On March 13, 2025 aTyr Pharma, Inc. (Nasdaq: ATYR) ("aTyr" or the "Company"), a clinical stage biotechnology company engaged in the discovery and development of first-in-class medicines from its proprietary tRNA synthetase platform, reported fourth quarter and full year 2024 results and provided a corporate update (Press release, aTyr Pharma, MAR 13, 2025, View Source [SID1234651134]).

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

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

                  Schedule Your 30 min Free Demo!

"2024 was an important year for aTyr, as we completed enrollment in our global pivotal Phase 3 EFZO-FIT study, which is the largest interventional study ever to be conducted in pulmonary sarcoidosis, a disease where incidence and prevalence are rising yet there are still limited treatment options," said Sanjay S. Shukla, M.D., M.S., President and Chief Executive Officer of aTyr. "The stage is set for 2025 to be a potential milestone year as we look toward reporting topline data for EFZO-FIT in the third quarter. Leading into this pivotal readout, we are very pleased with the execution of the study to date and the continued favorable safety profile demonstrated for efzofitimod, including our most recent positive DSMB review, which recommended the study continue as designed. Efzofitimod is poised to potentially become a safe and effective alternative to the current standard of care and improve patients’ lives."

Fourth Quarter 2024 and Subsequent Period Highlights

Enrollment complete in the global pivotal Phase 3 EFZO-FIT study to evaluate the efficacy and safety of efzofitimod in patients with pulmonary sarcoidosis. This is a randomized, double-blind, placebo-controlled, 52-week study consisting of three parallel cohorts randomized equally to either 3.0 mg/kg or 5.0 mg/kg of efzofitimod or placebo dosed intravenously monthly for a total of 12 doses. The study enrolled 268 patients with pulmonary sarcoidosis at 85 centers in nine countries. The trial design incorporates a forced steroid taper. The primary endpoint of the study is steroid reduction. Secondary endpoints include measures of sarcoidosis symptoms and lung function. Topline data from the study are expected in the third quarter of 2025. Patients who complete the study and wish to receive treatment with efzofitimod outside of the clinical trial are eligible to participate in an Individual Patient Expanded Access Program.
Held a Type C meeting with the U.S. Food and Drug Administration (FDA) to discuss the statistical analysis plan (SAP) for the Phase 3 EFZO-FIT study. The main objective of the meeting was to finalize the way in which the study endpoints are assessed from a statistical standpoint. Based on FDA feedback, steroid reduction will be measured as the absolute change from baseline to week 48.
Announced the fourth positive data and safety monitoring board (DSMB) review for the Phase 3 EFZO-FIT study. The independent DSMB recommended that the study continue without modifications based on the pre-planned analysis.
Enrollment ongoing in the Phase 2 EFZO-CONNECT study to evaluate the efficacy, safety and tolerability of efzofitimod in patients with limited and diffuse systemic sclerosis (SSc, or scleroderma)-related interstitial lung disease (SSc-ILD). This proof-of-concept study is a randomized, double-blind, placebo-controlled, 28-week study consisting of three parallel cohorts randomized 2:2:1 to either 270 mg or 450 mg of efzofitimod or placebo dosed intravenously monthly for a total of six doses. The study intends to enroll up to 25 patients at multiple centers in the United States. Patients who complete the study are eligible to participate in a 24-week open-label extension. Interim data from the study are expected in the second quarter of 2025 and will focus on skin assessments measured at baseline and week 12 in approximately 8 patients, including patients on drug and placebo. The data will include skin histopathology, including immune biomarkers, and the modified Rodnan skin score.
Manuscript demonstrating the immunomodulatory activity for efzofitimod in lung inflammation and fibrosis published in the peer-reviewed journal Science Translational Medicine. The publication describes efzofitimod’s unique anti-inflammatory effect on macrophages through neuropiln-2 (NRP2) and details the preclinical data supporting its development. The publication, which is entitled, "A human histidyl-tRNA synthetase splice variant therapeutic targets NRP2 to resolve lung inflammation and fibrosis," is available on the journal’s website and at: View Source
Posters for efzofitimod accepted for presentation at the upcoming American Thoracic Society (ATS) 2025 International Conference. The conference is scheduled to take place May 16 – 21, 2025, in San Francisco, CA.
Poster 9320 – Real-World Treatment Patterns Among Pulmonary Sarcoidosis Patients with Parenchymal Involvement in the US on Sunday May 18, 2025, at 11:30 a.m. PDT.
Poster 6808 – EFZO-FIT, Largest Placebo-Controlled Trial in Pulmonary Sarcoidosis – Trial Design and Patient Characteristics on Monday, May 19, 2025, at 11:30 a.m. PDT.
Poster 9092 – Incidence, Prevalence, and Mortality of Pulmonary Sarcoidosis with Parenchymal Involvement in the US on Tuesday May 20, 2025, at 11:30 a.m. PDT.
Presented preclinical research demonstrating anti-fibrotic effects of ATYR0101 in lung and kidney fibrosis in two posters at the Keystone Symposia on Fibrosis: Inflammation, Drivers, and Therapeutic Resolution. The findings demonstrated that ATYR0101 interacts with LTBP-1 to induce myofibroblast apoptosis through a novel anti-fibrotic mechanism and suggest that ATYR0101 has the potential to be a next generation anti-fibrotic drug for lung and kidney fibrosis.
Appointed Eric Benevich to the Company’s Board of Directors. Mr. Benevich currently serves as Chief Commercial Officer at Neurocrine Biosciences, Inc., where he is responsible for all aspects of commercial development, marketing, and sales of the Neurocrine product portfolio.
Year Ended 2024 Financial Highlights and Cash Position

