Ibrexafungerp First Representative of a Novel Oral/IV Antifungal Family Corporate Presentation - Dec. 2019 - cloudfront.net
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Ibrexafungerp
First Representative of a Novel Oral/IV
Antifungal Family
Corporate Presentation – Dec. 2019
“Committed to positively impacting the lives of patients suffering from difficult-to-treat
and often life-threatening infections”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, 2018 and in the Company’s quarterly report on Form 10-Q for the quarter ended
September, 30 2019, 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.
2Company Overview | Introduction
scynexis.comFungal Infections: a Growing Public
Health Threat
1. The Clinical Problems
• In the Hospital: rising Invasive Fungal Infections with high mortality
• In the Community: difficult-to-treat Mucosal Fungal Infections in millions of women
2. The Medical Needs
• Very few systemic drugs available to treat fungal infections and even fewer oral
options
3. The Emerging Concerns
• Antifungal resistance and appearance of new alarming fungal species
April 6, 2019
4Ibrexafungerp: A Potential Solution for
the Fungal Infection Crisis
Outpatient/Community Setting Hospital Setting
Vulvovaginal Candidiasis (VVC) Phase 3 Refractory Invasive Fungal Phase 3
Recurrent VVC (SPA agreement) Phase 3 Infections (rIFI) - LPAD
Refractory Mucocutaneous Phase 2/3 C. auris infections - LPAD Phase 3
Infections Aspergillosis in Combination Phase 2
• Only ONE systemic oral product approved for VVC • Only 3 classes and less than 10 approved
and NO approved treatment for rVVC systemic products
• >14mm fluconazole TRx/year for VVC in the U.S. • Growing resistance to azoles, the only oral drug
• Ibrexafungerp as single-day oral treatment for VVC • Multidrug-resistant emerging fungi
with a potential $400-$600mm peak sales in the U.S. • Still high mortality with current SoCs
NDA anticipated in 2nd Half Worldwide Rights with 10 to 12 years of Regulatory
2020 for VVC Composition Matter Patent Exclusivity in the U.S
(Cash runway past NDA submission) Protection up to 2035 (QIDP/Orphan Drug Status/Fast Track)
Ibrexafungerp is an investigational drug. 5Ibrexafungerp: 1st Representative of a
Novel Antifungal Class
Broad Spectrum Activity vs.
Candida, Aspergillus, Resistant Strains
Pneumocystis & others MDR strains,
2000+ strains tested including C. auris
Oral Formulation Fungicidal vs.
in Phase 3 Candida
IV in pre-clinical Benefits over
development fungistatic agents
20-hour Half-Life
Validated MoA
No Safety Signals High Tissue
Minimal risk of off-target effects
900+ subjects exposed Differentiated binding vs. echinocandins
Penetration
Low Risk of DDIs
Ibrexafungerp is an investigational drug. Items listed on this slide illustrate ibrexafungerp target attributes 6Antifungal Innovation is Lacking
Ibrexafungerp combines the best attributes of all other classes
Ibrexa Echinocandin Azole Polyene
Market Intro ~2021 2000s 1980s 1960s
Active vs. Candida albicans
Spectrum of Activity
Active vs. non-albicans Candida
Active vs. azole-resistant
Active vs. echinocandin-resistant*
Active vs. Aspergillus spp.
Lack of renal, hepatic, CNS Tox.
