DNA Medicines and HPV - January 2023
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DNA Medicines and HPV :INO January 2023
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2
About this Presentation: Disclaimer
The following presentation is intended to be a primer on INOVIO’s DNA medicines science and technology
acquired in connection with INOVIO’s investigational, pre-clinical and clinical development work with Human
Papillomavirus (HPV)-associated diseases. The presentation includes data generated from preclinical
activities and clinical trials with respect to the following programs: VGX-3100, INO-3106, INO-3107, and INO-
3112. VGX-3100 is being studied as a potential treatment for HPV-16/18-positive high-grade squamous
intraepithelial lesions (HSIL) in the cervix, anus and vulva. INO-3106 was studied in a pilot trial for a potential
treatment for recurrent respiratory papillomatosis (RRP). INO-3107 is being studied as a potential treatment
for HPV-6/11-positive RRP. INO-3112 has been studied alone and in combination with AstraZeneca's PD-L1
checkpoint inhibitor (durvalumab) as a potential treatment for HPV-16/18-positive head and neck and
cervical cancers.
Disclaimer – As this presentation contains background and summary information only, please note
that it does not present full, complete and/or balanced information, including information about the
status or results of the foregoing programs.
For more complete information about INOVIO and the status and results of the foregoing programs, please
refer to (i) our SEC Form 10-K for the year ended December 31, 2021 and our SEC Form 10-Q for the
quarter ended September 30, 2022 and (ii) our Investor Presentation available on our website at
www.inovio.com.
3
Table of Contents
Page
5 • Executive Summary – DNA Medicines and HPV
6 • INOVIO’s Technology
9 • Human Papillomavirus – Patients in Need of Effective Therapeutic Options
13 • INOVIO's Commitment to Developing HPV Therapies
15 • Recurrent Respiratory Papillomatosis
20 • Pre-Cancer and Cancer-Focused Indications
28 • Conclusions and Upcoming Milestones
30 • Appendix – Immunology: A Reference Guide
4
Executive Summary: DNA Medicines and HPV
• Human Papillomavirus (HPV) is one of the most common viral infections globally
o HPV causes nearly all cervical cancers and many cancers of the vagina, vulva, penis, anus, rectum, and
oropharynx, as well as dysplasia, warts and papillomas, which can cause recurrent respiratory papillomatosis (RRP)
• DNA medicines offer the potential to treat HPV disease and clear the underlying viral infection
o DNA Medicines work by generating antibody and cellular immune responses that induce antigen-specific, long-
lived memory helper and killer T cells
o Triggering the cellular immune system helps clear the virus which leads to tissue regression in precancerous lesions
and potentially tumor shrinkage
• DNA medicines have been well-tolerated in 15,000+ administrations across 5,000+ participants
• Recent news and upcoming announcement in HPV-related disease portfolio:
o Results from Phase 1/2 trial with INO-3107 in RRP patients announced 4Q/22:
▪ 16 of 21 (76%) participants with a reduction in number of surgical interventions compared with previous year,
of which 6 required no surgical intervention during the trial
▪ Demonstrated statistical significance based on clinical endpoint of reduction in overall number of surgical
interventions compared with previous year and INO-3107 was found to be well-tolerated and immunogenic
o VGX-3100 Phase 3 cervical high-grade squamous intraepithelial lesions (HSIL) data: 1Q23
5
INOVIO's Technology
DNA Medicines
6
INOVIO's DNA Medicines Platform
OPTIMIZED PLASMID DESIGN AND DELIVERY TECHNOLOGY
PRECISELY PROPRIETARY
SMART DEVICES* IN VIVO
DESIGNED PLASMIDS
(CELLECTRA®)
Intramuscular Intradermal
(IM) Device (ID) Device
for Pre-Cancers & for Vaccines
Cancers
7 *Investigational
Key Attributes of DNA Medicines for HPV-Associated Diseases1
Topic Attribute Effect
Generates antibody, helper T cell, Complete immune response with induction of antigen-
and killer T cell responses specific long-lived memory, helper, and killer T cells2,3
Immunogenicity
Antigen expression optimized based
Potential for enhanced immunogenicity
on Inovio’s proprietary technology
