AMABIOTICS Amabio otics is a bio opharmaceeutical comp pany develo oping innovvative micro obiome med dicines to fight ag ge‐related d diseases tha at are linked d to mitoch hondrial dyssfunction. Contact:: Patrice Garn nier (CEO) E‐mail: p p.garnier@am mabiotics.com Cellphonee: +33 6 62 2 28 67 66 PRO OJECT SUMM MARY Amabiottics is a biopharmaceuticcal company developing innovative m microbiome m medicines to o fight age‐ related d diseases thatt are linked to o mitochond drial dysfuncttion. We havee a pipelinee of productt candidates led by AMA A‐101 as a potential firrst‐in‐class therapy for Parkinso on disease. Our pipelin ne also includes R&D programs in nvestigating the improvvement of mitochondrial functio ons in obesitty (AMA‐201) and tissuess regeneratio on (AMA‐301). An experimented exeecutive team m manages th he company:: Dr Patrice G Garnier, CEO and Professsor Antoine Danchin (member off the French A Academy of SScience), CSO O and Founder. We aim tto become th he leading provider of no ovel medicinees based on tthe human m microbiome. To build our portfolio o of compou unds, we are exploring th he meta‐mettabolism of tthe human m microbiome and the application o of co‐evolved d metabolitees as therapies to treat m mitochondriaal dysfunction n, whether environm mental or gen netic. We disccover and d develop an emerging e claass of comp pounds from m the humaan microbiome. These compounds have co‐‐evolved sym mbiotically w with people aand may reduce the riskss, side effectts and high costs asssociated with h chemically driven drug developmen nt. SCIENCEE AND TECHN NOLOGY: Our science and tech hnology reliees on the und derstanding of the “chasssis” using th he engineer’ss reasoning of Synthetic Biology w we can summ marize as thee following: “What sh hould not I fforget if I weere to constru uct a living o organism?” Synthetic Biology aim ms at creating microbial cell factories. From an engineer’s point of view, it deals with the genetic program ms that are rread by cellular machinery. The elusive and multtifunctional mostly w cellular “chassis” is the « hardw ware » that eenables execcution of insstructions from this program. It is ork equally w well for all tyypes of progrrams. Howevver, besides expressing usually tthought to be able to wo the geneetic program,, cells reprod duce, maturee, age, becom me senescentt and die. 1 We analyze the funcctions involvved in copingg with these inevitable processes p an nd focus on solving s the ms associated d with chassis‐imposed cconstraints. This has allo owed us to develop a p portfolio of problem compounds that, wee believe, haave a positivee influence on o healthy lo ongevity, and in particullar provide or age‐relateed diseases such as Parkin nson’s. powerful therapies fo developed H HTBiome, a unique, proprrietary microbiome dicovvery platform m, to screen Amabiottics has also d for addittional promissing compounds. MARKETT: Affectingg over 1.5 m million peoplle across thee seven major markets (the United States, Japaan, France, Germanyy, Italy, Spain and the U United Kingdo om), Parkinsson’s diseasee (PD) is a prrogressive neeurological condition that is caused by the d degeneration n of dopamin ne receptors in the basal ganglia. To d date, there are no available treaatments thatt are capablee of curing PD, and the current goal o of therapy iss to reduce symptom ms. The Parkkinson’s diseease market was valued at 2.8 billio on euros in 2 2019 and afffects about 1.5 million people in the major pharmaceuttical marketss. An efficien nt neuroprottectant would allow to ggain a large share of the market. OUR INTTEREST IN ESSTABLISHING G A COLLABO ORATION: Establish h strategic paartnerships w with biotechn nology companies or R&D D institutes to o: ‐ Acceleerate and maximize m thee potential o of our candidate products worldwide and/or co‐develop c extended d products (ee.g. diagnosttic test); ‐ Co‐develop a much wider portfo olio of poten ntial candidatte we have id dentified. 2 Presenting our strategic plan to investors to raise funds for the preclinical phase development scheduled in 2015.  About the company and the project At AMABIOTICS we aim to become the leading provider of novel medicines based on the human microbiome. We discover and develop an emerging class of compounds from the human microbiome. We have a pipeline of product candidates led by AMA‐101 as a potential first‐in‐class therapy for Parkinson disease. Our pipeline also includes R&D programs investigating the improvement of mitochondrial functions in obesity (AMA‐201) and tissues regeneration (AMA‐301). These compounds have co‐evolved symbiotically with people and may reduce the risks, side effects and high costs associated with chemically driven drug development. Our candidate products address diseases that are not well served by currently available treatments and represent large potential commercial market opportunities. We believe that our candidate products offer innovative therapeutic approaches and may provide significant advantages relative to current therapies. RESEARCH PROGRAM To build our portfolio of compounds we are exploring the metabolism of the human microbiome with HTBiome, a unique proprietary microbiome discovery platform to screen for additional promising compounds. OUR SCIENCE Understanding the “chassis” using the engineer’s reasoning of Synthetic Biology, addressing this question: What should I not forget if I were to construct a living organism? Synthetic Biology aims at creating microbial cell factories. From an engineer’s point of