A Randomized, Placebo-Controlled, Double-Blind, Multi-Center Phase 3 Study of Zipalertinib Plus Adjuvant Chemotherapy Versus Placebo Plus Adjuvant Chemotherapy in Stage IB-IIIA NSCLC Patients With Uncommon EGFR Mutations Following Complete Tumor Resection (REZILIENT4)

The purpose of this study is to compare the efficacy of zipalertinib combined standard with adjuvant chemotherapy versus placebo combined standard with adjuvant chemotherapy in participants with early stage (stage IB-IIIA) resected non-small cell lung cancer (NSCLC) harboring uncommon epidermal growth factor receptor mutation (EGFRmt).

Start Date01 Oct 2025

Sponsor / Collaborator

Taiho Oncology, Inc.

CTIS2023-503865-48-00

/ RecruitingPhase 2

An Open-Label, Phase 2b, Global Multicenter Cohort Trial to Assess the Safety and Efficacy of Zipalertinib in Patients with Locally Advanced or Metastatic Non-Small Cell Lung Cancer with Exon 20 Insertion and Uncommon/Single or Compound Epidermal Growth Factor Receptor Mutations - TAS6417-201

Start Date21 Feb 2024

Sponsor / Collaborator

Taiho Oncology, Inc.

NCT05967689

/ RecruitingPhase 2

An Open-Label, Phase 2b, Global Multicenter Cohort Trial to Assess the Safety and Efficacy of Zipalertinib in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer With Exon 20 Insertion and Uncommon/Single or Compound Epidermal Growth Factor Receptor Mutations.

The purpose of this study is to evaluate the safety, efficacy and pharmacokinetics (PK) of zipalertinib in participants with locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC) harboring EGFR ex20ins mutations and other mutations.

Start Date31 Jul 2023

Sponsor / Collaborator

Taiho Oncology, Inc.

100 Clinical Results associated with Zipalertinib

100 Translational Medicine associated with Zipalertinib

100 Patents (Medical) associated with Zipalertinib

Literatures (Medical) associated with Zipalertinib

19 Feb 2025·Future Oncology

REZILIENT3: randomized phase III study of first-line zipalertinib plus chemotherapy in patients with EGFR exon 20 insertion-mutated NSCLC

Article

Author: Tan, Daniel SW. ; Cheng, Ying ; Heymach, John V. ; Besse, Benjamin ; Wacheck, Volker ; Yu, Helena A. ; Nishio, Makoto ; Wei, Li

There remains a significant unmet need for effective and tolerable treatments for patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations in the first-line setting. First and later generation EGFR tyrosine kinase inhibitors (TKIs) have shown efficacy for common EGFR mutations; however, their effectiveness against ex20ins mutations is limited, and platinum-based chemotherapy remains part of the standard of care. Data suggest that combining chemotherapy with EGFR inhibitors offers promise for EGFR ex20ins-mutated NSCLC. REZILIENT3 is an ongoing phase III study evaluating the efficacy and safety of zipalertinib (an orally available, irreversible EGFR-TKI) plus first-line standard-of-care platinum-based chemotherapy with chemotherapy alone in previously untreated patients with nonsquamous NSCLC harboring EGFR ex20ins mutations.Clinical Trial Registration: NCT05973773 (ClinicalTrials.gov).

05 Nov 2024·PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Biochemical analysis of EGFR exon20 insertion variants insASV and insSVD and their inhibitor sensitivity

Article

Author: Eck, Michael J. ; Beyett, Tyler S. ; Rana, Jaimin K. ; Schaeffner, Ilse K. ; Zhao, Hanchen ; Jiang, Jie ; Santana, Jhasmer ; Jänne, Pasi A.

Somatic mutations in the epidermal growth factor receptor (EGFR) are a major cause of non–small cell lung cancer. Among these structurally diverse alterations, exon 20 insertions represent a unique subset that rarely respond to EGFR tyrosine kinase inhibitors (TKIs). Therefore, there is a significant need to develop inhibitors that are active against this class of activating mutations. Here, we conducted biochemical analysis of the two most frequent exon 20 insertion variants, V769_D770insASV (insASV) and D770_N771insSVD (insSVD) to better understand their drug sensitivity and resistance. From kinetic studies, we found that EGFR insASV and insSVD are similarly active, but have lower K m, ATP values compared to the L858R variant, which contributes to their lack of sensitivity to 1st-3rd generation EGFR TKIs. Biochemical, structural, and cellular studies of a diverse panel of EGFR inhibitors revealed that the more recently developed compounds BAY-568, TAS6417, and TAK-788 inhibit EGFR insASV and insSVD in a mutant-selective manner, with BAY-568 being the most potent and selective versus wild-type (WT) EGFR. Cocrystal structures with WT EGFR reveal the binding modes of each of these inhibitors and of poziotinib, a potent but not mutantselective inhibitor, and together they define interactions shared by the mutant-selective agents. Collectively, our results show that these exon20 insertion variants are not inherently inhibitor resistant, rather they differ in their drug sensitivity from WT EGFR. However, they are similar to each other, indicating that a single inhibitor should be effective for several of the diverse exon 20 insertion variants.

