On November 9, 2022 Xilio Therapeutics, Inc. (Nasdaq: XLO), a biotechnology company developing tumor-activated immuno-oncology therapies for people living with cancer, reported pipeline progress, reported financial results for the third quarter ended September 30, 2022 (Press release, Xilio Therapeutics, NOV 9, 2022, View Source [SID1234623576]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We continued to make meaningful progress advancing our clinical-stage cytokine programs, XTX202 and XTX301, during the quarter," said René Russo, Pharm.D., chief executive officer of Xilio. "XTX202, our tumor-activated IL-2, has successfully reached the target dose range of 1 mg/kg in an outpatient setting in our ongoing Phase 1 clinical trial with no signs of vascular leak syndrome, and preliminary clinical data indicate evidence of IL-2 specific biology, including intra-tumoral pharmacodynamic effects in one patient for whom a tumor biopsy was available. We expect to report initial anti-tumor activity data for XTX202 in the third quarter of 2023. In addition, with the recent FDA clearance of our IND application for XTX301, our tumor-activated IL-12, we look forward to initiating a Phase 1 clinical trial in the first quarter of 2023 and evaluating the therapeutic potential of XTX301 across ‘cold’ and ‘hot’ tumor types."

Dr. Russo continued, "While we remain enthusiastic about the potential for XTX101, our tumor-activated anti-CTLA-4, we plan to focus our existing resources on advancing our clinical-stage cytokine programs, and we will seek to partner XTX101 to advance the program beyond the ongoing Phase 1 monotherapy cohorts."

Pipeline and Business Updates

XTX202: tumor-activated, engineered IL-2

XTX202 is an investigational tumor-activated beta-gamma biased (non-alpha), engineered IL-2 molecule designed to potently stimulate CD8+ effector T cells and natural killer (NK) cells without concomitant stimulation of regulatory T cells when activated (unmasked) in the tumor microenvironment. XTX202 is currently being evaluated in monotherapy dose-escalation of an ongoing Phase 1 clinical trial in patients with advanced solid tumors.

●Xilio recently began dosing patients at the 1 mg/kg dose level, which is in the target clinical dose range for XTX202, making it one of the first engineered IL-2 molecules to achieve a dose that is in line with that of traditional high dose treatment with aldesleukin.
●As of November 7, 2022, 11 patients have been treated with XTX202 as outpatients in monotherapy dose-escalation at four dose levels ranging from 0.27 mg/kg to 1.0 mg/kg.

●Preliminary analyses indicated evidence of IL-2 specific biology in patients consistent with data observed in preclinical studies, including CD8+ effector T cells and NK cells increasing in peripheral circulation steadily over time.
●No signs of vascular leak syndrome (VLS) or decreases in albumin (an early sign of VLS) have been observed in patients to date.
●In addition, Xilio today reported preliminary intra-tumoral pharmacodynamic data for a single patient treated with XTX202 who had an optional on-treatment tumor biopsy and was the first patient for whom a tumor biopsy analysis was available to date. This patient tumor biopsy featured increased numbers of stromal tumor infiltrating lymphocytes (TILs), increased frequency of CD8+ effector T cells among these TILs and decreased frequency of immune suppressive regulatory T cells (TREGs). Importantly, in this patient, at the time of the tumor biopsy, these changes occurred in the absence of peripheral changes to either CD8+ effector T cells or TREGs.
●A maximum tolerated dose has not yet been determined, and enrollment in monotherapy dose-escalation is ongoing.

Xilio anticipates multiple milestones for XTX202 through the end of 2023:

●Initiate patient enrollment in a monotherapy expansion cohort of the Phase 1 clinical trial in the fourth quarter of 2022.
●Initiate patient enrollment in a Phase 2 monotherapy clinical trial in the first half of 2023.
●Report preliminary anti-tumor activity and safety data from the Phase 1/2 clinical trial in the third quarter of 2023.

XTX301: tumor-activated, engineered IL-12

XTX301 is an investigational tumor-activated, engineered IL-12 molecule designed to potently stimulate anti-tumor immunity and reprogram the tumor microenvironment (TME) of poorly immunogenic "cold" tumors towards an inflamed, or "hot," state. IL-12 plays a key role in bridging innate and adaptive cellular immunity, making it a compelling target for immunotherapy. However, life-threatening toxicity observed with systemically active IL-12, including severe liver toxicity, have limited the therapeutic potential of IL-12 agents. Preclinical studies using a murine surrogate molecule for XTX301 demonstrated in vivo anti-tumor activity at doses as low as 0.04 mg/kg, and XTX301 demonstrated favorable tolerability in non-human primates at doses up to 2 mg/kg given weekly over four cycles.

●Xilio reported that the U.S. Food and Drug Administration has cleared the company’s investigational new drug (IND) application for the evaluation of XTX301 as a potential treatment for patients with advanced solid tumors.

Xilio anticipates multiple milestones for XTX301 through the end of 2023:

●Initiate patient enrollment in monotherapy dose-escalation in a Phase 1 clinical trial in the first quarter of 2023 evaluating the safety and tolerability of XTX301 in patients with advanced solid tumors.
●Report preliminary safety data from the Phase 1 clinical trial in the fourth quarter of 2023.

