NP-001

Physician, Former NFL Player Joins Neuvivo to Advance Effective ALS Treatments for Patients PALO ALTO, Calif., Jan. 17, 2024 /PRNewswire/ -- Neuvivo, a private, late-clinical-stage biopharmaceutical company focused on creating and delivering advanced treatments for Amyotrophic Lateral Sclerosis (ALS) and other neurodegenerative diseases, today announced the appointment of Dr. James Kovach, MD, JD, as its new Chief Medical Affairs Officer. Continue Reading Dr. James J. Kovach, Chief Medical Affairs Officer, Neuvivo Dr. Kovach, previously a member of the Neuvivo Advisory Board and the former Executive Director of the UC Davis Health Translational Entrepreneurship program and Chief Innovation Officer and Co-Founder of innovation center Aggie Square, brings to Neuvivo 30 years of unrivaled expertise in the advancement of novel technology and late-stage drug development, with a focus on neurodegenerative diseases. Ari Azhir, PhD, Founder and CEO of Neuvivo, commented, "Dr. Kovach's appointment to our leadership team represents a significant milestone for Neuvivo. His distinguished career, clinical expertise, and biotechnology and biopharmaceutical experience with neurodegenerative diseases make him an invaluable asset as we move into a critical phase of development and innovation." Azhir added, "Jim has firsthand experience, as a physician and as a former professional football player who has advised the NFL on the disproportionate impact of ALS on former athletes. His experience fuels his passion and resolve - and ours." A former NFL linebacker for the New Orleans Saints and San Francisco 49ers, Dr. Kovach has served as a member of the NFL Head, Neck and Spine Committee and currently serves on the Scientific Advisory Boards of the National Football League Alumni Association and Harvard Football Players Study. He also has served previously as the President of the Buck Institute, an NIH designated Center of Excellence for Research on Aging. "I feel the breadth of my experiences have been a training set for this moment," said Dr. Kovach, Chief Medical Affairs Officer, Neuvivo. "ALS has a vast, unmet need for treatments, including our military personnel and football players, who are four times more likely to develop the disease. I couldn't be more honored or committed to advancing Neuvivo's mission to bring new, effective treatments to our community." At Neuvivo, Dr. Kovach will lead key global functions related to the development and commercialization of Neuvivo's therapeutic pipeline, including medical affairs and the presentation and communication of clinical and scientific information about Neuvivo's lead drug candidate, NP001, to key stakeholders, including the medical community, patient groups, payers and others. This strategic announcement comes as the company prepares to present new clinical data regarding NP001 and valuable insights into ALS treatment advancements at the 14th Annual California ALS Research Summit on January 19, 2024. About Neuvivo Neuvivo is a private, late-clinical stage biopharmaceutical company dedicated to creating and delivering advanced treatments for ALS and other neurodegenerative diseases. Neuvivo has developed a proprietary technology platform that includes a patented macrophage-targeting technology, NP001, and its manufacture. NP001 is designed to address the heterogeneity and progression of ALS by reducing chronic inflammation through the regulation of the innate immune system, a key factor in the loss of motor and respiratory function in ALS, and pathology seen in other neurological diseases. For more information, please visit . Media Contact: Andrew Lee andrew.lee@720strategies.com SOURCE Neuvivo, Inc.