01 Nov 2024·LUNG CANCER

The prediction of treatment outcome in NSCLC patients harboring an EGFR exon 20 mutation using molecular modeling

Article

Author: Groen, H J M ; van der Wekken, A J ; van Veggel, B.A.M.H. ; Zwierenga, F. ; van der Wekken, A.J. ; Zwierenga, F ; Zhang, L. ; Groves, M R ; Melcr, J ; Groen, H.J.M. ; de Langen, A J ; van Veggel, B A M H ; Schuuring, E. ; Groves, M.R. ; Melcr, J. ; Zhang, L ; Schuuring, E ; de Langen, A.J.

INTRODUCTION:

The structural effect of uncommon heterogenous in-frame deletion and/or insertion mutations within exon 20 (EGFRex20+) in relation to therapy response is poorly understood. This study aims to elucidate the structural alterations caused by EGFRex20+ mutations and correlate these changes with patient responses.

MATERIAL AND METHOD:

We selected EGFRex20+ mutations from advanced NSCLC patients in the Position20 and AFACET studies for computational analysis. Homology models representing both inactive and active conformations of these mutations were generated using the Swiss-Model server. Molecular docking studies with EGFR-TKIs was conducted using smina, followed by Molecular Dynamic (MD) simulations performed with GROMACS. These computational findings were compared with clinical outcomes to evaluate their potential in predicting patient response.

RESULTS:

Our docking studies of 29 EGFRex20+ mutations revealed that the binding energies of afatinib, osimertinib, zipalertinib, and sunvozertinib, compared to the wild type, do not significantly impact either TKI's efficacy. MD simulations for eight EGFRex20+ mutations (A763_Y764insFQEA, A767_V769dup, S768_D770dup, D770_N771insG, D770_P772dup, N771_H773dup, H773_V774insY and H773_V774delinsLM) revealed varying degrees of instability. For six variants, predicted activation based on the αC-helix stability and orientation, as well as TKI sensitivity, aligned well with clinical observations from the Position20 and AFACET studies. Two mutations (D770_N771insG and N771_H773dup) predicted as poor to moderate responders, showed minimal activation of the αC-helix region, warranting further investigation.

CONCLUSION:

In conclusion, MD simulations can effectively predict patient outcomes by connecting computational results with clinical data and advancing our understanding of EGFR mutations and their therapeutic responses.

News (Medical) associated with Zipalertinib

07 Aug 2025

·www.globenewswire.com

Cullinan Therapeutics Provides Corporate Update and Reports Second Quarter 2025 Financial Results

