Rezafungin: A Novel Echinocandin. Taylor Sandison, MD MPH Chief Medical Officer ISHAM- Amsterdam July 2, PDF Free Download

: 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 Discovery Research/ in vitro in vivo INDenabling Phase 1 Phase 2 Phase 3 IV Treatment (Candida) Infectious Disease Focus IV Fungal prophylaxis Hematology/Transplant Focus Subcutaneous Fungal Infections With NIH, 3Q18 Cloudbreak TM Immunotherapy Platform Cloudbreak Antibody Drug Conjugates (ADC) Gram (-) Infections

Significant Mortality Due to IFIs in Immunocompromised 90 day mortality % by patient category 1 Bone marrow transplant HSCT 63% Hematologic malignancy 52% Solid tumor General medicine 40% 38% Surgical (nontransplant) HIV/AIDS Solid organ transplant 26% 24% 23% 1 The PATH (Prospective Antifungal Therapy) Alliance registry and invasive fungal infections: update 2012 (2012).

Increasing Complexity of Immunocompromised Hosts Host and Macroenvironment ISSUES Older patients More comorbidities Chronic immunosuppression Novel biologics Shifting epidemiology Azole-resistant Aspergillus Flu-resistant Candida Antifungal Therapies ISSUES Drug-Drug Interactions GI Intolerance Hepatotoxicity Nephrotoxicity QT prolongation Bone marrow suppression Allergy Underdosing/TDM

: A Better Echinocandin. A Better Antifungal. Structural modification yields improved chemical & biological properties 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 ICAAC 2015

Data Favors in Severe Infections Accumulates to Higher Levels than Micafungin at Infection Site Intra-abdominal Invasive Candidiasis Abscess Model Tissue Drug Level (µg/ml) 60 50 40 30 20 10 48 HOURS 72 HOURS 1 dose of rezafungin vs. 2 doses of micafungin 60 50 40 30 20 10 1 dose of rezafungin vs. 3 doses of micafungin Mica Reza Mica Reza Zhao, Perlin et al, AAC July 2017

STRIVE Part A: Candidemia & Invasive Candidiasis Not Powered for Inferential Statistics 400/400/(400)mg n=30 400/200/(200)mg n=30 Mycological response Mycological & clinical response: 1 ENDPOINT Dose Optional dose All cause mortality Week 1 2 3 4 5 6 7 8 9 1 5 8 15 22 28 Day 70mg 50mg Dose Dose Mycological & clinical response (IC only) Mycological & clinical response 35 42 45 49 56 59 Caspofungin Week 1 2 3 4 5 6 7 8 9 70/50/(50)mg n=30 1 5 8 15 22 28 35 42 45 49 56 59 Day 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

Summary of Adverse Events Safety Population Parameter 1 TEAE Severe 400 mg/400 mg (QWk) N= 35 31 (88.6) 13 (37.1) 400 mg/200 mg (QWk) N= 36 n (%) 34 (94.4) 10 (27.8) Caspofungin 70 mg/50 mg (QD) N= 33 27 (81.8) 13 (39.4) Study-drug related TEAE 4 (11.4) 6 (16.7) 4 (12.1) Serious AE Study-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.

Overall Response and PI Assessment of Clinical Response Day 14 mitt Population Response 400 mg/400 mg (QWk) N= 33 400 mg/200 mg (QWk) N= 31 n (%) Caspofungin 70 mg/50 mg (QD) N= 28 Overall Response- Success 19 (57.6) 22 (71.0) 18 (64.3) - Failure 7 (21.2) 6 (19.4) 8 (28.6) - Indeterminate a 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) Clinical Cure b 25 (75.8) 24 (77.4) 20 (71.4) - Failure 7 (21.2) 4 (12.9) 8 (28.6) - Indeterminate a 1 (3.0) 3 (9.7) 0 a Indeterminate response indicates inability to assess outcome due to missing data point(s) b Outcome most closely approximating primary outcome from prior IC clinical trials

Overall Response and PI Assessment of Clinical Response Day 14 mitt Population Response 400 mg/400 mg (QWk) N= 33 400 mg/200 mg (QWk) N= 31 n (%) Caspofungin 70 mg/50 mg (QD) N= 28 Overall Response- Success 19 (57.6) 22 (71.0) 18 (64.3) - Failure 7 (21.2) 6 (19.4) 8 (28.6) - Indeterminate a 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) Clinical Cure b 25 (75.8) 24 (77.4) 20 (71.4) - Failure 7 (21.2) 4 (12.9) 8 (28.6) - Indeterminate a 1 (3.0) 3 (9.7) 0 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) a Indeterminate response indicates inability to assess outcome due to missing data point(s) b 13 Outcome most closely approximating primary outcome from prior IC clinical trials

