ORPHAN DRUGS & RARE

DISEASES GLOBAL

CONGRESS 2015 EUROPE

Ultra-orphan drugs: what is the long term strategy to support ultra-orphan drugs &

how commercially viable are these drugs to stakeholders

Presenter: Christian Girard, MiM

Chief Editor, Orphan Drugs Industry Insider

Founder & CEO, ABCrowdFunding Advisors

Orphan disease prevalence: < 1/2.000

Ultra-rare disease prevalence: < 1/50.000

Picture: Alexion Pharmaceuticals

ULTRA-ORPHAN DISEASES: WHAT ARE WE TALKING ABOUT?

Atypical Hemolytic Uremic Syndrome (aHUS)

N-acetylglutamate synthase deficiency (NAGS deficiency)

Hutchinson-Gilford progeria syndrome (Progeria)

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Ribose-5-phosphate isomerase

deficiency (RPI deficiency)

& many others…

http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

1-9/1.000.000 prevalence

<1/1.000.000 prevalence

1/8.000.000 prevalence

1-9/1.000.000 prevalence

1 case identified (1999)

ANY DRUGS FOR THESE DISEASES? YES, AT LEAST FOR A FEW ONES Atypical Hemolytic Uremic

Syndrome (aHUS)

N-acetylglutamate synthase deficiency (NAGS

deficiency)

Hutchinson-Gilford progeria syndrome (Progeria)

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Ribose-5-phosphate isomerase deficiency (RPI

deficiency)

Soliris (eculizumab)

Carbaglu (carglumic acid)

Pravastatin / zoledronic acid (not approved yet)

Soliris (eculizumab)

Not to our knowledge

ULTRA-RARE DRUGS PRICING (YEARLY) Carbaglu Glybera Soliris Orfadin Vimizim Juxtapid Cinryze Procysbi

Up to 2.000k$ Up to 1.600k$ Up to 410k$ Up to 400k$ Up to 380k$ Up to 380k$ Up to 300k$ Up to 250k$

VERY SMALL PREVALENCE & DRUG PRICING IMPACT ON PAYOR BUDGET

PATIENTS $50 000 $100 000 $250 000 $500 000 $1 000 000US 6 000 $300 000 000 $600 000 000 $1 500 000 000 $3 000 000 000 $6 000 000 000EU 10 000 $500 000 000 $1 000 000 000 $2 500 000 000 $5 000 000 000 $10 000 000 000

US+EU 16 000 $800 000 000 $1 600 000 000 $4 000 000 000 $8 000 000 000 $16 000 000 000

Assumptions: 100% patients treated; disease prevalence = 1/50.000

POTENTIAL SALES (INCREASING PRICING VALUE)

ULTRA-RARE DRUGS SALES

2014 SALESSoliris $2 146 000 000Cinryze $503 000 000Procysbi $70 000 000Vimizim $37 000 000

ULTRA-RARE DRUGS = ULTRA-RARE TECHNOLOGY? Small molecules Biologics Gene therapies

Ultra-rare drugs do not necessarily imply advanced technology. Some are « simply » repurposed small molecules

THREAT: EVOLVING PAYORS POLICIES Global cost of orphan drugs under scrutiny:

120B$ (ever increasing) – more than 10% of the overall pharmaceutical market in 2014

Ultra-rare drugs = high pricing (in investors’ opinion at least)

Trend: increasing number of ultra-rare drugs Ultra-rare drugs efficacy? Room for negotiation with payors: very low

prevalence – patients registries – staged payment terms

As a result, stellar pricing belongs to the past

BUT STILL, AN ATTRACTIVE MARKET OPPORTUNITY 7.000+ orphan diseases identified ca. 500 drugs approved ca. 6.500 diseases without dedicated

treatment About 50% of them are ultra-rare disorders Orphan regulations incentives (7 to 10 year

market exclusivity starting at approval) Clinical trials cost lower (very few patients in

trials due to very low prevalence) Small-sized sales forces Historically, premium pricing (will this last?) Little or no competition… blue ocean strategy

GOVERNMENTAL SUPPORT OR PATIENTS EMPOWERMENT? National plans or strategies for rare

diseases EUROPLAN Budgets for ultra-rare diseases, but

drops in the ocean

National & international patients organizations much more active and motivated

Patients association offer support (initial financing and in clinical trials)

VALUE CREATION IN ULTRA-RARE DRUGS Leading orphan drugs players’ products

& R&D portfolio include ultra-rare drugs and candidates

Genzyme (Sanofi group) Shire Alexion Pharmaceuticals BioMarin Pharmaceutical Ultragenyx Pharmaceutical SOBI

ULTRA-RARE DRUGS PLAYERS MARKET CAPITALIZATION

Alexion Pharmaceuticals: 37B$

BioMarin Pharmaceutical: 22B$

Ultragenyx Pharmaceutical: 3.7B$

Raptor Pharmaceuticals: 1B$

Aegerion Pharmaceuticals: 0.5B$

M&A IN ULTRA-RARE DRUGS

Alexion / Synageva: 8.4B$

Horizon Pharma / Hyperion: 1.1B$

AbbVie / Pharmacyclics: 21B$

Sanofi / Genzyme: 20B$

Shire / NPS Pharma: 5.2B$

Alexion / Enobia: 1.1B$

INVESTMENT IN ULTRA-RARE PLAYERS PROVED SUCCESSFUL (1)

INVESTMENT IN ULTRA-RARE PLAYERS PROVED SUCCESSFUL (2)

REGIONAL COMPANIES VS. ULTRA-RARE DRUGS INVOLVEMENT Any orphan drugs regulatory incentives

in the country (region)? If not, opt for development where these

incentives exist (US, EU, JP, AU, KR…) Ultra-rare diseases markets are not

local: they are global Out-licensing is an option

ULTRA-RARE VS. «ONLY» ORPHAN

Ultra-low prevalence justified (in industry’s and investors’ view) high pricing for ultra-rare drugs

Non-ultra-rare drugs price tags can also be stellar (eg. Vertex’ Kalydeco for Cystic Fibrosis- 294k$)

PTC Therapeutics’ Translarna (for Duchenne Muscular Dystrophy – not an ultra-rare disease) pricing questioned by payors

Ultra-rare and «only» orphan drugs face the same issues: can the payor (ie. the citizens) accept to pay and how long?

Q&A

Please contact Christian Girard at:

christian@orphandrugsindustry.com

Thank you.