Safety
Low risk for DDIs
Oral Bioavailability
* Active against most echinocandin-resistant Candida isolates
Ibrexafungerp is an investigational drug – 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
7Ibrexafungerp: Ongoing Programs / Timing
2018 2019 2020 2021
Positive Data
1 P3 (VANISH 303)
Acute Complete
Nov.’19
NDA
DOVE P2b
Vulvovaginal H2:20
Outpatient
(Jul. 2018) 1 P3 (VANISH 306)
Candidiasis Ongoing
Data by
early Q2’20
Recurrent
1 P3 (CANDLE) – SPA agreement
Vulvovaginal sNDA
Ongoing H2:21
Candidiasis
Invasive
Aspergillosis 1 P2 study (SCYNERGIA)
(Combination Ongoing
Therapy)
Hospital
FURI Study (open-label, refractory IFIs) Potential
Refractory 2nd interim
Invasive analysis
Prelim Data (Jan ‘19)
Fungal Est. Q1’20
Infections CARES Study
(open-label, emergency protocol, C. auris)
Key Milestones 8
Other potential oral indications: Prophylaxis, Chronic Fungal Infections
Ibrexafungerp is an investigational drug
Estimated NDA filing 8Ibrexafungerp: Significant Near-Term
Milestones
SCYNERGIA
rVVC sNDA
P2 top-line
Submission
data
VANISH-306 CANDLE-304
FURI 2nd aVVC NDA aVVC
P3 aVVC top- P3 rVVC top-
data review Submission Approval
line data line data
Q1'20 Q2'20 H2'20 H1'21 H2'21
Potential other milestones in 2020-2021: FURI and CARES interim analyses and
Business Development opportunities
Ibrexafungerp is an investigational drug 9SCYX: Stock Highlights & Financial
Information
$1.90 | $0.35 ~$64M | $50M ~300K shares
52-week high/low Market Cap | Enterprise Value 3-month average trading volume
$28.4M | $14M 58M | 88M 1.3% | 57M
Cash | Long-term debt Basic | fully-diluted shares out. Insider ownership | Free float
Top Institutional Holders (as of Q3’19)
Top Insiders:
• Dr. Marco Taglietti: 527K shares
• Dr. David Angulo: 124K shares
• Guy MacDonald: 40K shares
10SCYX: Experienced Team
Leadership Board of Directors
Positive track record in drug development, Diverse backgrounds &
commercial & antifungal expertise operating experience in healthcare
CEO: Marco Taglietti, M.D. Guy Macdonald, Chairman (Tetraphase, Merck)
Schering-Plough, Stiefel, Forest Labs
Armando Anido (Zynerba, NuPathe, Auxilium)
CMO: David Angulo, M.D.
Schering-Plough, Stiefel, Brickell Biotech Steven Gilman, PhD (Contrafect, Cubist)
CFO: Eric Francois Ann Hanham, PhD (BAR Capital, Burrill, FDA)
Cowen, Lazard, Topi
David Hastings (Arbutus Biopharma, Unilife, Incyte)
General Counsel: Scott Sukenick
Cooley, Simpson Thacher
Women’s Health Commercial: David Stern
Full-time consultant
Symbiomix Therapeutics, Celmatix, OvaScience, Merck Serono Total of 27 employees:
Hospital Infections Commercial: Tom Chen • 70% R&D
Full-time consultant • 30% SG&A, Commercial, BD
Basilea Pharmaceutical, Cubist
11Outpatient/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
scynexis.comOral Ibrexafungerp in VVC
Highly prevalent infection affecting 125M+ women Strong
worldwide Competitive
Clear Regulatory Path with high
Positioning
2nd most common
• New oral option to
cause of vaginitis chance of technical success address high rate of
Only one oral fluconazole failures
approved product 3 Phase 3 Studies vs. Strong Phase 2 Data
(fluconazole) Placebo: vs. Fluconazole • No current approved
- 2 in aVVC (1st Phase treatment for rVVC
14MM/Year 3 study highly Strong short- and long-
Fluconazole Rx (U.S.) statistically positive term efficacy High U.S.
