Published Phase 2 Results Demonstrate 
Neuraltus Pharmaceuticals’ NP001 Potential 
Efficacy and Safety in ALS

Slowing of Disease Progression in ALS Patients with High Levels of Inflammation Supports Further Clinical Research

PALO ALTO, Calif. (April 20, 2015) – Published results from a Phase 2 clinical study demonstrate positive trends in the ability of Neuraltus Pharmaceuticals’ NP001 investigational treatment to slow the progression of amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig's disease) over a 6-month treatment period. While NP001’s slowing of decline in the primary and secondary measures of the study was not statistically significant, clinically meaningful slowing of progression was observed in patients with greater baseline inflammation, such that patients who received the high dose of NP001 (2 mg/kg) achieved a 41 percent improvement versus placebo. Additionally, the data suggest that NP001 may have a dose-dependent ability to halt ALS progression in a subset of patients exhibiting elevated levels of select inflammation biomarkers. The results appeared online in the April issue of Neurology: Neuroimmunology & Neuroinflammation, an official journal of the American Academy of Neurology.

Post hoc analysis of the study showed 25 percent of patients who received 2 mg/kg NP001 had no progression of disease during the six-month dosing period, compared to 11 percent in the concurrent placebo group, although it did not reach statistical significance (p=0.22). When matched historical placebo controls were included, the difference versus placebo became statistically significant (p=0.02). In addition, results from the study demonstrated trends of clinical benefit for the 2 mg/kg patient cohort in the change in slope of the ALS Functional Rating Score Revised (ALSFRS-R), and in change from baseline in ALSFRS-R through six months and a joint rank analysis of change of ALSFRS-R adjusted for mortality. NP001 was also found to be generally safe and well tolerated..

“These newly published results are encouraging, demonstrating the potential of NP001 to slow or halt ALS disease progression in certain patients, as well as a safety and tolerability profile that supports further study of the investigational treatment,” said Robert Miller, M.D., Clinical Professor of Neurosciences, Stanford University, and Director of the Forbes Norris ALS Research Center at California Pacific Medical Center in San Francisco, and the lead author of the study. “The NP001 Phase 2 study is the first time we’ve observed a halting of disease progression in an ALS clinical trial.”

NP001 is an intravenous investigational therapy that reduces neuroinflammation through regulation of macrophage white blood cells within the central nervous system, which are believed to be associated with the progression of ALS. Most patients in the study who responded to NP001, such as having their progression halted, had an elevated biomarker of inflammation, interleukin-18 (IL-18), and were positive for lipopolysaccharide (LPS) in blood plasma at baseline, both of which are believed to play a role in the progression of ALS.[1, 2] IL-18 and LPS levels decreased in most patients (80 percent and 70 percent, respectively) who responded to treatment with 2mg/kg NP001.

“Given the current lack of effective treatments for this deadly disease, NP001 could represent a novel approach for treating people with ALS,” said Richard S. Bedlack, M.D., Ph.D., associate professor of Neurology at the Duke University School of Medicine, and director of the Duke ALS Clinic. “If the Phase 2 results can be replicated, it could mark one of the greatest advances in ALS research. I eagerly await the start of the next NP001 clinical study and continued investigation of the factors that may lead to improved responses to this treatment by certain patients.”

Adverse events (AEs) occurred in 96 percent, 94 percent and 98 percent of patients in the 2 mg/kg, 1 mg/kg and placebo groups, respectively. Overall, the majority of AEs were considered typical of those observed in ALS patients, and were not considered to be related to NP001. A higher percentage of patients treated with NP001 reported infusion site pain and dizziness versus placebo (33 percent (2 mg/kg) and 18 percent (1 mg/kg) versus 5 percent for placebo; and 20 percent and 8 percent versus 7 percent for placebo, respectively). Treatment-emergent AEs, or those occurring during or after the first dose and within 30 days after the last dose NP001, were 71 percent (2 mg/kg) and 57 percent (1 mg/kg) versus 55 percent for placebo. Serious adverse events, including eight deaths during the trial, were considered unlikely or unrelated to NP001.

“This first peer-reviewed publication of the NP001 Phase 2 study results represents a major step forward in our effort to develop an effective treatment for people with ALS,” said Rich Casey, president and CEO, Neuraltus Pharmaceuticals. “We’re working swiftly to secure funding to initiate additional studies with the goal of seeking marketing approval for this investigational treatment as quickly as possible.”

About the Phase 2 Study of NP001

The Phase 2 randomized, double-blind, placebo-controlled study enrolled 136 patients with ALS. Patients received either NP001 2 mg/kg, NP001 1 mg/kg or placebo over a period of 6 months, followed by a 3-month follow-up period. The study was designed to evaluate the change in slope of ALSFRS-R and the safety and tolerability of NP001, as well as change from baseline in ALSFRS-R through 6 months, a joint rank analysis of change of ALSFRS-R adjusted for mortality and changes in readily measured peripheral inflammation biomarkers. A post-hoc analysis of the percentage of patients (“responders”) whose ALSFRS-R did not change from baseline was also conducted. Results of the study were first presented in December 2013 at the 24th International Symposium on ALS/MNS in Milan, Italy.

An additional secondary endpoint, agreed upon with the FDA, was the inclusion of matched historical placebo control ALS patients to increase signal detection and power. Placebo outcomes, in patients matched for inclusion criteria, from a large database of 616 historical placebo controls from six recent clinical trials, showing consistent rates of decline over the past 9 years, were used as historical controls.

About Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease) is a rare and fatal neurodegenerative disease characterized by degeneration of motor neurons in the spinal cord and brain. The cause of the disease is currently unknown, but there is increasing evidence that implicates neuroinflammation with the progression of the disease. It is believed that in people with ALS, there are increased levels of inflammatory (activated) macrophage white blood cells resulting in the release of factors in the central nervous system that leads to damage of motor neurons. NP001, a regulator of macrophage activation, exerts its effect by converting these activated inflammatory macrophages back to their normal state.

There are approximately 400,000 ALS patients worldwide; however, little is known about their condition or treatment outside of the United States and Europe, where there are approximately 30,000 and 50,000 patients, respectively. Most patients and physicians report no meaningful slowing of ALS progression from existing treatment for ALS, underscoring the need for new and effective drug therapy.

About Neuraltus Pharmaceuticals, Inc.

Neuraltus Pharmaceuticals, Inc. is a privately-held biopharmaceutical company dedicated to developing and commercializing high-impact therapeutics that address critical unmet needs for patients and physicians, primarily in the treatment of neurodegenerative diseases. Neuraltus recognizes that ALS is a devastating condition, with only one approved therapy, and is focused on developing and bringing its investigational treatments to market as quickly as possible. The Company is collaborating with global ALS specialists and seeking input from patient advocacy organizations to help inform the clinical development path and better understand the needs of people affected by the disease. In addition to NP001, Neuraltus also has a pre-clinical program, NP003, for the treatment of lysosomal storage disorders such as Fabry's disease and Gaucher's disease.

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[1] Italiani P, Carlesi C, Giungato P, et al. Evaluating the levels of interleukin-1 family cytokines in sporadic amyotrophic lateral sclerosis. J Neuroinflammation 2014, 11:94.

[2] Zhang R, Hadlock KG, Do H, et al. Gene expression profiling in peripheral blood mononuclear cells from patients with sporadic amyotrophic lateral sclerosis. J Neuroimmunol 2011;230:114-123.