New Hope For Serious Infections

Transcription

1 New Hope For Serious Infections

2 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 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 and long-acting nature of CD101 IV and the intended design of current and future Cloudbreak compounds. 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 documents most recently filed with the United States Securities and Exchange Commission (SEC), including its Registration Statement on Form S-1 declared effective by the SEC on April 14, 2015, under the heading "Risk Factors." 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. CONFIDENTIAL

3 Cidara update: August 2015 CD101 IV 1 st patient dosed in Phase 1 trial July 28 CD101 Topical IND filing on schedule 1H 2016 Cloudbreak Expanding across infectious disease

4 Cidara accomplishments since inception Series B: $42M Feb, 2015 Cidara formed Jan, 2014 Series A: $32M Jun, 2014 IPO: $77M Apr, Acquires CD101 portfolio May, 2014 Initiates CD101 Topical program Oct, 2014 Initiates Phase 1 for CD101 IV Jul, 2015 Submits IND to FDA for CD101 IV Jun, 2015 FDA fast-track & QIDP for CD101 IV May, 2015

5 Fungal infections: high mortality U.S. 12-Week Mortality per Annum by Species Candida 67,500 Aspergillus 22,500 Cryptococcus 4,500 97,000 deaths per year Rare fungi Fungi 2,500

6 Cidara pipeline Program Indication Discovery Research/ In Vitro In Vivo IND Enabling Phase 1 CD101 IV Candidemia/ Invasive Candidiasis CD101 Topical Acute and Recurrent VVC

7 Cidara pipeline Program Indication Discovery Research/ In Vitro In Vivo IND Enabling Phase 1 CD101 IV Candidemia/ Invasive Candidiasis CD101 Topical Acute and Recurrent VVC Cloudbreak TM Platform 1 st Generation Invasive Aspergillosis & Candidemia 2 nd Generation Fungal, bacterial, viral infections

8 CD101 A novel echinocandin antifungal Structural modification yields advantageous chemical & biological properties Permanent charge and highly stable ring structure ü Prolongs PK: targeting once weekly dosing ü Eliminates toxic degradation products: improved safety & dose range ü Allows high exposures: treats less susceptible pathogens ü Enables multiple formulations: systemic and topical ICAAC Poster Sessions Friday to Sunday, Sept 18-20

9 CD101: excellent potency against Candida MIC 90 (µg/ml) results Strain (number) CD101 Anidulafungin Caspofungin Candida albicans (25) Candida glabrata (25) Candida tropicalis (21) Candida krusei (20) Candida parapsilosis (15) Source: ICAAC 2014

10 1 st generation echinocandins: PK/PD not optimized 10 Concentration in Plasma (µg/ml) Anidulafungin 100 mg IV QD; AUC = 95 µg hr/ml per dose Anidulafungin MIC 90 range for echinocandin resistant Candida spp Days Above graphic is a model

11 CD101 IV dosing designed to optimize outcome CD101 IV 200 mg IV Q7D; AUC = 700 µg.hr/ml per dose Concentration in Plasma (µg/ml) 10 For echinocandins exposure (not MIC) improves outcomes 5 0 CD101 MIC 90 range for echinocandin resistant Candida Days Above graphic is a model

12 CD101 IV: superior efficacy at equivalent doses CFU in Kidneys of Mice 24 Hours after Infection with C. albicans and treatment with Anidulafungin or CD101 IV DOSE 0.0 mg/kg 0.5 mg/kg* 1.5 mg/kg** Log 10 CFU/Kidneys 5 Anidulafungin 4 3 CD101 IV Untreated Control Cohort 2 Cohort 3 *Statistically Significant at p < **Statistically Significant at p < 0.05

13 CD101 IV has large safety margins Safety margins = toxicology NOAEL AUC/human AUC at use dose Echinocandin Rat Monkey Anidulafungin 1 0.6x 0.3x Micafungin 2 1.3x ND Caspofungin 3 1.4x 1.6x CD x 9x 1 Anidulafungin margins based on human AUC exposure of 112 µg h/ml (200 mg LD/100 mg MD). 2 Micafungin margins based on human AUC exposure of 167 µg h/ml (150 mg). 3 Caspofungin margins based on human AUC exposure of 86.9 µg h/ml (70 mg LD and 50 mg MD). 4 CD101 margins based on a 50 mg dose or mg/kg based on 60 kg person and 31 mg/m2 based on 1.62m2 person (FDA Guidance, 2005). ICAAC Poster: New Anti-Fungal Agents Friday, Sept 18 Preclinical Evaluation Shows CD101, a Novel Echinocandin, is Highly Stable with No Hepatotoxicity in Rats V. Ong, et al.

