1. BUSINESS MODEL ANALYSIS CLÉMENT DUBOS JULIETTE PAILLARD
MARÍA ALCÁZAR DUQUE
SIHEM ALLOTI
SOSSANE NOURESTANI
BUSINESS
MODEL
ANALYSIS

2. PRESENTATION MAP About the company Governance Pipeline
Financial statement
SWOT

3. About The Company Features Headquarter: Basel, Switzerland.
Innovative pharmaceutical products
Bacterial infections, fungal infections, oncology.
Resistance and nonresponse.
Founded in 2000 as spin-off of Roche.
Publicly traded since 2004 on the SIX Swiss Exchange.
Spin off means the parent company will list the subsidiary on the public market as an independent public company, so that investors who are only interested in the subsidiary business can invest only in this section rather than invest in the whole chunk of business
Spin out means the parent company will sell the subsidiary to another company, where M&A will happen

4. Basilea Pharmaceutica ltd.
About The Company
Basilea Pharmaceuticals A/S
Basilea Pharmaceuticals ltd.
Basilea Pharmaceutica Deutschland gmbh
Basilea Pharma SAS
Basilea Pharmaceuticals iberia s.l.
Basilea Pharmaceutica China ltd.
Structure: (mettre adresse pays + voir dans le RA2015 ce qui est fait où. Location des sites de Prod ???
-Parent company : Basilea Pharmaceutica Ltd (« Basilea »).
-Swiss operating subsidiary : Basilea Pharmaceutica International Ltd (« Basilea international).
-Subholding company : Bph Investitionen Ltd (Bph).
-Chinese operating subsidiary held through Bph : Basilea Pharmaceutica China Ltd (« Basilea china »), founded in 2002.
-Wholly-owned subsidiaries in Denmark, France, Germany, Italy, Spain, UK.
(Voire map archive)
Basilea Pharmaceutica ltd.
Basilea Pharmaceutica s.r.l.

5. Research Center In China
About The Company
Research Center In China
-Wholly-owned subsidiary of Basilea
-Near Shangai, Jiangsu Province
People’s Republic of China
-Basilea’s key R&D projects
Chemical synthesis
Analytical development
Process research and development
-Awards:
High-tech Enterprise
“A” class for safety operation
Best Safety Performance
Development of the local R&D
Basilea China represents an important strategic advantage for Basilea, allowing a high degree of flexibility for future growth.

6. Dr. Thomas M. Rinderknecht
Governance
Board of Directors
Mr. Domenico Scala, Chairman
Changements dans le Board of Directors en 2016
Chairman ( ): Dr Martin Nicklasson (PhD) => Avril 2016 : Domenico Scala (economics and executive development),
Vice-chairman ( ): Domenico Scala
Members:
-Hans-Beat Gürtler ( ): commercial diploma
-Pr Daniel Lew ( ): clinical infectious disease physician
-Dr Thomas M. Rinderknecht ( ): lawyer (PhD)
-Steven D. Skolsky ( ): Biologist
-Dr Thomas Werner ( ): Chemist (PhD)
Dr. Thomas M. Rinderknecht
Dr. Martin Nicklasson
Prof. Daniel Lew
Mr. Steven D. Skolsky
Dr. Thomas Werner

7. Dr. Laurenz Kellenberger
Governance
Management Committee
Ronald Scott, CEO
Chief officers:
-Economic: Ronald Scott, commercial.
-Technology: Dr Ingrid Heinze-Krauss, organic chemistry.
-Medical: Pr Achim Kaufholf, professor of medical microbiological and Infectious Diseases..
-Scientific: Dr Laurenz Kellenberger, organic chemistry.
-Human resources: Mr Heidi McDaid, business management and human resources qualifications.
-Financial: CFO: Mr Donato Spota, business administration and information technology.
-Commercial: Mr David Veitch, biology.
Dr. Günter Ditzinger
Prof. Achim Kaufhold
Dr. Laurenz Kellenberger
Ms. Heldi McDaid
Mr. Donato Spota
Mr. David Veitch