Cash & Investment Position: Cash, cash equivalents, restricted cash and available-for-sale investments as of December 31, 2024, were $75.1 million. Subsequent to the end of the fourth quarter 2024, the Company raised approximately $18.8 million in gross proceeds from its at-the-market (ATM) offering with Jefferies LLC.
Financial Guidance: The Company updated its prior guidance and believes its cash runway will be sufficient to fund its operations for a period of one year following the Phase 3 EFZO-FIT readout, which includes the potential filing of a Biologics License Application (BLA) for efzofitimod in pulmonary sarcoidosis.
R&D Expenses: Research and development expenses were $54.4 million for the year ended 2024, which consisted primarily of clinical trial costs for the Phase 3 EFZO-FIT and Phase 2 EFZO-CONNECT studies, manufacturing costs for the efzofitimod program and research and development costs for the efzofitimod and discovery programs.
G&A Expenses: General and administrative expenses were $13.8 million for the year ended 2024.
Collaboration and License Revenue: Collaboration and license revenue related to the Kyorin Agreement was $0.2 million for the year ended 2024, which consisted of drug product material sold to Kyorin for the Japan portion of the EFZO-FIT study.
Conference Call and Webcast Details

aTyr will host a conference call and webcast today at 5:00 p.m. EDT / 2:00 p.m. PDT to discuss its financial results and provide a corporate update. Interested parties may access the call by registering here in order to obtain a dial in, personalized passcode and webcast information. Links to a live audio webcast and replay may be accessed on the aTyr website Events page at: View Source An audio replay will be available for at least 90 days following the event.

About Efzofitimod

Efzofitimod is a first-in-class biologic immunomodulator in clinical development for the treatment of interstitial lung disease (ILD), a group of immune-mediated disorders that can cause inflammation and fibrosis, or scarring, of the lungs. Efzofitimod is a tRNA synthetase derived therapy that selectively modulates activated myeloid cells through neuropilin-2 to resolve inflammation without immune suppression and potentially prevent the progression of fibrosis. aTyr is currently investigating efzofitimod in the global Phase 3 EFZO-FIT study in patients with pulmonary sarcoidosis, a major form of ILD, and in the Phase 2 EFZO-CONNECT study in patients with systemic sclerosis (SSc, or scleroderma)-related ILD. These forms of ILD have limited therapeutic options and there is a need for safer and more effective, disease-modifying treatments that improve outcomes.

On March 13, 2025 Medigene AG (Medigene, FSE: MDG1, Prime Standard), an oncology platform company focused on the research and development of T cell receptor (TCR)-guided therapies for the treatment of cancer, reported the submission of a patent for a novel natural killer (NK) cell-specific TCR construct to the European Patent Office. With that, Medigene is advancing its TCR-guided strategy by expanding the application of its proprietary 3S (sensitive, specific, and safe) TCRs into NK cells (Press release, MediGene, MAR 13, 2025, View Source [SID1234651135]). This patent application marks a major expansion of Medigene’s intellectual property portfolio, broadening its therapeutic reach and reinforcing its commitment to developing innovative, off-the-shelf immunotherapies for cancer treatment.

