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Your B-School Partner
Using Your Business School to Enhance Both Technology Transfer Office and
Educational Activities
www.domain.com 2
Introduction
AGENDA
1.
Overview of Discovery to Market2.
Perspective from partners3.
Sample student project4.
Discovery to Market (D2M)
2010• New MBA curriculum at Carey Business School • Year-long Discovery to Market (D2M) course required • Fundamentals of technology commercialization and entrepreneurship• No science background prerequisite
2011• D2M is launched as a part of the Global MBA curriculum• Builds on core MBA coursework.
2012• D2M is extended to other part time programs and Executive MBA
programs
Learning Model First Term – Boot Camp
Feasibility Analysis When is an idea an invention? Design theory and systemic generation of innovation Intellectual property – legal framework and strategy Market segmentation/sizing Competitive analysis Overcoming regulatory hurdles and barriers to entry Commercialization strategy Funding and financing
• Second Term– Experiential Project
MBA student teams (4-5 students) assigned prescreened inventions from project partner organizations
Inventor meeting Complete feasibility analysis
• Market Feasibility Analysis• Preliminary Recommendation on Go/No-Go
decision• Define Next Steps
Readings
CaseStudies
Team Projects
Learning the Business
Translating the Science
Tuning to the Market
Shared Learning
InteractiveLearningSession
ExpertsBriefing
Classroom Learning
Experiential
Learning
Project Partner Organizations Early-stage scientific innovations are sourced from research community at JHU and outside
organizations.
Johns Hopkins Technology Transfer OfficeJohns Hopkins Department of Medicine
Johns Hopkins School of EngineeringCenter for Bioengineering Innovation and
DesignKennedy Krieger Institute
Telemedicine and Advanced Technology Research Center
National Institute of Health University of Maryland
Local incubators, start up companies
Range of ProjectsMedical diagnostic
Medical devicesHealth ITRobotics
Life science therapiesVaccines
Renewable Energy
Critical Success Factors in Creating an Innovation Ecosystem for D2M
Outcome Highlights
2010 2011 2012 20130
5
10
15
20
25
30
OthersNIHTATRCJHTTO
Project successTo date, student teams have worked on more than 50 technology commercialization projectsProjects are early stage so long term metrics are not available A number of projects have gained additional funding
Students successfully participated in business case competitionsStudents have gained new appreciation for technology commercialization and technology transfer -Students launched entrepreneurship club -Graduates from the inaugural class have pursued related careers
A standard course syllabus, policy (NDA, COI) and procedures were developed for a successful implementation of the D2M project
D2M curriculum is a part of funding proposal “The PhD Translational Excellerator: Transitioning from the lab to product” with Medical and Education Perspectives (“MEP”), a non-profit organization led by Hopkins Medical and Graduate Schools students to offer technology commercialization course to PhD students
D2M Project Example
With more specificity and less toxicity
ENGINEERED BACTERIAL TOXIN TOTARGET AND KILL CANCER CELLS
THE PROBLEM
Can we kill only cancer cells, sustain insignificant side effects, and leave healthy cells alone?
