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.

On November 9, 2022 Immunocore Holdings plc (Nasdaq: IMCR) ("Immunocore" or the "Company"), a commercial-stage biotechnology company pioneering the development of a novel class of T cell receptor (TCR) bispecific immunotherapies designed to treat a broad range of diseases, including cancer, autoimmune and infectious diseases, reported its financial results for the third quarter ended September 30, 2022 and provided a business update (Press release, Immunocore, NOV 9, 2022, View Source [SID1234623569]).

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"We are proud to have delivered the world’s first soluble TCR therapy to patients, and to have achieved such uptake in academic and community treatment centers," commented Bahija Jallal, Chief Executive Officer of Immunocore. "The promising clinical data from our PRAME candidate, presented at ESMO (Free ESMO Whitepaper) Congress 2022, has demonstrated the potential of our platform in multiple tumor types and confirmed that there is high and homogeneous expression of the antigen across these tumors. We are recruiting patients in the expansion arms of the Phase 1/2 trial to further assess efficacy."

"With the strong commercial performance of KIMMTRAK, our PIPE financing in the third quarter, and the refinancing of the existing debt facility on improved terms, we are well-positioned to confidently deliver the next stages of the Company’s growth, including the further development of the PRAME clinical program," commented Brian Di Donato, Chief Financial Officer & Head of Strategy of Immunocore.

Third Quarter 2022 Highlights (including post-period)

KIMMTRAK (tebentafusp-tebn)

Total net product and net pre-product revenue arising from the sale of KIMMTRAK and tebentafusp was £36.3 million (or $40.4 million) in the three months ended September 30, 2022, an increase of 20% in USD over 2Q 2022 (converted using respective end-of-period convenience rates), and £74.5 million (or $83.0 million) in the nine months ended September 30, 2022.

During the third quarter of 2022, the Company continued to add new accounts prescribing KIMMTRAK in the United States, Germany, and France. As of September 30, there were 180 new accounts prescribing KIMMTRAK in the United States, which brings the capture rate of these accounts, according to the company’s estimates, to 50% of potentially eligible patients. There were 80 new accounts prescribing KIMMTRAK in Germany and France, which brings the capture rate to approximately 70% of the eligible patient population. In September, the Company began selling KIMMTRAK as a commercial product in France, and these net sales are reflected in product revenue.

KIMMTRAK’s clinical benefit to patients continues to be recognized, with the G-BA (Gemeinsamer Bundesausschuss) granting a considerable added benefit rating to KIMMTRAK. KIMMTRAK is one of only two orphan oncology medicines for rare diseases to receive a considerable added benefit rating – the second-highest possible – in more than ten years of the German reimbursement process, Arzneimittelmarkt-Neuordnungsgesetz (AMNOG). This recommendation builds upon the positive recommendations by American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) and National Comprehensive Cancer Network (NCCN) in the second quarter of this year.

In November, the Company and Medison Pharma Ltd. ("Medison") amended and restated their exclusive distribution agreement for KIMMTRAK originally entered into in September 2021. Medison is the exclusive distribution partner for KIMMTRAK in Canada, Australia, New Zealand, Israel, Central and Eastern Europe, and following this amendment South and Central America, and the Caribbean.

KIMMTRAK (tebentafusp) developmental programs

In August, the Company announced its plans to evaluate tebentafusp in a randomized Phase 2/3 trial in previously treated advanced melanoma. The trial will enroll patients with advanced melanoma, excluding uveal melanoma, who have progressed on an anti-PD1, received prior ipilimumab and, if applicable, received a tyrosine kinase inhibitor (TKI). The Phase 2 portion of the trial will include 40 patients per arm and has a dual primary endpoint of overall survival (OS) and circulating tumor DNA (ctDNA) reduction. The Company is on track to start the trial in the fourth quarter of 2022.

In September, the Company presented four posters at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2022:

A propensity score weighted comparison of tebentafusp or pembrolizumab versus combination ipilimumab and nivolumab in untreated metastatic uveal melanoma
Safety and efficacy of infrequent tebentafusp treatment omissions in patients with metastatic uveal melanoma
Long-term survivors on tebentafusp in phase 2 trial of previously treated patients with metastatic uveal melanoma
ImmTAC redirect T cells against patient-derived tumor organoids and three-dimensional melanospheres; effects augmented by type I interferons
In November, the Company had two posters accepted for presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 37th Annual Meeting. SITC (Free SITC Whitepaper) 2022 is being held November 8-12, 2022 in Boston Massachusetts. The titles of the company’s poster presentations are as follows:

Molecular features in tumors at time of progression on tebentafusp associated with overall survival (OS)
Tebentafusp induced T and B cell epitope spread in patients with advanced melanoma
IMC-F106C Targeting PRAME

In September, the initial Phase 1 data from the dose escalation study of IMC-F106C, the first off-the-shelf PRAME x CD3 ImmTAC bispecific protein, was presented as a proffered paper (oral presentation) during an "Investigational Immunotherapy" session at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress. IMC-F106C demonstrated a well-tolerated safety profile. Durable RECIST responses and reduction in circulating tumor DNA (ctDNA) were observed across multiple solid tumors. Doses of ≥ 20 mcg were clinically active and had consistent and robust interferon gamma induction, a specific marker of T cell activation.

The Company has initiated patient enrollment into four expansion arms in cutaneous melanoma, ovarian, non-small cell lung cancer (NSCLC), and endometrial cancers. The Company will also study IMC-F106C in combination with standards-of-care, including with tebentafusp.

IMC-C103C Targeting MAGE-A4

Data from the Phase 1 ovarian expansion arm of the dose escalation study with IMC-C103C, the MAGE-A4 x CD3 ImmTAC bispecific protein, was accepted for a poster presentation at the ESMO (Free ESMO Whitepaper) Immuno-Oncology Congress 2022, in December. In this expansion arm, the Company enrolled all comers and evaluated MAGE expression retrospectively.

In the initial dose escalation data reported at ESMO (Free ESMO Whitepaper) I-O in December 2021, there were 15 response evaluable ovarian carcinoma patients in the active dose range (≥90 mcg). Only half were positive for MAGE-A4, with a median H score of 35 out of 300, and one patient had a confirmed partial response.

ImmTAV clinical programs

In July, the Company dosed the first patient in the first-in-human clinical trial of IMC-M113V, a new class of bispecific protein immunotherapy that is being developed for the treatment of patients with human immunodeficiency virus (HIV) infection. IMC-M113V is an immunotherapeutic approach designed to specifically eliminate CD4+ cells that are persistently infected with HIV (‘reservoirs’). IMC-M113V targets a peptide derived from the Gag protein that is presented by HLA*A02 on the surface of HIV infected cells. Reduction of the number of these cells is one way to potentially achieve a state of viral suppression in the absence of anti-retroviral medications, or a ‘functional cure’.

Corporate and financial updates

For the third quarter ended September 30, 2022, Immunocore reported net KIMMTRAK / tebentafusp revenues of £36.3 million (or $40.4 million). U.S. net product revenue from the sale of KIMMTRAK in the second quarter was £22.5 million (or $25.1 million), and European revenue (primarily in German and France) from the sale of KIMMTRAK and early access tebentafusp was £13.0 million (or $14.5 million).

Third quarter net KIMMTRAK / tebentafusp revenues of £36.3 million (or $40.4 million) increased by 31% (or 20%) compared to our previously reported second quarter KIMMTRAK / tebentafusp revenues of £27.7 million (or $33.7 million).1

In July, the Company announced a private investment in public equity ("PIPE") financing with four existing investors for net proceeds of $139.6 million. This financing, along with anticipated revenue from KIMMTRAK and cash and cash equivalents on hand, are expected to fund the Company through 2025.

The Company has entered into a loan agreement with investment funds managed by Pharmakon Advisors, LP, providing the Company with up to $100 million committed. The initial $50 million drawn from the credit facility will be used to refinance the Company’s existing debt with Oxford Finance, LLC on improved terms and the remaining $50 million, if and when drawn, is intended to be used to support the continued development and commercialization of the Company’s pipeline and for other general purposes.

Anticipated Upcoming Milestones 2022

KIMMTRAK
Q4 2022 – start the Phase 2/3 clinical trial in previously treated advanced melanoma

ImmTAC pipeline
Q4 2022 – report initial data from IMC-C103C (MAGE-A4) Phase 1 ovarian expansion arm

Financial Results

Basic and diluted earnings per share for the three months ended September 30, 2022, was £0.13 (or $0.14) and £0.12 (or $0.13), respectively, compared to a basic and diluted loss per share of (£0.69) for the three months ended September 30, 2021. Basic and diluted loss per share for the nine months ended September 30, 2022, was (£0.36) (or ($0.40)), compared to (£2.19) for the nine months ended September 30, 2021.

