Immunity to Fight Cancer

About

CHIME BioTherapeutics is an immuno-oncology company focused on the development of cancer immunotherapies based on the breakthrough concept of recalling and harnessing pre-existing, natural immune memory from childhood vaccines to treat a variety of cancers. CHIME’s disruptive approach is to recall long-lived immune responses from certain childhood vaccines and redirect them against cancer cells after administration of a biologic, CBTx-500 (viral vector expressing childhood vaccine T-cell epitopes). CHIME is the first corporate spin-off from La Jolla Institute for Allergy and Immunology (LJI, San Diego), one of the top five biomedical research institutes in the world uniquely focused on understanding the immune system in relation to human diseases such as cancer. CHIME has worldwide exclusive licenses to specific intellectual property from LJI. CHIME leverages expertise, know-how and bioinformatics tools that have been developed for validated epitopes at LJI. CHIME was selected for residency at JLABS in San Diego in May 2017. CHIME's innovative biologic (CBTx-500) is envisioned to promote the recruitment and activation of pre-existing vaccine-derived memory T cells to the cancerous tissue. By selective administration of CBTx-500 to tumor cells, a rapid, potent, non-self-derived CD8 and CD4 T-cell response is expected to (i) increase immune cell infiltration into the tumor, (ii) induce more rapid direct tumor killing, (iii) diminish tumor-mediated immune suppression due to the inflammatory response, and (iv) drive the development of a systemic tumor-specific immunity through release of tumor-associated antigens that are taken up by antigen presenting cells and presented to T cells to generate tumor-specific effector cells and tumor- specific immune memory. Cancer-specific epitope presentation is achieved through available viral vectors. Tumor presentation of CBTx-500 is designed to lead to childhood vaccine-derived memory T -cell expansion, activation, and tumor cell killing. T -cell-mediated tumor killing causes a cascade of events: T-cell cytolytic effect induces inflammation and thereby reduces tumor-mediated immune suppression; The inflammatory response enables expansion and activation of resident tumor-specific immune cells (TILs) and allows infiltration of a variety of new immune cells (e.g., monocytes, macrophages, dendritic cells, B cells and T cells) to the tumor site; The co-localization and activation of these cells enables a broader immune reaction that creates new tumor-specific immune cells and the eventual development of systemic tumor-specific immune memory. 
 The approach of recalling pre-existing memory T cells, initially generated by standard childhood vaccines, to produce a robust memory cellular response directed against tumors is unique and differentiated through several key functional attributes: Leverage of pre-existing immune memory from safe and routinely administered childhood vaccines; Promotion of rapid, non-self, tumor-targeted cytolytic activity; Less stringent requirements for activation than naïve T cells; 
 Memory T cells respond to lower doses of peptide antigen(s) with greater magnitude Memory T-cell activation is less dependent on costimulatory signals and not dependent on long duration of antigenic stimulation Production of a wider array of inflammatory and/or antiviral cytokines; 
 Contribution to the development of tumor-specific systemic immunity and reduction 
of tumor immune suppression; 
 No requirement for time/cost consuming ex vivo culture and transplantation (e.g., 
CAR-T cells); 
 Administration in vivo as conventional biologics and amenable to delivery through 
numerous platforms; and 
 Potential treatment of a variety of cancer types. 
 CHIME BioTherapeutics has raised initial seed funding and is currently conducting preclinical studies to validate the proof-of-concept in tumor models.  Additional funding will be used to complete the preclinical studies and perform the human product candidate selection over 12-18 months, with i) recruitment of healthy volunteers with different HLA background and ethnicity for blood donation under IRB approval (pre-and post-booster vaccine), ii) synthesis of the predicted peptide epitopes from childhood vaccines and generation of peptide pools based on HLA class, specific virus and viral antigen, iii) testing of peptide pools for T-cell reactivity in donor PBMCs, iv) deconvolution of positive peptide pools to identify individual CD8+ and CD4+ T-cell epitopes, v) selection of epitopes with the greatest frequency and magnitude of cytokine responses that provide diverse HLA coverage and vi) incorporation of epitope sequence into a viral vector for delivery to tumors. Upon completion of the two milestones described above, IND-enabling studies will be initiated.  Those will include the evaluation of CBTx-500 in safety/toxicology GLP studies, including a biodistribution study, the preparation of detailed clinical plans for the Phase 1b/2 study in a cancer indication, the scale-up and cGMP manufacturing of CBTx-500 and the preparation and regulatory filing of an Investigational New Drug (IND) application.  Following the allowance of an IND, CBTx-500 will be evaluated in a Phase 1b/2 clinical study in cancer patients (e.g., bladder cancer) and an application for orphan drug designation will be filed.