On August 20, 2025 I-Mab (NASDAQ: IMAB) (I-Mab or the Company), a U.S.-based, global biotech company, focused on the development of precision immuno-oncology agents for the treatment of cancer, reported financial results for the three and six months ended June 30, 2025, and highlighted recent pipeline progress and business updates (Press release, I-Mab Biopharma, AUG 20, 2025, View Source [SID1234655401]).

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"The first half of 2025 has been transformative for I-Mab," said Sean Fu, PhD, Chief Executive Officer of I-Mab. "Our presentation at ESMO (Free ESMO Whitepaper) GI showcased compelling Phase 1b combination data for givastomig, reinforcing our confidence in its potential to be a best-in-class Claudin 18.2-directed therapy for metastatic gastric cancers in the 1L setting. Thanks to strong study momentum and active investigator engagement, we completed enrollment of the planned Phase 1b dose expansion cohorts ahead of schedule and expect to report topline data in Q1 2026. We believe our strong cash position and unwavering focus on value creation, position I-Mab to deliver meaningful clinical data and improve the lives of patients."

Recent and Anticipated Upcoming Clinical Milestones

Givastomig (CLDN18.2 x 4-1BB bispecific):

Recent Developments:

•
Positive Phase 1b Dose Escalation Data in Combination with Immunochemotherapy Presented at ESMO (Free ESMO Whitepaper) GI 2025 – Data from the dose escalation cohorts of the study were presented on July 2, 2025 in a Mini Oral presentation at the European Society for Medical Oncology Gastrointestinal Cancers Congress (ESMO GI) 2025 in Barcelona, Spain, accessible here. The data showed that givastomig in combination with immunochemotherapy demonstrated an 83% (10/12) objective response rate (ORR) at the doses (8 mg/kg and 12 mg/kg) selected for dose expansion. The responses were rapid, durable and deepened over time, with a favorable overall safety profile.
I-Mab hosted a virtual investor event on July 8, 2025 reviewing the Phase 1b dose escalation data (accessible for viewing here).

•
Givastomig Monotherapy Data Published in Clinical Cancer Research – First-in-human monotherapy data for givastomig were published in Clinical Cancer Research, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (CCR), and a highly-ranked clinical oncology publication. The CCR paper details promising clinical data showing that givastomig monotherapy achieved an ORR of 16% in heavily pretreated Claudin 18.2-positive gastric cancer patients without encountering a dose limiting toxicity or maximum tolerated dose. The publication can be accessed here. The study provided the foundation for the ongoing Phase 1b combination study.
Upcoming Potential Clinical Milestones: I-Mab completed enrollment in the planned Phase 1b dose expansion study evaluating givastomig in combination with nivolumab and mFOLFOX6 for first line (1L) metastatic gastric cancers. The Company expects to present topline data in Q1 2026.

Other Programs: I-Mab anticipates updates in 2026 for ragistomig (PD-L1 x 4-1BB bispecific) and uliledlimab (monoclonal antibody targeting CD73), which are currently under development by ABL Bio and TJ Biopharma, respectively.

Corporate Developments

•
I-Mab Announces Pricing of $65 Million Underwritten Offering – I-Mab completed an underwritten offering of American Depositary Shares (ADSs) representing ordinary shares that raised total net proceeds of approximately $61.2 million. The offering included participation from new and existing investors including Everest Medicines, Janus Henderson Investors, Adage Capital Partners LP and Exome Asset Management.

•
Givastomig Intellectual Property Portfolio Strengthened with Acquisition of Bridge Health – The acquisition provides I-Mab with upstream rights to the Claudin 18.2 parental antibody for use in bispecific and multi-specific applications, eliminates all royalty obligations and reduces future milestones for givastomig due to Bridge Health Biotech Co., Ltd. (Bridge Health) by I-Mab. The transaction is expected to close in Q3 2025.
Cash Position

As of June 30, 2025, the Company had cash and cash equivalents, and short-term investments of $165.6 million. The Company expects that its existing cash and cash equivalents, and short-term investments, together with the net proceeds from the August 2025 underwritten offering, will be sufficient to fund its operating expenses and capital expenditure requirements through the fourth quarter of 2028, including through a randomized Phase 2 trial of givastomig.

Shares Outstanding

As of June 30, 2025, the Company had 188,108,178 ordinary shares issued and outstanding, representing the equivalent of 81,786,164 ADSs, assuming the conversion of all ordinary shares into ADSs. In August 2025, the Company announced an underwritten offering of 76,666,659 ordinary shares, representing the equivalent of 33,333,330 ADSs.