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

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

                  Schedule Your 30 min Free Demo!

To enable this innovation, Medigene combined TCR-guided precision targeting with innate NK cell killing. The Company has developed a proprietary universal scaffold that allows its 3S TCRs to function in NK cells without requiring CD3 co-expression. This novel NK-TCR system enhances NK cell production and therapeutic potential by facilitating the efficient transfer of all 3S TCRs into NK cells, streamlining the manufacturing process for future allogeneic TCR-NK therapies. By eliminating CD3 dependency, this approach overcomes a critical limitation in TCR-based NK cell therapy development, delivering a scalable, clinically viable solution that accelerates therapeutic timelines and reduces costs.

"This innovative approach supports our strategy to apply Medigene’s 3S TCRs into new TCR-guided modalities, such as TCR-TCEs and now TCR-NKs, to create additional value for both patients and our shareholders," said Selwyn Ho, CEO of Medigene. "Expanding our TCR-guided therapies to include NK cells aligns with our commitment to developing off-the-shelf, highly specific, and effective immunotherapies for cancer treatment."

The global NK cell therapeutics market is rapidly expanding, driven by rising cancer prevalence, an aging population, and demand for innovative immunotherapies. Valued at ~$0.55B in 2024, it is projected to reach $2.13B by 2033 (Source:Business Research Insights). Medigene’s proprietary TCR-NK technology is well-positioned to drive this growth with highly specific, scalable NK cell-based therapies.

Medigene continues to strengthen its intellectual property portfolio through the generation of new 3S TCRs, development of advanced technologies, and strategic expansion of existing patents across additional geographies. With over 29 unique patent families worldwide, Medigene safeguards its proprietary TCR and End-to-End Platform technologies, ensuring a strong competitive position in the immunotherapy space.

On March 12, 2025 Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688) reported that China’s National Medical Products Administration (NMPA) has accepted the Biologics License Application (BLA) for TIVDAK (tisotumab vedotin-tftv) for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after systemic therapy (Press release, Zai Laboratory, MAR 12, 2025, View Source [SID1234651105]).

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

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

                  Schedule Your 30 min Free Demo!

"In China, cervical cancer is a serious health concern with approximately 150,000 new cases diagnosed annually1," said Dr. Rafael Amado, M.D., President, Head of Global Research and Development at Zai Lab. "Treatment options for patients experiencing recurrence or metastasis after initial treatment are limited. TIVDAK, the only antibody-drug conjugate (ADC) therapy in cervical cancer, demonstrated promising benefits including a clinically meaningful improvement in overall survival (OS) in the pivotal global innovaTV 301 trial. If approved, TIVDAK will leverage our existing commercial infrastructure for ZEJULA, expanding our ability to offer treatment for women’s cancer."

The BLA submission is supported by the results from the global, randomized, Phase 3 innovaTV 301 clinical trial (NCT04697628) and the results from the China subpopulation of this study. As reported in January 2025, the China subpopulation results were consistent with those in the global population:

TIVDAK demonstrated a 45% reduction in the risk of death compared to chemotherapy (HR: 0.55 [95% CI: 0.27-1.15] in the China subpopulation who had received prior standard systemic therapies, with more than half of this Chinese population having received prior anti-PD(L)1 therapy. After a median follow-up of 11.5 months, the median OS was not reached in the TIVDAK arm versus 10.7 months in the chemotherapy arm.
Secondary endpoints of progression-free survival (PFS) and confirmed objective response rate (ORR) also favored treatment with TIVDAK.
The safety of TIVDAK in the China subpopulation was manageable and consistent with the global profile.
About TIVDAK (tisotumab vedotin-tftv)

TIVDAK (tisotumab vedotin) is an antibody-drug conjugate (ADC) composed of Genmab’s human monoclonal antibody directed to tissue factor (TF) and Pfizer’s ADC technology that utilizes a protease-cleavable linker that covalently attaches the microtubule-disrupting agent monomethyl auristatin E (MMAE) to the antibody. Nonclinical data suggest that the anticancer activity of tisotumab vedotin is due to the binding of the ADC to TF-expressing cancer cells, followed by internalization of the ADC-TF complex, and release of MMAE via proteolytic cleavage. MMAE disrupts the microtubule network of actively dividing cells, leading to cell cycle arrest and apoptotic cell death. In vitro, tisotumab vedotin also mediates antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity.