Does not contain whole or
Cannot cause HPV infection
weakened HPV virus
Safety &
Tolerability Repeat administrations have been
Booster doses possible
well-tolerated
Substantial clinical trial experience Favorable adverse event profile across programs
8 Reference citations available in endnotes slide
Image created with BioRender.com
Human Papillomavirus
Patients in Need of Effective Therapeutic Options
9
Human Papillomavirus (HPV): A Concern for All
• HPV is a group of viruses with approximately 200 types4
• Nearly everyone will become infected with some HPV type in their lifetime
− The good news: ~90% of all infections clear naturally and don't result
in disease1
− The bad news: persistent infection can lead to cancer and other
debilitating, life-threatening diseases affecting quality of life
• HPV types fall into 2 groups:4
o Low-risk HPV (e.g., HPV 6 and HPV 11) can lead to benign growths
(warts or papillomas) that can develop into conditions such as RRP
o High-risk HPV (e.g., HPV 16 and HPV 18) can lead to cell changes
and lesions (precancerous dysplasia) that can become malignant, such Electron microscope photograph of HPV
Image courtesy CDC/NCI
as cervical HSIL, which can lead to cervical cancer (https://www.cdc.gov/hpv/hcp/photos.html)
10 Reference citations available in endnotes slideSpectrum of HPV-Associated Disease
• The spectrum of HPV-associated disease goes
from relatively benign lesions to cancer4
• HPV causes nearly all cervical cancers and many
cancers of the vagina, vulva, penis, anus, rectum,
and oropharynx4
• HPV also causes:
o Dysplasias – abnormal cells that are
potential precursors to cancer
o Warts
o Papillomas - benign growths that can lead
to recurrent respiratory papillomatosis (RRP)
11 Reference citations available in endnotes slide
Image created with BioRender.comNeed for Effective Treatments for HPV-Associated Diseases
Limitations of Preventative Vaccines Additional Therapeutic Options Needed
Preventative HPV vaccines have reduced the Surgery
prevalence of HPV infections, but have not • Standard of care for many HPV-associated
eliminated them – nor can they clear or treat diseases, including cervical dysplasia
established infections and cancer, as well as RRP
• Relative low rate of vaccination in US vs. other • Invasive - often needed repeatedly
especially in RRP and anal dysplasia
vaccines5,6
• May not eliminate underlying HPV infection
• Vaccination rates range significantly globally
Drugs and Therapeutic Vaccines
• Unvaccinated people remain at risk of
developing HPV-associated diseases • Off-label options may cause adverse reactions
and discontinuation may lead to rebound of
disease
• Checkpoint blockade appears limited in ability
to trigger adequate HPV-specific T cells in RRP
patients7
12 Reference citations available in endnotes slideHistorical HPV Studies
INOVIO's Commitment to Developing
HPV Therapies
Therapeutic Clinical Studies to Date
13INOVIO’s Development Efforts Across HPV Disease Spectrum
Status/DNA Medicine Clinical Target Estimated Disease Prevalence/Incidence (U.S.)
Incidence:
Recurrent
Phase 1/2 Reduction of recurrence of papillomas and Children - 4.3 per 100,000 (2,354)*8
Respiratory
INO-3107 clearance of HPV 6/11 in airway Adults - 1.8 per 100,000 (3,623)*8
Papillomatosis
Regression of HPV 16/18-associated HSIL
Phase 3
Cervical HSIL (CIN2/3) and clearance of virus in cervix in Incidence** = 196,000 cases (2016)9
VGX-3100
biomarker-selected population
Phase 2 Regression of HPV 16/18-associated HSIL Prevalence** = 30,243 cases (2019)10
Vulvar HSIL
VGX-3100 (CIN2/3) and clearance of virus in vulva Incidence** = 10,960 to 13,700 (2019)10
Phase 2 Regression of HPV 16/18-associated HSIL Prevalence** = 33,965 cases (2019)11
Anal HSIL
VGX-3100 (CIN2/3) and clearance of virus in anus Incidence** = 9,580 to 11,975 cases (2019)11
Head and Neck
Phase 1/2 Treatment of HPV-16/18 head and neck
Squamous Cell Incidence = 66,470 cases (2022)12
INO-3112 squamous cell carcinoma
Carcinoma
14 Reference citations available in endnotes slide *Figures likely impacted due to the introduction of the preventative HPV vaccine **Not specific to HPV16 and HPV18-associated HSILRecurrent Respiratory Papillomatosis
INO-3107 and INO-3106
15What is Recurrent Respiratory Papillomatosis (RRP)?
