Gamma-secretase modulator with best-in-class properties enters phase 1 study with additional combination therapies to follow
BOSTON--(BUSINESS WIRE)--#alzheimers--Acta Pharmaceuticals, Inc. (Acta) today announced $24 million in total seed financing to advance a pipeline of therapies designed for early intervention (EI) in Alzheimer’s disease. Acta was created to translate more than four decades of scientific discoveries by renowned neuroscientist and its scientific founder, Dr. Rudolph E. Tanzi, into new Alzheimer’s disease (AD) therapies. The company’s lead program, GSM-779690T, is a next-generation gamma-secretase modulator (GSM) intended to treat and ultimately prevent AD. Designed to be best-in-class, GSM-779690T is the culmination of approximately 25 years of gamma-secretase modulator research by GSM inventors Dr. Tanzi and the late Dr. Steven L. Wagner at Massachusetts General Hospital (MGH) and the University of California, San Diego. Acta Chief Scientific Officer Dr. Kevin Rynearson led the optimization of the GSM portfolio that delivered GSM-779690T for clinical investigation.
Alzheimer’s disease is a major public health crisis, affecting more than seven million Americans. Current FDA-approved therapies are designed to either treat symptoms or slow disease progression by removing amyloid beta (Aβ) after it has accumulated in the brain as senile plaques. GSMs are designed to prevent the production of Aβ protein forms that drive plaque formation while promoting the generation of protective Aβ forms that reduce plaque formation. Specifically, GSM-779690T decreases levels of Aβ42, which drive plaque formation, while increasing levels of Aβ37 and Aβ38, which interfere with it. Importantly, unlike earlier gamma-secretase inhibitors (GSIs), which broadly block the enzyme’s activity, GSMs selectively modulate gamma-secretase while preserving its normal biological functions. Preclinical studies for GSM-779690T showed no inhibition of cleavage of the important gamma secretase substrate, Notch, at concentrations up to 20 micromolar. By restoring a healthier Aβ balance, GSM-779690T is being developed as a potential long-duration therapy for use in early intervention and ultimately, disease prevention for at-risk populations.
Acta’s Combination Therapies program is also designed to support early intervention. It builds on Dr. Tanzi and his MGH colleagues’ decade of research using Alzheimer’s-in-a-Dish™, laboratory models of human brain cells in mini-organoids and “assembloids” that recreate key pathological features of AD and the aging brain. It dramatically accelerates the discovery of new therapies by enabling researchers to screen hundreds of FDA-approved drugs and natural products simultaneously in just six weeks. Since creating the platform, Dr. Tanzi and his MGH colleagues have screened thousands of known drugs and natural compounds, identifying over 30 validated combinations that curb AD pathology. Acta has licensed intellectual property from MGH related to these combinations and is advancing select therapy candidates toward clinical evaluation. This offers the potential to significantly expand Acta’s pipeline of Alzheimer's disease treatment and prevention options.
“We founded Acta Pharmaceuticals to translate more than four decades of Dr. Rudolph Tanzi’s discoveries into new Alzheimer’s disease treatments to enable early intervention and prevention,” said George Alex, Acta Pharmaceuticals’ co-founder and CEO. “GSM-779690T is the culmination of 25 years of research at Massachusetts General Hospital and the University of California, San Diego and approximately $70 million in preclinical development funding. We're privileged to build on Drs. Tanzi and Wagner’s pioneering GSM research and decades of discoveries to give the broadest group of people the opportunity for early prevention and treatment of one of the world’s most devastating and costly diseases."
Dr. Tanzi’s co-discovery of the three familial Alzheimer’s disease genes—APP, PSEN1 and PSEN2—helped transform scientific understanding of the disease and laid the foundation for decades of research that ultimately led to Acta’s clinical programs. Dr. Tanzi commented: “We’re entering a golden age in Alzheimer’s research. Our understanding of genetic risk, new diagnostic tools and growing evidence showing that lifestyle habits can delay and even prevent disease give us an unprecedented opportunity to proactively protect brain health, just as we protect heart health today—before symptoms start. Our vision is that GSM-779690T could someday serve as the equivalent of a ‘statin for the brain’: a once-daily oral therapy designed to restore a healthier balance of amyloid-beta protein generation in the brain before irreversible damage occurs, giving people an opportunity to intervene with the AD pathological process as early as possible. All the Alzheimer’s research undertaken during the past four decades is coming to fruition at this moment, and I've never been more optimistic that Alzheimer’s prevention is within reach.”
