Mallinckrodt Pharmaceuticals Investor Briefing October 14, 2014 Mallinckrodt Pharmaccuiicals John Moten Vice President, Investor Relations Mallinckrodt Pharmaceuticals Forward-Looking Statements Statements in this presentation that are not strictly historical, including statements regarding, future financial condition and operating results, economic, business, competitive and/or regulatory factors affecting our business and any other statements regarding events or developments that we believe or anticipate will or may occur in the future, may be “forward-looking” statements within the meaning of the Private Securities Litigation Reform Act of 1995, and involve a number of risks and uncertainties. There are a number of important factors that could cause actual events to differ materially from those suggested or indicated by such forward-looking statements and you should not place undue reliance on any such forward-looking statements. These factors include risks and uncertainties related to, among other things: ► ► ► ► ► ► ► ► ► ► ► ► 3 General economic conditions and conditions affecting the industries in which we operate; The commercial success of our products, including H.P. Acthar® gel (“Acthar"); Our ability to protect intellectual property rights; Our ability to maintain important business relationships; The lack of patent protection for Acthar, and the possible United States Food and Drug Administration ("FDA") approval and market introduction of additional competitive products; Our reliance on certain individual products that are material to our financial performance; Our ability to continue to generate revenue from sales of our products to treat on-label indications and to develop other therapeutic uses for them; Our ability to receive procurement and production quotas granted by the U.S. Drug Enforcement Administration; Our ability to obtain and/or timely transport molybdenum-99 to our technetium-99m generator production facilities; Customer concentration; cost containment efforts of customers, purchasing groups, third-party payers and governmental organizations; Our ability to successfully develop or commercialize new products; Competition; Forward-Looking Statements ► Our ability to achieve anticipated benefits of price increases; ► Our ability to successfully integrate acquisitions of operations, technology, products and businesses generally and to realize anticipated growth, synergies and cost savings; ► The reimbursement practices of a small number of large public or private issuers; ► Complex reporting and payment obligations under healthcare rebate programs; ► Changes in laws and regulations; ► Conducting business internationally; ► Foreign exchange rates; ► Material health, safety and environmental liabilities; ► Product liability losses and other litigation liability; and ► Information technology infrastructure and restructuring activities. Additional information regarding the factors that may cause actual results to differ materially from these forward-looking statements is available in (i) our SEC filings, including our Annual Report on Form 10-K for the fiscal year ended September 27, 2013 and our Quarterly Reports on Form 10-Q for the quarterly periods ended December 27, 2013, March 28, 2014 and June 27, 2014; (ii) the SEC filings of Cadence Pharmaceuticals, Inc., which was acquired by Mallinckrodt on March 19, 2014, including its Annual Report on Form 10-K for the fiscal year ended December 31, 2013; and (iii) the SEC filings of Questcor Pharmaceuticals, Inc.’s, which was acquired by Mallinckrodt on August 14, 2014, including its Annual Report on Form 10-K for the year ended December 31, 2013 (and the amendment thereto on Form 10-K/A), its Quarterly Reports on Form 10-Q for the quarterly periods ended March 31, 2014 and June 30, 2014, and its Current Report on Form 8-K filed with the SEC on July 10, 2014. The forward-looking statements made herein speak only as of the date hereof and neither Mallinckrodt nor any of its affiliates assume any obligation to update or revise any forward-looking statement, whether as a result of new information, future events and developments or otherwise, except as required by law. 4 Agenda for our session ► Mallinckrodt Business Transformation ► Specialty Pharmaceuticals ► H.P. Acthar Gel ► Business Background ► Physician and Patient Experience ► Fiscal Year 2015 Guidance ► Summary ► Investor Q&A 5 Mark Trudeau President and Chief Executive Officer r1 Mallinckrodt Pharmaccuiicals Mallinckrodt – Transformative growth built on a solid foundation We are: Well diversified global Specialty Biopharmaceutical company with focus in Brands and Specialty Generics Focus: Growth, profitability to drive value for shareholders and deliver solutions for patients Mastering Complexity Core Strength: ► Exceptional execution of concurrent transformational initiatives ► Management of highly regulated raw materials ► Expertise in regulatory, formulation, manufacturing processes ► Development of complicated products Our Goal: Top quartile performance based on total shareholder return 7 Transforming the portfolio At Spin1 FY2015 Guidance Global Medical Imaging 44% Global Medical