A Broad Clinical Pipeline of Innovative Diabetes / Renal & Oncology Programs. European Business Development Conference Düsseldorf 24 Sept 2013

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1 A Broad Clinical Pipeline of Innovative Diabetes / Renal & Oncology Programs European Business Development Conference Düsseldorf 24 Sept 2013

2 Key facts about NOXXON Developing a new class of proprietary therapeutics called Spiegelmers - L-stereoisomer RNA aptamers Chemically synthesized Resistant to nuclease degradation Non-immunostimulatory, non-immunogenic Large Pipeline with - 3 clinical candidates in 4 Phase IIa trials all with promising interim efficacy - NOX-E36 for Diabetic Nephropathy - NOX-A12 for Chronic Lymphocytic Leukemia and for Multiple Myeloma - NOX-H94 for Anemia of Chronic Disease in Dialysis and Oncology Patients - 4 preclinical candidates for various indications with high unmet need: Inflammation, Diabetes, Metastasis and Pain Comprehensive IP coverage with over 110 granted patents Strong syndicate of international investors Approx. 60 employees, located in Berlin, Germany 2

3 Diabetes & Renal Diseases Diabetic nephropathy (DN) occurs in ~1/3 rd of diabetics, with 18m DN patients and 1.5m end stage renal disease (ESRD) patients in the 7MM In the US, Medicare costs of for 594,400 ESRD patients reached $33 billion in 2010 (approx. $55,600 per patient), representing more than 6% of its total spending Agents to stop or reverse progression of diabetic nephropathy needed 75% of ESRD patients are anemic (of which 50% present functional iron deficiency) and 10% of ESRD patients are Erythropoietin stimulating agent (ESA) hypo-responders ESA treatment costs for ESRD hypo-responders are an important part of the cost for ESRD patients, totaling $22,500 - $50,000 per patient per year ($880m-$2.2b in 2012) New mechanisms of action needed in ESA hypo-responders e.g. anti- Hepcidin agents Sources: Diabetes Care, Volume 36, Supplement 1, January 2013; Keane WF, et al. Kidney Int. 2003; 63: Global data, Kidney.org, USRDS annual data report & Fresenius medical care report Noxxon analysis 3

4 NOX-E36: Diabetic Nephropathy Program Status: Phase IIa Drug Product Properties 40 nucleotide L-RNA oligo + 40 kda PEG Route of administration: s.c. or i.v. Phase Ib MAD Pharmacodynamics Mechanism of Action Binds and neutralizes MCP-1 / CCL2 Anti-inflammatory action that reduces: pro-inflammatory cells in kidney kidney scarring negative effects on podocytes Dosing Standard of Care Blood pressure control Control of blood sugar and lipids No therapy to stop or reverse progression of CKD Reduction in monocyte (CD14+CCR2+ cell) number is maintained throughout the dosing period demonstrating sustained activity 4

5 NOX-E36: Clinical Program Program Status: Phase IIa 75 patient Phase IIa DN study recruitment completed June 2013 Majority of study patients are high risk patients based on their ACR (Albumin/Creatinine Ratio) and egfr (estimated Glomerular Filtration Rate) Interim Data Analysis 6 parameters in first 51 Patients shows: - Improvement of ACR - Improvement of HbA1c (glycosylated hemoglobin) To be confirmed in subsequent interim analyses and final analysis First Phase II evidence for beneficial effects on proteinuria and glycemic control, to date safe and well tolerated 75 patient top-line efficacy available in October-2013, full un-blinding March

6 NOX-H94 Anemia of Chronic Disease Program Status: Phase IIa Drug Product Properties 44 nucleotide L-RNA oligo + 40 kda PEG Route of administration: i.v. Mechanism of Action NOX-H94 Binds and neutralizes Hepcidin, a peptide hormone that regulates iron release from storage cells High hepcidin levels lead to in hypoferremia and anemia. Key Competitor Molecules EPO pathway: HIF prolyl hydroxylase inhibitors o FG4592 in Phase III by Astellas / Astra- Zeneca / Fibrogen o AKB-6548 in Phase II by Akebia o GSK128863A in phase II by GSK Others mechanisms o ACE-011/Sotatercept, Growth differentiation factor (GDP) trap, in Phase II by Acceleron/Celgene o Anti-Hepcidin and Anti-Ferroportin mabs by Lilly in Phase I Standard of Care Erythropoietin pathway with Erythropoiesis Stimulating Agents (ESAs) like EPO i.v. iron Blood transfusion Differentiation NOX-H94 MoA does not increase risk to patient via excessive EPO exposure No risk of iron overload 6

