity and cell resistance and no modality based on a specific cell target has yet been developed. Some promising recent clinical data suggests that immune checkpoint blockade (Keytruda) may be beneficial for 15-20% of TNBC patients. We project, based on our preclinical work, that combining checkpoint blockade inhibition with MembrexTM will significantly increase the response rate and survival of TNBC patients.

Melanoma
Melanoma is an attractive candidate for the Metaclipse approach to personalized cancer therapy. Melanoma responds well to immunotherapies. In addition, radiation and chemotherapy do not work effectively. Therapy typically includes chemotherapy in combination with immune checkpoint blockade, however only 15-20% of patients respond to the therapy. We anticipate that MembrexTM will substantially increase the response rate when given in combination with immune checkpoint blockade.

Lymphoma
Lymphoma is a cancer of blood cells called lymphocytes. Refractory (failing to respond to initial therapy) and relapsed (reappearing after treatment) lymphomas are promising indications for the personalized immunotherapy (MembrexTM) developed by Metaclipse Therapeutics. Lymphoma was the first cancer successfully treated by an immunotherapy agent (anti-CD20 monoclonal antibody-Rituximab). Following this, several monoclonal antibodies for a number of cancer cell surface antigens were developed to treat various subtypes of lymphoma. Recently, adoptive T cell therapies using chimeric antigen receptor (CAR) - modified T cells are producing promising results in the treatment of Diffuse Large B cell Lymphoma (DLBCL) and Follicular lymphoma (FL). Although these therapies are often initially effective, the disease relapses in some patients due to a dependence upon response to a limited number of cancer cell-specific antigens or targets.  In addition, CAR-T cell therapies are costly and take several months to produce. Since MembrexTMincorporates the complete spectrum of patient-specific tumor antigens and takes less than two weeks to produce, it is an attractive cost-effective approach for treating lymphoma either as a monotherapy or in combination with other immunotherapies.

Prostate Cancer
Metaclipse anticipates that men suffering from late-stage prostate cancer could benefit significantly from its patient-specific immunotherapy. Based on analysis of the Dendreon Provenge Phase 3 clinical trial selection criteria and results, Metaclipse considers its approach to be useful for patients with metastatic, castration-resistant prostate cancer and having an expected median survival of at least 6 months.

Renal Carcinoma
Current therapy typically consists of nephrectomy or partial nephrectomy. Radio or cryoablation are also used in some instances. As with melanoma, renal carcinomas have responded well to immunotherapies. Immunotherapies such as Interferon-alpha, IL-2, Bevacizumab (anti-VEGF), Avastin, or mTOR inhibitors (Temsirolimus) are common first–line treatment options.  Therefore, renal cell carcinoma is also an attractive candidate for the Metaclipse approach to personalized cancer therapy.