• RRP is a rare disease caused by HPV types 6 and 11, impacting both children and adults13
• Symptoms result from benign tumors – papillomas – in throat and on voice box14
o Can obstruct airway and cause difficulty speaking
o Can lead to chronic cough, infections, pneumonia, hoarseness and failure to thrive
o Rare risk of progression to lung disease and cancer
• Surgery is current standard of care14
o Patients can require hundreds of surgeries during their lifetime
o In severe cases with aggressive tumor growth, tracheostomies may be needed to help with
breathing15
• Incidence (US): Children - 4.3 per 100,000 (2,354); Adults - 1.8 per 100,000 (3,623)16
• Active Cases (US): Children – 5,970 active cases; Adults – 9,015 active cases16
16 Reference citations available in endnotes slidePotential Benefits of Therapeutic DNA Medicine in Treating
HPV 6 and HPV 11-Associated RRP
• INO-3107 represents a potential first-in-class non-surgical
therapeutic option for HPV 6 and HPV 11-associated RRP
• Potential benefits include:
− Reduced number of surgical interventions needed to
control regrowth of papillomas
− Clearance of underlying HPV infection
− Increased quality of life by eliminating and/or
controlling symptoms
− Reduced risk associated with repeat surgical
interventions
• INO-3107 granted Orphan Drug Designation in July 2020
Image Source: National Institute on Deafness and Other Communication Disorders; Available at www.nidcd.nih.gov/health/recurrent-respiratory-papillomatosis; accessed July 27, 2022;
Photographs courtesy Aaron Friedman MD, University of Cincinnati College of Medicine (https://voicesurgeon.net/voice-disorders/recurrent-respiratory-papillomatosis-rrp/). Used with permission.
17INO-3107: Results of Phase 1/2 Trial for RRP
TRIAL Design17 Study Results from First Cohort
• Demonstrated statistical significance based on clinical endpoint
of reduction in overall number of surgical interventions
x32 compared with previous year
• 16 of 21 (76%) participants saw a reduction in the number of
surgical interventions compared to previous year, of which 6
Phase 1/2 open-label, Fully enrolled 4 doses of vaccine,
participants required no surgical intervention during the trial
multi-center clinical trial 3 weeks apart on
Day 0, Weeks 3, 6, 9 • Median decrease of 3 surgical interventions (95% CI 1, 3)
• Cellular response observed:
o INO-3107 generated cellular responses against both
• Enrollment criteria: Participants who have required at least two HPV 6 and HPV 11, inducing both CD4 and CD8 T cells
surgical interventions per year for the past year for the removal
of HPV-6/11-associated papilloma(s) o T-cell activity against HPV 6 and HPV 11 was present at
study end (43 weeks after treatment completion),
• Efficacy endpoint: Change in median number of surgical indicating persistent cellular memory response
interventions in year prior to Day 0 when compared with year • INO-3107 was observed to be well-tolerated
following Day 0
18 Reference citations available in endnotes slideINO-3106: Pilot Study in HPV6-Positive RRP
• INO-3106 targets HPV 6-associated RRP18
• Initiated September 2014
• Two participants enrolled
• Participant 603:
− >5-fold increase in time between surgical
interventions
− Higher levels of CD8+ T cells may be
associated with longer time between surgeries
• Participant 604: 3-fold increase in time between
surgical interventions
• Results led to development of INO-3107 program
for treatment of HPV 6 and 11-associated RRP
19 Reference citations available in endnotes slidePre-Cancer and
Cancer-Focused Product Candidates
VGX-3100: Cervical HSIL
INO-3112: Head and Neck Cancer
20VGX-3100: Product Candidate for HPV16/18 Cervical HSIL
• First DNA medicine candidate to show regression of lesion and viral clearance
against HPV16/18-associated cervical HSIL in a Phase 2B trial
o Data published in The Lancet in 201519
• Current Status: Phase 3
o REVEAL1:20
▪ Data announced in 2021
▪ Study led to the identification of a potential pre-treatment biomarker
o REVEAL2:21
▪ Ongoing study; data expected 1Q23
▪ Trial design amended to revise primary analysis population from all-
comers to a biomarker-positive population
21 Reference citations available in endnotes slideVGX-3100: Current Phase 3 Trial for Cervical HSIL (REVEAL2)
TRIAL Design Key Updates & Catalysts
• In 2022, FDA recommended using
x198 REVEAL2 as an exploratory study to
evaluate the biomarker-positive population
Phase 3, randomized (2:1), Fully enrolled Dosing: month 0, 1, 3 and then conduct 1 or 2 additional trials in
double-blind, placebo- the biomarker-positive population to
controlled clinical trial support marketing application.
