FGFR4

Phase 3 EFZO-FIT™ study of efzofitimod in pulmonary sarcoidosis anticipated to complete enrollment in the second quarter of 2024. Company launches Individual Patient Expanded Access Program (EAP), allowing access to efzofitimod for patients who complete EFZO-FIT™. Phase 2 EFZO-CONNECT™ study of efzofitimod in SSc-ILD currently enrolling. Ended 2023 with $101.7 million in cash, cash equivalents and investments. Company to host conference call and webcast today, March 14th, at 5:00 p.m. EDT / 2:00 p.m. PDT. SAN DIEGO, March 14, 2024 (GLOBE NEWSWIRE) -- aTyr Pharma, Inc. (Nasdaq: LIFE) (“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, today announced fourth quarter and full year 2023 results and provided a corporate update. “Throughout 2023 we made meaningful progress with our clinical development program for our lead therapeutic candidate, efzofitimod, in interstitial lung disease (ILD),” said Sanjay S. Shukla, M.D., M.S., President and Chief Executive Officer of aTyr. “Our primary focus for 2024 is completing enrollment in our global pivotal Phase 3 EFZO-FIT™ study in patients with pulmonary sarcoidosis, a major form of ILD, which is anticipated in the second quarter.” “We ended 2023 with more than $100 million in cash, restricted cash, cash equivalents and investments. Based on our current cash position and operational plans, we believe our financial resources are sufficient to fund the Company’s operations through the filing of a Biologics License Application (BLA) for efzofitimod in pulmonary sarcoidosis." Fourth Quarter 2023 and Subsequent Period Highlights Continued enrollment 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 intends to enroll up to 264 patients with pulmonary sarcoidosis. The study is currently enrolling at more than 90 centers in 9 countries. A positive data and safety monitoring board review assessed that the study could continue unmodified. Based on current enrollment projections, the Company anticipates completing enrollment in the study in the second quarter of 2024.Announced an Individual Patient Expanded Access Program (EAP) for efzofitimod for patients with pulmonary sarcoidosis. The EAP has been initiated based on blinded EFZO-FIT™ study investigator and patient participant feedback. The program is designed to allow access for patients who complete the Phase 3 EFZO-FIT™ study and wish to receive treatment with efzofitimod outside of the clinical trial.Continued enrollment in the Phase 2 EFZO-CONNECT™ study to evaluate the efficacy, safety and tolerability of efzofitimod in patients with 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 6 doses. The study intends to enroll up to 25 patients with SSc-ILD and is open for enrollment at multiple centers in the U.S.Poster for efzofitimod accepted for presentation at the upcoming American Thoracic Society (ATS) 2024 International Conference. The conference is scheduled to take place May 17 – 22, 2024, in San Diego, CA. Poster 8837 – Efzofitimod is an Immunomodulator of Myeloid Cell Function and Novel Therapeutic Candidate for Interstitial Lung Diseases on Sunday, May 19, 2024, at 2:15 p.m. PDT. Presented two posters highlighting the importance of neuropilin-2 (NRP2) in immune regulation at the Keystone Symposia on Myeloid Cell Diversity. The findings further demonstrate that efzofitimod modulates myeloid cells via the NRP2 receptor to promote a unique anti-inflammatory mechanism and validates the role of NRP2 in the immune system by the activity of an NRP2 blocking antibody in preclinical models. Announced Wayne A. I. Frederick, M.D., President Emeritus of Howard University, as an advisor to the Company. Dr. Frederick is a distinguished physician executive with extensive knowledge on disparities in healthcare and will advise the Company on its efzofitimod program in ILD.Poster for ATYR0750 accepted for presentation at the upcoming Gordon Research Conference Fibroblast Growth Factors in Development and Disease. The conference is scheduled to take place March 24 – 29, 2024, in Galveston, TX. Poster – Alanyl-tRNA Synthetase Fragment Binds to FGFR4 and Induces Morphological Changes and Downstream Signaling in Liver Cells with Functional Similarities to FGF2. Year Ended 2023 Financial Highlights and Cash Position Cash & Investment Position: Cash, cash equivalents, restricted cash and investments as of December 31, 2023, were $101.7 million. Based on the Company’s current operational plans and existing cash, the Company maintains its prior guidance and believes its cash runway will be sufficient to fund the Company’s operations through the filing of a BLA for efzofitimod in pulmonary sarcoidosis.R&D Expenses: Research and development expenses were $42.3 million for the year ended 2023, 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 $13.0 million for the year ended 2023. 