Ibrexafungerp First Representative of a Novel Oral/IV Antifungal - - PowerPoint PPT Presentation

First Representative of a Novel Oral/IV Antifungal Family

Ibrexafungerp

Corporate Presentation – May 2020

Pioneering innovative medicines to overcome and prevent difficult-to-treat and drug- resistant infections

2

Forward-Looking Statements

Certain statements regarding SCYNEXIS, Inc. (the “Company”) made in this presentation constitute forward-looking statements, including, but not limited to, statements regarding our business strategies and goals, plans and prospects, market size, adoption rate, potential revenue, clinical validity and utility, growth opportunities, future products and product pipeline. Forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially from our

• expectations. These risks and uncertainties include, but are not limited, to: risks inherent

in SCYNEXIS's ability to successfully develop and obtain FDA approval for ibrexafungerp; the expected costs of studies and when they might begin or be concluded; whether the positive results from the FURI trial to date will continue to be achieved as the study continues; uncertainties about the regulatory standards for approval through LPAD; and SCYNEXIS's reliance on third parties to conduct SCYNEXIS's clinical studies. Forward-looking statements may be identified by the use of the words “anticipates,” “expects,” “intends,” “plans,” “could,” “should,” “would,” “may,” “will,” “believes,” “estimates,” “potential,” or “continue” and variations or similar expressions. These statements are based upon the current expectations and beliefs of management and are subject to certain risks and uncertainties that could cause actual results to differ materially from those described in the forward- looking statements. These risks and uncertainties include, but are not limited to, risks and uncertainties discussed in the Company's most recent reports filed with the Securities and Exchange Commission ("SEC"), including under the caption “Risk Factors” in the Company’s annual report on Form 10-K for the year ended December 31, 2019 and in the Company’s subsequent quarterly reports

• n Form 10-Q, which factors are incorporated herein by reference. Readers are cautioned not to place

undue reliance on any of these forward-looking statements. The Company undertakes no obligation to update any of these forward-looking statements to reflect events or circumstances after the date of this presentation, or to reflect actual outcomes.

scynexis.com

Company Overview | Introduction

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The Comeback of Anti-infectives

1. Microbes are resilient: pathogens – viruses, bacteria or fungi – were here

billions of years before us and they are not going away

2. They are adaptable: becoming resistant to our current antimicrobial agents 3. They are innovative: focus is on COVID-19 now, but other pathogens are

emerging

• Candida auris, a deadly fungi identified in 2009 in Japan is spreading across

the world and in the United States

• The mission of anti-infective companies is critical
• Potential increase in value recognition for innovative anti-infective research

– by both the public and the government COVID-19 pandemic is a powerful reminder of our never-ending warfare against infectious diseases

5

Fungal Infections: A Growing Public Health Threat

1. The Clinical Problems – In the Hospital: rising Invasive Fungal Infections with high mortality, much higher than Coronavirus. COVID-19 associated Pulmonary Aspergillosis reported in several centers – In the Community: difficult-to-treat Vaginal Fungal Infections in millions of women 2. The Medical Needs – In the Hospital: few systemic drugs available (3 classes available with only one oral class) – In the Community: only one oral treatment

• ption available for vaginal yeast infections

3. The Emerging Concerns – Antifungal resistance and appearance of new alarming fungal species – Lack of broad-spectrum oral treatments

April 6, 2019

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COVID-19 Preparedness

• 1. VANISH program: Positive Phase 3 data reported. On track for NDA

submission in H2:2020

• 2. CANDLE-304 (Phase 3 in rVVC patients): Enrollment ongoing
• 3. Hospital programs*: Enrollment ongoing
• For our ongoing programs, we have implemented several adjustments

– Our plans are consistent with the newly issued FDA and EMA guidance

• n conduct of clinical trials during COVID-19 pandemic

* Includes FURI and CARES Phase 3 studies in refractory invasive fungal infection patients, and SCYNERGIA Phase 2 study in Invasive Aspergillosis patients. Ibrexafungerp is an investigational drug.

As of today, we don’t believe the COVID-19 pandemic will have substantial impact on our programs and our clinical and regulatory timelines remain unchanged

Ibrexafungerp (”ibrexa” or ”IBX”) is an investigational drug.

