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| file | filename |
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| 8-K - FORM 8-K - Cidara Therapeutics, Inc. | a8-k2018x03x19_02.htm |
| EX-99.1 - STRIVE PHASE 2 PART A TOPLINE DATA CONFERENCE CALL TRANSCRIPT - Cidara Therapeutics, Inc. | ex9912018-03x19_02.htm |
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STRIVE Part A Phase 2 topline data
March 2018
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Cidara Pipeline
Programs
Indication
Discovery
Research/
in vitro
in vivo
IND
Enabling
Phase 1
Phase 2
Phase 3
Rezafungin
Treatment
(Candida)
Rezafungin
Fungal
Prophylaxis
in alloBMT
CloudbreakTM Immunotherapy Platform
Cloudbreak
Antibody Drug
Conjugates
(ADC)
Gram (-)
Infections
Infectious Disease Focus
Hematology/Transplant Focus
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STRIVE Part A: Candidemia & Invasive Candidiasis
400/400/(400)mg n=30
400/200/(200)mg n=30
Week 1 2 3 4 5 6 7 8 9
Day
1 5 8 15 22 28
Dose Optional dose
Mycological
response
Mycological &
clinical response:
1 ENDPOINT
Mycological &
clinical response
(IC only)
45 35 42 49 56 59
Mycological &
clinical response
Caspofungin
70/50/(50)mg n=30
Week 1 2 3 4 5 6 7 8 9
Day
1 5 8 15 22 28 45 35 42 49 56 59
70mg Dose 50mg Dose
All cause mortality
Not powered for inferential statistics.
Rezafungin
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
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Major objectives of STRIVE Part A
Select a dosing regimen for STRIVE Part B and Phase 3 based on:
• Clinical and mycological cure by time, severity and empiric treatment
• Tolerability, safety and adverse events
• Relative performance vs caspofungin in light of 20% NI margin in Phase 3
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Topline Baseline Characteristics
ITT Population
Parameter
Rezafungin
400 mg/400 mg (QWk)
N= 35
Rezafungin
400 mg/200 mg (QWk)
N= 36
Caspofungin
70 mg/50 mg (QD)
N= 36
n (%)
Age
Mean age, yrs (SD)
[Range]
56.9 (15.90)
[24.0, 88.0]
57.0 (14.26)
[26.0, 84.0]
60.7 (17.23)
[24.0, 93.0]
Diagnosis
Candidemia 32 (91.4) 31 (86.1) 33 (91.7)
IC 3 (8.6) 5 (13.9) 3 (8.3)
APACHE II
score
0-9 12 (34.3) 9 (25.0) 9 (25.0)
10-19 16 (45.7) 18 (50.0) 21 (58.3)
≥20 6 (17.1) 8 (22.2) 3 (8.3)
Missing 1 (2.9) 1 (2.8) 3 (8.3)
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Topline Overall Response (Primary Outcome)
Day 14 – mITT Population
Response
Rezafungin
400 mg/400 mg (QWk)
N= 33
Rezafungin
400 mg/200 mg (QWk)
N= 31
Caspofungin
70 mg/50 mg (QD)
N= 28
n (%)
Success 19 (57.6) 22 (71.0) 18 (64.3)
Failure 7 (21.2) 6 (19.4) 8 (28.6)
Indeterminate 7 (21.2) 3 (9.7) 2 (7.1)
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)
*Indeterminate response indicates inability to assess outcome due to missing data point(s)
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Topline Investigator Assessment of Clinical Response
Day 14 – mITT Population
Response
Rezafungin
400 mg/400 mg (QWk)
N= 33
Rezafungin
400 mg/200 mg (QWk)
N= 31
Caspofungin
70 mg/50 mg (QD)
N= 28
n (%)
Clinical Cure 25 (75.8) 24 (77.4) 20 (71.4)
Clinical Failure 7 (21.2) 4 (12.9) 8 (28.6)
Indeterminate 1 (3.0) 3 (9.7) 0
Excluding Indeterminate Response
Clinical Cure 25/32 (78.1) 24/28 (85.7) 20/28 (71.4)
Clinical Failure 7/32 (21.9) 4/28 (14.3) 8/28 (28.6)
Outcome most closely approximating primary outcome from prior IC clinical trials
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Topline Overall Response
Day 5 – mITT Population
Response
Rezafungin
400 mg/400 mg (QWk)
N= 33
Rezafungin
400 mg/200 mg (QWk)
N= 31
Caspofungin
70 mg/50 mg (QD)
N= 28
n (%)
Success 19 (57.6) 21 (67.7) 15 (53.6)
Failure 10 (30.3) 8 (25.8) 12 (42.9)
Indeterminate 4 (12.1) 2 (6.5) 1 (3.6)
Excluding Indeterminate Response
Success 19/29 (65.5) 21/29 (72.4) 15/27 (55.6)
Failure 10/29 (34.5) 8/29 (27.6) 12/27 (44.4)
Comparing single dose of Rezafungin to five doses of Caspofungin
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Topline Overall Success by Severity and Prior Therapy
