SCY-078 ECMM Symposium Cologne, Germany October 2017

A New Path for Antifungal Treatments SCY-078 ECMM Symposium Cologne, Germany October 2017 David Angulo, M.D. Chief Medical Officer

SCYNEXIS at a Glance Company created in 2000 Spin-off of Sanofi, initially as a contract service business Transitioned to a biotechnology company in late 2014 SCY-078 discovered at SCYNEXIS Part of an internal platform of enfumafungin semi-synthetic derivatives (triterpenoids) Glucan synthase inhibitors Public Company since May 2014 Nasdaq-listed: SCYX Based in Jersey City, NJ, USA 2

SCY-078 Novel Glucan Synthase Inhibitor (GSI) Key Attributes Activity against: Candida spp Aspergillus spp Pneumocystis spp 3 Structurally district from other GSIs (echinocandins) CAS IC 50 against purified glucan synthase from C. albicans is 0.6 ng/ml Different enzyme-drug interaction lower impact of common FKS mutations Oral Bioavailability Active against azole- and most echinocandin-resistant strains ORAL and IV formulations Favorable Safety profile > 300 exposed Low risk of Drug-Drug Interactions Extensive tissue distribution (V dss > 8 L/kg)

SCY-078 Addressing Critical Needs Invasive Candidiasis SCY-078 Broad Spectrum IV and Oral Active vs. Resistant Strains High Tissue Penetration Activity against resistant strains (azole and echinocandins) Ease of transition from IV to oral, without sacrificing efficacy Aspergillosis Invasive: Alternative approach to improve outcomes (e.g., combination therapy) Chronic: Oral alternative for azole resistant strains Vulvovaginal Candidiasis Oral fungicidal agent with high tissue penetration and activity in vaginal milieu Prophylaxis Oral, well-tolerated agent with activity vs. Candida/Aspergillus/Pneumocystis and low risk for DDIs 4

SCY-078 is less affected by FKS mutations than echinocandins (36 isolates) 5 AAC, August 2017

SCY-078 Activity against Candida auris Scanning electron micrograph of C. auris (A)no drug (control) (B) with SCY-078 at 0.5 mg/l. A collection of 100 isolates: MIC values of SCY-078 ranged from 0.0625 µg/ml to 2 µg/ml Mode was 1 µg/ml - MIC50 = 0.5 µg/ml - MIC90 = 1 µg/ml 6 Larkin E., et al. AAC, May 2017 ; Berkow E., et al. AAC, July 2017

Figure 1. SEM images of the activity of SCY-078 against biofilms (a) C. albicans, untreated control. (c) C. albicans treated with SCY-078 (0.062 mg/l). SCY-078 was highly active in vitro against invasive Candida and non-candida yeast isolates in both sessile and planktonic forms 7

SCY-078 PK/PD Target Exposure for Invasive Candidiasis - Preclinical Target therapeutic exposure, expressed as the plasma AUC0 24, was comparable across 3 murine models, with an upper value of 11.2 µg h/ml (15.4 µm h); 8 AAC, April 2017 - Volume 61 - Issue 4 Efficacy target

SCY-078 In Vitro Activity vs. Aspergillus spp. Broad activity against Aspergillus spp, including azole resistant strains Itraconazole-resistant Aspergillus spp (MIC, >4 μg/ml) as determined by CLSI broth microdilution methods SCY-078 MEC μg/ml a (range) Wild-type Aspergillus spp Azole-Resistant Aspergillus strains A. fumigatus (21) 0.25 (0.03-1) A. flavus (23) 0.12 (0.06-0.12) A. terreus (18) 0.12 (0.03-0.25) A. fumigatus (6) (0.03 0.5) a MEC that encompasses 90% of isolates tested by CLSI broth microdilution method Pfaller M. A and Col., J. Antimicrobial Agents and Chemotherapy, 2013; 68(4); 858-863 & 2013; 57(2); 1065-1068. 9