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: http://investors.atyrpharma.com/events-and-webcasts. 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. About aTyr aTyr is a clinical stage biotechnology company leveraging evolutionary intelligence to translate tRNA synthetase biology into new therapies for fibrosis and inflammation. tRNA synthetases are ancient, essential proteins that have evolved novel domains that regulate diverse pathways extracellularly in humans. aTyr’s discovery platform is focused on unlocking hidden therapeutic intervention points by uncovering signaling pathways driven by its proprietary library of domains derived from all 20 tRNA synthetases. aTyr’s lead therapeutic candidate is efzofitimod, a first-in-class biologic immunomodulator in clinical development for the treatment of interstitial lung disease, a group of immune-mediated disorders that can cause inflammation and progressive fibrosis, or scarring, of the lungs. For more information, please visit www.atyrpharma.com. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are usually identified by the use of words such as “anticipates,” “believes,” “designed,” “expects,” “intends,” “may,” “plans,” “potential,” “project,” “will,” and variations of such words or similar expressions. We intend these forward-looking statements to be covered by such safe harbor provisions for forward-looking statements and are making this statement for purposes of complying with those safe harbor provisions. These forward-looking statements include statements regarding our belief that we will have sufficient cash runway to fund the Company’s operations through the filing of a BLA for efzofitimod for pulmonary sarcoidosis; the expected size of, and number and nationality of patients to be enrolled in, the EFZO-FIT™ and EFZO-CONNECT™ studies; the design and benefits of our EAP for efzofitimod for patients with pulmonary sarcoidosis; the potential therapeutic benefits and applications of efzofitimod; and timelines and plans with respect to certain development activities and development goals, including our expectation that our Phase 3 EFZO-FIT™ study of efzofitimod in patients with pulmonary sarcoidosis will complete enrollment in the second quarter of 2024. These forward-looking statements also reflect our current views about our plans, intentions, expectations, strategies and prospects, which are based on the information currently available to us and on assumptions we have made. Although we believe that our plans, intentions, expectations, strategies and prospects, as reflected in or suggested by these forward-looking statements, are reasonable, we can give no assurance that the plans, intentions, expectations, strategies or prospects will be attained or achieved. All forward-looking statements are based on estimates and assumptions by our management that, although we believe to be reasonable, are inherently uncertain. Furthermore, actual results may differ materially from those described in these forward-looking statements and will be affected by a variety of risks and factors that are beyond our control including, without limitation, our assumptions and expectations underlying our belief that we will have sufficient cash runway to fund the Company’s operations through the filing of a BLA for efzofitimod for pulmonary sarcoidosis may not be accurate, the fact that NRP2 and tRNA synthetase biology is not fully understood, uncertainty regarding the ultimate long-term impact of evolving macroeconomic and geopolitical conditions, the risk of delays in our clinical trials, risks associated with the discovery, development and regulation of our product candidates, including the risk that results from clinical trials or other studies may not support further development, the risk that we may cease or delay preclinical or clinical development activities for any of our existing or future product candidates for a variety of reasons, the fact that our collaboration agreements are subject to early termination, and the risk that we may not be able to raise the additional funding required for our business and product development plans, as well as those risks set forth in our most recent Annual Report on Form 10-K, Quarterly Reports on form 10-Q and in our other SEC filings. Except as required by law, we assume no obligation to update publicly any forward-looking statements, whether as a result of new information, future events or otherwise. ATYR PHARMA INC. Consolidated Statements of Operations (in thousands, except share and per share data) Three Months Ended Years Ended December 31, December 31, 2023 2022 2023 2022 Revenues: License and collaboration agreement revenues $— $10,386 $353 $10,386 Total revenues — 10,386 353 10,386 Operating expenses: Research and development 12,755 14,910 42,293 42,808 General and administrative 3,204 3,426 