NASDAQ: ANTH Corporate Presentation January 2013 1
Forward Looking Statements This presentation contains "forward-looking" statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, that involve risks and uncertainties. These forward-looking statements include statements about our business outlook and strategy, and statements about historical results that may suggest trends for our business. You can identify these statements by the use of terminology such as guidance, believe, expect, will, or similar forward-looking terms. You should not rely on these forward-looking statements as they involve risks and uncertainties and may cause actual results to vary materially from the forward-looking statements. Factors that might contribute to such differences include, among others, economic downturns and the general state of the economy, our ability to retain and hire necessary employees; our ability to develop on a timely basis our clinical program; unforeseen changes in expense levels; and competition, which could lead to pricing pressure. For more information regarding the risks and uncertainties that could cause actual results to differ materially from those expressed or implied in these forward-looking statements, as well as risks relating to our business in general, we refer you to the Risk Factors sections of the company s SEC filings, which are available on the Securities and Exchange Commission s Web site at www.sec.gov. These forward-looking statements are based on current expectations and the company assumes no obligation to update this information. Anthera has filed a registration statement (including a prospectus) with the Securities and Exchange Commission for the offering to which this communication relates. Before you invest, you should carefully read the prospectus supplement and the accompanying prospectus, together with the information incorporated by reference, as well as any free writing prospectus that Anthera or the underwriters provide you in connection with the offering, for more information about Anthera and the offering. You may obtain those documents that are filed for free by visiting EDGAR on the Securities and Exchange Commission's website at www.sec.gov. Alternatively, you may obtain a copy of the prospectus supplement and accompanying prospectus, when available, by calling Jefferies & Company, Inc. at 877-547-6340. 2
Late Stage Clinical Pipeline Targeting BAFF Inhibition Phase 1 Phase 2 Phase 3 IgA Nephropathy Orphan Indication with few Tx Options Leading Cause of Renal Failure Large ROW Opportunity and US Orphan Lupus Nephritis Large Unmet Medical Need Orphan Indication BAFF, Membrane Bound BAFF target Initiation Pending Results from BRIGHT SC Study Systemic Lupus Erythematosus Targeted Patient Population Greater clinical improvement Clear commercial differentiation 3
Data from PEARL-SC Informs Development Strategy Compelling Renal Disease Data from PEARL-SC Guides Orphan Strategy IgA Nephropathy Lupus Nephritis Partner/Option Systemic Lupus Erythematosus 4
Promising Orphan Opportunities In Renal Disease IgA Nephropathy Orphan disease: ~40,000 in US Most common cause of primary glomerulonephritis in Asia Elevated BAFF increases production of immunogenic IgA from elevated plasma cells Immunogenic IgA leads to kidney damage Level of proteinuria predicts risk of eventual renal failure Lupus Nephritis Orphan disease: US prevalence 1 case per 2000 population Kidney expression of membranebound BAFF in lupus nephritis Proteinuria and egfr clinically meaningful endpoints Double-stranded DNA (dsdna) antibody leads to kidney damage Rate of decline in egfr predicts risk of eventual renal failure Clinical Hypothesis: Inhibition of BAFF with Blisibimod will Improve Outcomes in B Cell Mediated Renal Diseases such as IgA Nephropathy and Lupus Nephritis 5 Ishani et al. 2006; Lai et al. 2012; Neusser et al. 2011; Pozzi et al. 2004; Ruggenenti et al. 1998; Yoshikawa et al. 2006;