Interpretation* Interpretation* Interpretation* MIC values (µg/ml) alone & in combination for SCY-078 with other antifungal agents against A. fumigatus (test performed in duplicate, representative value displayed) MIC Alone SCY-078 with Isavuconazole (ISA) MIC Combo FICI MIC Alone SCY-078 with Voriconazole (VRC) MIC Combo FICI MIC Alone SCY-078 with Amphotericin B (AmB) MIC Combo FICI Strai n 10 SC Y- 078 ISA SCY -078 ISA SCY -078 + ISA SCY -078 VRC SCY -078 VRC WT 4 1 0.016 0.5 0.50 SY 4 1 0.125 0.25 0.27 SY 4 4 0.016 0.5 0.13 SY WT 4 1 0.125 0.25 0.28 SY 4 0.25 0.5 0.16 0.19 SY 4 2 0.016 0.5 0.25 SY WT 4 1 0.063 0.25 0.27 SY 8 0.5 0.5 0.125 0.31 SY 4 4 0.016 1 0.25 SY WT 4 1 0.25 0.25 0.31 SY 8 2 0.25 0.5 0.28 SY 4 4 0.016 1 0.25 SY Azole- R Azole- R 4 >8 0.063 >8 1.02 AD 8 >16 0.031 >16 1.00 AD 4 2 0.125 2 1.03 AD 4 >8 0.125 >8 1.03 AD 4 >16 1 >16 1.25 AD 4 4 0.016 1 0.25 SY SCY-078 in combination with Voriconazole, Isavuconazole and Amphotericin B demonstrates synergistic activity against the majority of A. fumigatus isolates tested SCY -078 + VRC SCY -078 Am B SCY -078 Am B SCY -078 + Am B

Neutropenic mice model of disseminated aspergillosis (IV inoculum) Treatment for 7 days: SCY-078 PO at 7.5 and 10 mg/kg q12h Caspofungin IP at 5mg/kg Ambisome IV at 10mg/kg Observation for 14 days SCY-078 exposure needed for efficacy AUC 0-24hr 15-20 μm hr Percent survival 110 100 90 80 70 60 50 40 30 20 10 F16216 Vehicle - Vehicle PO q12h SCY-078 7.5mg dose SCY-078 10mg dose Caspofungin Ambisome F16216 - SCY-078 7.5mg/kg PO q12h F16216 - SCY-078 10mg/kg PO q12h F16216 - Caspofungin 5mg/kg IP q24h F16216 - AmBisome 10mg/kg IV q24h 0 0 50 100 150 200 250 300 350 Treatment Monitoring Number of hours post-infection A. fumigatus (F16216) Azole-resistant - TR34 L98H 11

SCY-078 in Combination with Azole for Invasive Pulmonary Aspergillosis -Rabbit Model Neutropenic rabbit model of pulmonary aspergillosis Cumulative Survival Probability (%) Treatment for 12 days 100 N=6 / group (QD doses): SCY-078 (IV) at 2.5 or 7.5mg/kg Isavuconazole (PO) 40mg/kg SCY-078 2.5 + Isavuconazole SCY-078 7.5 + Isavuconazole 75 50 25 Control SCY2.5 SCY7.5 ISA40 SCY2.5+ISA40 SCY7.5+ISA40 66% 33% Preliminary results Study conducted at Cornell University, NY by Dr. Tom Walsh 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 Time Combination of SCY-078 + Isavuconazole resulted in improved survival 12

SCY-078 Drug-Drug Interaction and QTc SCY-078 no clinically meaningful effect expected on CYP substrates SCY-078 co-administration showed no clinically significant effect on rosiglitazone (CYP2C8 substrate) pharmacokinetics SCY-078 no clinically meaningful effect expected on Tacrolimus SCY-078 co-administration result in <0.4 fold increase in Tacrolimus AUC 12 SCY-078 is not significantly affected by moderate CYP inhibitors Diltiazem (moderate CYP 3A4 inhibitor) had a only modest effect on SCY- 078 AUC 0-24 increased (~2 fold) 13 SCY-078 did not have a clinically meaningful effect on the QTcF interval Phase 1 studies - within the range of observed plasma concentrations up to ~4000 ng/ml

Randomized SCY-078 - Phase 2 in Invasive Candidiasis (Step Down) - Completed Design: Echinocandin IV 3 to 10 Days Oral SCY-078 1000mg (D1), 500mg QD Oral SCY-078 1250mg (D1), 750mg QD Standard of Care Fluconazole 400mg/d po or Micafungin 100mg IV/d Results: 14 to 28 days (at least 14 days after first negative culture) Pop PK = SCY-078 PO, 750mg QD achieves target exposure (AUC 0-24hr of 15 µm hr) AEs frequency and severity - comparable for all groups Global Response at EOT Favorable Reasons for Unfavorable SCY-078 500 mg N = 7 n (%) SCY-078 750 mg N = 7 n (%) Fluconazole 400 mg N =7 n (%) 5 (71.4) 6 (85.7) 5 (71.4) 1. Never received study drug 2. Discontinued due to a non-drug related AE 1. Withdraw consent after one dose 1. Died (abdominal sepsis) 2. Discontinued (new + blood culture for Candida spp) 14

