Origami Therapeutics is taking a precision medicine approach to discover disease-modifying treatments for neurodegeneration caused by toxic protein misfolding. Our platform enables discovery of both protein degraders and conformation correctors, allowing us to match the best drug to treat each disease using patient-derived disease models. Currently, we are selecting the optimal compound to advance into clinical testing for Huntington’s disease and initiating programs for additional indications.
Meet Origami Therapeutics

Why is your company the best option to solve the problem you're solving?
Origami Therapeutics is the best option for generating a transformational therapy for Huntington’s disease because we are targeting the underlying genetic and mechanistic cause of the disease using small molecules. The use of a small molecule provides better biodistribution and enables greater access to therapy for patients by avoiding the need for invasive delivery, a trained neurosurgeon and a neurosurgical suite, key distinctions from our competitors. By targeting the root cause of disease, we mitigate the risk of side effects caused by targeting more general cellular pathways. By sparing normal function of the huntingtin protein, we maintain normal cellular function and physiologic balance, preventing loss-of-function negative consequences. This increased benefit to risk ratio should enable treatment before symptoms develop, and more importantly before brain cells die. These factors contribute to a therapy with the potential to prevent, halt or slow progression of disease, resulting in a normal quality of life and normal productivity for the patient.
What nuggets of info make you interesting? Why do people care about what you're doing?
What makes us interesting is our dedication to the patients and their families, driven by our courage and determination to succeed, trust in our team (everyone has a significant contribution to make) and cool cutting-edge science. We believe that the greatest successes arise from accepting the biggest challenges. That is why we were not afraid to strike out on our own to seek the best solution for patients using all of the cutting-edge science and technology available. Origami is a little unusual in the San Diego biotech ecosystem in that we arose neither from academic research nor as a spin-out/license from another company. Instead, we are a boot-strapped, homegrown San Diego company leveraging the founders’ previous successes in multiple therapeutic areas. We do feel it is important to contribute to our San Diego community and that is why we continue to build a collaborative network with local companies and service providers whenever possible. This makes our success their success. People care about what we are doing because we engage with our future patients and their families through our longstanding interactions with the San Diego Chapter of the Huntington’s Disease Society of America, the premier patient advocacy group for Huntington’s disease, as well as key clinicians and researchers in the therapeutic space. It is our honor and privilege to sponsor and contribute to fund-raising efforts for patient services and advocacy.
BEHIND THE COMPANY
CEO/Founder: Beth Hoffman

What is your company's secret sauce?
Origami’s secret sauce is a unique combination of profound technical insights, passion and dedication to finding enduring solutions for patients and the ability to build high-performing teams to execute on our vision. With this as a foundation, we have assembled a skilled and enthusiastic team willing to put in the effort to achieve something novel and great.
What inspired you to start/run this company?
I was inspired by my realization that modulating conformation of large proteins with small molecules drugs was not only possible but that such drugs could completely change the treatment paradigm for disease. I reasoned that neurological diseases could be approached in this way. My experience provided a unique opportunity to attack this problem by marrying my expertise in neuroscience, drug discovery and discovery of small-molecule protein conformation modulators. The unmet need in neurological disorders was too great for me not to step up to meet the challenge.
What's the best entrepreneurial advice you've received?
Be prepared to pivot but don’t abandon your vision.