BAFF Involvement in B Cell Maturation and Survival (Healthy individuals) BAFF Receptor Normal IgA Blisibimod BCMA BAFF Immunogenic IgA Anti-dsDNA ab Normal Kidney Bone Marrow Peripheral Lymphoid Tissue CD19/CD20 CD19/CD20 CD19/CD20 Plasma Cell Immature B Cell Mature (naïve) Activated B Cell Memory B Cell Healthy individuals have normal levels of B cells, plasma cells, and normal IgA antibodies which protect against infection 6
IgA Nephropathy BAFF and B Cell Mediated Pathology Serum BAFF Levels Correlate with Severity of Disease Segmental glomerulosclerosis grade Atrophy/Interstitial fibrosis grade Serum BAFF (ng/ml) 14 12 10 8 6 4 2 p<0.001 p<0.001 N=55 N=26 N=127 14 12 10 8 6 4 2 p<0.001 p<0.001 p<0.001 p<0.001 N=55 N=96 N=45 N=12 0 healthy control Mild Moderate 0 healthy control Mild Moderate Severe 7 * p<0.05; ** p<0.01; *** p<0.001 Adapted from Xin J Nephrol 2012; Stohl ACR 2010; PEARL-SC data
Disease State in Nephritic Patients Elevated BAFF Promotes B Cell and Plasma Cell Proliferation BAFF Receptor Normal IgA Blisibimod BCMA BAFF Immunogenic IgA Anti-dsDNA ab Nephrotic Kidney Bone Marrow CD19/CD20 CD19/CD20 CD19/CD20 Plasma Cell Immature B Cell Mature (naïve) Activated B Cell Memory B Cell + Inflammatory Mediators IL-6, TNF-α, IFN-γ In IgA Nephropathy excessive BAFF leads to proliferation of B cells and plasma cells, increased immunogenic IgA, and kidney injury 8
Treatment of IgA Nephropathy with BAFF Receptor BCMA BAFF Normal IgA Immunogenic IgA Anti-dsDNA ab Blisibimod Bone Marrow CD19/CD20 CD19/CD20 CD19/CD20 Plasma Cell Immature B Cell Mature (naïve) Activated B Cell Memory B Cell rapidly reduces plasma cells, gradually reduces B cells, and decreases immunogenic IgA and dsdna antibodies 9
Clinical Evidence From BLISS and PEARL-SC Studies Plasma cells express immunogenic IgA leading to nephropathy ** *** ** *** Plasma cells are affected rapidly and dose-proportionally by BAFF inhibition 1.2 CD19+CD20+ B cells Blisibimod decreases total B cells (CD19+CD20+) Elevated CD19+CD20+ B cells amplify systemic inflammation Fraction of Baseline 1 0.8 0.6 0.4 0.2 0 *** *** *** *** *** *** *** *** *** Placebo Pooled Pooled blisibimod 0 4 8 12 16 20 24 28 36 44 52 Study Week 10 * p<0.05; ** p<0.01; *** p<0.001 Stohl American College of Rheumatology 2010, PEARL-SC Study in SLE
Improving Renal Function with Blisibimod Proteinuria Patients with baseline 1g-6g/24hr (PEARL-SC, n=49) Mean Percent Change (%) 20 0-20 0 4 8 12 16 20 24 * * * a reduction in proteinuria after 6 months, and no increase in proteinuria were independent predictors of a beneficial outcome. 1-40 Study Week ** 0.06 * ** Complement 3 mitt with baseline C3 (PEARL-SC, n=543) Mean Change (g/l) 0.04 0.02 0 0 4 8 12 16 20 24 decreased circulating C3 levels and mesangial C3 deposition were independently associated with poor renal outcome in patients with IgA Nephropathy. 2-0.02 Study Week 11 * p<0.05; ** p<0.01; *** p<0.001 1 Pozzi et al. 2004; 2 Kim et al., 2012
IgA Nephropathy Outcomes Evidence 1.0 0.9 Effect of magnitude of proteinuria on renal survival in IgA Nephropathy <0.3 g/day Renal Survival 0.8 0.7 0.6 0.5 0.4 Mean Proteinuria Baseline= 2.4g/24hr 0.3-1g/day 1-2 g/day 2-3 g/day 0.3 0.2 N=542 >3 g/day 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Years Reich J Am Soc Nephrol 2007 These results underscore the relationship between proteinuria and prognosis in IgA nephropathy and establish the importance of remission. 12
Phase 2 IgA Nephropathy Disease Improvement Study Unlocking the Potential for Blisibimod in Patients with Renal Disease 13
IgA Nephropathy Study Design: Phase 2 IgA Nephropathy 28-days 8-Week Induction 24-Week Maintenance N=24 Blisibimod 100mg TW Blisibimod 200mg QW N=24 Placebo TW Placebo QW Biopsy Proven 18 65 years Proteinuria > 1g/24hr egfr > 30 Induction Biomarker Endpoint Reduction in proteinuria Renal function: egfr Change in serum creatinine Primary Endpoint Reduction in proteinuria Secondary Endpoints Renal function: egfr Reduction in plasma B Cells Change in disease relevant biomarkers (IgA) Urinary sediment Orphan Disease with Unmet Medical Need Induction Interim Analysis Power: ~86% Alpha: 0.05 Positive Interim Triggers Phase 3 Upsize Final Data Provides Insight to Phase 3 14