8. Pipeline - overview

9. Pipeline - overview

10. New Antifungal Market :
ANTIFUNGALS
Medical Need
New Antifungal Market :
USD 2.35 billion sales
CANDIDA ASPERGILLUS MUCORALES
CAGR : + 17%
Mortality rates for invasive fungal infections
WW sales (mn standard units)
Commercial potential AR2006
Rationel d’utilisation (mode d’action / résultats)
Fungal infections are caused by fungi, a group of organisms abundant in nature such as molds and yeast. Fungal infections are quite common, affecting 20-25% of the general population, are typically superficial restricted to the skin or mucosal surfaces and do not
cause much harm. Invasive or systemic fungal infections are infections where the molds or yeasts have entered the bloodstream or airways and are life-threatening if not treated timely. Mortality rates are high in invasive fungal infections ranging between 25-35% in candida (yeast) infections, 34-58% in aspergillus (mold) infections, and 40-80% in mucorales (emerging mold) infections. Timely intervention with an effective broad-spectrum antifungal is key to improve outcomes.
Invasive fungal infections on the rise with frequent use of immunosuppressants
Almost 8 mn patients globally per year with an average treatment days
Availability of generic versions of Pfizer’s Vfend in the US
Pfizer = voriconazole
Astellas = amphoB liposomale, micafungine
Merck = caspofungine
CRESEMBA targets a USD 2.3 bn global invasive fungal infection market.
Three major drug classes target invasive fungal infections, including:
1. (Tri)azoles
2. (Echino)candins
3. Amphotericin B reformulations
COMMERCIAL POTENTIAL

11. Weakening of fungal cell membrane structure & function
Mechanism of action
Prodrug activation
process
Weakening of fungal cell membrane structure & function
Plasma esterase
Acetyl CoA
Squalene
Lanosterol
PharmacoD : L’isavuconazole démontre un effet fongicide en bloquant la synthèse de l’ergostérol, un composant essentiel de la membrane des cellules fongiques, via l’inhibition de l’enzyme lanostérol 14-alpha- démethylase dépendant du cytochrome P-450, qui est responsable de la conversion du lanostérol en ergostérol. Cela entraîne une accumulation des précurseurs stéroliques méthylés et une diminution de la quantité d’ergostérol dans la membrane cellulaire, ce qui affaiblit la structure et le fonctionnement de la membrane de la cellule fongique.
Prodrug de l’isavuconazonium sulfate, metabolisme par CYP 3A4 (inhibiteur) et CYP 3A5
The phase III program with CRESEMBA to investigate its role in treating invasive fungal
infections included three trials:
1. “SECURE” a global double-blind randomized phase III trial, designed to evaluate
the safety and efficacy of once-daily CRESEMBA versus Pfizer’s twice-daily Vfend
(voriconazole) in the primary treatment of invasive fungal disease caused by
Aspergillus species or other filamentous fungi: Primary & secondary endpoints met
2. “VITAL” an open-label phase III trial of CRESEMBA in the treatment of
aspergillosis patients with pre-existing renal impairment or patients with invasive
fungal disease caused by emerging and often fatal molds, yeasts or dimorphic
fungi: Effective in aspergillosis patients with renal impairment & effective in
mucormycosis
3. “ACTIVE” a phase III trial evaluating the safety and efficacy of intravenously (IV)
and orally administered CRESEMBA versus Merck & Co’s IV Cancidas
(caspofungin) followed by Pfizer’s oral Vfend in the treatment of invasive Candida
infections: Primary endpoint missed, secondary endpoints met
Lanosterol 14α-demethylase
Ergosterol
Fungi cell
Completed three phase 3 clinical trials:
ACTIVE SECURE VITAL
Cell membrane
CANDIDA ASPERGILLUS MUCORALES

12. DEVELOPMENT & REGULATORY STATUS Europe the USA MENA Latin America
Currently marketed by Basilea in Germany, Italy, the United Kingdom, Austria and France,
 Collaboration with Quintiles
Orphan Drug designation
 10 years of market exclusivity
Marketed by Basilea’s license partner :
 Astellas Pharma US
2Q16 sales = USD 12 million
Orphan drug status + Qualified Infectious Disease Product designation
 12 years of market exclusivity
MENA
Quintiles : CRO services. Assistance prix et remboursement.
En France SMR important mais ASMR V (HAS)
PIP en cours (2 years of additional protection when the Pediatric Investigation Plan is completed)
Potentielle extension pédiatrique.
Développé en collaboration avec Astellas (license exclusive pour les US et le Canada)
Basilea announced in september 2016 that it has entered into a supply, distribution and license agreement with Grupo Biotoscana for CRESEMBA® (isavuconazole) and antibiotic Zevtera® (ceftobiprole) in 19 countries in Latin America including Brazil, Mexico, Argentina and Colombia.
Under the terms of the agreement, GBT holds an exclusive license to commercialize isavuconazole and ceftobiprole in key Latin American countries.
Latin America
Distribution agreement with HIKMA
License agreement with GBT