14 Positioning CD101 in the Clinic Higher Polyenes Efficacy* Azoles Echinocandins Lower Lower Safety Higher *against less susceptible pathogens

15 Positioning CD101 in the Clinic Polyenes CD101 IV Higher Efficacy* Azoles Lower Lower Safety Higher *against less susceptible pathogens

16 CD101 IV: streamlined development plan IND I II III Phase I Phase 2 Phase 3 PK and safety in healthy volunteers Double-blind vs. echinocandin in candidemia Non-inferiority vs. echinocandin in candidemia + High unmet need prophylaxis Broader initial label claim: invasive candidiasis

17 Vulvovaginal candidiasis (VVC) VVC: 75% of all women RVVC: 4-5 million annually (no drugs approved) Existing echinocandins cannot be formulated topically CD101 Topical: first topical echinocandin

18 CD101 Topical: advantages over standard-of-care Fluconazole CD101-Topical Administration Activity against Candida spp. Activity against Non-albicans Candida Recurrence Oral Fungistatic Resistant Common: 50% relapse/6mo Topical Fungicidal Susceptible Anticipate significant decrease Safety Fetal cardiac abnormalities; potential oral contraceptive interactions Current data supports safe profile; drug interactions unlikely Regulatory Not approved for RVVC New MOA targeting superiority in acute VVC and RVVC

19 CD101 Topical eradicates infection in VVC 6 Vulvovaginal Candidiasis (VVC) in Rats Log 10 CFU/mL lavage Infect: Day 0 Treat: Days 2,3,4 CFU: Days 5,7,9,12 1 Topical LOD 0 D1 D5 D7 D9 D12 D5 D7 D9 D12 D5 D7 D9 D12 No Treatment Monistat tm CD 101 3% Gel ICAAC Poster: New Anti-Fungal Agents Saturday, Sept 19 Novel Echinocandin CD101 Gel Formulation is Highly Effective in Eradicating Candida albicans in a Rat Model of VVC, L. Miesel, et al.

20 CD101 Topical development plan IND I II III Phase I/2 Pivotal Study 1 Dose-ranging safety & efficacy in VVC patients Superiority in acute VVC vs. fluconazole Pivotal Study 2 Superiority in RVVC vs. fluconazole

21 Cloudbreak: a transformational technology Cloudbreak Physically connects the immune system with the pathogen Primes the immune system Vaccine Targets the pathogen Therapeutic The strengths of both systems

22 Cloudbreak concept and compound design Cell EM TM Microbe HUMAN CELL EFFECTOR MOIETY TARGETING MOIETY MICROBE Neutrophil fmlp Echinocandin Fungi Neutrophils Cidara Compound Fungal Hyphae

23 Ex-vivo experimental design Microfluidic Schematic Actual microfluidics chamber Conidia Loading Neutrophil Input Well

24 Ex-vivo proof of concept for C-001 No drug 1 nm C-001 (1/70 th MEC) ICAAC Poster: New Anti-Fungal Agents Saturday, Sept 19 Bifunctional Small Molecule Immunotherapy. C-001 and C-016 Attract Neutrophils (PMNs) to Inhibit Aspergillus fumigatus (Af) Growth in Microfluidic Chambers, D. Irimia, et al.

25 Cloudbreak platform expansion 1 st Generation 2 nd Generation TM EM Microbe TM EM Cell Microbe Cell TM EM TARGETING MOIETY EFFECTOR MOIETY TARGETING MOIETY EFFECTOR MOIETY Approved anti-microbial Small molecule & peptide-based immune engagers Antibody that binds cell-surface antigen Antibody that engages immune system

26 Cloudbreak Platform Expansion Anti-Bacterial Anti-Viral Indwelling Hardware Influenza

27 Upcoming Milestones Program Next Milestone Expected Timing CD101 IV Phase 1 data 2H 2015 CD101 Topical Phase 1/2 start 1H 2016 Cloudbreak Platform Development candidate 2H 2015 (1 st gen) 1H 2016 (2 nd gen)

28 New Hope For Serious Infections