Investment proposition

1. Company Profile and Portfolio
Corfù Innovation Summit
October 5-7, 2015 - Corfù
Industry: Healthcare
Sector: Pharmaceuticals - Oncology
Founded in: Jesi- Italy, Dec 2013
info@aesistherapeutics.eu
Cristina Geroni, CEO
Carmela Salvatore, COO

2. Hispano-Italian Biopharma spin-out from
&
Shell Company focused on R&D of
innovative oncology drugs
Company Overview

3. 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

4. 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, Chrysalon
CEO of Naxospharma (Italy)
>60 patents
Carmen Plasencia, Co-founder
CEO of Aromics
(Barcelona, Spain)
Narcis Clavell, Co-founder
Engineer, MBA
Co-owner of Aromics
Founder and owner of Ateknea
Solution.
Federico M Arcamone
40+yr Oncology R&D
Farmitalia, Menarini Ricerche
Board of Naxospharma
>100 patents
People who know how to do the job because they have already done it

5. Two different unmet Cancer
medical needs

6. Two different unmet Cancer
medical 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

7. The Solution
(US Patent 8,188,109B2)
Innovative proprietary compoundsInnovative proprietary compounds
viavia rational chemical modifications of plantrational chemical modifications of plant
alkaloid berberinealkaloid berberine
 Active on clinically validated targets in cancer treatmentActive on clinically validated targets in cancer treatment
 First in class compounds with high antitumor efficacy andFirst in class compounds with high antitumor efficacy and
good tolerabilitygood tolerability

8. The Solution
(US Patent 8,188,109B2)
Innovative proprietary compoundsInnovative proprietary compounds
viavia rational chemical modifications of plantrational chemical modifications of plant
alkaloid berberinealkaloid berberine
 Active on clinically validated targets in cancer treatmentActive on clinically validated targets in cancer treatment
 First in class compounds with high antitumor efficacy andFirst 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

9. NAX035
Activity on TS overexpressing MT cells
STO
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)

10. Therapeutic focus Mesotheliomas
Competitive Landscape
Compound (Company) Mechanism of Action
NGR-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 Antibody
against 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

11. HER2 positive Human BC cells (SK-BR-3)
NAX014
Activity on HER-2 positive BC
Antitumor efficacy on spontaneous mammary tumor
HER-2/neu transgenic mice (oral)
HER2
p-HER2
β-actin
NAX
014
Effect on HER2/neu expression
and phosphorylation
SK-BR-3 cells
NAX014 shows unique
ability to reduce HER-2
expression in breast
cancer

12. 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 Cancer
Competitive Landscape

13. Business Model

14. Investment and Use of Funds
>3YR INVESTMENT PLAN FOR TWO COMPOUNDS AND INDUSTRIAL COSTS
Funds
(€ Million)
Seed
investment
€M 0.485
1st
investment round
€M2,420
2nd
investment round
€M 3,675
Time
Y1
1Q
Y1
2Q
Y1
3Q
Y1
4Q
Y2
1Q
Y2
2Q
Y2
3Q
Y2
4Q
Y3
1Q
Y3
2Q
Y3
3Q
Y3
4Q
Y4
1Q
Use of
funds
Preclinical
requirements of
drug candidate
Preclinical development
and Fist Patient In
To 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)

15. Project Value and ROI

16. 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
Payment
(in cash)
Total
Announced
Deal Value
Lpath/Merck Serono (Asonep in Phase I) $23 M $445 M
S*BIO/Onyx (SB1518/SB1578 in
preclinical/PhaseI)
$25 M $575 M
Ardea 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

17. InnovativeInnovative
CandidateCandidate
CompoundsCompounds
to overcome currentto 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.e
u

18. Compound Annual Growth Rate (CAGR)
Market OpportunityMarket Opportunity
Breast CancerBreast Cancer
MesotheliomasMesotheliomas
Global pharma market was valued USD 9.8 bn in 2013
with forecast CAGR of 5.8% reaching USD 18.2 bn in 2023
The 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 2010
with forecast CAGR of 4.1% to reach USD 218m by 2017.
The major incidence peak expected in the next 15-20 years