Imaging ~20% 56% ~80% Specialty Pharmaceuticals 1 8 FY2013 Q3 YTD Net Sales, excluding sales to related parties Specialty Pharmaceuticals Diversified, durable portfolio of brands and specialty generic products in four growth platforms Office Brands Hospital Brands Autoimmune & Rare Diseases (ARD) Brands Specialty Controlled Substance Generics1 Goal is straightforward: Create Sustainable Value for Patients and Shareholders ► Develop and acquire durable, late stage complex products ► Invest in pipeline extensions of key portfolio assets ► Divest lower margin, slower growing businesses 9 1 Compete in 43 different categories Hugh O?Neill Senior Vice President and President, Specialty Pharmaceuticals r1 Mallinckrodt Pharmaccuiicals Durable assets and platforms positioned for sustained Specialty Pharmaceuticals growth Near term Long term 11 1Abbreviated Office Brands Hospital Brands Invest for long term growth Drive growth and profitability ► Drive XARTEMIS XR up-take in surgical specialties ► Expand OFIRMEV volume growth ► Grow Intrathecal ► Maximize commercial opportunity for XARTEMIS XR and MNK-155 New Drug Application ► Drive pharmacoeconomic value ► Pursue next generation OFIRMEV development Specialty Controlled Substance Generics Drive profit and generate cash ► Continue strong methylphenidate/pain portfolio performance ► Optimize hydrocodone rescheduling ► Advance ANDAs1 in pipeline ► Further Abuse Deterrent Technologies OFIRMEV is well positioned for growth in 2015 and beyond Units ~20% ~100% Sales May 2013 Sept 2013 Jan 2014 May 2014 Sept 2014 Sales are up ~100% since reset1 Volume is flat year over year, down ~20% from peak OFIRMEV is positioned to return to unit growth ► OFIRMEV enjoys broad formulary access ► Opportunity to further penetrate surgical market and increase vials per procedure ► Synergy of OFIRMEV and XARTEMIS XR as the post-op treatment continuum 12 1 Feb-April vs. May-July Surgical pain management continuum for multimodal pain treatment Location Sales Force Call Point 13 ► Inpatient Facilities ► Outpatient Facilities ► Physician Practices ► Hospital Specialists ► Outpatient Specialists ► Office Specialists ► Surgeons ► Pharmacy ► Anesthesiology ► ► ► ► ► Surgical Specialties Infusion Clinics Rehab Centers Surgery Centers Emergency Medicine Gary Phillips, M.D. Senior Vice President and President, Autoimmune and Rare Diseases Business Mallinckrodt Pharmacmiicals Acthar is a complex, naturally-derived biological product, mixture of organic molecules FDA approved in 19 debilitating diseases/conditions; currently marketed in only 9 indications* Neurology ► Infantile spasms* ► Multiple sclerosis flares in adults* Rheumatology Multiple organs (including muscle and joint): ► Lupus* ► Dermatomyositis/polymyositis* ► Rheumatoid arthritis flares* ► Psoriatic arthritis flares* ► Ankylosing spondylitis flares* Pulmonology ► Symptomatic sarcoidosis* Nephrology ► Edematous state* (remission of proteinuria in nephrotic syndrome) 15 See http://www.acthar.com/pdf/Acthar-PI.pdf for specific label and safety information Ophthalmology Eye inflammation such as: ► Keratitis ► Iritis ► Iridocyclitis ► Diffuse posterior uveitis ► Optic neuritis ► Chorioretinitis ► Anterior segment inflammation Dermatology Rare skin diseases such as: ► Stevens-Johnson syndrome ► Severe erythema multiforme Allergic States ► Serum sickness Acthar manufacturing is well-established and conducted under FDA current Good Manufacturing Practices CSL Behring Potency testing Results for MNK approval Potency testing Results for approval Porcine Pituitary Glands Final product release API release 1 Emergent Biosolutions2 ► Quality and potency monitoring throughout all stages of processing ► Manufacturing and purification process, precise characterization and ratio of organic elements in Acthar remain trade secrets 1 16 Owned by Mallinckrodt Pharmaceuticals 2 Formerly Cangene bioPharma Acthar is the foundation of our broad Autoimmune and Rare Diseases business In 9 currently promoted indications, only 3% of addressable Acthar patients are now treated ~ 4,000,000 ~ 300,000 ~ 9,000 1 17 Source: Internal estimates US patient population with Acthar indicated conditions Addressable but currently untreated1 Patients currently treated with Acthar2 2 Moving Mallinckrodt’s Strategy ► Document and publish clinical experience and health economic outcomes ► Grow utilization of Acthar in appropriate, but underserved, patient populations ► Initiate commercial efforts in other approved indications with high unmet medical need ► Increase payer engagement to support reimbursement ► Focus R&D investment ► We believe current regulatory guidelines drive complicated development and make a generic unlikely annual total (MAT) ending August 2014, 9,059 unique patients treated with Acthar Acthar growth historically strong; driven by market entry of therapeutic areas Acthar Net Revenue Pulmonology Rheumatology Nephrology Neurology FY 12 18 FY 13 FY 14 Mallinckrodt plans to enhance Science and Technology investment Substantial Historical Investment Science and Technology Spending ► Well-funded, diverse program • ~$190M invested in company and investigator sponsored