Synergy Therapeutics is a Delaware corporation founded by BusStim LLC in 2021. The scientific founders were Jerome J Schentag PharmD and Zhiyu Li PhD. Synergy Therapeutics is leveraging the Patents defining dual agonist/antagonist peptides for p53. The cholestosome technology enabled intracellular target site potency.
This slide and video link describes the cholestosome technology that we use to enable our lead product ch-p53HSA.
The lead peptide under development at Synergy Therapeutics is ch-p53HSA. This compound has a wide therapeutic index. ch-p53HSA kills cancer cells when the cancer cells are treated with targeted kinase inhibitors, a class comprised of over 60 small molecules widely used in cancer therapy. It does not harm normal cells, as long as they are not mutating p53 or severely stressed by nucleotide modifiers.
The kinase inhibitors all have the problem of a short duration of efficacy followed by selection of tumor mutations leading to resistance. Also, as a class, they are not tumor-cidal compounds. Inhibition of enzyme pathways can be lethal to cells, but it depends very much on the concentration applied and the duration of exposure. If lower than cidal concentrations are given, the tumor simply “works around” the target block and often tumor resistance develops. In clinical use, you might only see tumor growth paused for a few weeks to a few months, and then resistance develops and the tumor resumes its growth via alternative pathways that are selected by the enzyme blockade applied. If the tumor has also mutated or inactivated the p53 pathways, the tumor generally survives and becomes resistant to the targeted kinase inhibitor. In a manner strikingly similar to the antibiotic resistance problem, it is an arms race. The tumor that mutates p53 and works around the block in the target usually wins! Of course, the tendency is to raise the dose of the kinase inhibitor in order to kill rather than only slow or stall tumor growth. When this is done, we discover that kinase inhibitors have a number of serious side effects largely based on their concentration dependent off-target actions on normal cells.
At Synergy Therapeutics, we believe we have created an alternative to tumor static action of kinase inhibitors, namely by both reactivating p53 and promoting apoptotic cell death. In technical terms, our ch-p53HSA concentrates in tumor cells preferentially and acts both non-transcriptionally and transcriptionally to restore p53 function in the cancer cell, forcing it into apoptotic cell death, instead of remaining alive with resistance. Thus we have identified our ch-p53HSA a dual agonist/antagonist. It is first-in-class since there is nothing like this at any stage of discovery or development.
ch-p53HSA is under development for use in combination therapy. Alone, it is non-toxic to normal cells and thus its full spectrum of beneficial actions require a tumor, require that tumor to be treated with compounds causing nucleic acid damage sufficient to trigger apoptotic death with or without the presence of p53 gene expression. Accordingly, Synergy Therapeutics has the primary mission to develop ch-p53HSA in synergistic combination with kinase inhibitors. We are now seeking partners and investors who share this vision, and are willing to help us get to the next steps and ultimately an FDA approval of synergistic combination therapies that are tumor-cidal, block the trend of accelerating resistance in cancers, and prolong the effective time of use for the class of Kinase inhibitors.
Here is a pitch deck describing Synergy Therapeutics: Slideset;
This 14min presentation describes the content of the pitch deck: Slides & audio