DeathA decline in heart functionIrregular heartbeatsHigh blood pressureSerious heart attackLung problemsSwelling of the lungs
tumor lysis syndrome (TLS) severe skin and mouth reactionsprogressive multifocal leukoencephalopathy (PML)hepatitis B serious infectionsheart problemslow blood cell counts
DeathA hole in the stomachWounds that don't heal Serious bleedingStroke or heart problemsSeizuresBlindnessKidney problemsInfusion reactionsFertility issuesSevere high blood pressure
Chemotherapies: Anemia, Appetite Changes, Bleeding Problems, Constipation, Diarrhea, Fatigue, Hair Loss, Infection, Memory Changes, Mouth and Throat, Nausea and Vomiting, Nerve Changes, Pain, Sexual and Fertility Changes, Skin and Nail Changes, Swelling , Urination Changes
Sources: http://www.herceptin.com/safety; http://www.rituxan.com/index.html; http://www.avastin.com/patient/lung/side-effects/serious; http://www.tarceva.com/patient/considering/effects.jsp; http://www.cancerresearchuk.org/cancer-help/about-cancer/treatment/cancer-drugs/methotrexate#common; http://www.cancer.gov/cancertopics/coping/chemo-side-effects
AGENDA
BACKGROUND & INTRO
BUSINESS MODEL
STRATEGIC MARKET ANALYSIS
INTELLECTUAL PROPERTY
SUMMARY OF FEASIBILITY RECOMMENDATIONS
THE INVENTION
A protein toxin derived from Bacillus anthracis (Anthrax)
Engineered to be activated by 2 enzymes (MMP and uPA)
MMP and uPA are highly expressed in tumors
In vivo data demonstrates effectiveness in a broad range of cancers & a high therapeutic index (3-8)
Source: T. Bugge, S. Leppla and D. Guerrero. Personal communication.
VALUE PROPOSITION
Invention
High Specificity
Systemic Delivery
Non Mutagenic
Low or no relapse
rates
Few Side Effects
Low Toxicity
Bacillus anthracis
Anthrax Toxin Receptor 1/2
Furin?
Source: Image from www.textbookofbacteriology.net/Anthrax.html
PrAg LF
Protective Antigen
Lethal Factor
Cytotoxicity
MECHANISM OF ANTHRAX TOXIN
MODIFYING THE LF BINDING SITE
Figure Modified from Liu, S. et al. Intermolecular complementation achieves high-specificity tumor targeting by anthrax toxin. Nat Biotechnol. 23 (6), 725-30 (2005).
ASSESSMENT OF NOVELTY AND FREEDOM TO OPERATE
IP HIGHLIGHTS1 U.S. composition patent issued US7,947,289 Expires on 02/09/2024
1 U.S. method of treating diseases patent US8,388,933 Expires on 02/09/2024
12+ related U.S patents by the inventors
Concurrent PCT applications in Africa and Europe
5+ scientific publications in recognized journals
NOVELTY
Altered the enzymatic activation of PA by uPA and MMP instead of furin
Modified formation of LF binding sites within PA heptamer so that only altered PA can bind to LF
Required activation by BOTH uPA and MMP for formation of functional LF binding sites
Over 600,000 hitsBacterial Toxin, Protein Toxin,
Tumor, Cancer
Over 48,000 results Filters: Anthrax, Protective Antigen, Bacillus anthracis
Over 1000 results Filters: uPA MMP
Relevant Patents:
6
IP SEARCH
↓ Immunotoxin therapies
↓ Affinity-targeted conjugates
↓ Vaccines↓ Live cell
approaches
RELEVANT PATENTSPriority Date
Status Patent/App No.
Claim Assignee
04/30/1997 Application PCT/IL2011/000680
Ricin-like toxin variants for treatment of cancer, viral or parasitic infections. Ricin toxin A and B chains linked by a sequence that is cleaved by cancer associated proteases such that cleavage results in activation of the toxin.
Twinstrand Therapeutics
09/24/1999 Patent Issued
US 7468352 Mutated anthrax toxin protective antigen proteins that specifically target cells containing high amount of cell-surface metalloproteinases or plasminogen activator. Mutated anthrax toxin that is activated by cleavage of the cancer associated proteases uPA and MMP.
NIH
02/9/2004 Patent Issued
US 83889337947289
Multimeric protein toxins to target cells having multiple identifying characteristics. Modified anthrax toxin that kills cells only in the presence of high levels of both uPA and MMP proteases.
NIH
11/21/2005 Application PCT/CA2006/001900
Modified pore-forming protein toxins and use thereof. A pore forming toxin fused to an inhibitory peptide that is cleaved and activated by cancer associated proteases.
Protox Therapeutics Inc.