CLN-978 program now actively enrolling across Phase 1 studies in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and Sjögren’s disease BCMA-directed bispecific T cell engager velinotamig in-licensed from Genrix Bio Zipalertinib REZILIENT1 pivotal results shared in oral presentation at ASCO 2025 and in Journal of Clinical Oncology; multiple new data sets across a range of disease settings to be shared at IASLC 2025 WCLC and ESMO Congress 2025 Company appoints Mittie Doyle, M.D., and Andrew Allen, M.D., Ph.D., to its Board of Directors CAMBRIDGE, Mass., Aug. 07, 2025 (GLOBE NEWSWIRE) -- Cullinan Therapeutics, Inc. (Nasdaq: CGEM; “Cullinan”), a biopharmaceutical company focused on developing modality-agnostic targeted therapies, today provided an update on recent and anticipated business highlights and announced its financial results for the second quarter ended June 30, 2025. “I am proud of the team’s strong execution throughout the first half of the year as we continue to advance the CLN-978 program across three active studies in SLE, RA, and Sjögren’s disease. With the addition of velinotamig, we further solidified our leadership position in the development of T cell engagers for autoimmune diseases. With these two programs, our portfolio covers the entire breadth of the B cell compartment. Recent data presented at the European Alliance of Associations for Rheumatology (EULAR) meeting reinforced the potential of T cell engagers as disease-modifying therapies across a wide spectrum of autoimmune diseases,” said Nadim Ahmed, Chief Executive Officer of Cullinan Therapeutics. “We also continue making important progress across our oncology portfolio, recently sharing results from the pivotal Phase 2b portion of the REZILIENT1 study of zipalertinib at the 2025 ASCO Annual Meeting, and we look forward to sharing multiple new data sets at upcoming medical conferences. Pending discussions with the U.S. FDA, our partner Taiho plans to submit an NDA in relapsed EGFR ex20ins NSCLC later this year and expects to complete enrollment of the frontline study REZILIENT3 in the first half of 2026. We also plan to share clinical data for CLN-049, our FLT3xCD3 bispecific T cell engager, in patients with relapsed/refractory AML and MDS later this year. With $510.9 million in cash and investments and runway into 2028, we have the resources to generate multiple value-driving catalysts near term and beyond across both our immunology and oncology programs. Lastly, I am pleased to welcome Drs. Mittie Doyle and Andrew Allen to our Board of Directors. They are proven leaders with deep strategic and development expertise in immunology and oncology, respectively, and I believe their contributions will be invaluable as we continue to advance our programs. I would also like to thank Drs. Anne-Marie Martin and David Ryan for their contributions to our progress and success over the last several years.” Portfolio Highlights Immunology CLN-978 (CD19xCD3 bispecific T cell engager): Systemic lupus erythematosus, rheumatoid arthritis, and Sjögren’s disease The global Phase 1 study in patients with moderate to severe SLE is enrolling in the United States, Europe, and Australia, and the Company plans to share initial safety data and B cell depletion data from Part A of the study in Q4 2025.The Phase 1 study in patients with active, difficult-to-treat rheumatoid arthritis is enrolling in Europe. This company-sponsored study is being led by sites at FAU Erlangen-Nuremberg in Germany and Università Cattolica del Sacro Cuore in Italy. The Company plans to share initial data from this study during the first half of 2026.The global Phase 1 study in patients with active, moderate to severe Sjögren’s disease is enrolling in the U.S. and is now also active in Europe following recent regulatory approval. Velinotamig (BCMAxCD3 bispecific T cell engager): Autoimmune diseases In June 2025, the Company entered into an agreement with Genrix Bio for an exclusive global (ex-Greater China) license to velinotamig. Under the agreement, Cullinan paid Genrix Bio an upfront license fee of $20 million. In the future, Genrix Bio will also be eligible to receive up to $292 million in development and regulatory milestones plus up to an additional $400 million in sales-based milestones, as well as tiered royalties on potential ex-Greater China net sales.Genrix Bio plans to initiate a Phase 1 study in patients with autoimmune diseases in China by the end of 2025. Cullinan intends to use the data generated to accelerate global clinical development of the program. Following the completion of the Genrix Bio Phase 1 study, Cullinan will conduct all further development of velinotamig in autoimmune diseases. Oncology Zipalertinib (EGFR ex20ins inhibitor), collaboration with Taiho Oncology: EGFR ex20ins NSCLC In June 2025, results from the pivotal Phase 2b portion of REZILIENT1 in patients with EGFR ex20ins NSCLC who have received prior therapy were shared at the 2025 ASCO Annual Meeting and published simultaneously in the Journal of Clinical Oncology. Cullinan plans to share updated efficacy and safety data in patients previously treated with amivantamab during a mini oral abstract session at the IASLC 2025 WCLC.Pending discussions with the U.S. Food and Drug Administration, Taiho plans to submit an NDA in relapsed EGFR ex20ins NSCLC by the end of 2025. Taiho expects to complete enrollment of the pivotal study REZILIENT3 in 1L EGFR ex20ins NSCLC in the first half of 2026.Taiho plans to share initial data from the REZILIENT2 cohort exploring zipalertinib in patients with uncommon EGFR mutations during a mini oral abstract session at the IASLC 2025 WCLC. Taiho also plans to share initial data from the REZILIENT2 cohort exploring zipalertinib in patients with active brain metastases at the ESMO Congress 2025. CLN-049 (FLT3xCD3 bispecific T cell engager): Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) Enrollment continues in the Phase 1 study in patients with relapsed/refractory AML or MDS and the company plans to share clinical data from this study in Q4 2025.Enrollment also continues in the Phase 1 study in patients with measurable minimal residual disease in AML. CLN-619 (Anti-MICA/MICB monoclonal antibody): NSCLC and multiple myeloma Enrollment continues in the Phase 1 expansion cohorts in patients with NSCLC and the Phase 1 study in patients with relapsed/refractory multiple myeloma. CLN-617 (IL-2 and IL-12 cytokine fusion protein): Solid tumors Enrollment continues in the Phase 1 study in patients with advanced solid tumors. Corporate Updates Mittie Doyle, M.D., and Andrew Allen, M.D., Ph.D., were appointed to the Board of Directors, effective August 7, 2025. Both