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Start-Up Spotlight: CuroNZ Ltd

Posted on March 3rd, 2017 by in Pharma R&D

Curo NZ

In Auckland, New Zealand, one biotech start-up has set its sights on research that can advance the treatment of diseases of the central nervous system. That company is CuroNZ, and Chief Scientist and Managing Director Dr. Frank Sieg describes their excellent progress so far, and what’s ahead.
What does the company do?

CuroNZ is a biotech company that is currently entering clinical stage with its novel chemical entity NRP2945 (peptidomimetic). NRP2945 is a systemically acting injectable that is readily crossing the blood brain barrier and being ultra-potent in providing neuroprotection, neural regeneration including synaptogenesis in the central nervous system (CNS) by working via a novel mechanism of action at plasma membrane level of CNS neurons.

By interacting with the receptor complex consisting of CXCR4 and a novel CCR receptor subunit, NRP2945 signals to the nucleus to provoke a transcriptome that induces anti-inflammatory cascades, neuroprotection, and regeneration genes. The respective encoded proteins of these genes are an important “self-healing” source of the body to tackle CNS injury and disease, and this technology will enable neural regeneration without the need of stem cell transplantation.

Initially, NRP2945 will be trialed in children diagnosed with severe refractory epilepsy where neural circuits are wrongly primed and a remodeling of the synaptic network is crucial to provoke long-lasting effects on seizure control. If proof of concept can be shown, CuroNZ will open follow-up compounds of NRP2945 to a variety of brain diseases.

Describe the background of the company and what it aims to achieve.

CuroNZ set out in 2010 to develop biological drug candidates consisting of synthetic peptides mimicking naturally occurring neural regeneration promoting proteins in humans. The initial discovery showed extensive regeneration within an ex vivo brain slice model showing migrating neurons after Neural Regeneration Peptide (NRP) contact from an intrinsically difficult to regenerate  area of the brain, the dorsal thalamus (Landgraf et al., 2005 published in FASEB J. 19: 225-227 and Gorba et al., 2006 published in Exp Cell Research,  312: 3060-3074).

The relevance of this finding and its correlation to epilepsy comes to light by considering the very difficult to treat absence seizures that are triggered by a dysfunctional thalamo-cortical neural network. This impairment of the respective network has mainly to do with wrongly primed GABAergic transmission of the synaptic and extra-synaptic GABA A receptors. The therapeutic intervention strategy of NRP2945 is to activate an increase in GABA production as well as increased protein expression of the GABA A receptors, and therefore put the entire neural network on enhanced inhibitory transmission. It has been shown in numerous publications that effective neural regeneration is possible only under inhibitory transmission.

CuroNZ will provide a chronic therapeutic intervention treatment with NRP2945 by providing long-lasting expression of environmental cues in the CNS of Lennox-Gastaut Syndrome diagnosed children. It is predicted that this treatment will re-set thalamo-cortical neural circuits and cause cessation of seizures.

Why is this research so significant? What impact will it have on the industry?

This NRP-related therapeutic intervention treatment will be one of the future for all human therapeutic applications where an ultra-low drug dosage will provide an effective phenotype change in disease states without having any off-target effects, therefore leading to a strong reduction of drug-related adverse effects in the human body.

If clinical proof-of-concept can be established, treatments with small receptor-targeting synthetic peptides (easy to manufacture to high purity) have the potential to revolutionize the biotech / pharmaceutical industry by providing effective and potentially self-administered treatments for severe CNS diseases.

What will the company’s next steps be?

CuroNZ has prepared an investigator brochure for NRP2945 and a clinical phase 1 protocol. The company is making use of the regulatory landscape in New Zealand / Australia, where a clinical phase 1 trial (adult healthy volunteer study) can be conducted first before the filing of the IND with CDER (FDA). CuroNZ expects to be ready for the clinical proof-of-concept (POC) children trial at the end of 2017.

In the meanwhile CuroNZ has further pre-clinical POC-studies in epilepsy ongoing and anticipates filing for breakthrough status with the FDA when human phase 1 are finalized.

Why is this important now?

Apart from intensively exploring genetic engineering of receptor targets, antibody technologies, and small molecule research, the pharmaceutical industry has been rather reluctant to trial synthetic peptides as human therapeutics with the exception of the diabetic and heart health arena. CuroNZ is adamant in its belief that specifically small synthetic peptides can make a difference in drug development in the future by providing safe and effective treatments that are unrivaled by antibodies or small molecules.

Are you currently looking for partners or investment?

CuroNZ Ltd is looking for the POC-investment in the second half of 2017. Because we are also in possession of a follow-up compound for NRP2945, which we will trial in other catastrophic and malignant CNS diseases, CuroNZ’s development strategy will be of a dual nature: 1) POC study for NRP2945, and 2) make the follow-up compound ready for clinical phase 1 trials. In regard to partners, CuroNZ is open to mutually beneficial arrangements that will fasten the pathway of Neural Regeneration Peptides to market in order to provide meaningful treatments for patients suffering from severe CNS diseases.

What are CuroNZ employees saying about the work they are doing?

“I find it really exciting to be working for a company that has a drug candidate that has very real potential to give benefit to people with a range of neurological conditions.”
— Mark Thomas, Senior Research Associate

To get in contact with Dr. Frank Sieg, or to follow CuroNZ:

Email: frank@curonz.com

Web: www.curonz.com

LinkedIn: https://nz.linkedin.com/in/franksiegcuronz


 

All opinions shared in this post are the author’s own.

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