XTX101: tumor-activated anti-CTLA-4

XTX101, an Fc-enhanced, tumor-activated anti-CTLA-4, is currently being evaluated in monotherapy dose-escalation of an ongoing Phase 1 clinical trial in patients with advanced solid tumors.

●Xilio is currently dosing patients at 150 mg once every six weeks (Q6W) in the monotherapy dose-escalation cohort, which the company anticipates completing by the end of 2022. Enrollment in a monotherapy dose expansion cohort is currently ongoing.
●Preliminary pharmacokinetic (PK) analyses continue to demonstrate dose-proportional drug exposure, with limited active (unmasked) XTX101 in peripheral circulation consistent with PK data observed in preclinical studies.
●Xilio anticipates reporting preliminary data from the Phase 1 clinical trial in the second quarter of 2023.
●Xilio plans to continue to explore opportunities for strategic collaborations to advance XTX101 and does not plan to initiate an anti-PD-1 combination cohort in the Phase 1 clinical trial or initiate a Phase 2 clinical trial for XTX101 without a partner.

Corporate Highlights

●In September 2022, Xilio announced the appointment of Tomas J. Heyman as a member of the board of directors and John Maraganore, Ph.D. joined as a strategic advisor to the company.
●In August 2022, Xilio announced the promotion of Uli Bialucha, Ph.D. to Chief Scientific Officer and Chris Frankenfield to Chief Legal and Administrative Officer.

Upcoming Presentations

Xilio will present a poster outlining preclinical data demonstrating anti-tumor activity and sustained memory T-cell response in mice for XTX202 in combination with immune checkpoint blockade at the Society for Immunotherapy in Cancer 37th Annual Meeting.

●Presentation title: XTX202, a tumor-activated protein-engineered IL-2, exhibited enhanced anti-tumor activity in combination with checkpoint inhibition in mice​
●Session date and time: Thursday, November 11, 2022, at 11:40 am to 1:10 pm and 7:30 pm to 9:00 pm ET
●Abstract number: 841

Uli Bialucha, Ph.D., Xilio’s chief scientific officer, will present at the 14th Annual Protein & Antibody Engineering Summit (PEGS) Europe meeting and will highlight preclinical data for XTX301, a tumor-activated IL-12, and Xilio’s emerging research portfolio developing tumor-activated multifunctional biologics.

●Presentation title: Engineering Tumor-Selective Biologics for Immune-Oncology
●Session date and time: Monday, November 14, 2022, at 3:20 pm CET (10:20 am ET)

Third Quarter 2022 Financial Results

●Cash Position: Cash and cash equivalents were $139.1 million as of September 30, 2022, compared to $198.1 million as of December 31, 2021.
●Research & Development (R&D) Expenses: R&D expenses were $13.0 million for the third quarter of 2022, compared to $10.5 million for the third quarter of 2021. The increase was primarily driven by higher personnel-related costs mainly due to increased headcount and a $0.2

million increase in non-cash equity-based compensation expense, as well as increased costs associated with XTX301 preclinical, clinical and manufacturing development activities.
●General & Administrative (G&A) Expenses: G&A expenses were $7.2 million for the third quarter of 2022, compared to $5.5 million for the third quarter of 2021. The increase was primarily driven by higher personnel-related costs, primarily due to increased headcount and a $0.6 million increase in non-cash equity-based compensation expense, as well as certain costs related to operating as a publicly traded company.
● Net Loss: Net loss was $19.8 million for the third quarter of 2022, compared to $16.3 million for the third quarter of 2021.

Financial Guidance

Xilio anticipates that its existing cash and cash equivalents will be sufficient to fund its operating expenses and capital expenditure requirements into the second quarter of 2024.

About the Phase 1/2 Clinical Trial for XTX202 (IL-2)

The Phase 1 clinical trial for XTX202 is a first-in-human, multi-center, open-label trial designed to evaluate the safety and tolerability of XTX202 as a monotherapy in patients with advanced solid tumors. The Phase 1 clinical trial is designed to enroll up to approximately 119 patients across all cohorts at multiple sites in the United States, Europe and other international sites. Please refer to NCT05052268 on www.clinicaltrials.gov for additional details.

The Phase 2 clinical trial for XTX202 is a multi-center, open-label trial designed to evaluate the safety and efficacy of XTX202 as a monotherapy in patients with melanoma and renal cell carcinoma at the recommended Phase 2 dose. The Phase 2 clinical trial is designed to enroll up to approximately 70 patients in the United States and Europe. Please refer to NCT05052268 on www.clinicaltrials.gov for additional details.

About the Planned Phase 1 Clinical Trial for XTX301 (IL-12)

The planned Phase 1 clinical trial for XTX301 is a first-in-human, multi-center, open-label trial designed to evaluate the safety and tolerability of XTX301 as a monotherapy in patients with advanced solid tumors. The Phase 1 clinical trial is designed to enroll up to approximately 94 patients across all cohorts at multiple sites in the United States.

About the Phase 1 Clinical Trial for XTX101 (anti-CTLA-4)

XTX101 is an investigational Fc-enhanced, tumor-activated anti-CTLA-4 monoclonal antibody designed to deplete regulatory T cells when activated (unmasked) in the TME. The Phase 1 clinical trial is a first-in-human, multi-center, open-label trial designed to evaluate the safety and tolerability of XTX101 for the treatment of adult patients with advanced solid tumors. Please refer to NCT04896697 on www.clinicaltrials.gov for additional details.

