A novel therapy and companion biomarker for Alzheimer’s disease

We have: Identified underlying mechanism driving neurodegeneration Developed patented molecules that prevent further neuron loss Identified biomarker to support pre-symptomatic diagnosis Patented compounds shown to block cell migration in metastatic cancers We are looking for: Partners to support drug development Investors to build the company Outlicence in other areas 2 There is global unmet need, with no drugs licensed since 2002

BIOMARKER in blood detects degeneration before symptoms appear += MEDICATION for stopping any further neuronal death PERMANENT PREVENTION of symptom onset! BUT needs identification of the basic brain mechanism... Neurodegeneration: Ideal treatment 3

Braak et al., 2011 And only spreads to the cortex in later stages, shown by red shading Alzheimer’s degeneration starts in the brainstem

Adult Neurodegeneration is cell development inappropriately activated Cells stabilise, lose plasticity Cell Death Compensation by extant cells Cell Death Mobilise development mechanisms: good in embryo brains The same process is toxic in mature brains Vulnerable cells remain sensitive to growth factors DAMAGE Continuing cycle of cell death : NEURODEGENERATION

This scenario proven: A novel peptide high in developing brain is reactivated in Alzheimer’s

Peptide drives production of amyloid and p-tau Peptide drives neurodegeneration Peptide increases production of its own target receptor Creating positive feedback loop of neurodegeneration

The peptide in spinal fluid is significantly higher in Alzheimer’s disease Promising biomarker Level of peptide

A novel therapeutic strategy – NBP-14 Neuro-Bio has designed molecule which protects neurons from the toxic actions of the peptide and of amyloid NBP-14 binds to the α7 receptor in place of the peptide preventing the continuing destructive cycle of neurodegeneration NBP-14 and all derivatives are fully patented NBP-14 is being engineered with the aim of producing a lead drug candidate 9

Next steps Presence of Peptide in post-mortem Alzheimer’s vs control tissue: understanding its biosynthesis Release of Peptide in ex vivo brain slices, into spinal fluid, into blood in pathological conditions: development as a biomarker Action of Peptide in evoking Alzheimer’s-like pathological profile in cell lines, brain slices, and in vivo models Blockade of Peptide by NBP14, peptide variants, peptidomimetics, antibodies Comparison Peptide presence, release, action and blockade in neurodegeneration and cancer Therapy: Modified peptides and peptidomimetics currently in primary and secondary stage screening and stability testing for selection of lead candidate. 10

11 Publications

BIOMARKER in blood detects degeneration before symptoms appear += MEDICATION for stopping any further neuronal death PERMANENT PREVENTION of symptom onset! BUT needs identification of the basic brain mechanism... Neurodegeneration: Ideal treatment 12 (Peptide)(NBP-14 variant)

Proof of T14 action and blockade in clinical tissue Progressing new approach KEY PROJECTS Biomarker development Complete ex-vivo model Establish in-vivo model Licensing options for cancer therapy Drug candidate efficacy and molecular optimisation Pharmacokinetics

Baroness Professor Susan Greenfield CBE Chief Scientific Officer & Founder Expertise: 40 years research on non-cholinergic functions of AChE Dr Charles Morgan Chairman Expertise in investment and growth of early stage companies Dominique Kleyn Business manager Expertise in licensing and business development for technology commercialisation Dr Sara Garcia Ratés Deputy Director of Research Expertise in the biology and pharmacology of the alpha-7 receptor; primary stage screening with cell lines Professor Margaret Esiri University of Oxford Professor Colin Masters University of Melbourne Professor Gary Small UCLA Neuro-Bio Executives 14 Scientific Advisory Board Dr Rod Porter Industrial Medicinal Chemist

Funds required and application focus 15 Neuro-Bio will build on recent successes and drive its drug candidate to Phase 1 in the shortest possible timeframe Capital is required to continue the pioneering research at its current rapid pace Identification of lead drug candidate (£2.0m) Preclinical (£3.0m) Phase 1 (£3.0m)

Partnering information 16 Neuro-Bio Limited, Building F5, Culham Science Centre, Oxford OX14 3DB, UK Important: This presentation was prepared by Neuro-Bio and the content herein is of a strictly confidential nature. It should not be reproduced, distributed or published by the recipient or used for any purpose whatsoever without the prior written consent of Neuro-Bio. Although the information contained in this presentation was obtained from sources considered reliable, Neuro-Bio cannot guarantee the accuracy and truth of the same. The opinions presented herein represent those of Neuro-Bio at the present time, and are, therefore, subject to amendment and alteration. Neuro-Bio is not responsible for any direct losses or reduced profits that may result from any use of the information contained herein.