mdna q4 2020 september · 2020. 10. 2. · forward-looking statements q4 2020 medicenna corporate...

Nasdaq: MDNATSX: MDNA

©2020 Medicenna. All Rights Reserved.

Q4 2020

Forward-Looking Statements

Q4 2020 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, including the Annual Information Form dated May 14, 2020. 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

Company Overview

Nasdaq MDNA

TSX MDNA

Headquarters Toronto, CA

Cash CDN $40.6 million (as of June 30, 2020)

Debt $0

Preferred Shares 0

Cash Runway Funded through 2022

Issued and Outstanding 48,814,933

Fully Diluted 60,016,733

“Medicenna is focused on fine tuning cytokine signaling to better direct the immune response against a patient’s disease.

3Medicenna Corporate OverviewQ4 2020

Candidate Indication Discovery Preclinical Phase 1 Phase 2 Pivotal

MDNA55IL-4 Toxin

Fusion

Recurrent Glioblastoma (GBM)

MDNA11IL-2 Super

Agonist

Cancer Immunotherapies

MDNA413IL-4/13 Super

AntagonistSolid Tumors

MDNA132IL13Rα2 selective

IL-13Solid Tumors

Expanding Pipeline Anchored by MDNA55 and MDNA11

4Medicenna Corporate OverviewQ4 2020

Multiple Near-Term Value Inflection Milestones

5Medicenna Corporate Overview

End of Phase 2 Meeting with FDA

MDNA55

MDNA11 to be IND Ready

MDNA11

CORPORATE

H2 2020 2021

End of Phase 2 meeting

with FDA

Pre-IND Meeting

Nasdaq Listing Strengthen Management and

Advisory Team

Initiate Phase 1 monotherapy

study in mid-2021

Q4 2020

Pursue Regional or Global

Partnering and Collaboration Opportunities

MDNA11IL-2 Super Agonist for Cancer Immunotherapy

7Q4 2020 Medicenna Corporate Overview

Targeting IL-2 Receptor Subunits in Cancer Therapy

Wild type IL-2 preferentially stimulates CD25

IL-2 Receptor

IL-2

(CD25)

(CD122)

(CD132)

The IL-2 receptor (IL-2R) consists of three subunits

• CD25 (IL-2Rα)

• CD122 (IL-2Rβ)

• CD132 (IL-2Rγ)

Stimulation of CD122

• Key for the activation of cancer killing immune cell such as CD8+ T cells, naïve T cells, and NK cells.

Stimulation of CD25

• Leads to activation of immunosuppressive Tregs, which abolishes the anti-tumor response

• Causes extreme toxicity

Proleukin (recombinant human [rh] IL-2) is approved for the treatment of metastatic melanoma and renal cell carcinoma

8

Improved IL-2 Variants are Needed

Medicenna Corporate Overview

Proleukin

Poor safety profile due to selective stimulation of CD25

• Patients are often unable to receive a full course of therapy

• Patients must be treated in the intensive care unit

Poor pharmacokinetic profile

• Half-life on the order of minutes

• Requires dosing every 8 hours for 9 days

Have low CD122 affinity• Limits efficacy

Often require complex manufacturing processes

• Increases cost of goods

Competing IL-2 variants

Q4 2020

Superkines: First-Generation IL-2 Variants via MDNA109 Platform

9

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


Medicenna’s MDNA109 platform produced firstgeneration IL-2 variants with 200-fold higheraffinity for CD122 (IL-2Rβ), which is key for theactivation of immune cells responsible for cancerkilling (CD8+ T cells, naïve T cells, NK cells), yetsimilar affinity to CD25

Similar affinity to CD25

200X increased affinity to CD122

MDNA11: Next-Generation IL-2 Superkine Derived from MDNA109

10Q4 2020 Medicenna Corporate Overview

MDNA 109

Enhanced PK

MDNA 109 - AlbMDNA 109 - Fc

Enhanced Selectivity

MDNA11(MDNA109FEAA-Alb)

MDNA19(MDNA109FEAA-Fc)

MDNA11 is a potentially best-in-class next-generation IL-2 superkine with superior

CD122 binding without CD25 affinity, thereby preferentially stimulating cancer killing effector

T cells and NK cells when compared to competing IL-2 programs.