• Efficacy and safety follow up data
Primary endpoint: expected 1Q23
Regression of HSIL (CIN2/3) AND clearance of HPV
16/18 in the cervix in biomarker-selected population • Path forward for the VGX-3100 program
will be assessed following the analysis of
REVEAL2
22VGX-3100: Results of Phase 3 Trial for Cervical HSIL (REVEAL1)
Study Results
TRIAL Design
• ITT population (N=201): primary endpoint was not
achieved
• 22.5% (31/138) in treatment arm vs 11.1%
x201 (7/63) in placebo
• 3 of 4 secondary endpoints achieved (did not
Phase 3, randomized (2:1), Fully enrolled Dosing: month 0, 1, 3 achieve "regression of cervical HSIL alone")
double-blind, placebo-
controlled clinical trial • mITT population (N=193): primary and
secondary endpoints were achieved
Primary endpoint: • 23.7% (31/131) in treatment arm vs. 11.3%
Histopathological regression of HSIL combined with (7/62) in placebo
virologic clearance of HPV16 and/or HPV18 at week 36. • Safety follow-up:
Secondary endpoints: • Participants who met primary endpoint at
a) Regression of cervical HSIL to normal tissue combined Week 36 remained clear of HPV16
with HPV-16/18 viral clearance, b) regression of cervical and/or HPV18 at Week 88
HSIL alone, c) regression of cervical HSIL to normal • Safety profile observed at Week 36
tissue, and d) HPV-16/18 viral clearance alone remained well-tolerated through Week 88
23VGX-3100: Results of Phase 2B Trial (Cervical HSIL)
Per-Protocol Analysis (vs. placebo)22 VGX-3100 Placebo
Primary Endpoint: Regression to LSIL or Normal 49.5% 30.6% P=0.017
Secondary Regression to Normal AND 40.2% 30.0% P=0.003
Endpoint: Virological Clearance
• In both per-protocol and mITT analyses, significantly higher numbers of participants receiving
VGX-3100 experienced histopathological regression vs. placebo (p=0.034)
• Peak T cell responses to HPV16 and HPV18 E6 and E7 antigens were 9.5 times higher for
VGX-3100 than placebo (pVGX-3100: Phase 2B (Cervical HSIL) Data
Increased Antigen-Specific T Cells22 Regression of High-Grade Lesions22
Increased and persistent
Regression of CIN3 & presence of CD8+ cells
HPV to normal (24 weeks post-last dose)
T Cell Responses Measured in Blood
800 VGX-3100
VGX-3100 Specific T Cells1
0
Placebo
Week
Pre
600
400
* * *
CD8+
* T Cell
Infiltration
200
36
Post
Week
0
0 5 10 15 20 25 30 35 40
Study Week
Treatment at wks 0, 4, & 12
IHC Staining: HPV IHC Staining: CD8 +
Images used from The Lancet (https://www.sciencedirect.com/journal/the-lancet), Volume 386 (10008);
*Statistically significant; bars are 95% Cl Trimble CL, Morrow MP, Kraynyak KA, et al. Safety, efficacy, and immunogenicity of VGX-3100, a
therapeutic synthetic DNA vaccine targeting human papillomavirus 16 and 18 E6 and E7 proteins for cervical
intraepithelial neoplasia 2/3: a randomised, double-blind, placebo-controlled phase 2b trial. Pp. 2078-2088.