On November 9, 2022 Arbutus Biopharma Corporation (Nasdaq: ABUS), a clinical-stage biopharmaceutical company leveraging its extensive virology expertise to develop novel therapeutics that target specific viral diseases, reported its third quarter 2022 financial results and provides corporate updates (Press release, Arbutus Biopharma, NOV 9, 2022, View Source [SID1234623575]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"This quarter we continued to advance our pipeline of clinical and preclinical programs in support of our mission to develop a functional cure for patients with chronic hepatitis B virus (cHBV) and to treat COVID-19 and future coronavirus outbreaks," said William Collier, Arbutus’ President and Chief Executive Officer. "We reported at AASLD off-treatment data which showed that AB-729 treatment results in long-lasting control of HBV biomarker levels. We continue to believe that AB-729 can be a cornerstone agent in a potential curative combination treatment for cHBV based on the body of data supporting its impact on HBV markers and immune activation properties, safety profile and convenient dosing schedule."

Mr. Collier continued, "Looking ahead, we are on-track to achieve our remaining 2022 milestones including reporting data from our Phase 2 clinical trial evaluating AB-729 with interferon, completing IND-enabling studies with AB-161, our RNAi destabilizer, and AB-101, our PD-L1 inhibitor, and nominating a compound that inhibits the SARS-CoV-2 nsp5 main protease and has pan-coronavirus inhibitor properties."

Pipeline Updates:
AB-729 (RNAi Therapeutic)

Presented additional off-treatment data from AB-729-001 at the AASLD Liver Meeting, showing that HBsAg levels remained well below pre-trial levels in nine of nine patients who were eligible and elected to stop therapy, suggestive of immunological control, with no patient meeting protocol-defined criteria to restart NA therapy.
The Phase 2a clinical trial evaluating AB-729 in combination with NA therapy and short courses of Peg-IFNα-2a (AB-729-201) in cHBV patients is continuing. The Company is on-track to report initial data this quarter.
Enrollment is on-going in the AB-729-202 Phase 2a clinical trial evaluating AB-729, in combination with VTP-300, Vaccitech plc’s (Vaccitech) therapeutic vaccine, and NA, in cHBV patients.
Presented preliminary data from the Phase 2a clinical trial evaluating AB-729 and NA in combination with vebicorvir (VBR), Assembly Biosciences, Inc.’s first generation HBV core inhibitor (capsid inhibitor), at AASLD showing that the combination of VBR+AB-729+NA does not result in greater on-treatment improvements in markers of active HBV infection as compared to AB-729+NA alone. The addition of VBR did not negatively impact the reduction of HBsAg, in the triple combination arm.
AB-101 (Oral PD-L1 Inhibitor)

At AASLD, presented preclinical data in mice infected with HBV showing that combination treatment with AB-101 and an HBV targeting GalNAc-siRNA agent resulted in activation and increased frequency of HBV-specific T-cells and greater anti-HBsAg antibody production. The Company is on-track to complete IND-enabling studies for AB-101 this year.
AB-161 (Oral RNA Destabilizer)

At the Discovery on Target Conference, presented preclinical data showing that AB-161 reduced HBV RNA and HBsAg in multiple preclinical models, with favorable liver centricity and lack of observed peripheral neuropathy. The Company is conducting the remaining IND-enabling studies which are expected to be complete by the end of the year.
AB-836 (Oral Capsid Inhibitor)

Discontinued development of AB-836 based on additional ALT elevations seen in the new healthy volunteer arm of the AB-836-001 clinical trial.
COVID-19 and Pan-Coronavirus Programs

The Company is on-track to nominate a lead candidate that inhibits the SARS-CoV-2 nsp5 main protease (Mpro) this year and then advance that compound into IND-enabling studies.
The Company is continuing lead optimization activities for an nsp12 viral polymerase candidate.
Financial Results

Cash, Cash Equivalents and Investments

As of September 30, 2022, the Company had cash, cash equivalents and investments in marketable securities of $190.2 million, as compared to $191.0 million as of December 31, 2021.

During the nine months ended September 30, 2022, the Company received a $40.0 million (net of withholding taxes) upfront payment from Qilu Pharmaceutical Co., Ltd. ("Qilu") related to a technology transfer and license agreement for AB-729 in greater China, $15.0 million of gross proceeds from Qilu’s equity investment in the Company and $9.2 million of net proceeds from the issuance of common shares under Arbutus’s "at-the-market" offering program. These cash inflows were partially offset by $62.4 million of cash used in operations. The Company expects a net cash burn between $90 to $95 million in 2022, not including the $55 million of proceeds received from Qilu, and believes its cash runway will be sufficient to fund operations into the second quarter of 2024.

Revenue

Total revenue was $6.0 million for the three months ended September 30, 2022 compared to $3.3 million for the same period in 2021. The increase of $2.7 million was due primarily to $2.3 million of revenue recognition from the Company’s license agreement with Qilu based on employee labor hours expended by the Company during the three months ended September 30, 2022 to perform its manufacturing obligations under the license agreement.

