5/15/17
New Market, New Players Biosimilars
A Pure Play Perspective
Brands (biologic) Generics
World Biosimilar Congress USA 2015
Brands (small molecule)
May 27, 2015
Medicinal drugs from natural sources (e.g., herbs, plants, roots, fungi)1
Pre-
Sarfaraz K. Niazi, Ph.D.,
2
Biosimilar Development has Accelerated
37 7
40 30 20 10 0
22 5
9 8 13-Jan
14
3
46
48
9
10
22
16
15
13-Aug
14-May
Approved
57
+4%
+24% +68%
Ph III
1906
1938
[KefauverHarris] Drug Amendments Pre-market proof of safety AND efficacy Required (IND)
First mass production of synthesized insulin using recombinant technology (1963-66 was small scale)3
Hatch-Waxman Act enacted Permits generic approval without new full NDA package
1962
1978
1984
US Food, Drug and Cosmetic ACT Pre-market safety evaluation for the first time (NDA)
1972
Biologics control transferred to the FDA from the National Institute of Health
1982
First BLA approved for Humulin (Eli Lilly & Co.’s human insulin)
First biosimilar approval in the US
2009
2015
BPCIA passed to allow for biosimilar versions of approved reference biologics
1. http://www.ncbi.nlm.nih.gov/pubmed/21698778, 2. http://pubs.acs.org/cen/coverstory/83/8325/8325emergence.html 3. http://www.karger.com/ProdukteDB/Katalogteile/isbn3_8055/_83/_53/Insulin_02.pdf
TheraProteins
+19%
50
1800’s
1869, first synthetic drug discovered1 Mid-late 1880’s, began wholesale production of drugs2
Founding Chairman TherapProteins® Chicago, Illinois, USA
60
Pure Food and Drugs Act passed, FDA modern regulatory functions begin
10
•
Focused only on biosimilars
•
Proprietary, patented, single-use technology platform
•
Fully integrated from cell line to fill-and-finish
•
cGMP compliant facility located in Chicago, Illinois
37 31
7
10
14-Oct
15-Apr
Ph I / Ph II
Double counting was avoided by using the most advanced status, i.e. a product with EU approval and US phase III counts as an approved product Source: 1st Annual Bernstein European Biosimilars Conference (FDA, EMA, Industry discussion, Bernstein analysis)
4
1
5/15/17
Who’s Who? Brand
What is a Pure Play Biosimilar Company? Generic
Pure Play
Other
?
Brand
Other
NON-PHARMA INDUSTRIES
BRANDS
Generic
GENERICS
Pure Play
BIOSIMILARS
CRO/CMO/Emerging Market Domestic Players
A Pure Play Biosimilar Company focuses solely on biosimilar products
5
6
New Market, New Paradigm Brand Launch
7
Generic Launch
Challenges for Pure Play Companies Biosimilar Launch
Product
• Fully branded product driven • New name • New INN
• Unbranded company driven • No brand name • Same INN
• Hybrid • Brand name • Same INN (qualifier?)
• Not applicable
Education
• New product, MOA, treatment regiment, clinical safety and efficacy results
• Analytical characterization data • Safety data
Sales
• Large sales force • Pull-through on a prescriber level • MSL support
• Limited sales force • Focus on relationships with intermediaries
• Hybrid sales force? • MSL support for science story
• Not applicable
• Continuity of service
Services
• Patient services (e.g., PAP, copay, etc.) • Provider services
• Full clinical program • Prove safety and efficacy
• Not applicable
Clinical
• Analytical foundation • Safety studies • Prove safety, purity and potency
New Molecular Entity
Bioequivalent
Biosimilar
1 Competition: nonpure players
2 Getting to market
w Existing business relationships and practices
w Recognition in market
w Infrastructure and technology
w Immediate resources
w Financial resources
w Image of quality w Scientific finesse
Solutions: In the end it will be the COGS 8
2
5/15/17
1
1
Traditional Infrastructure is a “Baggage”
1
Deep Tank System
2
3
Roller Bottle System
Single-use Bioreactor
u Single Container Expression, Harvest and Purification u Proprietary sparging and capture u ISO9 Friendly—no infrastructure u Modular, no scale-up u Transportable u Fast to Market u High Consistency—gentle movement u Lowest COGS—globally competitive
4
TPI Single-use System
Bioreactor technology has experienced innovation over time, but what has to be given up to move to something new? Biologic Facility (2015)1 › ~323,000 ft2 › Six 15,000 L bioreactors › 400 employees › $900M investment › 4 Years › Ireland
9
1
Biologic Facility (1994)2 › 300 employees › $150M investment › 3 Years for phase I Plant Expansion (2004)3 › 1,000+ employees › $600M investment
Biologics Facility (2012)4
Single-use Facility (2013)5
› $500M investment › 3 Years › Singapore
› $200M investment › 2 Years › Singapore
MayaBio® Bioprocess Platform (45 Patents)
› 5 Years
1. http://news.bms.com/press-release/financial-news/bristol-myers-squibb-construct-new-large-scale-biologics-manufacturing- 2. http://www.gene.com/media/press-releases/4420/1994-10-31/genentech-locatesmajor-new-facility-in- 3. http://articles.latimes.com/2004/apr/02/business/fi-genentech2 5. http://www.fiercepharmamanufacturing.com/story/amgen-opens-200m-continuous-purification-plant-singapore/2014-11-20 Roller Bottle Credit: REUTERS/V. RICHARD HARO/WIREPIX Source: http://www.reuters.com/article/2007/08/16/usamgen-idUSN8F26518720070816 (accessed June 2014)