12/14/2006 Application PCT/US2007/087664
Human cancer therapy using engineered matrix metalloproteinase-activated anthrax lethal toxin that targets tumor vasculature. Use of MMP activated anthrax toxin to target the tumor vasculature.
NIH
04/5/2010 Application PCT/IB2011/051433
Protease-activatable pore-forming polypeptides. A pore forming toxin fused to an inhibitory peptide that is cleaved and activated by cancer associated proteases.
Bar-llan University
09/20/2010 Application PCT/CA2007/001018
Activatable toxin complexes comprising a cleavable inhibitory peptide. Broad claims to concept of protease activated toxins. Specific embodiment are diphtheria and ricin toxins activated by the HCV protease NS3.
Tel Aviv University
RELEVANT PATENTSPriority Date
Status Patent/App No.
Claim Assignee
04/30/1997 Application PCT/IL2011/000680
Ricin-like toxin variants for treatment of cancer, viral or parasitic infections. Ricin toxin A and B chains linked by a sequence that is cleaved by cancer associated proteases such that cleavage results in activation of the toxin.
Twinstrand Therapeutics
09/24/1999 Patent Issued
US 7468352 Mutated anthrax toxin protective antigen proteins that specifically target cells containing high amount of cell-surface metalloproteinases or plasminogen activator. Mutated anthrax toxin that is activated by cleavage of the cancer associated proteases uPA and MMP.
NIH
02/9/2004 Patent Issued
US 8388933 Multimeric protein toxins to target cells having multiple identifying characteristics. Modified anthrax toxin that kills cells only in the presence of high levels of both uPA and MMP proteases.
NIH
11/21/2005 Application PCT/CA2006/001900
Modified pore-forming protein toxins and use thereof. A pore forming toxin fused to an inhibitory peptide that is cleaved and activated by cancer associated proteases.
Protox Therapeutics Inc.
12/14/2006 Application PCT/US2007/087664
Human cancer therapy using engineered matrix metalloproteinase-activated anthrax lethal toxin that targets tumor vasculature. Use of MMP activated anthrax toxin to target the tumor vasculature.
NIH
04/5/2010 Application PCT/IB2011/051433
Protease-activatable pore-forming polypeptides. A pore forming toxin fused to an inhibitory peptide that is cleaved and activated by cancer associated proteases.
Bar-llan University
09/20/2010 Application PCT/CA2007/001018
Activatable toxin complexes comprising a cleavable inhibitory peptide. Broad claims to concept of protease activated toxins. Specific embodiments are diphtheria and ricin toxins activated by the HCV protease NS3.
Tel Aviv University
PRIMARY RESEARCHExpert Panel:Robert E. McBride, Esq. Thomas Woods, Esq. Dr. Daniel J. Nevrivy, Esq. Brian Andrea, Esq.
IP Considerations
How do very general claims to use anthrax toxin as a therapeutics impact FTO in other patents?
•Obviousness. Depends on where the claims end up as they are narrowed down. Would be concerned if the prior art says you can mutate in manner A and manner B for diseases. Then obviousness problem. If their method is similar (can tell by way of chemical compound search/amino acid sequence) then a problem….. There are likely a finite no of ways to modify the compound. If the technology patent has more than a few ways and not one way (substitutions of different variables in compound), then not obvious enough to infer from general claim. •Predictability test. is there a way to tell the new compound would work from the onset? If you can’t predict which one will work until you test and trial, then doesn't satisfy predictability test.
How do patents on MMP and uPA as diagnostics impact FTO?
•Patentable Subject Matter under Section 101. If there is something unique about detecting then very valid. They may have had a specific method in mind but realized the biomarkers (not the method) are key, so they may have felt the need to make the claims broader. If too broad then we can get into litigation about the patentable subject matter under Section 101. •Machine or Transformation Test. Recently the court tightened the standard for diagnostics – has to be tied into a particular machine or has to transform something to different state or thing. If claim has been allowed despite this and too broad; it is going to be something to flag. Doesn’t mean it is a 100% roadblock.