Operating Expenses

Research and development expenses were $20.1 million for the three months ended September 30, 2022, compared to $16.7 million for the same period in 2021. The increase of $3.4 million was due primarily to an increase in expenses related to the Company’s multiple, ongoing AB-729 Phase 2a clinical trials, including its collaborations with Assembly and Vaccitech, and an increase in expenses for its early-stage development programs, including AB-101 and AB-161. General and administrative expenses were $3.5 million for the three months ended September 30, 2022, compared to $4.2 million for the same period in 2021. This decrease was due primarily to an arbitrator’s award of $0.5 million during the three months ended September 30, 2022 for recovery of costs and attorneys’ fees related to an arbitration matter with the University of British Columbia.

Net Loss

For the three months ended September 30, 2022, the Company’s net loss attributable to common shares was $17.6 million, or a loss of $0.12 per basic and diluted common share, as compared to a net loss attributable to common shares of $24.2 million, or a loss of $0.24 per basic and diluted common share, for the three months ended September 30, 2021. Net loss attributable to common shares for the three months ended September 30, 2021 included $5.1 million of non-cash expense for the accrual coupon on the Company’s convertible preferred shares, which converted into 22.8 million common shares in October 2021.

Outstanding Shares

As of September 30, 2022, the Company had approximately 152.7 million common shares issued and outstanding, as well as approximately 15.9 million stock options outstanding. Roivant Sciences Ltd. owned approximately 25% of the Company’s outstanding common shares as of September 30, 2022.

COVID-19 Impact

The COVID-19 pandemic has resulted in and will likely continue to result in significant disruptions to businesses. Measures implemented around the world in attempts to slow the spread of COVID-19 have had, and will likely continue to have, a major impact on clinical development, at least in the near-term, including shortages and delays in the supply chain and prohibitions in certain countries on enrolling subjects and patients in new clinical trials. While the Company has been able to progress with its clinical and pre-clinical activities to date, it is not possible to predict if the COVID-19 pandemic will materially impact the Company’s plans and timelines in the future.

Conference Call and Webcast Today

Arbutus will hold a conference call and webcast today, Wednesday, November 9, 2022, at 8:45 AM Eastern Time to provide a corporate update. To dial-in for the conference call by phone, please register using the following link: Registration Link. A live webcast of the conference call can be accessed through the Investors section of Arbutus’ website at www.arbutusbio.com.

An archived webcast will be available on the Arbutus website after the event.

About AB-729

AB-729 is an RNA interference (RNAi) therapeutic specifically designed to reduce all HBV viral proteins and antigens including hepatitis B surface antigen which is thought to be a key prerequisite to enable reawakening of a patient’s immune system to respond to the virus. AB-729 targets hepatocytes using Arbutus’ novel covalently conjugated N-Acetylgalactosamine (GalNAc) delivery technology enabling subcutaneous delivery. Clinical data generated thus far has shown single- and multi-doses of AB-729 to be generally safe and well-tolerated, while also providing meaningful reductions in hepatitis B surface antigen and hepatitis B DNA. AB-729 is currently in multiple Phase 2a clinical trials.

About AB-101

Immune checkpoints such as PD-1/PD-L1 play an important role in the induction and maintenance of immune tolerance and in T-cell activation. We have identified a class of small molecule oral PD-L1 inhibitors that we believe will allow for controlled checkpoint blockade, enable oral dosing, and mitigate systemic safety issues typically seen with checkpoint antibody therapies. Our lead oral PD-L1 inhibitor candidate, AB-101, is currently in IND-enabling studies. We believe AB-101, when used in combination with other approved and investigational agents, could potentially allow us to realize our mission of achieving a functional cure for HBV chronically infected patients. We are also exploring oncology applications for our internal PD-L1 portfolio.

About HBV

Hepatitis B is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV). HBV can cause chronic infection which leads to a higher risk of death from cirrhosis and liver cancer. Chronic HBV infection represents a significant unmet medical need. The World Health Organization estimates that over 290 million people worldwide suffer from chronic HBV infection, while other estimates indicate that approximately 2.4 million people in the United States suffer from chronic HBV infection. Approximately 820,000 people die every year from complications related to chronic HBV infection despite the availability of effective vaccines and current treatment options.

On November 9, 2022 SCYNEXIS, Inc. (NASDAQ: SCYX), a biotechnology company pioneering innovative medicines to overcome and prevent difficult-to-treat and drug-resistant infections, reported financial results for the third quarter ended on September 30, 2022 (Press release, Scynexis, NOV 9, 2022, View Source [SID1234623574]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Recently we have taken important steps to strategically refocus the Company on the successful development of ibrexafungerp in hospital-based indications where there is an urgent unmet need in patients with life-threatening infections," said Marco Taglietti, M.D., President and Chief Executive Officer of SCYNEXIS. "We believe there is great potential in this area. Separately, we are seeking a commercialization partner to maximize the value of BREXAFEMME in the U.S. We also look forward to the November 30, 2022, PDUFA date for BREXAFEMME, which, if approved, would make it the only antifungal for both the treatment of vulvovaginal candidiasis (VVC) and prevention of recurrent VVC."

BREXAFEMME Commercial Update

BREXAFEMME achieved $1.6 million in net sales in Q3 2022. According to IQVIA data, there were 5,785 total prescriptions for BREXAFEMME written in Q3 2022, a 13 percent increase of total prescriptions over Q2 2022.