13. ANTIBIOTICS Medical Need
Over the last 30 years, no major new types of antibiotics have been developed

14. MRSA HAP HAP is the second most common nosocomial infection
Frequent Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most frequent causes of hospital-acquired bacterial pneumonia
Between 10-30% of patients with Staphylococcus aureus bacterieia will die from the infection
MRSA
HAP is the second most common nosocomial infection
Among the highest mortality rates (62 %)
Main causes of HAP: MRSA +++ (> 20 %)
CAP up to 60 % hospitalisations
HAP

15. COMMERCIAL POTENTIAL

16. Synthesis of Peptidoglycane
Zevtera®/
Mabelio®
Mechanism of action
Prodrug activation
First broad-spectrum anti-MRSA cephalosporin authorized for HAP (excl. VAP) + CAP (Community Acquired Pneumonia)
Single agent with broad-spectrum bactericidal activity that includes MRSA and Pseudomonas spp
Ceftobiprole Modecaril (sodium)
Ceftobiprole
Enzymatic cleavage
(Plasmatique esterase)
Diacetyl
Potential to replace antibiotic combinations
Synthesis of Peptidoglycane
Ceftobiprole
Bacterial Lysis

17. DEVELOPMENT & REGULATORY STATUS Europe The USA Latin America
Currently marketed by Basilea in Germany, Italy, the United Kingdom , France , Austria, and Switzerland
→ Collaboration with Quintiles
Marketed in the Nordic Countries sept 2016
→ Collaboration with Unimedic Pharma
Market access activities ongoing in Spain
Not approved yet → Two cross-supportive phase 3 trials (ABSSSI and Bacteriema)
Special Protocol Assessment’s agreement by the FDA on going → phase III development program H1 2017
Qualified Infectious Disease Product Designation (ABSSSI and CABP)
→ 10 years of market exclusivity
Fundings: Biomedical Advances Research and Development Authority (BARDA) under contract
Latin America
CHANGEMENT
Licence agreement with Biotoscana S.L

18. Intellectual Property
MA 2015
EU MA 2014
Industrial property
Industrial property
PATENT
PATENT
SPC 1
2000
2020
2030
1999
2019
2024
2025
Commercial exclusivity
Commercial exclusivity
Industrial prop
Exclusivite commerciale : on peut la perdre. Au bout de 5 ans des 10 ans si on respecte plus la prévalence ou si on a le retour sur investissement
– 5 ans = 0 pour le SPC
USA
ORPHAN
QIDP
NCE
QIDP
2015
2022
2027 MA
MA+5
MA+10 EU
ORPHAN
PIP
2015
2025
2027

19. ANTIBIOTICS Medical Need Cystic Fibrosis prevalence
Infections caused by multidrug ­resistant Gram­ negative bacteria with newly acquired resistance mechanisms  Chronic bacterial pulmonary infection: serious concern in patients with
cystic fibrosis
bronchiectasis
70,000 and 100,000 people worldwide
COMMERCIAL POTENTIAL

20. BAL30072 Mechanism of action Non Cinical data
Novel siderophore (iron-binding) sulfactam antibiotic potent bactericidal activity againts GN pathogens.
Stable towards many of the extended-spectrum beta lactamase enzymes and metalo-beta-lactamase.
Mechanism of action
Non Cinical data
Potent antibacterian in vitro- in vivo activity against:
Enterobacter spp.,
Klebsiella spp,
Acinetobacter spp.
Pseudomonas aeruginosa

21. Synergy with Meropenem
Clinical studies
Development of IV formulations with the US BARDA
Inhaled formulation : ND4BB Program
15 august 2016
Completed PH1 study
Discontinuation of the inhaled formulation

22. ONCOLOGY Global cancer burden
12.7 mn new cases in 2008, 21.4 mn by 2030
During the past two decades, cancer incidence has steadily increased due to aging populations, lifestyle and environmental factors
Oncology research and development (R&D) has the highest failure rate for new molecular entities (NME) and significantly higher development costs
Témozolomide.
Increase of cancer incidence :
Aging populations
Lifestyle
Environmental factors
2/3 of all cancer diagnoses occurring in LMIC