Would modifications to the protein sequence that reduced immunogenicity of the toxin qualify for a new patent with 20 year life, or only count as a divisional patent of the existing technology?
•There is a test. Test for new patent vs. Continuation: Look back at specifications if opportunity to change/reduce immunogenicity is disclosed, you can file continuation and add claims if you have an open/pending application. If not covered in prior specs and immunogencity is really new, you can either file a new application altogether or a continuation in part (claiming priority back to first application). If there was a continuation/app filed right before new patent was issued. Look at continuity data. What continuations or divisionals have been filed and if any still pending in PAIR. If new and non-obvious you get a fresh patent term 20 yrs. If you still have applications co-pending which we can claim priority to, then you can just do continuation or divisional but you forfeit the time. You can check to see if someone filed a divisional app right before patent issuing using PAIR.
DEPENDENT TECHNOLOGIES
Companion diagnostic
DNA recombinant techniques
Manufacturing processes
IP SUMMARY
Protection
Novelty
Non-Obvious
Freedom to Operate
TARGET MARKET
Non Small-Cell Lung Cancer
TARGET MARKETLUNG (NSCLC) HNSCC MELANOMA COLON
uPA / MMP YES YES YES YESIncidence HIGH (230K) MED (54K) MED (77K) MED (143K)Prevalence MED (390K) MED (350K) HIGH (875K) HIGH (1.1M)Deaths HIGH (160K) LOW (11K) LOW (10K) MED (51K)5 Yr Survival LOW (15%) MED (59%) HIGH (89%) MED (62%)
Lung Non-Small Cell Carcinoma (NSCLC)
Critical unmet medical need Large market
Potential for fast-track designation
from FDA
Potential off label usage for broad
range of cancers
STATUS QUO
Source: Mayo Clinichttp://www.mayoclinic.com/health/lung-cancer/DS00038/DSECTION=treatments-and-drugs
Surgery, sometimes chemotherapy
Surgery, chemotherapy, radiation
Combined chemotherapy and radiation, chemotherapy alone, surgery based
Chemotherapy, targeted drug therapy, clinical trials, supportive care
I
II
III
IV
Treat options for NSCLC at different stages
PRIMARY MARKET SEGMENT
Recurrent cases are extremely difficult to
treat
Poor prognosis; thus willing to enroll in experimental trials
62% of patients have high uPA and MMP
levels*
High MMP and uPA correlate with poor
prognosis*
New stage III/IV NSCLC patients
* Correlates with poor prognosis [Hofmann et al. Oncology Reports 16:587-595 ]
ESTIMATING MARKET SIZE
American Cancer Society report: Cancer Facts and Figures (2013)NCI SEER Database; Fast Stats on NSCLCHofmann et al. Oncology Reports 16:587-595Lou et al. General Thoracic Surgery. 145: 75-82
St. I/II(15%)
St. III(22%)
St. IV(56%)
Remission:(80%)
New Cases:230,000
Survivors:170,000
Recur.(20%)
uPA & MMPHIGH (62%)
111,000
uPAMMP
21,000
YEAR 2020
ESTIMATING MARKET SIZE
YR 2020111,000
Discount FactorsInsured
Willingness to treat
Contraindications Reimbursement
Penetration
4,286
Discount factors based on comparables (Herceptin) and US census data
NSCLC MARKET SIZE FORECAST
2020 2021 2022 2023 2024 2025 2026 20270
2000
4000
6000
8000
10000
12000
Best (50%)Worst (5%)
Num
ber o
f NSC
LC P
atien
ts
Note: Herceptin has 90% market share of market segment [eligible EGFR+ve Breast cancer patients]
Year
2020 2021 2022 2023 2024 2025 2026 20270
100200300400500600700800900
1000
BestWorst
