Investor Presentation
January 2012 www.myrexis.com
Forward Looking Statements This presentation contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to statements relating to Myrexis’ corporate strategy and the attributes, expected development, and potential efficacy of our product candidates. These "forwardlooking statements" are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by these forward-looking statements. These risks and uncertainties include, but are not limited to those factors discussed under the heading "Risk Factors" contained in Myrexis’ Form 10-K, for the year ended June 30, 2011, which was filed with the Securities and Exchange Commission on September 13, 2011, as well as any updates to those risk factors filed from time to time in its Quarterly Reports on Form 10-Q or Current Reports on Form 8-K. All information in this presentation is as of the date of the presentation, and Myrexis undertakes no duty to update this information unless required by law.
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Investment Highlights Robust development pipeline • Discovered and developed internally • Unmet medical needs and large market opportunities
Three programs in development • Novel structures, distinct mechanisms of action • Potential first-in-class/best-in-class
Active partnering strategy to maximize value Extensive intellectual property portfolio Strong cash position • $109.1 M at September 30, 2011 3
Development Pipeline Drug Development Candidate
Hsp90 Inhibitors
Oncology Cancer Metabolism Inhibitor
Anticipated Next Steps
MPC-3100
Completed Phase 1
Initiate Phase 2a study 1H12
MPC-0767 (Prodrug)
IND-Enabling Studies
File IND 1Q12 Conduct Phase 1 relative bioavailability study
MPC-8640
Late Preclinical
Complete IND-enabling studies Prepare IND Filing
Autoimmune Oral AntiLead MPI-0485520 Interferon Optimization Diseases
Complete lead optimization Initiate IND-enabling studies
All drug candidates discovered internally and covered by issued composition of matter patents or patent applications 4
Hsp90 Inhibitor Program Lead Candidate:
MPC-0767, novel prodrug of MPC-31001
Potential for best-in-class Issued composition of matter patent Program attributes: Structurally distinct, fully synthetic Orally bio-available, ~12h half-life Generally safe and well-tolerated Opportunity:
Multiple solid and hematological cancers
Preclinical data:
Active in all cancer models2 Wide therapeutic index
Status:
Completed Phase 1 study (MPC-3100) 3
Next steps:
Initiate Phase 2a, open MPC-0767 IND
1
5
Papac et al., AACR poster presentation 2011
2 Baichwal
et al., AACR poster presentation 2011
3
Samlowski et al., EORTC/NCI/AACR poster 2011
MPC-3100
Superior Hsp90 Inhibitor Her2+ gastric tumor xenograft 500
Tumor Volume (%)
0
44% tumor regression with MPC-3100
400
300
200
1
Vehicle 2
BIIB-021 (125 mg/kg PO)
100
5FU (100 mg/kg IP)
0
n = 10 mice/group 0
MPC-3100 (200 mg/kg PO) 0
5
10
15
20
Days
25 0 No deaths 1 One death 2 Two deaths
6
Wettstein et al., EORTC-NCI-AACR, poster presentation (2008)
MPC-3100 Phase 1 First-in-Human Study Dose-escalation, safety and tolerability study Inclusion criteria • Enrolled 26 patients with cancers refractory to available systemic therapies
Primary objectives • Characterize safety and tolerability (max. tolerated dose) • Determine appropriate dose for Phase 2
Secondary objectives • Define pharmacokinetics and pharmacodynamics • Assess antitumor activity
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Phase 1 Study Meets Key Objectives Primary Well-tolerated, most common AEs observed • Grade 1 & 2 diarrhea, nausea, vomiting, fatigue
Dose for Phase 2 established • AUC and Cmax similar to efficacious doses in mice
Secondary Confirmed oral bioavailability in humans Confirmed on-target activity; inhibits Hsp90 in humans Dose proportional PK; mean ½-life 11.2 hours Best clinical response was stable disease 8
Samlowski et al., EORTC/NCI/AACR poster presentation 2011
MPC-3100 Inhibits Hsp90 in Humans
400
Increasing Hsp70 induction with increasing dose and duration of MPC-3100 treatment
300 200
Cohorts 1-5
50 mg/m2
100
100 mg/m2 165 mg/m2
0
21 D ay
8 ay D
ho ur s 24
8
Pr eD 9
ho ur s
245 mg/m2
os e
Amount of Hsp70 Induced (ng/mg total protein)
Activity Biomarker: Hsp70 induction in patient PBMCs
Data from Samlowski et al., EORTC/NCI/AACR poster presentation 2011
340 mg/m2
Hsp90 Inhibitor Program: Next Steps Initiate MPC-3100 efficacy study in 1H12 • Phase 2a in oncogene-addicted tumor population Open IND for MPC-0767 in 1Q12 • Prodrug of MPC-3100 • Significantly improved aqueous solubility