Pro-forma for the underwritten offering, the Company had 264,774,837 ordinary shares issued and outstanding, representing the equivalent of 115,119,494 ADSs, assuming the conversion of all ordinary shares into ADSs.

Research and Development Expenses

Research and development (R&D) expenses were $3.3 million and $4.1 million for the three and six months ended June 30, 2025, respectively, compared to $5.2 million and $11.3 million for the three and six months ended June 30, 2024, respectively. R&D expenses for the three months ended June 30, 2025 were $1.9 million lower than the comparable period in 2024, primarily due to lower contract research organization costs driven by streamlined clinical pipeline activities and a decrease in employee-related expenses resulting from a lower headcount. R&D expenses for the six months ended June 30, 2025 were $7.2 million lower than the comparable period in 2024, primarily due to reimbursements recognized under an existing collaboration agreement and lower contract research organization costs due to streamlined clinical pipeline activities.

Administrative Expenses

Administrative expenses were $3.8 million and $8.3 million for the three and six months ended June 30, 2025, respectively, compared to $11.9 million and $14.4 million for the three and six months ended June 30, 2024, respectively. Administrative expenses for the three months ended June 30, 2025 were $8.1 million lower than the comparable period in 2024, primarily due to lower legal expenses and a decrease in employee-related expenses resulting from a lower headcount. Administrative expenses for the six months ended June 30, 2025 were $6.1 million lower than the comparable period in 2024, primarily due to a decrease in legal expenses and lower employee benefit and compensation expenses resulting from a lower headcount. This decrease was partially offset by a higher employee share-based compensation expense in the current period. The employee share-based compensation expense during the six months ended June 30, 2024 included forfeitures in connection with the divestiture of our Chinese assets and related operations (the Greater China assets and business operations).

Interest Income

Interest income was $1.8 million and $3.7 million for the three and six months ended June 30, 2025, respectively, compared to $2.1 million and $2.8 million for the three and six months ended June 30, 2024, respectively. Interest income for the three months ended June 30, 2025 was $0.3 million lower than the comparable period in 2024 due to lower average cash balances and lower market interest rates. Interest income for the six months ended June 30, 2025 was $0.8 million higher than the comparable period in 2024, primarily due to greater interest earned on cash balances as a result of cash management strategies.

Other Income (Expenses), Net

Other income (expenses), net were $(0.2) million and $0.1 million for the three and six months ended June 30, 2025, respectively, compared to $6.1 million and $5.5 million for the three and six months ended June 30, 2024, respectively. The $6.3 million and $5.4 million decreases in other income (expense), net for the three and six months ended June 30, 2025, respectively, were primarily attributable to the changes in fair value and extinguishment of certain put right liabilities. The decrease was partially offset by smaller impacts from foreign exchange losses recognized during the current period.

Equity in Loss of Affiliates

Equity in loss of affiliates was $(1.0) million for the six months ended June 30, 2024 due to recognition of the employee stock ownership plan expenses from the Company’s unconsolidated investee as a result of the divestiture of the Greater China assets and business operations. There was no equity in loss of affiliates for the three months ended June 30, 2024 or the three and six months ended June 30, 2025.

Net Loss from Continuing Operations

Net loss from continuing operations were ($5.5) million and $(8.7) million for the three and six months ended June 30, 2025, respectively, compared to $(8.9) million and $(18.4) million for the three and six months ended June 30, 2024, respectively. Net loss from continuing operations per share attributable to ordinary shareholders were $(0.03) and $(0.05) for the three and six months ended June 30, 2025, respectively, compared to $(0.05) and $(0.10) for the three and six months ended June 30, 2024, respectively.

Net Gain from Discontinued Operations

On April 2, 2024, the Company closed the divestiture of the Greater China assets and business operations announced on February 7, 2024 (the Transaction). In accordance with ASC 205-20, the Company determined that the Transaction represented a strategic shift that had a major effect on the business and therefore, met the criteria for classification as discontinued operations. As a result, the Company recognized a loss from discontinued operations of $6.9 million for the six months ended June 30, 2024 and a gain from sale of discontinued operations of $34.4 million for the three and six months ended June 30, 2024.

Net Income (Loss)

Net income (loss) was $(5.5) million and $(8.7) million for the three and six months ended June 30, 2025, respectively, compared to $25.4 million and $9.1 million for the three and six months ended June 30, 2024, respectively. Net income (loss) per share attributable to ordinary shareholders was $(0.03) and $(0.05) for the three and six months ended June 30, 2025, respectively compared to $0.13 and $0.05 for the three and six months ended June 30, 2024, respectively.

