july 2019 institutional presentationfilecache.investorroom.com/mr5ircnw_medicenna/180... · 2019....

TSX: MDNAOTCQB: MDNAF

©2018 Medicenna. All Rights Reserved.

Q3 2019

Forward-Looking Statements

Q3 2019 Medicenna Corporate Overview

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”, or 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 24, 2019. Should one or more of 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

Q3 2019 3

MDNA55 — LEAD PROGRAM SUPERKINE PLATFORM CORPORATE SNAPSHOT

TARGETS IL4R: EXPRESSED IN GBMCompelling Clinical Data in 112 rGBM

Patients

ORPHAN/FAST TRACK Orphan Drug (FDA, EMA)

Fast Track (FDA)

IL-2; IL-4; IL-13Tunable cytokines

MULTIPLE NEAR TERM MILESTONES

PHASE 2B TRIAL ENROLMENT COMPLETED

4,000Brain tumor patients can be treated with 1 gram

of MDNA55

MDNA109: BEST IN CLASS IL-2 SUPER-

AGONIST

WORLD CLASS EXPERTISE

Clinical and scientific advisors, collaborators and inventors

250,000Annual incidence

of GBM and metastatic brain cancer2

$2 BILLIONPotential market of MDNA55 market for brain cancer ($US)1,3

EXCEPTIONAL CD122 SELECTIVITY

Boosts cancer killing immune cells

13 PATENT FAMILIESStrong technology platform protection

1. BioXcel Strategic Analysis Report, 2014.2. Globocan 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide 2012.3. Decision Resources, Inc Glioblastoma Report, Sept 2013.

Medicenna Corporate Overview

4

Multiple Near-Term Value Inflection Milestones


MDNA55• Completed enrollment in Phase 2b rGBM trial• Reported promising rGBM Phase 2b preliminary top-line results• End of Phase 2 meeting with FDA• Commence Phase 2a clinical trial in newly diagnosed glioblastoma

MDNA109• Select lead candidate with extended half life• Complete dose range finding studies for pre-IND meeting with FDA• Complete IND enabling studies in preparation for Phase 1 clinical trial

Phase 2 clinical results for MDNA55

in rGBM

MDNA109 to be IND Ready

5

Financial Snapshot


• Funding to date: CDN$20 M + Up to US$14.1M Non-Dilutive CPRIT Grant

• Cash and cash receivable balance at March 31, 2019: CDN$4.8 million

• Available to be drawn under CPRIT grant: Up to US$2.3 million

• Total available cash excluding warrant exercises: Up to CDN$7.5 million

• No Debt, No Preferred Shares

Issued and Outstanding28,802,792

Fully Diluted37,048,220

TSX: MDNAOTCQB: MDNAF

MDNA55A Powerful Molecular Trojan Horse Targeting Glioblastoma

MDNA55: A Powerful Molecular Trojan Horse

7

Targeteddelivery of toxin

Tumor Targeting Domain

Circularly Permuted Interleukin-4 (cpIL-4)

ENDOCYTOSIS

FURIN PROTEASEADP RIBOSYLATION

Inhibit Protein Synthesis

CELL DEATH

NUCLEUS

Tumor Killing “Cytotoxic” DomainCatalytic domain of Pseudomonas Exotoxin A (PE)

• Bypass the BBB via convection enhanced delivery (CED)

• Potently toxic to tumor cells

• Simultaneously purges the tumor microenvironment (TME)


> 300 Patient Biopsies Analyzed Show IL-4R Over-Expression1-7

8

Targeting the IL-4 Receptor in Brain Tumors

Glioblastoma

76%Mixed Adult

Glioma

>83%Mixed Pediatric

Glioma

76%Pediatric DIPG

71%

Medulloblastoma

100%Adult Pituitary

Adenoma

100%Meningioma

77%Normal Brain

Tissue

0%1. Joshi BH, et. al. Cancer Res 2001;61:8058-8061.2. Puri RK, et. al., Cancer Res 1996;56:5631-5637. 3. Kawakami M, et. al., Cancer. 2004 Sep 1; 101(5):1036-42. 4. Berlow NE, et al. PLoS One. 2018 Apr 5; 13(4):e0193565.