Ongoing Clinical Trials in EU 15 FURI: (sites initiated in Germany) Phase 3, open-label study in patients that are refractory to or intolerant of approved antifungal agents Currently with Oral SCY-078 may include IV in the future Examples of intended population includes: Objective: Invasive candidiasis, including C.auris Patients with clinical and/or microbiological failure under SOC Oral step-down therapy from IV echinocandin when azole is not adequate (e.g. high MIC for fluconazole or risk of DDIs) Extended therapy (e.g., up to 90 days) with a GSI is desirable and long term IV administration is logistically difficult Severe mucocutaneous candidiasis - azole resistant or intolerant Provide access to SCY-078 for the treatment of difficult-to-manage fungal infections Evaluate the safety and clinical utility in SCY-078 in salvage therapy

Clinical Trials Ongoing and Planned Ongoing: DOVE: Phase 2, randomized, double blind, dosefinding study in patients with acute VVC (US) Exploring 5 dose regimens of Oral SCY-078 vs. Fluconazole Planned: Randomized, double blind, active controlled study in subjects with invasive candidiasis (Global) IV SCY-078 followed by oral SCY-078 compared against IV echinocandin followed by azole 16

SCY-078 Summary Novel Oral and IV glucan synthase inhibitor Spectrum of activity: Broad anti-candida activity Including azole-resistant, ~ 70% FKS mutants (echinocandin-resistant) and C.auris Broad anti-aspergillus activity Including azole-resistant Anti-Pneumocystis activity Extensive tissues distribution High concentrations in key organs such lung, kidney, liver, spleen, mucosa - several fold higher than plasma Target exposure attainable with well-tolerated oral doses 17 Low risk for DDI and no QTc effect

A New Path for Antifungal Treatments Back-Up

SCY-078 distributes extensively to key tissues associated with invasive fungal infections Spleen Lung Kidney Estimated Volume of Distribution at Steady State (human) Drug a Vdss L/kg Mean SCY-078 8.3 Caspofungin 0.15 Liver Micafungin 0.39 Anidulafungin 0.8 L-AMB 0.7 19 Salivary glands Autoradiogram of the Radioactivity Distribution Rat at 4h Following a Single Oral Dose of [ 14 C]SCY-078 Fluconazole 0.7 Voriconazole 4.6 a Felton T. et al, Tissue penetration of antifungal agents. Clin. Microbiol. Rev. 2014, 27(1):68.

SCY-078 Broad Anti-Candida Activity 20 Pfaller M., et al. AAC, August 2017 - Volume 61 - Issue

21 (mg/ml) US Study1 2009 a (N=15) US Study 2 2012 b (N=19) US Study 3 2013 c (N=43) US Study 4 2013 d (N=19) EU Study 1 2012 e (N=27) EU Study 2 2015 f (N=32) EU Study 3 2016 g (N=36) SCY-078 MIC 50 MIC 90 0.25 0.5 0.5 2 0.5 1 0.25 0.25 0.25 0.5 0.25 0.5 1 2 CSP MIC 50 MIC 90 0.5 0.5 0.5 1 0.5 1 0.25 0.5 0.5 1 NA MCF MIC 50 MIC 90 NA NA 2 2 1 2 NA 0.5 1 2 4 ANF MIC 50 MIC 90 a Pfaller et al. JAC 2013, b Jimenez-Ortigosa et al. AAC 2014, c Pfaller et al. AAC 2017, d Shell et al. AAC 2017, e Data on file (Eurofin), f Marcos-Sabrano et al. JAC 2017, g Borroto-Esoda et al. ASM Microbe 2017 1 2 NA NA 2 4 1 2 NA NA 2 4