Copyright 2015, with permission from Elsevier.
25 Reference citations available in endnotes slideINO-3112: Product Candidate for HPV-associated Head & Neck
Cancer
• Investigated alone and in combination with AstraZeneca’s PD-L1 checkpoint inhibitor, durvalumab
o Monotherapy: Phase 1/2a trial, initiated May 2014
▪ 22 HPV-positive HNSCC participants
▪ Observed T cell responses and infiltration of CD8+ immune cells into the head and neck tumors
▪ Published in Clinical Cancer Research, 2019
▪ Post study 2 of 4 subjects who progressed received PD-1 checkpoint inhibitor had a CR
o Combination: Phase 1b/2a trial, initiated May 2017
▪ 35 HPV-positive HNSCC participants
▪ ORR was 27.6% (4 CR, 4 PR) in 29 evaluable patients
▪ Peripheral HPV-specific T cells and tumoral CD8+ T cells were increased
▪ Abstract presented at ESMO 2020
▪ Updated and published in Clinical Cancer Research, 2022
• INOVIO continues to believe in potential benefit of investigating the antigen-specific T cell generation
and tumor infiltration abilities of INO-3112 in head and neck cancers, especially when used in novel
combinations
26INO-3112: Data from Phase 1/2a trial in HNSCC
• Treatment with INO-3112 resulted in infiltration of • Robust antigen-specific T cell responses
CD8+ immune cells into the head and neck tumors observed in peripheral blood (as measured
(measured by staining of cells before (below left) by expression secretion of IFNg) (below)23
and after (below right) treatment)23
CD8 staining prior to dosing CD8 staining after dosing
27 Reference citations available in endnotes slideConclusions: DNA Medicines Have Potential to Treat HPV Disease
• HPV infection is one of the most common global infections; persistent infection can lead to a number of
potentially debilitating and life-threatening diseases
• INOVIO’s investigational DNA medicines have the potential to become important therapeutic options for a
variety of HPV-associated diseases
• In connection with clinical trials evaluating INOVIO’s investigational DNA medicines INOVIO has observed:
o Viral clearance and regression of precancerous lesions to normal tissue in participants with cervical HSIL
o Generation of antigen-specific killer (CD8+) T cells that infiltrate tumors in participants with head and
neck cancer
o Statistically significant reduction in the overall number of surgical interventions in participants with RRP
o DNA medicines are well-tolerated, immunogenic and can be re-administered
• Upcoming catalyst in HPV-related disease portfolio:
o VGX-3100 Phase 3 cervical HSIL data (REVEAL2): 1Q23
28Endnotes
• Slide 8:
1. Cheng MA, Farmer E, Huang C, Lin J, Hung CF, Wu TC. Therapeutic DNA Vaccines for Human Papillomavirus and Associated Diseases. Hum Gene Ther. 2018;29(9):971-996.
2. Patel A, Reuschel EL, Kraynyak KA, et al. Protective Efficacy and Long-Term Immunogenicity in Cynomolgus Macaques by Ebola Virus Glycoprotein Synthetic DNA Vaccines. J Infect Dis. 2019;219(4):544-555.
3. Sales NS, Silva JR, Aps LRMM, et al. In vivo electroporation enhances vaccine-mediated therapeutic control of human papilloma virus-associated tumors by the activation of multifunctional and effector memory CD8+ T cells. Vaccine.
2017;35(52):7240-7249.
• Slides 10 and 11:
4. National Cancer Institute (NCI). HPV and Cancer. Available at: https://www.cancer.gov/about-cancer/causes-prevention/risk/infectious-agents/hpv-and-cancer#what-is-hpv. Accessed September 19, 2022.
