Oral Ibrexafungerp in Moderate to Severe Acute Vulvovaginal - - PowerPoint PPT Presentation

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Oral Ibrexafungerp in Moderate to Severe Acute Vulvovaginal - - PowerPoint PPT Presentation

Oct 20, 2022 11 likes •234 views

A Phase 2b, Dose-Finding Study Evaluating Oral Ibrexafungerp in Moderate to Severe Acute Vulvovaginal Candidiasis (DOVE) Nkechi Azie, MD, FIDSA Vice-President of Clinical Development SCYNEXIS, Inc. 1 Forward-Looking Statements Certain

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A Phase 2b, Dose-Finding Study Evaluating Oral Ibrexafungerp in Moderate to Severe Acute Vulvovaginal Candidiasis (DOVE)

Nkechi Azie, MD, FIDSA Vice-President of Clinical Development SCYNEXIS, Inc.

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SLIDE 2

Forward-Looking Statements

2 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 “Risks Factors” in the Company’s annual report on Form 10-K, 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.

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SLIDE 3

Disclosures

  • Nkechi Azie, MD is an employee and shareholder of

SCYNEXIS, Inc

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SLIDE 4

Ibrexafungerp (formerly SCY-078)

  • New WHO INN designation
  • SCY-078, Triterpenoid class provided new stem
  • Fungal Triterpenoid

“fungerp”

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SLIDE 5

CONFIDENTIAL

Ibrexafungerp A Novel Triterpenoid Antifungal

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Key Attributes

  • Activity against: Candida spp.; Aspergillus

spp.; Pneumocystis spp.; Endemic fungi

  • Active against azole-R and Candin-R strains
  • Oral formulations
  • Enhanced activity at low PH
  • Large tissue distribution (Human Vdss > 8 L/kg)
  • No Preclinical fetal Toxicity
  • Favorable safety profile > 700 exposed
  • Low risk of drug-drug Interactions

Novel Glucan Synthase Inhibitor (GSI)

Structurally distinct from other GSIs (echinocandins)

  • Different enzyme-drug interaction

→ lower impact of common FKS mutations

  • Oral bioavailability

CASPO

Ibrexa

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SLIDE 6

CONFIDENTIAL

In Vitro Activity of Ibrexafungerp vs. Fluconazole-Resistant Strains

Ibrexafungerp displayed activity against fluconazole resistant Candida spp. similar to that observed against Wild-Type

Candida glabrata (N) UAB study Ibrexafungerp (mcg/mL) [MIC50 (MIC90)] Fluconazole susceptible (N=137) 0.5 (0.5) Fluconazole resistant (N=162) 0.5 (0.5)

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Ibrexafungerp is Fungicidal vs. Candida spp.

Scorneaux B., et al. AAC, March 2017; 61 (3)

  • Fluconazole is fungistatic against Candida spp. = inhibits the growth but doesn’t kill the fungi

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In Vitro Activity is Enhanced at Low (Vaginal) pH

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Larkin et al., IDSOG 2017

Ten strains each of vaginal Candida isolates from a recent clinical trial were tested

pH level 7.0 5.72 4.5 C.glabrata MIC50 (mg/L) Ibrexafungerp 0.5 - 1 0.5 0.031 - 0.063 Fluconazole 0.5 - 2 2 – 16 1 - 16 C.albicans MIC50 (mg/L) Ibrexafungerp 0.125 – 0.5 0.125-0.25 0.16-0.031 Fluconazole <0.125 - 1 <0.125-1 0.25 - 8

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SLIDE 9

Vaginal Tissue Concentration

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Plasma to Genital Tissue Ratio: Fluconazole – 1:1 Ibrexafungerp – 1:9

Felton et al, CMR, 2014; Wring et al, AAC, 2019

Highest Tissue Concentration among antifungals reported.

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SLIDE 10

Completed Studies

Over 500 subjects received at least one dose of ibrexafungerp in Phase 1 studies and Phase 2 studies.

  • Sixteen Phase I studies completed including

– SAD; MAD studies – Food effect – Age and Gender studies – DDI

  • Three phase 2 studies completed

– 2 in VVC

– 1 in Invasive Candidiasis

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SLIDE 11

scynexis.com

A Phase 2, Multicenter, Randomized, Double- Blind, Double-Dummy, Active-Controlled, Dose-Finding Study to Compare the Safety and Efficacy of Oral Ibrexafungerp vs. Oral Fluconazole in Subjects with Acute Vulvovaginal Candidiasis (DOVE)

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Ibrexafungerp- 204 (DOVE): Study Objectives

  • Primary Objectives:
  • To identify the recommended dose of oral ibrexafungerp in

subjects with moderate to severe acute vulvovaginal candidiasis (aVVC) by comparing the efficacy of different dose levels and dosing regimens of oral ibrexafungerp

  • Secondary Objectives:
  • To evaluate the efficacy of oral ibrexafungerp in subjects

with aVVC based on mycological and clinical outcomes

  • To evaluate the safety and tolerability of different dose

levels and dosing regimens of oral ibrexafungerp in subjects with aVVC

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SLIDE 13

DOVE Study Design

Key Inclusions: ✓ Moderate to severe VVC (signs and symptoms of ≥7) ✓ KOH + ✓ pH <4.5 ~30 patients per arm Primary population for analysis mITT = Culture-confirmed VVC

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  • Key Endpoints:
  • At Test-of-Cure (T.O.C.) and Follow-up visit (F.U.)
  • Clinical Cure (Signs and Symptoms = 0)
  • Significant improvement (Signs and Symptoms = 0 or 1)
  • Mycological eradication (negative culture for yeast)
  • Use of rescue antifungal treatment
  • Safety and tolerability
  • 186 subjects enrolled

– 153 with culture-confirmed VVC, (mITT) – Median age 32 years – Race: White 59%, Black or African American 39%, Other 2%

DOVE Study Design / Demographics

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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.