5. Joshi BH, et. al. British J of Cancer (2002) 86, 285 –291.6. Chen L, et al. Neurosci Lett. 2007 Apr 24; 417 (1):30-5.7. Puri S, et. al., Cancer. 2005 May 15; 103(10):2132-42.


IL4R Predicts Poor Survival in GBM

9

Kohanbash G et al. Cancer Res 2013;73:6413-6423

IL4R +/+ (n=10); symptom-free survival = 55.5 daysSymptom-free survival = 90 daysIL4R -/- (n=15); symptom-free survival = 90 days

Survival in Subjects with GBM

-- No expression of IL-13Rα1 (n=32): mOS = 693 days-- High expression of IL-13Rα1 (n=65): mOS = 350 days

Survival in Glioma Mouse Model

Han J. and Puri R. J of Neuro-Oncology (2018) 136:463–474

Expression of IL-13Rα1 mRNA positively correlates with IL-4Rα indicating that these two receptors may form a complex in GBM.

Medicenna Corporate OverviewQ3 2019

10

TME-Infiltrating MDSCs Express IL4R and Predict Poor Survival in GBM

MDSC gene signature (based on the combined positive expression of CD11b,

CD33, CD45, CD244, and CXCR2) negatively correlates with GBM patient

prognosis. Statistical significance of survival was based on log-rank analysis.

Otvos B et. al., (2016). Stem Cells 34:2026–2039Surface expression of IL-4Ra on tumor-infiltrating and splenic CD11b+/Gr-1+

MDSCs from GL26 tumor-bearing mice.

TME-MDSCs show 12-fold increase in IL-4R⍺expression compared to splenic myeloid cells

p < 0.001

Kamran N, et. al., (2017). Mol Ther 25:232-248


MDNA55 Treatment

Direct infusion into tumor

convection enhanceddelivery (CED)

75%

INOPERABLE rGBM

11

Treatment Pathway for GBM

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

DIAGNOSISADJUVANT TEMODARSURGERY

(85-90%) 55% of GBM Temodar-Resistant*

RADIOTHERAPY TEMODAR

RELAPSE

25%

OPERABLE rGBM

GBM IS UNIFORMLY FATAL – VIRTUALLY ALL TUMORS WILL RECUR (rGBM)

MDNA55 treatment can also provide benefit in newly diagnosed and

operable rGBM settings


Convection-Enhanced Delivery (CED)

Bypassing the BBB with Image-Guided Direct Drug Delivery

12

Treatment duration of 1 day

Image-guidedcatheter placement

Catheters prevent backflow

Real-time monitoring ensures tumor coverage


Open-Label Single Arm Study in Recurrent GBM Patients (NCT02858895)

13

MDNA55-05 Phase 2b Study Design Summary

DIAGNOSIS PLANNING TREATMENT FOLLOW UP


14

Promising Survival of MDNA55 Compared to Approved Therapies for rGBM

Monotherapy Population (n) SurvivalmOS (mos.)

MDNA55-05 Low Dose(median 63 µg) rGBM (n=21) 11.8

Avastin1 rGBM (n=85) 9.2

Avastin2 rGBM (n=50) 8.0

Lomustine2 rGBM (n=46) 8.0

Temozolomide3 rGBM (n=31) 5.6

Temozolomide4 rGBM (n= 792) NA

MDNA55-05 High Dose Cohort(median 180 µg)

Enrolment completed; currently collecting survival data

1 Friedman et al., Bevacizumab Alone and in Combination With Irinotecan in Recurrent Glioblastoma. J Clin Oncol. 2009 Oct 1;27(28):4733-40.2 Taal et al, Single-agent bevacizumab or lomustine versus a combination of bevacizumab plus lomustine in patients with recurrent glioblastoma (BELOB trial): a randomisedcontrolled phase 2 trial. Lancet Oncol 2014 Aug;15(9):943-533 Kim et al., Outcome of salvage treatment for recurrent glioblastoma. J Clin Neuroscience 22 (2015) 468–473, 2015.4 Chen et al., The efficacy of temozolomide for recurrent glioblastoma multiforme (Meta-analysis). Eur J Neurol, 2013 Feb; 20(2):223-30.