23. Some Unmet Medical Needs
Growth sector
TNBC
NSCLC
Pancreatic cancer
Glioblastoma
Balisea’s product targets markets such as the USD
3.5 bn taxane market
increasing need for new agents in taxane-resistant cancer patients.
COMMERCIAL POTENTIAL

24. Some Unmet Medical Needs
Growth sector
TNBC
NSCLC
Pancreatic cancer
Glioblastoma
Balisea’s product targets markets such as the USD
3.5 bn taxane market
increasing need for new agents in taxane-resistant cancer patients.
COMMERCIAL POTENTIAL

25. Some Unmet Medical Needs
Growth sector
TNBC
NSCLC
Pancreatic cancer
Glioblastoma
Balisea’s product targets markets such as the USD
3.5 bn taxane market
increasing need for new agents in taxane-resistant cancer patients.
COMMERCIAL POTENTIAL

26. Highly water-soluble lysine prodrug
BAL101553
Tumor checkpoint controller
Highly water-soluble lysine prodrug
La tubuline possède 3 sites de liaison, qui sont les cibles de médicaments anticancéreux ; le site du Taxol, de la Vinblastine et de la colchicine. La colchicine et la Vinblastine se lient à la tubuline et inhibent sa polymérisation, c'est-à-dire la formation de microtubules, immobilisant les neutrophiles et abaissant l'inflammation. Le Taxol inhibe la dépolymérisation des microtubules.
Lysine décarboxylase ?
Lisavanbulin
Binds the colchicine site of tubulin
prevents tubulin polymerization and destabilizes microtubules, ultimately leading to cell cycle arrest, blockage of cell division and an induction of cell death in cancer cells.
Address the issue of frequent resistance to approved microtubule-targeting agents (MTA’s)
No other approved oncology agent targets BAL27862’s binding site
Address the issue of resistance to (MTA’s)

27. Highly water-soluble lysine prodrug
Non-clinical data :
Good oral bioavailability
Passes through the blood-brain-barrier
Potent activity in many tumor cell lines
Activity in treatment-refractory glioblastoma models. (AARC)
Clinical trials :
IV : phase 2 : Potential  colorectal, gastric, non-small cell lung, ovarian, pancreatic and triple- negative breast cancer
Oral : Phase 1/2a, patients with advanced solid tumor cancers + glioblastoma new arm by year-end
BAL101553
Protease
Phase 2 ongoing : results in 2017
Passes through the blood-brain-barrier potential to open up development opportunities not addressed by standard MTA’s, such as brain cancer (glioblastoma).
Potent activity in many tumor cell lines that are insensitive or resistant to taxanes or other microtubule-targeting agents
BAL27862

28. biomarker strategy
What’s next?
Could trigger a lucrative partnering agreement with a major cancer player :
 phase III development
 broader range of phase IIb
indications
Forecast : Peak sales of CHF 500+ mn
Optimize dose selection
Identify cancer patient groups more likely to respond.
BubR1
EB1
BubR1, controller of the spindle assembly checkpoint and tumor cell division
 required for BAL activity in vitro
EB1, microtubule regulator,
required for optimal BAL activity in glioblastoma stem-like tumor models in vitro and in vivo
Forecast : Peak sales of CHF 500+ mn or if the compound proves to provide clinical benefit in multiple indications.

29. Estimated rates of deaths by melanoma worldwide (2012)
ONCOLOGY
Medical Need
BRAF mutant in 50% of the melanoma
Estimated rates of deaths by melanoma worldwide (2012)

30. BAL3833 Commercial potential Mechanism of action Research:
Launch
Profit (2015)
Vemurafenib
ROCHE
2011
US, CA, EU
CHF 214 millions
Dabrafenib/Trametinib NOVARTIS
2014
US, EU
CHF 453 millions
BAL3833: targets BRAF, CRAF and SRC.
Orally active drug targeting kinase inhibitors
Vemurafenib: inhibition of mutant BRAF
Dafrabenib: inhibition of mutant BRAF
Trametinib: inhibition of MEK1 and MEK2
Research:
University of Manchester at The Institute of Cancer Research
Fundings:
Wellcome trust
Cancer Research UK Cancer Institute