No CD25 Binding and Enhanced Affinity for CD122 Compared to rhIL-2

0 200 400 600 800 1000 1200

0.0

0.2

0.4

0.6

0.8

1.0

1.2

Time (sec)

CD

25 B

LI S

igna

l (nm

) 200 nM

100 nM

50 nM

25 nM

12.5 nM

6.25 nM

50 nM (No CD25 control)

KD = 24 ± 1 nM

CD

25 B

indi

ngC

D12

2 B

indi

ng

CD

25 B

indi

ngC

D12

2 B

indi

ng

Q4 2020 11

MDNA11rhIL-2


Competing IL-2 Variants NKTR-214 & THOR-707 Weak CD122 Binders

IL2Rβ (CD122)

THOR-707: Reduced Binding to IL2Rβ (CD122) 1-PEG-IL2 (Most Active Form of NKTR-214)is a Weak IL2Rβ (CD122) Binder

Q4 2020 12


THOR-707

MDNA11

MDNA11: Enhanced Selectivity & Potency Toward Immune Effector Cells

13

Naïv

e C

D8+

T-c

ells

0.01 0.1 1 10 100 1000 10000 1000000

20

40

60

80

100

Conc (pM)

pSTA

T5+

(%)

Signaling in CD8+ T Cells

rhIL-2MDNA11

0.01 0.1 1 10 100 1000 10000 1000000

20

40

60

80

100

Conc (pM)

pSTA

T5+

(%)

MDNA11

MDNA11rhIL-2

EC50 pM

rhIL-2 3390

MDNA11 460

EC50 pM

rhIL-2 5.6

MDNA11 160

Compared to WT IL-2

(proleukin) MDNA11

exhibits both:

Enhanced potency toward

anti-tumor CD8+ T-cells

Reduced potency toward

pro-tumor Treg cells

Compared to WT IL-2

(proleukin) THOR-707 has:


anti-tumor CD8+ T-cells


pro-tumor Treg cells

Naïv

e C

D8+

T-c

ells

Tre

gs

Tre

gs

Q4 2020

Superior Effect in Combo with Checkpoint Inhibitor in CT26 Tumor Model

14

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

MDNA11 (5 mg/kg, IP, 1x/wk for 2 wks)Anti-CTLA4 (4F10, 100 µg, 2x/wk for 2 wks)

Average tumor size at initiation of dosing ~ 90 mm3

NKTR-214 (0.8 mg/kg, IP, 1x/9 days for 3 doses)Anti-CTLA4 (4F10, 100 µg, 2x/wk through day 18)

Average tumor size at initiation of dosing ~ 100 mm3

Treatment duration

0 5 10 15 20 25 30 35

0

500

1000

1500

2000

2500

3000

Days Post Implant

Tum

or V

olum

e (m

m3 )

Vehicle

Anti-CTLA4

MDNA11 + Isotype

MDNA11 + Anti-CTLA

Vehicle + IsotypeAnti-CTLA4

MDNA11 + Anti-CTLA4MDNA11

Days0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75

0

500

1000

1500

2000

2500

3000

Tum

or V

olum

e (m

m3 )


MDNA11 + Anti-CTLA4 (n=10/group) NKTR-214 + anti-CTLA4 (n=12/group)

Days

Q4 2020

MDNA11 + ⍺CTLA4 Inhibits Tumor Growth & Induces Memory Response

15

Vehicle + Isotype

0 25 50 75 100 125 150 175 2000

500

1000

1500

2000

2500

3000

3500

Days Post Implant

Tum

or v

olum

e (m

m3 )

Vehicle

4/8 CR

Anti-CTLA4

0 25 50 75 100 125 150 175 2000

500

1000

1500

2000

2500

3000

3500

Days Post Implant

Tum

or v

olum

e (m

m3 )

⍺CTLA4

5/8 CR

MDNA11 + Isotype

0 25 50 75 100 125 150 175 2000

500

1000

1500

2000

2500

3000

3500

Days Post Implant

Tum

or v

olum

e (m

m3 )

MDNA11

8/8 CR

MDNA11 + Anti-CTLA4

0 25 50 75 100 125 150 175 2000

500

1000

1500

2000

2500

3000

3500

Days Post Implant

Tum

or v

olum

e (m

m3 )

MDNA11 + ⍺CTLA4

CT26 tumor (~60 mm3) bearing Balb/c mice were treated with MDNA11 (5 mg/kg 1x/week, 2 weeks) or Anti-CTLA4 (200 µg 2x/week, 2 weeks) by IP injection.