research1 • ~300 funded studies ► Publication ramp up planned for 2015 ~55% CAGR Future Research Focus ► Health economic and outcomes research ► New clinical data in approved indications ► New clinical indications research ► Broaden Acthar’s scientific foundation 19 1 2011-2014 2012 2013 2014 E2015 Expanding the body of knowledge for Acthar1 20 ~35 ~140 ~60 YEARS Acthar studies on clinicaltrials.gov2 studies initiated or ongoing in 20142 of Acthar efficacy and safety experience ~80 19 ~6,000 publications referencing Acthar in the medical literature indications in FDA-approved label prescribers of Acthar since 2007 1Bibliography reference included in presentation appendix 2 Includes company and investigator sponsored research Planned and ongoing studies will provide the basis for potential publications Fiscal Year 2015 2016 2017 Non-clin Study Clinical Study External Study New and ongoing study strategy 21 Short-term (1-6 months): Document differentiation from steroids through non-clinical studies in animal models Medium-term (6-15 months): Expand on safety and efficacy data and healthcare economics with ongoing studies and available data Long-term (>15 months): Strengthen clinical confidence and healthcare economics with ongoing and new designed clinical studies Four ongoing in progress company sponsored clinical studies on clinicaltrials.gov 22 Study Objective Study Design Study Size Current Status Amyotrophic Lateral Sclerosis (ALS) ► Safety and tolerability ► Open label, randomized ► 40 patients ► Active, not enrolling Systemic Lupus Erythematosus (SLE) ► Efficacy, safety, pharmacodynamics ► Double blind, randomized ► 36 patients ► Active, not enrolling Membranous Nephropathy ► Efficacy and safety ► Double blind, randomized ► 60 patients ► Enrolling Diabetic Nephropathy ► Efficacy and safety ► Double blind, randomized ► 40 patients ► Enrolling Acthar reimbursement will continue to be important to reach underserved addressable patient populations Expect growth in appropriate patients to continue to outweigh reimbursement challenges % of Referrals Filled Acthar Referrals (per quarter) Strong, established foundation ► Support network established to help patients with reimbursement process ► Primary focus: appropriate access and accelerated reimbursement time Building on this foundation ► Engage payers at plan-wide policy level ► Document and communicate patient benefits of Acthar treatment FY12 FY13 % Reimbursed Pulmonology 23 FY14 Rheumatology Nephrology Neurology ► Publish clinical experience and health economic outcomes James A. Tumlin, M.D. Professor Medicine/Nephrology University of Tennessee Chattanooga Director Southeast Renal Research Institute Dr. Tumlin is a paid consultant and on the Speakers’ Bureau of Mallinckrodt Nephrotic Syndrome: Definition & Contributing Diseases High Grade Loss of Protein in the Urine >3000 mg/24rhs (Normal up to 150 mg/24 hrs. Low Serum Albumin < 3.0 mg/dl Hyperlipidemia: Elevated Cholesterol & Triglycerides Anasarca: Total Body Swelling and Edema 25 Proteinuria: Causes Massive Lower Extremity Swelling Weight Gain Nephrotic Syndrome: Definition & Contributing Diseases Amyloidosis Diabetic Nephropathy Membranoproliferative GN Focal Segmental GN Membranous GN Lupus Nephritis IgA Nephropathy C1Q Nephropathy 27 Podocyte Loss ContributesTo Protein Losses in Urine Gd Blood Proteins Blood Proteins Diabetic Podocytopathy: Cellular Target of Injury and Focus of Therapeutic Interventions Altered Hemodynamics Increased Transglomerular Pressures Ang- II-Aldo Induced Podocyte Apoptosis/Detachment Ang-II-Aldo Induced ROS Injury Loss of Capillary Anionic Charge: Heparin SO4 Podocalyxin TGF-β Induced Podocyte Apoptosis/Detachment Hyperglycemia RAGE Receptor ROS Injury Reduced Production Podocyte VEGF-A 29 Corticotrophins: Podocyte Stabilizers? Acthar Binds to Five Different Melanocortin Receptors1-3 Cortisol-dependent Biologic effect Cortisol-independent effects (direct MCR binding) While the exact mechanism of action of Acthar is unknown, further investigation is being conducted. This information is based on nonclinical data, and the relationship to clinical benefit is unknown. 1) Catania A, et al. Sci World J. 2010;10:1840-1853.; 2) Lindskog A, et al. J Am Soc Nephrol. 2010;21:1290-1298. 3) Gong R, et al. Nat Rev Nephrol. 2011;8:122-128.; 4( Data on file: RD-010-00. 31 ACTH & Tacrolimus Blocks Degredation of Podocyte Synaptopodin: Mechanism for Protein Reduction TRPC-6 gain of function mutation Increases intracellular Ca++ ACTH Rising intracellular Ca stimulates Calcineurin-mediated dephosphorylation of Synaptopodin leading to accelerated Protein degredation PKA PO4 TRPC6 B7 Ca++ Tacro x Tacrolim us PO4 α-Actinin-4 Ca++ α Tacrolimus also inhibits Calcineurin Mediated dephosphorylation of Synaptopodin thereby reducing protein degradation ACTH binds Podocyte MCR-1 receptors Stimulating PKA phosphorylation of Synaptopodin thus further reducing protein degradation β Ca++ α3-Integrin Tacrolimus binds to FKBP12 protein Of TRPC-6 complex and reduces Channel activity β1-Integrin Collagen 3,4 and 5 32 ACTH and Protein Kinase A Activation Reduces Proteinuria Through Inhibition of Podocyte Apoptosis