31. Currently ongoing for patients with advanced solid tumors
Preclinical studies
-Results presented at the AACR conference
-Mutant BRAF cancers: melanoma, colorectal, ovarian
Treatment of refractory melanoma
Inhibition of mutant BRAF and cRAF/SRC
-Potential in K-RAS driven cancers : pancreatic, colorectal, non-small-cell lung
New therapeutic option
Inhibition of panRAF/and SRC kinase
Phase 1/2a study
Currently ongoing for patients with advanced solid tumors
Biomarker evaluation initiated : tumor type selection
AACR = American Association for Cancer Research

32. Action Plan against antimicrobial resistance
Commercial Strategies
Funding partners & Academic institutions :
DISARM
BARDA
iABC
ADAPT
Action Plan against antimicrobial resistance
SPA
NCE
BBND
QIDP

33. Commercial Strategies
Partnering and Licensing deals :

34. Financial Statement (in CHF thousands) 2012 2013 2014 2015 Revenue
58 336
41 376
42 634
52 825
R&D
(58 863)
(53 350)
(54 377)
(60 075)
100.9%
128.9%
127.5%
113%
Net profit
(53 033)
(33 019)
(41 520)
(61 520)
Equity
70 874
57 931
14 856
Cash
Earning per share
(5.53)
(3.40)
(4.17)
(6.09)
Burn rate
(in years)
2.0
1.6
1.8
2.7

35. Financial Statement

36. Financial Statement
Evolution of stock price in 2016 :

37. Financial Statement TOCTINO’s timeline Bottom line :
Developped by Basilea in the early 2000’s
License agreement with Stiefel (GSK),
→ Contract with 200 CHF million and subsequent milestones for FDA approval
FDA denied the approval in 2016
GSK isn’t willing to continue developing Toctino
Impacted the stock price of Basilea (-35%)
Basilea is considering buying it back in order to find another partner in the future
Bottom line :
Even though it didn’t get the FDA’s approval, it still was a great help in Basilea’s development strategy

38. Financial Statement

39. Financial Statement

40. O W T S 2 products on the market 3 products in development
Several therapeutic areas with high medical needs
Numerous partners and license agreement
Growth employment
Communication force
Cash increase
Commercialization dependent on external partners
No dedicated sell force outside major EU countries
Loss of WW Cresemba license in 2027
Toctino’s discontinuation
Discontinuation of BAL30072
Positive regulatory environment
Unmet medical needs
Incentives & encouraging initiatives across the globe
BAL : solid preclinical & early clinical data → could trigger major cancer player
Implantation in China
Price and reimbursement policies reinforcement
Antimicrobial stewardship
Oncology R&D (solid tumors) : highest failure rate for NME, higher development costs
Upcoming drugs
M&A activity → Basilea becoming a potential target O W S T
SWOT SOCIETE

41. RESISTANCE MARKETING RECOGNITION MARKETING PARTNERS INCENTIVES
BOLDNESS
SCIENTIFIC
RECOGNITION
BOLDNESS
BOLDNESS
INAPPROPRIATE
DANS LA TENDANCE : EN GROS
Immature : Maria
S rec : sihem
Inappropriate marketing + Trend follower : Juliette (manque un élément pour faire la différence)
Incentives & partners: Clément
Boldness & Resistance
Clément : partners + incentives
Sihem : scientific recognition
Marketing, anappropriate : juliette
Boldness et résistance
Maria : immature
Trend follower
MARKETING
IMMATURE
RESISTANCE

42. DANS LA TENDANCE : EN GROS
Immature : Maria
S rec : sihem
Inappropriate marketing + Trend follower : Juliette (manque un élément pour faire la différence)
Incentives & partners: Clément
Boldness & Resistance
Clément : partners + incentives
Sihem : scientific recognition
Marketing, anappropriate : juliette
Boldness et résistance
Maria : immature
Trend follower

43. Thank you for your attention !

44. Sources … Basilea website (www.basilea.com)
Half-year report 2016 (Basilea Ltd)
Annual report 2015 (Basilea Ltd)
Financial analysis of Basilea Pharmaceutica (Valuation LAB)
The role of funding and policies on innovation in cancer drug development
Smpc Cresemba
Smpc Zevtera/Mabelio
Investors presentation Bellevue 2016
European Patent Office website
WHO website
WIPO website
Pubmed …