board directors bring significant leadership experience, with Dr. Doyle having extensive immunology clinical development expertise, and Dr. Allen with extensive oncology clinical development experience. Anne-Marie Martin, Ph.D., and David Ryan, M.D., will resign from Cullinan’s Board of Directors effective August 7, 2025. Second Quarter 2025 Financial Results Cash Position: Cash, cash equivalents, short- and long-term investments, and interest receivable were $510.9 million as of June 30, 2025. Cullinan continues to expect its cash resources to provide runway into 2028 based on its current operating plan.R&D Expenses: Research and development expenses were $61.0 million for the second quarter of 2025, compared to $36.3 million for the same period in 2024.G&A Expenses: General and administrative expenses were $14.8 million for the second quarter of 2025, compared to $13.8 million for the same period in 2024.Net Loss: Net loss attributable to Cullinan was $70.1 million for the second quarter of 2025, compared to $42.0 million for the same period in 2024. About Cullinan Therapeutics Cullinan Therapeutics, Inc. (Nasdaq: CGEM) is a biopharmaceutical company dedicated to creating new standards of care for patients. Cullinan has strategically built a diversified portfolio of clinical-stage assets that inhibit key drivers of disease or harness the immune system to eliminate diseased cells in both autoimmune diseases and cancer. Cullinan’s portfolio encompasses a wide range of modalities, each with the potential to be best and/or first in class. Anchored in a deep understanding of oncology, immunology, and translational medicine, we create differentiated ideas, identify the most appropriate targets, and select the optimal modality to develop transformative therapeutics across a wide variety of autoimmune and cancer indications. We push conventional boundaries from candidate selection to differentiated therapeutic, applying rigorous go/no go criteria at each stage of development to fast-track only the most promising molecules to the clinic and, ultimately, commercialization. With deep scientific expertise, our teams exercise creativity and urgency to deliver on our promise to bring new therapeutic solutions to patients. Learn more about Cullinan at https://cullinantherapeutics.com/, and follow us on LinkedIn and X. Forward-Looking Statements This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. These forward-looking statements include, but are not limited to, express or implied statements regarding the company’s beliefs and expectations regarding: our preclinical and clinical developments plans and timelines for our product candidates, the clinical and therapeutic potential of our product candidates, the strategy of our product candidates, our research and development activities, our plans regarding future data presentations, our cash runway, and other statements that are not historical facts. The words “believe,” “continue,” “could,” “estimate,” “expect,” “intends,” “may,” “plan,” “potential,” “project,” “pursue,” “will,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management's current expectations and beliefs of future events and are subject to known and unknown risks and uncertainties that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. These risks include, but are not limited to, the following: uncertainty regarding the timing and results of regulatory submissions; the risk that any INDs, NDAs or other global regulatory submissions we may file with the United States Food and Drug Administration or other global regulatory agencies are not cleared on our expected timelines, or at all; the success of our clinical trials and preclinical studies; the risks related to our ability to protect and maintain our intellectual property position; the risks related to manufacturing, supply, and distribution of our product candidates; the risk that any one or more of our product candidates, including those that are co-developed, will not be successfully developed and commercialized; the risk that the results of preclinical studies or clinical studies will not be predictive of future results in connection with future studies; the effect of changes in global economic conditions, including uncertainties related to international trade policies, tariffs and supply chain dynamics on our business and operations; and the success of any collaboration, partnership, license or similar agreements. These and other important risks and uncertainties discussed in our filings with the Securities and Exchange Commission, including under the caption “Risk Factors” in our most recent Annual Report on Form 10-K and subsequent filings with the SEC, could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change, except to the extent required by law. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release. Moreover, except as required by law, neither the company nor any other person assumes responsibility for the accuracy and completeness of the forward-looking statements included in this press release. Any forward-looking statement included in this press release speaks only as of the date on which it was made. Cullinan Therapeutics, Inc.Selected Condensed Consolidated Balance Sheet Data(unaudited)(in thousands) June 30, 2025 December 31, 2024 Cash, cash equivalents, investments, and interest receivable $510,898 $606,917 Total assets $520,329 $621,824 Total current liabilities $28,058 $30,647 Total liabilities $28,183 $31,496 Total stockholders’ equity $492,146 $590,328 Cullinan Therapeutics, Inc.Consolidated Statements of Operations(unaudited)(in thousands, except per share amounts) Three Months Ended June 30, Six Months Ended June 30, 2025 2024 2025 2024 Operating expenses: Research and development $61,030 $36,259 $102,489 $66,905 General and administrative 14,768 13,768 28,305 26,111 Total operating expenses 75,798 50,027 130,794 93,016 Loss from operations (75,798) (50,027) (130,794) (93,016)Other income (expense): Interest income 5,924 8,071 12,504 13,764 Other income (expense), net (181) (72) (266) (116)Net loss (70,055) (42,028) (118,556) (79,368)Net loss attributable to noncontrolling interests — — — (192)Net loss attributable to Cullinan $(70,055) $(42,028) $(118,556) $(79,176) Basic and diluted net loss per share attributable to Cullinan: Common stock $(1.07) $(0.68) $(1.81) $(1.43)Preferred stock $(10.70) $(6.83) $(18.12) $(14.26)Weighted-average shares used in computing net loss per share attributable to Cullinan: Common stock 59,015 55,052 58,960 49,031 Preferred stock 648 648 648 648 Contacts: InvestorsNick Smith+1 401.241.3516nsmith@cullinantx.com Media  Rose Weldon +1 215.801.7644 rweldon@cullinantx.com

