one Target: infinite Hope Corporate Presentation Q3, 2017 Forward - - PowerPoint PPT Presentation

• ne Target: infinite Hope™

Corporate Presentation Q3, 2017

Forward Looking Statements

Certain statements in this presentation are “forward-looking statements. Any statements that express or involve discussions with respect to predictions, expectations, beliefs, plans, projections, objectives, assumptions or future events or performance (often, but not always using words or phrases such as “expect”, “seek”, “endeavour”, “anticipate”, “plan”, “estimate”, “believe”, “intend”,

• r stating that certain actions, events or results may, could, would, might or will occur or be taken, or achieved) are not

statements of historical fact and may be “forward-looking statements”. Forward-looking statements are based on expectations, estimates and projections at the time the statements are made that involve a number of risks and uncertainties which would cause actual results or events to differ materially from those presently anticipated. Forward-looking statements are based on expectations, estimates and projections at the time the statements are made and involve significant known and unknown risks, uncertainties and assumptions. A number of factors could cause actual results, performance or achievements to be materially different from any future results, performance or achievements that may be expressed or implied by such forward-looking

• statements. These include, but are not limited to, the risk factors discussed in the public filings made by Medicenna with the

applicable securities commissions in Canada, including the Annual Information Form dated June 15, 2017. Should one or more

• f these risks or uncertainties materialize, or should assumptions underlying the forward-looking statements prove incorrect,

actual results, performance or achievements could vary materially from those expressed or implied by the forward-looking statements contained in this document. These factors should be considered carefully and prospective investors should not place undue reliance on these forward-looking statements. Although the forward-looking statements contained in this document are based upon what Medicenna currently believes to be reasonable assumptions, Medicenna cannot assure prospective investors that actual results, performance or achievements will be consistent with these forward-looking statements. Except as required by law, Medicenna does not have any obligation to advise any person if it becomes aware of any inaccuracy in or omission from any forward-looking statement, nor does it intend, or assume any obligation, to update or revise these forward-looking statements to reflect new events or circumstances.

2

Medicenna: Corporate Highlights

➢ Publicly listed (TSXV: MDNA), clinical-stage, immuno-oncology company developing a novel therapy targeting the Interleukin-4 Receptor (IL4R) biomarker ➢ Every year >1 million cancer patients afflicted with IL4R tumors1 ➢ MDNA55 (lead): highly compelling, Phase II clinical data for recurrent glioblastoma (rGB), the most common and aggressive form of brain cancer ➢ MDNA55 market opportunity: $650 million in annual sales for rGB; >$2 billion including other brain cancers1,2 ➢ MDNA55 has Orphan Drug (FDA, EMA) & Fast Track Designations (FDA) ➢ Exciting pre-clinical IL-2, IL-4 and IL-13 Superkine platform ➢ Well funded with $14M US non-dilutive grant and $14M CAD Private Placement ➢ Seasoned management with technology platform protected by 12 patent families

1. BioXcel Strategic Analysis Report, 2014. 2. Decision Resources, Inc Glioblastoma Report, Sept 2013

3

Treatment Pathway for Glioblastoma (GB)

Surgery (85-90%) GB

Diagnosis

Radiotherapy + Chemotherapy Relapse Chemotherapy Surgery

MDNA NA55 55 Treatm tment ent

(Dir irect ect infusi fusion

• n into

to tumor

• r - CED)

D)

Add’l Chemo.or Experimental Therapies

GB is uniformly fatal; virtually all tumors will recur (rGB)

55% of GB Chemo. Resistant*

* Expression of the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) is responsible for resistance to alkylating agents used in GB treatment.

25% 75% of rGB is non-operable

4

MDNA55: Targeted Dual-Action Immunotherapeutic

A Powerful Molecular Trojan Horse

➢ Potently toxic to tumor cells with a wide therapeutic window ➢ Simultaneously purges the Tumor Microenvironment (TME) and un-blinds the immune system to cancer cells ➢ Proven payload efficacy– identical to Medimmune’s anti-CD22 immunotoxin, Moxetumomab Pasudotox, currently in PhIII trial for Hairy Cell Leukemia1 ➢ Reliable, cost-efficient fermentation-based manufacture