TIVDAK received full approval from U.S. Food and Drug Administration (FDA) in April 2024 for adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.

Please see full U.S. prescribing information, including BOXED WARNING for TIVDAK here.

Zai Lab has an exclusive license from Seagen Inc., acquired by Pfizer in 2023, to develop and commercialize TIVDAK in Greater China (mainland China, Hong Kong, Macau, and Taiwan, collectively).

About Cervical Cancer in China

Cervical cancer remains one of the leading causes of cancer death in women in China. An estimated 150,000 new cases of cervical cancer occur annually in China1. Current treatment options are limited for patients with recurrent or metastatic cervical cancer with disease progression on or after systemic therapy. TIVDAK is well positioned to provide a new option for previously treated advanced cervical cancer patients who currently have limited treatment options and poor outcomes.

On March 12, 2025 Faeth Therapeutics (Faeth), a clinical-stage biotechnology company focused on metabolism, and The GOG Foundation, Inc. (GOG-F), a not-for-profit organization with the purpose of promoting excellence in the quality and integrity of clinical and translational scientific research in the field of gynecologic malignancies, reported the first patient has been dosed in its Phase 2 combination trial of PIKTOR, which is FTH-001 (serabelisib) and FTH-003 (sapanisertib) with paclitaxel (Press release, Faeth Therapeutics, MAR 12, 2025, View Source [SID1234651106]). The trial is the most advanced of its kind to investigate a novel approach of dual PI3Kɑ-mTORC1/2 inhibition targeting cancer metabolism in patients with endometrial cancer.

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

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

                  Schedule Your 30 min Free Demo!

The PI3K/AKT/mTOR pathway is the most frequently mutated pathway in cancer and is essential for tumor metabolism. Endometrial cancer has the highest frequency of PI3K pathway mutations of any solid tumor, yet there are no approved therapies addressing this need. FTH-001, a PI3Kɑ inhibitor, and FTH-003, an mTORC 1/2 inhibitor, have both demonstrated potential in multiple previous cancer clinical trials and their combination represents a unique "multi-node" approach to targeting this pathway.

The current study, An Open-label, Multi-Center, Phase 2 Clinical Trial Evaluating Sapanisertib and Serabelisib (PIKTOR) With Paclitaxel, and a Substudy Evaluating PIKTOR With Paclitaxel Plus Diet, in Patients With Advanced or Recurrent Endometrial Cancer (FTH-PIK-201, GOG-3111)2 will expand on the strong Phase 1b data1 showing an 80% ORR in patients with endometrioid endometrial cancer with 11 months of progression-free survival. The Phase 2 study is based on Faeth’s metabolism-focused platform for developing novel therapeutic approaches. Endometrial cancer is one of the leading causes of cancer death in women and there is a high unmet need in patients with advanced and relapsed disease who have progressed after first line carboplatin-based therapy.

"Thanks to Faeth’s ability to uncover novel metabolism-targeting strategies, we are positioned to leverage the PIKTOR approach for endometrial cancer and other solid tumors," said Anand Parikh, J.D., Chief Executive Officer of Faeth Therapeutics. "Over its five decades, the GOG Foundation has established itself as a leading clinical partner against gynecologic cancers, and we are confident they will help us pave the way for the next generation of cancer treatments."

"This unique approach to target cancer metabolism has demonstrated impressive early results. We look forward to this trial to hopefully confirm these early findings and perhaps transform the way we treat patients with endometrial cancer," said David Starks, MD, Principal Investigator and Associate Professor, Avera Cancer Institute and University of South Dakota Sanford School of Medicine.

"Endometrial cancer is the leading cause of deaths among all gynecologic cancers. Finding better treatment options remains our highest priority. We are excited to partner with Faeth Therapeutics to further investigate this novel therapeutic approach," said Brian Slomovitz, MD, Director, Gynecologic Oncology, Mount Sinai Medical Center and Uterine Cancer Trial Lead, GOG Partners.