About Givastomig

Givastomig (TJ033721 / ABL111) is a bispecific antibody targeting Claudin 18.2 (CLDN18.2)-positive tumor cells. It conditionally activates T cells through the 4-1BB signaling pathway in the tumor microenvironment where CLDN18.2 is expressed. Givastomig is being developed for first line (1L) metastatic gastric cancers, with further potential in other solid tumors. In Phase 1 trials, givastomig has shown promising anti-tumor activity attributable to a potential synergistic effect of proximal interaction between CLDN18.2 on tumor cells and 4-1BB on T cells in the tumor microenvironment, while minimizing toxicities commonly seen with other 4-1BB agents.

An ongoing Phase 1b study is evaluating givastomig for the treatment of gastric cancer in the 1L setting in combination with standard of care, nivolumab (an anti-PD-1 checkpoint inhibitor) plus chemotherapy, in dose escalation (n=17) and dose expansion (n=40) cohorts. The study builds on positive Phase 1 monotherapy data.

Givastomig is being jointly developed through a global partnership with ABL Bio, in which I-Mab is the lead party and shares worldwide rights, excluding Greater China and South Korea, equally with ABL Bio.

On August 20, 2025 Agilent Technologies Inc. (NYSE: A) reported that its MMR IHC Panel pharmDx (Dako Omnis) has received FDA approval as a companion diagnostic (CDx) test for colorectal cancer (Press release, Agilent, AUG 20, 2025, View Source [SID1234655417]). This test aids in identifying mismatch repair deficient (dMMR) colorectal cancer (CRC) patients who are eligible for treatment with Bristol Myers Squibb’s Opdivo (nivolumab) alone or Opdivo (nivolumab) in combination with Yervoy (ipilimumab). The MMR IHC Panel pharmDx (Dako Omnis) is approved for exclusive use with the Agilent Dako Omnis automated staining solution.

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The mismatch repair (MMR) pathway corrects DNA replication errors to maintain genomic stability1. Dysfunction in key MMR proteins (MLH1, PMS2, MSH2, and MSH6) causes MMR deficiency, leading to elevated mutations, tumorigenesis, and neoantigen accumulation—features that make dMMR tumors more responsive to immunotherapy due to enhanced immune recognition2.

MMR IHC Panel pharmDx (Dako Omnis) is an immunohistochemical (IHC) panel specifically developed and validated to detect the loss of function of any of the four MMR proteins in formalin-fixed paraffin-embedded (FFPE) colorectal cancer tissue. Agilent’s panel is the only FDA-approved companion diagnostic IHC panel to diagnose colorectal cancer patients eligible for treatment with Opdivo alone or in combination with Yervoy.

"This approval marks an important step forward in the ongoing effort to improve colorectal cancer care," stated Nina Green, vice-president and general manager of Agilent’s Clinical Diagnostics Division. "Our new CDx product offers healthcare providers an additional tool to identify mismatch repair deficiency in patients, complementing existing options and enhancing the ability to tailor immunotherapy treatments. By providing more choices, we aim to support better tumor control and potentially improve progression-free survival, ultimately contributing to patient care and well-being."

Agilent partnered with Bristol Myers Squibb to develop the MMR IHC Panel pharmDx (Dako Omnis). This highlights the collaborative efforts between Agilent and Bristol Myers Squibb in developing and gaining approval for diagnostic assays that aid in selecting patients for specific treatments.

Opdivo and Yervoy are registered trademarks of Bristol-Myers Squibb Company.

On August 20, 2025 Larkspur Biosciences, a company pioneering a new wave in cancer therapy that destroys tumors by targeting cancer cell fitness, reported the discovery of LRK-4189, a first-in-class degrader of the lipid kinase PIP4K2C for the treatment of microsatellite stable (MSS) colorectal cancer (CRC) and other solid tumors (Press release, Larkspur Biosciences, AUG 20, 2025, View Source [SID1234655402]). The announcement was made at a presentation Larkspur was invited to give at the prestigious MEDI First Time Disclosures: Breakthroughs on New Medicines session at ACS Fall 2025, a meeting of the American Chemical Society in Washington, DC.

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Cancer cells maintain their fitness by developing survival adaptations that foster escape from intrinsic and extrinsic mechanisms of cell death in conditions of stress. Phosphatidylinositol 5-phosphate 4-kinase, type II, gamma (PIP4K2C) is a lipid kinase associated with poor outcomes in a range of cancers including CRC and breast cancers. PIP4K2C is co-opted by cancer cells to increase their fitness by evading immune surveillance and adapting to stress.