1 https://www.medimmune.com/our-therapy-areas/oncology.html

PE AAs s 253-364 364, 381 81-60 608

Tumor Targeting Domain Tumor Killing “Cytotoxic” Domain

5

MDNA55: Brain Cancer Market Opportunity

Tumor Type Annual Incidence Projected Market

Recurrent Glioblastoma (rGB) 33,3001 $650M2 Metastatic Brain Cancer 91,5003 $1.30B4 Pediatric Glioma 3,8001 $50M4 TOTAL 133,500 $2.0B

1. Decision Resources Glioblastoma Report, Sept 2013 2. Assumes peak sales for rGB monotherapy and combination therapy at $43K per patient – BioXcel Strategic Analysis Report, 2014 3. Breast, Colon and Kidney Cancer Metastasis to Brain – BioXcel Strategic Analysis Report, 2014 4. Assumes 33% treatable with MDNA55 and priced at $43K per patient - BioXcel Strategic Analysis Report, 2014

6

Current Therapies Do Not Address Key Challenges

Therapeut peutic ic Challen enge ges Rationale ionale for MDNA5 DNA55 ➢ 55% of GBs are chemo-resistant 1 ➢ Immunosuppressive tumor microenvironment (TME) comprises 40% of GB tumor mass 2 ➢ Blood Brain Barrier (BBB) blocks transport of therapeutic to tumor ➢ High doses are required due to BBB causing systemic toxicities ➢ MDNA55 targets resistant tumors3 ➢ IL4R over-expressed in GB and its TME (Myeloid Derived Suppressor Cells) but not in normal brain 4 ➢ Delivery by direct injection (CED) of MDNA55 by-passes the BBB ➢ Precision delivery achieves high doses without systemic exposure

1. Hegi ME (2005). N Engl J Med;352(10):997-1003. 2. Kennedy B, et al (2013). J Oncol. Vo; 2013: 486912. 3. Shimamura, et al.(2007.Cancer Res;67:9903-9912. 4. Kohanbash et al (2013).Cancer Res.;73(21):6413-23

7

Compelling Efficacy in Non-Resected rGB (n=25)

Pre-treatment 9 months Pre-treatment Week 26

Complete Response (CR): 5/25 Partial Response (PR): 9/25

High Objective Response Rate

8

Kawakami, et al (2003) Interleukin-4-Pseudomonas exotoxin chimeric fusion protein for malignant glioma therapy Journal of Neuro-Oncology Vol 65 p 15-25

MDNA55: Clinical Efficacy

Long Term Survival Results Consistent With Immunotherapy Benefits

Superior Long Term Survival When Compared to Avastin Despite Poorer Patient Population (N =57)

300 600 900 1200 1500 50 100

Days Percent survival

Non-Resectable Recurrent GBM: Survival of Responders vs Non Responders

Responders (CR + PR): MS = 379 days (n=14) Non-Responders (SD + PD) MS = 98 days (n=11)

9 SD – Stable disease PD PD – Progressive disease Investigators Brochure (page 82)

2nd Generation Infusion Will Improve Outcomes

Images courtesy of John Sampson, Duke University

• Inaccurate catheter

placement

• Drug leakage due to

backflow

• Inadequate tumor

coverage

• Image-guided

catheter placement

• New catheters

prevent backflow

• Real-time monitoring

ensures tumor coverage

Real-Time Monitoring

• f Drug

Distribution 1st Generation CED: Past Studies 2nd Generation CED: Future Studies

Saito and Tominaga (2012), Neurol Med Chir (Tokyo) 52, 531 10

Open-Label Single Arm Study in 43 Patients

Primary Objectives:

ORR

SECONDARY OBJECTIVES:

MOS Safety PFS-6

TERTIARY OBJECTIVES:

Correlate IL4R Expression with Efficacy

DIAGNOSIS ONE TREATMENT FOLLOW-UP

1 2 3 4

PLANNING

11

Phase 2b Study Design Summary

CED Of MDNA55 in IL4R Up-Regulated GB Patients At First Relapse (COUGAR)

Efficacy Analysis

Statistical Design and Sample Size

Primary Endpoint: Objective Response Rate (ORR) per modified RANO (Response

Assessment for Neuro-Oncology) Criteria relative to pre-treatment baseline in adult subjects with GB that has recurred or progressed following standard therapy

Test Hypothesis: Null hypothesis that ORR is 6% (kill) versus the alternative hypothesis

(pursue) that ORR is 18% following treatment with MDNA55. Assumptions regarding primary end point are based on ORR from previous rGB studies1

Primary Efficacy Analysis: Assessed according to a single-arm, single-stage binomial

design at 1-sided alpha = 0.10. A total of 43 Subjects will provide 80% power.