Re-challenge experiment performed by implanting 2 x 106 CT26 cells in opposite flank (Day 49, Day 116 and Day 165), without further treatment.

0 25 50 75 100 125 150 175 2000

500

1000

1500

2000

2500

3000

3500

Days Post Implant

Tum

or v

olum

e (m

m3 )

Re-challenge

N = 8

Re-challenge

#1

Re-challenge

#2

Re-challenge

#3


Prim

ary

Tum

or

Re-

chal

leng

e

Q4 2020

MDNA11 + ⍺CTLA4

MDNA11 in combination with ⍺CTLA4 exhibited synergistic effect

generating 100% complete response in CT26 tumor mice

models. Additionally when re-challenged, all mice in MDNA11 +⍺CTLA4 group exhibited strong memory response with no tumor

growth.

PilotNon-human Primate (Cynomolgus Monkey) Study

17

Adult cynomolgus monkeys (age: 8-12 years) received 2 doses of MDNA11 by slow IV bolus 14-days apart and monitored for total of 28 days.

• Dose: 10, 30, 100, 300, and 600 mcg/kg

• One male monkey per group

• One monkey also received single dose of 300 mcg/kg MDNA11 and total of 21 days monitoring

Study measurements included

(1) Clinical observations

(2) Clinical chemistry

(3) Hematology

(4) Immune-profiling with Ki67 analysis of peripheral blood

(5) organ weights and macroscopic pathology

Sample collection also for (1) PK , (2) ADA and (3) cytokines/chemokines.

Study Design to Evaluate Safety, PK and PD Profile

Medicenna Corporate OverviewQ4 2020

Proliferation & Expansion of Immune Cells but Not Tregs

18Medicenna Corporate Overview

-4 -2 0 2 4 6 8 10 12 14 16 18 20 22 24 26 280

1000

2000

3000

4000

5000

Day

Cel

l/uL

of

blo

od

MDNA110.3 mg/kg

MDNA11 - 0.6

MDNA11 - 0.6

MDNA11 - 0.6

MDNA11 - 0.6

Tregs CD4+ T Cell CD8+ T Cell NK Cell

0

2

4

6

8

10

12

Control 0.01 0.03 0.1 0.3 0.6

MDNA11 (mg/kg)

% K

i67+

Fold

-cha

nge

to P

re-d

ose

0.6 mg/kg 0.6 mg/kg

Q4 2020

MDNA11 induced up to 10-fold expansion in cancer-fighting immune cells (CD4+ T, CD8+ T, and NK Cells) in

non-human primate study without: (a) Treg expansion, (b) generating anti-drug antibodies, (c) causing hypotension

associated with vascular leak syndrome, (d) cytokine storms, or (e) other undesirable immune mediated side effects.

19

Durable, Dose-Dependent Ki67 Expression and CD8+ T-Cell Expansion

• Ki67 is a key marker of anti-tumor CD8+ T-cell proliferation

• Target Ki67 expression of >50% clearly demonstrated with MDNA11 treatment


Dose Dose

-4 -2 0 2 4 6 8 10 12 14 16 18 20 22 24 26 280

20

40

60

80

100

Day

Ki6

7+ (%

of C

D8)

CD8 Ki67% - MDNA11

CTL

MDNA11-0.01

MDNA11-0.03

MDNA11-0.1

MDNA11-0.3MDNA11 - 0.6

-2 0 2 4 6 8 10 12 14 16 18 20 22 24 26 280

2

4

6

8

10

Day

CD8

T Ce

ll Fo

ld-C

hang

e

CD8 Normalzied to Pre-D - MDNA11

CTLMDNA11-0.01

MDNA11-0.03

MDNA11-0.1

MDNA11-0.3

MDNA11 - 0.6

DoseDose

Vehicle

0.1 mg/kg

0.3 mg/kg

0.6 mg/kg

0.01 mg/kg0.03 mg/kg

-2 0 2 4 6 8 10 12 14 16 18 20 22 24 26 280

2

4

6

8

10

Day

CD

8 T

Cel

l Fo

ld-C

han

ge


CTLMDNA11-0.01

MDNA11-0.03

MDNA11-0.1

MDNA11-0.3

MDNA11 - 0.6-2 0 2 4 6 8 10 12 14 16 18 20 22 24 26 280

2

4

6

8

10

Day

CD

8 T

Cel

l Fo

ld-C

han

ge


CTLMDNA11-0.01

MDNA11-0.03

MDNA11-0.1

MDNA11-0.3

MDNA11 - 0.6

MDNA11 Dosing

20

IL-2 Superkine Program: Next Steps


• Pre-IND meeting with the FDA (H2 2020)