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Ibrexafungerp: A Potential Solution for the Fungal Infection Crisis

Ibrexafungerp: First member of the ‘fungerp’ family

Ibrexafungerp (”ibrexa” or ”IBX”) is an investigational drug.

Vulvovaginal Candidiasis (VVC) Pre-NDA Recurrent VVC (SPA agreement) Phase 3 Refractory Mucocutaneous Infections Phase 2/3 Refractory Invasive Fungal Infections (rIFI) - LPAD Phase 3

• C. auris infections - LPAD

Phase 3 Aspergillosis in Combination Phase 2

Two positive VVC Phase 3 studies Anticipated NDA in H2:2020 Expected Priority Review Worldwide Rights Composition of Matter Patent Protection up to 2035 10 to 12 years of Regulatory Exclusivity in the U.S. (QIDP/ Orphan Drug Status/Fast Track)

Outpatient/Community Setting

• Only ONE systemic oral product approved for VVC

and NO approved treatment for rVVC

• >14mm fluconazole TRx/year for VVC in the U.S.
• Ibrexafungerp as single-day oral treatment for VVC

with a potential $400-600mm peak sales in the U.S.

• Only 3 classes and fewer than 10 approved systemic

products

• Growing resistance to azoles, the only oral drug
• Multidrug-resistant emerging fungi
• Still high mortality with current SoCs

Hospital Setting

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Clear Path to VVC NDA Submission for Ibrexafungerp

Both VANISH-303 and VANISH-306 met their study endpoints, providing a clear path to NDA submission of oral ibrexafungerp for the treatment of vaginal yeast infections

• VANISH Phase 3 Program:

ü The first large Phase 3 program for the treatment of VVC in over 20 years ü Success on all primary and secondary efficacy endpoints achieved ü Sustained effect confirmed at Day 25 ü Generally safe and well tolerated

• NDA submission expected in 2nd half of 2020
• Vision for ibrexafungerp as the first and only oral, non-azole agent

addressing BOTH treatment of VVC and prevention of recurrent VVC

Ibrexafungerp (”ibrexa” or ”IBX”) is an investigational drug.

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Ibrexafungerp: 1st Representative of a Novel Antifungal Class

No Safety Signals

1,000+ subjects exposed

Oral Formulation in Phase 3

IV in pre-clinical development

Broad Spectrum

Candida, Aspergillus, Pneumocystis & others 2,000+ strains tested

Activity vs. Resistant Strains

MDR strains, including C. auris

Fungicidal vs. Candida 20-hour Half-Life High Tissue Penetration Low Risk of DDIs

Validated MoA Minimal risk of off-target effects Differentiated binding vs. echinocandins Cell Membrane and Cell Wall

Fungal Cell

Nucleus Cell Wall β-(1,6)-glutan β-(1,3)-glucan Mannoproteins Chitin Phospholipid bilayer

• f cell membrane

Ergosterol

(Polyenes site

• f interaction)

Ergosterol Synthesis Pathway

(Azoles site of interaction)

β-(1,3)-glucan synthase

(SCY-078 and echinocandins site of interaction)

Depletion of β-(1,3)-glucans in cell wall Ibrexafungerp (”ibrexa” or ”IBX”) is an investigational drug. Items listed on this slide illustrate ibrexafungerp target attributes.

10 Polyene Azole Echinocandin Fungerp Market Introduction 1960s 1980s 2000s ~2021 Spectrum of Activity Active vs. Candida albicans

ü ü ü ü

Active vs. non-albicans Candida

ü ü ü

Active vs. azole-resistant

ü ü ü

Active vs. echinocandin-resistant*

ü ü

Active vs. Aspergillus spp.

ü ü ü ü

Safety Lack of renal, hepatic, CNS Tox.

ü ü

Low risk for DDIs

ü ü ü

Oral Bioavailability

ü ü

Antifungal Innovation is Lacking

* Active against most echinocandin-resistant Candida isolates. items listed on this chart illustrate its target attributes. 2021 target market intro based on estimated 2020 NDA filing. “SoC” = Standard of Care. a. Company-reported Sales (filings) and IMS data.