ACTH ACTH Binding to MCR-1 receptors in The podocyte leads to activation of Protein Kinase A (PKA) PKA TRPC6 Activated PKA directly phosphorylates BAD on serine 112 increasing docking With 14-3-3 PO4 Ca++ X Apoptosis α3-Integrin Bound BAD in blocked from complexing with other Pro-Apoptotic proteins Release of cytochrome C from the Mitochondria is blocked and Podocyte Apoptosis is reduced β1-Integrin Collagen 3,4 and 5 33 Corticotrophin Use in Protein Loosing Renal Diseases Membranoproliferative GN Focal Segmental GN Membranous GN Lupus Nephritis IgA Nephropathy C1Q Nephropathy 34 Mallinckrodt Pharmaceuticals Investor Briefing October 14, 2014 Mallinckrodt Pharmaccuiicals Todd D. Levine, M.D. Clinical Assistant Professor University of Arizona Adjunct Professor Kansas University Dr. Levine is a paid consultant and on the Speakers’ Bureau of Mallinckrodt Mallinckrodt Pharmaceuticals Investor Briefing October 14, 2014 Mallinckrodt Pharmaccuiicals Physician Mallinckrodt Pharmaceuticals Gary Phillips, M.D. Senior Vice President and President, Autoimmune and Rare Diseases Business Mallinckrodt Pharmacmiicals Acthar is a durable asset with significant growth potential ► Reach underserved patient populations in current indications, build on near-term opportunities in rheumatology and pulmonology ► Solidify, enhance publication strategy to expand Acthar awareness ► Support reimbursement access for appropriate patients in need ► Invest in infrastructure to continue to ensure quality and uninterrupted supply 40 Matt Harbaugh Senior Vice President and Chief Financial Officer r1 Mallinckrodt Pharmaceuticals Guidance – Fiscal Year 2015 $ in millions, except per share data Metric (excluding foreign currency impact) Adjusted diluted EPS 42 FY15 Guidance $6.70 to $7.20 Total company net sales $3,650 to $3,750 Specialty Pharmaceuticals net sales $2,870 to $2,930 Global Medical Imaging net sales $760 to $800 Non-GAAP effective tax rate 20% to 23% Capital expenditures $130 to $150 Mark Trudeau President and Chief Executive Officer r1 Mallinckrodt Pharmaccuiicals Mallinckrodt – Where we’re going ► Leverage four platforms to accelerate growth ► Focus on integration and expansion of the durable Acthar asset ► Execute on hospital/surgical specialty/pain synergy ► Advance pipeline, seek BD&L opportunities in core business and growth platforms ► Continue flawless execution of our growth and profitability strategy; operate a lean and efficient business model Our Goal: Top quartile performance based on total shareholder return 44 Mallinckrodt Pharmaceuticals Thank You Mallinckrodt Pharmaceuticals Closing Remarks Thank You Mallinckrodt, the “M” brand mark, the Mallinckrodt Pharmaceuticals logo and other brands are trademarks of a Mallinckrodt company. © 2014 Mallinckrodt. 49 Mallinckrodt Pharmaceuticals Investor Briefing October 14, 2014 Mallinckrodt Pharmaccuiicals Appendix Mallinckrodt Pharmaceuticals Reference Bibliography Infantile Spasms – Manuscripts 1. Baram TZ, Mitchell WG, Tournay A, Snead OC, Hanson RA, Horton EJ. High-dose corticotropin (ACTH) versus prednisone for infantile spasms: A prospective, randomized, blinded study. Pediatrics. 1996;97(3):375-379. 2. Hrachovy RA, Frost JD,Jr., Glaze DG. High-dose, long-duration versus low-dose, short-duration corticotropin therapy for infantile spasms. J Pediatr. 1994;124(5 Pt.1):803-806. 3. Hrachovy RA, Frost JD,Jr., Kellaway P, Zion T. A controlled study of ACTH therapy in infantile spasms. Epilepsia. 1980;21(6):631-636. 4. Hrachovy RA, Frost JD,Jr, Kellaway P, Zion TE. Double-blind study of ACTH vs prednisone therapy in infantile spasms. J Pediatr. 1983;103(4):641-645. 5. Hussain SA, Shinnar S, Kwong G, et al. Treatment of infantile spasms with very high dose prednisolone before high dose adrenocorticotropic hormone. Epilepsia. 2014;55(1):103-107. 6. Kossoff EH, Hedderick EF, Turner Z, Freeman JM. A case-control evaluation of the ketogenic diet versus ACTH for new-onset infantile spasms. Epilepsia 2008;49 (9 ):1504 -9. 7. Partikian A, Mitchell WG. Major adverse events associated with treatment of infantile spasms. J Child Neurol. 2007;22(12):1360-1366. 8. Snead III OC, Benton JW, Myers GJ. ACTH and prednisone in childhood seizure disorders. Neurology. 1983;No. 8:966. 9. Snead OC,III, Benton JW,Jr., Hosey LC, et al. Treatment of infantile spasms with high-dose ACTH: Efficacy and plasma levels of ACTH and cortisol. Neurology 1989;39 (8 ):1027 -31. Infantile Spasms – Reviews 10. Arya R, Shinnar S, Glauser TA. Corticosteroids for the treatment of infantile spasms: A systematic review. J Child Neurol. 2012;27(10):1284-1288. 11. Bonkowsky JL, Filloux FM, Byington CL. Herpes simplex virus central nervous system relapse during treatment of infantile spasms with corticotropin. Pediatrics. 2006;117(5):e1045-e1048. 12. Dunagan DP, Rubin BK, Fasano MB. Pneumocystis carinii pneumonia in a child receiving ACTH for infantile spasms. . Pediatr Pulmonol. 1999;27(4):286-289. 13. Go T. Sequential MRI in chronic meningitis during adrenocorticotropic hormone treatment for west syndrome. Childs Nervous System. 2001;17(8):497-499. 14. Kongelbeck SR. Discharge planning for the child with infantile spasms. J Neurosci Nurs. 1990;No. 4:238-244. 