12,979 13,982 Total operating expenses 15,959 18,336 55,272 56,790 Loss from operations (15,959) (7,950) (54,919) (46,404)Total other income (expense), net 1,198 427 4,522 1,061 Consolidated net loss (14,761) (7,523) (50,397) (45,343)Net loss attributable to noncontrolling interest in Pangu BioPharma Limited 1 2 8 5 Net loss attributable to aTyr Pharma, Inc. $(14,760) $(7,521) $(50,389) $(45,338)Net loss per share, basic and diluted $(0.25) $(0.26) $(0.94) $(1.60)Shares used in computing net loss per share, basic and diluted 59,261,219 29,116,524 53,606,488 28,419,569 ATYR PHARMA INC. Condensed Consolidated Balance Sheets (in thousands) December 31, December 31, 2023 2022 Cash, cash equivalents, restricted cash and available-for-sale investments $101,650 $69,311 Other receivables 2,436 11,775 Property and equipment, net 5,531 3,059 Operating lease, right-of-use assets 6,727 7,250 Financing lease, right-of-use assets 1,788 1,248 Prepaid expenses and other assets 2,521 3,143 Total assets $120,653 $95,786 Accounts payable and accrued expenses $15,088 $12,968 Current portion of operating lease liability 831 630 Current portion of financing lease liability 497 264 Long-term operating lease liability, net of current portion 12,339 9,633 Long-term financing lease liability, net of current portion 1,428 1,007 Total stockholders’ equity 90,470 71,284 Total liabilities and stockholders’ equity $120,653 $95,786 Contact:Ashlee DunstonDirector, Investor Relations and Public Affairsadunston@atyrpharma.com

Pictured: J&J's business center in Switzerland/iStock, yuelan Johnson & Johnson announced on Friday that the FDA has granted its FGFR kinase inhibitor Balversa (erdafitinib) full approval for the treatment of locally advanced or metastatic urothelial carcinoma. Friday’s full approval amends Balversa’s previous indication, which allowed its use in patients with susceptible mutations on the FGFR3 or FGFR2 genes, after platinum-based chemotherapy, according to the FDA’s announcement of the approval. J&J’s pill is now indicated for patients with susceptible genetic alterations on the FGFR3 gene—as determined by an approved test—with disease progression after at least one prior line of systemic therapy. Balversa is not approved to treat patients who are eligible for, but have not yet undergone, PD-1 or PD-L1 inhibitor therapies. Designed to be taken orally once-daily, Balversa is a small molecule FGFR kinase inhibitor that works by targeting and binding to FGFR1, FGFR2, FGFR3 and FGFR4, blocking their enzymatic activity, according to J&J’s website. This mechanism of action cuts off several signaling cascades and suppresses the uncontrolled division and survival of cancer cells. Balversa won the FDA’s accelerated approval in April 2019 for certain types of locally advanced or metastatic urothelial carcinoma (mUC), becoming the first FDA-authorized FGFR inhibitor. At the time, Balversa was backed by findings from a small single-arm Phase II trial with 87 enrolled patients, demonstrating a 32.2% objective response rate and a median duration of response of 5.4 months. To keep Balversa on the market, J&J ran the confirmatory Phase III THOR trial, which enrolled nearly 630 patients and compared the oral FGFR kinase inhibitor against the standard of care regimen, consisting of chemotherapy or Merck’s Keytruda (pembrolizumab). Patients who had undergone at least one prior line of anti-PD-(L)1 therapy were assigned to Cohort 1 of THOR, while those who had not were placed in Cohort 2. Data from Cohort 1, which ultimately became the basis for the FDA’s full approval on Friday, showed that Balversa cut the risk of death by 36% versus chemotherapy. Patients in the Balversa arm also lived a median of four months longer than those on chemotherapy, an effect that was statistically significant, according to J&J’s announcement. Kiran Patel, vice president of clinical development, solid tumors at J&J Innovative Medicine, said in a statement that “Balversa continues to demonstrate the promise of targeted therapy in the treatment of cancer with advanced bladder cancer,” given its performance in THOR. Friday’s full approval for Balversa continues J&J’s winning streak in cancer. In December 2023, the pharma posted promising data from the Phase III PERSEUS study showing that a Darzalex Faspro-based quadruplet regimen could significantly improve progression-free survival in newly diagnosed multiple myeloma patients. In October 2023, J&J’s head-to-head MARIPOSA study showed that the combination of Rybrevant and lazertinib could potentially best AstraZeneca’s Tagrisso (osimertinib) in EGFR-mutated non-small cell lung cancer. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

