On November 12, 2019 SCYNEXIS, Inc. (NASDAQ: SCYX), a biotechnology company delivering innovative therapies for difficult-to-treat and often life-threatening infections, reported financial results for the quarter ended September 30, 2019, and provided an update on recent clinical developments (Press release, Scynexis, NOV 12, 2019, View Source [SID1234550997]). Ibrexafungerp (formerly SCY-078), the first representative of a novel family of compounds referred to as triterpenoids, is being developed for oral and intravenous administration and is in clinical development for the treatment of several serious fungal infections, including vulvovaginal candidiasis (VVC), invasive candidiasis (IC), invasive aspergillosis (IA) and refractory invasive fungal infections. If approved, ibrexafungerp would be the first agent approved for the treatment of VVC and prevention of recurrent VVC and the only oral alternative to azoles.
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"We are thrilled with the positive top-line results from the VANISH-303 study and are increasingly confident in an anticipated NDA submission for the treatment of VVC next year as we work to bring ibrexafungerp, potentially the first new class of antifungals approved in over 20 years, to patients in need," said Marco Taglietti, M.D., President and Chief Executive Officer of SCYNEXIS. "We believe the VVC market is quite large and underserved by existing agents, with only one FDA-approved oral drug in the market, which has lacked innovation since the introduction of fluconazole in the 1990s. We’re confident in the commercial potential of ibrexafungerp given its differentiated attributes as a new oral, non-azole antifungal and the eagerness of women with VVC and their treating physicians to try new therapies."
Dr. Taglietti continued: "We are also enthusiastically advancing our hospital-based development programs of ibrexafungerp as a novel treatment to fight invasive, increasingly drug-resistant and often life-threatening fungal infections, such as Candida auris. As part of this effort, we recently announced the expansion of our FURI protocol to a broader range of refractory, serious fungal infections that are potentially eligible for a limited-population FDA approval under the LPAD regulatory pathway. Given the robust evidence collected to date across all of our programs, we believe ibrexafungerp can have the same positive impact fluconazole had when it was first introduced nearly 30 years ago, leveraging ibrexafungerp’s versatility and strong attributes in many different treatment settings – from women’s health with VVC to deadly, hospital-based infections."
Ibrexafungerp Update
Positive top-line data reported for the first of two studies in the VANISH Phase 3 program evaluating the safety and efficacy of oral ibrexafungerp (300mg BID for one day) versus placebo as a treatment for women with VVC
SCYNEXIS recently announced positive results from the VANISH-303 study, a Phase 3, randomized, double-blind, placebo-controlled, study that enrolled 376 patients at 28 U.S. centers. These results were reported earlier than originally anticipated due to rapid enrollment in the study.
The primary endpoint required for registration is clinical cure, defined as complete resolution (score of 0) of all signs and symptoms (S&S) at the Day-10 test-of-cure (TOC) visit. The observed clinical cure for ibrexafungerp was 50.5%, showing highly statistically significant superiority to placebo (p=0.001). Mycological eradication (secondary endpoint) at TOC in ibrexafungerp patients was 49.5%, also showing superiority to placebo (p<0.001). Clinical improvement (S&S score of 0 or 1) at TOC, another secondary endpoint that is a clinically relevant assessment of treatment response, was achieved in 64.4% of ibrexafungerp patients (p<0.001 against placebo). The VANISH-303 ibrexafungerp efficacy results confirm results observed in the Phase 2b DOVE study and achieve the superiority versus placebo required for regulatory approval.
Oral ibrexafungerp was generally safe and well tolerated. Severe and serious adverse events (AEs) were rare, with more cases reported in the placebo group than the ibrexafungerp group, and there were no drug-related serious AEs. The majority of Treatment-Emergent AEs (TEAEs) observed at a higher frequency in the ibrexafungerp group were gastrointestinal in nature, with the three most common GI events (diarrhea/loose stool, nausea and abdominal pain) occurring at rates of 25.5%, 16.6% and 7.3%, respectively, similar to the rates seen in the Phase 2b DOVE study. These events were predominantly regarded as mild, of short duration and did not lead to discontinuation.
A second global Phase 3 study (VANISH-306), with identical design, is being conducted in the U.S. and Europe. Enrollment continues to progress rapidly, and the Company anticipates top-line data early in the second quarter of 2020. The combined results from the VANISH-303 and VANISH-306 pivotal studies are expected to provide the safety and efficacy data to support a New Drug Application (NDA) for ibrexafungerp for the treatment of VVC, with submission to the U.S. Food and Drug Administration (FDA) planned in the second half of 2020.
Ongoing enrollment in Phase 3 CANDLE study evaluating the safety and efficacy of oral ibrexafungerp versus placebo for the prevention of recurrent VVC
The CANDLE study is a global Phase 3, randomized, double-blind, placebo-controlled trial designed to evaluate the safety and efficacy of oral ibrexafungerp (300mg BID for one day, given once per month for a total of six treatment days) compared to placebo in female patients with recurrent VVC (defined as three or more episodes of VVC in the past 12 months, including the episode at screening). The study is being conducted at approximately 50 sites and is expected to enroll approximately 320 patients. Pending a positive outcome, the Company anticipates filing a supplemental NDA for the prevention of recurrent VVC with the FDA in 2021.
