01 — What is the purpose of rareSHIFT?

We are building a more efficient model for drug development to treat rare diseases previously overlooked due to high financial risk of drug development. Thanks to new computational tools, we are now able to unravel molecular similarities in disease pathology and treatment response regardless of the clinical diagnosis or root cause, but we need additional data representing as many of the 10,000+ rare disorders as possible to do this. We are creating a centralized database and drug discovery platform to collaboratively drive the discovery of therapeutics that benefit more than one orphan disorder at a time, for disorders caused by genetic changes from a single gene all the way to whole chromosomes and of unknown/undiagnosed origins. Through rareSHIFT, Unravel is offering services through its drug discovery platform that can identify repurposed drug candidates and develop them all the way through clinical proof of concept trials.

02 — Who can use the data?

We believe in supporting rare disease scientific research. By generating often the very first clinical molecular datasets for rare disorders, we a committed to facilitating additional reserach programs. All resulting de-identified data will be shared with participants for research use. In parallel, Unravel Biosciences will process the data using its AI analytical platform to predict potential Therapeutic Response Groups and shared drug targets to make rare disease therapeutic development massively faster and less expensive.

03 — What is a Therapeutic Response Group?

Therapeutics are currently developed to treat a specific indication, or diagnosis. However, we already know that a drug developed to treat one disease can be used to treat another. Clinicians also know that similar symptoms or even an identical diagnosis between two patients does not mean they will both be treated by a drug approved for that disease. Unravel has developed the concept of a Therapeutic Responder Group to stratify or cluster patients using Unravel’s proprietary AI algorithms and patient RNA signatures based on potential treatment response rather than the root cause of a disorder. No matter if the disorder is caused by a single gene, multiple genes, or genetic and environmental factors, Therapeutic Response Groups are used to find shared ways to treat them.

04 — Why do you want to sequence RNA?

Although DNA sequencing of the genome has gotten far more attention, RNA tells a different story. DNA mutations are mostly unchanged over the life of a patient. RNA on the other hand tells a dynamic story of each patient’s specific condition, not just the genetic contributions of their entire genome but also the impact of their environment, sleep, diet, medications, activity, and even the microbiome! As a patient’s disorder progresses or is treated, RNA keeps informing on what is happening. Even for disorders with clear disruption of proteins, RNA still provides a view of the biological system, offering strategies for treatment. The historical lack of RNA data, unlike DNA data, is a major motivator for creating this database.

05 — Why should you participate?

rareSHIFT enables researchers to leverage RNAseq data towards developing new therapeutics for ultra-rare disorders that traditional pharma overlooks. Lack of access to relevant data creates a bottleneck and limits the rate at which researchers and drug developers can discover new theraputics. rareSHIFT aims to generate and mobilize RNAseq datasets to anyone interested in freely using this data for biomedical research, including research groups you may already be supporting. Additionally, Unravel’s discovery platform is now available for families and foundations to meet their repurposing and new target/drug development needs.

06 — How will you benefit?

In addition to serving as a source of data for research, Unravel Biosciences is making drug discovery and development more efficient, including new and repurposed drugs. Reports from each study are shared with the participants to provide personalized analyses of their condition as well as possible drug repurposing candidates that can drive additional research. Unravel Bio has already identified two existing drugs that will soon enter four separate clinical trials, including the first ever for a particular orphan neurodegenerative disorder. By identifying shared therapeutic responses among unrelated rare disorders, Unravel Bio is finding opportunities for multiple foundations to syndicate resources to more efficiently support drug development. Our partners have expertise conducting clinical trials in rare pediatric neurological disorders and provide an opportunity to quickly translate potential candidates to the clinical. Together we are accelerating the discovery of therapeutics that will benefit multiple patient populations at once.

PLEASE NOTE THAT WE DO NOT PROVIDE DIAGNOSTIC OR THERAPEUTIC SERVICES. ALL DATA AND REPORTS ARE INTENDED FOR RESEARCH USE ONLY.

07 — Is the rareSHIFT project authorized to conduct biomedical research on human subjects?

rareSHIFT is building on the effort of clinical researchers who banked specimens under appropriate and valid human subject protocols overseen by an Institutional Review Board (IRB) that permit sharing of deidentified data for research purposes while prividing strict privacy and confidentiality protection to participants. We offer new sample collection using our proprietary nasal swab RNAseq method under an existing IRB protocol and are happy to continue to support your drug development and clinical translation strategy.

08 — Will the identity of our patients be protected?

Absolutely! Patient identifiers, including genetic sequence data and Protected Health Information, will be removed by us or our clinical research insitutional partners as per IRB protocol guidelines prior to any data sharing or publication.

09 — How have your previous research efforts using RNA led to significant impact for rare disorders?

Unravel Biosciences harnessed patient RNA data to uncover a promising breakthrough for Rett Syndrome in just one year, discovering a new therapeutic mechanism that can be engaged using an existing prescription drug. The discovered novel therapy surpasses the only approved drug in mouse models and is poised for upcoming clinical trials. Unravel has repeated this approach with other neurodevelopmental and neurodegenerative disorders, including saving months of screening by analyzing RNA with the BioNAV discovery engine. Additionally, multiple patients have opted to use the generated data and drug hit lists to work with their clinical teams to evaluate drugs off-label and have found promising results. As an example of how robust the approach is, Unravel’s lead drug prediction for a neurodegenerative disorder, generated and validated in under one year, has been nominated for the supporting foundation’s very first clinical trial. We are partnered with multiple foundations to develop custom repurposing and target discovery programs based on patient RNAseq data and enabling clinical trials in rare and ultra-rare disorders. rareSHIFT will amplify this impact exponentially! See Unravel’s science here.

10 — How will my funding be handled?

Unravel contracts with foundations/families through a template service agreement to enable RNAseq data generation, in silico drug screening, and potentially animal model development and screening. Unravel’s mission is to develop effective therapeutics in a collaborative manner. To that end, we charge families and nonprofit foundations only what it costs us to perform the work and in return own resulting intellectual property to enable long-term drug development, including for new formulations of existing drugs as well as entirely new molecules. For drug repurposing and other programs, we offer standard services and custom studies depending on scope and needs. Request a customized quote here.