Defeating Malaria Together

MMV Stakeholders meeting Siem Reap, Cambodia, 24-26 February 2015 OZ439 Development Update Wiweka Kaszubska, PhD, Head of Product Development

OZ439 is in phase IIb development

Single Dose Cure (SDC) in combination with a drug partner for the treatment of acute uncomplicated malaria

in children and adults

OZ439 development strategy

Select one 4-AQ (PQP or FQ) drug combination

partner for OZ439 for next stage development

Continuously evaluate other drug combination

partners for OZ439 as data becomes available

Test OZ439 activity in

ART resistant parasites as part of the main

clinical program

Single Dose Cure (SDC) in combination with a drug partner for the treatment of acute uncomplicated malaria

in children and adults

Completed phase I and IIa clinical studies with OZ439

OZ439 alone Number of treated subjects

First in Human MMV_OZ439_09_001 56

PhIIa Patient PoC MMV_OZ439_10_002 81

Formulation prototype BA MMV_OZ439_11_001 52

Formulation prototype BA MMV_OZ439_12_003 11

3-Day dose escalation MMV_OZ439_12_005 22

Induced Blood Stage Malaria QP12C10 24

OZ439 in combination Number of treated subjects OZ/MQ combination safety MMV_OZ439_12_001 27

OZ/PQP combination safety MMV_OZ439_12_002 75

OZ/PQP prototype BA MMV_OZ439_13_002 24

OZ/PQP prototype BA MMV_OZ439_13_004 55

OZ/PQP prototype BA MMV_OZ439_13_007 22

OZ/FQ combination safety TDU12511 55

TOTAL 504

To-date OZ439 has an acceptable safety profile

• Acceptable safety and tolerability for single and multiple

(3 day) doses up to 800 mg

• GI dose limiting effects at doses >800mg (diarrhea, hypermotility, nausea)

• Adverse Effects (AEs) generally mild in intensity and reversible up to 800 mg doses

6

log10 Parasite Reduction Ratio

Median Parasite Clearance Half Life (h)

Median Fever Clearance Time (h)

P. falciparum 2.8 - 3.6 4.1 - 5.3 8

P. vivax 3.9 - 4.8 2.3 - 3.2 14

Phase IIa study: OZ439 clears 98% of pf and pv parasites by 36 hours in Thai patients

0

2,000

4,000

6,000

8,000

10,000

12,000

14,000

16,000

18,000

20,000

-1 4 9 14 19 24 29

200 mg

400 mg

800 mg

1,200 mg

Time /h

para

sites

/µl

0

2,000

4,000

6,000

8,000

10,000

12,000

14,000

16,000

18,000

-1 4 9 14 19 24 29

200 mg

400 mg

800 mg

1,200 mg

P. falciparum P. vivax

para

sites

/µl

Time /h

7

Phase IIa study: no significant difference in clearance of Kelch mutant vs. wild-type parasites by OZ439

• P. falciparum Kelch 13 status was assessed in parasite isolates from each patient

• Parasites from 19 out of 40 patients carried mutations

N. White manuscript in preparation

8

Induced Blood Stage Malaria (IBSM) model

• Volunteers inoculated with ~1,800 viable P.falciparum-infected human erythrocytes

• Daily qPCR from day 3

• Parasite levels reach 1,000/ml on day 6-7

• Start treatment

• F/U for 28 days

9

IBSM study: defining the OZ439 dose-range

Australian volunteers

Log10 Parasite Reduction Ratio

Average Parasite Clearance Half Life

Minimal Inhibitory Concentration

4.0 (3.8-4.3) 3.6 h (3.4-3.8 h)

2.4 ng/ml (56% CV)

10

Single dose cure: two active pharmaceutical ingredients

O

OO O

N

O

NCl

N

N

NN

N

Cl

Targeting fixed dose combination

OZ439 PQP

11

OZ439/PQP Phase IIb trial started in July 2014

• Primary Endpoint: PCR-adjusted adequate clinical and parasitological response (ACPR) at Day 28 >95%

• Other Endpoints: parasite clearance times, fever clearance time and safety (particularly cardiac)

• Doses: for patients >35kg and scaled down A) OZ439 800mg + PQP 1440mg

B) OZ439 800mg + PQP 960mg

C) OZ439 800mg + PQP 640mg

• Adaptive design: max 495 patients

NB: OZ439/FQ phase IIb protocol about to be submitted for first country approval

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OZ439/PQP Phase IIb trial recruitment status

Patients with 'Higher' Immunity

Africa >15 yr 45

Africa >5 yr and <15 yr 22

Patients with 'Lower' Immunity

Africa >2 yr and <5 yr 36

Africa >6 mo and <2 yr 0

Vietnam (all age groups) 34

Total

137

Sites open

Burkina Faso (3)

Gabon (2)

Mozambique (1)

Uganda (1)

Vietnam (4)

Sites waiting for approval

Colombia

Benin

DRC

13 13

THANK YOU and the OZ439 Project Team

Project Leader: Marc Adamy Clinical Lead: Fiona Macintyre CMO: Stephan Duparc Medical Director: Steve Toovey (consultant) Clinical Operations Lead: Helen Demarest Clinical Scientist: Myriam El Gaaloul Regulatory Lead: Angela Windt (consultant) Technical Lead: Anil Patel (consultant) Discovery Lead: Didier Leroy Non-clinical Lead: Thomas Rueckle Access & Product Management: Adam Aspinall Business Development: Joan Herbert

14

Site Status

Nanoro, Burkina Faso Screening (FPI - 11/20/2014)

Banfora, Burkina Faso Screening (FPI – 09/03/2014)

Niangoloko, Burkina Faso Screening (FPI – 09/22/2014)

Lambarene, Gabon Screening (FPI – 07/23/2014)

Libreville, Gabon Screening (FPI - 11/12/2014)

Maputo, Mozambique Approval target February

Tororo, Uganda Screening (FPI – 12/15/2014)

Gai Lai, Phu Thien, Vietnam Screening (FPI - 11/28/2014)

Binh Phuoc, Bu Dang, Vietnam Screening (FPI – 12/17/2014)

Quang Tri, Huong Hoa, Vietnam Screening (FPI – 12/18/2014)

Khanh Hoa, Khanh Vinh, Vietnam Screening (FPI – 12/02/2014)

Cali, Colombia Approval granted Dec, import license target February

Benin Approval target May

DRC Approval target March

OZ439/PQP Phase IIb recruitment site status

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Study population

Assumption – a therapy that treats the most vulnerable / most difficult to treat population ( low/ no immunity) will be able to treat everyone

Safety and efficacy: • African Patients < 5 years old:

• A targeted minimum of 60% of total number of patients (maximum 80%)

• African Patients < 2 years old:

• A targeted minimum of 10% of the total number of patients

• Asian Patients:

• Minimum of 18% of total number of patients

• Maximum of 36% of total number of patients recruited

Safety: • African Patients > 5 years old

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Phase IIb safety step-down process