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Cidara Therapeutics Provides Clinical Data Updates for its Lead Antifungal Rezafungin

Additional data and analyses from STRIVE Phase 2 clinical trial confirm positive efficacy results in both rezafungin arms

Definitive Phase 1 QT clinical trial showed no cardiac abnormalities

SAN DIEGO, March 21, 2018 (GLOBE NEWSWIRE) -- Cidara Therapeutics, Inc. (Nasdaq:CDTX), a biotechnology company developing novel anti-infectives including immunotherapies, today is providing additional details from the positive safety and efficacy findings in the Phase 2 STRIVE trial relating to the principal investigators’ efficacy assessments of programmatic indeterminate patients from the global, randomized Phase 2 STRIVE clinical trial of rezafungin. In addition, the results of its recently completed definitive Phase 1 QT clinical trial of rezafungin conducted in accordance with FDA guidance are provided for the first time.

“Based on feedback after our release of topline STRIVE clinical data earlier this week, we determined that this supplemental information would assist in the evaluation of the Phase 2 results,” said Jeffrey Stein, Ph.D., president and chief executive officer of Cidara.

The supplemental data show that the principal investigators’ assessments of the programmatic indeterminate outcomes confirm that both rezafungin dosing regimens were equally efficacious as predicted by the company’s Phase 2 pharmacokinetic data, which showed that both dosing regimens provided therapeutic exposure substantially above that needed to eradicate Candida infections.

“These data from STRIVE are very encouraging,” said Peter Pappas, M.D., Professor of Medicine in the Division of Infectious Diseases at the University of Alabama in Birmingham, and Chair of the Mycoses Study Group. “What they have demonstrated is that rezafungin appears to be safe and well tolerated, and the overall response rates achieved in the two rezafungin dosing arms were similar as predicted. Indeterminate responses in clinical studies are not unusual, despite investigators’ best efforts to avoid them. I am very pleased that the data support advancing rezafungin into future Phase 3 trials in both treatment and prophylaxis to address very real, clinical needs we experience every day.”

Update on STRIVE Phase 2 clinical trial topline efficacy data

Cidara previously reported topline data from the STRIVE Phase 2 trial, including that the trial:

  • met all of its primary objectives, as once-weekly intravenous dosing of rezafungin was observed to be generally well tolerated and safe in patients with candidemia and/or invasive candidiasis; and
  • showed evidence of the efficacy of rezafungin, which was defined in the trial by clearance of Candida from the blood or other normally sterile sites, resolution of signs related to the infection, investigator assessment of clinical response and overall survival.

With respect to the topline data relating to efficacy, Cidara noted the imbalance in the numbers of patients with indeterminate responses in the 400mg/400mg dosing Group. Indeterminate responses indicate an inability to assess outcome due to one or more missing data points, most of which related to missed visits or difficulties in obtaining the multiple repeat blood draws for the culture required for full assessment.

Cidara further evaluated the 12 indeterminate outcomes in the Overall Success primary endpoint (Table 1), as well as the reasons for these indeterminate outcomes (Table 2). The company assessed whether the principal investigator designated these outcomes as cure or failure, irrespective of any missing data points.

When the investigator-assessed outcomes are considered as surrogates for the programmatic indeterminate responses for the Overall Response outcome at Day 14, Overall Success rates are as follows:

Table 1      
       
  Group 1:
RZF once weekly
400 mg
N= 33
Group 2:
RZF once weekly
400mg Wk1/200mg
N= 31
Group 3:
CSF once daily
70 mg D1/50 mg
N= 28
n (%)
Overall Success (D14)
24 (72.7)
23 (74.2)
20 (71.4)
       
-Failures 9 (27.3) 8 (25.8) 8 (28.6)
       

A summary of the 12 patients with indeterminate outcomes on the primary endpoint of Overall Success is as follows:

Table 2: Assessment of Programmatic Indeterminate Overall Response
 
 

 

 

