BACKGROUND
GI cancers cause over 3.5 million deaths per year globally, accounting for 35% of all cancer-related deaths. Colorectal carcinoma (CRC) is the world’s second leading cause of cancer death. Current immunotherapy treatments for CRC are hamstrung by low response rate, acquired resistance, relapse and severe side effects. ImmuNovation presents a disruptive nanomodular technology utilizing personalized immunotherapy as a new frontier for GI cancer patient’s treatment.

THE NEED
Dendritic cell (DC) therapies for GI cancers harness great therapeutic potential by generating immunological memory unlike passive antibodies and T-cell therapies, however, it involves ex-vivo manipulation of cancer patient’s cells which is a complex, risky, long, and expensive process. Alternative cost effective and off-the-shelf DC therapies for the treatment of GI cancer patients are urgently needed.

THE PRODUCT
Targeted Nano-Immuno-Modulator (TNM-101, TNM-201) (Fig. 1) is delivering combinations of personalized cancer peptide antigens (e.g., CEACAM5) with adjuvants and gene regulators of immunosuppressive functions (e.g., toll-like receptor (TLR)9 ligand as CpG, RNAi) into targeted circulating DC (antigen-presenting cells) in-vivo. TNM is a modular nano-platform which harnesses the capability to trigger cellular and humoral immune responses against broad types of primary and metastatic tumors by custom design of relevant peptides using bioinformatics tools.

THE ADVANTAGES
• TNM platform targeting an array of primary and metastatic tumors.
• Scalable manufacturing process (industrial-translatable).
• Easy in-vivo administration (no ex-vivo cell manipulation).
• Safe, well-characterized and fully biodegradable.
• Generates tumor-infiltrating T cells and blocks immunosuppression granting long-term memory preventing recurrence.
• Differentiates between tumor and healthy cells.

THE COMPETITION

THE STATUS
• Proven preclinical efficacy using different tumor types. TNM-101 therapy successfully reprogrammed host immunity against CEACAM5+ CRC tumors inhibiting tumor growth and prolonging survival (Fig. 2).
• TNM-101 antigen specific immunity was verified by replacing the loaded peptides to melanoma antigens. TNM-101 strongly restricted melanoma growth and prolonged survival in mice.
• Positive feedback from the FDA on the development and filing plan regulated by CDER and given a reference number.
• Safety and tolerability were confirmed in several cancer models.
• TNM does not affect primary DC viability, neither induce red blood cell lysis, change mice behavior (motor coordination, imbalance, learning and neurotoxicity), nor alters blood chemistry and count.

SEEKING
• Investments for the development of TNM-101 through the first-in-human within 24 months.

INTELECTUAL PROPERTY
Polymeric Nanovaccines and Uses Thereof – PCT/IL2019/051420 application 28 December 2019
Polymeric Nanovaccines and Uses Thereof – National phase entry 28 June 2021; US and India phase entries.
The Team

Prof. Ronit Satchi-Fainaro, Ph.D. Co-Founder
Full Professor, Sackler Faculty of Medicine, Tel Aviv university. Head, Cancer Research and Nanomedicine Laboratory; Director, Cancer Biology Research Center; The Hermann and Kurt Lion Chair in Nanosciences & Nanotechnologies; Director, Kahn 3D-BioPrinting Initiative; Director, Board of Directors of Teva Pharmaceutical Industries Ltd.; SAB member of several Hospitals, Foundations, Drug Discovery Centers, Societies and VCs.

Prof. Helena Florindo, Pharm.D., Ph.D. Co-Founder
Associate Professor with Habilitation, Faculty of Pharmacy at the University of Lisbon. Head, BioNanoSciences – Drug Delivery & Immunotherapy Research Group. Executive Board Member, Research Institute for Medicines. Member, Finance Committee FARMID-Univ. Lisbon. Co-Chair Pharmaceutics and Pharmaceutical Technology. Member, Medicines Evaluation Board, Portuguese National Medicines Agency. Expert Advisor, European Medicines Agency.