0 100 200 300 400 500 600 700 8000

50

100

Days elapsed

Perc

ent s

urvi

val

IL4R+ (H-Score > 75); n=8

IL4R- (H-Score ≤ 75); n=10

Log-Rank Test p-value = 0.0147

IL4RHigh (H-Score > 75); n=8

IL4RLow (H-Score ≤ 75); n=10

Time Since MDNA55 Treament (Days)

IL4R+ve is Associated with Longer Survival Following MDNA55 Treatment

15

IL-4R Status

mOS(months) OS-6 OS-9 OS-12

IL4R+ve 15.2 100% 88% 60%

IL4R-ve 8.1 70% 30% 20%

IL4R+ve (H-Score > 75); n=8

IL4R-ve (H-Score ≤ 75); n=10


16

Pseudo-Progression in GBM Following Immunotherapy

https://www.immunooncologyhcp.bmsinformation.com/clinical-expectations/pseudo-progression


Immunotherapy Response Assessment in Neuro-Oncology (iRANO)

17

Patient classified as PD

Duration on Immunotherapy Regimen

> 6 months ≤ 6 months

Continue on study as long as no significant clinical decline

Repeat imaging after initial imaging progression and compare to the new reference scan (Nadir)

CR, PR, or SD Confirms PD

Chukwueke UN et al., CNS Oncol. 2019 Mar 1;8(1):CNS28

(CR): 100% volume decrease(PR): ≥ 65% volume decrease(SD): < 65% volume decrease to

< 40% volume increase(PD): ≥ 40% volume increase


Tumor response or stabilization seen in 14 of 19 evaluable subjects = Disease control rate of 74%

18

Disease Control Seen from Nadir in Low Dose Cohort

IL4R PositiveIL4R NegativeNo IL4R data available


Longer Survival is Associated with Stable Disease or Better

19

ResponseStatus

mOS(months)

SD or better 13.7PD 8.5

p-value 0.0635

0 200 400 600 8000

50

100

Best Response from Nadir (Survival)

Days Since MDNA55 Treatment

Per

cent

sur

viva

l

Progressive Disease (n=5)

Stable Disease or Better (n=14)



20

Disease Control Seen from Nadir in High Dose Cohort




21

Disease Control Seen with MDNA55 from Nadir



MDNA55 Brain Cancer Market Opportunity

Tumor Type Annual Incidence1 Projected Market2

Recurrent Glioblastoma (rGBM) 33,300 $650M

Metastatic Brain Cancer3 91,500 $1.30B

Pediatric Glioma 3,800 $50M

Total 133,500 $2.0B

22

1. GLOBOCAN 2012 http://globocan.iarc.fr/Default.aspx2. U.S., Europe and Japan3. Metastatic Brain Cancer numbers from colon, breast and kidney cancer only

Market Size Estimated at $2B Annually


>2000 Patient Biopsies Analyzed Consistently Show IL4R Over-Expression

23

Future Opportunity: 1 Million IL4R Cancers Annually

Glioblastoma

76%

Bladder

73%Breast

82%Colorectal

89%Head and Neck

75%

NSCLC

79%Mesothelioma

96%Ovarian

60%Pancreatic

60%


MDNA109: IL-2Super Agonist for Cancer Immunotherapy

Proleukin (hIL-2): first targeted immunotherapy

25

Rationale for an IL-2 Superkine Agonist (MDNA109)

• Proleukin is approved for skin and renal cancer

• High-dose Proleukin is required to stimulate effector cells

• IL-2 preferentially stimulates the high-affinity receptor, causing:

• Activation of Tregs; Tregs abrogate anti-tumor responses

• Extreme toxicity – hard to complete full course of therapy

• Treatment in Intensive Care Unit

Has very high affinity for IL-2

High-affinity receptor

IL-2

(CD25)

(CD122)

(CD132)


MDNA109: 200-fold Higher Affinity for CD122 (IL-2Rβ) Than Native IL-2

26

• Mutations in the core of IL-2 improves

affinity to CD122 on CD8 T cells and NK

cells

• CD122 affinity is key for the activation of

immune cells responsible for cancer killing

(CD8+ T cells, naïve T cells, NK cells,…)

IL-2Rβ binding site

Helix C

Helix A

Helix B

Helix D

Levin, Bates, and Ring et. al, Nature, 2012

SPR data (nM) CD25 CD122

IL-2 6.6 280

MDNA109 6.6 1.4

Similar affinity to

CD25

200 X increase affinity to

CD122


Stimulation of Intermediate Affinity Receptor Required for Anti-Tumor Effect

27

Rationale for an IL-2 Superkine Agonist (MDNA109)