• Eliminates need for solubilizing agent Reduced cost Reduced risk of side effects Reduced tablet burden
• Anticipate streamlined Phase 1 program Only the active drug (MPC-3100) detected in plasma Relative Bioavailability Study to precede Phase 2a 10
Cancer Metabolism Inhibitor (CMI) Program Lead Candidate:
MPC-8640
Unique attributes:
Potent, selective Nampt inhibitor Orally bio-available, flexible dosing schedule1 Niacin enhances therapeutic index2
Opportunity:
Cancers targeted by companion diagnostics
Preclinical Data:
Tumor regression in mice Synergy with variety of chemotherapies3 (e.g. 5-FU, temozolomide, PARP inhibitors)
Status:
Preclinical IND-enabling studies ongoing
Next steps:
IND filing
1
11
Carlson et al., EORTC poster presentation 2011
2 Fleischer
et al., AACR poster presentation 2011
3
Terry-Lorenzo et al., AACR poster presentation 2011
MPC-8640: Cancer Metabolism Inhibitor Cancer cells have very high energy needs • Survival • Growth • DNA repair
NMN
NAD
Nampt1
primary energy source
Nam
MPC--8640 MPC Inhibits NAD production
Cancer cells are more susceptible to NAD depletion 1
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Nicotinamide phosphoribosyltransferase (Nampt)
Striking Anti-tumor Activity Tumor Regression in HT1080 Xenograft Model MPC-8640 once daily dosing for one week 700 median tumor volume (mm3)
vehicle 600
MPC-8640 (36 mg/kg PO)
MPC-8640 causes dramatic tumor regression and durable responses following short treatment period
500 400 300 200 100 0 0
5
10
Treatment period
13
15
20
25
30
time (days)
Carlson et al., AACR-NCI-EORTC poster presentation 2011
MPC-8640: Objective Response and Cure Rates Responses Rates in HT1080 Xenograft Model
Objective Response Cure
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Carlson et al., AACR-NCI-EORTC poster presentation 2011
..................................
MTD
Treatment with MPC-8640 results in high cure rate at well tolerated doses
Potential Biomarkers for Tumor Sensitivity LOW
HIGH
NA = Nicotinic acid, Niacin, Vitamin B3
LOW 15
Development of Companion Diagnostic Niacin (Vitamin B3) Provides Alternative Pathway for NAD Synthesis Naprt1
Niacin
NaMN
NAD
Naprt1 enzyme required to produce NAD from niacin ~40% of all tumors are naturally Naprt1-deficient1 Simple companion diagnostic selects patients for treatment • Detects Naprt1 expression in tumors
Niacin can selectively protect normal cells from damage • Enhances therapeutic index of Nampt inhibitors 1
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Fleischer et al., AACR poster presentation 2011
MPC-8640: Novel Cancer Metabolism Inhibitor MPC-8640 induces tumor regressions and cures in xenograft models at well-tolerated doses Potent, selective, orally administered small molecule inhibitor of Nampt Reduces tumor cell NAD levels and induces cell death Demonstrated preclinical efficacy as monotherapy or in combination with antimetabolites and alkylating agents1 Biomarkers may identify sensitive tumors
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1Terry-Lorenzo
et al., AACR poster presentation 2011
Small Molecule Oral Anti-interferon (OAI) Program Lead Candidate:
MPI-0485520 First-in-class Oral Anti-interferon
Unique attributes:
Picomolar inhibitor of novel kinases, IKKε and TBK1 Highly selective (relative to > 120 protein kinases) Orally bio-available small molecule
Opportunities:
Autoimmune diseases (RA, Lupus, Psoriasis)
Preclinical data1:
In vivo inhibition of interferon (IFN) response1 Active in rheumatoid arthritis (RA) model2
Status:
Lead optimization ongoing
Next steps:
IND-enabling studies with lead compound
1
Richards et al., ACR poster presentation 2010
2
Richards et al., EULAR poster presentation 2011
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First Small Molecule, Anti-interferon IFN-α α and -β β • Regulators of chronic inflammation and autoimmunity
IKKεε and TBK1 • Novel targets for inhibition of IFN-α and -β expression
OAI
IFN-a mAbs • In development targeting pathway (psoriasis and lupus)
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X
MPI-0485520 Selectively Inhibits IFN Response IFN Pathway: IKKεε
NFκ κB Pathway: IKKα α 1000
100
10
100% Inhibition p=0.007
1
*
0.1
0.01
TNF-α α mRNA (% of Poly I:C median)
100
10
1
0.1
)
)
ly (I: C
C
Po
ly (I:
20
* interferon response gene
m g/ kg 10 0
10 0
m
g/ kg
+
+
Po
) Po ly (I : C
C ) Po ly (I:
ve hi c
le
0.01
Ve hi cl e
ISG56 mRNA (% of Poly I:C median)
1000
MPI-0485520 Efficacious in RA model Collagen-induced Arthritis Model
Disease Severity Score
20
Vehicle 100 mg/kg QD 150 mg/kg QD
15
p