- Enrollment and dose escalation ongoing in SURF301 Phase 1/2 oncology - - Presented additional preclinical data on TYRA-300 in achondroplasia at ASBMR and ASHG - - First patient to be dosed in TYRA-200 Phase 1 by YE 2023 - - Strong cash position of $215.7 million as of Q3 2023 - CARLSBAD, Calif., Nov. 7, 2023 /PRNewswire/ -- Tyra Biosciences, Inc. (Nasdaq: TYRA), a clinical-stage biotechnology company focused on developing next-generation precision medicines that target large opportunities in Fibroblast Growth Factor Receptor (FGFR) biology, today reported financial results for the quarter ended September 30, 2023 and highlighted recent corporate progress. "From the start, TYRA has focused on developing precision therapies that target large opportunities that exist in FGFR biology, and we continue to follow the data. We continue to advance TYRA-300, our oral FGFR3-selective inhibitor, as we dose expand and escalate in our SURF301 oncology study and strengthen our preclinical data package in achondroplasia," said Todd Harris, CEO of TYRA. "Before the end of the year, we expect to update our guidance on the timing and design of our planned Phase 2 study in achondroplasia and the dosing of our first patient with TYRA-200." Third Quarter 2023 and Recent Corporate Highlights TYRA-300 SURF301 Phase 1/2 Study for Oncology Continued to Advance. SURF301 ( Study in Untreated and Resistant FGFR3+ Advanced Solid Tumors) (NCT05544552) is a multi-center, open label study designed to determine the optimal and maximum tolerated doses (MTD) and the recommended Phase 2 dose of TYRA-300, as well as to evaluate the preliminary antitumor activity of TYRA-300. Enrollment is ongoing in Part A and Part B and dose escalation is ongoing in Part B in Phase 1 of the study at multiple clinical sites in the U.S., Europe, and Australia. In this study, multiple doses and schedules of TYRA-300 will be evaluated to inform dosing decisions in future metastatic urothelial carcinoma (mUC), non-muscle invasive bladder cancer (NMIBC) and achondroplasia studies. Presented Positive Preclinical Data for Achondroplasia at ASBMR and ASHG Meetings. In October and early November 2023, TYRA presented additional preclinical results on TYRA-300 in achondroplasia at the American Society for Bone and Mineral Research (ASBMR) and the American Society of Human Genetics (ASHG) 2023 annual meetings, respectively. In preclinical mice models of achondroplasia conducted at The Imagine Institute in Paris, TYRA-300 increased bone growth, improved the shape of the skull, improved the shape of the foramen magnum, restored the architecture of the growth plate, and increased chondrocyte proliferation and differentiation. Granted Orphan Drug Designation for Achondroplasia from FDA. In July 2023, TYRA-300 was granted Orphan Drug Designation (ODD) for the treatment of achondroplasia from the U.S. Food and Drug Administration (FDA). TYRA-200 Phase 1 Study on Track to be Initiated by YE '23. TYRA continued to advance activities to support the initiation of the planned Phase 1 clinical study of TYRA-200, an FGFR1/2/3 inhibitor with potency against activating FGFR2 gene alterations and resistance mutations. The trial will be focused on intrahepatic cholangiocarcinoma resistant to prior FGFR inhibitors. TYRA remains on track to dose the first patient in this trial before year-end 2023. SNÅP Platform and Pipeline TYRA continued to advance its in-house precision medicine discovery engine, SNÅP, to develop therapies in targeted oncology and genetically defined conditions including FGF19+/FGFR4-driven cancers and others. Third Quarter 2023 Financial Results Third quarter 2023 net loss was $21.2 million compared to $12.5 million for the same period in 2022. Third quarter 2023 research and development expenses were $19.3 million compared to $10.9 million for the same period in 2022. Third quarter 2023 general and administrative expenses were $4.7 million compared to $2.7 million for the same period in 2022. As of September 30, 2023, TYRA had cash and cash equivalents of $215.7 million that are expected to support TYRA's important clinical and operational milestones over at least the next two years. About TYRA-300 TYRA-300 is the Company's lead precision medicine program stemming from its in-house SNÅP platform. TYRA-300 is an investigational, oral, FGFR3-selective inhibitor currently in development for the treatment of cancer and skeletal dysplasias, including achondroplasia. In oncology, TYRA-300 is being evaluated in a multi-center, open label Phase 1/2 clinical study, SURF301 ( Study in Untreated and Resistant FGFR3+ Advanced Solid Tumors). SURF301 (NCT05544552) was designed to determine the optimal and MTD and the recommended Phase 2 dose (RP2D) of TYRA-300, as well as to evaluate the preliminary antitumor activity of TYRA-300. SURF301 is currently enrolling adults with advanced urothelial carcinoma and other solid tumors with FGFR3 gene alterations. In skeletal dysplasias, TYRA-300 has demonstrated