• IL-2 Superkine (MDNA109) signals via the intermediate affinity receptor

• Preferentially activates effector T cells that attack tumor cells (naïve T cells, NK cells, and CD8 T cells)

• Mediates anti-tumor effect

• Derive therapeutic benefits without the underlying toxicity

Weak Signaling

Intermediate affinity receptor

IL2 MDNA109

Signaling

(CD122)(CD132)

(CD122)(CD132)


MDNA109 More Potent and Less Toxic then Wild-type IL-2

28

Levin, Bates, and Ring et. al, Nature, 2012

Reduced Adverse Effects in Vivo

Selective Expansion of CD8+ T Cells in Vivo

10

5

0

15

Cel

ls p

er s

plee

n (x

106 )

PBSIL-2

MDNA109

PBSIL-2 MDNA109

0.20

0.15

0.10

0.25Pu

lmon

ary

wet

wei

ght (

g) 0.30

PBS IL-2

MDNA109

Anti-tumor response against pulmonary B16F10 nodules. B6 mice received 3x 105 B16F10 cells intravenously, followed by five daily injections of either PBS, 20 μg IL-2, or 20 μg MDNA109, starting three days after tumor injection. Shown are photographs of fixed whole lungs on day 16 after tumor injection.

CD8+Treg


5 10 15 20 25 30 35 40 450

500

1000

1500

2000

Days Post-Implant

Mea

n Tu

mor

Vol

ume

(mm

3 )

PBSanti-PD-1MDNA109 (5 ug q.d.)MDNA109 (25 ug q.d.)anti-PD-1 + MDNA109 (5 ug q.d.)anti-PD-1 + MDNA109 (25 ug q.d.)

9/10 cures

1/10 cures

0/10 cures

29

MDNA109 Synergizes with Anti-PD-1 Immunotherapy

C57BL/6 mice were implanted with 106 MC38 murine colon tumor cells

subcutaneously above hind limb. When tumor reached approximately 125mm3,

animals were randomized into groups and dosing was initiated by intraperitoneal

injections; q.d. = daily. **p=0.01; ***p=0.001

**

**

**

***

Combination Therapy Produces Robust Dose-Dependent Responses in MC38 Colon Cancer Model

• MDNA109 and anti-PD-1 are not

fully efficacious alone

• Dose-dependence observed with

monotherapy and anti-PD-1

• Combination treatment sufficient to

cure most mice

• Increased efficacy of combination

was well-tolerated


0 20 40 60 80 100 1200

500

1000

1500

2000

2500

Study Day

Tum

or v

olum

e (m

m3 )

30

TxStart

***

****

****

MDNA109 Synergizes with Anti-CTLA-4 Immunotherapy

MDNA109 (1mg/kg) and IL2 (1mg/kg) administered IP daily x5 for 2 cycles; anti-CTLA4 (200 µg) administered IP twice weekly for two cycles; average tumor volume at treatment start was 18 mm3; asterisks indicate significant differences as compared to Isotype control group (*p<0.05; **p<0.01; ***p<0.001; ****p<0.0001).

Combination Therapy Produces Robust Tumor Responses in CT26 Colon Cancer Model

• MDNA109 and anti-CTLA4 are not fully efficacious alone

• Dramatically superior response when compared to IL-2 combination

• MDNA109 combination with anti-CTLA4 is sufficient to cure most mice

• MDNA109 can synergize with checkpoint inhibition to fully unleash the immune system against cancer


40 50 60 70 80 90 1000

500

1000

1500

Days Post Implant

Tum

or v

olum

e (m

m3 )

Secondary Challenge

TertiaryChallenge

MDNA109-LA + Anti-CTLA4 (n=8)

MDNA109-LA Synergizes with Anti-CTLA4 Immunotherapy

31

8 CR (100%)

Vehicle (n=9)

0 10 20 30 40 50 60 70 80 90 1000

500

1000

1500

2000

Days Post Implant

Tum

or V

olum

e (m

m3 )

Dose

Anti-CTLA4 (n=9)

0 10 20 30 40 50 60 70 80 90 1000

500

1000

1500

2000

Days Post Implant

Tum

or V

olum

e (m

m3 ) Dose

MDNA109-LA (n=9)