Total operating loss for the nine months ended September 30, 2022, was £17.3 million (or $19.2 million), compared to £97.3 million for the nine months ended September 30, 2021. For the three months ended September 30, 2022, we generated an operating profit of £6.2 million (or $6.9 million) compared to an operating loss of £31.0 million for the three months ended September 30, 2021. The operating profit of £6.2 million (or $6.9 million), for the three months ended September 30, 2022, reflects foreign exchange gains of £15.2 million (or $16.9 million) due to the significant changes arising in the exchange rates between pounds sterling and U.S. dollars during this period.

Total net product and net pre-product revenue arising from the sale of KIMMTRAK and tebentafusp was £36.3 million (or $40.4 million) in the three months ended September 30, 2022, and £74.5 million (or $83.0 million) in the nine months ended September 30, 2022. In the three and nine months ended September 30, 2021, we recorded pre-product revenue of £0.5 million.

For the three and nine months ended September 30, 2022, our research and development expenses were £23.3 million (or $25.9 million) and £62.0 million (or $69.1 million), respectively, as compared to £16.8 million and £53.2 million for the three and nine months ended September 30, 2021, respectively. For the three and nine months ended September 30, 2022, our selling and administrative expenses were £11.7 million (or $13.0 million) and £50.6 million (or $56.3 million) compared to £20.0 million and £64.0 million for the three and nine months ended September 30, 2021, respectively.

Cash and cash equivalents were £347.2 million or $386.6 million as of September 30, 2022 compared to £237.9 million as of December 31, 2021.

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About ImmTAV molecules and infectious diseases
ImmTAV (Immune mobilising monoclonal TCRs Against Virus) molecules are novel bispecific molecules that, like ImmTAC (Immune mobilising monoclonal TCRs Against Cancer) molecules, are designed to enable the immune system to recognize and eliminate virally infected cells.

Immunocore is advancing clinical candidates to cure patients with HIV and hepatitis B virus (HBV). The Company aims to achieve sustained control of HIV after patients stop anti-retroviral therapy (ART), without the risk of virological relapse or onward transmission. This is known as ‘functional cure’. For the treatment of HBV, the Company aims to achieve sustained loss of circulating viral antigens and markers of viral replication after stopping medication for people living with chronic HBV.

About ImmTAC molecules for cancer
Immunocore’s proprietary T cell receptor (TCR) technology generates a novel class of bispecific biologics called ImmTAC (Immune mobilizing monoclonal TCRs Against Cancer) molecules that are designed to redirect the immune system to recognize and kill cancerous cells. ImmTAC molecules are soluble TCRs engineered to recognize intracellular cancer antigens with ultra-high affinity and selectively kill these cancer cells via an anti-CD3 immune-activating effector function. Based on the demonstrated mechanism of T cell infiltration into human tumors, the ImmTAC mechanism of action holds the potential to treat hematologic and solid tumors, regardless of mutational burden or immune infiltration, including immune "cold" low mutation rate tumors.

About TEBE-AM Phase 2/3 Trial
IMCgp100-203 (also known as TEBE-AM) is a randomized Phase 2/3 trial in previously treated advanced melanoma that will evaluate the effect of KIMMTRAK (tebentafsup) on overall survival (OS). The trial will enroll patients with advanced melanoma, excluding uveal melanoma, that have progressed on an anti-PD1, received prior ipilimumab and, if applicable, received a tyrosine kinase inhibitor (TKI). The Phase 2/3 trial will randomize to one of three arms including KIMMTRAK, as monotherapy or in combination with an anti-PD1, and a control arm. Patients randomized to the control arm will immediately enter overall survival (OS) follow-up where they may be treated per the investigator decision including other clinical trials. This design effectively randomizes patients to "real world" treatment since clinical trials are the preferred option. The Phase 2 portion of the trial will include 40 patients per arm and has a dual primary endpoint of OS and circulating tumor DNA (ctDNA) reduction. The Phase 3 portion currently plans to enroll 170 patients per arm and has a primary endpoint of OS. However, the design of the Phase 3 portion including eligibility, whether to discontinue an arm and powering may be adapted based on results from the Phase 2 portion.

About the IMC-F106C-101 Phase 1/2 Trial
IMC-F106C-101 is a first-in-human, Phase 1/2 dose escalation trial in patients with multiple solid tumor cancers including non-small cell lung cancer (NSCLC), small-cell lung cancer (SCLC), endometrial, ovarian, cutaneous melanoma, and breast cancers. The Phase 1 dose escalation trial was designed to determine the maximum tolerated dose (MTD), as well as to evaluate the safety, preliminary anti-tumor activity and pharmacokinetics of IMC-F106C, a bispecific protein built on Immunocore’s ImmTAC technology, and the Company’s first molecule to target the PRAME antigen. The Company has initiated patient enrollment into four expansion arms in cutaneous melanoma, ovarian, NSCLC, and endometrial cancers. The IMC-F106C-101 trial is adaptive and includes the option for Phase 2 expansion, allowing for approximately 100 patients treated per tumor type in the Phase 1 and 2 expansion arms. Dose escalation continues in additional solid tumors as well as plans for combination arms with standards-of-care.