positive preclinical results, and the Company expects to submit an IND for the initiation of a Phase 2 clinical study in pediatric achondroplasia in 2024. In July 2023, TYRA-300 was granted Orphan Drug Designation for the treatment of achondroplasia from the FDA. About Tyra Biosciences Tyra Biosciences, Inc. (Nasdaq: TYRA) is a clinical-stage biotechnology company focused on developing next-generation precision medicines that target large opportunities in FGFR biology. The Company's in-house precision medicine platform, SNÅP, enables rapid and precise drug design through iterative molecular SNÅPshots that help predict genetic alterations most likely to cause acquired resistance to existing therapies. TYRA's initial focus is on applying its accelerated small molecule drug discovery engine to develop therapies in targeted oncology and genetically defined conditions. TYRA is based in Carlsbad, CA. For more information about our science, pipeline and people, please visit and engage with us on LinkedIn. Forward-Looking Statements TYRA cautions you that statements contained in this press release regarding matters that are not historical facts are forward-looking statements. The forward-looking statements are based on our current beliefs and expectations and include, but are not limited to: the potential to develop next-generation precision medicines and the potential safety and therapeutic benefits of TYRA-300 and other product candidates; the sufficiency of our cash position to support clinical and operational milestones; expected cash runway; the expected timing and phase of clinical development of TYRA-300 and TYRA-200, including timing of a submission of an IND for TYRA-300 in pediatric achondroplasia and patient dosing for TYRA-200; expected timing regarding updated guidance on the timing and design of our planned Phase 2 study in achondroplasia and dosing of our first patient with TYRA-200; and the potential for SNÅP to develop therapies in targeted oncology and genetically defined conditions. Actual results may differ from those set forth in this press release due to the risks and uncertainties inherent in our business, including, without limitation: we are early in our development efforts, have only recently begun testing TYRA-300 for oncology in clinical trials and the approach we are taking to discover and develop drugs based on our SNÅP platform is novel and unproven and it may never lead to product candidates that are successful in clinical development or approved products of commercial value; potential delays in the commencement, enrollment, and completion of preclinical studies and clinical trials; results from preclinical studies or early clinical trials not necessarily being predictive of future results; our dependence on third parties in connection with manufacturing, research and preclinical testing; we may expend our limited resources to pursue a particular product candidate and/or indication and fail to capitalize on product candidates or indications with greater development or commercial potential; acceptance by the FDA of INDs or of similar regulatory submissions by comparable foreign regulatory authorities for the conduct of clinical trials of TYRA-300 in pediatric achondroplasia; an accelerated development or approval pathway may not be available for TYRA-300 or other product candidates and any such pathway may not lead to a faster development process; unexpected adverse side effects or inadequate efficacy of our product candidates that may limit their development, regulatory approval, and/or commercialization; the potential for our programs and prospects to be negatively impacted by developments relating to our competitors, including the results of studies or regulatory determinations relating to our competitors; we may not realize the benefits associated with ODD, including that orphan drug exclusivity may not effectively protect a product from competition and that such exclusivity may not be maintained; regulatory developments in the United States and foreign countries; we may use our capital resources sooner than we expect; unstable market and economic conditions and adverse developments with respect to financial institutions and associated liquidity risk may adversely affect our business and financial condition and the broader economy and biotechnology industry; and other risks described in our prior filings with the Securities and Exchange Commission (SEC), including under the heading "Risk Factors" in our annual report on Form 10-K and any subsequent filings with the SEC. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and we undertake no obligation to update such statements to reflect events that occur or circumstances that exist after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Contact: Amy Conrad [email protected] SOURCE Tyra Biosciences