Multi-center, multi-tracer PET studies harmonized to detect neuroinflammation in ALS

Reston, VA–A novel ALS (amyotrophic lateral sclerosis) study has pooled data from multiple sites to effectively visualize neuroinflammation, which is key to developing drugs to treat the disease. Pooling data acquired from different scanners, different neuroinflammation positron emission tomography (PET) markers and different sites enhanced researchers’ ability to detect neuroinflammation in ALS patients. This research was published in the November issue of The Journal of Nuclear Medicine.

ALS is a rare and fatal neurodegenerative disease that causes progressive weakness, respiratory failure and eventual death. Developing drugs to treat the disease is uniquely challenging because it is so rare. “In rare diseases such as ALS, only a limited pool of participants is available to participate in imaging studies,” noted Donatienne Van Weehaeghe, MD, PhD, researcher in the department of imaging and pathology at University Hospital Leuven in Leuven, Belgium. “Therefore, conducting collaborative research across various sites and bringing in data to a common analysis pool is valuable to accelerate imaging biomarker development.”

The study investigated two second-generation translator protein (TSPO) tracers, 18F-DPA714 and 11C-PBR28, that are currently being developed in the United States and Europe as promising ALS biomarkers. Researchers first sought to validate the established 11C-PBR28 PET pseudo reference analysis technique (which is used as a substitute for full dynamic modeling) for 18F-DPA714; they then evaluated whether multicenter data pooling of 18F-DPA714 and 11C-PBR28 data was feasible.

ALS patients and healthy volunteers from the United States and Belgium were recruited for the study and underwent dynamic 18F-DPA714 or 11C-PBR28 PET/MRI (magnetic resonance imaging). Data from the 18F-DPA714 or 11C-PBR28 images were analyzed, and results were compared.

The pseudo reference analysis technique was found to produce results comparable to those of gold standard PET analyses obtained by full dynamic modeling. The most sensitive pseudo reference region was whole brain without ventricles. Analysis of the 18F-DPA714 and 11C-PBR28 data from multiple sites showed a much greater power to detect inflammation compared to individual site data alone.

“In this exciting study, we have shown the ability to pool together and analyze brain neuroinflammation PET imaging data acquired at multiple institutions with varying scanner capabilities, using state-of-the-art analytical tools. This is the essential first step for bringing cutting-edge research closer to ALS patients globally and for accelerating the pace of biomarker readouts for future ALS clinical trials,” said Suma Babu, MBBS, MPH, assistant professor of neurology at Harvard Medical School and physician investigator at Massachusetts General Hospital in Boston, Massachusetts. “This approach could reduce time and travel burden for patients, allowing them to participate in novel biomarker research while remaining close to home. From a scientific study conduct standpoint, this approach retains scientific rigor, increases statistical power, reduces trial durations and reduces risks of attrition.”

“Developing mechanistic central nervous system biomarkers that can be acquired across multiple study sites would greatly accelerate the pace of finding effective treatments for neurodegenerative diseases, including ALS,” said Nazem Atassi, MD, MMSc, associate professor of neurology at Harvard Medical School and head of early neuro-development at Sanofi-Genzyme.

PET imaging of neuroinflammation is relevant to multiple neurological conditions, not just ALS. “The ability to combine data across different radiotracers allows researchers to build on the foundation laid by prior research without the need to start from scratch every time with a new radioligand. If ongoing and future collaborative research in this field is successful, it could directly impact the use of PET imaging markers in future clinical trials testing anti-neuroinflammatory medications in ALS and other neurological conditions,” remarked Van Weehaeghe.

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This study was made available online in March 2020 ahead of final publication in print in November 2020.

The authors of “Moving toward Multicenter Therapeutic Trials in Amyotrophic Lateral Sclerosis: Feasibility of Data Pooling Using Different Translocator Protein PET Radioligands,” include Donatienne Van Weehaeghe, Michel Koole, Ahmadreza Rezaei, Georg Schramm and Koen Van Laere, Nuclear Medicine Subdivision, Department of Imaging and Pathology, University Hospital Leuven, Leuven, Belgium; Suma Babu, Sheena Chew and Nazem Atassi, Department of Neurology, Sean M. Healey and AMG Center for ALS, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Joke De Vocht and Philip Van Damme, Department of Neurology, University Hospital Leuven, and Laboratory of Neurobiology, Center for Brain and Disease Research, VIB, Leuven, Belgium; and Nicole R. Zürcher, Chieh-En J. Tseng, Marco L. Loggia and Jacob M. Hooker, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts.

Please visit the SNMMI Media Center for more information about molecular imaging and precision imaging. To schedule an interview with the researchers, please contact Rebecca Maxey at (703) 652-6772 or rmaxey@snmmi.org.