Phase 1Phase 2License out/inExecutive ChangeFinancial Statement

07 Aug 2025

·investors.cullinantherapeutics.com

Cullinan Therapeutics Provides Corporate Update and Reports Second Quarter 2025 Financial Results

CLN-978 program now actively enrolling across Phase 1 studies in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and Sjögren’s disease BCMA-directed bispecific T cell engager velinotamig in-licensed from Genrix Bio Zipalertinib REZILIENT1 pivotal results shared in oral presentation at ASCO 2025 and in Journal of Clinical Oncology; multiple new data sets across a range of disease settings to be shared at IASLC 2025 WCLC and ESMO Congress 2025 Company appoints Mittie Doyle, M.D., and Andrew Allen, M.D., Ph.D., to its Board of Directors CAMBRIDGE, Mass., Aug. 07, 2025 (GLOBE NEWSWIRE) -- Cullinan Therapeutics, Inc. (Nasdaq: CGEM; “Cullinan”), a biopharmaceutical company focused on developing modality-agnostic targeted therapies, today provided an update on recent and anticipated business highlights and announced its financial results for the second quarter ended June 30, 2025. “I am proud of the team’s strong execution throughout the first half of the year as we continue to advance the CLN-978 program across three active studies in SLE, RA, and Sjögren’s disease. With the addition of velinotamig, we further solidified our leadership position in the development of T cell engagers for autoimmune diseases. With these two programs, our portfolio covers the entire breadth of the B cell compartment. Recent data presented at the European Alliance of Associations for Rheumatology (EULAR) meeting reinforced the potential of T cell engagers as disease-modifying therapies across a wide spectrum of autoimmune diseases,” said Nadim Ahmed, Chief Executive Officer of Cullinan Therapeutics. “We also continue making important progress across our oncology portfolio, recently sharing results from the pivotal Phase 2b portion of the REZILIENT1 study of zipalertinib at the 2025 ASCO Annual Meeting, and we look forward to sharing multiple new data sets at upcoming medical conferences. Pending discussions with the U.S. FDA, our partner Taiho plans to submit an NDA in relapsed EGFR ex20ins NSCLC later this year and expects to complete enrollment of the frontline study REZILIENT3 in the first half of 2026. We also plan to share clinical data for CLN-049, our FLT3xCD3 bispecific T cell engager, in patients with relapsed/refractory AML and MDS later this year. With $510.9 million in cash and investments and runway into 2028, we have the resources to generate multiple value-driving catalysts near term and beyond across both our immunology and oncology programs. Lastly, I am pleased to welcome Drs. Mittie Doyle and Andrew Allen to our Board of Directors. They are proven leaders with deep strategic and development expertise in immunology and oncology, respectively, and I believe their contributions will be invaluable as we continue to advance our programs. I would also like to thank Drs. Anne-Marie Martin and David Ryan for their contributions to our progress and success over the last several years.” Portfolio Highlights Immunology CLN-978 (CD19xCD3 bispecific T cell engager): Systemic lupus erythematosus, rheumatoid arthritis, and Sjögren’s disease The global Phase 1 study in patients with moderate to severe SLE is enrolling in the United States, Europe, and Australia, and the Company plans to share initial safety data and B cell depletion data from Part A of the study in Q4 2025. The Phase 1 study in patients with active, difficult-to-treat rheumatoid arthritis is enrolling in Europe. This company-sponsored study is being led by sites at FAU Erlangen-Nuremberg in Germany and Università Cattolica del Sacro Cuore in Italy. The Company plans to share initial data from this study during the first half of 2026. The global Phase 1 study in patients with active, moderate to severe Sjögren’s disease is enrolling in the U.S. and is now also active in Europe following recent regulatory approval. Velinotamig (BCMAxCD3 bispecific T cell engager): Autoimmune diseases In June 2025, the Company entered into an agreement with Genrix Bio for an exclusive global (ex-Greater China) license to velinotamig. Under the agreement, Cullinan paid Genrix Bio an upfront license fee of $20 million. In the future, Genrix Bio will also be eligible to receive up to $292 million in development and regulatory milestones plus up to an additional $400 million in sales-based milestones, as well as tiered royalties on potential ex-Greater China net sales. Genrix Bio plans to initiate a Phase 1 study in patients with autoimmune diseases in China by the end of 2025. Cullinan intends to use the data generated to accelerate global clinical development of the program. Following the completion of the Genrix Bio Phase 1 study, Cullinan will conduct all further development of velinotamig in autoimmune diseases. The global Phase 1 study in patients with moderate to severe SLE is enrolling in the United States, Europe, and Australia, and the Company plans to share initial safety data and B cell depletion data from Part A of the study in Q4 2025. The Phase 1 study in patients with active, difficult-to-treat rheumatoid arthritis is enrolling in Europe. This company-sponsored study is being led by sites at FAU Erlangen-Nuremberg in Germany and Università Cattolica del Sacro Cuore in Italy. The Company plans to share initial data from this study during the first half of 2026. The global Phase 1 study in patients with active, moderate to severe Sjögren’s disease is enrolling in the U.S. and is now also active in Europe following recent regulatory approval. In June 2025, the Company entered into an agreement with Genrix Bio for an exclusive global (ex-Greater China) license to velinotamig. Under the agreement, Cullinan paid Genrix Bio an upfront license fee of $20 million. In the future, Genrix Bio will also be eligible to receive up to $292 million in development and regulatory milestones plus up to an additional $400 million in sales-based milestones, as well as tiered royalties on potential ex-Greater China net sales. Genrix Bio plans to initiate a Phase 1 study in patients with autoimmune diseases in China by the end of 2025. Cullinan intends to use the data generated to accelerate global clinical development of the program. Following the completion of the Genrix Bio Phase 1 study, Cullinan will conduct all further development of velinotamig in autoimmune diseases. Oncology Zipalertinib (EGFR ex20ins inhibitor), collaboration with Taiho Oncology: EGFR ex20ins NSCLC In June 2025, results from the pivotal Phase 2b portion of REZILIENT1 in patients with EGFR ex20ins NSCLC who have received prior therapy were shared at the 2025 ASCO Annual Meeting and published simultaneously in the Journal of Clinical Oncology. Cullinan plans to share updated efficacy and safety data in patients previously treated with amivantamab during a mini oral abstract session at the IASLC 2025 WCLC. Pending discussions with the U.S. Food and Drug Administration, Taiho plans to submit an NDA in relapsed EGFR ex20ins NSCLC by the end of 2025. Taiho expects to complete enrollment of the pivotal study REZILIENT3 in 1L EGFR ex20ins NSCLC in the first half of 2026. Taiho plans to share initial data from the REZILIENT2 cohort exploring zipalertinib in patients with uncommon EGFR mutations during a mini oral abstract session at the IASLC 2025 WCLC. Taiho also plans to share initial data from the REZILIENT2 cohort exploring zipalertinib in patients with active brain metastases at the ESMO Congress 2025. CLN-049 (FLT3xCD3 bispecific T cell