Day 14 – mITT Population
Population
Rezafungin
400 mg/400 mg (QWk)
Rezafungin
400 mg/200 mg (QWk)
Caspofungin
70 mg/50 mg (QD)
n/N (%)
Overall Response 19/33 (57.6) 22/31 (71.0) 18/28 (64.3)
High APACHE II
score
≥15 6/10 (60) 8/10 (80) 7/12 (58.3)
Prior antifungal
therapy
No 8/11 (72.7) 10/10 (100) 7/9 (77.8)
Yes 11/22 (50) 12/21 (57.1) 11/19 (57.9)
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Topline Day 30 All-Cause Mortality (1º Endpoint for Ph3)
mITT Population
Parameter
Rezafungin
400 mg/400 mg (QWk)
N= 33
Rezafungin
400 mg/200 mg (QWk)
N= 31
Caspofungin
70 mg/50 mg (QD)
N= 28
Deaths, n (%) 5 (15.2) 3 (9.7) 5 (17.9)
Deaths at Day 30 (%) 5 (15.2) 1 (3.2) 3 (10.7)
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Topline Summary of Adverse Events
Safety Population
Parameter
Rezafungin
400 mg/400 mg (QWk)
N= 35
Rezafungin
400 mg/200 mg (QWk)
N= 36
Caspofungin
70 mg/50 mg (QD)
N= 33
n (%)
≥1 TEAE
Severe
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)
TEAE leading to study drug
discontinuation
4 (11.4) 1 (2.8) 1 (3.0)
Serious AE 13 (37.1) 18 (50.0) 13 (39.4)
Study-drug related SAE 0 1 (2.8) 1 (3.0)
AE=adverse event
TEAE=treatment-emergent adverse event: AE that occurs after the first dose of study drug is administered
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STRIVE A Topline Conclusions
Based on topline data, Phase 2 STRIVE trial met objectives with
favorable safety and efficacy data for RZF in candidemia/IC to support
advancing to Phase 3 clinical trials
400 mg/200 mg: Efficacy trended the highest in all assessments
• Higher rates on all response endpoints compared to CSF
• Lower rates for overall mortality and all-cause 30-day mortality (the
primary outcome measure in planned Phase 3 study) compared to CSF
• Trends towards improved efficacy outcomes despite >2-fold prevalence
of most severely ill patients compared to CSF
No concerning AE trends: RZF appears to be safe and well-tolerated
• No deaths related to study drug
Topline results strongly support advancing RZF into Phase 3 trials
• And selection of 400/200mg for ReSTORE (RZF Phase 3 treatment trial)
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STRIVE Part B provides an early read on treatment Phase 3
Seamless Phase 2 to Phase 3 Strategy
Phase 2
STRIVE ( Part A )
Phase 2
STRIVE ( Part B )
Phase 3
ReSTORE
Dosing Regimen
Global , multicenter , randomized , double blind ,
active comparator ( caspofungin ) , / invasive candidiasis
Low Dose
Selected Dose
:
1 1
20
%
3
High Dose Selected Dose
from Part A
)
2 :
1
Enrollment
momentum
Original
Protocol
Amended
Protocol
Phase 3
Protocol
Rollover Rollover
Increasing statistical
robustness
Not powered for inferential statistics 20 NI Margin %
The patient populations from STRIVE and ReSTORE will bolster the
global safety database needed for regulatory filings.
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…two P3 studies, one in each population, with distinct commercial opportunities
Topline
Phase 2
STRIVE A
Data
Phase 3
Treatment
Trial Start
Phase 3
Prophylaxis
Trial Start
Phase 3
Prophylaxis
Interim data
STRIVE B
Treatment
Data
Phase 3
Prophylaxis
Data
2018 2019 2020
Phase 3
Treatment
Data
STRIVE Program Enables Phase 3 Treatment and Prophylaxis
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Rezafungin Overall Phase 3 Development Plan
Phase 3 Treatment Trial
Indication
Phase 3
Size
Duration of therapy,
Endpoints and
Comparators
Timing
for initiation
and data
Treatment of
Candidemia & Invasive
Candidiasis in patients with
limited treatment options
~ 150 patients
2-4 week treatment
Day 30 all-cause mortality
Caspofungin
Mid-2018
Mid-2020
Phase 3 Prophylaxis Trial
Prophylaxis of Aspergillus,
Candida & PCP in patients
undergoing allogeneic bone
marrow transplant
~450 patients
w/ adaptive design
90 day prophylaxis
90 day fungal free survival
Fluconazole, Posaconazole,
Bactrim
Mid-2018
Mid-2020
Based on meetings with FDA in 4Q17
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