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]).

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"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]).

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"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]).

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"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.

On November 9, 2022 ZentalisTM Pharmaceuticals, Inc. (Nasdaq: ZNTL), a clinical-stage biopharmaceutical company focused on discovering and developing clinically differentiated small molecule therapeutics targeting fundamental biological pathways of cancers, reported financial results for the third quarter ended September 30, 2022 and highlighted recent corporate accomplishments (Press release, Zentalis Pharmaceuticals, NOV 9, 2022, View Source [SID1234623571]).

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"During the third quarter, we made tremendous progress advancing our clinical strategy and corporate capabilities. We have established a three-pronged development plan for ZN-c3, our potentially first-in-class Wee1 inhibitor investigation as a monotherapy, in combination with chemotherapy and in combination with targeted therapies," said Kimberly Blackwell, MD, Chief Executive Officer of Zentalis. "Building on ZN-c3’s favorable safety profile in the monotherapy setting across tumor types, we are pleased to announce Cyclin E gene amplification and protein overexpression as our biomarker strategy in high grade serous ovarian cancer. This biomarker defined trial in ovarian cancer will allow us to demonstrate potential efficacy in an enriched patient population that has shown evidence of clinical sensitivity to Wee1 inhibition. This trial also has the potential to show initial proof of concept for Wee1 inhibition in Cyclin E driven cancers, which have higher levels of chemotherapy and targeted therapy resistance. On the combination front, there is strong data demonstrating Wee1 inhibition’s synergy with DNA-damaging therapies, such as PARP inhibitors, and with targeted agents in mutationally driven cancers. There is significant interest in these approaches, and we currently have collaborations with Pfizer, GSK and the Dana-Farber Cancer Institute to explore these combinations in the clinic."

Dr. Blackwell continued, "Our development of ZN-c3 includes ongoing dose optimization activities across the clinical program. Although we have demonstrated a favorable safety profile and monotherapy efficacy when ZN-c3 was given on a continuous daily dosing schedule, data show that higher doses delivered on an intermittent schedule have the potential to lead to higher pharmacokinetic exposures and a more favorable therapeutic index. We believe our dose optimization work will allow us to benefit the broadest range of cancer patients and maximize value for all of our stakeholders. With our strong cash position and strengthened management team, we believe we are well-positioned to execute on our clinical development plans and further our mission to improve the lives of cancer patients."

Wee1 Inhibitor (ZN-c3)Program Highlights
•Monotherapy in USC safety and enrollment update: As of a data cutoff on September 14, 2022, a total of 43 patients were enrolled and dosed in the Phase 2 monotherapy uterine serous carcinoma (USC) trial. ZN-c3 was well tolerated and the safety profile was similar or improved relative to previously disclosed data, exhibiting a better hematological and gastrointestinal tolerability profile. The U.S. Food and Drug Administration has granted Fast Track designation to ZN-c3 in this setting.

•Cyclin E biomarker strategy in high-grade serous ovarian cancer: The Company announced that Cyclin E overexpression and/or amplification in high-grade serous ovarian cancer will become the focus of its ongoing Phase 1/2 clinical study examining biomarker-driven enrichment strategies for ZN-c3. Cyclin E overexpression acts at the G1-S checkpoint by driving premature entry into S-phase resulting in replicative stress and significantly increases sensitivity to ZN-c3. The Company has generated preclinical data showing that Cyclin E overexpression sensitizes cancer cells to the anti-tumor effects of ZN-c3 as well as preliminary retrospective clinical data that Cyclin E protein levels may be associated with clinical benefit from ZN-c3. The Company plans to present the preclinical data in the first half of 2023. The two new cohorts of patients will be given monotherapy, which will potentially generate meaningful data sets in patients with Cyclin E gene amplification and patients with Cyclin E protein overexpression independent of gene amplification.

•Dose optimization: The Company highlighted that it continues to optimize dosing across the ZN-c3 clinical portfolio to maximize exposure, improve normal tissue tolerability and enable maximum probability of success. The Company anticipates that the Phase 2 USC trial dose will be modified based on these ongoing dose optimization studies and that, as a result, the timeline of the USC study will be extended. The Company anticipates providing an update on ZN-c3 dosing in the first half of 2023, including expected program timelines and potential paths to registration.