15. Mackay MT, Weiss SK, Adams-Webber T, et al. Practice parameter: Medical treatment of infantile spasms: Report of the american academy of neurology and the child neurology society. Neurology. 2004;62(10):1668-1681. 16. Pellock JM, Hrachovy R, Shinnar S, et al. Infantile spasms: A U.S. consensus report. Epilepsia. 2010;51:2175-2189. 17. Stafstrom CE, Arnason BG, Baram TZ, et al. Treatment of infantile spasms: Emerging insights from clinical and basic science perspectives. J Child Neurol. 2011;26:1411-1421. 18. Taylor JB, Young WO, Rutar T. Posterior subcapsular cataracts in children receiving adrenocorticotropic hormone (ACTH) for infantile spasms. J Child Neurol. 2010;25(8):1017-1019. 19. Wang J, Wang J, Zhang Y, et al. Proteomic analysis of adrenocorticotropic hormone treatment of an infantile spasm model induced by N-methyl-D-aspartic acid and prenatal stress. PLoS One. 2012;7(9):e45347. Infantile Spasms – Abstracts 20. Knupp K, Wirrell E, Berg A, Khan S. The national infantile spasms consortium (NISC), A US multicenter initiative to improve treatment and outcomes of infantile spasms: Etiologies, initial therapies and early follow up. American Epilepsy Society Annual Meeting. 2013:Abst. 1.149. 21. Mytinger JR, Weber A, Heyer GL. The response to ACTH is determined early in the treatment of infantile spasms. American Epilepsy Society Annual Meeting 2013. 2013:360-, Abstract 3.144. 52 Reference Bibliography Nephrotic Syndrome - Manuscripts 22. Bomback AS, Tumlin JA, Baranski J, et al. Treatment of nephrotic syndrome with adrenocorticotropic hormone (ACTH) gel. Drug Des Devel Ther. 2011;5:147-153. 23. Bomback AS, Canetta PA, Beck LH,Jr., Ayalon R, Radhakrishnan J, Appel GB. Treatment of resistant glomerular diseases with adrenocorticotropic hormone gel: A prospective trial. American Journal of Nephrology. 2012;36(1):58-67. 24. Hladunewich MA, Cattran D, Beck LH, et al. A pilot study to determine the dose and effectiveness of adrenocorticotrophic hormone (H.P. acthar gel) in nephrotic syndrome due to idiopathic membranous nephropathy. Nephrology. 2014;29(8):1570-1577. 25. Hogan J, Bomback AS, Mehta K, et al. Treatment of idiopathic FSGS with adrenocorticotropic hormone gel. Clinical Journal of the American Society of Nephrology. 2013;8(12):2072-2081. 26. Lieberman, K. Adrenocorticotropic hormone for steroid-resistant and oral steroid-intolerant children with minimal change nephrotic syndrome, Journal of Clinical Pediatric Nephrology, In press, 2014 27. Watson MJ. Membranous glomerulopathy and treatment with acthar(R): A case study. Int J Nephrol Renovasc Dis. 2013;6:229-232. Nephrotic Syndrome - Reviews 28. Bomback AS, Radhakrishnan J. Treatment of nephrotic syndrome with adrenocorticotropic hormone (ACTH). Discovery Medicine. 2011;12(63):91-96. 29. Gong R. The renaissance of corticotropin therapy in proteinuric nephropathies. Nat Rev Nephrol. 2012;8:122-128. Nephrotic Syndrome - Abstracts 30. Arif H, Ellie K, Monalisa J. "Repository ACTH". novel therapy in treatment of resistant nephrotic syndrome. Am J Kidney Dis - National Kidney Foundation 2013 Spring Clinical Meetings. 2013;61(4):A21. 31. Beck LH, Fervenza FC, Bomback AS, Ayalon R, Irazabal MV, Eirin A, Cattran DC, Appel GB, Salant DJ. Response of Anti-PLA2R to adrenocorticotropic hormone (ACTH) gel in membranous nephropathy. ASN 2011 (TH-OR135) 32. Bomback AS, Jai R, James EB, et al. The treatment of resistant nephrotic syndrome with acthar gel (ACTH). J Am Soc Nephrol - Kidney Week 2010. 2010;21:93A-Abstract SA-FC409. 33. Bomback ASJ,Radhakrishnan, Pietro AC, Gerald BA. Treatment of resistant glomerular diseases with ACTH gel: A prospective trial. J Am Soc Nephrol - Kidney Week 2011. 2011;22:776A-Abstract SA-PO2864. 34. Faizan MK, Ruchir SP. Successful remission of treatment-resistant minimal change disease with adrenocorticotropic hormone gel. ASN - Kidney Week 2013. 2013:906. 35. Gaurav K, Gera M. Experience with acthar for treatment of nephrotic range proteinuria of different etiologies. A case series. National Kidney Foundation 2013 Spring Clinical Meetings Abstracts. 2013:225. 36. Hladunewich M,A, Fervenza F,C, Beck L,H., et al. A pilot study to determine dose, effectiveness and depletion of anti-PLA2R antibodies of adrenocorticotrophic hormone (ACTH acthar gel) in subjects with nephrotic syndrome and idiopathic membranous nephropathy (IMN). ASN - Kidney Week 2012. 2012:Abstract FR-OR125. 37. Hogan JJ, Jai R, Gerald BA, Andrew SB, Pietro AC, Maya KR. Treatment of resistant primary focal segmental glomerulosclerosis (FSGS) with adrenocorticotropic hormone (ACTH) gel. ASN - Kidney Week 2012. 2012:170. 38. Koppula S, Amy NS, Barry RG. Reemergence of adrenocorticotropin hormone as novel therapy for focal segmental glomerulosclerosis. ASN - Kidney Week 2012. 2012:Abstract SA-PO1031. 53 Reference Bibliography Nephrotic Syndrome - Abstracts (Con’t) 39. Lafayette R,A, Jai R, Jonathan JH, et al. Treatment of primary focal segmental glomerulosclerosis with adrenocorticotropic hormone (ACTH) gel. Iranian Society of Nephrology International Congress 2013. 2013:Abstract SA251. 