Ibrexafungerp may combine the best attributes of all other classes

Ibrexafungerp (”ibrexa” or ”IBX”) is an investigational drug.

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Outpatient

Treatment of Vulvovaginal Candidiasis (VVC) Prevention of Recurrent VVC

Hospital

Invasive Aspergillosis (Combination Therapy) Refractory Invasive Fungal Infections

Ibrexafungerp: Ongoing Programs / Timing

8 Key Milestones

Ibrexafungerp (”ibrexa” or ”IBX”) is an investigational drug. Estimated NDA filings and approval timing.

Other potential oral indications: Prophylaxis, Chronic Fungal Infections

CARES Study (open-label, emergency protocol, C. auris) 1 P2 study (SCYNERGIA) Ongoing DOVE P2b

(Jul. 2018)

FURI Study (open-label, refractory IFIs)

1st Positive Prelim Data (Jan. ‘19)

1 P3 (VANISH- 303) Complete 1 P3 (CANDLE) – SPA agreement Ongoing NDA H2:20

sNDA H2:21

1 P3 (VANISH-306) Complete

Positive Data Nov 2019 Positive Data Apr 2020 2nd Positive Prelim Data (Jan. ‘20) Potential Approval Mid-2021

2018 2019 2020 2021

Top-line Data Mid- 2021

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Ibrexafungerp: Significant Near-Term Milestones

Positive top-line data VVC VANISH-306 P3 (Apr. 2020) Positive 2nd FURI data review (Jan. 2020) CANDLE-304 P3 Prevention of rVVC Top-line data SCYNERGIA P2 top-line data

Potential other milestones in 2020-2021:

• FURI and CARES interim analyses
• IV update
• Business Development opportunities

Ibrexafungerp (”ibrexa” or ”IBX”) is an investigational drug. Estimated timelines.

Q1‘20 Q2’20 H2’20 H1’21 H2’21

Treatment of VVC NDA Submission Treatment of VVC Approval Prevention of Recurrent VVC sNDA Submission

13

SCYX: Stock Highlights & Financial Information

$1.52 | $0.50

52-week high/low

~$85M | $50M

Market Cap | Enterprise Value

~750K shares

3-month average trading volume

~$46.5M* | $24M*

Cash (as of Q1) | Long-term debt

~98M | 195M

Basic | fully-diluted shares out.

1% | 97M

Insider ownership | Free float

Top Institutional Holders (as of Q4’19) Top Insiders:

• Dr. Marco Taglietti: 694K shares
• Dr. David Angulo: 124K shares
• Guy MacDonald: 40K shares

* Pro-forma for $10mm convertible debt completed in April 2020 and $3.1mm cash receipt from sale of NJ NOLs. Firm % OS Position CHANGE Federated Hermes 19.3 18,610,412 11,742,012 Caxton Corp 8.3 7,936,111 3,611,111 Armistice Capital 6.5 6,222,778 6,222,778 Decheng Capital 5.8 5,555,556 5,555,556 Vanguard Group 2.9 2,771,679 191,600 Kingdon Capital 2.4 2,294,444 2,294,444 Broadfin Capital 2.1 2,000,000 2,000,000 Firm Analyst Status Rating PT Aegis Capital Nathan Weinstein Active Buy $4.00 Brookline Capital Kumar Raja Active Buy $5.00 HC Wainwright Oren Livnat Active Buy $3.50 Ladenburg Mike Higgins Active Buy $6.00 Maxim Jason McCarthy Active Buy $4.00 Needham Alan Carr Active Buy $5.00 WBB Securities Stephen Brozak Passive Buy $8.00

Existing Coverage

14 Guy Macdonald Chairman Armando Anido Steven Gilman, PhD Ann Hanham, PhD David Hastings Phil Tinmouth CEO Marco Taglietti, M.D. CMO David Angulo, M.D. CFO Eric Francois GC Scott Sukenick

Leadership

Positive track record in drug development, commercial & antifungal expertise

Total of 27 employees:

• 70% R&D
• 30% SG&A, Commercial, BD

SCYX: Experienced Team

Board of Directors

Diverse backgrounds & operating experience in healthcare

scynexis.com

Outpatient/Community Infections: Vulvovaginal Candidiasis (VVC)

“Many of the unresolved clinical issues in managing women with rVVC would disappear if truly fungicidal drugs and regimens were available.”