0 10 20 30 40 50 60 70 80 90 1000

500

1000

1500

2000

Days Post Implant

Tum

or V

olum

e (m

m3 )

Dose

MDNA109-LA+ Anti-CTLA4 (n=9)

0 10 20 30 40 50 60 70 80 90 1000

500

1000

1500

2000

Days Post Implant

Tum

or V

olum

e (m

m3 )

Dose

6 CR (67%)2 PR (22%)

6 CR (75%)

1

2

Primary CT26 tumor challenge

3

Secondary challenge with

2x106 CT26 cells re-injected into

left flank

2

Tertiary challenge with

2x106 CT26 cells re-injected into

right flank


MDNA109-LA + Anti-CTLA-4 Immunotherapy Improves Survival

32

Survival Curve

0 20 40 60 80 1000

25

50

75

100

Days Post Implant

Per

cent

sur

viva

l


MDNA109-LA1: Does not Bind to CD25 (IL-2⍺)

33

Surface Plasmon Resonance (SPR) Assay


MDNA109-LA1 Selectively Activates CD8 T Cells vs. Tregs

34

STAT5 Phosphorylation Assay Using Human PBMCs

0.01 0.1 1 10 100 1000 10000 1000000

20

40

60

80

100

Tregs

Conc (pM)

pSTA

T5+

(%)

IL2LAMDNA109LAMDNA109LA1

1 10 100 1000 10000 1000000

20

40

60

80

100

Conc (pM)

pSTA

T5+

(%)

CD8+ CD25-

IL2LA

MDNA109LA1MDNA109LA

IL2L

A

MDNA109L

A

MDNA109L

A11

10

100

1000

10000

CD

8/Tr

eg E

C50

rat

io

5,800

170

3


8 10 12 14 16 18 200

250

500

750

1000

1250

Days Post Implant

Tum

or V

olum

e (m

m3 )

0 2 4 6 8 10 12 14 16 18 20 220

500

1000

1500

2000

2500

3000

3500

Days Post Implant

Tum

or v

olum

e (m

m3 )

MDNA109-LA1: Similar In Vivo Potency But Superior PK Profile

35

Treatment Start

Treatment Start

MDNA109-LA1 enables effective B16F10 tumor control with a once weekly schedule.

MDNA109-LA enables effective B16F10 tumor control with a biweekly schedule, a similar schedule as anti-PD-1 antibodies used in mice.


MDNA109 Variants are Not Immunogenic

36

Immunogenicity Assessment using the Epibase™ in silico T-cell epitope screening platform to predict

whether peptides derived from a given protein of interest bind to the HLA class II histocompatibility antigen,

DRB1 beta chain. Scores are generated and compared to chicken ovalbumin protein (a xenoantigen known

to trigger a potent immune response) as a positive control.

Compound DRB1 Score Proleukin 310

MDNA109 213

MDNA109-LA 296

MDNA109-LA1 555

Chicken ovalbumin (pos control) 4404


37

MDNA109-LA1: A Best-in-Class Long Acting IL-2/IL-15 Cytokine for Cancer Immunotherapy

PRODUCT MANUFACTURINGCD122

POTENCYPROTEIN

VERSATILITYHALF-LIFE SAFETY IMMUNOGENICITY

Proleukin® Simple Low High Minutes Poor Low

NKTR-214 Complex Low Low Days Better than IL-2 Low

ALKS 4230 Simple Low Low Minutes toHours

Better than IL-2 N/A

Synthorins Complex Low Low Potentially Days N/A Potentially High

MDNA109-LA1 Simple High HighPotentially

DaysBetter than

IL-2Potentially Low


Q3 2019 38

MDNA55 — LEAD PROGRAM SUPERKINE PLATFORM CORPORATE SNAPSHOT

TARGETS IL4R: EXPRESSED IN GBMCompelling Clinical Data in 112 rGBM

Patients

ORPHAN/FAST TRACK Orphan Drug (FDA, EMA)

Fast Track (FDA)

IL-2; IL-4; IL-13Tunable cytokines

MULTIPLE NEAR TERM MILESTONES

PHASE 2B TRIAL ENROLMENT COMPLETED

4,000Brain tumor patients can be treated with 1 gram

of MDNA55

MDNA109: BEST IN CLASS IL-2 SUPER-

AGONIST

WORLD CLASS EXPERTISE

Clinical and scientific advisors, collaborators and inventors

250,000Annual incidence

of GBM and metastatic brain cancer2

$2 BILLIONPotential market of MDNA55 market for brain cancer ($US)1,3

EXCEPTIONAL CD122 SELECTIVITY

Boosts cancer killing immune cells

13 PATENT FAMILIESStrong technology platform protection

1. BioXcel Strategic Analysis Report, 2014.2. Globocan 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide 2012.3. Decision Resources, Inc Glioblastoma Report, Sept 2013.