18MM/Year Topical vs. Placebo) Lower need for rescue Commercial
OTC Units (U.S.) - 1 in rVVC (SPA medication compared
agreement) to fluconazole (4% vs. Potential
29%) • Estimated potential
VVC NDA planned for U.S. Peak Sales of
2nd half of 2020 No safety signal ~$400 to
rVVC sNDA planned Good tolerability 600MM/year
for 2nd half of 2021
Ibrexafungerp is an investigational drug. 13Attractive Characteristics of the Women’s
Health (VVC) Opportunity
Several precedents of successful Solosec (secnidazole;
commercial launches in the Women’s antimicrobial) is one of the most
Health space recent commercial launches
• Launched in 2018 for the treatment of Bacterial Vaginosis
Not a High Impact Large Patient • “me-too” product in generic market; convenience-play only
Crowded on Quality of • Reached ~$21M U.S. sales in its 1st year; expected to
Population
Market Life High reach ~$30mm in year 2
(~8mm per year -
(only 1 available
Unmet Need ~2mm with
class – 1 oral recurrent or
product – (up to 30-40% of
patients unsatisfied moderate/severe First Full Year Sales: ~$21 million
fluconazole; not infections)
First Half of 2019 Sales: ~$14 million
approved for rVVC) with fluconazole)
Efficient Estimated
Attractive Commercial Peak Sales of
Pricing Model $500M-$1BN+
(low barrier for (concentration of
(Fluconazole peak
market access) high-volume
sales
prescribers, limited
of $1.2BN)
promotion)
14Ibrexafungerp VVC Commercial Opportunity
Our vision for VVC: The only novel oral non-azole agent to treat VVC
and prevent recurrent VVC
Key Ibrexafungerp Attributes Potential Ibrexafungerp Uses
Fungicidal (kills the pathogen) via novel Moderate to severe VVC patients
MoA to provide sustained activity versus Complicated VVC patients with co-
fluconazole (fungistatic) morbidities (i.e., diabetics)
Broad spectrum, incl. fluconazole-resistant Patients with 2 or more episodes where
Candida strains the physician wants to try another
therapy
Non-azole oral therapy - no concerns about
Recurrent Patients
liver toxicity
Fluconazole single-day dose failures-
Enhanced activity at low vaginal pH providing a different class of therapy for
High vaginal tissue penetration one day versus 1 week of fluconazole
No safety signals (>600 subjects exposed) Fluconazole-resistant Candida patients
No pregnancy warning - important with - When fluconazole fails, most
recurrent patients who may become clinicians feel that it is because the
pregnant while on 6-month therapy organism was resistant to fluconazole
Women of child-bearing age who plan
to become pregnant (or are at risk of
becoming pregnant)
Ibrexafungerp is an investigational drug 15Ibrexafungerp VVC U.S. Opportunity
Recurrent Moderate/Severe Mild
(~9% | ~650K cases) (~21% | ~1.6M cases) (~70% | ~5.2M cases)
Ibrexafungerp’s Target Population OTC + Fluconazole satisfactory
Target Label for Ibrexafungerp: ”Treatment of VVC and prevention of recurrent VVC”
Recurrent Moderate/Severe
~650K ~1.6M U.S. Target Population
~30% ~15% Ibrexa Penetration Rates
~$1,800 to $2,400 ~$300 to $400 Ibrexa Pricing per Course
~$350-470M ~$70-100M Ibrexa U.S. Net Sales
Ibrexa U.S. Sales Potential ~$420-570M
Conservative estimates Ibrexa potential sales represent ~5% of overall fluconazole units (~29M) in V VC
ROW opportunity expected to be similar to U.S. market, pricing TBD
Ibrexafungerp is an investigational drug
Preliminary assessment (to be further validated). Sources: Blue Print/SCYNEXIS Primary HCPs and Payers Market Research
Symphony Data 2018 16Ibrexafungerp Path Forward for VVC
2018 2019 2020 2021
Positive
1 P3 (VANISH Data
Acute VVC P2 DOVE 303) Complete Nov.’19 NDA
(VANISH) Results 1 P3 (VANISH Data by H2:20
306) Ongoing early
Q2’20
Recurrent VVC One Phase 3 recurrent VVC Study Potential
sNDA Filing
(CANDLE) (SPA agreement)
H2:2021
Two Phase 3 acute VVC studies ongoing (~350 patients per study
superiority vs. placebo) – one in the U.S. and one global
• U.S. study (VANISH 303): positive top-line data released in Nov 2019
• Global study (VANISH 306): top-line data expected early Q2 2020
• Program adequate also for European Approval
One global Phase 3 recurrent VVC study (~350 patients superiority vs.