•Pfizer collaboration in mCRC: Zentalis and Pfizer are collaborating on a Phase 1/2 dose escalation study of ZN-c3 in combination with encorafenib and cetuximab (BEACON regimen) in BRAF V600E-mutated metastatic colorectal cancer (mCRC) patients. In preclinical studies, Wee1 inhibition has shown synergy with many targeted agents in mutationally driven cancers and the addition of ZN-c3 to the BEACON regimen enhanced anti-tumor activity in a cell-line-derived xenograft model. Additional information on this clinical development collaboration is available here.

•GSK collaboration in ovarian cancer: Zentalis and GSK are expanding their ongoing collaboration looking at the clinical synergy of ZN-c3 and niraparib in PARP resistant ovarian cancer. The Phase 1/2 dose escalation study, currently enrolling with concurrent dosing of the two drugs, will be expanded to include a cohort that will be given ZN-c3 and niraparib on a dose escalating, alternating schedule of one week of ZN-c3 followed by one week of niraparib.

•Chemotherapy combination in platinum-resistant ovarian cancer: The Company continues to enroll its dose escalation trial of standard chemotherapy (paclitaxel, gemcitabine, and carboplatin) in platinum-resistant ovarian cancer.

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•Chemotherapy combination in osteosarcoma: The Company will be presenting initial data from its Phase 1/2 combination trial of ZN-c3 and chemotherapy in osteosarcoma in a poster session at the upcoming Connective Tissue Oncology Society (CTOS) 2022 Annual Meeting, being held November 16-19 in Vancouver. Details for the CTOS poster presentation are as follows:
oTitle: Preliminary Data from a Phase 1 Dose Escalation Study of ZN-c3 Plus Gemcitabine in Relapsed/Refractory Osteosarcoma (NCT04833582)
oSession: Medical & Pediatric Oncology and Trials
oDate/Time: November 17, 2022 from 5:00pm to 7:00pm ET
oPresenter: Viswatej Avutu, MD, Assistant Attending Physician at Memorial Sloan Kettering Cancer Center

•Dana-Farber combination study in platinum-resistant pancreatic cancer: Zentalis announced an investigator-initiated trial with Dana-Farber Cancer Institute, funded by Stand Up To Cancer and the Lustgarten Foundation, to explore the combination of ZN-c3 with gemcitabine in platinum-resistant advanced pancreatic adenocarcinoma. James Cleary, MD, PhD, Director, Clinical Research, Division of Gastrointestinal Oncology at the Dana-Farber Cancer Institute and Brandon Huffman, MD, Adult Medical Oncology Fellow at the Dana-Farber Cancer Institute, will be running this trial. "We are pleased to announce this important trial which builds on the growing body of clinical evidence supporting the use of ZN-c3 across a range of tumor types," said Dr. Cleary. "Pancreatic cancer continues to be area of high unmet patient need, and we look forward to understanding the potential role of ZN-c3 in helping these patients."
BCL-2 Inhibitor (ZN-d5) Update
•Monotherapy dose optimization continues in NHL and amyloidosis: Dosing with food is ongoing in patients in non-Hodgkin lymphoma (NHL) and amyloidosis, and the combination study of ZN-d5 and ZN-c3 in acute myeloid leukemia (AML) is scheduled to initiate in the fourth quarter of 2022.

BCL-xL Degrader Update
•Declared candidate and initiated IND-enabling studies: BCL-xL degrader candidate demonstrates potent anti-cancer activity in several preclinical models and has the potential to have platelet sparing benefits over clinical-stage BCL-xL targeted inhibitors.

Corporate Highlights
•In September, Zentalis appointed Jan Skvarka, PhD, MBA, to its Board of Directors. Dr. Skvarka is an accomplished biopharmaceutical executive bringing over three decades of extensive operational, strategic and financial expertise to Zentalis. Dr. Skvarka was formerly Chief Executive Officer of Trillium Therapeutics, Inc., which was acquired by Pfizer under his leadership.
•In October, the Company promoted co-founder Kevin Bunker, PhD, to Chief Scientific Officer. In this new role, Dr. Bunker will focus on leading Research and Development, advancing the preclinical pipeline with the Company’s Integrated Discovery Engine.
•In October, Zentalis appointed Carrie Brownstein, MD, as Chief Medical Officer. Dr. Brownstein, a leading oncologist and hematologist, joins Zentalis with over two decades of medical and biopharmaceutical experience, successfully executing clinical program strategies across all phases of product development.