Reason for Indeterminate Response:
Group 1:
RZF once weekly
400 mg
N= 7
Group 2:
RZF once weekly
400mg Wk1/200mg
N= 3
Group 3:
CSF once daily
70 mg D1/50 mg
N= 2
Investigator Assessment of Clinical Response
  Cure   Indeterminate (I)/
 Failure  (F)
  Cure  Indeterminate (I)/
 Failure (F)
  Cure   Indeterminate (I)/
 Failure (F)
Systemic Signs assessment not completed 2 1 (F)     1  
Inadequate number of cultures 2   1   1  
Lost to Follow-up prior to Day 14       1 (I)    
Withdrew consent       1 (I)    
Missed systemic signs at baseline 1          
Non-compliance with study   1 (I)        
             

The trial enrolled 92 patients in the microbiological intent-to-treat, or mITT, population and these patients were randomized to one of two rezafungin arms or the comparator arm, in which patients received caspofungin. In the two rezafungin arms of the trial, patients received either 400 mg of rezafungin administered intravenously once weekly for two to four weeks (Group 1), or 400 mg for the first week followed by 200 mg once weekly for up to four weeks in total (Group 2). In the comparator arm (Group 3), patients received daily caspofungin administered intravenously according to the approved prescribing information, with an optional step down to oral fluconazole. The trial was not statistically powered to demonstrate superiority or non-inferiority and therefore comparisons of efficacy are directional. The trial was intended to provide data for dose selection for Phase 3 studies, which was accomplished.

Results of Definitive QT Trial

Cidara also announced the results of its definitive QT clinical trial. This clinical trial was a Phase 1, single-center, randomized, comparative study of the effect of single-ascending doses of rezafungin, IV placebo, and a single oral dose of moxifloxacin (positive control) in healthy adult subjects. The primary objective was to assess the effects of rezafungin on QT interval. Secondary objectives included assessments of other cardiac conduction parameters, including PR intervals, QRS intervals and heart rate.

The trial enrolled 60 healthy adult subjects into two cohorts of 30 subjects, each with three dose groups, rezafungin (600 mg IV in Cohort 1 and 1400 mg IV in Cohort 2), IV placebo and oral moxifloxacin.  The rezafungin doses of 600 mg and 1400 mg were selected to achieve peak concentrations up to 2.5-fold higher than the expected peak concentration of the 400 mg dose given once-weekly for three weeks. The trial was conducted in accordance with FDA feedback and relevant guidance.

The results of the trial indicated that rezafungin in single doses up to 1400 mg IV had no significant effect on QT prolongation or on any of the other cardiac conduction parameters tested.

About Cidara Therapeutics

Cidara is a clinical-stage biotechnology company focused on developing new anti-infectives that have the potential to transform the standard of care and save or improve patients’ lives. The company is currently advancing its novel echinocandin antifungal, rezafungin acetate, formerly known as CD101 IV, through late stage clinical trials, and developing its antibody-drug conjugates for the treatment of multi-drug resistant Gram-negative bacterial infections. Rezafungin has improved pharmacokinetics compared to existing echinocandins and has the potential for expanded utility across patient settings. Rezafungin is the only once-weekly product candidate in development for the treatment and prevention of life-threatening invasive fungal infections. Cidara is developing its antibody-drug conjugates as part of its novel Cloudbreak™ platform, the first immunotherapy discovery platform designed specifically to create compounds that directly kill pathogens and also direct a patient’s immune cells to attack and eliminate bacterial, fungal or viral pathogens. Cidara is headquartered in San Diego, California. For more information, please visit www.cidara.com.

Forward-Looking Statements

Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements regarding the effectiveness, safety, and other attributes of rezafungin and other potential product candidates, including the potential for these compounds to successfully treat or prevent infections, including those caused by resistant pathogens, potentially transform the way infectious diseases are treated, and the potential for rezafungin to have advantages over the current standard of care in the treatment or prevention of invasive fungal infections, the design and timing of rezafungin Phase 3 clinical trials, and the potential for the Cloudbreak platform to result in future drug candidates. Risks that contribute to the uncertain nature of the forward-looking statements include: the success and timing of Cidara’s preclinical studies and clinical trials; regulatory developments in the United States and foreign countries; changes in Cidara’s plans to develop and commercialize its product candidates; Cidara’s ability to obtain additional financing; Cidara’s ability to obtain and maintain intellectual property protection for its product candidates; and the loss of key scientific or management personnel. These and other risks and uncertainties are described more fully in Cidara’s Form 10-K most recently filed with the United States Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made. Cidara undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.

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Westwicke Partners, LLC
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