SCY-078 and Tacrolimus Drug Interaction Loading dose of oral 1250-mg SCY-078 Single 2-mg dose of Tacrolimus on Day 1 15 DAY WASHOUT Oral 750-mg SCY-078 QD for 7 additional days Single 2-mg dose of Tacrolimus on Day 3 (Predicted to be at steady-state exposure for SCY- 078) Pharmacokinetic Parameters for Tacrolimus Alone and Co-administered with SCY-078 Treatment C max (ng/ml) a C 12 hr (ng/ml) a AUC (0- ) (ng*hr/ml) a AUC (0-12 hr) (ng*hr/ml) a Tacrolimus + SCY-078 8.29 (6.93, 9.93) 1.71 (1.38, 2.13) 116.9 (94.53, 114.7) 47.06 (38.98, 56.81) Tacrolimus 8.03 (6.71, 9.61) 1.03 (0.83, 1.28) 82.50 (66.68, 102.1) 35.89 (29.73, 43.33) Geometric Mean 1.03 Ratio (90% CI) (0.89, 1.20) a : Geometric Mean (95% CI). 1.67 (1.45, 1.91) 1.42 (1.25, 1.61) 1.31 (1.15, 1.49) 22

In vitro data show that SCY-078 has potential to inhibit CYP2C8 and an ~5x lower potential to inhibit CYP3A; it does not inhibit other CYP isozymes. PK Rosiglitazone Co-administered with SCY-078 vs. Rosiglitazone Alone Treatment Test (Rosiglitazone + SCY-078) Reference (Rosiglitazone Alone) GMR c Test/Reference (90% CI). AUC 0-Inf (h*nm) a 1451 (1334, 1578) 1461 (1344, 1589) 0.99 (0.90, 1.10) C max (nm) a 235.1 (211.9, 260.7) 295.6 (266.5, 327.8) 0.80 (0.70, 0.90) T max (h) b 1.0 (0.5-4.0) 0.53 (0.5-1.0) a LS Geometric Mean and its 95% CI were calculated based on linear model: log(pk Result)=Sequence of Treatment. ; b Median (Min-Max).; c Geometric Means Ratio, GMR 23 SCY078 is not a clinically meaningful inhibitor of CYP2C8 or other CYP isozymes where the inhibitory potency of SCY-078 is even lower

The proarrhythmic potential of SCY-078 was evaluated in a Phase 1 study using exposure response analysis of the relationship between SCY-078 plasma concentrations and the heart rate corrected QT interval Predicted ΔΔQTcF at the geometric mean peak SCY-078 plasma concentration Treatment 125 mg SCY-078 (1 hour infusion) 250 mg SCY-078 (1 hour infusion) 375 mg SCY-078 (1 and 2 hour infusions) Geometric Mean (90% CI*) of C max (ng/ml) 1547.55 (1405.62;1703.8) 3489.07 (2767.37;4398.97) 2914.19 (2418.89;3510.91) Predicted ΔΔQTcF (msec) 90% CI of ΔΔQTcF (msec) -2.29 (-4.11;-0.47) -4.25 (-7.41;-1.09) -3.67 (-6.35;-0.99) * The 90% CI of the geometric mean was calculated in the logarithmic domain and presented after back-transformation to the original concentration domain. 24 Exposure-response analysis demonstrated that SCY-078 does not have a clinically meaningful effect on the QTcF interval within the range of observed plasma concentrations up to ~4000 ng/ml

70 subjects had cultured-confirmed VVC (per protocol population) Efficacy Evaluation at Day 24 (per protocol population) N Rates % SCY-078 1250mg (D1), 750mg (D2-3) (n= 24) SCY-078 1250mg (D1), 750mg (D2-5) (n= 26) SCY-078 (Combined) (n= 50) Fluconazole 150mg (D1) (n= 20) % D SCY-078 (combined) vs. Fluconazole Clinical Cure 19 79.2% 19 73.1% 38 76% 13 65% +11% Efficacy Evaluation at Month 4 Recurrences Requiring Antifungal Therapy 1 4.2% 1 3.8% 2 4% 3 15% -11% The rate of mycological eradication at Day 24 and Month 4 was 70% and 74% for the SCY-078 combined arms vs. 65% and 60% for the fluconazole arm 25 There were no severe or serious adverse events in any treatment groups. A higher rate of GI adverse events (e.g., nausea, diarrhea) were reported in the SCY-078 treatment arms, which were mild to moderate in severity and transient in nature