placebo) ongoing
• SPA agreement with FDA received in July 2019
Ibrexafungerp is an investigational drug. 17Ibrexafungerp Phase 3 VANISH-303 Study
Key Design Elements Key Findings
Achieved superiority versus placebo at
Randomized, multi-center, double-blind,
placebo-controlled (Age ≥12 years)
Test-of-Cure (TOC):
Primary = Clinical cure (0 signs & symptoms) –
p=0.001
Secondary =Mycological eradication (secondary)
mITT patients with moderate-to-severe – pKey Efficacy of Ibrexafungerp from
Phase 3 VANISH-303 at TOC (mITT)
Ibrexafungerp met its endpoints and achieved superiority vs. placebo
Ibrexafungerp - Endpoint at TOC (~Day 10) p-Value (vs. placebo)
Clinical Cure (0 S&S) P=0.001
Primary
50.5% (95 % CI)= (1.20, 2.43)
Mycological Eradication PKey Efficacy of Ibrexafungerp from P2b
DOVE Study – FDA Clinical Endpoints
Day 10 Day 25
Comparable activity of 600mg ibrexafungerp and fluconazole
New FDA at Day 10… with improved sustained benefit of ibrexafungerp
over time Previous FDA
primary endpoint
primary endpoint
ADDITIONAL CLINICALLY RELEVANT FINDINGS:
• Greater need for rescue antifungal therapy in the fluconazole group
• Sustained effect of ibrexafungerp (greater reduction of S&S vs. fluconazole) over 25 days
Results based on mITT population | * No rescue antifungal use.
Ibrexafungerp is an investigational drug 20CANDLE Program: rVVC Pivotal Study
+ Sub-Study for Fluconazole Failures
Randomized, double-blind,
placebo-controlled
Subjects who fail the Fluconazole
Acute Phase Fluconazole Treatment (Days treatment (i.e., not randomized) will be
-14, -11 & -8)
assigned to a single day ibrexafungerp
treatment (open label study)
If significant resolution of signs and
symptoms at Baseline (Day 1) If NO resolution
(DAY1) Treatment
No Randomization
Study Treatment Period
(Day 1 through Week 24 [TOC])
Double-blind
Prevention of Recurrence Phase
IBX 300-mg
BID for 1 day
SCY-078 once every 4 Placebo once every 4
weeks for a total of 6 weeks for a total of 6
doses doses
(D1 through W20) (D1 through W20)
Test of Cure TEST OF CURE (DAY 8 -DAY 14)
(Week 24)
FOLLOW UP (DAY 25)
Ibrexafungerp is an investigational drug 21Hospital:
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)
scynexis.comDifferences Between Antifungals and
Antibacterials in Hospital Setting
A more attractive systemic antifungal Cresemba (isavuconazole) is the
market has resulted in many successful most recent antifungal
commercial stories commercially launched
• Launched in 2015 only for the treatment of Aspergillus
and Mucor infections (less than 50K patients in the U.S.)
Not a High Mortality Long • Already reached ~$150M U.S. sales in CY2018
Crowded Need for Treatment
Market New Tx Durations $45,000
(only 3 available (up to 40-50% (up to 6-12 weeks
$40,000 Cresemba
classes and less depending depending on the
than 10 products) on the infection) infection) $35,000
Avg. last 4 antibiotics launch*
$30,000 * Includes Avycaz, Dalvance,
$ Sales ('000)
Orbactiv, Zarbaxa
$25,000
Different Estimated $20,000
Treatment Peak Sales of $15,000
Attractive $500M-$1BN+
Pricing Paradigm $10,000
(Fluconazole peak
(immediate use of $5,000
sales
most potent agents)
of $1.2BN) $-
Q1
Q2
Q3
Q4
Q5
Q6
Q7
Q8
Q9
Q10
Q11
Q12
Q13
Q14
Q15
23Ibrexafungerp Hospital Commercial
Opportunity
Key Ibrexafungerp Attributes Potential Ibrexafungerp Uses
Broad spectrum - Candida, Aspergillus, Salvage use in patients failing
Pneumocystis, dimorphic fungi other antifungals
Fungicidal vs. Candida Oral step-down after IV
Validated MoA - low cross resistance with echinocandins for patients with
echinocandins due to different binding site azole-resistant Candida spp.