BREXAFEMME was prescribed by approximately 2,500 individual healthcare professionals (HCPs) in the third quarter, an increase of 11% over Q2 2022.

SCYNEXIS signed an agreement with an additional national Pharmacy Benefit Manager (PBM), providing coverage for BREXAFEMME to an added 21 million commercially insured lives, and bringing total coverage to 130 million, or 70% of commercially insured lives.

In order to build on the positive sales trajectory to date and maximize BREXAFEMME’s value, SCYNEXIS announced plans to out-license commercial rights and is actively pursuing a U.S. commercialization partner for vulvovaginal candidiasis (VVC). During this process, SCYNEXIS has started winding down promotional activities, while keeping BREXAFEMME on the market and available to patients.

SCYNEXIS reported the Company’s submission of a supplemental NDA for a second indication for BREXAFEMME for the prevention of recurrent VVC remains on track. The U.S. Food and Drug Administration (FDA) granted the submission Priority Review and assigned the Prescription Drug User Fee Act (PDUFA) target decision date as November 30, 2022.
Ibrexafungerp Clinical Updates

Enrollment continues for the MARIO trial, a global Phase 3 study to evaluate ibrexafungerp as an oral step-down treatment for invasive candidiasis (IC) in the hospital setting. Additional sites are being opened globally, and SCYNEXIS anticipates study completion and results to enable regulatory filing and potential approval for IC, including candidemia, in 2024

The FURI Phase 3 trial has surpassed its target enrollment, and study closure activities are progressing. Enrollment for the CARES Phase 3 trial is expected to be completed by the end of 2022.

Enrollment continues for the SCYNERGIA Phase 2 study evaluating the safety and efficacy of ibrexafungerp co-administered with voriconazole in patients with invasive pulmonary aspergillosis. Enrollment closure is anticipated by the end of 2022.

Following the positive Phase 1 data with the IV formulation reported previously, SCYNEXIS is planning to begin a Phase 2 study of the IV formulation in 2023.
Ibrexafungerp Scientific Presentations and Publications

Publication of an article in the Journal of Fungi in October 2022 highlighting the potential use of ibrexafungerp as a novel treatment option for invasive infections caused by opportunistic molds. The article emphasizes ibrexafungerp’s advantages versus available antifungal drugs, including its oral bioavailability and its broad-spectrum efficacy against various fungal infections, including those caused by azole-resistant Aspergillus species. Data from preclinical and clinical studies showcased in the article provide rationale for the continued development of ibrexafungerp for the treatment and prevention of invasive fungal and mold infections.

Peer-reviewed publication of positive results from a pooled analysis of two Phase 3 studies (VANISH-303 and VANISH-306) in the Journal of Women’s Health in October 2022. Clinical cure rates, in the pooled analysis, were statistically significantly greater for ibrexafungerp when compared with placebo (p < 0.0001). In the pooled analysis, patients receiving ibrexafungerp experienced significantly higher rates of clinical improvement, complete symptom resolution, and mycological cure compared to placebo (all p < 0.0001). Ibrexafungerp demonstrated efficacy in important patient sub-populations, characterized by race, body mass index, symptom severity, and Candida species infection. Ibrexafungerp was well-tolerated in the pooled analysis.

Presented cumulative interim outcomes and all-cause mortality data in patients with refractory candidiasis treated with oral ibrexafungerp from the ongoing Phase 3 FURI study. The analyses were presented during IDWeek 2022 held in Washington, D.C., October 19-23, 2022. Presentations included a platform overview of a cumulative interim analysis of 113 patients enrolled in the ongoing FURI Phase 3 study who had a variety of serious fungal infections, demonstrating 82.3% positive clinical outcomes in patients treated with ibrexafungerp. In addition, a poster was presented highlighting all-cause mortality outcomes through 30 days post completion of ibrexafungerp treatment in 56 patients from the ongoing FURI study who had a diagnosis of invasive candidiasis or candidemia, demonstrating 94.6% overall survival.

Presented positive interim data in patients with refractory candidiasis treated with oral ibrexafungerp from the ongoing Phase 3 FURI study, as well as data from the ongoing CARES study of patients with Candida auris (C. auris) infections. The interim analyses were presented during the Mycoses Study Group Education and Research Consortium (MSGERC) Biennial Meeting held in Albuquerque, N.M., September 7-9, 2022. Posters included: An interim analysis of 64 patients from the FURI study with refractory Candida infections, including failure of or resistance to previous standard-of-care antifungal therapy, demonstrating 56% of patients with complete or partial response, 27% had stable response, 9% showed disease progression, and 8% were indeterminate. SCYNEXIS also presented an interim analysis of 18 patients from the CARES study with invasive candidiasis/candidemia due to C. auris, demonstrating 78% of patients had a complete or partial response, 11% had stable response, one patient died of other causes, and one outcome was indeterminate.

