Transcript AESIS Therapeutics Presentation - Next Project 12-05 - Adriatic-next

Dual Hispano-Italian spin-out from Aromics SL and
Naxospharma SRL
Company Overview
[email protected]
Business Model
Products and Cancers
Two first-in class compounds NAX014 and NAX035, chemically related to
berberine, in preclinical development targeted to the treatment of:
Poor prognosis breast cancer (BC), by impairing the human epidermal growth
factor receptor 2 (HER2) expression.
BC is worth USD 10bn with forecast 5% CAGR reaching more than USD 15bn in 2022.
Sales for HER2 + BC accounted for about 45% of major markets in 2013 and will
continue to do so through 2022.
Malignant mesotheliomas (MTs), by downregulating cellular levels of overexpressed thymidylate synthase (TS).
MTs are worth USD 165m with forecast 4.1% CAGR reaching more than USD 218m in
2017. Major incidence peak in the next 15-20 years. Market dominated by Pemetrexed +
Cisplatin; Pemetrexed patent expires in 2016.
Berberine
Berberine is an interesting and attractive natural lead compound
Innovative proprietary* compounds
obtained via rational chemical
modifications of berberine structure leading
to a new class of derivatives presenting more
selective medical indications
Berberine
Compounds with a new mechanism of action, high antitumour
efficacy and good tolerability
*) Patent Protection: freedom to operate on US Patent 8,188,109B2
Granted on May 29, 2012 to Naxospharma - priority July 20, 2009.
Application extended in EU, Japan, Australia, New Zealand
Product Candidate - NAX014
Project: Berberine-derived anticancer drugs against HER2+
tumours a .
First Clinical Candidate Compound: NAX014
Therapeutic focus: HER2+ Breast Cancer
NAX014
Unique ability to reduce HER2 expression in breast
cancer cells, trough a mechanism different from
available drugs
In vitro activity at µM concentrations
In vivo antitumour and anti-metastatic efficacy by
oral administration on HER2 expressing breast
cancer transgenic model
Tolerability at the effective doses
a) HER2 (human epidermal growth factor receptor 2) is amplified and overexpressed in 20–30% of invasive, poorly responsive breast cancers.
Today’s Therapies for
HER2+ BC
DRUG
Company
MOA
Use - Cost x mth &
FDA Approval (yr)
Trastuzumab
Herceptin®
Genentech (US)
Roche (EU)
Monoclonal Antibody
against HER2 receptor
Combo with 2006
Chemio
$4,500
Pertuzumab
Perieta®
Genentech
Monoclonal Antibody
against HER2 receptor
Combo with 2012
Chemio &
Herceptin
$6,000
TDM-1
Kadcycla®
Genentech
Antibody-drug conjugate
Single agent 2013
$9,800
Lapatinib
Tykerb®
GSK
Ado-Trastuzumab
emtansine
EGFR & HER-2
tyrosine kinases inhibitor
Combo with 2007
Chemio
$3,625
Competitive landscape
Drugs in Phase III clinical development
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" of currently used antibodies
(e.g. trastuzumab),
Targeting the transmembrane HER2 receptor domain
UDT1 (Beijing Biostar Technologies)
Tubulin inhibitor (epothilone)
Product Candidate - NAX035
Project: Berberine-derived anticancer drugs modulating overproduction of Thymidylate Synthase (TS)
First Clinical Candidate Compound: NAX035
Therapeutic focus: Malignant mesotheliomas and (drug-resistant) cancers
overproducing TS
NAX035
Novel mechanism of action, targeting the
expression of TS protein differently from
available TS inhibitor anticancer drugs
In vitro activity at µM concentrations
Efficacy on chemo-resistant tumour cells
In vivo antitumour efficacy by oral route on
human mesothelioma
Tolerability at the effective doses
Today’s Pleural MT Therapies
Drug
Pemetrexed
Alimta®
Company
EliLilly
MOA, schedule and Toxicity
Folate antimetabolite, TS inhibitor,
and dihydrofolate reductase,
glycinamide ribonucleotide formyl
transferase inhibitor.
Dose: 500 mg/m2 IV infusion; 21-day
cycle, followed 30 min later by
cisplatin (recommended dose 75
mg/m2).