view, it deals mostly with the genetic program that is read by cellular machinery. The elusive and multifunctional cellular “chassis” is the « hardware » that enables execution of instructions from this program. It is usually thought to be able to work equally well for all types of programs. However, besides expressing the genetic program, cells reproduce, mature, age, become senescent and die. We analyze the functions involved in coping with these inevitable processes and focus on solving the problems associated with chassis‐imposed constraints. This has allowed us to develop a portfolio of compounds that, we believe, have a positive influence on healthy longevity, and in particular provide powerful therapies for age‐related diseases such as Parkinson’s. PARTNERING As part of our strategy, we selectively pursue collaborations to advance and maximize the commercial potential of our pipeline. We are interested to co‐develop extended products such as diagnostic test with a biotech company and/or R&D institute for our molecule. We have identified a much wider portfolio of potential candidate that we aim to develop through collaboration. 3 We are aalso looking ffor opportun nities to workk with US invvestors.  T The innovat tive and cre eative aspeccts of the project The future of drug‐oriented pharrmacology will lie in the eexploitation o of compound ds that co‐evvolved with their hossts and theirr ancestors. TThe frequentt failure of paassing stage III clinical triials for manyy drugs is a direct co onsequence o of absence of co‐evolutio on of the chemical with th he organism’’s metabolism m. In fact, because enzzymes are generally pro omiscuous (i.e. they can recognize aa variety of substrates beside ttheir preferrred one) it is expected that one among the m many presen nt in an orgganism will recognizze any novel ccompound, b becoming an n unwanted ttarget. AMAbiottics expects tto play a sign nificant role iin this paradiigm shift. We disccover and d develop an emerging e claass of comp pounds from m the humaan microbiome. These compounds have co‐‐evolved sym mbiotically w with people aand may reduce the riskss, side effectts and high costs asssociated witth chemicallyy driven dru ug development. Our can ndidate prod ducts addresss diseases that are not well seerved by currrently availaable treatmeents and rep present largee potential ccommercial market o opportunitiess.  S Social impa act, feasibility and econ nomic viability of the p project SOCIAL IMPACT Accordin ng to the American Journal of Manageed Care, the annual econ nomic impactt of Parkinson’s disease in the United States is around $ $10.8 billion, including bo oth direct m medical expen nses and ind direct costs such as lost income, disability payyments and medical costts. 4 The financial burden of Parkinson’s disease on individuals and their families is immense. Drugs commonly used to treat Parkinson’s disease can cost up to $6,000 per year per patient. Surgical treatments for Parkinson’s disease can cost $25,000 or more. As the disease progresses, institutional care at an assisted‐living facility or nursing home may be required and these costs can exceed $100,000, per person annually. The mental and emotional cost of PD on patients, families and friends cannot be quantified. What is clear is that investment in medical research that leads to better treatments for Parkinson’s disease can save millions of dollars each year. Studies have indicated that for every dollar spent on high quality research $13 could be saved in direct and indirect costs. If new therapies could be found that could produce even a modest ten percent delay in the progression of Parkinson’s disease, hundreds of millions of dollars could be saved every year. ECONOMIC VIABILITY & FEASIBILITY Affecting over 1.5 million people across the seven major markets (United States, Japan, France, Germany, Italy, Spain and United Kingdom), Parkinson’s disease (PD) is a progressive neurological condition that is caused by the degeneration of dopamine receptors in the basal ganglia. To date, there are no available treatments that are capable of curing PD and the current goal of therapy is to reduce symptoms. Over 40 years since its introduction, levodopa (l‐DOPA) remains the most effective therapy for reducing the symptoms associated with PD. In addition to l‐DOPA, several drugs from various different classes are also available to treat PD; however, they all ultimately modulate dopamine levels (Dopamine agonists, COMPT, MAO). There is an unmet need for drugs that can slow or prevent disease progression. The next groundbreaking therapy that will change the market landscape will be the development of a neuroprotective candidate. As the aetiology of PD becomes clearer, the identification of genes or proteins that mediate the neurodegeneration of dopaminergic neurons in the substantia nigra will eventually lead to the advancement of disease‐modifying candidates targeting these mutations. Big Pharma dominates the Parkinson’s disease market however innovative neuroprotective candidate are now in hand of early stage biotech. Our strong experience concerning all the aspect of such early stage specific development with compounds coming from the microbiome (R&D, IP, reglementation, etc.) would allow to develop extended product (such as diagnostic test) or bring very new promising molecules quickly in preclinical phases. Our partnership with the ICM (Brain and Spine Institute) in Paris will give us the capacities to conduct preclinical phase and give strong chances of success. 5