Paper Published in "Cells" Identifies Disease Pathogenesis and Highlights Role of Inflammation PALO ALTO, Calif., March 30, 2023 /PRNewswire/ -- Neuvivo today announced the publication of a peer-reviewed paper titled: "Regulation of the Innate Immune System as a Therapeutic Approach to Supporting Respiratory Function in ALS". The biomarker study used vital capacity (VC), a quantitative test for respiratory function, to highlight the relationship between a compromised innate immune system and ALS disease activity. ALS is a heterogeneous, currently terminal neurodegenerative disease, involving progressive loss of voluntary muscle function. The disease typically leads to death in 2-5 years, generally due to respiratory failure. In this study, NP001 was shown to have a significant positive impact on respiratory activity by augmenting the natural function of the innate immune system. The study evaluated data and newly obtained biomarker results from patients who were enrolled in the NP001 Phase 2 placebo-controlled 6-month clinical trial (Jan 2011-Nov 2012 at 17 sites in the US). Patients under 65 years old receiving 2mg/kg NP001 treatment, plus placebo arms, who completed the 6-month trial and had accessible plasma from baseline and at end of trial (stored at -80) were included. The study, in accordance with FDA guidance published in 2019, defined a subgroup of patients that responded clinically to NP001. The objective was to test whether regulation of the innate immune system with NP001 would be associated with effects on respiratory vital capacity. Role of CRP and the Immune System Patients in this vital capacity study were stratified based on plasma levels of a well-known marker of inflammation, C-reactive protein (CRP). Levels defined patients as "high CRP" (>1.13mg/L) and "low CRP" (<1.13mg/L) (CRP levels of under 3mg/L are typically considered within normal range, thus a 1.13mg/L level would not generally cause concern). CRP plays an important role in the body clearing misfolded proteins, dying cells and infectious agents as part of a normal innate immune system response. Once stimuli that caused the inflammatory response have been cleared, CRP levels in a healthy person return to normal. An ongoing elevated plasma CRP level indicates that there is disturbance of the cycle, such that the inflammatory response does not resolve. In the study reported by McGrath and colleagues at UCSF and Neuvivo in "Cells", data showed that patients treated with NP001 and with high CRP were able to better maintain lung function – treated patients had a 64% slower rate of VC loss than patients on placebo. These observations showed that patients with high CRP had stable vital capacity, leading to the possibility that high CRP values may be a biomarker for an immune system that is engaged but has been compromised. Key points presented in the study: NP001-treated patients with high CRP lost 0.75% of vital capacity per month Placebo group patients with high CRP lost 2.1% of vital capacity per month These data represent a 64% slower rate of decline in high CRP patients receiving NP001 (p=0.05) Importantly, plasma TGFB1, a dominant regulator of inflammation, was 95% higher after 6 months in high CRP treated patients compared with controls. (p < 0.02). The 95% increase in plasma TGFB1 that occurred after treatment with NP001 vs placebo and the elevated level of this factor one month after the last dose of treatment, suggests that NP001 may have acted in part to reset the innate immune system. Vital Capacity and Inflammation Recent studies of ALS pathogenesis have confirmed that inflammation caused by misfolded proteins such as SOD1 and TDP-43, begins at the neuromuscular junction (NMJ) and involves innate immune system activated macrophages. When the immune system is dysfunctional, inflammation in this area compromises the phrenic nerve - the nerve responsible for supplying motor signals to the diaphragm, essential for breathing. Vital capacity tests objectively assess the operation of the NMJ between the phrenic nerve and the diaphragm - potentially linking innate immune function with a measurable, survival-associated clinical outcome. "In terms of immune system regulation, the presence of high CRP (plasma level > 1.13 mg/kg) is a strong signal that the innate immune system, including other acute phase reactants, is engaged and trying to regulate an inflammatory process, contributing to ALS pathogenesis" said Michael McGrath, MD, PhD, CSO Neuvivo and Professor Emeritus of Medicine, UCSF. "NP001 treatment acts to augment the naturally occurring immune response and supports resolution of the CRP-mediated process related to ongoing loss of respiratory function. Data regarding treatment initiation and effect on vital capacity confirm that respiratory function is measurably failing early in the disease course as NP001 slows VC loss early on. These observations are important even if vital capacity is near normal at date of diagnosis. Given its objectivity, the VC test used as a biomarker may allow for the direct evaluation of innate immune activity in relation to ALS disease progression." "Results of this study demonstrate the role of the innate immune system in ALS pathogenesis and importantly, in the maintenance of respiratory capacity," said Ari Azhir, PhD, CEO, Neuvivo. "Given elevated levels of necessary anti-inflammatory proteins induced well after dosing, we postulate it may be possible to regulate immune function to the point where no further damage would be forthcoming in patients adequately controlled with NP001 treatment. A notable area of interest would be in additional neurodegenerative diseases with evidence of CRP elevation." Link to Study in Cells: Cells | Free Full-Text | Regulation of the Innate Immune System as a Therapeutic Approach to Supporting Respiratory Function in ALS (mdpi.com) – McGrath, et al. Editor's Note: The macrophage is the most primordial cell in the innate immune system. It is a type of white blood cell involved in the functioning of the inflammation-resolution cycle. Normally, in response to infection/activation, a subset of macrophages become inflammatory, and another subset become wound healing to maintain immune activation equilibrium. In ALS, the process is compromised, resulting in unchecked inflammation. Macrophage-targeted treatment with NP001 restores the innate immune activation balance. About Neuvivo: Neuvivo is a private, late-clinical stage biopharmaceutical company developing advanced treatments for ALS and other neurodegenerative diseases. The company was formed by industry leaders and scientists, focused on improving the prognosis for patients diagnosed with ALS and a range of diseases for which few current treatment options exist. Lead candidate NP001 has been shown to be effective in a large subset of people living with ALS and has an exceptional safety profile. Neuvivo is working to make this treatment broadly available to patients as soon as possible. For more information please visit: Contact: Jennifer Larson 415 409 2729 Jennifer@neuvivo.com