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•In October, the Company appointed Mark Lackner, PhD, as Chief Translational Officer, Head of Biomarker Strategy. Dr. Lackner, a recognized and respected cancer biologist, joins Zentalis with over two decades of oncology-focused drug development expertise, including significant experience in biomarker discovery and clinical biomarker strategies.

Third Quarter 2022 Financial Results
•Cash and Marketable Securities Position: As of September 30, 2022, Zentalis had cash, cash equivalents and marketable securities of $421.7 million. The Company believes that its existing cash, cash equivalents and marketable securities as of September 30, 2022 will be sufficient to fund its operating expenses and capital expenditure requirements into the first quarter of 2025.
•Research and Development Expenses: Research and development, or R&D, expenses for the three months ended September 30, 2022 were $42.2 million, compared to $54.0 million for the three months ended September 30, 2021. The decrease of $11.8 million was primarily due to non-recurring R&D impairments and licensing milestones of $8.8 million and $5.0 million, respectively, recorded during the three months ended September 30, 2021. Other decreases in R&D expenses included $4.6 million in decreased manufacturing and collaborative expenses and $0.3 million of additional reimbursement from Zentera under our cost sharing arrangement. These decreases were offset by increases of $3.4 million, $3.1 million and $0.4 million of clinical trial related costs, personnel and consulting costs and overhead allocations, respectively.
•General and Administrative Expenses: General and administrative expenses for the three months ended September 30, 2022 were $12.0 million, compared to $8.9 million during the three months ended September 30, 2021. This increase of $3.1 million was primarily attributable to an increase in non-cash stock based compensation expense of $1.8 million and $0.3 million related to other compensation expense. Increases of $1.9 million, $0.6 million and $0.5 million were seen in rent and depreciation expense, external consulting expense and legal expense, respectively. These amounts were partially offset by a decrease in permits and fees and allocation of overhead expenditures to R&D of $1.6 million and $0.4 million, respectively.

On November 9, 2022 Galera Therapeutics, Inc. (Nasdaq: GRTX), a clinical-stage biopharmaceutical company focused on developing and commercializing a pipeline of novel, proprietary therapeutics that have the potential to transform radiotherapy in cancer, reported financial results for the third quarter ended September 30, 2022 and provided recent corporate updates (Press release, Galera Therapeutics, NOV 9, 2022, View Source [SID1234623570]).

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"During the quarter, we added to the package of data supporting our planned avasopasem New Drug Application in radiotherapy-induced severe oral mucositis, which we are on track to submit by the end of the year," said Mel Sorensen, M.D., Galera’s President and CEO. "We presented long-term follow-up data from ROMAN at ASTRO, the major annual radiation oncology conference, affirming what we saw in GT-201, specifically that avasopasem reduced severe oral mucositis while maintaining the clinical benefit of radiation therapy. Moreover, patients were also evaluated for renal function during the one-year follow-up period, and the data showed a 50% reduction in chronic kidney disease, a known cisplatin-related superoxide toxicity."

Dr. Sorensen continued: "Our market research continues to indicate that radiation and medical oncologists treating head and neck cancer view the avasopasem profile favorably and that the majority would prescribe avasopasem if approved by the FDA. The research also indicates that physicians view SOM — the most burdensome side effect of radiation therapy for head and neck cancer — as something best characterized by several key measures. These include not only whether a patient develops SOM, but also how long they suffer from it, when it first develops and whether it worsens into the most severe grade, Grade 4 OM. The meta-analysis of the already positive results from both the ROMAN and GT-201 trials underscores that avasopasem improves SOM across these measures."