• Dr. Jack Sobel
• Curr. Infect. Dis. Rep.2006,8:481–486

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Oral Ibrexafungerp in VVC

Ibrexafungerp (”ibrexa” or ”IBX”) is an investigational drug.

2nd most common cause of vaginitis 14MM/Year Fluconazole Rx (U.S.) 18MM/Year Topical OTC Units (U.S.) Only one oral approved product (fluconazole) 3 Phase 3 Studies vs. Placebo:

• 2 in aVVC met their key

endpoints

• 1 ongoing study in rVVC (SPA

agreement) Planned VVC NDA H2:2020 | Expected approval mid-2021 Planned rVVC sNDA in H2:2021 | Expected approval in 2022 Efficacy at both Day-10 and Day-25 visits Lower need for rescue medication compared to fluconazole (4% vs. 29%) in small DOVE P2 study No safety signal Good tolerability

Strong Competitive Positioning

• New oral option
• One-day therapy for treatment of VVC
• No FDA-approved therapy for rVVC

Significant Commercial Potential

• Estimated potential U.S. Peak Sales of

~$400 to $600mm per year

Highly prevalent infection affecting 125M+ women worldwide Clear regulatory path with high chance of technical success Clinical studies suggest high and sustained clinical benefit

17

Attractive Characteristics of the Women’s Health (VVC) Opportunity

Solosec (secnidazole) is a good analogue of a recent commercial launch in the women’s health space – relevant to ibrexafungerp in VVC

Not a Crowded Market

• nly 1 available

class – 1 oral product – fluconazole; not approved for rVVC

High Impact on Quality of Life à High Unmet Need

up to 30-40% of patients unsatisfied with fluconazole

Large Patient Population

~8mm per year - ~2mm with recurrent or moderate/severe infections

Attractive Pricing

low barrier for market access

Estimated Peak Sales of $500M- $1BN+

Fluconazole peak sales of $1.2BN

Efficient Commercial Model

concentration of high-volume prescribers, limited promotion

• Launched in 2018 for the treatment of Bacterial Vaginosis
• “me-too” product in generic market (Nitroimidazole

antimicrobial - same class as metronidazole and benzinidazole)

• Convenience-play only
• Reached U.S. sales of ~$20M in its 1st year and ~$30mm

in the first 9 months of the 2nd year

• Expected to reach ~$150M at peak (~4 years post launch)

Solosec Ibrexafungerp

Targets PCP, OB/GYN PCP, OB/GYN Acute Infection Dose One-day dose One-day dose Chronic Infection NA 6-month dose for rVVC Novel Therapy No Yes Activity vs. SoC Similar Broader Cost per Acute Tx ~$300 ~$300-400 Managed Care Tier 3 (no restriction) Target: Tier 3 (no restriction)

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Ibrexafungerp VVC Commercial Positioning

Key Attributes

New MoA

• Fungicidal (kills the pathogen)
• Broad spectrum (including fluconazole-

resistant Candida strains)

• Enhanced activity at low vaginal pH
• High vaginal tissue penetration

Favorable Safety Profile

• No observed safety signals

(>1,000 subjects exposed)

• No evidence of embryo/fetal risk
• No evidence of liver toxicity or QT

prolongation Convenient Dosing

• Novel oral therapy
• Single-day dose for treatment of VVC

Potential Patient Types

Mild-to-severe VVC patients

• Patients where the physician wants to try

another therapy with a new MoA

• Physicians concerned about Candida-

resistant strains

• Fluconazole failures
• Recurrent patients
• Complicated patients with co-morbidities
• Women of child-bearing age where physicians

prefer an agent that has shown no fetal toxicity in preclinical studies

Ibrexafungerp (”ibrexa” or ”IBX”) is an investigational drug.