On March 12, 2025 City of Hope, one of the largest and most advanced cancer research and treatment organizations in the U.S. with its National Medical Center named top 5 in the nation for cancer by U.S. News & World Report, reported that its phase 1 clinical trial has demonstrated the safety and early efficacy of targeted chemotherapy using PIPAC combined with systemic chemotherapy for patients with colorectal and appendiceal cancer that has spread to the peritoneum of the abdominal cavity (Press release, City of Hope, MAR 12, 2025, View Source [SID1234651107]). This data will be presented at a March 18 press briefing spotlighting some of the most consequential research to be shared at this year’s Society of Surgical Oncology Annual Meeting (SSO).

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

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

                  Schedule Your 30 min Free Demo!

Of all the possible sites that cancer can spread to, the abdomen’s peritoneum is the worst when it comes to survival rates because it is difficult for systemic chemotherapy to reach this region due to a low number of blood vessels. When surgery is not an option and peritoneal metastases are left untreated, these patients survive only a few months and few make it past one year with standard treatment.

"Up until recently, delivering a uniform dose of chemotherapy in the abdomen has not been possible. At City of Hope, we have been evaluating the use of pressurized intraperitoneal aerosolized chemotherapy, or PIPAC, which is the most optimized way to deliver chemotherapy in the abdominal cavity. It increases targeted medicinal exposure while limiting toxicity," said Mustafa Raoof, M.D., M.S., assistant professor in City of Hope’s Division of Surgical Oncology and first author of the SSO abstract entitled "Dose escalation Phase 1 trial of Mitomycin C Pressurized Intraperitoneal Aerosolized Chemotherapy in Combination with Systemic Chemotherapy for Unresectable Appendiceal and Colorectal Carcinomatosis," which will be featured in the SSO press briefing at 9 a.m. PST on March 18.

The Society of Surgical Oncology is an international community of cancer surgeons and care professionals who are shaping advances in the delivery of the highest quality surgical care for cancer patients. City of Hope was the first U.S. institution to offer PIPAC in a clinical trial, and has hosted the first and second U.S. PIPAC training workshops.

The City of Hope-led multicenter phase 1 trial, in collaboration with Northwell Health and Mayo Clinic in Florida, included 19 patients with a median age of 60 who had colorectal or appendiceal cancer that had spread to the peritoneum and was inoperable even after four months of first- or second-line systemic chemotherapy. These patients received treatments that included Mitomycin C chemotherapy targeted to the abdomen via PIPAC and standard-of-care FOLFIRI systemic chemotherapy. This combination treatment is necessary to maximize the medicinal delivery via systemic and regional exposure.

"While we were able to demonstrate safety in this study, what we are really excited about is the early efficacy results seen as measured by several response criteria — histologic, laparoscopic, radiographic and tumor marker CEA," Dr. Raoof said. "This trial provides strong rationale for a multicenter randomized trial, which City of Hope will open soon. The new trial will determine if the addition of PIPAC to standard therapy could both improve survival and preserve quality of life. At this time, we caution against off-label use of PIPAC until the definitive efficacy of PIPAC in this population is proven."

In addition to Dr. Raoof’s oral abstract to be presented March 28 at 8:26 p.m. ET in TCC Ballroom BC, City of Hope also will have five poster abstracts at SSO 2025 happening March 27 to 29 in Tampa, Florida:

P64: Genetic Pathogenic Variants in Asian American/Pacific Islander Women with Breast Cancer: Implications for Surgical and Oncologic Care
Presenter: Jennifer Tseng, M.D.
P167: Impact of Systematic Discontinuation of Mitomycin C HIPEC for Colorectal Peritoneal Metastasis on Oncologic Outcomes at an NCI Cancer Center
Presenter: Muhammad Talha Waheed, M.D.
P187: Upfront Colectomy vs. Initial Appendectomy followed by Completion Colectomy for Appendiceal Cancer: Comparison of Outcomes
Presenter: Muhammad Talha Waheed, M.D.
P453: Percutaneous Transesophageal Gastrostomy as an Alternative Approach for Palliative Decompression of Malignant Bowel Obstruction
Presenter: Kristofor Olson, M.D., Ph.D.
P114: Reduced hepatotoxicity and equivalent survival with a lower hepatic arterial floxuridine starting dose in the adjuvant treatment of colorectal cancer liver metastases
Presenter: Kevin Labadie, M.D.