Neuren reports successful NNZ-2566 Phase 1b safety trial results
Key points
· Neuren successfully completes all cohorts of the Phase 1b study for NNZ-2566 to enable mild-moderate and
severe Traumatic Brain Injury (TBI) trials to proceed
· NNZ-2566 development on track for Phase 2 mild-moderate and severe TBI trials to be conducted under a US IND
· World-leading TBI research institutes identified to participate in the Phase 2 trials
Neuren Pharmaceuticals Ltd (ASX: NEU) has successfully completed its final high dose Phase 1b safety and tolerability
trial for its second lead candidate, NNZ-2566, which is being developed to treat traumatic brain injury (TBI).
The completion of the Phase 1b trial will now enable Neuren to proceed with two Phase 2 trials, one in severe TBI and
one in mild-to-moderate TBI. The trials, due to start in mid 2008, are planned to be conducted in the United States and
New Zealand in collaboration with the US Army.
The results from the Phase 1b study were referred to the independent Data Safety Monitoring Committee (DSMC) for review.
The DSMC confirmed the safety profile of NNZ-2566 for the fourth and final cohort which involved the maximum dose of 20
mg/kg bolus followed by a 6mg/kg/hour infusion over 72 hours. This dose provides a significant safety margin over the
doses planned for future trials and will enable Neuren to proceed into Phase 2.
Planning is now well under way for two 2008 Phase 2 trials in patients with TBI. The Phase 2 mild-moderate and severe
TBI trials will be conducted under a US IND which will enable Neuren to obtain early regulatory input into the final
outcome measures for its major efficacy trials and will pave the way for a fast-track approval status for the drug. It
will also enable access to world-leading experts in TBI (civilian and military) and very high recruiting US sites, which
will expedite the study timelines.
Dr Parmjot Bains, Chief Operating Officer of Neuren, stated: “The completion of our Phase 1b clinical trial is a
significant milestone for the company and represents a major step toward the potential development of a viable treatment
option for traumatic brain injury. Moving forward into Phase 2 trials under a US IND will greatly help to accelerate
development on the path to possible drug approval.”
Five world-leading investigators and research sites in the US have been identified for the trials (University of
Rochester, University of Miami, US Army Institute of Surgical Research; Inova Fairfax Hospital, University of California
at Los Angeles) and three sites in New Zealand (Department of Neurosurgery, Auckland Hospital; Department of Emergency
Medicine, Middlemore Hospital; Van Der Veer Institute, Christchurch Hospital).
The Phase 1b trial involved 28 healthy volunteers in four groups who received one of four escalating doses of a bolus (a
large single dose) plus infusion of NNZ-2566 at the Royal Melbourne Hospital in Melbourne, Australia. Five volunteers in
each of the four cohort groups received either 20mg/kg bolus of NNZ-2566 followed by a 1mg/kg/hr infusion for 12 hours,
3mg/kg/hr infusion for 24 hours, 3mg/kg/hr infusion for 48 hours or a 6mg/kg/hr infusion for 72 hours respectively. The
remaining two in each group received placebo.
Clinical Appendix
The following additional information is provided in accordance with the Code of Best Practice for ASX Reporting by Life
Science Companies.
Trial Title: A Phase 1b, single ascending dose, safety and pharmacokinetic study of NNZ-2566 in healthy volunteers.
Objectives: The unblinded trial aims to establish the safety of NNZ-2566 in humans. Data will also be obtained to
understand the distribution of NNZ-2566 in the body to allow for the establishment of safe dosing levels for future
trials. Proposed future trials will aim to test both the efficacy and safety of NNZ-2566 in patients with
mild-to-moderate and severe traumatic brain injury (TBI).
Investigators:
Clinical Investigator: Dr Peter Hodsman
Project Manager: Dr Kathleen Durbin, Neuren Pharmaceuticals
Primary Objective: To establish safety, tolerability and pharmacokinetic action of NNZ-2566 in humans.
Secondary Objective: To understand the distribution of NNZ-2566 in the body to allow for the establishment of safe
dosing levels for future trials.
Method: Four cohorts, each comprising seven healthy male volunteers. Starting from a very low dose the health and safety
of each volunteer will be thoroughly checked before further higher dose levels are administered to other volunteers.
Cohort 1: Five volunteers receive 20 mg/kg of NNZ-2566, via 10-min infusion, followed by 1 mg/kg/hr of NNZ-2566 for 12
hours. The remaining two receive placebo.
Cohort 2: Five volunteers receive 20 mg/kg, 10-min infusion, followed by 3 mg/kg/hr for 24 hours. The remaining two
receive placebo.
Cohort 3: Five volunteers receive 20 mg/kg of NNZ-2566, via 10-min infusion, followed by 3 mg/kg/hr of NNZ-2566 for 48
hours. The remaining two receive placebo.
Cohort 4: Five volunteers receive 20 mg/kg of NNZ-2566, via 10-min infusion, followed by 6 mg/kg/hr of NNZ-2566 for 72
hours. The remaining two receive placebo.
Trial Endpoints: The results of Cohorts 1-4 were submitted to the DSMC for review of safety, tolerability and
pharmacokinetic action of NNZ-2566. The DSMC reviewed the final cohort and were satisfied that there were no major
concerns regarding the safety of NNZ-2566.
About NNZ-2566
NNZ-2566 is a novel molecule that has a profile suitable for both intravenous infusion and chronic oral delivery. It
has been shown to be protective in numerous in vitro and in vivo models of brain injury, and is currently in development
to treat traumatic brain injury. Since 2004, NNZ-2566 has been developed in collaboration with the US Army’s Walter Reed
Army Institute of Research under a Cooperative Research and Development Agreement which includes Clinical Protocol
development and regulatory filings.
About Neuren Pharmaceuticals
Neuren Pharmaceuticals (ASX: NEU) is a biopharmaceutical company developing novel therapeutics in the fields of brain
injury and diseases and metabolic disorders. The Neuren portfolio consists of eight product families, targeting markets
with large unmet needs and limited competition. Neuren has four lead candidates, Glypromate®, MotivaTM, NNZ-2566 and
NNZ-2591 targeting a range of acute and chronic neurological conditions. Neuren has commercial and development
partnerships, including with the US Army Walter Reed Army Institute of Research, Metabolic Pharmaceuticals, UCLA Medical
Center and the National Trauma Research Institute in Melbourne.
Ends