• Initiate Phase 1 clinical trial (Mid 2021)

• Complete safety portion of Phase 1 monotherapy study (H2 2021)

MDNA11 Next Steps

Q4 2020

MDNA109 Platform

Expansion

Arming Oncolytic Viruses or CAR-T

Cells

Ex Vivo and/or combination with Adoptive Cell Therapy

Mutations to create IL-2 Super-antagonists (MDNA209)

Fc or Albumin Fusions for Long Acting MDNA-109FEAAFuse Checkpoint

Inhibitors with cytokines (CHeCK Cancer™)

Dual or TrispecificCytokines (TRiCK

Cancer™)

Fusion with Cytokines to Create

New Class of Synthekines

Superkine Targeting with Antibodies

(STAb Cancer™)

MDNA55A Powerful Molecular Trojan Horse Targeting Glioblastoma

MDNA55 TreatmentDirect infusion

into tumorvia convection

enhanceddelivery (CED)

75%

INOPERABLE rGBM

22

Current Treatment Strategies for GBM are Ineffective

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

25%

OPERABLE rGBM


Glioblastoma (GBM) & IL4 Receptor

• Uniformly fatal – virtually all tumors will recur

• New treatment strategies are needed

• IL4 receptor (IL4R) is overexpressed in GBM cells and the tumor microenvironment making it a promising target for GBM treatments

DIAGNOSIS

(85-90%)55% of GBM

Temodar-Resistant* RELAPSE

SURGERY RADIOTHERAPY TEMODAR ADJUVANT TEMODAR+

Q4 2020

23

MDNA55: A Targeted Immunotherapy for GBM

MDNA55

Targets the IL4R, which is expressed in brain tumors and in the tumor microenvironment(TME), but not the healthy brain

Highly Selective

Avoids off-target toxicity

Disrupts the TME

By targeting IL4R positive cells found throughout the TME, MDNA55 unblinds the tumor to the body’s immune system

Sustained Immune Memory Response

Anti-tumor immunity is initiated and remains active after MDNA55 is cleared

Targeting DomainCircularly Permuted

Interleukin-4 (cpIL-4)

Lethal PayloadCatalytic domain of Pseudomonas Exotoxin A(FDA approved Moxetumomab pasudotox)

ENDOCYTOSIS

FURIN PROTEASEADP RIBOSYLATION

Inhibit Protein Synthesis

CELL DEATH

NUCLEUS


High Tumor Control Rate & Extended Survival in All-Evaluable Patients

24

92%

78% 74%

51%

26%20% 19%

14% 10% 10% 9% 6% 6% 2%

0% 0%-6%

-11%-16%-16%

-24%-24%-26%-28%

-39%-47%-48%

-55%-56%-59%

-71%-73%-74%-75%

-90%-98%

-100%

-80%

-60%

-40%

-20%

0%

20%

40%

60%

80%

100%

32 10 14 35 41 11 6 22 29 27 7 1 33 4 9 13 16 19 8 25 40 5 38 43 21 45 12 46 3 39 2 18 15 37 28 30 31 36 17 34 23

% C

hang

e in

SP

D (c

m2)

Subject #

Response from Nadir

Tumor Control Rate = 76% (31/41)

Best Response per Modified RANO (following initial PsP)

PDSD or better

0 10 20 300

50

100

Months From Start of MDNA55 Treatment

Per

cent

sur

viva

l MDNA55 (n=44)MDNA55 All-comers (n=44)mOS = 11.6 monthsOS-12 = 46%

*Tumor response based on radiologic assessment


25

Improved Tumor Control Rate & Survival in Proposed Population

74%

51%

26%14% 10% 10% 6% 6% 2%

0% 0% -6% -11%-16%-16%-24%-26%-28%-39%-47%-48%-55%-56%-59%

-71%-74%-75%-90%-98%

-100%-80%-60%-40%-20%0%20%40%60%80%100%

32 14 41 22 29 27 33 4 9 16 19 8 25 40 5 38 43 21 45 46 3 39 2 18 15 37 28 30 36 17 34 23