"Genetic studies have long highlighted PIP4K2C as a key player in cancer stress adaptation, but its extremely low kinase activity made it resistant to conventional inhibition approaches," said Catherine Sabatos-Peyton, PhD, CEO of Larkspur Biosciences. "With our novel degrader, LRK-4189, we’ve finally unlocked this critical pathway. By reducing cancer cell fitness, triggering intrinsic apoptosis, and engaging the immune system to clear residual tumor cells, LRK-4189 has the potential to overcome the limitations of earlier therapies. We’re excited to advance this promising therapy to the clinic later this year."

According to the American Cancer Society, in the United States, approximately 150,000 cases of CRC are diagnosed annually, with MSS CRC accounting for about 85% of all CRC cases.

About LRK-4189

LRK-4189 is an orally bioavailable, selective degrader of PIP4K2C with subnanomolar potency in primary human cells.
LRK-4189-mediated degradation of PIP4K2C leads to intrinsic cancer cell death and activates interferon signaling, triggering multiple killing mechanisms in difficult-to-treat MSS CRC cells.
In vivo, LRK-4189 demonstrates dose dependent PKPD with single agent efficacy in multiple models of CRC and synergy with first-line standard of care chemotherapy.
In primary human CRC patient-derived spheroids, 50% of patient samples respond to LRK-4189 with a preferential response in MSS CRC, which compares favorably to benchmark cetuximab in the same platform (35%). Cetuximab may be either a first- or second-line treatment in people with RAS wild type CRC.
LRK-4189 has completed IND-enabling studies and expects to initiate a Phase 1 clinical trial in Q4 2025.

On August 20, 2025 Mural Oncology plc (Nasdaq: MURA), a clinical-stage immuno-oncology company ("Mural"), and XOMA Royalty Corporation (Nasdaq: XOMA), a biotechnology royalty aggregator ("XOMA Royalty"), reported they have entered into a definitive agreement pursuant to which XRA 5 Corp., a newly formed company wholly owned by XOMA Royalty ("Sub"), has agreed to acquire the entire issued and to be issued share capital of Mural for cash (the "Acquisition") subject to the satisfaction of the closing conditions set out in Appendix I of this Announcement (the "Conditions"), including approval by Mural Shareholders (Press release, Mural Oncology, AUG 20, 2025, View Source [SID1234655403]). Following a strategic review process, the Mural board of directors (the "Mural Board") determined the acquisition and cash offer by XOMA Royalty is in the best interests of all Mural Shareholders and has approved the Acquisition. The Acquisition has also been approved by the boards of directors of XOMA Royalty and Sub.

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Under the terms of the Acquisition and subject to certain conditions, at closing, each Mural Shareholder (i) would receive a base cash price of $2.035 per share (the "Base Price Per Share") and (ii) may receive an additional cash amount per share of up to $0.205 (the "Additional Price Per Share") which would be calculated on the basis of the amount by which Mural’s Closing Net Cash on the Closing Net Cash Date exceeds its Estimated Closing Net Cash (the "Excess Cash") as set out in more detail below and in accordance with the provisions of the transaction agreement entered into between Mural, Sub and XOMA Royalty in respect of the Acquisition (the "Transaction Agreement"), as appended at Appendix IV of this Announcement.

The Base Price Per Share has been calculated on the basis of Mural having approximately $36.2 million in Closing Net Cash on the Closing Net Cash Date (the "Estimated Closing Net Cash"), and would be payable to Mural Shareholders on closing of the Acquisition regardless of the actual quantum of Mural’s Closing Net Cash on the Closing Net Cash Date. The Additional Price Per Share is intended to return any Excess Cash to Mural Shareholders. As a result, the Additional Price Per Share would only be payable to Mural Shareholders on closing of the Acquisition if Mural’s Closing Net Cash on the Closing Net Cash Date exceeds the Estimated Closing Net Cash. There is no certainty that Mural’s Closing Net Cash on the Closing Net Cash Date will exceed the Estimated Closing Net Cash and, if Mural’s Closing Net Cash does not the exceed Estimated Closing Net Cash, the amount of the Additional Price Per Share will be zero and each Mural Shareholder would receive only the Base Price Per Share.

The Additional Price Per Share is subject to a cap of a maximum amount of $0.205 per share.

The Acquisition, excluding any amount that may be payable in respect of the Additional Price Per Share, values the entire issued and to be issued share capital of Mural at approximately $36.2 million.

Excluding any Additional Price Per Share which may be payable as described above, the Acquisition represents a:

premium of approximately 13.1% to Mural’s closing share price of $1.80 on August 19, 2025, being the Business Day immediately before the date on which this Announcement has been released; and
premium of approximately 97.6% to Mural’s undisturbed closing share price of $1.03 on April 14, 2025 (being the last Business Day prior to the announcement of the commencement of the strategic review by the Mural Board on April 15, 2025).
Capitalised terms used in this Announcement and not otherwise defined have the meaning given to them in Appendix I.