Continued advancement of oral ibrexafungerp for hospital-based, invasive fungal infections with two Phase 3 studies (FURI in refractory infections and CARES in Candida auris infections) and one Phase 2 study in invasive aspergillosis (SCYNERGIA)
The protocol for the FURI study, investigating the safety and efficacy of oral ibrexafungerp as a salvage treatment for patients with resistant or refractory severe fungal infections, was expanded to include a broader range of infections. Under the amended study design, patients with aspergillosis, coccidioidomycosis, histoplasmosis, blastomycosis and infections caused by other emerging fungi, including yeasts and molds, are now eligible for enrollment along with those suffering from Candida infections. Additionally, the maximum allowed duration of treatment with ibrexafungerp has been extended from 90 days to up to 180 days, as needed, for chronic conditions. Ibrexafungerp will also be available as a combination therapy with standard of care for selected patients.
Continued and expanded patient enrollment is expected to support future NDA submissions and potential approval through the Limited Population Pathway for Antibacterial and Antifungal Drugs (LPAD). The Company anticipates reporting a second interim data review from the FURI study by an independent data review committee in the first quarter of 2020.
Enrollment is ongoing for the CARES and SCYNERGIA studies.
Data presented at 3rd International Society of Infectious Diseases in Obstetrics and Gynecology (ISIDOG), IDWeek 2019 and the 9th Congress on Trends in Medical Mycology (TIMM-9) further highlighting the scientific and clinical evidence of ibrexafungerp’s activity against multiple fungal pathogens
Post-hoc data from the Phase 2b DOVE study presented at ISIDOG 2019 highlighted ibrexafungerp’s improved trend in signs and symptoms versus fluconazole on a per patient basis.
Data presented at IDWeek 2019 highlighted a large body of evidence demonstrating the activity and efficacy of ibrexafungerp against Candida auris, both in vivo and in vitro.
In an oral presentation at TIMM-9, studies demonstrating ibrexafungerp’s broad spectrum of activity against Candida, Aspergillus, and Pneumocystis were presented, along with evidence of its activity against resistant organisms and ibrexafungerp’s potential utility for the treatment of hospital-based resistant and refractory fungal infections. Additional posters presented provided in vitro, in vivo and clinical evidence of ibrexafungerp’s broad utility against multiple fungal pathogens.
Corporate Highlight
SCYNEXIS received notification from the State of New Jersey of its available unused Net Operating Losses (NOLs) and R&D credits and expects to receive approximately $3.3 million in cash by the end of 2019.
The New Jersey Economic Development Authority’s (NJEDA) Technology Business Tax Certificate Transfer (NOL) Program allows eligible companies to sell their New Jersey NOLs and research and development tax credits up to a maximum lifetime benefit of $15 million per company. This may be the second non-dilutive NOL-related cash injection through the NJEDA for SCYNEXIS. In January 2019, SCYNEXIS announced the receipt of approximately $6.7 million of net cash proceeds through the sale of unused New Jersey NOLs.
Third Quarter 2019 Financial Results
Cash, cash equivalents and short-term investments totaled $28.1 million as of September 30, 2019, with net working capital of $20.9 million. Based upon its existing operating plan, SCYNEXIS believes its existing cash, cash equivalents, short-term investments, and the sale of a portion of its New Jersey NOLs, may enable SCYNEXIS to fund operating requirements past an anticipated NDA submission for acute VVC in the second half of 2020.
Research and development expenses increased to $9.3 million for the quarter ended September 30, 2019, compared to $3.9 million in the third quarter of 2018. The increase of $5.3 million, or 136%, was primarily driven by an increase of $4.1 million in clinical development costs, an increase of $0.7 million in chemistry, manufacturing, and controls (CMC) costs, and a net increase in other research and development costs of $0.5 million.
Selling, general and administrative expenses in the third quarter of 2019 increased to $2.5 million, compared with $2.4 million in the third quarter of 2018.
Total other income decreased to $3.8 million in the third quarter of 2019, compared to $6.7 million in the third quarter of 2018. The decrease in other income is attributable to a $6.9 million non-cash gain recorded on the fair value adjustment of the warrant liabilities during the third quarter of 2018.
Net loss for the third quarter of 2019 was $7.9 million. This compares with net income for the third quarter of 2018 of $0.4 million.
About Ibrexafungerp
Ibrexafungerp [pronounced eye-BREX-ah-FUN-jerp] is an investigational antifungal agent and the first representative of a novel class of structurally-distinct glucan synthase inhibitors, triterpenoids. This agent combines the well-established activity of glucan synthase inhibitors with the potential flexibility of having oral and intravenous (IV) formulations. Ibrexafungerp is currently in development for the treatment of fungal infections caused primarily by Candida (including C. auris) and Aspergillus species. It has demonstrated broad spectrum antifungal activity, in vitro and in vivo, against multidrug-resistant pathogens, including azole- and echinocandin-resistant strains. The FDA has granted Qualified Infectious Disease Product (QIDP) and Fast Track designations for the formulations of ibrexafungerp for the indications of invasive candidiasis (IC) (including candidemia), invasive aspergillosis (IA) and VVC (including prevention of recurrent VVC) and has granted Orphan Drug Designation for the IC and IA indications. Ibrexafungerp is formerly known as SCY-078.