40. Lieberman K, Ettinger L, Picarelli C. ACTH gel for treating steroid resistance (SR) and oral steroid intolerance (OSI) in pediatric minimal change nephrotic syndrome (MCNS). Pediatr Nephrol IPNA Congress. 2013;28(8):1598. 41. Madan A, Milward AS, Khastgir A. Treatment of nephrotic syndrome with acthar gel: A retrospective case series. Am J Kidney Dis - National Kidney Foundation Conference. 2014;63(5):A75. 42. McHugh P,P., Muhammad AM, Asif AS, Muhammad SY, Tim ET. Treatment of post-transplant immunosuppression resistant focal segmental glomerulosclerosis with adrenocorticotropic gel. ASN Kidney Week 2013. :Abstract FR-PO1135. 43. Melhem AY, Schmitz P. Single center experience with ACTH for the treatment of resistant nephrotic syndrome ASN - Kidney Week 2013. 2013:Abstract SA-PO677. 44. Meliambro K, Sharma S, Campbell KN. Treatment-refractory histologic tip-variant FSGS in a patient with systemic lupus erythematosus. Am J Kidney Dis - National Kidney Foundation Conference. 2014;63(5):A35. 45. Nguyen V, El-Meanawy A. Acth a novel treatment for IgA nephropathy. J Investig Med - 2014 Combined Annual Meeting of the Central Society for Clinical and Translational Research and the Midwestern Section American Federation for Medical Research. 2014;62(4):720. 46. Patel A,B, Markell M,S. Use of ACTH gel in a patient with progressive nephrotic syndrome secondary to transplant glomerulopathy (TG). ASN - Kidney Week 2012. 2012:Abstract: TH-PO1140. 47. Shirsat PD, Habib SY. Use of ACTH gel in a patient with progressive nephrotic syndrome secondary to transplant glomerulopathy (TG) ASN - Kidney Week 2013. :614-Abstract FR-PO1088. 48. Tumlin JA. Safety and efficacy of acthar gel (ACTH) on albuminuria and progression of diabetic nephropathy in patients with nephrotic range proteinuria: A randomized prospective study. J Am Soc Nephrol - Kidney Week 2010. 2010;21:678A-Abstract: SA-PO2471. 49. Tumlin JA, Galphin CM, Rovin BH. Advanced diabetic nephropathy with nephrotic range proteinuria: Long- term efficacy of subcutaneous adrenocorticotrophic hormone (ACTH ) therapy on proteinuria and urinary vascular endothelial growth factor (VEGF) levels. J Am Soc Nephrol - Kidney Week 2011. 2011;22:24A-Abstract: TH-OR073. 50. Welik RA. Adrenocorticotropic hormone therapy for idiopathic glomerulonephritis: 6-week interim data from an ongoing, 6-month trial . J Am Soc Nephrol - Kidney Week 2012. 2012;23:1051A-Abstract PUB712. Multiple Sclerosis Relapses - Manuscripts 51. Alexander L, Cass LJ. The present status of ACTH therapy in multiple sclerosis. Ann Intern Med. 1963;58:454-471. 52. Alexander L, Cass LJ. Significance of dosage in ACTH therapy of multiple sclerosis. Transactions of the American Neurological Association. 1963;88:184-185. 53. Alexander L, Cass LJ, Enders M, Sarai K. Adrenocortical response to high dosage ACTH therapy in patients with multiple sclerosis. Confinia Neurologica. 1966;28:1-17. 54. Berkovich R, Agius MA. Mechanisms of action of ACTH in the management of relapsing forms of multiple sclerosis. Ther Adv Neurol Disord. 2014;7(2):83-96. 55. Molitor RE, Stewart J. Home intravenous administration of adrenocorticotropic hormone in patients with multiple sclerosis. J Intraven Nurs. 1988;11(4):249-251. 56. Rose AS, Kuzma JW, Kurtzke JF, Namerow NS, Sibley WA, Tourtellotte WW. Cooperative study in the evaluation of therapy in multiple sclerosis. ACTH vs. placebo--final report. Neurology. 1970;20(5):1-59. 57. Ross AP, Halper J, Harris CJ. Assessing relapses and response to relapse treatment in patients with multiple sclerosis: A nursing perspective. Int J MS Care. 2012;14(3):148-159. 58. Simsarian JP, Saunders C, Smith DM. Five-day regimen of intramuscular or subcutaneous self-administered adrenocorticotropic hormone gel for acute exacerbations of multiple sclerosis: A prospective, randomized, open-label pilot trial. Drug Design. 2011;5:381-389. 54 Reference Bibliography Multiple Sclerosis Relapses -Reviews 59. Arnason BG, Berkovich R, Catania A, Lisak RP, Zaidi M. Mechanisms of action of adrenocorticotropic hormone and other melanocortins relevant to the clinical management of patients with multiple sclerosis. Mult Scler. 2013;19:130-136. 60. Berkovich R. Treatment of acute relapses in multiple sclerosis. Neurotherapeutics. 2013;10(1):97-105. 61. Ross AP, Ben-Zacharia A, Harris C, Smrtka J. Multiple sclerosis, relapses, and the mechanism of action of adrenocorticotropic hormone. Front Neurol. 2013;4:21. Multiple Sclerosis Relapses - Abstracts 62. Amezcua L, Axtell R, Cen S, et al. Pilot study of monthly pulse adrenocorticotropic hormone (ACTH) or methylprednisolone as an add-on therapy to beta interferons for long-term treatment of multiple sclerosis. Multiple Sclerosis Conference: 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis, ECTRIMS , 18th Annual Conference of Rehabilitation in MS. 2013:Abstract 1097. 63. Bailey R,O., Carina GS, Randy RH, Vu AN. Use of acthar GEL for MS exacerbations during natalizumab induction and maintenance. CMSC and ACTRIMS Cooperative Meeting. 2013:1549. 64. Berkovich R,R., Maura F, Dawood S. Adrenocorticotropic hormone treatment of multiple sclerosis exacerbations. CMSC and ACTRIMS Cooperative Meeting. 2012:88-Abstract DX66. 