7 NOX-H94: Clinical Program Pilot group of 12 anemic cancer patients enrollment complete (Sept 2013) Interim results from 8 patients show a clear response to NOX-H94 treatment in a subset of patients including Reductions in serum ferritin (reflecting mobilization of stored iron) Hemoglobin increase 1g/dL To date safe and well tolerated Program Status: Phase IIa Data from single clinical responder Next steps: Expansion of development to dialysis patients Phase II in EPO-Resistant Dialysis Patients in preparation 7

8 Oncology Market Hematological malignancies: >$8 billion in 2013 projected >$14 billion by 2018 Glioblastoma: >$1b Chronic Lymphocytic Leukemia Multiple Myeloma World 7 MM World 7 MM Prevalence 0,52 0,14 1,61 0,41 Incidence 0,12 0,03 0,18 0,04 Prevalence 0,22 0,11 0,28 0,12 Incidence 0,12 0,05 0,19 0,07 Glioblastoma Incidence 0,26 0,05 0,36 0,07 Recurrence and resistance to chemotherapy is linked in part to residual cancer cells in bone marrow and lymph node niches Tumor microenvironment protects cancer cells from chemotherapy NOX-A12 targets resistance and trafficking mechanisms of cancer cells to increase patient response to chemotherapy or radiation treatment Addition to standard of care Source: Datamonitor, GlobalData 8

9 NOX-A12: CLL and MM Drug Product Properties 45 nucleotide L-RNA oligo + 40 kda PEG Route of administration: i.v. Program Status: Phase IIa Mobilization kinetics of CLL cells Mechanism of Action NOX-A12 binds and neutralizes the chemokine SDF-1/CXCL12 preventing interaction with its receptors CXCR4 & CXCR7 This results in: De-adhesion and decreased homing to the protective BM/LN niches Reduced survival Chemosensitization Standard of Care Multiple SoC algorithms for CLL & MM, many patients on experimental therapies Mobilization of CLL cells after a single dose of NOX-A12 alone (n = 10 patients) PoP achieved with an effective and prolonged mobilization of CLL cells into the peripheral blood. CXCL12 (SDF-1): C-X-C motif chemokine 12 (Stromal Cell-Derived Factor-1); CXCR4-7: C-X-C motif chemokine receptor 4-7 BTK: Bruton's tyrosine kinase; SoC: standard of care Source: NOXXON analysis 9

10 NOX-A12: Clinical Program in CLL Program Status: Phase IIa PoC study in 33 relapsed CLL patients Interim Data Analysis of first 9 CLL patients upon completion of 6 months treatment 9/9 patients responded to NOX-A12 + Bendamustine+Rituximab Lymphocyte count NOX-A12 as single agent and in combination with BR was safe and well tolerated also in comparison to historical controls and benchmarks Final results expected in Q Provided that this promising clinical picture will be maintained in the total sample of 33 patients, further development of this novel anti-cxcl12/sdf-1 Spiegelmer NOX-A12 is warranted 10

11 NOXXON's Development Pipeline Pathology Indication Target Program Discovery Preclinical Phase I Phase II Phase III Market Diabetic Nephropathy MCP-1 / CCL2 NOX-E36 Diabetes & Renal Diseases Anemia of Chronic Disease Hepcidin NOX-H94 Diabetes (Type I & II) Glucagon NOX-G15/16 Chronic Lymphocytic Leukemia SDF-1 / CXCL12 NOX-A12 Multiple Myeloma SDF-1 / CXCL12 NOX-A12 Oncology Anemia of Chronic Disease Hepcidin NOX-H94 Glioblastoma SDF-1 / CXCL12 NOX-A12 Metastasis S1P NOX-S93 Inflammtion SIRS, Sepsis C5a NOX-D20/21 Pain Migraine CGRP NOX-L41 *SIRS: Systemic Inflammatory Response Syndrome 11

12 Summary 3 Spiegelmer drugs in 4 Phase IIa studies Excellent safety & tolerability First efficacy data promising for all studies Strong clinical data-flow in Spiegelmer-based drugs have been administered to over 300 subjects, de-risking the NOXXON platform Objectives Pursue development of the 3 main assets Expand NOX-A12 into solid tumors with Phase I/II in Glioblastoma & NOX-H94 into anemic dialysis population Establish partnerships based on promising Phase IIa interim data 12

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