Medicenna Corporate Overview

39

Multiple Near-Term Value Inflection Milestones


MDNA55• Completed enrollment in Phase 2b rGBM trial

• Reported promising rGBM Phase 2b preliminary top-line results

• End of Phase 2 meeting with FDA

• Commence Phase 2a clinical trial in newly diagnosed glioblastoma

MDNA109• Select lead candidate with extended half life

• Complete dose range finding studies for pre-IND meeting with FDA

• Complete IND enabling studies in preparation for Phase 1 clinical trial

Phase 2 clinical results for MDNA55

in rGBM

MDNA109 to be IND Ready

Thank You!Elizabeth WilliamsChief Financial Officer

www.medicenna.com

Fahar Merchant, PhDPresident & CEO

Supplementary Slides

KD (MDNA109LA1+CD25)=nobinding

KD (IL2LA+CD25)=0.7nM

KD (LAMDNA109+CD25)=2 nM

KD (MDNA109LA+CD25)=3nM

Long-Acting MDNA109 Does not Bind CD25

MDNA109-LA1 does not bind to CD25

THOR-707 does not bind CD25

NKTR-214 shows reduced affinity to CD25

Charych D. et al, PLOS ONE, 2017

Milla, M. et al, Abstract P417, SITC 2018

ILR⍺ (CD25) KD IL2 = 8.6 nMKD 1-PEG-IL2 = 190 nMKD 2-PEG-IL2 = 487 nM

KD = 1.7 nM

Q3 2019 Medicenna Corporate Overview 42

Long-Acting MDNA109 Retains Powerful CD122 Binding Compared to IL2

43

MDNA109-LA1 binds to CD122 with high affinity

THOR-707 shows reduced affinity to CD122

NKTR-214 shows reduced affinity to CD122

Charych D. et al, PLOS ONE, 2017

ILRβ (CD122)


KD IL2 = 239 nMKD 1-PEG-IL2 = 1770 nMKD 2-PEG-IL2 = 3952 nM

KD = 360 nM

LA-MDNA109

MDNA109-LA1

MDNA109-LA2

MDNA109-LA

IL2-LA


Long-Acting MDNA109 Shows Superior Potency in PBMC Studies

44

THOR-707 increases EC50of both Tregs and CD8

0.01 0.1 1 10 100 1000 10000 1000000

20

40

60

80

100

CD4+ Tregs

Conc (pM)

pSTA

T5+

(%)

IL2-FcMDNA109FEAA-Fc

Protein EC50 (pM)

IL2-Fc 0.7678

MDNA109FEAA-Fc 241.4

Protein EC50 (pM)

IL2-Fc 2595

MDNA109FEAA-Fc 597

1 10 100 1000 10000 1000000

20

40

60

80

100

Conc (pM)

pSTA

T5+

(%)

CD8+ Teff

IL2-FcMDNA109FEAA-Fc

Long-Acting MDNA109 increases EC50 of Tregs but lowers EC50 of CD8 T cells

IL2-LAMDNA109-LA1

IL2-LAMDNA109-LA1



Long-Acting MDNA109 Show Better Potency in Combination with ICI in CT26 Model

45

Charych, D. et al, Clin Cancer Res, 2016


Long-Acting MDNA109 Shows Better Survival in Combination with ICI in CT26 Model

46

MDNA109-LA + ICIOverall Survival (n=9)

0 20 40 60 80 1000

25

50

75

100

Days Post Implant

Per

cent

sur

viva

l

THOR-707 + ICIOverall Survival (n=14)

MDNA109-LA 2.5 mg/kg IP 2x/week

MDNA109-LA + Anti-CTLA4 IP 2x/week

H.C. Wainwright Global Life Sciences Conference, London, April 2019


july 2019 institutional presentationfilecache.investorroom.com/mr5ircnw_medicenna/180... · 2019....

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