No Compromise on Science—Smart Science Required
10
1
Similarity Bar—Thinking Differently
Primary Structure
Product-related Impurities Intrinsic variants related to the protein
Processrelated Impurities Impurities that can be introduced from downstream process
The core DNA sequence and any post-translational modifications of the molecule
Higher Order Structure Secondary, tertiary and quaternary structure
Stability Particles and Aggregates
Product Properties
Biological Function How the molecule works including receptor binding
Finished drug properties including strength and formulation
w It takes a holistic approach to demonstrate a product is highly similar
11
w It is in some sense more complex than producing a new molecular entity
w First test that measures 4D structure of protein solutions—replaces many tests, removes more residual uncertainty
12
3
5/15/17
Education is one of the Biggest Hurdles to Adoption
2
Biosimilars Knowledge Remains Low 202
100
19%
16% 27%
38%
Extremely Familiar Very Familiar Moderately Familiar
39%
Not familiar
32% 10% 1% US
Slightly Familiar
17% 1%
“efforts to undermine trust in these products are worrisome and represent a disservice to patients who could benefit from these lower-cost treatments.”2
Key Takeaways u Pure play companies better poised to produce affordable biosimilars u Existing infrastructure is an archaic “baggage” u In the long run, it is the COGS that will determine market success u Cost of science will determine survival
Former FDA Commissioner Margaret Hamburg
Flexibility and Speed to Execution
EU5
As a pure play, there is only one story to tell 13
1. FirstWord: 2014 Physician Views Poll Results – A Tale of Two Continents; US and EU physicians paint contrasting picture of biosimilar educational space (80 US and 100 EU) and Xcenda pole of 122 US oncologists, 2014 2. http://www.worldipreview.com/article/biosimilar-biologics-is-the-us-being-left-behind
Reassess Every Aspect of the Process
Leverage Novel Technology Reduce Timelines One Focus, One Goal
14
2
Thank You
Progress is Being Made, But More is Needed The FDA has Consistently Spoken about the New Paradigm of Biosimilars
› Fact based educational resources are emerging in the market › Industry groups are being formed with the goals of education and influencing policy in a positive way for biosimilars
16
4
5/15/17
1
The Bar is Set Extremely High; Passing Puts you on the Playing Field
1
New Brand Biologic
The Key will be the Value and the Value Add that each Competitor can Provide • Can you demonstrate biosimilarity? • Do you have a strong characterization package and can that story be told effectively? • Do you have the same product elements as the reference product? - Same presentation and delivery device? - Similar stability? - Similar packaging?
A New Type of Model Requires a New Set of Capabilities
w w w w
• Can you demonstrate confidence in quality?
New Biosimilar
w Being without “baggage” enables a certain level of flexibility and agility that is valuable in the biosimilar market
17
w Reproduction of an reference biologic w Match the critical quality attributes of the reference product, including the productrelated impurities w Be within the band of acceptable variability of the reference product w Prove safety, purity, and potency, which comes first from matching structure
Analytics
Analytics
Drug Product
Upstream Downstream
Cell Line Analytics
Fill Finish Analytics
Within Reference Product Variability
• Can you provide consistency of patient experience?
w Replica of an branded small molecule product w No clinical studies required w 100% characterization of reference possible
New molecular entity Complex Prove efficacy and safety Set the criteria for acceptable variability batch to batch
• Can you provide a affordable alternative? • Can you be flexible and nimble in relationships, contracts etc.?
New Generic
18
1
Requirements Rooted in Analytics and Science
1
Ingenuity Unleashed with a Clean Slate
New Biosimilar Clinical Studies
Clin Pharm
MayaBio® Bioreactors
MayaBio®
Clinical Studies
Clinical Pharmacology
w Proprietary and patented system (45 IP)
Nonclinical
w Mammalian or microbial cell expression systems
Nonclinical
w Single container expression, harvesting and purification
Analytical
w A flexible container with a proprietary sparging system w Suitable for ISO9 environment
Analytical Clinical Studies
w Completely closed system prevents cross-contamination Clin Pharm Nonclinical Analytical
19
New Biologic
w Modular, transportable and instantly scaled w The base for biosimilarity is structural ‘sameness’ proven through analytical methods
w Consistent and gentle reliable expression and quality
w Clinical pharmacology studies are emphasized for function and safety w A pivotal phase III study to prove efficacy is not the model for biosimilars
20
5