engager): Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) Enrollment continues in the Phase 1 study in patients with relapsed/refractory AML or MDS and the company plans to share clinical data from this study in Q4 2025. Enrollment also continues in the Phase 1 study in patients with measurable minimal residual disease in AML. CLN-619 (Anti-MICA/MICB monoclonal antibody): NSCLC and multiple myeloma Enrollment continues in the Phase 1 expansion cohorts in patients with NSCLC and the Phase 1 study in patients with relapsed/refractory multiple myeloma. CLN-617 (IL-2 and IL-12 cytokine fusion protein): Solid tumors Enrollment continues in the Phase 1 study in patients with advanced solid tumors. In June 2025, results from the pivotal Phase 2b portion of REZILIENT1 in patients with EGFR ex20ins NSCLC who have received prior therapy were shared at the 2025 ASCO Annual Meeting and published simultaneously in the Journal of Clinical Oncology. Cullinan plans to share updated efficacy and safety data in patients previously treated with amivantamab during a mini oral abstract session at the IASLC 2025 WCLC. Pending discussions with the U.S. Food and Drug Administration, Taiho plans to submit an NDA in relapsed EGFR ex20ins NSCLC by the end of 2025. Taiho expects to complete enrollment of the pivotal study REZILIENT3 in 1L EGFR ex20ins NSCLC in the first half of 2026. Taiho plans to share initial data from the REZILIENT2 cohort exploring zipalertinib in patients with uncommon EGFR mutations during a mini oral abstract session at the IASLC 2025 WCLC. Taiho also plans to share initial data from the REZILIENT2 cohort exploring zipalertinib in patients with active brain metastases at the ESMO Congress 2025. Enrollment continues in the Phase 1 study in patients with relapsed/refractory AML or MDS and the company plans to share clinical data from this study in Q4 2025. Enrollment also continues in the Phase 1 study in patients with measurable minimal residual disease in AML. Enrollment continues in the Phase 1 expansion cohorts in patients with NSCLC and the Phase 1 study in patients with relapsed/refractory multiple myeloma. Enrollment continues in the Phase 1 study in patients with advanced solid tumors. Corporate Updates Mittie Doyle, M.D., and Andrew Allen, M.D., Ph.D., were appointed to the Board of Directors, effective August 7, 2025. Both board directors bring significant leadership experience, with Dr. Doyle having extensive immunology clinical development expertise, and Dr. Allen with extensive oncology clinical development experience. Anne-Marie Martin, Ph.D., and David Ryan, M.D., will resign from Cullinan’s Board of Directors effective August 7, 2025. Second Quarter 2025 Financial Results Cash Position: Cash, cash equivalents, short- and long-term investments, and interest receivable were $510.9 million as of June 30, 2025. Cullinan continues to expect its cash resources to provide runway into 2028 based on its current operating plan. R&D Expenses: Research and development expenses were $61.0 million for the second quarter of 2025, compared to $36.3 million for the same period in 2024. G&A Expenses: General and administrative expenses were $14.8 million for the second quarter of 2025, compared to $13.8 million for the same period in 2024. Net Loss: Net loss attributable to Cullinan was $70.1 million for the second quarter of 2025, compared to $42.0 million for the same period in 2024. About Cullinan Therapeutics Cullinan Therapeutics, Inc. (Nasdaq: CGEM) is a biopharmaceutical company dedicated to creating new standards of care for patients. Cullinan has strategically built a diversified portfolio of clinical-stage assets that inhibit key drivers of disease or harness the immune system to eliminate diseased cells in both autoimmune diseases and cancer. Cullinan’s portfolio encompasses a wide range of modalities, each with the potential to be best and/or first in class. Anchored in a deep understanding of oncology, immunology, and translational medicine, we create differentiated ideas, identify the most appropriate targets, and select the optimal modality to develop transformative therapeutics across a wide variety of autoimmune and cancer indications. We push conventional boundaries from candidate selection to differentiated therapeutic, applying rigorous go/no go criteria at each stage of development to fast-track only the most promising molecules to the clinic and, ultimately, commercialization. With deep scientific expertise, our teams exercise creativity and urgency to deliver on our promise to bring new therapeutic solutions to patients. Learn more about Cullinan at https://cullinantherapeutics.com/, and follow us on LinkedIn and X. Forward-Looking Statements This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. These forward-looking statements include, but are not limited to, express or implied statements regarding the company’s beliefs and expectations regarding: our preclinical and clinical developments plans and timelines for our product candidates, the clinical and therapeutic potential of our product candidates, the strategy of our product candidates, our research and development activities, our plans regarding future data presentations, our cash runway, and other statements that are not historical facts. The words “believe,” “continue,” “could,” “estimate,” “expect,” “intends,” “may,” “plan,” “potential,” “project,” “pursue,” “will,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management's current expectations and beliefs of future events and are subject to known and unknown risks and uncertainties that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. These risks include, but are not limited to, the following: uncertainty regarding the timing and results of regulatory submissions; the risk that any INDs, NDAs or other global regulatory submissions we may file with the United States Food and Drug Administration or other global regulatory agencies are not cleared on our expected timelines, or at all; the success of our clinical trials and preclinical studies; the risks related to our ability to protect and maintain our intellectual property position; the risks related to manufacturing, supply, and distribution of our product candidates; the risk that any one or more of our product candidates, including those that are co-developed, will not be successfully developed and commercialized; the risk that the results of preclinical studies or clinical studies will not be predictive of future results in connection with future studies; the effect of changes in global economic conditions, including uncertainties related to international trade policies, tariffs and supply chain dynamics on our business and operations; and the success of any collaboration, partnership, license or similar agreements. These and other important risks and uncertainties discussed in our filings with the Securities and Exchange Commission, including under the caption “Risk Factors” in our most recent Annual Report on Form 10-K and subsequent filings with the SEC, could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change, except to the extent required by law. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release. Moreover, except as required by law, neither the company nor any other person assumes responsibility for the accuracy and completeness of the forward-looking statements included in this press release. Any forward-looking statement included in this press release speaks only as of the date on which it was made. Contacts: InvestorsNick Smith+1 401.241.3516nsmith@cullinantx.com Media  Rose Weldon +1 215.801.7644 rweldon@cullinantx.com

