A Phase 3 Clinical Trial to Evaluate theSafety and Efficacy of Treatment with

2 mg Intralesional Allovectin-7® Compared toDacarbazine (DTIC) or Temozolomide (TMZ)

in Subjects with Recurrent Metastatic Melanoma

Presented at the 10th International Meeting of the Society for Melanoma Research – November 18, 2013

Robert H.I. Andtbacka,1 Rene Gonzalez,2 Mary K. Wloch,3 Linda Strause,3Kristrun Stardal,3 Alice Chu,3 Alain Rolland,3 and Sanjiv S. Agarwala4

1Huntsman Cancer Institute, University of Utah, Salt Lake City, UT; 2University of Colorado Cancer Center, Aurora, CO; 3Vical Incorporated, San Diego, CA;

4St. Luke’s Hospital & Health Network, Bethlehem, PA

2

Disclosure InformationRelationships Relevant to this SessionDr. Robert Andtbacka has been a consultant to Vical Incorporated and has received research support and/or honoraria from the company, but not within the past 12 months. Dr. Andtbacka does not own stock or patent rights in the company.

Velimogene AliplasmidProposed Mechanisms of Action

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Induction of CTL response against an allogeneic target HLA-B7 MHC class I

Induction of CTL response against tumor antigens following restoration of tumor MHC class I 2-microglobulin

Induction of innate immunity and inflammatory responses pDNA-lipid complexes

Plasmids transfect tumor cells at site of intralesionalinjection, enhanced by lipid formulation

HLA-B7 and β2-microglobulin expression; MHC class I antigen presentation to immune system

Tumor immune destruction;tumor antigen recognition leads to systemic surveillance

LOCAL EFFECT

SYSTEMICEFFECTMoA expected to be complementary to

other therapies (CTLA-4, PD-1, PD-L1)Doukas J, Rolland A. Cancer Gene Ther 2012 Dec;19(12):811-7.

High-dose Phase 2 TrialOverview and Results Open-label, multi-center, single-arm, dose escalation trial

Stage III-IV M1b melanoma with injectable lesion Stage III (52%) or IV (48%)

N=133 [0.5 mg (N=3); 1 mg (N=3); 2 mg (N=127)]

2 mg efficacy stage (N=127) Stage III-IV M1b (no visceral mets exc. lung; no brain mets)

Demonstrated safety and efficacy No withdrawals for toxicity or adverse events No grade 3 or 4 drug-related adverse events 11.8% objective response rate (RECIST) 18.8 months median overall survival

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Phase 3 Trial Design

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Multinational open label trial at 90 clinical sites in 15 countries

Enrolled 390 subjects Jan ’07-Feb ’10Stage III-IV M1b metastatic melanomaNo visceral mets except lung; no brain metsChemo-naïve, normal LDH

2:1 randomized260 velimogene aliplasmid / 130 DTIC/TMZStratified by disease stage (III/IV), ECOG status (0/1), number of injectable lesions (1/>1)

260 subjects dosed with 2 mg velimogene aliplasmid by intralesional injection in the same

lesion repeated once per week for 6 weeks every 8 weeks until CR or PD up to 2 years

130 subjects dosed with 1000 mg/m2 IV DTIC or 150-200 mg/m2 oral TMZ

1x daily for 5 days repeated every 28 days until CR or PD up to 2 years

Follow for safety & disease

progression for 2 years and survival until death or lost

to follow-up

Endpoints:Clinical response

at ≥24 weeks, survival, safety

Enrollment & Randomization

Study Endpoints / Analyses

Endpoints Primary: response rate by RECIST at ≥24 weeks

(based on independent EAAC) Secondary: overall survival and safety

Analyses Efficacy analyses based on intent to treat (ITT)

population Safety analyses based on modified ITT (treated

subjects)*

6*MITT Population: 1 patient randomized to velimogene aliplasmid and 10 patients randomized to DTIC/TMZ did not receive study drug and were excluded from the safety analysis

Statistical Considerations

Primary Endpoint: best overall response (CR + PR by RECIST at ≥24 weeks) as assessed by independent Endpoint Assessment and Adjudication Committee.

Powering: Planned 375 subjects (250 velimogene aliplasmid, 125 DTIC/TMZ) would provide 90% power to detect a response rate difference of 12.5% (treatment arm) vs 2.5% (control arm), at two-sided alpha level of ≤0.05.

Primary Statistical Comparison: “Responders” vs “Non-Responders” in ITT population using the Cochran-Mantel-Haenszel (CMH) test stratified by disease stage (III/IV), ECOG status (0/1), and number of injectable lesions (1/>1).