65. Berkovich R, Amezcua L, Fernandez M, Subhani D, Kravtsova I. Monthly pulse adrenocorticotropic hormone (acth) or methylprednisolone therapy for long-term treatment of multiple sclerosis as an add-on therapy to beta-interferons: Current status of the pilot study. Neurology. 2012;78(Suppl. 1):22-Abstract P04147. 66. Berkovich R, Amezcua L, Subhani D, Cen S. Pilot study of monthly pulse adrenocorticotropic hormone (ACTH) or methylprednisolone as an add-on therapy to beta-interferons for long-term treatment of multiple sclerosis. Neurology Conference: 65th American Academy of Neurology Annual Meeting San Diego, CA United States Conference Start:. 2013:07. 67. Butterfield T, Maquera V,A. Preventing new enhancing lesions and relapses after discontinuing tysabri. CMSC and ACTRIMS Cooperative Meeting. 2013;5th:DX14. 68. Lehrer GM. Treatment of MS with ACTHar gel-clinical experience and case presentation. Ann Neurol. 2012;72(Sup 16):S114. 69. Williamson A, Smrtka J, Flemming Tracy T, et al. Assessing relapse in multiple sclerosis (ARMS) questionnaire: Initial pilot data. Mult Scler. 2012;18(4 SUPPL. 1):329-330. Rheumatic disorders - Manuscripts 70. Bacon PA, Daly JR, Myles AB, Savage O. Hypothalamo-pituitary-adrenal function in patients on long-term adrenocorticotrophin therapy. Annals of the Rheumatic Diseases. 1968;27(1):7-13. 71. Carey RA., Harvey AM., Howard JE. The effect of adrenocorticotropic hormone (ACTH) and cortisone on the course of disseminated lupus erythematosus and peri-arteritis nodosa. Bull Johns Hopkins Hosp. 1950;87(5):425-460. 72. Carter ME, James VH. Effect of corticotrophin therapy on pituitary-adrenal function. Ann Rheum Dis. 1970;29(1):73-80. 73. Clark WS, Tonning HO, Kulka JP, Bauer W. Observations on the use of cortisone and ACTH in rheumatoid arthritis. N Engl J Med. 1953;249(16):635-642. 74. Donnelly P, Cooke D. A study of the combined effect of ACTH(gel) and D-penicillamine on the functional disability of patients with rheumatoid disease. J Rheumatol. 1982;9(6):867-872. 75. Fiechtner JJ, Montroy T. Treatment of moderately to severely active systemic lupus erythematosus with adrenocorticotropic hormone: A single-site, open-label trial. Lupus. 2014;23(9):905-912. 76. Friedman M, Marshall-Jones P, Ross EJ. Cushing's syndrome: Adrenocortical hyperactivity secondary to neoplasms arising outside the pituitary-adrenal system. Q J Med. 1966;35(138):193-214. 77. Glass D, Daly JR. Development of antibodies during long-term therapy with corticotrophin in rheumatoid arthritis. I. porcine ACTH. Ann Rheum Dis. 1971;30(6):589-592. 78. Hench PS, Kendall EC, Slocumb CH, Polley HF. Effects of cortisone acetate and pituitary ACTH on rheumatoid arthritis, rheumatic fever and certain other conditions. Arch Intern Med. 1950;85(4):545-666. 79. Levine T. Treating refractory dermatomyositis or polymyositis with adrenocorticotropic hormone gel: A retrospective case series. Drug Des Devel Ther. 2012;6:133-139. 55 Reference Bibliography Rheumatic disorders - Manuscripts (Con’t) 80. Nelson JK, Mackay JS, Sheridan B, Weaver JA. Intermittent therapy with corticotrophin. Lancet. 1966;2(7454):78-83. 81. Nelson SD, Mackay JS, Sheridan B, Weaver JA. Intermittent corticotrophin therapy. study of lymphocyte transformation in vitro in rheumatoid arthritis. Ann Rheum Dis. 1969;28(5):524-528. 82. Savage O, Davis PS, Chapman L, Wickings J, Robertson JD, Copfman WS. Corticotrophin (ACTH) in rheumatoid arthritis. Ann Rheum Dis. 1959;18:100-110. 83. Wedgwood RJ, Janeway CA. Serum complement in children with collagen diseases. Pediatrics. 1953;11(6):569-581. 84. West HF. Purified ACTH gel control of therapy in rheumatoid patients. Ann Rheum Dis. 1954;13(1):56-58. 85. West HF, Newns GR. Allergy to bovine ACTH (adrenocorticotropic hormone). Lancet. 1952;262:1308. 86. Zutshi DW, Friedman M, Ansell BM. Corticotrophin therapy in juvenile chronic polyarthritis (still's disease) and effect on growth. Arch Dis Child. 1971;46(249):584-593. Rheumatic disorders - Conference Abstracts 87. Montroy T, Fiechtner JJ. A single-site, investigator initiated, open-label trial of the adrenocorticotropic hormone (acth) analogue hp acthar gel (repository corticotropin injection) among subjects with moderately to severely active systemic lupus erythematosus (sle). Ann Rheum Dis. 2013;72(Suppl. 3):904. Sarcoidosis - Manuscripts 88. Solomons B,Jr. Sarcoidosis; an aetiological and therapeutic appraisal. Ir J Med Sci. 1956;369:417-421. Ophthalmic diseases - Manuscripts 89. Bowden AN, Bowden PM, Friedmann AI, Perkin GD, Rose FC. A trial of corticotrophin gelatin injection in acute optic neuritis. Journal of Neurology, Neurosurgery & Psychiatry. 1974;37(8):869-873. 90. Eadie S, Thompson M. Kerato-conjunctivitis sicca treated with cortisone and ACTH. Br J Ophthalmol. 1955;39(2):90-97. 91. Thorpe HE. ACTH and cortisone in ocular trauma in eye surgery: A preliminary report. Proceedings of the Second Clinical ACTH Conference. 1951;2(25):340-361. Opsoclonus-Myoclonus – Manuscripts 92. Pranzatelli MR, Chun KY, Moxness M, Tate ED, Allison TJ. Cerebrospinal fluid ACTH and cortisol in opsoclonus-myoclonus: Effect of therapy. Pediatr Neurol. 2005;33(2):121-126. 