Presented positive outcomes from its global Phase 3 CANDLE study investigating the safety and efficacy of oral ibrexafungerp for prevention of recurrent vulvovaginal candidiasis (RVVC), also known as vaginal yeast infection. The results were presented during the Infectious Diseases Society for Obstetrics and Gynecology (IDSOG) Annual Meeting held in Boston August 4-6, 2022. The CANDLE study met its primary endpoint, with 65.4% of patients who received monthly single-day ibrexafungerp treatment achieving clinical success with no recurrence at all, either culture-proven, presumed or suspected, through Week 24. In addition, ibrexafungerp demonstrated superiority over placebo in preventing mycologically proven recurrence of RVVC through Week 24, a key secondary endpoint. No mycologically proven recurrence was detected in 70.8% of patients receiving ibrexafungerp. The advantage of ibrexafungerp over placebo was sustained over the three-month follow-up period and remained statistically significant in both primary and secondary endpoints (p=0.034 and 0.029, respectively). In the study, ibrexafungerp was generally safe and well-tolerated. There were no serious drug-related adverse events, and no patients treated with ibrexafungerp discontinued therapy due to adverse events. The most commonly-reported adverse events, headaches and gastrointestinal in nature (i.e., diarrhea, nausea), were mostly mild and generally consistent with the current approved product label.

Presented positive outcomes from the CANDLE nested sub-study investigating oral ibrexafungerp in patients with recurrent vulvovaginal candidiasis (RVVC) who failed fluconazole treatment. The results were presented during the International Society for the Study of Vulvovaginal Diseases (ISSVD) XXVI World Congress and International Vulvovaginal Disease Update 2022 held in Dublin, Ireland, July 15-20, 2022. Data show that 71% of 24 patients with recurrent vulvovaginal candidiasis (RVVC) who failed to respond to a three-day regimen of fluconazole achieved a substantial reduction or complete elimination of signs and symptoms after receiving a one-day treatment with ibrexafungerp.
Corporate Developments

In October 2022, Ivor Macleod joined the Company as Chief Financial Officer. Mr. Macleod is an accomplished biopharma industry executive who brings deep experience spanning financial and operational roles.
In connection with the new strategic direction of the company, SCYNEXIS announced changes to its executive leadership team:

Marco Taglietti, M.D., President and Chief Executive Officer of SCYNEXIS, will retire as of December 31, 2022.

David Angulo, M.D., Chief Medical Officer since 2015, will become President and Chief Executive Officer and join the Board of Directors, effective January 1, 2023.

Christine Coyne, Chief Commercial Officer, will transition from the Company as of November 30, 2022.
Third Quarter 2022 Financial Results

BREXAFEMME increased its net product revenues from $1.3 million in Q2 2022 to $1.6 million in Q3 2022.

Research and development expense for Q3 2022 was $6.4 million, compared to $4.4 million for Q3 2021. The increase is primarily attributed to increased costs associated with the MARIO clinical trial.

Selling, general & administrative (SG&A) expense for Q3 2022 increased to $16.7 million from $15.4 million for Q3 2021. The increase was primarily driven by increased commercial costs and professional fees recognized to support the commercialization of BREXAFEMME.

Total other expense was $7.8 million for Q3 2022, versus total other income of $18.8 million for Q3 2021. During Q3 2022 and Q3 2021, SCYNEXIS recognized a non-cash loss of $6.5 million and a non-cash gain of $18.8 million, respectively, on the fair value adjustment of the warrant liabilities.

Net loss for Q3 2022 was $29.6 million, or $0.62 basic loss per share, compared to a net loss of $600,000, or $0.02 basic loss per share for Q3 2021.

Cash Balance

Cash, cash equivalents and short-term investments totaled $96.1 million on September 30, 2022, compared to $104.5 million in cash and cash equivalents on December 31, 2021. Based upon its current operating plan, SCYNEXIS believes that its existing cash, cash equivalents and short-term investments will enable the Company to fund its operating requirements into Q2 2024.

About Ibrexafungerp

Ibrexafungerp [pronounced eye-BREX-ah-FUN-jerp] is an 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 in late-stage development for multiple indications, including life-threatening fungal infections caused primarily by Candida (including C. auris) and Aspergillus species in hospitalized patients. It has demonstrated broad-spectrum antifungal activity, in vitro and in vivo, against multidrug-resistant pathogens, including azole- and echinocandin-resistant strains. The U.S. Food and Drug Administration (FDA) granted ibrexafungerp Qualified Infectious Disease Product (QIDP) and Fast Track designations for the IV and oral formulations of ibrexafungerp for the indications of invasive candidiasis (IC) (including candidemia) and invasive aspergillosis (IA) and has granted Orphan Drug Designation for the IC and IA indications. Ibrexafungerp is formerly known as SCY-078.

On November 9, 2022 Applied Therapeutics, Inc. (NASDAQ: APLT) (the "Company"), a clinical-stage biopharmaceutical company developing a pipeline of novel drug candidates against validated molecular targets in indications of high unmet medical need, reported financial results for the third quarter ended September 30, 2022 (Press release, Applied Therapeutics, NOV 9, 2022, View Source [SID1234623573]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"In the third quarter, we made significant progress across all three of our late-stage programs," said Shoshana Shendelman, PhD, Founder, CEO and Chair of the Board of Applied Therapeutics. "We remain focused on successful completion of our ongoing Phase 3 trials in Galactosemia, SORD Deficiency and Diabetic Cardiomyopathy, and look forward to sharing data in 2023, with the potential to bring new treatment options to these patients with limited to no available therapies."