Overall Survival: defined as days from randomization to death. Subjects alive at last follow-up were censored. Displayed using Kaplan-Meier methodology. Differences in OS by treatment arm using log-rank test.

ITT Population: (all subjects randomized into trial) used for efficacy analyses.

MITT Population: (all subjects receiving treatment on trial) used for safety analyses.

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Velimogene Aliplasmid

(N=260)

DTIC/TMZ(N=130) P-value

Gender (%) Female 47.3% 37.7%0.071

Male 52.7% 62.3%Age (years) Median 64 63

0.531Range 25-90 21-91<65 years 50.8% 52.3%

0.774>65 years 49.2% 47.7%

Clinical Stage (%) III 36.5% 38.5%0.121IV M1a (no lung lesions) 25.4% 33.1%

IV M1b (lung lesions) 38.1% 28.5%

Patient DemographicsITT Population

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Patient DemographicsITT Population

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Velimogene Aliplasmid

(N=260)

DTIC/TMZ(N=130) P-value

# Injectable Lesions (%) 1 45.0% 44.6%0.943

>1 55.0% 55.4%HLA-B7 Negative 73.1% 75.4%

0.570Positive 18.5% 16.2%Unknown 8.5% 8.5%

LDH (%) ≤ ULN 99.2% 96.2%0.031

> ULN 0.8% 3.8%ECOG PS (%) 0 79.2% 82.3%

0.4721 20.8% 17.7%

Primary EndpointResponse Rate at ≥24 Weeks (ITT Population)

EAAC Best ResponseCR + PR at ≥ 24 Weeks

VelimogeneAliplasmid

N=260n (%)

DTIC/TMZN=130n (%)

P-valuec

Nonresponders 248a (95.4%) 114b (87.7%)0.010

Responders 12 (4.6%) 16 (12.3%)

Investigator’s Best Response 13 (5.0%) 19 (14.6%) N/A

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Response Difference % Difference 95% CIVelimogene aliplasmidminus DTIC/TMZ -7.7 (-13.9,-1.5)

a Includes 11 velimogene aliplasmid subjects with no scans after baseline not evaluated by EAACb Includes 22 DTIC/TMZ subjects with no scans after baseline not evaluated by EAACc P-value from Cochran-Mantel-Haenszel statistic stratified by disease stage, ECOG and number

of injectable lesions

Duration of ResponseEAAC Responders

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Secondary EndpointOverall Survival in ITT Population

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Overall SurvivalResponders

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DTIC/TMZ responders5 Stage IIIB3 Stage IIIC5 Stage IV M1a3 Stage IV M1b

Velimogene aliplasmid responders7 Stage IIIB1 Stage IIIC1 Stage IV M1a3 Stage IV M1b

Follow-on Treatments

Therapy

VelimogeneAliplasmid

N=188a

n (%)b

DTIC/TMZN=94a

n (%)bP-value

Ipilimumab 32 (17.0) 28 (29.8) 0.014BRAFi 18 (9.6) 9 (9.6) 1.000T-VEC 7 (3.7) 7 (7.4) 0.243Treated, but with none of the abovec 140 (74.5) 58 (61.7) 0.027

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a Includes only post-treated subjects for whom follow-on treatment data were availableb Totals >100% due to some subjects receiving multiple follow-on treatmentsc Other follow-on treatment include surgery, radiation, chemotherapy, targeted therapies, and

cytokines

Treatment ReceivedMITT Population

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VelimogeneAliplasmid

( N=259)

DTIC(N=80)

TMZ(N=40)

Treatment Duration (weeks)MedianMin, Max

13.11.1, 101.3

8.60.1, 82.1

7.40.1, 100.9

Discontinuation Due to Adverse Event [n/N (%)] 6/259 (2.3%) 11/120 (9.2%)

MITT Population: 1 patient randomized to velimogene aliplasmid and 10 patients randomized to DTIC/TMZ did not receive study drug and were excluded from the safety analysis

Safety in MITT PopulationOverall and Drug-related Adverse Events

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Treatment

Subjects w/ Grade ≥3

AEsN (%)

Subjects w/ drug-related

Grade ≥3 AEs

N (%)

Subjects w/SAEs N (%)

Subjects w/drug-related SAEs N (%)

Velimogene aliplasmid 55 (21.2) 9 (3.5) 25 (9.7) 0 (0.0)

DTIC/TMZ 28 (23.3) 12 (10.0) 15 (12.5) 5 (4.2)

MITT Population: 1 patient randomized to velimogene aliplasmid and 10 patients randomized to DTIC/TMZ did not receive study drug and were excluded from the safety analysis