To reduce toxicity, patients are
supplemented with folic acid and
vitamin B12 and are pre-medicated
with a corticosteroid
USE, Cost x Year &
FDA approval (yr)
Pleural MT
in Combo
with
Cisplatin
$24,000
2004
Competitive landscape
Drugs in Phase III clinical development
Compound (Company)
MOA
MT Type
NGR-hTNF (MolMed)*
Vascular target agent
Pleural
Raltitrexed (Astra Zeneca)
Folate antimetabolite
Pleural
Tremelimumab (Astra Zeneca)
Mab CTLA-4
Pleural, peritoneal
Onconase with Doxorubicin
(Alfacell Corporation)
Ribonuclease enzyme
Pleural , peritoneal
Vorinostat (Merck Sharp &
Dohme)
Histone deacetylase inhibitor
Pleural
Pemetrexed and Cisplatin +
Monoclonal Antibody
Bevacizumab (Genentech/Roche) against VEGF
May 2014: Fails to improve OS in 2nd-line mesothelioma (Add On to invest. choice)
Pleural
Activity Plan, Costs and Milestones (1)
from PC selection to PC approval
NAX014 or NAX035 – Activity Plan
from PC selection to PC approval
Activity
Project Milestones
CHEMISTRY
PHARMACOLOGY
TOXICOLOGY
PK-ADME
CMC MANUFACTURING
REGULATORY DOCUMENTS
Year 1 (500 K€)
Q1 Q2 Q3 Q4
PC Approved
Abbreviations: PC = Product candidate.
Milestone
Activity
Achievements
PC
Approved
Pharmacology
MOA demonstrated in vivo on experimental
tumour model
Acceptable toxicity profile (manageable,
monitorable, reversible) (go/no go)
Acceptable bioavailability
Toxicology (non-GLP)
PK/ADME
Milestones (2)
from PC to Clinical PoC
NAX014 or NAX035
Milestones and go/no go decision points from PC approved to Clinical PoC
Milestone
1: FTIM
Activity
Achievements
Toxicology (GLP)
Acceptable toxicity profile (manageable, monitorable,
reversible, predictable) (go/no go)
Viable formulation (capsule) for oral administration with
CMC Manufacturing
shelf life of at least 1 years at RT
Regulatory Documents Protocol approval by Health Authorities
Clinical
2:
Clinical PoC
Tolerability as single agent better than/comparable with
other approved agents (go/no go)
PK reached in man should reach exposures sufficient to
achieve PoC
Efficacy
Abbreviations: PC = Product candidate; FTIM = First Time in Man; PoC = Proof-of-Concept; RT = Room
Temperature
Management Team
Management & Co-founders
Cristina Geroni, CEO
•35+yr Oncology R&D
Farmitalia, Pharmacia, Pfizer
•Licensing-out oncology drugs
•>55 patents
Carmen Plasencia.
•CEO of Aromics (Barcelona, Spain)
•biochemistry, biomedicine, molecular
biology, proteomics, genomics in oncology
research
Carmela Salvatore , COO
Narcis Clavell,
•15+yr preclinical Oncology R&D
Menarini Ricerche
•Development of oncology clinical
candidates
•Engineer, MBA
•Co-owner of Aromics (Barcelona, Spain)
•Founder and owner of ATEKNEA
SOLUTIONS S.A.
Paolo Lombardi, CSO
•35+yr Oncology R&D
Farmitalia, Menarini, IBI, Chrysalon
•CEO of Naxospharma (Italy)
•Discovered Aromasin for BC therapy
(global market)
•>60 patents
Advisor
Federico M Arcamone
•40+yr Oncology R&D
Farmitalia, Menarini Ricerche
•Discovered anticancer drugs doxorubicin,
idarubicin, epirubicin (global market)
•Board of Naxospharma
•>100 patents
we-know-how-to-do-because-we-have-already-done-it
Company profile
City: Jesi (AN)
Country: ITALY
Industry: Healthcare
Sector: Pharmaceuticals
Subsector: ONCOLOGY
Founded in: 2013
Skilled Team
with a track record of
achievements in
Innovative compounds
Oncology R&D
to overcome current
therapies drawbacks
[email protected]