Recent Highlights

·Presented Data on AT-001 Treatment in Diabetic Cardiomyopathy at the 2022 American Heart Association Scientific Sessions. In November 2022, the Company presented data in multiple sessions featuring mechanistic support for AT-001, a selective Aldose Reductase inhibitor, in a Diabetic Cardiomyopathy (DbCM) mouse model, demonstrating that AT-001 treatment prevents fibrosis and adverse cardiac remodeling, baseline data from the ongoing Phase 3 ARISE-HF study on quality of life impact of disease and correlation of cardiac functional capacity (peak VO2) with physical function and additional DbCM diagnosis and prevalence data.

·Announced Full Enrollment in the Registrational Phase 3 ARISE-HF Trial of AT-001 in Diabetic Cardiomyopathy. In October 2022, the Company announced full enrollment in the Phase 3 registrational ARISE-HF trial studying AT-001 in patients with DbCM. The primary endpoint is cardiac functional capacity (as measured by Peak VO2) at 15 months of treatment. The Company continues to expect topline data around year-end 2023 or early 2024, and if positive, the Company plans to submit for potential regulatory approval. Patients will continue in blinded format for an additional 12 months of treatment (up to 27 months total) to produce secondary endpoint data on progression to overt heart failure, hospitalization, morbidity and mortality, which is not anticipated to be required for regulatory approval, but will support long-term market access.

·Reported Positive Data Trend in AT-007 ACTION-Galactosemia Kids Pediatric Trial. In October 2022, the Company announced that the ACTION-Galactosemia Kids Phase 3 trial demonstrated a trend in clinical benefit favoring AT-007 vs. placebo. Review of the data at 12 months of treatment by the DMC indicated that while the study primary endpoint has not yet reached statistical significance, a trend exists favoring AT-007 vs. placebo. The clinical benefit at this early time point was most pronounced in patients with significant deficits in clinical performance at baseline. Safety data demonstrated that AT-007 continues to be safe and well tolerated. The study will continue to proceed in blinded format to the next review at 18 months of treatment. In the meantime, the Company will meet with the EMA to discuss potential submission of an MAA based on existing data for conditional approval.

Financial Results

·Cash and cash equivalents and short-term investments totaled $47.4 million as of September 30, 2022, compared with $80.8 million at December 31, 2021.

·Research and development expenses for the three months ended September 30, 2022 were $13.1 million, compared to $17.6 million for the three months ended September 30, 2021. The decrease of $4.5 million was primarily related to a decrease in drug manufacturing and formulation costs of $2.9 million related to the completion and release of AT-007 drug product batches and purchase of raw materials in the three months ended September 30, 2021; a decrease in clinical and pre-clinical expense of $1.7 million, primarily due to reduced clinical trial spend on the AT-007 ACTION-Galactosemia Kids pediatric registrational study and AT-007 ACTION-Galactosemia long-term extension adult study; and a decrease in regulatory and other expenses of $0.4 million. This was partially offset by an increase in personnel expenses of $48,000 due to the increase in headcount in support of our clinical program pipeline; and an increase in stock-based compensation of $0.5 million due to new stock option and restricted stock units grants and due to the incremental stock-based compensation expense recognized as a result of the stock option repricing.

·General and administrative expenses were $6.2 million for the three months ended September 30, 2022, compared to $10.8 million for the three months ended September 30, 2021. The decrease of $4.6 million was primarily due to a decrease in legal and professional fees of $0.2 million due to lower external legal fees; a decrease in commercial expenses of $2.8 million related to a decrease in spend for commercial operations; a decrease in personnel expenses of $0.5 million related to a decrease in headcount; a decrease in stock-based compensation of $0.3 million relating to options being forfeited during the current period; a decrease in insurance expenses of $0.3 million related to decreased insurance costs; and a decrease in other expenses of $0.5 million relating to decreased costs of other office expenses.

·Net loss for the third quarter of 2022 was $19.1 million, or $0.40 per basic and diluted common share, compared to a net loss of $28.4 million, or $1.09 per basic and diluted common share, for the third quarter 2021.

On November 9, 2022 TScan Therapeutics, Inc. (Nasdaq: TCRX), a clinical-stage biopharmaceutical company focused on the development of T cell receptor (TCR)-engineered T cell therapies (TCR-T) for the treatment of patients with cancer, reported financial results and provided a business update for the third quarter ended September 30, 2022 (Press release, TScan Therapeutics, NOV 9, 2022, View Source [SID1234623572]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We continued to make meaningful progress across the entirety of our pipeline during the third quarter and look forward to providing an update on our Phase 1 clinical trial by the end of this year. We plan to commence clinical development for the solid tumor program with multiple TCRs next year," said David P. Southwell, President and Chief Executive Officer. "On the financing side, we are pleased to have secured a debt facility for up to $60 million with K2 HealthVentures during the third quarter. The initial $30 million that we drew at the close provides TScan with a cash runway into the second quarter of 2024."

Debora Barton, M.D., Chief Medical Officer added: "Based on recent FDA interactions, we have a clear path to file INDs for multiple solid tumor TCRs and to conduct a Phase 1 umbrella trial which will enable us to bring our ImmunoBank of highly selective TCRs to patients. We look forward to sharing further details on our solid tumor program development plans during a virtual event later this month."