Summary Results / Observations

DTIC/TMZ was more effective than velimogene aliplasmid for best overall response rate at ≥24 weeks in this trial

Overall survival was not significantly different with velimogene aliplasmid than with DTIC/TMZ in this trial

The responses with velimogene aliplasmid were more durable than with DTIC/TMZ in this trial Median OS (mos.) was greater for velimogene aliplasmid responders

[n/a (19.7, n/a)] than for DTIC/TMZ responders [40.7 (28.9, n/a)] A substantial majority (83%) of velimogene aliplasmid responders were

still alive at last contact Follow-on treatments may have had an effect on overall survival

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Conclusions

Velimogene aliplasmid was not an effective treatment for the patient population selected for this study

The treatment landscape for metastatic melanoma is rapidly changing

Recently approved or investigational follow-on treatments may affect overall survival

Chemotherapy may not be an appropriate control in an immunotherapeutic treatment study Faster progression on chemotherapy may provide quicker access to new

follow-on treatments, potentially affecting overall survival Duration of response and overall survival for responders tended to be

longer with immunotherapy than with chemotherapy in this study

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Acknowledgements

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United StatesRavindranath Patel, MDArkadiusz Z Dudek, MDDavid J Perry, MDDoru Alexandrescu, MDKelly B Pendergrass, MDRobert J Belt, MDJeffrey George, MDPaul O Schwarzenberger, MDSigrun Hallmeyer, MDJon M Richards, MD, PhDEric D Whitman, MD, FACSLaura F Hutchins, MD, FACPAli Khojasteh, MD, FACPMadhavi L Venigalla, MDDouglas S Reintgen, MDSanjiv Agarwala, MDHoward L Kaufman, MDRene Gonzalez, MDJohn Richart, MDKelly M McMasters, MD, PhDMichael H Greenhawt, MDSvetomir N Markovic, MD, PhDJulian A Kim, MDGregory A Daniels, MD, PhDRobert HI Andtbacka, MDTawnya Bowles, MDR Dirk Noyes, MDJohn J Nemunaitis, MDMinal Barve, MDJoseph M Weresch, MD

FranceEve Maubec, MDCéleste Lebbe, MDBrigitte Dreno, MDThomas Jouary, MDLuc Thomas, ProfessorJean-Jacques Grob, ProfessorBernard Guillot, ProfessorCaroline Robert, MDGermanyCord Sunderkötter, MDAnja Gesierich, MDSelma Ugurel, MDRalf Gutzmer, MDPatrick AM Terheyden, MDAxel Hauschild, MDUwe Trefzer, MDClaus Garbe, MDSabine Sell, MDMartin Kaatz, MDHans Starz, MDAnnette Stein, MDEdgar Dippel, MDItalyAlessandro Testori, MDPaolo Ascierto, MDVanna Chiarion Sileni, MDMichele Maio, MDPaola Queirolo, MDThe NetherlandsGeke A Hospers, MD

PolandAndrzej Mackiewicz, MDAndrzej Kaiser, MDSpainAlfonso Berrocal Jaime, MDPere Vilaplana Gascón, MDRaquel Andrés, MDJose Ignacio Mayordomo, MDSwitzerlandReinhard Dummer, MDIsraelHaim Gutman, MDJacob Schachter, MDMichal Lotem, MDRussiaSvetlana A Protsenko, MDVladimir M Moiseyenko, MDMaria M Konstantinova, MDLev V. Demidov, MD, ProfessorMaria Matrosova, MDV. A. Lubennikov, MDMV Kopp, ProfessorNV Kovalenko, MDTurkeyAhmet Demirkazik, MD

Patients and their supportive familiesTrial sponsor Vical IncorporatedVical’s product development team and supporting departmentsFinancial sponsor AnGes MG

United States (cont’d)Michael A Warso, MDJohn T Vetto, MDArmando Sardi, MDRobert S Alter, MDLee D Cranmer III, MD, PhDPhilip D Leming, MDRobert W Weber, MDMelanie E Royce, MD, PhDClaire F Verschraegen, MDHoward Safran, MDGerald A Colvin, DOCanadaJ Gregory McKinnon, MDOliver R Keller, MDRalph Wong, MDBrazilAlberto Julius Alves Wainstein, MDLeandro Brust, MDNils Gunnar Skare, MDRoberto Odebrecht Rocha, MDCarlos Henrique EscosteguyBarrios, MDFábio André Franke, MDGélcio Luiz Quintella Mendes, MDFernanda Maris Peria, MDBelgiumJean François Baurain, MDAndrée Rorive, MDCroatiaZvonko Kusic, MD