About the Society of Nuclear Medicine and Molecular Imaging

The Journal of Nuclear Medicine (JNM) is the world’s leading nuclear medicine, molecular imaging and theranostics journal, accessed close to 10 million times each year by practitioners around the globe, providing them with the information they need to advance this rapidly expanding field. Current and past issues of The Journal of Nuclear Medicine can be found online at http://jnm.snmjournals.org.

JNM is published by the Society of Nuclear Medicine and Molecular Imaging (SNMMI), an international scientific and medical organization dedicated to advancing nuclear medicine and molecular imaging–precision medicine that allows diagnosis and treatment to be tailored to individual patients in order to achieve the best possible outcomes. For more information, visit http://www.snmmi.org.

Koen Van Laere and Philip Van Damme are senior clinical investigators of the Fund for Scientific Research, Flanders, Belgium (FWO). Donatienne Van Weehaeghe is a PhD fellow of the FWO (1179620N). Philip Van Damme is supported through the E. von Behring Chair for Neuromuscular and Neurodegenerative Disorders, the ALS Liga Belgi¨e and KU Leuven funds ”Een Hart voor ALS” and ”Laeversfonds voor ALS Onderzoek,” and the ”Val´ery Perrier race against ALS” fund. Nazem Atassi is supported through NIHK23-NS083715, the Muscular Dystrophy Association, the ALS Association, and ALS Finding a Cure. The postdoc position of Georg Schramm is funded by NIH grant 1P41EB017183-01A1. No other potential conflict of interest relevant to this article was reported.

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Source: https://www.eurekalert.org/pub_releases/2020-12/sonm-mmp120120.php

Novus Therapeutics Announces First Patient Enrolled in Phase 2a Clinical Trial of Anti-CD40L Antibody AT-1501 in Amyotrophic Lateral Sclerosis

IRVINE, Calif.–(BUSINESS WIRE)– Novus Therapeutics, Inc. (“Novus”) (NASDAQ: NVUS), a clinical stage biopharmaceutical company focused on developing life-changing, targeted medicines for patients undergoing organ or cellular transplantation, as well as those living with immunological diseases, today announced that the first subject has been enrolled in the Phase 2a clinical trial evaluating AT-1501, the Company’s lead product candidate, in adults with amyotrophic lateral sclerosis (ALS). AT-1501 blocks the activation of the CD40L pathway, which has been shown to improve muscle function, slow disease progression, and improve survival in a pre-clinical animal model of ALS. AT-1501 previously received orphan drug designation from the U.S. Food and Drug Administration for the treatment of ALS.

“Novus is committed to providing people living with ALS and their families with a therapeutic solution to treat this progressive and devastating disease as expeditiously as possible,” said Steven Perrin, Ph.D., President and Chief Scientific Officer of Novus. “We look forward to the safety and biomarker insights from this study and we anticipate top-line data from this important trial in 2022.”

“There is strong evidence that the reduction of peripheral neuroinflammation has the capacity to influence disease progression in ALS,” said Dr. Merit Cudkowicz, Director of the Sean M. Healey & AMG Center for ALS, and Chief of Neurology at Massachusetts General Hospital, Boston. “I am excited to see the clinical advancement of AT-1501, which targets a key signaling pathway in the generation of pro-inflammatory responses.”

The AT-1501 Phase 2a trial in ALS is a 12-week, open label, dose escalating, safety and biomarker study. The endpoints of the study are safety and tolerability, and changes in pro-inflammatory biomarkers as well as neurofilament light chain. Exploratory clinical endpoints will also be assessed.

“We are in urgent need of new therapies for people living with ALS,” said Dr. Michael Rivner, Charbonnier Professor of Neurology and Director of the ALS Clinic at Georgia Regents Medical Center, Augusta. “AT-1501 and the CD40/CD40L pathway represent a highly promising approach to treating this disease.”

Novus Therapeutics has completed a Phase 1a/1b single ascending dose trial in healthy volunteers and adults living with ALS. In that trial, AT-1501 was well tolerated at all doses tested and demonstrated a good safety profile. AT-1501 also demonstrated linear dose proportionality across the dose range and a half-life of up to 26 days.

About AT-1501

AT-1501 is a humanized IgG1 anti-CD40L antibody with high affinity for CD40L, a well-validated target with broad therapeutic potential. The CD40/CD40L pathway plays a central role in generating pro-inflammatory responses in autoimmune disease, allograft transplant rejection, and neuroinflammation. In a Phase 1 safety study of healthy volunteers and adults with ALS, AT-1501 was well tolerated at all doses tested.

The discovery and early development of AT-1501 for ALS received support from The ALS Therapy Development Institute, Augie’s Quest, The Muscular Dystrophy Association, The ALS Association, ALS One, ALS Finding a Cure, and The ALS Ice Bucket Challenge.

