February 01, 2022

Neuvivo Announces Publication of Paper on ALS Drug Candidate NP001 in Peer-Reviewed Journal, Muscle & Nerve

In Large Subset of Patients, NP001 Slowed the Decline in ALSFRS-R Score by 36% and Slowed Vital Capacity Loss by 51%

Palo Alto CA, Feb 1, 2022 - Neuvivo today announced the publication of a paper on its lead candidate drug NP001 for the treatment of ALS in the peer-reviewed journal Muscle & Nerve. Authored by 14 of the leading ALS researchers in the world, the study titled: ‘Phase 2B randomized controlled trial of NP001 in amyotrophic lateral sclerosis: pre-specified and post-hoc analysis” showed that NP001 significantly slowed or in some cases, halted, progression of this disease in a subset of patients during a 6-month period.

The post-hoc analysis of a Phase 2B trial showed that those ALS patients with C reactive protein (CRP) levels greater than 1.13mg/L (CRP is a marker of inflammation), and between ages 40-65 with symptom onset within 3 years prior, demonstrated a 36% slower rate of decline of ALSFRS-R scores (disease activity score) and a 51% slower rate of decline of respiratory function (vital capacity). In addition, 34% of NP001 treated vs. 11% of placebo patients did not progress over the 6-month studies (p = 0.004); those with higher levels of inflammation showed a 10-fold higher rate of non-progression than placebos with NP001 treatment (p = 0.001). Importantly, the study showed the drug to be safe and well-tolerated.

“We saw in earlier studies that NP001 had an excellent safety profile and a number of patients reported that they had much slower progression of symptoms and in some cases, no progression of symptoms,” said Ari Azhir, PhD, Founder and CEO of Neuvivo. “It was clear to us that we needed to re-analyze the data from the earlier trials and in doing so we identified a large subset of patients who experienced benefits from treatment with NP001.”

There is currently no marketed ALS treatment that halts disease progression and no known drug that has been shown to slow the progressive decline of a patient’s ability to breathe on their own, a debilitating hallmark of late-stage disease. Once vital capacity declines to a certain level, patients must be placed on a ventilator.

“Beyond the valuable effects on a patient's overall disease manifestation, there was another even more important effect on preservation of vital capacity,” said Robert Miller, MD, Forbes Norris MDA/ALS Research Center, California Pacific Medical Center. “The mITT analysis of the 40-65 years old group showed that vital capacity was preserved by a wide margin compared to placebo (p value= 0.001). This is key from a clinical perspective and is the first time any drug has had an effect on vital capacity. This effect alone is very supportive of NP00l use in ALS patients, as it should provide a longer lifespan for ALS patients who respond.”

“This Phase 2 post hoc analysis is welcome progress in the development of new and much needed ALS treatments,” said Merit Cudkowicz, M.D., investigator in the Phase 2 studies, co-founder of the Northeast ALS Consortium, Director of the Healey & AMG Center for ALS and Chair of Neurology at Massachusetts General Hospital and the Julianne Dorn Professor of Neurology at Harvard Medical School. “NP001 has been shown to have a good safety profile so it was a natural next step to review the data to identify participants who may benefit. This will inform future studies of NP001 in people with ALS.”

“NP001’s mechanism of action targets disease promoting white blood cells known as macrophages and transforms them back to their non-inflammatory state.” said Michael McGrath, MD, PhD, Chief Scientific Officer of Neuvivo and Professor Emeritus of Medicine at UCSF. ‘Macrophage’ means ‘big eater’ in Latin and when healthy, these cells – present in all tissues in the body - engulf and eliminate harmful pathogens and cellular debris. In chronic disease states such as ALS abnormal macrophages lose this function and contribute to disease by promoting inflammation. In theory, NP001 treatment reverses this process.

The goal of the post hoc combined trial analysis was to identify characteristics of ALS patients responsive to NP001. The analysis combines data from a phase 2A clinical study with a previously unpublished phase 2B clinical trial for treatment of ALS patients with NP001 or placebo. The analysis presented includes data on approximately 300 patients’ data from two 6-month Phase 2 studies.

The full study can be accessed on Muscle & Nerve: https://onlinelibrary.wiley.com/share/author/YYQSBQVGANR6PQMUCIZ4?target=10.1002/mus.27511

Pub Med Abstract: Phase 2B randomized controlled trial of NP001 in amyotrophic lateral sclerosis: pre-specified and post-hoc analyses - PubMed (nih.gov)

The study was authored by investigator Robert G. Miller, MD, of California Pacific Medical Center in San Francisco. Co-authors are Rongzhen Zhang and Paige Bracci PhD, of UCSF; Ari Azhir, PhD, or Neuvivo; Richard Barohn, MD, of University of Missouri, Columbia; Richard Bedlack, MD, of Duke University Medical Center; Michael Benatar, MD, of University of Miami Miller School of Medicine; James D. Berry, MD, and Merit Cudkowicz, MD, of Massachusetts General Hospital; Edward Kasarskis, MD, PhD, of University of Kentucky, Lexington; Hiroshi Mitsumoto, MD, of Columbia University Medical Center; David Walk, MD, of University of Minnesota Medical School; Jeremy Shefner, MD, PhD, of Barrow Neurological Institute, University of Arizona College of Medicine, Phoenix and corresponding author, Mike McGrath, MD, PhD of UCSF and Neuvivo.

*ALSFRS-R scores is a rating scale for evaluating the physical functional status of a person living with ALS. The maximum score is 48, the minimum is zero. Higher scores are reflective of greater physical functionality.

Required Notes and Disclaimers: The information stated above was prepared by Neuvivo and reflects solely the opinion of the company. Nothing in this statement shall be construed to imply any support or endorsement of Neuvivo, or any of its products, by the Regents of the University of California, its officers, agents and employees.

Michael McGrath, MD, PhD is a co-founder of Neuvivo and is compensated by the company.

About NP001: NP001 is a multifactorial immune system regulator. It is a first-in-class NCE with a known mechanism of action that targets diseased macrophages in the central nervous system to restore equilibrium to the immune system.

About Neuvivo: Neuvivo is a private, late-clinical stage biopharmaceutical company focused on creating and delivering advanced treatments for ALS and other neurodegenerative diseases. The company was formed by successful industry leaders and scientists, committed to improving the prognosis for patients diagnosed with ALS and a range of diseases for which few current treatment options exist. For more information please visit: www.Neuvivo.com.