IgA Nephropathy Study Design: Phase 3 IgA Nephropathy 28-days N=120 8-Week Induction Blisibimod 100mg TW 96-Week Maintenance Blisibimod 200mg QW Biopsy Proven 18 65 years Proteinuria > 1g/24hr egfr > 30 N=120 Placebo TW Placebo QW Proposed Primary Endpoint Renal Response (any of) <50% increase in serum creatinine <25% decrease in egfr >50% decrease in proteinuria Secondary Endpoint Need for escape steroid therapy Proteinuria Renal function: egfr Urinary sediment Orphan Disease with Unmet Medical Need Interim Analysis on Proteinuria Guides Expansion Upsize or Stand Alone Phase 3 Design Option Reduce Progression to ESRD 15
Clinical Data from PEARL-SC Provides Valid Approach Compelling Efficacy Data from PEARL-SC Provides Clear Path in Lupus IgA Nephropathy Lupus Nephritis Partner/Option Systemic Lupus Erythematosus 16
Addressing the Dilemma for New Products in Lupus Blisibimod Fast-follower Advantage Compelling and Large Clinical Effects Demonstrate Early Benefit Subcutaneous Launch Clear Trigger for Patient Identification (steroid failures) SRI-8 Unclear Patient Identification (all comers) Modest and Questionable Clinical Benefit Slow Onset IV Infusion Launch 17 Challenges
Ideal Product for Patients with Severe Active Disease Baseline SELENA-SLEDAI 10 AND Non Responsive to Steroids 60 SRI-8 Earlier Onset Responders (%) 50 40 30 20 10 0 Steroid Modulation n=48 *** * ** * n=47 0 4 8 12 16 20 24 Study Week +31.1% Independent of Steroid Tapering Greater Treatment Effect in More Severe Patients 2X the Clinical Improvement of SRI-4 18 QW = Once weekly; * p<0.05; ** p<0.01; *** p<0.001 * P-value versus same dosage placebo cohort.
Further Validation of Clinical Benefit of Blisibimod Responders (%) 45 40 35 30 25 20 15 10 5 0 * * ** *** ** ** 0 4 8 12 16 20 24 Study Week 1.00 85% of SRI-8 Benefit Due to Clinical Improvement^ (versus serology) Increased Time to First Severe Flare Cumulative Probability 0.75 p=0.22 0 60 120 180 240 300 360 Time (days) Average Duration of Therapy 19 * p<0.05; ** p<0.01; *** p<0.001;qw = Once weekly ^Without low complement, increased DNA binding, thrombocytopenia and leukopenia
The Program: Targeting Patients in Need 52 Weeks Treatment Open Label Extension Seropositive SLE Patients (Randomization 28Days) N 400 Blisibimod 200mg Weekly SC Weekly Placebo Blisibimod 200mg Weekly SC FAILING ON STEROIDS AND SELENA-SLEDAI 10 AND ANA+ or ds-dna+ N 400 Blisibimod 200mg Weekly SC Weekly Placebo Option Pending Lupus Nephritis Discussion with FDA Long-Term Safety 92% Power p<0.05 Placebo Response: 26% Treatment Benefit: 16% End of Phase 2 and European Advice Process Complete Primary SRI-8* Endpoint Differentiated Product Profile for Unmet Need Systemic Lupus Responder Index (SRI) is a composite endpoint comprised of a >8 point improvement in the SELENA-SLEDAI clinical assessment instrument AND no new BILAG 1A or 2B organ domain flares AND no worsening in Physician s Global Assessment (PGA) (< 0.3 increase) 20 Study will use imbalanced randomization (approximately 5:4 Active:Placebo) to maximize collection of safety data.
Investment Highlights PEARL-SC Results Provide Clear Path Forward Results support use in auto-immune diseases Blisibimod treatment offers renal benefit Safe and well-tolerated at all dose levels IgA Nephropathy Unmet Medical Need Orphan Indication Renal disease with involvement of BAFF Proteinuria correlated with disease progression Clear patient identification (proteinuria, history) Provides Phase 3 Path In Renal Disease Phase 2 disease improvement study Biomarker endpoints similar to PEARL-SC Differentiated dosing to maximize early effect Pipeline Multiple Market Opportunities $500-750M IgA Nephropathy market data provides renal development path Option on $1+ billion SLE US market 21