12

1 Levin VA, Tonge PJ, Gallo JM, et al. CNS Anticancer Drug Discovery and Development Conference White Paper. Neuro-Oncology, v17:1–26, 2015

13

US Sites Participating in the Study

OSU (Columbu bus, s, OH) Clevel eland and Clinic (Clev evel elan and, d, OH) Weill Cornel ell + MSKCC (New York, , NY) Duke e (Durham am, , NC) UT Southweste estern rn (Dallas, as, TX) UT San Antonio (San Antonio, , TX) UCSF (San Fran ancisco, CA) JWCI (Santa ta Monica, , CA) Marcus Neuro roscien ence ce Institu tute te

(Boca

ca Raton, , FL FL)

Future Indications: 1 Million IL4R Cancers Annually

>2000 Patient Biopsies Analyzed Consistently Show IL4R Over-Expression1-14

78%

B

• C

ell C L L

67%

H

• dgkins L

ymphoma

56%

B iliary T ract

73%

B ladder

82%

B reast

89%

C

• lorectal

75%

H ead and Neck

79%

NSC L C

96%

Mesothelioma

60%

O varian

60%

P ancreatic

91%

A naplastic Thyroid

1. BioXcel Strategic Analysis Report, 2014 2. Ishige et al (2008); Int J Cancer;123(12):2915-22. 3. Joshi et al (2014 Cancer Med. 3(6):1615-28. 4.

• P. Leland, et al (2000) Mol Med; 6(3): 165–178.

5. Koller , et al (2010); Carcinogenesis 31(6), 1010-17

• 6. Strome SE, et al (2002).Clin Cancer Res.n;8(1):281-6.

7. Puri, et al (1996). Cell Immunol.10;171(1):80-6. 8. Kawakami, et al (2005) Blood; 105(9): 3707–3713. 9. Kay, et al (2005) Leuk Res.;29(9):1009-18.

• 10. Kawakami, at al (2002). Clin Cancer Res.;8(11):3503-11.
• 11. Burt, et al (2012) Clin Cancer Res;18(6):1568-77
• 12. Kioi, et al (2005) Cancer Res;65(18):8388-96
• 13. Kawakami et al (2002) Cancer Res.;62(13):3575-80.
• 14. Joshi et al (2015) Discov. Med.;20(111):273-84.

14

IL-2 Superkines: Tunable Immune Modulators

15

Secured Exclusive World Wide Rights from Stanford University

TARGET AND MECHANISM CANDIDATE POTENTIAL INDICATION(S)

MDNA109 IL-2 Super- Agonist Cancer Immunotherapy Autoimmune Diseases IL-2 Super- Antagonist MDNA209 Solid Tumors Respiratory, Fibrotic and Atopic Diseases IL4/13 Dual Super- Antagonist MDNA413

RECENT TRANSACTIONS DEAL SIZE

$2 Billion with $60M Upfront

UNDISCLOSED

$775M with $300M Upfront

UNDISCLOSED

Deep Early Stage Pipeline

Targets Validated by Multiple Big Pharma Transactions

16

$400M with $150M Upfront

Combination Therapy Produces Robust Responses

➢ MDNA109 and anti-PD-1 produce limited efficacy alone ➢ Combination treatment sufficient to cure most mice without increased toxicities

17

17

MDNA109 Synergizes With Anti-PD-1 Immunotherapy

18

Multiple Near Term Value Inflection Milestones

Pursue Accelerated Approval for rGB in 2018

Milestone Estimated Timing Commenced Enrollment in Phase 2b rGB Trial First Patient In - Phase 2b rGB Trial Commence Phase 2 Metastatic Brain Cancer Trial Q4/2017 Complete Enrollment in Phase 2b rGB Trial Q4/2017 Report rGB Phase 2b Interim Top-Line Results Q1/2018 End of Phase 2 Meeting with FDA Q2/2018 Commence IND Enabling Studies with MDNA109 Q2/2018 Pursue Accelerated Approval for rGB Q3/2018 Report Interim Top-Line Results from P2 Metastatic Brain Cancer Trial Q3/2018 Commence IND Enabling Studies with MDNA57 Q4/2018

