Rezafungin: A Novel Echinocandin

Taylor Sandison, MD MPH

Chief Medical Officer

ISHAM- Amsterdam

July 2, 2018

Disclosures

Dr. Sandison is an employee of and stockholder in Cidara Therapeutics.

Cidara Pipeline

Program Indication DiscoveryResearch/in vitro in vivo

IND-enabling Phase 1 Phase 2 Phase 3

Rezafungin

Rezafungin IV Treatment (Candida)

Rezafungin IV Fungal prophylaxis

RezafunginSubcutaneous

FungalInfections

With NIH, 3Q18

CloudbreakTM Immunotherapy Platform

CloudbreakAntibody Drug Conjugates (ADC)

Gram (-) Infections

Infectious Disease Focus

Hematology/Transplant Focus

Significant Mortality Due to IFIs in Immunocompromised

1 The PATH (Prospective Antifungal Therapy) Alliance registry and invasive fungal infections: update 2012 (2012).

90 day mortality % by patient category1

63%

52%

40%

38%

26%

24%

23%

HSCT

Hematologic malignancy

Solid tumor

General medicine

Surgical (nontransplant)

HIV/AIDS

Solid organ transplant

Bone marrow transplant

Increasing Complexity of Immunocompromised Hosts

Host and Macroenvironment

Antifungal Therapies

ISSUES ISSUESOlder patients

More comorbidities

Chronic immunosuppression

Novel biologics

Shifting epidemiology

Azole-resistant Aspergillus

Flu-resistant Candida

Drug-Drug Interactions

GI Intolerance

Hepatotoxicity

Nephrotoxicity

QT prolongation

Bone marrow suppression

Allergy

Underdosing/TDM

Rezafungin: A Better Echinocandin. A Better Antifungal.

ICAAC 2015

• Designed for prolonged PK

• Designed for high exposures

• Eliminates toxic degradation products

• Enables multiple formulations

once weekly dosing in clinical studies

potential for improved efficacy vs Candida and Aspergillus infections

potential for improved safety

intravenous; subcutaneous under development

Structural modification yields improved chemical & biological properties

Zhao, Perlin et al, AAC July 2017

10

20

30

40

50

60Tissue Drug Level(µg/ml)

Data Favors Rezafungin in Severe Infections

1 dose of rezafungin vs.2 doses of micafungin

1 dose of rezafungin vs.3 doses of micafungin

10

20

30

40

50

60

48 HOURS 72 HOURS

RezaMica RezaMica

Intra-abdominal Invasive Candidiasis Abscess Model

Accumulates to Higher Levels than Micafungin at Infection Site

400/400/(400)mg n=30

400/200/(200)mg n=30

Week 1 2 3 4 5 6 7 8 9

Day1 5 8 15 22 28

Dose Optional dose

Mycological response

Mycological & clinical response: 1° ENDPOINT

Mycological & clinical response (IC only)

4535 42 49 56 59

Mycological & clinical response

Caspofungin70/50/(50)mg n=30

Week 1 2 3 4 5 6 7 8 9

Day1 5 8 15 22 28 4535 42 49 56 59

70mg Dose

50mgDose®

All cause mortalityRezafungin

Analysis Populations:§ The Intent-to-treat (ITT) population: all randomized subjects § The Safety population: all subjects who received any amount of study drug§ The Microbiological Intent-to-treat population (mITT): all subjects in safety population who had documented

Candida infection

STRIVE Part A: Candidemia & Invasive CandidiasisNot Powered for Inferential Statistics

Summary of Adverse EventsSafety Population

Parameter

Rezafungin400 mg/400 mg (QWk)

N= 35

Rezafungin400 mg/200 mg (QWk)

N= 36

Caspofungin70 mg/50 mg (QD)

N= 33

n (%)

≥1 TEAESevere

31 (88.6)13 (37.1)

34 (94.4)10 (27.8)

27 (81.8)13 (39.4)

Study-drug related TEAE 4 (11.4) 6 (16.7) 4 (12.1)

Serious AEStudy-drug related SAE

13 (37.1)0

18 (50.0)1 (2.8)

13 (39.4)1 (3.0)

AE=adverse event.TEAE=treatment-emergent adverse event: AE that occurs after the first dose of study drug is administered.

