Nasdaq: MAXY UBS Global Life Sciences Conference Dr. Russell Howard, CEO

Transcription

1 Nasdaq: MAXY 2007 UBS Global Life Sciences Conference Dr. Russell Howard, CEO September 25, 2007

2 Safe Harbor Statement Information in this presentation includes forward-looking statements that involve risks and uncertainties. Actual results could differ materially from the results discussed here. Factors that could cause or contribute to such differences include those discussed in Maxygen s Annual Report on Form 10-K for the year ended December 31, 2006 available from from the SEC at This presentation will also include disclosure of non-gaap financial measures. Reconciliation of such measures to the nearest GAAP financial measure can be found on our website at under the News tab. 1

3 Maxygen Makes Biosuperiors: Superior Protein Drugs 2006 Revenues from Biosuperior Blockbusters $4.5B $2.0B $2.2B $39M 1 $1.2B $2.7B 1 Launched Sep $837M $4.1B 2

4 The Maxygen Approach Minimizes Risk and Maximizes Reward Large validated markets + Unmet clinical need Target Product Profile Identify Proof-of-Concept Assay Expert IP Review/Design Create Protein Variants w/technology Toolbox Rigorous Screen Against Proof-of-Concept Assay Maxygen Toolbox DNA Shuffling Rational Design Mutagenesis PEGylation Glycosylation Novel Product Concept 3

5 Maxygen Product Portfolio Product Indication Discovery Preclinical MAXY-G34 MAXY-alpha MAXY- VII Neutropenia Hepatitis C Hemophilia Trauma Other Acute Research Programs Autoimmunity Autoimmunity Thrombosis Hematology Avimers Ph I NovoSeven $1B Ph II Pegasys / Peg-Intron $2.0B Neulasta $2.7B 4

6 MAXY-G34: A Superior PEGylated G-CSF Clinical Program 5

7 MAXY-G34: an Improved G-CSF for Chemotherapy-Induced Neutropenia Many chemotherapy patients still experience some degree of neutropenia Neutrogin $306M GRAN $131M Current drug choices limited Neulasta and Neupogen have 90% market share MAXY-G34 Target: Novel G-CSF with Improved Efficacy Neupogen $1.2B Neulasta $2.7B Technical Approach: Use mutagenesis and directed pegylation to create a more efficacious G-CSF $4.4 Billion G-CSF Market in 2006; 11% growth 1 1 Top 20 Biologics, LaMerie Business Intelligence, February

8 Proof-of-Concept: MAXY-G34 More Efficiacious than Neulasta in Multiple Pre-clinical Models Rat study White Cell Count (10 9 /L) Cyclophosphamide G-CSF MAXY-G34 Neulasta Control (no GCSF) Time (hr) Single shot administration (100 ug/kg) Superior to Neulasta in multiple models of chemotherapy and radiation-induced leucopenia in mouse, rat & non-human primates 7

9 Summary of Phase I Results: MAXY-G34 is a Safe, Potent, Long-acting Drug MAXY-G34 was shown to be safe in Phase I study No serious adverse events reported (5-150 µg/kg) Adverse events all consistent with other approved G-CSFs Most common AE was bone pain Did not reach dose-limiting toxicities at highest dose (150 µg/kg) No binding or neutralizing Ab detected at any dose level MAXY-G34 is a potent stimulator of ANCs and peripheral mobilization of CD34+ cells Comparison of MAXY-G34 and Neulasta in healthy volunteers (6 individuals per group) Confirmed tolerability and potency of MAXY-G34 MAXY-G34 has a longer T 1/2 and longer duration of neutrophil enhancement (Higher AUC with MAXY-G34) 8

10 Phase I Trial in Healthy Volunteers MAXY-G34 is a Potent, Durable Stimulator of Neutrophil Generation ANC ug/kg 100 ug/kg 60 ug/kg 30 ug/kg 10 ug/kg 5 ug/kg Placebo Days 9

11 Phase I Trial in Healthy Volunteers MAXY-G34 Pharmacodynamics Differentiated from Neulasta Mean ANC Maxy-G34 Neulasta Time (days) Normal Range 10

12 Phase IIa Initiated June 2007 Goal: Identify Safe, Tolerated Doses for Phase IIb Multicenter, open label study in breast cancer patients (Stage I IIIa) TAC: docetaxel, adriamycin and cyclophosphamide common protocol, elicits severe neutropenia 6 cycles of TAC, 21-day intervals, 1 dose MAXY-G34 per cycle, fixed dose for all cycles Treatment arms MAXY-G34 - escalating doses of 10, 30, 60 and 100 µg/kg (6 patients per dose) Neulasta - 6 mg fixed dose (6 patients) Next-day administration of MAXY-G34 and Neulasta Dose escalation after Safety Monitoring Board assessment of 2 cycles of data Clinical endpoints Safety, tolerability and immunogenicity Efficacy - duration of severe neutropenia (ANC<500/mm 3 ) Study target: completion in