Acta will evaluate GSM-779690T as an oral small-molecule drug candidate designed for early-stage, long-duration disease modification and prevention. The phase 1 study (ClinicalTrials.gov ID NCT07690228) is a randomized, double-blind, placebo-controlled, single- and multiple-ascending-dose study designed to evaluate the safety, tolerability and pharmacokinetics of GSM-779690T in healthy adult volunteers. In preclinical studies, GSM-779690T demonstrated a highly differentiated profile, including single-digit nanomolar potency against Aβ42, supporting potential best-in-class efficacy, a near 1:1 brain-to-plasma ratio in mice and oral bioavailability across multiple species.
“As the culmination of more than 25 years of structural innovation, we believe GSM-779690T is a potential best-in-class gamma-secretase modulator for the treatment and potential prevention of Alzheimer’s disease,” said Kevin Rynearson, Ph.D., Acta Pharmaceuticals’ chief science officer. “Acta evaluated hundreds of analogues to optimize potency, brain penetration and drug-like properties, ultimately identifying a single structurally distinct development candidate. Published preclinical studies demonstrated single-digit nanomolar potency against amyloid-beta 42 together with exceptional brain penetration, supporting efficacy at lower dose levels. It’s a true honor to build upon the pioneering work of our Scientific Founder, Dr. Rudolph Tanzi, and my mentor, Dr. Steven Wagner, as we advance what we believe is the next generation of Alzheimer's therapeutics.”
Acta is grateful for the support of shareholders committed to translating Dr. Tanzi’s pioneering discoveries into new therapies for earlier intervention and ultimately, Alzheimer’s disease prevention. The company’s shareholders include Alzheimer’s Disease Research Foundation, Dolby Family Ventures, Gamma Bio Investors and several family offices and mission-driven investors.
About Dr. Rudolph E. Tanzi
Dr. Rudolph Tanzi’s scientific accomplishments span more than 40 years, 50 patents, and over 800 published papers and have guided the understanding and treatment of neurodegenerative diseases for decades. Dr. Tanzi co-discovered all three genes for familial early-onset Alzheimer’s disease and co-created Alzheimer’s-in-a-Dish,™ a laboratory model of human brain cells in mini-organoids that recreates key features of the aging brain's biology, making drug discovery significantly faster and less expensive. He has received the highest awards in his field and is a N.Y. Times best-selling author of several books. Dr. Tanzi is a member of the National Academy of Medicine and was included on the 2015 list of the TIME100 Most Influential People in the World. He is Director of the Genetics and Aging Research Unit and Director of the McCance Center for Brain Health at Massachusetts General Hospital and serves as the Joseph P. and Rose F. Kennedy Professor of Neurology at Harvard Medical School. For additional information, please visit his full biography, website and follow him at LinkedIn.
About GSM-779690T
GSM-779690T is a gamma-secretase modulator being developed as a potent once-daily oral therapy for the treatment and potential prevention of Alzheimer's disease. Designed to selectively reduce Aβ42 while increasing the neuroprotective peptides Aβ37 and Aβ38, GSM-779690T is the culmination of 25 years of gamma-secretase modulator research pioneered by Drs. Rudolph E. Tanzi and Steven Wagner at Massachusetts General Hospital and the University of California, San Diego. A 2021 publication validated preclinical studies showing single-digit nanomolar potency for reducing toxic Aβ42, exceptional brain penetration with a nearly 1:1 brain-to-plasma ratio, oral bioavailability across multiple species, and no Notch inhibition at 20 micromolar. A 2022 laboratory study further supported the approach by showing that shorter amyloid-beta peptides, Aβ37 and Aβ38, slowed Aβ42 aggregation, with greater inhibition when combined with Aβ40. Acta will evaluate GSM-779690T in a phase 1 clinical trial planned for October 2026. GSM-779690T is an investigational drug that is not approved by any regulatory authority, and its safety and efficacy have not been established.
About Acta Pharmaceuticals, Inc.
Acta Pharmaceuticals, Inc. is helping to redefine how Alzheimer’s disease (AD) is treated and prevented by advancing the breakthrough discoveries of renowned Harvard Medical School-Massachusetts General Hospital neuroscientist and Acta’s scientific founder, Dr. Rudolph E. Tanzi. Acta’s pipeline leverages more than 40 years of Dr. Tanzi’s scientific accomplishments and $70 million in research and corporate funding to create safe, effective therapies that are affordable and accessible. Created in 2022, the Boston-based company has secured $24 million in seed funding and is currently investigating GSM-779690T, a next-generation gamma-secretase modulator (GSM) designed for the treatment and potential prevention of Alzheimer’s disease, in clinical studies (ClinicalTrials.gov ID NCT07690228). For more information, please visit www.actapharmaceuticals.com and follow the company at LinkedIn.
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Shanti Skiffington
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