• Slide 12:
5. Lu PJ, Hung MC, Srivastav A, et al. Surveillance of Vaccination Coverage Among Adult Populations-United States, 2018. MMWR Surveill Summ. 2021;70(3):1-26.
6. Walker TY, Elam-Evans LD, Yankey D, et al. National, Regional, State, and Selected Local Area Vaccination Coverage Among Adolescents Aged 13-17 Years - United States, 2018. MMWR Morb Mortal Wkly Rep. 2019;68(33):718-723.
7. Allen CT, Lee S, Norberg SM, et al. Safety and clinical activity of PD-L1 blockade in patients with aggressive recurrent respiratory papillomatosis. J Immunother Cancer. 2019;7(1):119.
• Slide 14:
8. Derkay CS. Task force on recurrent respiratory papillomas. A preliminary report. Arch Otolaryngol Head Neck Surg. 1995;121(12):1386-1391.
9. McClung NM, Gargano JW, Park IU, et al. Estimated Number of Cases of High-Grade Cervical Lesions Diagnosed Among Women - United States, 2008 and 2016. MMWR Morb Mortal Wkly Rep. 2019;68(15):337-343.
10. Herring T et al. Vulvar High-Grade Squamous Intraepithelial Lesions (HSIL): US Epidemiology Burden in the Post-HPV Vaccine Introduction Era of 2015-2019. Poster presented at IPVC 2021 (Abstract 156).
11. Herring T et al. Anal High-Grade Squamous Intraepithelial Lesion (HSIL): US Epidemiology Burden in the Post-HPV Vaccine Introduction Era, 2015-2019. Oral presentation at IPVC 2021 (Abstract 161).
12. Cancer.Net. Head and Neck Cancer: Statistics. Available at: https://www.cancer.net/cancer-types/head-and-neck-cancer/statistics. Accessed October 4, 2022.
• Slide 16:
13. Benedict JJ, Derkay CS. Recurrent respiratory papillomatosis: A 2020 perspective. Laryngoscope Investig Otolaryngol. 2021;6(2):340-345.
14. Ouda AM et al. HPV and Recurrent Respiratory Papillomatosis: A Brief Review. Life (Basel). 2021;11(11):1279.
15. National Organization of Rare Diseases (NORD). Recurrent Respiratory Papillomatosis. Available at: https://rarediseases.org/rare-diseases/recurrent-respiratory-papillomatosis/. Accessed October 4, 2022.
16. Derkay CS. Task force on recurrent respiratory papillomas. A preliminary report. Arch Otolaryngol Head Neck Surg. 1995;121(12):1386-1391.
• Slide 18
17. ClinicalTrials.gov. INO-3107 With Electroporation (EP) in Participants With HPV-6- and/or HPV-11-Associated Recurrent Respiratory Papillomatosis (RRP). Available at: https://clinicaltrials.gov/ct2/show/NCT04398433. Accessed October
4, 2022.
• Slide 19
18. Aggarwal C, Cohen RB, Morrow MP, et al. Immune Therapy Targeting E6/E7 Oncogenes of Human Papillomavirus Type 6 (HPV-6) Reduces or Eliminates the Need for Surgical Intervention in the Treatment of HPV-6 Associated
Recurrent Respiratory Papillomatosis. Vaccines (Basel). 2020;8(1):56.
• Slide 21
19. Trimble CL, Morrow MP, Kraynyak KA, et al. Safety, efficacy, and immunogenicity of VGX-3100, a therapeutic synthetic DNA vaccine targeting human papillomavirus 16 and 18 E6 and E7 proteins for cervical intraepithelial neoplasia 2/3:
a randomised, double-blind, placebo-controlled phase 2b trial. Lancet. 2015;386(10008):2078-2088.
20. ClinicalTrials.gov. REVEAL 1 (Evaluation of VGX-3100 and Electroporation for the Treatment of Cervical HSIL) (REVEAL 1). Available at: https://clinicaltrials.gov/ct2/show/NCT03185013. Accessed October 4, 2022.
21. ClinicalTrials.gov. REVEAL 2 Trial (Evaluation of VGX-3100 and Electroporation for the Treatment of Cervical HSIL). Available at: https://clinicaltrials.gov/ct2/show/NCT03721978. Accessed October 4, 2022.