13 MAXY-G34 is a Proprietary, Patent-Protected Molecule Neupogen Neulasta MAXY-G34 Wild Type Human G-CSF Variant Human G-CSF Five amino acid changes in G-CSF sequence provide novel PEGylation pattern Three 5 kda PEGs attached vs. mono-pegylated at N-terminus 12

14 MAXY-G34 Program Summary Superior to Neulasta in preclinical models Development Status Successful Phase I trial Phase IIa completion expected 2008 BLA projected 2012 MAXY-G34 Next-generation G-CSF with solid IP position Proprietary, patent-protected product Unique G-CSF sequence Multiple attached PEG groups increase half-life 13

15 14 MAXY-alpha (R7025) Clinical Program on Hold

16 MAXY-alpha (Roche R7025) Program Status MAXY-alpha, partnered with Roche, is a next-generation interferon alpha for treatment of HCV Roche put program on hold (21 st Sept) due to preliminary results from a repeat dosing Phase Ia study Loss of pharmacokinetic and pharmacodynamic effects in majority of subjects who received two doses Antibodies identified in some subjects (competition binding assay) Results of Phase Ia SAD study showed potential to separate efficacy and side effects Terms of Partnership No cost to Maxygen; double-digit royalty and milestones All on-going development fully funded by Roche 15

17 MAXY-alpha Target: Next-generation Alpha-interferon with Improved Efficacy Technical Approach Exploit natural diversity of human alpha-interferons by DNA shuffling Remove known epitopes, optimize PEGylation, and retain the novel ratio of biological activities Selected Property Not Selected MAXY-alpha Activity vs. PEGASYS Antiviral activity T-helper cell activation Antiproliferative activity ~50X ~6X Dendritic cell maturation 10 50X 2 9X 16

18 MAXY-alpha (Roche R7025) Next Steps Resolve hold on clinical program Determine meaning and significance of unanticipated loss of drug pharmacokinetics and pharmacodynamics from repeat dosing in extension of Phase Ia SAD study We believe these results to be specific to MAXY-alpha, related to either its novel biological properties or a new epitope Roche and Maxygen reviewing schedule for reporting results Roche/Maxygen to present Phase Ia SAD results at AASLD 17

19 MAXY-alpha is Similar to Natural Interferons Explanation for observed results under investigation Trivial cause not yet excluded; work ongoing to explore the data The number of amino acid changes alone is uninformative Pair-wise, individual natural human IFN-alphas are 85-93% homologous MAXY-alpha (166 amino acids) has 85-89% sequence homology with individual natural human IFN-alphas, as does consensus IFN-alpha (Infergen) Clinical development of Infergen did not reveal this problem amino acids are different in pair-wise comparisons Altered biological activity of MAXY-alpha (eg. dendritic cell activation) may account mechanistically for antibody induction Alternatively, an epitope we did not predict may be responsible 18

20 Immunogenicity of Protein Drugs Protein immunogenicity is idiosyncratic, a case-by-case issue dependent on protein structure and clinical context Protein manufacturing specifications are paramount low denaturation and low aggregation are critical Minimizing the number and novelty of amino acid changes is obvious, but not alone a strong correlate with immunogenicity Likely all protein drugs elicit binding antibodies, with no obvious clinical effect. Binding antibodies are not necessarily neutralizing 19

21 MAXY-VII: A Superior Factor VIIa Preclinical Program 20

22 About Hemophilia ~400,000 hemophiliacs WW, ~1 in 10,000 births % of Hemophilia A and 1 3% of Hemophilia B patients generate antibodies to FVIII and FIX replacement therapies, respectively 1 FVIIa provided to such inhibitor patients can provide effective hemostasis. Essential and lifelong therapy Currently One Factor VIIa on the Market: NovoSeven from NovoNordisk $1B Sales in 2006; 11% growth Approved for treatment of hemophilia inhibitor patients On-going clinical trials by NovoNordisk explore NovoSeven use in acute bleeding 1 World Federation of Hemophilia Guidelines; 2 Parmeswaran et al 2005; 3 Santagostino et al

23 Hemophilia: The Unmet Need NovoSeven has sub-optimal dosing and is very expensive Injections of NovoSeven every 2-3 hrs 4-5 doses per bleeding episode typical Average cost per injection ~$10,000 1 MAXY-VII Target: Next-generation Factor VIIa with less frequent dosing (1-2 doses of MAXY-VII per bleeding episode) Technical Approach: Independently optimize potency and PK, combine improved Factor VII variants into one protein with BOTH properties 1 Magnetti et al., An Evaluation of Off-Label Use of Recombinant Activated Human Factor VII, Pharmacy & Therapeutics, 2007, 32,

24 MAXY-VII: Optimization of Efficacy Factor VII binding to activated platelets is critical for clotting Protease The Gla domain of Factor VII is responsible for binding to activated platelets Concept: Increase binding of Gla domain to activated platelets Screen for increased Tissue Factorindependent Factor X activation and increased thrombin burst Technology Used: DNA Shuffling of natural human Gla domain diversity Gla EGF Activated Platelet 23

