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Company Overview

Innovation: Therapeutics & drug discovery -converting oncology laboratory achievements into commercial products with market demands and regulatory approvals
Targeted Cancer(s): Multiple
Leadership: Joseph Swiader & Kenneth Sorensen, Co-Founders
Stage of Business: Early stage. Prepare to apply for clinical trial

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Opportunity
Tuning Molecules (TMs) are proteins that act to modulate or “tune” the strength of the signal transduced by the T-cell receptor (TCR) and are critical to the selection, survival and effectiveness of T-cells. As the tumor microenvironment supports tumor growth and defends against therapeutic intervention, tumor infiltrating lymphocytes become exhausted and refractory to re-activation. Tuning molecules may be new targets and treatment options to strengthen and sustain the immune system’s response to cancer.
MicroRNAs are non-coding RNAs that regulate the cell cycle and transcription factors. Certain let-7 miRNAs play an important role in the post-transcriptional translation of CD8+ T-cell differentiation and effector function. Inhibition of let-7 is a novel mechanism that sustains T-cell effector function and may expand the immune system anti-cancer strategy.
Unmet Medical Need
The diverse and complex range of cancer cases facing the clinical oncologist today requires a broader array of treatment options than are available. The recent advancements in CAR-T and TIL therapy strategies and checkpoint molecule inhibition have shown beneficial effects as tumor treatment but also have limitations efficacy and/or side effect limitations. Additional “druggable” targets are needed to sustain the immune system’s attack on cancer.
Combination therapy strategies attempt to counter the evolution of drug resistance in cancer and have shown higher responses rates than monotherapies in a number of cases. By attacking multiple mechanisms of disease, combination therapies weaken barriers to cancer treatment effectiveness but also have the potential for increased side effects. Future combination therapies need novel and safe combination.
Differentiation
Results from Nonpareil’s in vivo research shows that miRNA inhibition is a novel mechanism that significantly increases the cancer killing ability of T-cells. miRNA inhibition may be an important addition to assist current CAR-T and TILs therapies to overcome T-cell exhaustion and increase their effectiveness or be used in combination with other anti-cancer drug-regimens.
Nonpareil’s tuning molecule program is a novel technology platform of over 500 proteins that offer a multitude of targets which subtly modify the immune response and portend a treatment regime with a low side effect profile and a unique effect. The subtle effect of tuning molecules in TCR signaling suggests a low side effect profile when targeted as a therapy
Tuning molecules include cell surface proteins and intracellular proteins which provide targets for both biologics and small molecule drugs. Small molecule drugs with immune-modulating characteristics present advantages in treatment and cost optionality for the clinician and patient.
Asset Profile & Development Plan
Proof-of-concept: miRNA inhibition has demonstrated profound anti-tumor effect in vitro and in a number of mouse models of cancer
Proof-of-concept: in vitro validation experiments have been conducted on a number of tuning molecules and has resulted in a number of candidates for further development.
Safety and tolerability: no significant in vitro or in vivo safety issues have arisen in either the miRNA or the tuning molecule research programs to date.
Intellectual property: Nonpareil Biotechnologies has created inventions related to the research programs and has rights to intellectual property produced in its research programs.
Clinical development plan: (1) miRNA program next step to generate data in 2020 to support an IND application; and (2) continued in vitro screening validation of tuning molecules that generate a pipeline of candidates for in vivo validation and clinical development
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