The first and only oral, non-azole agent addressing BOTH treatment of VVC and prevention of recurrent VVC

Our vision for ibrexafungerp:

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Ibrexafungerp: a Novel Fungicidal Oral Agent for the Treatment of VVC

Ibrexafungerp Fluconazole

MoA beta-(1,3)-D-glucan synthase inhibitor 14α-demethylase inhibitor Cidal/Static vs. Candida Fungicidal Fungistatic Active vs. azole-resistant Candida Yes No Activity at low vaginal pH Yes No Vaginal tissue/Plasma ratio 9:1 1:1 Evidence of drug-drug interactions No Yes Evidence of Fetal Toxicity (pre-clinical) No Yes Evidence of QTC prolongation No Yes Evidence of Liver Toxicity No Yes One-day Oral dose Yes Yes

The Vaginal Yeast Infection market only has treatments from one class (azoles) and no treatment options with different MoA

Ibrexafungerp (”ibrexa” or ”IBX”) is an investigational drug.

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Ibrexafungerp VVC U.S. Opportunity

ROW opportunity expected to be similar to U.S. market, pricing TBD Preliminary assessment (to be further validated). Sources: SCYNEXIS Primary HCPs and Payers Market Research Symphony Data 2018

Ibrexafungerp (”ibrexa” or ”IBX”) is an investigational drug.

Patient Segments First Episode

• f VVC

Second Episode

• f VVC

Third Episode

• f VVC

4+ Episodes (Prevention) U.S. Prescriptions ~7.6M ~4.1M ~1.7M ~700k Ibrexa Penetration Rates ~3% ~14% ~18% ~25% Ibrexa Pricing per Course ~$300 to $400 ~$300 to $400 ~$300 to $400 ~$1,800 to $2,400 Ibrexa U.S. Peak Net Sales ~$220-300M ~$210-280M

U.S. Peak Sales Potential ~$430-580M

Target Label for Ibrexafungerp: “Treatment of VVC and prevention of recurrent VVC” Conservative estimates, particularly for penetration into non-recurrent market Ibrexafungerp potential sales represent ~10% of overall fluconazole scripts (~14M) in VVC

21

Staggered VVC Approvals in 2021 and 2022

• Two Phase 3 acute VVC studies completed | superiority vs. placebo

– U.S. study (VANISH 303): positive top-line data released in Nov. 2019 – Global study (VANISH 306): positive top-line data released in Apr. 2020 – Program adequate also for European Approval

• One global Phase 3 recurrent VVC study (~350 patients à superiority vs.

placebo) ongoing

– SPA agreement with FDA received in July 2019 – Top-line data and sNDA anticipated in H2:2021 | potential approval in 2022

Ibrexafungerp (”ibrexa” or ”IBX”) is an investigational drug.

Outpatient

Treatment of Vulvovaginal Candidiasis (VVC) Prevention of Recurrent VVC

8 Key Milestones

DOVE P2b

(Jul. 2018)

1 P3 (VANISH- 303) Complete 1 P3 (CANDLE) – SPA agreement Ongoing NDA H2:20 Potential sNDA H2:21 1 P3 (VANISH-306) Complete

Positive Data Nov 2019 Positive Data Apr 2020 Potential Approval Mid-2021

2018 2019 2020 2021

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VANISH Phase 3 Program

Key Design

• Two identical Phase 3 Studies in vulvovaginal

candidiasis (VVC)

– VANISH-303 in 371 patients (28 centers in U.S.) – VANISH-306 in 449 patients (42 centers in U.S. and Europe)

• Randomized, placebo-controlled (2:1 ratio),

double-blind design

• Patients enrolled with VVC episode ranging

from mild to severe

• Convenient one-day treatment of 600mg

– Administered as two doses of 300mg, 12 hours apart

• Primary efficacy population: Modified-intent-

to-treat (mITT)

– Treated patients with positive Candida vaginal culture at baseline

• Safety Population: all treated patients

Key Assessments

• Two study visits

– “Test-of-Cure” visit (TOC) at Day 10 – “Follow-Up” visit (FU) at Day 25

• Signs and Symptoms [S&S*] score is a

composite scale ranging from 0 (no S&S) to 18 points (maximum severity in all S&S)

• Primary efficacy endpoint

– Clinical Cure at TOC: complete resolution of all signs and symptoms (S&S=0)

• Key secondary efficacy endpoints

– Mycological Eradication at TOC visit: negative Candida culture – Clinical Improvement at TOC visit: complete or almost complete resolution of signs and symptoms (S&S of 0 or 1) – Complete resolution of symptoms at FU visit

* Signs and Symptoms [S&S] score defined as a composite endpoint of the subject’s reported symptoms (burning, itching and irritation) and the investigator’s assessed signs (swelling, redness and excoriations). Each sign and symptom can be absent, mild, moderate or severe, with a corresponding score from 0 to 3. The total composite scale goes from 0 to 18 points.