Reve
nue
in M
illio
ns
* Source: STIFLING NEW CURES - The True Cost of Lengthy Clinical Drug Trials by Avik S. A. Roy Senior Fellow Manhattan Institute for Policy Research
NSCLC REVENUE OPPORTUNITY
Year
PRICING
Invention
Avasti
n
Erbitu
x
Herceptin
Gleevec
Rituxa
n
Tarceva
Nexava
r
Revlimid
020406080
100120140160180
80
45
8070
9280
6069
163
Cost
/ Y
ear
(In T
hous
ands
)
Drug name
Source: http://money.cnn.com/2013/04/25/news/economy/cancer-drug-cost/index.html
BENEFIT ANALYSIS
Invention Herceptin Erbitux Avastin0
102030405060708090 80
7080
45
13 9 11
Avg Cost / Yr ($'000s)Median OS*Median PFS*Number of MCAR*
Comparison against other block buster cancer drugs
OS – Overall Survival MonthsPFS – Progression Free Survival Months
MCAR – Most Common Adverse Reactions
Source: National Cancer Institute; Hofmann et al. Oncology Reports 16:587-595
PATIENT NEEDS ANALYSISTotal Customer
Costs
Psychological Cost
Short TermPhysical
Cost
Monetary Cost
Total Customer Benefit
Long TermQuality of Life
Benefit
Longer LifeBenefit
Time Spent In Treatment Cost
Time After Treatment
Benefit
Clarity Benefit
Source: http://blogs.webmd.com/cancer/2012/11/as-a-cancer-patient-what-do-you-want.html; http://www.cancerforums.net/threads/19080-Informnation-on-new-drug-Xalkori-(Crizotinib)-in-NSCLC?s=d344ffdd9e5c3bfaa69ddee16e1ce17b
BUSINESS MODEL
Preclinical Phase I Phase II Phase III Market Entry
•Mouse trials•Feline trials•Toxicology•Pharmacology•Manufacturing data •IND
Cost : $2M*
•Demonstrate low toxicity, absorption, metabolic distribution, excretion•Identify dosage
Cost: $1-$5M**
2013-2014 2015 2015-2016 2016-2019 2020-2021
•Controlled trials with patients for efficacy and side effects
Cost:$10-$40**
•Trials on large population of patients
Cost: $250-$400M**
•NDA •FDA approval•Manufacturing •Market launch • Marketing & Sales
MILESTONES TO MARKET
*Quotes from Bioreliance and Covance; ** STIFLING NEW CURES - The True Cost of Lengthy Clinical Drug Trials by Avik S. A. Roy Senior Fellow Manhattan Institute for Policy Research
PRIMARY RESEARCHExpert Panel:Dr. Art Frankel: S&W Memorial Hospital Dr. Susan Keating: CCS AssociatesDr. William Grady: FHCC Rosemarie Truman: RHT ConsultingDr. David Agus: USC
Technical Assessment• Innovative and promising technology• Need more realistic models, since native microenvironment is key• Compare effectiveness to existing drugs• Other protease dependent pro-drugs failed trials, may have side effects
due to uPA and MMP expression in normal tissues• Concerned about partial response or targeting small disseminated
tumors• Concerns about immune response to anthrax toxin proteins
PRIMARY RESEARCHExpert Panel:Dr. Art Frankel: S&W Memorial Hospital Dr. Susan Keating: CCS AssociatesDr. William Grady: FHCC Rosemarie Truman: RHT ConsultingDr. David Agus: USC
Licensing Considerations• Hard sell to “Big Pharma”
• Resistant to new ideas• Lung Cancer Pipeline “full”
• Pharmacology and toxicology data critical to progress• in vitro toxicity studies (test on normal cell types)• 14 or 28 day study in rats – Multiple doses toxicity (Systemic Delivery)
• Data supporting manufacturing questions• Scalability, reproducibility, scalability• Concern over the need to manufacture 3 components
PATHWAY TO COMMERCIALIZATION
Preclinical Phase I Phase II Phase III
Market Entry
PATHWAY TO COMMERCIALIZATION
Funding options
