Company Profile and PortfolioCorfù Innovation SummitOctober 5-7, 2015 - Corfù

Industry: Healthcare Sector: Pharmaceuticals - OncologyFounded in: Jesi- Italy, Dec 2013info@aesistherapeutics.eu

Cristina Geroni, CEOCarmela Salvatore, COO

Hispano-Italian Biopharma spin-out from

& Shell Company focused on R&D of innovative oncology drugs

Company Overview

The Mission To move validated inventive findings by the two parent companies into clinical development To offer first-in-class drug candidates to commercial partners

Hispano-Italian Biopharma spin-out from

& Shell Company focused on R&D of innovative oncology drugs

Company Overview

Management Team

Skilled industry veterans and senior entrepreneurs

Expertise in oncology R&D combining 180+ years experience and 220+ patents

Advisor

Cristina Geroni, CEO 35+yr Oncology R&D Farmitalia, Pharmacia, Pfizer>55 patents

Carmela Salvatore, COO 15+yr Oncology R&D Menarini Ricerche

Paolo Lombardi, CSO 35+yr Oncology R&D Farmitalia, Menarini, IBI, ChrysalonCEO of Naxospharma (Italy)>60 patents

Carmen Plasencia, Co-founderCEO of Aromics (Barcelona, Spain)

Narcis Clavell, Co-founderEngineer, MBACo-owner of Aromics Founder and owner of Ateknea Solution.

Federico M Arcamone 40+yr Oncology R&DFarmitalia, Menarini RicercheBoard of Naxospharma>100 patents

People who know how to do the job because they have already done it

Two different unmet Cancermedical needs

Two different unmet Cancermedical needs

Malignant Mesothelioma (MT) rare treatment-resistant cancer one drug approved (Alimta)

Thymidilate Synthase a marker of drug responsiveness

HER2-positive breast cancer (BC) aggressive, poor prognosis metastatic type of cancer

Gold standard drugs targeting HER-2 show modest efficacy and side effects

The Solution(US Patent 8,188,109B2)

Innovative proprietary compoundsInnovative proprietary compoundsviavia rational chemical modifications of plant rational chemical modifications of plant

alkaloid berberinealkaloid berberine

Active on clinically validated targets in cancer treatment Active on clinically validated targets in cancer treatment First in class compounds with high antitumor efficacy and First in class compounds with high antitumor efficacy and

good tolerabilitygood tolerability

The Solution(US Patent 8,188,109B2)

Innovative proprietary compoundsInnovative proprietary compoundsviavia rational chemical modifications of plant rational chemical modifications of plant

alkaloid berberinealkaloid berberine

Active on clinically validated targets in cancer treatment Active on clinically validated targets in cancer treatment First in class compounds with high antitumor efficacy and First in class compounds with high antitumor efficacy and

good tolerabilitygood tolerability

NAX035

Active on tumours with high levels of

Thymidilate Synthase

NAX014

Active on HER-2 positive tumours

NAX035Activity on TS overexpressing MT cells

STO

MesoII

Human peritoneal mesothelioma

(STO) cells

NAX035 shows target inhibition in vitro and in

vivo mesothelioma

Effect of NAX035 on TS protein levels in mesothelioma tissues (STO)

Therapeutic focus MesotheliomasCompetitive Landscape

Compound (Company) Mechanism of ActionNGR-hTNF (MolMed)* Vascular target agent

Raltitrexed (Astra Zeneca) Folate antimetabolite

Onconase with Doxorubicin (Alfacell Corporation)

Ribonuclease enzyme

Vorinostat (Merck Sharp & Dohme) Histone deacetylase inhibitor

Pemetrexed and Cisplatin + Bevacizumab (Genentech/Roche)

Monoclonal Antibodyagainst VEGF

May 2014: Fails to improve OS in 2nd-line mesothelioma (Add On to invest. choice)

The current market dominated by Alimta (in combination with cisplatin)Alimta patent expires in 2016

HER2 positive Human BC cells (SK-BR-3)

NAX014Activity on HER-2 positive BC

Antitumor efficacy on spontaneous mammary tumorHER-2/neu transgenic mice (oral)

HER2

p-HER2

β-actin

NAX014

Effect on HER2/neu expressionand phosphorylation

SK-BR-3 cells

NAX014 shows unique ability to reduce HER-2

expression in breast cancer

HER2 pathway and targets

NAX014 “unique” mechanism

to inhibit HER-2 expression

Compound (Company) Mechanism of Action

BKM120, LEE011 (Novartis); Palbociclib (Pfizer);Neratinib (Puma Biotechnology); Afatinib (Boehringer Ingelheim)

Kinase inhibitors Targeting HER2 downstream pathway

MM-302 (Merrimack) HER2 targeted antibody-drug conjugated nanoliposomal doxo

SB3 (Samsung Bioepis Co); PF-05280014 (Pfizer); APB980 (Amgen) trastuzumab biosimilar: "me-too's"

UDT1 (Beijing Biostar Technologies) Tubulin inhibitor (epothilone)

Therapeutic focus HER2+Breast CancerCompetitive Landscape

Business Model

Investment and Use of Funds

>3YR INVESTMENT PLAN FOR TWO COMPOUNDS AND INDUSTRIAL COSTS

Funds(€

Million)

Seedinvestment€M 0.485

1st investment round

€M2,420

2nd investment round

€M 3,675Time Y1

1QY12Q

Y13Q

Y14Q

Y21Q

Y22Q

Y23Q

Y24Q

Y31Q

Y32Q

Y33Q

Y34Q

Y41Q

Use of funds

Preclinical requirement

s of drug candidate

Preclinical development and

Fist Patient InTo perform Phase I clinical study

Milestone

PC Approved

First Time in Man Clinical Proof of Concept

Euro 6,6 million in capital to finance product candidates development up to Phase I clinical study completion (3+years)

Project Value and ROI

Project Value and ROI

The median total value for Oncology Deals is higher Projects Revenue for Aesis at first possible exit: IND = €10M plus milestones

Oncology Companies(Drug – Phase)

Upfront Payme

nt(in

cash)

Total Announced Deal Value

Lpath/Merck Serono (Asonep in Phase I) $23 M $445 MS*BIO/Onyx (SB1518/SB1578 in preclinical/PhaseI) $25 M $575 MArdea Biosciences/Bayer (RDEA119/other MEK inhibitors in Phase I/preclinical)

$35 M $407 M

EOS/CLOVIS Oncology (Lucitanib in Phase I/Iia) $10 M $400 M

Innovative Innovative Candidate Candidate

CompoundsCompoundsto overcome current to overcome current therapy drawbackstherapy drawbacks

Skilled Team with a track record of achievements in

Oncology R&D

Sustainable Portfolio

in unmet medical need in cancer

HER-2+ Breast Cancer

info@aesistherapeutics.eu

Compound Annual Growth Rate (CAGR) 

Market Opportunity Market Opportunity Breast CancerBreast Cancer

MesotheliomasMesotheliomas

Global pharma market was valued USD 9.8 bn in 2013with forecast CAGR of 5.8% reaching USD 18.2 bn in 2023The highest-growing segment of the market is the HER2-positive subtype, with a CAGR of 7.6% over the period, rising from USD 5.6 bn to USD 12.5 bn

Global pharma market was valued USD 165m in 2010with forecast CAGR of 4.1% to reach USD 218m by 2017.The major incidence peak expected in the next 15-20 years