Phase 1License out/inPhase 2Financial StatementExecutive Change

25 Jul 2025

·www.prnewswire.com

Taiho Oncology Announces Acceptance of Abstract for Zipalertinib at the ESMO Congress 2025

Preliminary findings to be shared from Cohort C (active brain metastases) of the REZILIENT2 trial of zipalertinib in patients with exon 20 insertion (ex20ins) or other uncommon mutation epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) PRINCETON, N.J., July 25, 2025 /PRNewswire/ -- Taiho Oncology, Inc., a company developing and commercializing novel treatments for hematologic malignancies and solid tumors, announced it will present new data from the REZILIENT2 trial of zipalertinib at the European Society for Medical Oncology (ESMO) Congress 2025, to be held Oct. 17-21, 2025, in Berlin, Germany. The abstract accepted for a mini oral presentation includes the preliminary efficacy and safety data from the Phase 2b REZILIENT2 trial of zipalertinib, an oral, highly selective, irreversible EGFR tyrosine kinase inhibitor (TKI), in patients with advanced or metastatic NSCLC harboring EGFR ex20ins mutations or EGFR uncommon non-ex20ins mutations and active brain metastases and/or leptomeningeal disease. "We look forward to presenting the latest findings from Cohort C of our REZILIENT2 trial, which focuses on a subset of patients with ex20ins NSCLC with central nervous system involvement, at this year's ESMO Congress," said Harold Keer, MD, PhD, Chief Medical Officer, Taiho Oncology. "We are excited to share more details from our zipalertinib program, building upon its potential to make a meaningful impact in a disease area of unmet need." The session title and information for the accepted abstract are listed below. Full abstract details will be available via the conference website at 12:05 CEST a.m. on Oct. 13, 2025. Title: Activity of Zipalertinib Against Active Central Nervous System (CNS) Metastases in Patients With Non-Small Cell Lung Cancer (NSCLC) Harboring EGFR Exon 20 Insertion (Ex20ins)/Other Uncommon Mutations Abstract Number: 3778 Session Name: Mini oral session 1: NSCLC metastatic Session Type: Mini Oral Presentation Session Date: Oct. 19, 2025 Session Time: 8:30 to 10 a.m. CEST About Zipalertinib Zipalertinib (development code: CLN-081/TAS6417) is an orally available small molecule designed to target activating mutations in EGFR. The molecule was selected because of its ability to inhibit EGFR variants with exon 20 insertion mutations, while sparing wild-type EGFR. Zipalertinib is designed as a next generation, irreversible EGFR inhibitor for the treatment of a genetically defined subset of patients with non-small cell lung cancer. Zipalertinib has received Breakthrough Therapy Designation from the FDA. Zipalertinib is investigational and has not been approved by any health authority. Zipalertinib is being developed by Taiho Oncology, Inc., its parent company, Taiho Pharmaceutical Co., Ltd., and in collaboration with Cullinan Therapeutics, Inc. in the U.S. About Taiho Oncology, Inc. The mission of Taiho Oncology, Inc. is to improve the lives of patients with cancer, their families and their caregivers. The company specializes in the development and commercialization of orally administered anti-cancer agents for various tumor types. Taiho Oncology has a robust pipeline of small-molecule clinical candidates targeting solid-tumor and hematological malignancies, with additional candidates in pre-clinical development. Taiho Oncology is a subsidiary of Taiho Pharmaceutical Co., Ltd. which is part of Otsuka Holdings Co., Ltd. Taiho Oncology is headquartered in Princeton, New Jersey and oversees its parent company's European and Canadian operations, which are located in Baar, Switzerland and Oakville, Ontario, Canada. For more information, visit , and follow us on LinkedIn and X. Taiho Oncology and the Taiho Oncology logo are registered trademarks of Otsuka Holdings Co., Ltd. or its subsidiaries. Taiho Oncology Contact: Leigh Labrie (609) 664-9878 [email protected] SOURCE Taiho Oncology WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Phase 2Breakthrough TherapyASCODrug Approval