Recent Corporate Highlights

During the quarter TScan announced the closing of a convertible debt facility for up to $60 million with K2 HealthVentures (K2HV). The initial $30 million provided at close, in addition to the current cash on hand, extends the Company’s cash runway into the second quarter of 2024. The Company has the option to draw the remaining tranches subject to certain conditions and by mutual agreement of TScan and K2HV to further support development of additional programs and/or business development.

TScan will present two posters at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 37th Annual Meeting:

Multiplexed TCR-T cell therapy targeting MAGE-A1 and PRAME enhances the activity of adoptive T cell therapy in pre-clinical models; Thursday, November 10, 2022, from 9:00am-9:00pm ET, Exhibition Hall C

Discovery of TSC-203-A02: A PRAME-specific TCR-T cell therapy candidate for the treatment of solid tumors; Friday, November 11, 2022, from 9:00am-8:30pm ET, Exhibition Hall C

TScan has successfully completed a pre-IND meeting with the U.S. Food and Drug Administration (FDA) regarding the manufacturing, preclinical and clinical development plans for its solid tumor program. The FDA has provided feedback to TScan regarding T-Plex, its customized TCR-T cell product mixture, a collection of two to three TCRs selected from the ImmunoBank based on a patient’s tumor antigen positivity and HLA expression.

The Company is hosting a virtual investor event Monday, November 14, 2022, at 5:00 p.m. ET to provide an in-depth review of the poster presentations at the SITC (Free SITC Whitepaper) Annual Meeting related to solid tumor TCR-T candidates, clinical development plans, and TScan’s approach to multiplexed therapy as a way to potentially overcome antigen heterogeneity and HLA loss. Registration for the live event can be found here. A replay will be available on the "Events and Presentations" section of the Company’s website at ir.tscan.com.

Anticipated Near-Term and Upcoming Catalysts

Hematologic Malignancies Program: TScan’s two lead TCR-T therapy candidates, TSC-100 and TSC-101, are designed to target HA-1 and HA-2, respectively, to prevent relapse in acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL) and myelodysplastic syndromes (MDS) patients undergoing allogeneic haploidentical hematopoietic cell transplantation (HCT) with reduced intensity conditioning (RIC). Up to 40% of patients who receive HCT with RIC relapse within two years after the transplant, at which point there are limited treatment options and poor prognosis. The longer-term objective is to enable more patients to maintain prolonged remission after HCT using RIC, a more tolerable chemotherapy than the myeloablative conditioning, followed by TScan’s TCR-T.

The Phase 1 umbrella trial (NCT05473910) for TSC-100 and TSC-101 is open for enrollment, and the Company will provide a progress update at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting:

Trial in Progress: A Phase 1 Umbrella Study of TCR-Engineered T Cells That Target HA-1 (TSC-100) and HA-2 (TSC-101) to Treat Residual Leukemia After Hematopoietic Cell Transplantation; Sunday, December 11, 2022, from 6:00-8:00pm CT, Ernest N. Morial Convention Center, Hall D

The Company expects to enroll the first two cohorts in this trial in the first half of 2023 and plans to report interim data for this study by the end of 2023.

Solid Tumor Programs: TScan’s TCR-T therapy candidates for solid tumors include a combination of validated targets, such as MAGE-A1 (TSC-204), HPV16 E7 (TSC-200), and PRAME (TSC-203), as well as novel targets for TCR-T therapy, such as those for TSC-201 and TSC-202. To address resistance that can arise from HLA loss and to provide therapeutic options for a diverse patient population, TScan is also developing TCRs for multiple HLAs across all of its targets.

The Company plans to progress IND-enabling studies for its solid tumor programs and submit IND applications for two MAGE-A1 TCRs (TSC-204-A2 and TSC-204-C7) by the end of 2022.

The Company plans to file INDs for HPV (TSC-200-A2) and PRAME (TSC-203-A2) in the first half of 2023 with two additional INDs to be filed by the end of 2023. The Company expects to release preliminary clinical safety data for the most advanced TCRs by the end of 2023.

Third Quarter 2022 Financial Results

As of September 30, 2022, TScan Therapeutics had cash and cash equivalents of $137.3 million, excluding $5.0 million of restricted cash. Based on current operating plans, the Company believes that existing cash and cash equivalents will be sufficient to fund its operating expenses and capital expenditure requirements into the second quarter of 2024.

Revenue for the third quarter ended September 30, 2022, was $3.4 million, compared to $2.4 million for the third quarter ended September 30, 2021 (2021 Quarter). This increase is due to research activities related to TScan’s collaboration agreement with Novartis Institutes for Biomedical Research, which commenced in September 2020.

Research and development expenses for the third quarter ended September 30, 2022, were $15.0 million, compared to $14.2 million for the 2021 Quarter. The increase of $0.8 million was primarily driven by increased personnel expense and an increase in clinical study expenses as the Company advances its trials, partially offset by a decrease in preclinical expenses as the Company shifts its focus towards clinical development.

General and administrative expenses for the third quarter ended September 30, 2022, were $4.9 million, compared to $4.0 million for the 2021 Quarter. The increase of $0.9 million in general and administrative expenses was primarily driven by an increase in personnel expense related to growth to support the business.

For the third quarter ended September 30, 2022, TScan Therapeutics reported a net loss of $16.2 million, compared to a net loss of $15.8 million for the 2021 Quarter.

As of September 30, 2022, the Company had issued and outstanding shares of 24,074,927.