• SBIR phase I & II grants• Philanthropic
foundations and Patient advocacy groups
Venture capital
Business Model
• Partnerships with biotech companies having interest in similar technologies
• CRADA agreementsPotential
CompaniesBrian Oncore, Clovis Oncology, Biotech Synergy and Daiichi Sankyo
S m a l l P h a r m a
Potential acquisition by big Pharma
L i c e n s i n g
Acquisition
PANCREATIC CANCER TARGET MARKET SIZE
2018 2019 2020 2021 2022 2023 2024 2025 2026 20270
2000
4000
6000
8000
10000
12000
Best (50%)Worst (5%)
Num
ber o
f Pati
ents
* Source: STIFLING NEW CURES - The True Cost of Lengthy Clinical Drug Trials by Avik S. A. Roy Senior Fellow Manhattan Institute for Policy Research
YearNote: Based on the similar discount factors used for estimating the market size for NSCLC
PANCREATIC CANCER REVENUE OPPORTUNITY
2018 2019 2020 2021 2022 2023 2024 2025 2026 2027 $-
$100 $200 $300 $400 $500 $600 $700 $800 $900
BestWorst
Reve
nue
in M
illio
ns
Preclinical Phase 1 Phase 2 Phase 3
< $0.5 M < $0.5 M < $1 M < $10 M
Estimated clinical trial expenditures for rare diseases*
* Source: STIFLING NEW CURES - The True Cost of Lengthy Clinical Drug Trials by Avik S. A. Roy Senior Fellow Manhattan Institute for Policy Research
Year
Assumed Treatment Cost - $100,000
FEASIBILITY SUMMARYTechnical feasibility
Freedom to operate
Remaining patent term
Legal, regulatory and reimbursement
Market opportunity (demand, revenue potential)
Funding
Overall – Needs more preclinical evidence
RECOMMENDATIONS
Publish all available toxicology and pharmacology data on OTT site
Seek venture philanthropy for pre-clinical
Consider orphan cancer indications for FDA fast track (even faster)
Consider optimizing immunogenic profile for possible new patent (new term)
Watch flagged PCT patent applications
ACKNOWLEDGEMENTSOncology:Dr. Art Frankel: UT SouthwesternDr. William Grady: FHCCDr. David Agus: USC
Intellectual Property:Robert McBride, Esq.Dan Nevrivy, Esq.Brian Andrea, Esq.Thomas Woods, Esq.
Reimbursement:Susan Downard, Medicare & Pharmacy Benefit Implementations at Kaiser PermanenteShaina Srivastava, Medicaid Director
Licensing and Commercialization:
Dr. Susan Keating: CCS Associates
Rosemarie Truman: RHT Consulting
Kristine Dehler: Covance
NIH Inventors:
Dr. Thomas Bugge
Dr. Stephen Leppla
Dr. Diane Guerrero
THANK YOU!!!
DISCOVERY TO MARKET CLASS
SREE NAMPALLYELAINE RUBINO
JON FRANCA-KOHSUSMITA SRIVASTAVA
APPENDIX
OVERVIEWProblem: Current treatments have significant adverse effects because their targets are either non-specific or are cells that play important roles in normal cells.
Need: Treatments with specificity, that kill cancer cells completely, have minimal side effects
Invention: Novel biotherapy to target only cancer cells without harming non-cancerous cells using engineered bacterial toxin.
Recommendation: Licensing currently not feasible.
SWOT
Value propositions
Excellent laboratory results
Licensed prior version
Long road to marketCompetition
Uncertain immune responsePublic perception
Growing target marketBroad Use / Potential off label
usage
FundingValley of death
Unfavorable clinical trial outcomesPatent term expiring soon
S W
O T
VALUE CHAIN
Vast OptionsService Culture
Rich Heritage
Suppliers Purchasers
Fiscal /ProductIntermediaries
Providers
SUPPLIERS
Vast OptionsService Culture
Rich Heritage
NIH(Bacillus anthracis spores)
Manufacturing Co.