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Indication	Highest Phase	Country/Location	Organization	Date
Non-small cell lung cancer stage IIIA	Phase 3	-	Taiho Oncology, Inc.	01 Oct 2025
EGFR ex20ins mutation in non-small cell lung cancer	Phase 3	United States	Taiho Oncology, Inc.	30 Jun 2023
EGFR ex20ins mutation in non-small cell lung cancer	Phase 3	Japan	Taiho Oncology, Inc.	30 Jun 2023
EGFR ex20ins mutation in non-small cell lung cancer	Phase 3	Belgium	Taiho Oncology, Inc.	30 Jun 2023
EGFR ex20ins mutation in non-small cell lung cancer	Phase 3	Brazil	Taiho Oncology, Inc.	30 Jun 2023
EGFR ex20ins mutation in non-small cell lung cancer	Phase 3	Bulgaria	Taiho Oncology, Inc.	30 Jun 2023
EGFR ex20ins mutation in non-small cell lung cancer	Phase 3	Canada	Taiho Oncology, Inc.	30 Jun 2023
EGFR ex20ins mutation in non-small cell lung cancer	Phase 3	Chile	Taiho Oncology, Inc.	30 Jun 2023
EGFR ex20ins mutation in non-small cell lung cancer	Phase 3	France	Taiho Oncology, Inc.	30 Jun 2023
EGFR ex20ins mutation in non-small cell lung cancer	Phase 3	Germany	Taiho Oncology, Inc.	30 Jun 2023

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04036682 (REZILIENT1, Pubmed \| J Clin Oncol)	Phase 1/2	EGFR positive non-small cell lung cancer EGFR exon 20 insertion	244	Zipalertinib 100 mg twice daily	tjgwqagumi(bfldwzoxda) = gszcpyghqs xmgykuhpiz (hioeqmyycx, 28.2 - 42.8) View more	Positive	01 Jun 2025
NCT04036682 (REZILIENT1, Pubmed \| J Clin Oncol)	Phase 1/2		244	Platinum-based chemotherapy without ex20ins-targeted therapy	tjgwqagumi(bfldwzoxda) = nutduhqdux xmgykuhpiz (hioeqmyycx ) View more	Positive	01 Jun 2025
NCT04036682 (REZILIENT1, ASCO2025) Manual	Phase 2	EGFR ex20ins mutation in non-small cell lung cancer EGFR Exon 20 Insertion	176	Zipalertinib 100mgZipalertinib 100mg+platinum-based chemotherapy	imtcugeegl(pdxabeilvf) = hmteoyocpg hvjiqbvmat (lfnyofxwzw ) View more	Positive	30 May 2025
NCT04036682 (REZILIENT1, ASCO2025) Manual	Phase 2		176	zipalertinib 100mgzipalertinib 100mg+platinum-based chemotherapy +amivantamab	imtcugeegl(pdxabeilvf) = jrlyyrouqy hvjiqbvmat (lfnyofxwzw ) View more	Positive	30 May 2025
NCT04036682 (REZILIENT1, PRNewswire) Manual	Phase 2	EGFR ex20ins mutation in non-small cell lung cancer Second line EGFR Exon 20 Insertion	-	Zipalertinib	wgebefvzjh(bnstfyyyiq) = met its primary endpoint of overall response rate ytagtonzcb (margngktdb ) Met	Positive	28 Jan 2025
NCT05973773 (REZILIENT3, ESMO_ASIA2024) Manual	Phase 3	EGFR ex20ins mutation in non-small cell lung cancer First line EGFR exon 20 insertion	6	Zipalertinib 100 mg PO BID + Chemotherapy	zngepcegnz(nifqllqvxi) = kbebmhypft tvnrkdjgay (ktdvkxeltp )	Positive	07 Dec 2024
NCT04036682 (REZILIENT1, ESMO2024) Manual	Phase 2	EGFR ex20ins mutation in non-small cell lung cancer Second line EGFR Exon 20 Insertion	45	Zipalertinib 100 mg oral twice daily	kccyibzjmj(inulshapuv) = wdlxobdefk bciwitbcsz (xajmxximmx ) View more	Positive	14 Sep 2024
NCT04036682 (REZILIENT1, Biospace) Manual	Phase 2	EGFR ex20ins mutation in non-small cell lung cancer	18	Zipalertinib	lcfgdawnli(zapzezmadq) = ldmprytorc nztsykttvb (bildrsnwlp ) View more	Positive	01 Jun 2024
NCT04036682 (Pubmed)	Phase 1/2	EGFR-mutated non-small Cell Lung Cancer	73	Zipalertinib	zvgecyftff(ntgaizvkgn) = xznpiwaqtw zbshgcvigf (gtfvolfzgm ) View more	-	29 Jun 2023
NCT04036682 (Ins20, ASCO2022) Manual	Phase 1/2	Non-Small Cell Lung Cancer EGFR Exon 20 Insertion	73	CLN-081	qetooplgyv(nptlrbzknt) = cbsmsnnzro bwfqmnmwot (dfklxaearb ) View more	Positive	02 Jun 2022
NCT04036682 (Ins20, ASCO 12021 \| ASCO 22021) Manual	Phase 1/2	Non-Small Cell Lung Cancer EGFR Mutation	37	CLN-081	qxffltjred(jmhirmsjgm) = dqudsywovr dfgmnltjkz (fzpyejfkyh ) View more	Positive	20 May 2021

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