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DOVE Study Key Efficacy Results Ibrexafungerp 600mg Dose (mITT)

Results based on mITT population | * No rescue antifungal use. Signs and Symptoms [S&S] score is 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 (0), mild (1), moderate (2) or severe (3).

Day 10 (Test-of-Cure) Day 25 (Follow-up)

52% 70% 63% 58% 71% 63%

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Clinical Cure (0 S&S) * 0 or 1 S&S * Mycological Eradication Ibrexafungerp 600mg Dose (n=27) FLU (n=24)

70% 81% 48% 50% 58% 38%

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%

0 S&S * 0 or 1 S&S * Mycological Eradication

Ibrexafungerp 600mg Dose (n=27) FLU (n=24)

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DOVE Study Additional Efficacy Results Ibrexafungerp 600mg Dose (mITT)

P value based on change from baseline score mean difference between Ibrexafungerp 600mg and FLU.

4% 29%

0% 5% 10% 15% 20% 25% 30% 35% Ibrexafungerp 600mg Dose (n=27) FLU (n=24)

DOVE - % of Required Rescue Therapy (mITT)

9.8 1.0 0.4 10.1 1.8 2.6

0.0 2.0 4.0 6.0 8.0 10.0 12.0 Baseline Day 10 TOC visit Day 25 FU visit

DOVE- Mean Signs and Symptoms Score

Ibrexafungerp 600mg Dose (n=27) FLU (n=24)

P=0.01

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Profile of Patients Requiring Rescue Therapy in DOVE Study

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Patient Candida spp. Timing of Rescue Medication Rescue Antifungal Therapy IBX Pt. 1

  • C. albicans

FU Oral Fluconazole FLU Pt. 1

  • C. glabrata

TOC Topical Terconazole FLU Pt. 2

  • C. albicans

Between TOC and FU Oral Fluconazole FLU Pt. 3

  • C. albicans

Between TOC and FU Oral Fluconazole Topical Clotrimazole FLU Pt. 4

  • C. albicans

FU Oral Fluconazole Topical Terconazole FLU Pt. 5

  • C. albicans

FU Oral Fluconazole FLU Pt. 6

  • C. kefyrs,
  • C. tropicalis

FU Oral Fluconazole FLU Pt. 7

  • C. albicans

FU Oral Fluconazole Ibrexafungerp 1 patient N=27 (4%) Fluconazole 7 patients N=24 (29%) TOC- Test-of-Cure (Day 10); FU- Follow-up (Day 25)

Almost all of the failures received Oral FLU

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SLIDE 18

2 4 6 8 10 12 14 16 Screening TOC FU

Vaginal S&S Score Patient Visit

Ibrexafungerp Vaginal S&S (n=27)

2 4 6 8 10 12 14 16 18 Screening TOC FU

Vaginal S&S Score Patient Visit

Fluconazole Vaginal S&S (n=24)

DOVE Study: Individual Patient Vaginal S&S Score during Study Period

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TOC- Test-of-Cure (Day 10) FU- Follow-up (Day 25)

Vaginal Signs & Symptoms Ibrexafungerp Fluconazole Mean score of patients with S&S score >0 at Follow-up visit 1.7 5.9

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.

TOC- Test-of-Cure (Day 10) FU- Follow-up (Day 25)

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DOVE Study Key Tolerability Results Ibrexafungerp 600mg Dose

Results based on safety population.

  • Most Adverse Events were mild to moderate and lasting 1 day
  • No Serious Adverse Events
  • No Discontinuations

10% 17% 3% 0% 6% 3% 16% 0% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%

Nausea Diarrhea Abdominal Pain Vomiting

DOVE - % of GI-Related Events (Safety Population) Ibrexafungerp 600mg Dose (n=30) FLU (n=32) 19

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  • All six arms showed evidence of antifungal activity.
  • The 1-day ibrexafugerp dose regimens overall comparable

efficacy to 3-days dose regimens.

  • The 300mg BID for 1 day dose showed the best combination
  • f clinical efficacy and tolerability.
  • This dose regimen was selected for Phase 3 program

DOVE Study Key Results

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Ibrexafungerp: Ongoing Programs / Timing

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Acute Vulvovaginal Candidiasis Invasive Aspergillosis (Combination Therapy) Refractory Invasive Fungal Infections

P3 - CARES Study (open-label, C. auris infections) Ongoing P2 – SCYNERGIA Ongoing DOVE P2b Complete July 2018 P3 - FURI Study (open-label, refractory or intolerant, IFIs) Ongoing P3 (VANISH 303) LP/LV complete

2018 2019 2020 2021

Ibrexafungerp is an investigational drug Estimated NDA filing.

Other potential oral indications: Prophylaxis, Chronic Fungal Infections, Invasive Candidiasis

Outpatient Hospital

Recurrent Vulvovaginal Candidiasis

P3 – CANDLE Study (under FDA SPA) Ongoing

NDA sNDA

P3 (VANISH 306) Ongoing

Anticipated Approval LPAD Potential Data by YE’19

Data by early Q2’19

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Thank you

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