Empirically for patients with a
Active vs. resistant strains, incl. C. auris
suspected fungal pathogen
Non-azole oral therapy - no concerns about Prophylactically for patients at risk
liver toxicity and low risk of DDIs of fungal infections
High tissue distribution, incl. abscess and Combination treatment with an
bone azole for invasive aspergillosis
No safety signals, >600 subjects exposed Chronic candidiasis patients
Ibrexafungerp is an investigational drug 24Ibrexafungerp Development Programs
FURI CARES SCYNERGIA
• Phase 3, open label, • Phase 3, open label, • Phase 2,
uncontrolled, global uncontrolled, global randomized, double
(ongoing) (ongoing) blinded,
• Subjects with • Subjects with ibrexafungerp in
invasive fungal combination with
infections refractory Candida auris
infections Voriconazole
or intolerant to SoC
• 2 positive case (ongoing)
• Amended protocol
to broaden range studies reported in • Subjects with
of infections Apr. 2019 Invasive
• 2nd interim analysis • Expending into Aspergillosis
planned for Q1 other countries
2020
Potential Eligibility for Limited Population Pathway for
Antibacterial and Antifungal Drugs (LPAD)
Ibrexafungerp is an investigational drug 25Ibrexafungerp vs. rIFI – FURI Study
Positive Results from Preliminary Data Review on 20 patients
Patient Populations Efficacy
By type of infections: • 85% (17 out of 20) showed clinical benefits
• 45% mucocutaneous • 11 patients with complete/partial response
candidiasis • 6 patients with stable disease
• 55% invasive candidiasis • 2 patients did not respond
By Pathogens: • 1 patient’s outcome was considered
• 55% C. glabrata
undetermined
• 20% C. krusei Safety/Tolerability
• 15% C. albicans • Generally well tolerated
• 5% C. parapsilosis
• Nausea and diarrhea most common treatment-
• 5% unidentified
related AEs
• No deaths related to progression of the fungal
disease or to the study drug were reported
Ibrexafungerp is an investigational drug.
Independent Data Review Committee (20 patients) 26Ibrexafungerp vs. C. auris – CARES Study
C. auris before Ibrexa
• In-Vitro Evidence
– CDC study against 100 C. auris strains
• No significant differences in MIC values between
strains indicating that genetic diversity does not
influence activity
• Echinocandin-resistant isolates susceptible to
ibrexafungerp
– CASE Western Study in 16 C. auris strains
C. auris after Ibrexa • 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 oral ibrexafungerp
Ibrexafungerp is an investigational drug. 27Ibrexafungerp vs. Invasive Aspergillosis (IA)
Unsatisfactory Clinical Combination therapy may provide
Outcomes improved outcomes
Why Oral Ibrexafungerp?
Pre-clinical synergistic activity with azoles
Mortality still up to 50%
Clinical benefit of combination therapy reported in
Long treatment durations
literature
High activity vs. azole-resistant
Emergence of A.
Aspergillus
fumigatus Resistance
High penetration to the lungs
Optimal for combination therapy
Need for New Treatment Oral
Approaches Safe and well-tolerated
Low risk of DDIs
Ongoing site initiation activities for Phase 2 Oral study (~60 patients)
Ibrexafungerp is an investigational drug 28Ibrexafungerp 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 is an investigational drug 29Thank You
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