Laboratory Equipment Vendors
Pharm/BioTech
PURCHASERS
Vast OptionsService Culture
Rich Heritage
Government Philanthropic Orgs.
HospitalsIndividuals
FISCAL INTERMEDIARIES
Vast OptionsService Culture
Rich Heritage
Medicare Insurance Companies
PROVIDERS
Vast OptionsService Culture
Rich Heritage
Hospitals Clinics
PhysiciansMCOs/HMOs
PRODUCT INTERMEDIARIES
Vast OptionsService Culture
Rich Heritage
WholesalersGroup Purchasing Organization
STRATEGIC MARKET ANALYSIS
WORLD MARKET
Revenues CAGR2013 ~ 43 Billion 2010-2015 ~ 10%2015 ~ 53 Billion
Source: Kalorama Information 2010
Roche; 54.4%
Novar-tis;
15.3%
Celgene; 6.0%Pfizer; 4.2%
Bristol-Myers Squibb;
3.8%
John-son & John-son; 3.5% Others;
12.9%
Market Share
RocheNovartisCelgenePfizerBristol-Myers SquibbJohnson & JohnsonOthers
LEGAL ISSUESBudget Control Act of 2011 affected the most expensive drug categories – cancer biotherapeutics
Biosimilar User Fee Act of 2012 (BsUFA), authorizes FDA to assess and collect fees for biosimilar biological products from October 2012 through September 2017
The Biologics Price Competition and Innovation Act of 2009 (BPCI Act) enacted as part of the Affordable Care Act of 2010, established new abbreviated approval pathway for biosimilars
Obama Healthcare Plan: mandates FDA to approve biosimilars, to render existing biotherapeutics drugs significantly affordable when their patents expire
PHARMACOVIGILANCE
US FDA Center for Biologics Evaluation and Research (CBER)
WHO standards through the Expert Committee on Biological Standardization (ECBS) serve as a basis for setting national requirements for production, quality control and overall regulation of biotherapeutics and biosimilars.
FDA
The IND application must contain:» Animal Pharmacology and Toxicology Studies » Manufacturing Information » Clinical Protocols and Investigator Information
FDA CHALLENGES
Q. Do the results of well-controlled studies provide substantial evidence of the treatment's effectiveness?
A. Murine studies are well controlled and showed excellent results – no side effects and low
toxicity. Feline studies in progress. Q. Do the results show the product is safe under the conditions of use in the proposed labeling? In this context, "safe" means that potential benefits have been determined to outweigh any risks.
A. Addressing safety of toxin by changing its molecular properties. Must prove this in human testing.
REIMBURSEMENT
Biotherapy physician administered only• Covered by Part B• No new CPT or ICD codes required• CPT code is 162.x, with the fourth-digit subcategory identifying the specified site of cancer
Not all costs covered by insurance
Strategy to improve reimbursement• Bundled payments for based on common protocol• Value-based insurance design • Shared savings models linked with pay-for-performance programs reward adherence to
standard protocols• Genentech has a Co-Pay Card program that covers some the out-of-pocket costs for patients
enrolled
Source: Strategies to Reduce Cancer-Care Costs: http://jnci.oxfordjournals.org/content/early/2013/01/30/jnci.djt020
IP EXPERTS
DRUGS APPROVED FOR NSCLC
1. Abitrexate (Methotrexate)2. Abraxane (Paclitaxel Albumin-stabilized
Nanoparticle Formulation) 3. Alimta (Pemetrexed Disodium)4. Avastin (Bevacizumab)5. Bevacizumab6. Carboplatin7. Cisplatin8. Crizotinib9. Erlotinib Hydrochloride10. Folex (Methotrexate)11. Folex PFS (Methotrexate)12. Gefitinib13. Gemcitabine Hydrochloride14. Gemzar (Gemcitabine Hydrochloride)
15. Iressa (Gefitinib)16. Methotrexate17. Methotrexate LPF (Methotrexate)18. Mexate (Methotrexate)19. Mexate-AQ (Methotrexate)20. Paclitaxel21. Paclitaxel Albumin-stabilized
Nanoparticle Formulation22. Paraplat (Carboplatin)23. Paraplatin (Carboplatin)24. Pemetrexed Disodium25. Platinol (Cisplatin)26. Platinol-AQ (Cisplatin)27. Tarceva (Erlotinib Hydrochloride)28. Taxol (Paclitaxel)29. Xalkori (Crizotinib)
Source: National Cancer Institutehttp://www.cancer.gov/cancertopics/druginfo/lungcancer
Therapy Marketer Phase
Cetuximab (Erbitux) ImClone III (U.S.)