Response

Rezafungin400 mg/400 mg (QWk)

N= 33

Rezafungin400 mg/200 mg (QWk)

N= 31

Caspofungin70 mg/50 mg (QD)

N= 28

n (%)

Overall Response- Success 19 (57.6) 22 (71.0) 18 (64.3)

- Failure 7 (21.2) 6 (19.4) 8 (28.6)

- Indeterminatea 7 (21.2) 3 (9.7) 2 (7.1)

Overall Response and PI Assessment of Clinical ResponseDay 14 – mITT Population

aIndeterminate response indicates inability to assess outcome due to missing data point(s)

Response

Rezafungin400 mg/400 mg (QWk)

N= 33

Rezafungin400 mg/200 mg (QWk)

N= 31

Caspofungin70 mg/50 mg (QD)

N= 28

n (%)

Overall Response- Success 19 (57.6) 22 (71.0) 18 (64.3)

- Failure 7 (21.2) 6 (19.4) 8 (28.6)

- Indeterminatea 7 (21.2) 3 (9.7) 2 (7.1)

Overall Response and PI Assessment of Clinical ResponseDay 14 – mITT Population

Excluding Indeterminate Response

Success 19/26 (73.1) 22/28 (78.6) 18/26 (69.2)

Failure 7/26 (26.9) 6/28 (21.4) 8/26 (30.8)

aIndeterminate response indicates inability to assess outcome due to missing data point(s)

Response

Rezafungin400 mg/400 mg (QWk)

N= 33

Rezafungin400 mg/200 mg (QWk)

N= 31

Caspofungin70 mg/50 mg (QD)

N= 28

n (%)

Overall Response- Success 19 (57.6) 22 (71.0) 18 (64.3)

- Failure 7 (21.2) 6 (19.4) 8 (28.6)

- Indeterminatea 7 (21.2) 3 (9.7) 2 (7.1)

Overall Response and PI Assessment of Clinical ResponseDay 14 – mITT Population

Clinical Cureb 25 (75.8) 24 (77.4) 20 (71.4)

- Failure 7 (21.2) 4 (12.9) 8 (28.6)

- Indeterminatea 1 (3.0) 3 (9.7) 0

Excluding Indeterminate Response

Success 19/26 (73.1) 22/28 (78.6) 18/26 (69.2)

Failure 7/26 (26.9) 6/28 (21.4) 8/26 (30.8)

aIndeterminate response indicates inability to assess outcome due to missing data point(s)bOutcome most closely approximating primary outcome from prior IC clinical trials

Response

Rezafungin400 mg/400 mg (QWk)

N= 33

Rezafungin400 mg/200 mg (QWk)

N= 31

Caspofungin70 mg/50 mg (QD)

N= 28

n (%)

Overall Response- Success 19 (57.6) 22 (71.0) 18 (64.3)

- Failure 7 (21.2) 6 (19.4) 8 (28.6)

- Indeterminatea 7 (21.2) 3 (9.7) 2 (7.1)

13

Overall Response and PI Assessment of Clinical ResponseDay 14 – mITT Population

Clinical Cureb 25 (75.8) 24 (77.4) 20 (71.4)

- Failure 7 (21.2) 4 (12.9) 8 (28.6)

- Indeterminatea 1 (3.0) 3 (9.7) 0

Excluding Indeterminate Response

Success 19/26 (73.1) 22/28 (78.6) 18/26 (69.2)

Failure 7/26 (26.9) 6/28 (21.4) 8/26 (30.8)

Excluding Indeterminate Response

Success 25/32 (78.1) 24/28 (85.7) 20/28 (71.4)

Failure 7/32 (21.9) 4/28 (14.3) 8/28 (28.6)aIndeterminate response indicates inability to assess outcome due to missing data point(s)bOutcome most closely approximating primary outcome from prior IC clinical trials

14

Mycological Response in Candidemia / Overall Response in ICDay 14 – mITT Population

Response

Rezafungin400 mg/400 mg (QWk)

N= 30

Rezafungin400 mg/200 mg (QWk)

N= 26

Caspofungin70 mg/50 mg (QD)

N= 25

n (%)

Mycological Success in Candidemia

20 (70.0) 17 (65.4) 18 (72.0)

- Failure 6 (20.0) 6 (23.1) 6 (24.0)

- Indeterminatea 3 (10.0) 3 (11.5) 1 (4.0)

aIndeterminate response indicates inability to assess outcome due to missing data point(s)

15

Mycological Response in Candidemia / Overall Response in ICDay 14 – mITT Population

Response

Rezafungin400 mg/400 mg (QWk)

N= 30

Rezafungin400 mg/200 mg (QWk)

N= 26

Caspofungin70 mg/50 mg (QD)

N= 25

n (%)

Mycological Success in Candidemia

20 (70.0) 17 (65.4) 18 (72.0)

- Failure 6 (20.0) 6 (23.1) 6 (24.0)

- Indeterminatea 3 (10.0) 3 (11.5) 1 (4.0)

Excluding Indeterminate Response

Success 21/27 (77.8) 17/23 (73.9) 18/24 (75.0)

Failure 6 (22.2) 6 (26.1) 6 (25.0)

aIndeterminate response indicates inability to assess outcome due to missing data point(s)

16

Mycological Response in Candidemia / Overall Response in ICDay 14 – mITT Population

Response

Rezafungin400 mg/400 mg (QWk)

N= 30

Rezafungin400 mg/200 mg (QWk)

N= 26

Caspofungin70 mg/50 mg (QD)

N= 25

n (%)

Mycological Success in Candidemia

20 (70.0) 17 (65.4) 18 (72.0)

- Failure 6 (20.0) 6 (23.1) 6 (24.0)