25 Improved Factor X-Activation vs. NovoSeven after Shuffling Gla Domain Coupled Amidolytic Activity Assay PL-Thrombin Generation Assay FXa activity (OD 405 /time) [FVIIa] Log[ng/ml] NovoSeven MAXY-VII ΔFU/s nM MAXY-VII 11nM MAXY-VII 3.7nM MAXY-VII 33nM NovoSeven 11nM NovoSeven Background Time (seconds) 24

26 MAXY-VII: Optimization of Drug Half-life Protein drug half-life can be increased by hyperglycosylation (e.g. Aranesp vs. EPO) Concept: Increase number and optimize positioning of additional N-glycan groups Screen in animals for increased half-life Technology Used: Directed glycosylation Additional N-glycans Natural N-glycans 25

27 Improved Half-Life of MAXY-VII vs. NovoSeven after Directed Glycosylation Exposure of MAXY-VII increased vs NovoSeven Half-life and Area Under Curve increased Similar half-life prolongation in rats Ln [FVII] (ng/ml) [FVIIa] (ng/ml) mg/kg MAXY-VII 1.0 mg/kg NovoSeven Time after administration (min) Time after administration (min) To optimize differential dosing vs. NovoSeven, MAXY-VII combines increased potency and half-life in the same molecule 26

28 Proof-of-Concept: MAXY-VII Improves Survival Rates in Murine FVIII-Knockout Hemophilia Model Survival of animals (%) Survival of animals Minutes after IV dosing Vehicle (n=8) 27

29 Proof-of-Concept: MAXY-VII Improves Survival Rates in Murine FVIII-Knockout Hemophilia Model Survival of animals (%) Survival of animals Minutes after IV dosing Vehicle (n=8) NovoSeven (1.0 mg/kg) (n=7) 28

30 Proof-of-Concept: MAXY-VII Improves Survival Rates in Murine FVIII-Knockout Hemophilia Model Survival of animals (%) Survival of animals Minutes after IV dosing Vehicle (n=8) NovoSeven (1.0 mg/kg) (n=7) NovoSeven (2.0 mg/kg) (n=8) 29

31 Proof-of-Concept: MAXY-VII Improves Survival Rates in Murine FVIII-Knockout Hemophilia Model Survival of animals (%) Survival of animals Minutes after IV dosing Vehicle (n=8) NovoSeven (1.0 mg/kg) (n=7) NovoSeven (2.0 mg/kg) (n=8) MAXY-VII (1.0 mg/kg) (n=8) 30

32 Proof-of-Concept: MAXY-VII Improves Survival Rates in Murine FVIII-Knockout Hemophilia Model Survival of animals (%) Survival of animals Minutes after IV dosing Vehicle (n=8) NovoSeven (1.0 mg/kg) (n=7) NovoSeven (2.0 mg/kg) (n=8) MAXY-VII (1.0 mg/kg) (n=8) MAXY-VII (0.5 mg/kg) (n=8) All Mice treated with MAXY-G34 survived <50% of mice treated with NovoSeven survived 0% of untreated mice survived 31

33 MAXY-VII Program Summary To optimize differential dosing vs. NovoSeven, MAXY-VII combines increased potency and half-life in the same molecule Our goal is 1-2 doses of MAXY-VII per bleeding episode Late preclinical stage Superior efficacy in diverse models Murine in vivo, human in vitro & human ex vivo Superior circulating half-life and exposure levels in animals Robust upstream and downstream manufacturing process Initial clinical development goal is hemophilia IND/CTA planned for H1 2008; clinical trial initiation 2008 Future expanded indications: trauma/acute bleeding 32

34 Guidance

35 Financial Overview 2007 Financial Guidance Operating revenues $15M Operating cash burn* <$55M Capital Cash (as of Jun 30 th, 2007) $168M No debt *Net Loss excluding Stock Compensation (FAS 123(R)) and Depreciation less Capital expenditures less decrease in deferred revenue 34

36 Creating Value from Non-Core Assets Verdia spun out in 2002 to focus on agricultural applications of Molecular Breeding directed evolution platform Purchased by DuPont in 2004 $64M to Maxygen Avidia spun out in 2003 to focus on new drug class (avimers) Purchased by Amgen in 2006 $17.8M to Maxygen Codexis formed in Focused on biofuel and other chemical applications of MolecularBreeding directed evolution platform Maxygen retains approx. 32% ownership (as of ) 35

37 Key Events and Goals MAXY-G34 Update on Phase IIa trial progress Q1, 2008 Complete Phase IIa trial for MAXY-G34 in 2008 MAXY-VII File IND/CTA for MAXY-VII for hemophilia in H MAXY-alpha Understand implications of unanticipated issues on repeat dosing New Program Announce 1 new lead moving from Discovery to Preclinical in 2007 Maintain strong financial position 36

38 37 BIOSUPERIORS