Vadimezan (DMXAA, ASA404)
Novartis II (E.U.)
Afatinib (BIBW 2992) Boehringer Ingelheim Pharmaceuticals
II, III ongoing (U.S. , E.U., Korea)
motesanib (AMG-706) Amgen II complete (U.S.)
sorafenib (Nexavar) Bayer II complete (U.S.)
sunitinib (Sutent) Pfizer II complete (U.S. , Canada, E.U)
Exelbine (ANX-530) Adventrx Pharmaceuticals Registration (U.S.)
NEW DRUGS
NSCLC CLINICAL TRIALS
All the major pharmaceutical players
Over 120 drugs and biologics in clinical trials
Stage 1 Stage 2 Stage 3 Stage 40
50
100
150
200
250
300
NSCLC REVENUE OPPORTUNITY
• Estimated investments prior to the market launch in 2020 are about $1 Billion. • This investment funds the pre-clinical development and Clinical Trials
2020 2021 2022 2023 2024 2025
Total Revenue 343$ 470$ 733$ 1,135$ 1,676$ 1,206$ Less: Cost of Revenue (COGS) 202$ 216$ 337$ 454$ 670$ 362$ Gross Profit 141$ 254$ 396$ 681$ 1,005$ 844$ Operating Expenses (70)$ (83)$ (85)$ (100)$ (115)$ (130)$
Research & Development (50)$ (50)$ (40)$ (40)$ (40)$ (30)$ SG &A (20)$ (33)$ (45)$ (60)$ (75)$ (100)$
EBITDA 71$ 171$ 311$ 581$ 890$ 714$ EBIT 71$ 171$ 311$ 581$ 890$ 714$ Provisions For Taxes 25$ 60$ 109$ 203$ 312$ 250$ % of EBIT 35.0% 35.0% 35.0% 35.0% 35.0% 35.0%Net Income ($) 46$ 111$ 202$ 378$ 579$ 464$
($ in Millions)
STAKEHOLDER ANALYSIS
Patients
DoctorsResearchers
FDA
Govt/Public Health
Patient Advocate Groups
Funders
National Cancer
Institute
Insurance
POTENTIAL LICENSEESAmbit Biosciences
ARIAD PharmaceuticalsGlobeImmuneHeat Biologics
Idera PharmaceuticalsActive Biotech
Oncolys BiopharmaOncoGenex Pharmaceuticals
GenprexBryan Oncor
ZIOPHARM OncologyTalon Therapeutics
VasGene Therapeutics
Criteria: Small Pharm, NSCLC, Phase I Trials, $$
STANDARD LICENSE TERMS
• If there is licensee interest:» An options based deal» Requires an upfront payment of approximately $3 million» In exchange if NIH achieves clinical proof of concept, Pharm
co. has option to pay $80 million for an exclusive license for the compound.
» Pharm co. would take over late-stage development and commercialization while NIH collects development, regulatory and commercial milestone payments totaling $400 million
» Eligibility to receive tiered royalties on worldwide product sales