Mycological Response in Candidemia / Overall Response in IC Day 14 mitt Population Response 400 mg/400 mg (QWk) N= 30 400 mg/200 mg (QWk) N= 26 Caspofungin 70 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) - Indeterminate a 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) a Indeterminate response indicates inability to assess outcome due to missing data point(s) 15

Mycological Response in Candidemia / Overall Response in IC Day 14 mitt Population Response 400 mg/400 mg (QWk) N= 30 400 mg/200 mg (QWk) N= 26 Caspofungin 70 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) - Indeterminate a 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) - Indeterminate a 1 (33.3) 0 0 a Indeterminate response indicates inability to assess outcome due to missing data point(s) 16

PK/PD: Dose Selection and Target Attainment Caspofungin (14 daily doses) (4 weekly doses) Free-drug Plasma AUC 0-24 : MIC Ratio 150 100 50 70mg 50mg Weekly fauc:mic Ratio 400 300 200 100 400mg 400mg 400mg 400mg 200mg 200mg 200mg Target fauc/mic 1 7 Days of Therapy 14 0 1 2 3 Weeks of Therapy 4 Target fauc/mic 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 (CD101) for Candida albicans and Candida glabrata. Submitted AAC 2018; revised with Phase 2 results.

ReSTORE: Candidemia & Invasive Candidiasis Phase 3 Pivotal Clinical Treatment Trial Global Response: Clinical and Mycological Response (DRC determined) 400 mg then 200mg qwk n=92 Global Response Global Response: 1 EMA ENDPOINT 1 5 8 15 22 28 Day 70mg 50mg Dose Dose EOT (latest): Global Response Global Response All Cause Mortality: Dose Optional dose 1 FDA ENDPOINT Week 1 2 3 4 5 6 7 8 9 35 42 45 52 56 59 Caspofungin 70 mg then Week 1 2 3 4 5 6 7 8 9 50mg qday n=92 1 5 8 15 22 28 35 42 45 52 56 59 Day

Antifungal Prophylaxis

Current Prophylaxis (Allo-HSCT) Requires Multiple Drugs for Coverage Day SOC for Candida and Aspergillus SOC for Pneumocyctis (PCP) -10 or 0 10 20 30 40 50 60 70 80 Fluconazole Posaconazole or Voriconazole Posaconazole or Voriconazole Anti-PCP: Bactrim, dapsone or atovaquone High Risk of IFI Low Candida Aspergillus Pneumocystis Pneumocystis Aspergillus Candida Transplant Pre-engraftment Engraftment Post-engraftment Day -10 0 10 20 30 40 50 60 70 80 29

: Potential for Simplified Single Drug Paradigm Day -10 0 10 20 30 40 50 60 70 80 SOC for Candida and Aspergillus SOC for Pneumocyctis (PCP) High Risk of IFI Low Candida Aspergillus Pneumocystis Pneumocystis Aspergillus Candida Transplant Pre-engraftment Engraftment Post-engraftment Day -10 0 10 20 30 40 50 60 70 80

ReSPECT: Antifungal Prophylaxis in Allogeneic HSCT Phase 3 Pivotal Clinical Prophylaxis Trial Arm (n=~300) Week 1 2 3 4 5 12 13 Azole placebo Bactrim placebo Day 1 1 Day 90 Fungal Free Survival Non-Inferiority 2 Day 90 Safety/Tolerability - Superiority 17 90 120 Follow up Comparator Arm (n=~150) Week 1 2 3 4 5 12 13 17 Placebo Azole* *Fluconazole or Posaconazole Bactrim Day 1 84 90 120 Adaptive design: interim analysis @ 50% enrollment for futility/sample size Apx. 20 sites globally. Size and timing pending additional regulatory input

Overall Phase 3 Development Plan* Phase 3 Treatment Trial Phase 3 Prophylaxis Trial Indication Treatment of candidemia & invasive candidiasis in patients with limited treatment options Prophylaxis against Aspergillus, Candida & PCP in patients undergoing allogeneic bone marrow transplant Phase 3 Size ~ 184 patients ~450 patients w/ adaptive design Duration of Therapy, Endpoints and Comparators 2- to 4-week treatment Day 30 all-cause mortality (US) Caspofungin 90-day prophylaxis 90-day fungal-free survival Fluconazole, 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

Rezafungin: A Novel Echinocandin. Taylor Sandison, MD MPH Chief Medical Officer ISHAM- Amsterdam July 2, 2018