Ibrexafungerp (”ibrexa” or ”IBX”) is an investigational drug.

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VANISH Phase 3 Program – Efficacy (mITT)

Efficacy at Day-10 TOC and Day-25 FU (mITT) VVC VANISH Program VANISH-306

IBX 300mg BID (n=188)

VANISH-303

IBX 300mg BID (n=188)

Clinical Cure (0 S&S) at TOC 63.3%* 50.5%** Mycological Eradication at TOC 58.5%** 49.5%** Clinical Improvement (0 or 1 S&S) at TOC 72.3%* 64.4%** Complete Symptom Resolution at FU 73.9%** 59.6%*

* p value ≤ 0.01 ** p value ≤ 0.001

Ibrexafungerp met its endpoints and achieved highly statistically significant superiority vs. placebo

Ibrexafungerp (”ibrexa” or ”IBX”) is an investigational drug.

24

Sustained Efficacy at Follow-up Visit (Day 25)

Results at Follow-Up (Day 25) for VANISH studies represent % of patients that completed the study without the need for antifungal rescue therapy and had no symptoms at Follow-Up visit.

Consistent efficacy of ibrexafungerp across studies Sustained efficacy with higher clinical cure rates at Day 25

Ibrexafungerp (”ibrexa” or ”IBX”) is an investigational drug.

63% 74% 51% 60% 52% 70% 58% 50%

0% 20% 40% 60% 80% TOC (Day-10) FU (Day-25) TOC (Day-10) FU (Day-25) TOC (Day-10) FU (Day-25) TOC (Day-10) FU (Day-25)

VANISH-306 IBX 300mg BID (n=188)

DOVE Phase 2 Study

Fluconazole Clinical Cure (0 S&S)

VANISH Phase 3 Studies

VANISH-303 IBX 300mg BID (n=188) DOVE P2 Study - IBX 300mg BID (n=27) DOVE P2 Study - FLU 150mg BID (n=24)

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VANISH-306 – Safety Consistent with Prior Findings

• No systemic safety issues | No discontinuations due to study drug
• The majority of Treatment-Emergent AEs (TEAEs) observed at a higher frequency in

the ibrexafungerp group were gastrointestinal in nature

• The three most common GI events were diarrhea/loose stool, nausea, abdominal pain
• Combined safety database of VANISH and DOVE programs includes more than 850

patients enrolled, with 575 ibrexafungerp-treated patients (one-day 300mg BID dose)

Ibrexafungerp (”ibrexa” or ”IBX”) is an investigational drug.

Safety Set VANISH-306

IBX 300mg BID (n=298)

VANISH + DOVE

IBX 300mg BID (n=575)

Diarrhea/Loose stool 9.4%

86% mild

16.7%

76% mild

Nausea 8.4%

92% mild

11.8%

87% mild

Abdominal pain 2.7%

100% mild

4.5%

92% mild

26

CANDLE Program: rVVC Pivotal Study + Sub-Study for Fluconazole Failures

Subjects who fail the Fluconazole treatment (i.e., not randomized) will be assigned to a single day ibrexafungerp treatment (open label study)

Prevention of Recurrence Phase (DAY1) Treatment No Randomization IBX 300-mg BID for 1 day TEST OF CURE (DAY 8 -DAY 14) FOLLOW UP (DAY 25)

Randomized, double-blind, placebo-controlled

Ibrexafungerp (”ibrexa” or ”IBX”) is an investigational drug.

