TriMix-MEL is a rationally designed, investigational immunotherapy comprising eTheRNA's core TriMix mRNAs, which include a unique combination of three mRNAs encoding proteins that act highly synergistically via three different pathways for the optimal activation of dendritic cells (DCs), a type of dedicated immune cell also known as an antigen presenting cell (APC). TriMix-MEL also contains mRNAs encoding five melanoma-associated antigens. The phase Ib study is designed to evaluate the immunogenicity, safety and tolerability of TriMix-MEL in-vivo, which is injected directly into lymph nodes (intranodal administration) in melanoma patients.
eTheRNA has generated clear signs of clinical anti-tumor activity in previous Phase I/II trials with TriMix ex-vivo immunotherapies, where immature DCs were extracted from the patient and activated ex-vivo using TriMix in combination with melanoma-associated antigens before being re-injected. The company has also generated strong pre-clinical evidence showing that TriMix in-vivo immunotherapies are at least as effective as the ex-vivo approach in activating DCs, enhancing potent antigen-specific T-cell immunity and stimulating a directed cytotoxic T-cell response in multiple cancer models.
This new phase Ib study will evaluate the safety and tolerability of intranodal administration of TriMix-MEL in stage IIc/III/IV melanoma patients after surgical removal of their tumor lesions. The study will additionally explore the immune response following five intranodal administrations of TriMix-MEL over a period of 14 weeks. The study will be conducted in different countries including Belgium and Spain and preliminary top-line results are expected in Q3 2018.
eTheRNA plans to start several further clinical studies over the next 12 months, designed to deliver results to confirm that: TriMix can become the cornerstone for cancer immunotherapy, either as an immune activator in combination with antigens or as a tumor environment enhancer alone, and TriMix in-vivo immunotherapies can deliver clinical proof-of-concept results alone and in combination with immune checkpoint inhibitors in melanoma and breast cancer.
A number of these new studies will also be used to determine the optimal route of administration for TriMix in-vivo immunotherapies (i.e. intranodal or intratumoral).
Kajo Kallen, chief marketing officer of eTheRNA, said: "We are delighted to begin the clinical development of TriMix-MEL, the novel in-vivo immunotherapy candidate derived from our unique TriMix technology platform. Based on the success of the TriMix ex-vivo approach in treating melanoma patients, and the positive pre-clinical results we have generated with an in-vivo approach, we are confident that TriMix-MEL has the potential to provide this patient population with improved treatment outcomes. We look forward to reporting the results from the Phase 1b study later in 2018."
Dirk Reyn, chief executive officer of eTheRNA, said: "This first patient in our own oncology clinical trial with TriMix-MEL represents an important milestone for eTheRNA and is a significant step from an academic spin-off to an independent biotech company. We are looking forward to generating more clinical data to validate the broader use of our TriMix technology platform. Based on the data we have generated to date, we are excited by the potential of our TriMix-based in-vivo immunotherapies to deliver long-lasting clinical remission, alone or in combination therapy, to a broad range of cancer patients so they can enjoy more years of good quality life."
