ImMucin

ImMucin is a 21-mer synthetic cancer therapeutic vaccine composed of a unique less studied signal peptide domain on the MUC1 antigen. ImMucin is intended to educate the patient's own immune system to control cancer by means of eliminating MUC1 positive residual tumor cells. ImMucin harbors a set of unique characters as depict in the follows list:

>Neoantigen: ImMucin's epitopes were shown to be expressed on the surface of MM tumors but unlike many other MUC1 epitopes not on naïve cells. This related to MUC1 SP neo antigen properties associated with cancer associated ER stress leading to MUC1 SP expression and the lake of MUC1 SP expression during “thymic section”.

>Tumor specific domain: Unlike other MUC1 vaccines which focus on the entire protein or against the TRA domain which appears as a soluble form in the circulation. ImMucin is a short defined cellular domain, thereby reducing potential dilution and distortion of non-specific immunity or in worst case scenario even autoimmunity.

> Diversified immunity: ImMucin harbors the ability to bind multiple MHC Class I and Class II alleles, i.e. promiscuous T-cell and B-cell epitopes. These characteristics were shown to offer;

- A broader and robust immunity of multiple T-cell clones both CD4⁺ and CD8⁺.
- Anti-tumor humoral immunity.

This combination of T and B- cell responses is important for any anti-MUC1 vaccine but was accomplished only in limited complicated products.

> Universal immunity (MHC wise): ImMucin induces a universal response e.g. it covers the majority of the MHC allelic repertoire without the need for personalization based on patients’ immune system.

> TAP-Independent presentation: ImMucin can deal with the immune escape mechanism in particular TAP-deficiencies mediated by cancer cells that can lead to chemo resistance. To the best of our knowledge, this crucial phenotype is not shared by most other vaccines.

> Sequence specific Adjuvant: Due to the unique lipophilic nature of ImMucin, it can effectively enter cells. Unlike other peptides, this property reduces the need for external sophisticated adjutants.

> Applicability for long term maintenance therapy: As a synthetic vaccine, ImMucin can be manufactured at large quantities and is therefore more appropriate for long term maintenance therapy which is known today to be more appropriate for therapeutic vaccines.

In preclinical studies including the use of MUC1 transgenic mice, ImMucin and its internal 9-mer epitopes manifested superior immunity, anti-tumor activity vs. a selection of other MUC1-TRA derived products. In addition, ImMucin’s epitopes were the most abundant MUC1 epitope in tens of non-vaccinated cancer patients.

In a Phase I/II clinical study (VAXIL-001) involving 15 MM patients, ImMucin induced a strong and specific response of both CD4+ and CD8+ T-cells in all patients, coupled with an antibody response in ~66% (10/15) of the patients. Moreover, as anticipated, ImMucin was able to cause this in patients with vastly different immune repertoires with no need for prior patient selection based on their immune MHC typing (universal immunity). Importantly, 9 out of 10 patients having abnormal soluble MUC1 blood levels prior to ImMucin therapy experienced a significant reduction in soluble MUC1. Significant reduction in the % of plasma cells in the bone marrow and other accepted measures such as M-protein and FLC was demonstrated post treatment in certain patients. Lastly, stable disease or improvement, persisting for 17.5-41.3 months (on-going) was achieved in 11/15 patients and appeared to be associated with low-intermediate PD-L1 (CD274) bone marrow levels pre- and post-ImMucin treatment.