Companies To Watch: Spinogenix

By Ben Comer, Chief Editor, Life Science Leader

Using small molecule drugs to restore synapses in neurological diseases.
Snapshot
Los Angeles-based Spinogenix, a privately held small molecule drug discovery and development company, is currently testing two clinical candidates in four diseases: SPG302 in amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, and schizophrenia, and SPG601 in Fragile X syndrome. Both candidates are orally administered small molecules. SPG302, discovered internally, is a part of the company’s TAG platform, which stands for “Transient Activators of Glutamatergic Synaptogenesis,” a technology that stimulates the formulation of new synapses, using glutamate as a neurotransmitter. SPG601 is a small molecule BK channel activator in-licensed from academia and aimed at correcting synaptic disfunction associated with Fragile X syndrome. On October 16, Spinogenix announced that it would launch an additional program in glaucoma for SPG302.
What’s At Stake
Biomarkers in neurological diseases are difficult to ascertain and elucidate, but from a regulatory standpoint they have become increasingly important. The reduction of amyloid beta (the most established, if imperfect, biomarker) in Alzheimer’s disease, and the approval last year of Biogen’s Qalsody (tofersen) in ALS, based on reduction in plasma neurofilament light (NfL), a blood-based biomarker, demonstrate the regulatory advantages of an objective endpoint. In other words, showing, not telling, is likely to improve a developer’s chances of receiving FDA approval for a new medicine treating a neurodegenerative or neurodevelopmental condition.
Stella Sarraf, Ph.D., a former senior research chemist at Merck who worked in venture capital (at Prospect Venture Partners and Foresite Capital) for nearly a decade, founded Spinogenix in 2016 for a few key reasons. The first reason was personal: “My dad got Parkinson’s disease.” By the time a Parkinson’s patient exhibits a cardinal motor symptom, such as involuntary tremors, a lot of irreversible brain damage has occurred. “I started to understand that neurology is decades behind oncology” in terms of early detection and medical intervention. Sarraf founded Amydis in 2013, a company focused on noninvasive disease detection but was frustrated by the fact that many neurological diseases, even with improved detection, didn’t have good treatment pathways, or an active investor base for new therapies.
As a VC, Sarraf stayed abreast of emerging literature on new drug mechanisms and discoveries and became increasingly interested in synaptic regeneration as a target for improving, for example, cognition, respiration, and motor function among ALS patients. “The beauty of working at the synaptic level, especially in ALS, is that no one else has worked even in that zip code. It’s completely new,” says Sarraf. With a new approach the question then became, how is effectiveness tracked and validated?
Existing technologies, such as electroencephalography (EEG) and transcranial magnetic stimulation (TMS), can be deployed as a “completely objective” tool for measuring synapses — and as a biomarker — another key reason for Sarraf’s focus on synaptic regeneration, she says. Importantly, synapses play an important role in several disease areas with high unmet need.
Sarraf describes a video of a TAR4/4 ALS mouse model treated with SPG302 by Justin Ichida, a professor and researcher at the University of Southern California, which created early excitement about the drug’s potential. Now in a small but fully enrolled Phase 2 clinical trial for ALS, with small Phase 2 trials in Alzheimer’s disease and schizophrenia currently enrolling, Sarraf says Spinogenix is using the smaller studies to get the doses right, and to establish an objective measurement. Previous research over the last year helped Spinogenix understand and establish safety, which Sarraf believes could position SPG302 as not only a stand-alone therapy, but also as a potential part of a cocktail therapy. A Phase 2 Fragile X trial with SPG601, which is a designated orphan drug, is currently enrolling patients as well. Sarraf anticipates multiple Phase 2 readouts across disease areas in 2025.
Spinogenix has benefited from close collaboration with academic institutions and has used grant funding to de-risk the company, says Sarraf. “All of our animal work was done by others [externally],” she adds, citing NIH grants in Alzheimer’s disease, and a spinal cord injury model conducted with the Mayo Clinic. The company has also received Department of Defense grants.
A small molecule, orally available treatment that is safe and effective in any of the disease areas Spinogenix is targeting would be a “game changer,” says Sarraf, not just for patients, but also for product manufacturing and scale-up. “This is something that no one else is doing … I don’t do me-too drugs or build better mouse traps,” she says. “I get really fired up about first mover advantage, thinking outside the box, and putting things together in a creative manner based on my previous experiences.”
Vital Statistics
Full-time Employees: 7
Headquarters: Los Angeles, CA
Significant Investors/Grantmakers: Stead Impact, family offices, high net worth individuals, NIH, and DoD
Latest Update:
October 2024: Launched a glaucoma program for SPG302 and added to its scientific advisory board Dr. Robert Weinreb, MD, director of the Shiley Eye Institute at UC San Diego.