19

USD$14M Non-Dilutive Grant Validates Platform

➢ Diligence by top-tier scientific, clinical, regulatory, chemistry manufacturing and control, intellectual property & venture capital teams ➢ Solid third-party platform validation ➢ Funds MDNA55 Phase 2b rGB clinical development and next generation pre-clinical IL-4 Empowered Cytokine program ➢ The USD$14.1M grant effectively provides 2:1 leverage on USD$7M investment1 ➢ Favorable grant repayment terms begin post-launch (low single digit royalties to a maximum payment amount of 4 times the original grant)

• 1. http://www.cprit.state.tx.us/images/uploads/rfa-172-txco.pdf

Recipient of Cancer Prevention & Research Institute of Texas (CPRIT) Grant

20

Use of Cash Resources

21

Lead Programs Funded Through 2018

Cost t Center Statu tus by end of 2018 18 Estimate ted Cost t (in Cdn Cdn)

MDNA55 Clinical Program

• Recurrent Glioblastoma (rGB)
• Metastatic Brain Cancer

Pursue Accelerated Approval Top-line Phase 2 data

$ 14,300,000 MDNA57 and MDNA109 Pre-Clinical Research

Complete PoC Studies: Ready for IND Enabling Studies

2,100,000 General and Administrative

On-going

6,000,000 Total Projected Spend $22,400,000 Balance of Grant Revenue from CPRIT

US$6.5million to be advanced

(8,700,000) Net Cash required $13,700,000 Cash available (as at 3/31/17)* $14,000,000

*As reported June 15, 2017

Capitalization

22

Publicly Listed as of March 3, 2017 ➢ Listed on the Toronto Stock Exchange Venture on March 3, 2017 at $2.00 per share following a successful Reverse Takeover ➢ Trading under the Ticker “MDNA” ➢ Funded for two years with cash on hand and funds remaining to be advanced under the CPRIT grant Number ber Issued and Outstanding 24,313,334 Fully Diluted* 28,899,096

* Fully diluted includes 3,294,105 warrants with a $2.00 exercise price and 1,291,657 stock options with a weighted average exercise price of $1.97

Medicenna Public Company Comparables

Company (Listing/Symbol) Price

(03-Jul-2017)

Market Cap (MM) Enterprise Value (MM) Lead Indication (Stage) ZIOPHARM Oncology, Inc.

(NASDAQ:ZIOP)

US$6.15 $873.9 $936.8

Breast Cancer (PhII), Recurrent or Progressive Glioblastoma (Ph I)(w/ CED*)

Agenus Inc.

(NASDAQ:AGEN)

US$4.00 $396.5 $384.3

Newly Diagnosed Glioblastoma (Ph II)

Tocagen Inc.

(NASDAQ:TOCA)

US$12.12 $240.1 $141.8

Recurrent High Grade Glioma (Ph II)

Stemline Therapeutics, Inc.

(NASDAQ:STML)

US$9.25 $232.3 $142.7

Recurrent Glioblastoma (Ph II)

Newlink Genetics Corporation

(NASDAQ:NLNK)

US$7.50 $219.2 $107.4

Malignant Brain Tumors (Ph II)

Kadmon Holdings, Inc.

(NYSE:KDMN)

US$3.98 $206.4 $234.2

Recurrent Glioblastoma (Ph II)

Vascular Biogenics Ltd.

(NASDAQ:VBLT)

US$4.50 $120.8 $81.2

Recurrent Glioblastoma (Ph III)

Diffusion Pharmaceuticals Inc.

(NASDAQ:DFFN)

US$2.40 $24.8 $15.0

Newly Diagnosed Glioblastoma (Ph II)

Average $289.2 $255.4 Median $225.8 $142.2

Medicenna Therapeutics1

(TSXV:MDNA)

C$1.95 $36.5

(C$47.4M)

$25.7

Recurrent Glioblastoma (Ph II)

(1) Medicenna market cap estimate based on current basic shares O/S and current share price. Enterprise value estimate based on net debt as of Mar. 31, 2017 Source: FactSet & Company filings

23

All amounts in USD, unless noted otherwise

Seasoned Management and Experienced Board

Management agement Team

Fahar ar Merch chan ant, t, PhD: : Chairman, President & CEO

Former CEO Sophiris Bio (TSX); Former Director, President & CTO at KS Biomedix (LSE); Founder, President & CEO of Avicenna Medica and IntelliGene Expressions

Jay Stoudemi demire, e, PhD: D: Chief Scientific Officer

Former VP Preclinical Development, Regulatory, and QA at Mirna Therapeutics, previously at Genentech, Ascenta, Chugai-Roche, Cytel, Genetics Institute, and Xoma