Recent Corporate Updates

Radiotherapy-Induced Toxicity Programs:

Severe Oral Mucositis (SOM)

The Company remains on track to submit a New Drug Application (NDA) for avasopasem manganese 90 mg for radiotherapy-induced SOM to the U.S. Food and Drug Administration (FDA) by the end of 2022.

Long-term follow-up data from the ROMAN trial was presented in an oral presentation at the 2022 American Society for Radiation Oncology (ASTRO) Annual Meeting. After one-year follow-up on ROMAN, patients receiving avasopasem in combination with the standard-of-care regimen demonstrated comparable tumor outcomes and overall survival to patients in the placebo arm, showing that avasopasem protected patients with head and neck cancer from SOM without affecting the treatment benefit of standard-of-care chemoradiotherapy.

In a prospectively defined component of the ROMAN long-term follow-up data, also presented at ASTRO, patients treated with avasopasem in combination with radiotherapy and cisplatin had a 10% incidence of chronic kidney disease (CKD) after one year of post treatment follow-up, half the 20% rate in the placebo arm (p=0.0043). This exploratory endpoint was based on mechanism-driven non-clinical studies and a retrospective analysis of GT-201 and suggests avasopasem may offer a further benefit for these patients.

Additionally, a meta-analysis of Galera’s two randomized placebo-controlled trials (ROMAN and GT-201; n=551) was included in the ASTRO presentation, and showed clinically meaningful reductions in the incidence, duration, onset and severity of SOM compared to placebo across both trials.

A poster presentation during ASTRO highlighted the completed Phase 2 EUSOM trial of avasopasem for radiotherapy-induced SOM in Europe.
Esophagitis

Final data from the open-label, single-arm Phase 2 AESOP trial of avasopasem for severe acute radiotherapy-induced esophagitis in patients with lung cancer receiving concurrent chemoradiotherapy were presented at ASTRO. The Company previously reported positive topline data from the trial demonstrating that avasopasem was well tolerated and the incidence of Grade 3 esophagitis was substantially reduced in comparison to expectations based on review of historical data in the literature. No patients experienced Grade 4 or 5 esophagitis at any point during the AESOP trial.
Anti-Cancer Programs:

Locally Advanced Pancreatic Cancer (LAPC)

Enrollment is ongoing in the randomized, placebo-controlled Phase 2b GRECO-2 trial of rucosopasem in combination with stereotactic body radiation therapy (SBRT) in patients with LAPC. The primary endpoint of the trial is overall survival. Completion of enrollment is expected in the second half of 2023.
Non-Small Cell Lung Cancer (NSCLC)

A poster presentation at ASTRO highlighted the ongoing randomized, placebo-controlled Phase 2 stage of the GRECO-1 trial of rucosopasem in combination with SBRT in patients with NSCLC. Completion of enrollment in the Phase 2 stage of this trial is expected in the second half of 2023.
General Corporate Updates:

The Company appointed Eugene P. Kennedy, M.D., F.A.C.S., as Chief Medical Officer. Dr. Kennedy is a renowned Johns Hopkins-trained surgical oncologist and former Chief of Pancreatic and Hepatobiliary Surgery at Thomas Jefferson University with over 15 years’ experience in clinical development and biopharma leadership. He will succeed Jon T. Holmlund, M.D., who plans to retire at the end of this year following the planned submission of the Company’s NDA for avasopasem to the FDA.
Third Quarter 2022 Financial Highlights

Research and development expenses were $8.1 million in the third quarter of 2022, compared to $14.8 million for the same period in 2021. The decrease was primarily attributable to a decrease in avasopasem development costs, partially offset by an increase in rucosopasem development costs.

General and administrative expenses were $4.9 million in the third quarter of 2022, compared to $5.5 million for the same period in 2021. The decrease was primarily attributable to the timing of spend for avasopasem commercial preparations.
Galera reported a net loss of ($16.0) million, or $(0.60) per share, for the third quarter of 2022, compared to a net loss of $(22.6) million, or $(0.86) per share, for the same period in 2021.

As of September 30, 2022, Galera had cash, cash equivalents and short-term investments of $42.8 million. Galera expects that its existing cash, cash equivalents and short-term investments will enable Galera to fund its operating expenses and capital expenditure requirements into the second half of 2023.