About Uveal Melanoma
Uveal melanoma is a rare and aggressive form of melanoma, which affects the eye. Although it is the most common primary intraocular malignancy in adults, the diagnosis is rare, and up to 50% of people with uveal melanoma will eventually develop metastatic disease. Unresectable or metastatic uveal melanoma typically has a poor prognosis and had no approved treatment until KIMMTRAK.

About KIMMTRAK
KIMMTRAK is a novel bispecific protein comprised of a soluble T cell receptor fused to an anti-CD3 immune-effector function. KIMMTRAK specifically targets gp100, a lineage antigen expressed in melanocytes and melanoma. This is the first molecule developed using Immunocore’s ImmTAC technology platform designed to redirect and activate T cells to recognise and kill tumour cells. KIMMTRAK has been approved for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma in the United States, European Union, Canada, Australia, and the United Kingdom.

About Phase 3 IMCgp100-202 Trial
IMCgp100-202 (NCT03070392) is a randomized pivotal trial that evaluated overall survival (OS) of KIMMTRAK compared to investigator’s choice (either pembrolizumab, ipilimumab, or dacarbazine) in HLA-A*02:01-positive adult patients with previously untreated mUM. KIMMTRAK demonstrated an unprecedented OS benefit with a Hazard Ratio (HR) in the intent-to-treat population favoring KIMMTRAK, HR=0.51 (95% CI: 0.37, 0.71); p< 0.0001, over investigator’s choice (82% pembrolizumab; 13% ipilimumab; 6% dacarbazine).

IMPORTANT SAFETY INFORMATION

Cytokine Release Syndrome (CRS), which may be serious or life-threatening, occurred in patients receiving KIMMTRAK. Monitor for at least 16 hours following first three infusions and then as clinically indicated. Manifestations of CRS may include fever, hypotension, hypoxia, chills, nausea, vomiting, rash, elevated transaminases, fatigue, and headache. CRS occurred in 89% of patients who received KIMMTRAK with 0.8% being grade 3 or 4. Ensure immediate access to medications and resuscitative equipment to manage CRS. Ensure patients are euvolemic prior to initiating the infusions. Closely monitor patients for signs or symptoms of CRS following infusions of KIMMTRAK. Monitor fluid status, vital signs, and oxygenation level and provide appropriate therapy. Withhold or discontinue KIMMTRAK depending on persistence and severity of CRS.

Skin Reactions

Skin reactions, including rash, pruritus, and cutaneous edema occurred in 91% of patients treated with KIMMTRAK. Monitor patients for skin reactions. If skin reactions occur, treat with antihistamine and topical or systemic steroids based on persistence and severity of symptoms. Withhold or permanently discontinue KIMMTRAK depending on the severity of skin reactions.

Elevated Liver Enzymes

Elevations in liver enzymes occurred in 65% of patients treated with KIMMTRAK. Monitor alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total blood bilirubin prior to the start of and during treatment with KIMMTRAK. Withhold KIMMTRAK according to severity.

Embryo-Fetal Toxicity

KIMMTRAK may cause fetal harm. Advise pregnant patients of potential risk to the fetus and patients of reproductive potential to use effective contraception during treatment with KIMMTRAK and 1 week after the last dose.

The most common adverse reactions (≥30%) in patients who received KIMMTRAK were cytokine release syndrome, rash, pyrexia, pruritus, fatigue, nausea, chills, abdominal pain, edema, hypotension, dry skin, headache, and vomiting. The most common (≥50%) laboratory abnormalities were decreased lymphocyte count, increased creatinine, increased glucose, increased AST, increased ALT, decreased hemoglobin, and decreased phosphate.

For more information, please see full Summary of Product Characteristics (SmPC) or full U.S. Prescribing Information (including BOXED WARNING for CRS).

About KIMMTRAKConnect
Immunocore is committed to helping patients who need KIMMTRAK obtain access via our KIMMTRAKConnect program. The program provides services with dedicated nurse case managers who provide personalized support, including educational resources, financial assistance, and site of care coordination. To learn more, visit KIMMTRAKConnect.com or call 844-775-2273.