- Indeterminatea 3 (10.0) 3 (11.5) 1 (4.0)

Excluding Indeterminate Response

Success 21/27 (77.8) 17/23 (73.9) 18/24 (75.0)

Failure 6 (22.2) 6 (26.1) 6 (25.0)

Overall Success in IC 1/3 (33.3) 5/5 (100.0) 1/3 (33.3)

- Failure 1 (33.3) 0 2 (66.7)

- Indeterminatea 1 (33.3) 0 0

aIndeterminate response indicates inability to assess outcome due to missing data point(s)

Rezafungin PK/PD: Dose Selection and Target Attainment

TargetfAUC/MIC

Free

-dru

g Pl

asm

a AU

C 0-2

4: M

IC R

atio

100

150

Caspofungin (14 daily doses)

70mg 50mg

Days of Therapy

14

50

1 7

MIC=0.25 for caspofungin. MIC=0.12 for CD101.

Bader et al. Emerging Candida glabrata Resistance and Echinocandin Dosing: A Call to Arms! IDWeek 2016. Bader et al. Overcoming the Resistance Hurdle: PK-PD Target Attainment Analyses of Rezafungin (CD101) for Candida albicans and Candida glabrata. Submitted AAC 2018; revised with Phase 2 results.

Weeks of Therapy

Rezafungin (4 weekly doses)

Wee

kly

fAU

C:M

ICRa

tio

400

300

200

100

01 2 3

400mg

200mg 200mg

TargetfAUC/MIC

400mg

400mg

4

200mg

400mg

ReSTORE: Candidemia & Invasive Candidiasis

400 mg then 200mg qWk n=92

Week 1 2 3 4 5 6 7 8 9

Day1 5 8 15 22 28

Dose Optional dose

Global Response

Global Response: 1° EMA ENDPOINT

EOT (latest): Global Response

4535 42 52 56 59

Global Response

Caspofungin70 mg then 50mg qDay n=92

Week 1 2 3 4 5 6 7 8 9

Day1 5 8 15 22 28 4535 42 52 56 59

70mg Dose

50mg Dose®

All Cause Mortality:1° FDA ENDPOINT

Phase 3 Pivotal Clinical Treatment Trial

Rezafungin

Global Response: Clinical and Mycological Response (DRC determined)

Antifungal Prophylaxis

Current Prophylaxis (Allo-HSCT) Requires Multiple Drugs for Coverage

Day

Risk of IFIHigh

Low

Post-engraftmentPre-engraftment

CandidaAspergillusPneumocystis

PneumocystisAspergillusCandida

0 10 20 30 6040 70 8050-10

SOC for Candidaand Aspergillus

Posaconazole or Voriconazole

Day 0 10 20 30 6040 70 8050-10

Anti-PCP: Bactrim, dapsone or atovaquone

Posaconazole or Voriconazole

or…

Fluconazole

Transplant Engraftment

SOC for Pneumocyctis

(PCP)

29

Rezafungin: Potential for Simplified Single Drug Paradigm

Day 0 10 20 30 6040 70 8050-10

SOC for Candidaand Aspergillus

Rezafungin

Risk of IFIHigh

Low

Post-engraftmentPre-engraftment

Day 0 10 20 30 6040 70 8050-10

Transplant Engraftment

SOC for Pneumocyctis

(PCP)

CandidaAspergillusPneumocystis

PneumocystisAspergillusCandida

Week 1 2 3 4 12

Azole placebo

Bactrim placebo

Rezafungin5 13

Day 1

17

90 120

1° Day 90 Fungal Free Survival – Non-Inferiority2° Day 90 Safety/Tolerability - Superiority

Follow upRezafungin Arm (n=~300)

Adaptive design: interim analysis @ 50% enrollment for futility/sample size Apx. 20 sites globally. Size and timing pending additional regulatory input

17Week 1 2 3 4 12

Azole*

Bactrim

Rezafungin Placebo5 13

Day 1 84 90 120

Comparator Arm (n=~150)

*Fluconazole or Posaconazole

Phase 3 Pivotal Clinical Prophylaxis Trial

ReSPECT: Antifungal Prophylaxis in Allogeneic HSCT

Rezafungin Overall Phase 3 Development Plan*

Phase 3 Treatment Trial

Indication

Phase 3Size

Duration of Therapy,

Endpoints and Comparators

Treatment ofcandidemia & invasive

candidiasis in patients with limited treatment options

~ 184 patients

2- to 4-week treatmentDay 30 all-cause mortality (US)

Caspofungin

Phase 3 Prophylaxis Trial

Prophylaxis against Aspergillus, Candida & PCP in patients undergoing allogeneic bone

marrow transplant

~450 patients w/ adaptive design

90-day prophylaxis90-day fungal-free survivalFluconazole, posaconazole,

Bactrim

*Plans and timelines for Phase 3 treatment trial subject to regulatory interactions and cash resources. Phase 3 prophylaxis trial subject to regulatory interactions, cash resources and preclinical studies to establish long term dosing