% C

hange in S

PD

(cm

2)

Subject #

Response from Nadir

Tumor Control Rate = 81% (26/32)

PD

SD or better

*Tumor response based on radiologic assessment

Best Response per Modified RANO (following initial PsP)


Su

rviv

al P

rob

abili

ty

32.0 31.0 20.0 12.0 5.0 1.0 0.0

33.9 25.7 10.5 5.5 5.1 3.8 3.6

MDNA55

SCA

Duration from Relapse (months)0 10 20 30

0.0

0.2

0.4

0.6

1.0

0.8

Group(weighted n)

mOS(months)

MDNA55 (n=32) 15.7

SCA (n=33.86) 7.2

Q4 2020

A Proposed Population comprised of all IL4R High (irrespective of dose) as well as IL4R Low patients receiving

the high dose showed over 100% improvement in survival when compared to a Synthetic Control Arm (SCA)

Encouraging Survival Rates Compared to Approved Therapies

26

All subjects (n=44) mOS is 11.6 months; a ~50% increase

compared to null hypothesis of 8 months for

FDA-approved therapies. OS at 12 months is

46%.

IL4R High + IL4R Low High Dose (n=32)mOS improves to 15 months, and OS at 12

months reaches 55% for proposed

population

IL4R High + IL4R Low High Dose Subgroups Improved outcomes also maintained in

unmethylated MGMT* (n=17)

1) Brada et al., 2001; 2) Gliadel FDA Label 2018; 3) Stupp et al., 2012; 4) Wick et al., 2017; 5) Friedman et al., 2009; 6) Reardon et al., 2020; TTF = Tumor Treating Fields; HD = High Dose


Favorable Comparison of MDNA55 with FDA-approved Therapies for rGBM

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

27

Favorable Safety Profile and Well Tolerated

To date 118 patients have been treated with MDNA55:

• No deaths attributed to MDNA55, no systemic toxicity, and no clinically significant laboratory abnormalities

• Drug-related adverse events were primarily neurological/aggravation of pre-existing neurological deficits characteristic with GBM and have generally been manageable with standard measures

• Maximum Tolerated Dose established at 240 μg for the current study. Notably, there is no evidence of a differential rate of neurological toxicities between doses of MDNA55 up to 240 µg and a range of up to 900 μg explored in previous studies.


Brain Cancer Represents a Significant 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

28

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 $2 Billion Annually


Brain Cancer Next Steps End of Phase 2 Meeting

with FDA in Q3 2020

Infinite Hope29

Visionary Medicines


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.

MDNA11: IL-2 SUPERKINE NEAR TERM MILESTONES CORPORATE SNAPSHOT

BEST IN CLASS IL-2 SUPER-AGONIST

EXCEPTIONAL CD122 SELECTIVITY

Boosts cancer killing immune cells without toxicity

EXCELLENT PHARMCOKINETIC

PROFILEVast improvement over Proleukin

COMPELLING CLINICAL EFFICACY

Positive Phase 2b clinical data in 44 glioblastoma (GBM) patients

ORPHAN/FAST TRACK

Orphan Drug (FDA, EMA) Fast Track (FDA)

$2 BILLIONPotential market of MDNA55 for

brain cancer ($US)1,3

SAFETY PORTION OF MDNA11 PHASE 1

MONOTHERAPY STUDYExpected completion in H2 2021

15 PATENT FAMILIESOffer strong protection for

proprietary technology platforms

WORLD CLASS EXPERTISE

Clinical and scientific advisors, collaborators and inventors

MDNA55: TARGETS IL4R

MDNA55 END OF PHASE 2 MEETING UPDATE

Held September 29, 2020

EXPERIENCED MANAGEMENT TEAM

C-suite has combined 6+ decades of experience in biotech/pharma

PRE-IND MEETING WITH FDA FOR MDNA11

In H2 2020

Q4 2020

Thank You!Elizabeth WilliamsChief Financial Officer

www.medicenna.com

Fahar Merchant, PhDPresident & CEO

mdna q4 2020 september · 2020. 10. 2. · forward-looking statements q4 2020 medicenna corporate...

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