Drug Development 101

Unlike other organizations, we do not have a research deadline, but instead maintain a rolling application process—enabling us to scoop up promising ideas as soon as they surface, while being proactive and recruiting the best in the world with novel ideas to work on Angelman syndrome. Each proposal is sent to three members of our Scientific Advisory Board (SAB), made up of 25 individuals who are each subject matter experts in different areas. (For more about the SAB, see here.) Currently, FAST has over 20 research grants that are active and ongoing in different research facilities around the world. You can learn more about our current and past grants here.

FAST has underwritten the development of a robust infrastructure that can be used by any researcher, biotech, or pharmaceutical company in order to test their AS drug. Our years of investment have yielded mice, rats, and pigs—all with AS—waiting to test curative treatments. This includes a full deletion mouse, to understand what the genes deleted other than UBE3A are doing (or not doing as the case may be). Additionally, we have cutting edge cell lines and organoids (or “mini brains”) for each genotype, through which therapeutics can be tested to help us understand how our loved ones’ neurons will react. We have also funded “landing pads” to test each gene or RNA—which may be under-expressed in deletion or over-expressed in ICD and UPD—to better understand the cause of that variance and the consequences of replacing or activating it.

We engage aggressively in the pharmaceutical space to ensure potential therapeutics do not languish in the laboratory or beyond—especially in the “valley of death” of drug development, the period during which innovative medical research discoveries are made, generally in an academic lab, and yet somehow get blocked from becoming new therapies for humans, or even making it to clinical trials. In rare disease, where the profits to pharmaceutical companies may be considered smaller than that of more common disorders, this is unfortunately common. Or, more tragically, even after seeing positive results in humans, drugs can languish. This is of vital importance. If you want to read a horror story scarier than any “Nightmare on Elm Street” for a rare disease patient or family, see this Los Angeles Times article from 2021, in which a cure for a rare and fatal disease was actually discovered, and was in the process of being administered successfully to patients—until the biotech company awarded an exclusive license to develop and market the cure shelved it. Why? Not because of any misgivings about its safety or efficacy, but for “‘business reasons,’ meaning that it wanted to invest instead in treatments for more common diseases with more potential for profits.” We know that no pharma wants to make this type of decision, but unfortunately, in companies the bottom line often comes down to finances and priorities. We can’t let this happen to any promising AS treatment, and that means not counting on Angelman syndrome being the priority of anyone other than us, our community.

Sometimes, the best way to avoid losing a promising therapeutic in the “valley of death”—especially one we’ve invested in from its inception, via one of our grants—is to build our own company around it. This allows us to guardrail the treatment through the toughest terrain of the drug pipeline, namely from basic research through discovery and IND enabling studies into phases 1/2 clinical trials. If it succeeds through all of these, it will then be an attractive asset for a pharmaceutical company big enough to take it through the pipeline’s most expensive final stages all the way to a possible FDA approval. Human data is more powerful than any cellular or animal data, and that gives Angelman syndrome the closest guarantee to attract the best partner to advance the therapy for all patients. Funds used in the establishment of for-profit entities initially are seeded by FAST, since we funded most of the work to get us there. The larger infusion of funds needed for the IND enabling studies and any potential clinical trial will generally come from outside investors, some of whom may have personal connections to AS (angel investors), and others who are not yet connected directly but believe in the science and see the potential. In some cases, these investors request that specific representatives of FAST stay involved in the program for a period of time, which could result in them being on payroll at the new company, expressly for the purpose of ensuring that the new entity maintains its primary commitment to AS. This decision would be made by an independent board that is leading the company, not leading FAST. In no instance can board members or any FAST-affiliated individuals acquire independent control over intellectual property rights of any technology or project seeded by FAST.