If NO resolution

Acute Phase Fluconazole Treatment (Days -14, -11 & -8) Study Treatment Period (Day 1 through Week 24 [TOC]) Double-blind If significant resolution of signs and symptoms at Baseline (Day 1) SCY-078 once every 4 weeks for a total of 6 doses

(D1 through W20)

Placebo once every 4 weeks for a total of 6 doses

(D1 through W20)

Test of Cure (Week 24)

scynexis.com

Hospital: Invasive Fungal Infections

“Invasive fungal infections will not go away any time soon. Therefore, we need to circumvent resistance to treatment by continued discovery and development of new antifungal agents and strategies.”

• Dr. John Perfect

Nature Reviews/Drug Discoveries (2017)

28

Differences Between Antifungals and Antibacterials in Hospital Setting

Not a Crowded Market

• nly 3 available

classes and less than 10 products

High Mortality à Need for New Tx

up to 40-50% depending on the infection

Long Treatment Durations

up to 6-12 weeks depending on the infection

Attractive Pricing Estimated Peak Sales of $500M-$1BN+

Fluconazole peak sales of $1.2BN

Different Treatment Paradigm

immediate use of most potent agents

$- $5,000 $10,000 $15,000 $20,000 $25,000 $30,000 $35,000 $40,000 $45,000

Q1 Q2 Q3 Q4 Q5 Q6 Q7 Q8 Q9 Q10 Q11 Q12 Q13 Q14 Q15 $ Sales ('000)

Cresemba

• Avg. last 4 antibiotics launch*
• Launched in 2015 only for the treatment of Aspergillus

and Mucor infections (less than 50K patients in the U.S.)

• Already reached ~$150M U.S. sales in CY2018

* Includes Avycaz, Dalvance,

Orbactiv, Zarbaxa

A more attractive systemic antifungal market has resulted in many successful commercial stories

Cresemba (isavuconazole) is the most recent antifungal commercially launched

29

Ibrexafungerp Hospital Commercial Opportunity

Key Ibrexafungerp Attributes

ü Broad spectrum - Candida, Aspergillus, Pneumocystis, dimorphic fungi ü Fungicidal vs. Candida ü Validated MoA - low cross resistance with echinocandins due to different binding site ü Active vs. resistant strains, incl. C. auris ü Non-azole oral therapy - no concerns about liver toxicity and low risk of DDIs ü High tissue distribution, incl. abscess and bone ü No safety signals, >600 subjects exposed

Potential Ibrexafungerp Uses

ü Salvage use in patients failing other antifungals ü Oral step-down after IV echinocandins for patients with azole- resistant Candida spp. ü Empirically for patients with a suspected fungal pathogen ü Prophylactically for patients at risk of fungal infections ü Combination treatment with an azole for invasive aspergillosis ü Chronic candidiasis patients

Ibrexafungerp (”ibrexa” or ”IBX”) is an investigational drug.

30

Ibrexafungerp Development Programs

• Phase 3, open label,

uncontrolled, global (ongoing)

• Subjects with invasive

fungal infections refractory or intolerant to SoC

• Amended protocol to

broaden range of infections and treatment duration

• Positive 2nd interim

analysis reported in

• Jan. 2020

FURI SCYNERGIA CARES

• Phase 3, open label,

uncontrolled, global (ongoing)

• Subjects with Candida

auris infections

• 2 positive case studies

reported in Apr. 2019

• Expanding into other

countries

• Phase 2, randomized,

double blinded, ibrexafungerp in combination with Voriconazole (ongoing)

• Subjects with Invasive

Aspergillosis Potential Eligibility for Limited Population Pathway for Antibacterial and Antifungal Drugs (LPAD)

Ibrexafungerp (”ibrexa” or ”IBX”) is an investigational drug.