Elizabeth abeth Willi lliam ams, s, CPA,CA ,CA: : Chief Financial Officer

Former VP Finance & Admin and interim CFO at Aptose (TSX and Nasdaq); Previously with Ernst & Young

Martin tin Bexon, , MD: : Head of Clinical Development

Former Medical Director at CSL Behring; Medical Director at Hoffman La Roche (UK and Switzerland)

Nina a Merch chan ant, t, MESc.: .: Chief Development Officer

Former SVP Development at Sophiris Bio; Formerly VP Development at KS Biomedix (LSE); Previously at Avicenna Medica, IntelliGene, Pharmacia and Sanofi Pasteur

Patrick ick Ward, d, MBA: : Chief Operating Officer

Former COO of Aviara Pharma; President/COO at Ocusoft, Executive Director at Encysive Pharma

Shafi fiqu que e Fidai, ai, PhD: : Head of Corp Development

Former VP of Business Development at Sophiris Bio; Formerly with Xenon Pharma, Chromos

Board rd of Directors ectors

Fahar ar Merch chan ant, t, PhD Chair airman man, , Presi siden ent t & CEO Alber ert t Beraldo aldo, , CPA, , CA Indep depen enden dent t Dir irector ctor Founder, President and CEO of Alveda Pharmaceuticals until its acquisition by Teligent, Inc. (NASDAQ: TLGT); Former President and CEO of Bioniche (TSX) and Director of Telesta (TSX); Currently Independent Director of Helix Biopharma (TSX). Chan andra dra Panch chal, al, PhD Indep depen enden dent t Dir irector ctor Founder, Chairman and CEO of Axcelon; Former Co-Founder, President, and CEO of Procyon Biopharma Inc (TSX); Former Senior Executive VP of Business Development at Ambrilia Biopharma Inc. (TSX) Andr drew ew Stron

• ng,

, JD Indep epen enden ent t Dir irector ctor Partner at Pillsbury Winthrop Shaw Pittman - leading the Life Sciences Team in Houston, TX. Formerly General Counsel and Compliance Officer for the Texas A&M University System. Led formation of bio-manufacturing company, Kalon Biotherapeutics; CEO of Kalon until its sale to FujiFilm Diosynth Biotech. Director of Ashford Hospitality Prime (NYSE) Nina a Merch chan ant, t, M.E.S .Sc Director ector, , Chief ief Develo elopmen pment t Office icer

16

World Class Advisors and Collaborators

Colla labora borator tors & I Inven vento tors rs Clinical ical & S Scie ientific tific Advi viso sors

Joh

• hn Samps

pson, MD, D, PhD, D, MBA BA Duke Unive iversity sity:

Principal Investigator and Expert in Drug Delivery to the Brain

Sam Den enmea eade de, MD D

Johns Hopkins University: Professor of Oncology: Targeted therapies for cancer

Nich chol

• las

as Butowsk

• wski,

i, MD UCSF: F:

Principal Investigator; Novel therapies for brain cancer

Guid ido

• Kroem

emer, er, MD, D, PhD D Unive iversity sity of Pari ris: s:

Chair: SAB and Expert in Cancer Immunotherapy

Ralph lph Small alling, ing, MSc Regulatory gulatory Adv dvisor isor:

Former VP Regulatory Affairs at Amgen; Filed 40 INDs; 5 NDAs

Micha ichael el Rose senblu blum, m, PhD D MD D Ande derson rson Cance cer Center ter

Head, , Immunoph

• phar

armac acol

• logy
• gy and

d Targete geted d Ther erapy apy Collaborator: MDNA57

Raj j Puri ri, MD USFDA FDA

Director ector at CBER Inventor of MDNA55

Aar aron

• n Ring,

g, MD, D, PhD Yale le Unive iversity sity

Asst.

• st. Prof

f Immunobiol biology gy & Cancer cer Biology

• gy

Co-Inventor of IL-2 Superkines

Chris is Garci rcia, PhD Stan anford ford Universit iversity

Co-Inventor of IL-2, IL-4 and IL-13 Superkines

Haya ya Lobe berbo rboum Galsk lski.

• i. PhD

Hebrew brew Unive iversity sity of Jerus erusale alem

Inventor of Fully Human Payloads

25

26

Medicenna: Corporate Highlights

Tha hank nk You

• u
• ne

ne Target: inf nfinite nite Hope™

www.medicenna.com