93. Pranzatelli MR, Huang Y-, Tate E, et al. Monoaminergic effects of high-dose corticotropin in corticotropin-responsive pediatric opsoclonus-myoclonus. Mov Disord. 1998;13(3):522-528. 94. Pranzatelli MR, Tate ED, Crowley JM, Toennies B, Creer M. Neurometabolic effects of ACTH on free amino compounds in opsoclonus-myoclonus syndrome. Neuropediatrics. 2008;39(3):164-171. 95. Pranzatelli MR, Tate ED, McGee NR, et al. Key role of CXCL13/CXCR5 axis for cerebrospinal fluid B cell recruitment in pediatric OMS. J Neuroimmunol. 2012;243(1-2):81-88. 96. Pranzatelli MR, Tate ED, Verhulst SJ, et al. Pediatric dosing of rituximab revisited: Serum concentrations in opsoclonus-myoclonus syndrome. J Pediatr Hematol Oncol. 2010;32(5):e167-e172. 97. Tate ED, Pranzatelli MR, Verhulst SJ, et al. Active comparator-controlled, rater-blinded study of corticotropin-based immunotherapies for opsoclonus-myoclonus syndrome. Journal of Child Neurology. 2012;27(7):No-875. 56 Reference Bibliography Hay-Fever - Manuscripts 98. Parr EJ. Hay fever treated with ACTH gel. Clin Allergy. 1976;6(5):479-486. Smoking- Manuscripts 99. McElhaney JL. Repository corticotropin injection as an adjunct to smoking cessation during the initial nicotine withdrawal period: Results from a family practice clinic. Clin Ther. 1989;11(6):854-861. Other - Manuscripts 100. Adler GK, Kinsley BT, Hurwitz S, Mossey CJ, Goldenberg DL. Reduced hypothalamic-pituitary and sympathoadrenal responses to hypoglycemia in women with fibromyalgia syndrome. Am J Med. 1999;106(5):534-543. 101. Fleischer N, Abe K, Liddle GW, Orth DN, Nicholson WE. ACTH antibodies in patients receiving depot porcine ACTH to hasten recovery from pituitary-adrenal suppression. J Clin Invest. 1967;46(2):196-204. 102. Landon J, Friedman M, Greenwood FC. Antibodies to corticotrophin and their relation to adrenal function in children receiving corticotrophin therapy. Lancet. 1967;1(7491):652-655. 103. Kater CE, Irony I, Biglieri EG, Faical S. Continuous adrenocorticotropin administration in hypopituitarism produces asynchronous increases of deoxycorticosterone and 11-deoxycortisol relative to other reduced zona fasciculata steroids. J Clin Endocrinol Metab. 1990;71(2):305-310. 104. Millar JH, Rahman R, Vas CJ, Noronha MJ, Liversedge LA, Swinburn WR. Effect of withdrawal of corticotrophin in patients on long-term treatment for multiple sclerosis. Lancet. 1970;1(7649):700701. 105. Millar JH, Vas CJ, Noronha MJ, Liversedge LA, Rawson MD. Long-term treatment of multiple sclerosis with corticotrophin. Lancet. 1967;2(7513):429-431. 106. Rosenblum AH, Rosenblum P. Anaphylactic reactions to adrenocorticotropic hormone in children. J Pediatr. 1964;64:387-395. 107. Tumlin JA, Galphin CM, Rovin BH. Advanced diabetic nephropathy with nephrotic range proteinuria: A pilot study of the long-term efficacy of subcutaneous ACTH gel on proteinuria, progression of CKD, and urinary levels of VEGF and MCP-1. Journal of Diabetes Research. 2013:489869. Healthy - Manuscripts 108. Brod SA, Morales MM. Bio-equivalence of IM and SQ H.P. acthar gel. Biomed Pharmacother. 2009;63:251-253. 109. Brod SA, Bauer V, Hood Z. Oral ACTH (H.P. ActharGel) inhibits IL-1 and IL-17 secretion in humans. Biomed Pharmacother. 2012;66(1):36-39. Healthy – Conference Abstracts 110. Bell S, Vincent J, Hammock V, et al. A comparison of the safety/tolerability and pharmacodynamics of acthar gel and methylprednisolone with regimens utilized for the treatment of MS exacerbations. Neurology Conference: 66th American Academy of Neurology Annual Meeting, AAN. 2014:08. 57 Reference Bibliography Non-Clinical - Manuscripts 111. Brod SA, Hood ZM. Ingested (oral) ACTH inhibits EAE. J Neuroimmunol. 2011;232(1-2):131-135. 112. Brunson KL, Khan N, Eghbal-Ahmadi M, Baram TZ. Corticotropin (ACTH) acts directly on amygdala neurons to down-regulate corticotropin-releasing hormone gene expression. Annals of Neurology. 2001;No. 3:304. 113. Cheng B, Chou SC, Abraham S, Kowal J. Effects of prolonged ACTH-stimulation on adrenocortical cholesterol reserve and apolipoprotein E concentration in young and aged fischer 344 male rats. Journal of Steroid Biochemistry and Molecular Biology. 1998;66(5-6):335-345. 114. Decker D, Grant C, Oh L, Becker P, Young D, Jordan S. Immunomodulatory effects of H.P. acthar gel on B cell development in the NZB/W F1 mouse model of systemic lupus erythematosus. Lupus. 2014;23:802-812. 115. Gentry PA, Liptrap RM, Tremblay RR, Lichen L, Ross ML. Adrenocorticotrophic hormone fails to alter plasma fibrinogen and fibronectin values in calves but does so in rabbits. Vet Res Commun. 1992;16(4):253-264. 116. Marques N, Sanchez de lP, Ungar F, Halberg F. Circadian stage-dependent effect of ACTH and melatonin on protein synthesis by rat adrenal cells. Braz J Med Biol Res. 1988;21(4):759-762. 117. Si J, Ge Y, Zhuang S, Wang LJ, Chen S, Gong R. Adrenocorticotropic hormone ameliorates acute kidney injury by steroidogenic-dependent and -independent mechanisms. Kidney International. 2013;83(4):635-646. 118. Tait JF, Tait SA, Bell JB, Hyatt PJ, Williams BC. Further studies on the stimulation of rat adrenal capsular cells: Four types of response. J Endocrinol. 1980;87(1):11-27. 58