31

FURI Study: Design/Demographics

• Phase 3: open-label, orally-administered

ibrexafungerp (IBX)

• Subjects: demonstrated invasive or severe

mucocutaneous Candida infections:

– Refractory to SoC antifungal agents, – Intolerant to to SoC antifungal agents, or – Other oral antifungal options are not adequate for continued therapy after initial IV standard

• f care antifungal
• Sites: US, Germany, UK, Spain, Austria,

Netherlands

• Dosing: Loading dose of oral IBX 750mg

twice a day x 2 days, followed by oral IBX 750mg QD

• Duration: 90 days maximum therapy

– Patients requiring more than 90 days were enrolled in an expanded access program

Aggregate Analysis to Date

# of Patients 41 Mean Days of Therapy 37.1 (5-90) Invasive Candidiasis Mucocutaneous Candidiasis 24 (59%) 17 (41%) Site of Fungal Infections

• Candidemia
• Intra-abdominal

abscesses

• Esophageal

candidiasis

• Oropharyngeal

candidiasis

• Bone infections

Most Common Fungal Pathogens

• Candida glabrata
• Candida albicans
• Candida krusei

Ibrexafungerp (”ibrexa” or ”IBX”) is an investigational drug.

32 Global Response 1st Interim DRC Analysis n=20 2nd Interim DRC Analysis n=21 Aggregate Analysis to Date n=41 Complete or Partial response 11 12 23 (56%) Stable Disease 6 5 11 (27%) Total 17 17 34 (83%) No Response 2 4 6 (15%) Indeterminate 1 1 (2%)

FURI Study: Key Outcomes

• Oral ibrexafungerp was generally safe and well-tolerated
• One death while on study drug was reported

– Due to underlying condition and deemed unrelated to study drug

• Most common treatment-related AEs were mild to moderate GI events

34 out of 41 (83%) patients experienced a clinical benefit from ibrexafungerp treatment (complete, partial or stable responses)

Ibrexafungerp (”ibrexa” or ”IBX”) is an investigational drug. Independent Data Review Committee (41 patients).

33

FURI Study: Conclusion

Ibrexafungerp (”ibrexa” or ”IBX”) is an investigational drug.

Results from the second cohort consistent with the first interim analysis

1

Confirmed clinical antifungal activity of oral ibrexafungerp in patients with difficult- to-treat, severe, mucocutaneous and invasive fungal infections

2

Confirmed clinical antifungal activity of oral ibrexafungerp in patients with difficult- to-treat, severe, mucocutaneous and invasive fungal infections

3

Ibrexafungerp was generally safe and well-tolerated

4

Results reinforce the potential of oral ibrexafungerp to be a much-needed alternative to existing fungal therapies and long-term IV treatment

5

Results further support a potential future submission under the LPAD regulatory pathway

6

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Ibrexafungerp vs. C. auris – CARES Study

• In vitro Evidence

– CDC study against 100 C. auris strains

• Echinocandin-resistant isolates susceptible to ibrexafungerp
• No significant differences in MIC values between strains

indicating that genetic diversity does not influence activity

– CASE Western Study in 16 C. auris strains

• In vivo Evidence

– 2 animal models of C. auris infections confirmed activity

• Clinical Evidence

– Phase 3 CARES study ongoing – First reported patients responded successfully to

• ral ibrexafungerp
• C. auris before Ibrexa
• C. auris after Ibrexa

Ibrexafungerp (”ibrexa” or ”IBX”) is an investigational drug.

35

Ibrexafungerp vs. Invasive Aspergillosis (IA)

Ongoing enrollment in Phase 2 Oral study (~60 patients)

Ibrexafungerp (”ibrexa” or ”IBX”) is an investigational drug.

Why Oral Ibrexafungerp? High activity vs. azole-resistant Aspergillus High penetration to the lungs Combination therapy may provide improved outcomes

Pre-clinical synergistic activity with azoles Clinical benefit of combination therapy reported in literature

Need for New Treatment Approaches Optimal for combination therapy

Oral Safe and well-tolerated Low risk of DDIs

Emergence of A. fumigatus Resistance Unsatisfactory Clinical Outcomes

Mortality still up to 50% Long treatment durations

36

Ibrexafungerp IA In Vivo Data to-Date

• Neutropenic rabbit model of pulmonary aspergillosis evaluating ibrexafungerp alone

and in combination with isavuconazole

• Doses: (IV) ibrexafungerp (SCY-078) 2.5, 7.5 mg/kg; (PO) isavuconazole 40 mg/kg for

12 days

• Combination therapy resulted in better efficacy vs. monotherapy for all efficacy

parameters, including significantly improved survival and pulmonary infarct score

Ibrexafungerp (”ibrexa” or ”IBX”) is an investigational drug.