About Novus Therapeutics

Novus Therapeutics, Inc. is a clinical stage biotechnology company using its expertise in targeting the CD40L pathway to develop potential treatments for people requiring an organ or cell-based transplant, and for people with autoimmune and neurodegenerative disease. Novus is headquartered in Irvine, California. For more information, please visit the company’s website at www.novustherapeutics.com.

Follow Novus Therapeutics on social media: @Novus_Thera and LinkedIn.

Forward-Looking Statements

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View source version on businesswire.com: https://www.businesswire.com/news/home/20201102005283/en/

Contacts
Amanda Sellers
asellers@vergescientific.com
301.332.5574

Source: Novus Therapeutics, Inc.

Aural Analytics To Power Speech-Based Endpoints For The Healey Center ALS Platform Trial at Mass General Hospital

The first-ever platform trial for ALS is set to kick off this month and is led by investigators at the Sean M. Healey & AMG Center for ALS at Mass General Hospital

Aural Analytics’ award-winning clinical trials platform will provide speech collection and speech-based digital endpoints for the HEALEY ALS Platform trial study regimens

August 06, 2020 02:03 PM Eastern Daylight Time
SCOTTSDALE, Ariz. & BOSTON–(BUSINESS WIRE)–Aural Analytics, Inc., a privately held digital health company developing the world’s most advanced suite of clinical-grade speech analytics, announced today it has entered into an agreement with Mass General Hospital’s Sean M. Healey & AMG Center for ALS to power speech collection and speech-based digital endpoints for the platform trial. The HEALEY ALS Platform Trial is the first-ever platform trial for the treatment of amyotrophic lateral sclerosis (ALS), which includes substantial financial support from the Healey Center, Tackle ALS, the ALS Association, and ALS Finding a Cure, and provides access to 54 expert ALS clinical trial Northeast ALS Consortium (NEALS) sites across the United States.

The platform trial is expected to greatly accelerate therapy development by allowing investigators to test more drugs, increase patient access to trials, reduce trial costs, and quickly and efficiently evaluate the effectiveness of multiple therapies simultanously. Shared infrastructure, common data and sample collection processes, and central governance within the platform trial will lead to operational efficiencies and time and cost savings.

Speech changes in ALS patients have been well-studied and speech represents an important biomarker for disease progression, patient stratification, and early detection of symptoms. Aural Analytics’ software architecture and suite of analytics are designed to meet the challenges of a multi-site, multi-sponsor, multi-language and multi-target trial. Aural Analytics’ speech-based digital endpoints have been used extensively in ALS clinical trials – both in clinic and at home – to measure clinically-relevant speech changes. The use of remote collection tools, like Aural Analytics’ Speech Vitals mobile application, significantly decreases the burden of patients with ALS, a disease that causes the progressive degeneration of motor neurons resulting in progressive muscle weakness and atrophy.

“Aural Analytics exists to be a catalyst for improving the lives of patients with neurological health issues. We are honored to be working alongside Mass General Hospital and the Sean M. Healey Center serving the ALS population,” said Daniel Jones, co-founder and chief executive officer of Aural Analytics, inc. “We are committed to, and share the long-term goal of the platform trial.”

“Our shared goal is to bring new therapies forward faster for people with ALS,” said Dr. Merit Cudkowicz, Director of the Healey center for ALS and chief of neurology at Mass General. “Speech analytics technology has the potential to provide important insights about the effects of treatments in the platform trial.”

Background on ALS

Amyotrophic lateral sclerosis, ALS, is the most prevalent adult-onset progressive motor neuron disease, affecting approximately 30,000 people in the U.S., and an estimated 500,000 people worldwide. There are currently three FDA therapies approved specifically for treating ALS—riluzole, nuedexta and edaravone.

About Aural Analytics, Inc.

Aural Analytics is a digital health company building the world’s most advanced clinical-grade speech analytics platform for neurological health conditions across the lifespan. The company is founded on nearly three decades of NIH and NSF funded research in the field of speech neuroscience and is backed by dozens of high-caliber scientific publications. Aural Analytics’ suite of mobile-first, patient- centric applications are easy to use, secure, and provide robust, clinically-relevant, interpretable and validated metrics reflecting the neurological health of its users. Currently available in 12 languages (android and iOS), the company has worked in large research study settings, pharmaceutical clinical trials and other clinical applications. The company has won several awards for their work in the field, including the prestigious Global SCRIP Award for Best Technology Development in Clinical Trials. The Company maintains headquarters in Scottsdale, AZ. For more information, please visit auralanalytics.com or follow Aural Analytics on Twitter, LinkedIn, Medium and Facebook.

Contacts
Aural Analytics, Inc.
John Caviness
press@auralanalytics.com