• Slides 24 and 25
22. Trimble CL, Morrow MP, Kraynyak KA, et al. Safety, efficacy, and immunogenicity of VGX-3100, a therapeutic synthetic DNA vaccine targeting human papillomavirus 16 and 18 E6 and E7 proteins for cervical intraepithelial neoplasia 2/3:
a randomised, double-blind, placebo-controlled phase 2b trial. Lancet. 2015;386(10008):2078-2088.
• Slides 26 and 27
23. Aggarwal C, Cohen RB, Morrow MP, et al. Immunotherapy Targeting HPV16/18 Generates Potent Immune Responses in HPV-Associated Head and Neck Cancer. Clin Cancer Res. 2019;25(1):110-124
24. Aggarwal C, Saba NF, Algazi AP et al. 916MO Safety and efficacy of MEDI0457 plus durvalumab in patients (pts) with human papillomavirus-associated recurrent/metastatic head and neck squamous cell carcinoma (HPV+ R/M HNSCC),
Annals of Oncology. 2020. 31 (Suppl 4), S661-S662.
25. Aggarwal C, Saba NF, Algazi AP et al. Safety and Efficacy of MEDI0457 Plus Durvalumab in Patients With Human Papillomavirus-associated Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Clin Cancer Res CCR-22-
1987.
29Appendix
Immunology: A Reference Guide
30The Importance of Understanding the Immune System
• DNA Medicines work by generating antibody and cellular responses that
induce antigen-specific, long-lived memory, helper, and killer T cells
• To fully understand the benefits DNA Medicines can have in treating and/or
preventing disease, it’s important to understand the basics of the human
immune system, especially the role T cells play
• The following information is intended to be a helpful primer on some key
basic facts
31Some Basics: Viruses & Antigens
• A virus is an infectious microorganism consisting of:1
− Viral genes composed of single- or double-stranded DNA or RNA
− Capsid – a protein shell encasing the viral genes
− Outer covering (envelope) made up of lipids; seen in only a subset of viruses
Image Courtesy:
Public Health Image Library, CDC • Virus enters host cells by binding to receptors on the host cell surface
− Cannot replicate by itself and takes over the host cell to do so
• A viral antigen is a molecule recognized by the host as being foreign, causing an immune
response, which includes:2
− Production of antibodies by B cells (humoral immunity) and
− Production of T cells and natural killer (NK) cells (cellular immunity)
Image created with BioRender.com
CDC, Centers for Disease Control and Prevention; DNA, deoxyribonucleic acid; RNA, ribonucleic acid
1. National Human Genome Research Institute, National Institutes of Health (NIH). Virus. 2022. Available at https://www.genome.gov/genetics-glossary/Virus. Accessed September 15, 2022.
32 2. Laing K. Immune responses to viruses. 2022. British Society for Immunology. Available at https://www.immunology.org/public-information/bitesized-immunology/pathogens-and-disease/immune-responses-viruses.
Accessed September 15, 2022.Some Basics: Antibodies
• Antibodies produced by B cells act before the virus infects the host cell1.
• Highly specific
• Prevent viruses from infecting host cells (neutralization)
• Cause viruses to stick together to be easily recognized and destroyed by other immune cells
1. Laing K. Immune responses to viruses. 2022. British Society for Immunology. Available at https://www.immunology.org/public-information/bitesized-immunology/pathogens-and-disease/immune-responses-viruses.
33 Accessed September 15, 2022.
Images created with BioRender.comSome Basics: T Cells
• There are several types of T cells:
• Cytotoxic (CD8+) T cells can directly kill
infected or cancerous cells
• Helper (CD4+) T cells help organize an
immune response by secreting cytokines and
activating B cells to secrete antibodies
• Memory T cells are antigen-specific T cells
that remain long-term after an infection has
been eliminated, providing a rapid response
when exposed to the same infection
• T cells are highly specific. They target infected or
cancerous cells by recognizing the foreign or tumor
antigens displayed on the cell surface, while
leaving normal, healthy cells alone.
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