Commenting on the Acquisition, Caroline Loew, Ph.D., Chief Executive Officer of Mural, said:

‘The Transaction Agreement with XOMA Royalty announced today is the result of a thorough and wide-ranging strategic review process, conducted with the support of our legal and financial advisors. We believe that this transaction, which is supported by our Board, achieves the goal of this strategic review process, which was to maximize shareholder value.’

Commenting on the Acquisition, Owen Hughes, Chief Executive Officer of XOMA Royalty, said:

‘XOMA Royalty looks forward to working with Mural to close the transaction as soon as possible.’

The Mural Directors, who hold Mural Shares representing, in aggregate, approximately 0.42% of Mural’s outstanding ordinary shares, Mural RSUs representing, in aggregate, approximately 1.27% of Mural’s outstanding ordinary shares and options to acquire Mural Shares representing, in aggregate, approximately 4.32% of Mural’s outstanding ordinary shares have entered into irrevocable undertakings to vote in favor of the Acquisition. All outstanding options to acquire Mural Shares held by the Mural Directors have a strike price above the maximum Consideration payable pursuant to the Acquisition and will be cancelled without the right to receive any Consideration in accordance with the terms of the Transaction Agreement.

Having taken into account the relevant factors, applicable risks and alternatives available to Mural, the Mural Board, which has been so advised by Lucid Capital Markets, LLC ("Lucid"), as financial adviser and Rule 3 adviser to Mural, as to the financial terms of the Acquisition, considers the terms of the Acquisition as set out in this Announcement to be fair and reasonable. Accordingly, the Mural Board intends to recommend that Mural Shareholders vote in favor of the Acquisition.

It is intended that the Acquisition will be implemented by means of a High Court sanctioned scheme of arrangement under Chapter 1 of Part 9 of the Irish Companies Act (or, if Sub elects, subject to the terms of the Transaction Agreement, compliance with the Irish Takeover Rules and with the consent of the Irish Takeover Panel, a Takeover Offer). The Acquisition is expected to close by the end of 2025, subject to the satisfaction of the Conditions, which include (i) the approval by Mural Shareholders of the Scheme Meeting Resolution and the Required EGM Resolutions; and (ii) the sanction of the Scheme by the High Court.

The Scheme Document, which will contain, among other things, further information about the Acquisition, notices convening the Scheme Meeting and the Extraordinary General Meeting (the "EGM"), the expected timetable for completion of the Acquisition and action to be taken by Mural Shareholders, will be published as soon as practicable following this Announcement. The Scheme Document will be included within the Proxy Statement to be filed by Mural with the U.S. Securities and Exchange Commission (the "SEC") and sent to Mural shareholders as of the record date(s) to be established for voting at the Scheme Meeting and EGM in respect of the Acquisition.

On August 20, 2025 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM:​HCM; HKEX:​13) reported the completion of patient enrollment of SANOVO, a China Phase III study of ORPATHYS (savolitinib) and TAGRISSO (osimertinib) as a first-line treatment in certain non-small cell lung cancer ("NSCLC") patients whose tumors harbor epidermal growth factor receptor ("EGFR") mutation and MET overexpression (Press release, Hutchison China MediTech, AUG 20, 2025, https://www.hutch-med.com/sanovo-phiii-enrollment-completion/ [SID1234655371]). The last patient was enrolled on August 18, 2025.

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This Phase III trial is a blinded, randomized, controlled study in previously untreated patients with locally advanced or metastatic NSCLC with activating EGFR mutations and MET overexpression. The study will evaluate the efficacy and safety of TAGRISSO in combination with ORPATHYS comparing to TAGRISSO alone, a standard-of-care treatment option for these patients. The primary endpoint of the study is progression free survival ("PFS") as assessed by investigators. Other endpoints include PFS assessed by an independent review committee, overall survival (OS), objective response rate ("ORR"), duration of response (DoR), disease control rate (DCR), time to response (TTR), and safety. Additional details may be found at clinicaltrials.gov, using identifier NCT05009836.

Topline results from the SANOVO study are estimated to be reported in the second half of 2026, followed by submission of results for presentation at an appropriate medical congress. If favorable, the results would enable a supplementary New Drug Application submission to China’s National Medical Products Administration ("NMPA").

ORPATHYS is an oral, potent and highly selective MET tyrosine kinase inhibitor ("TKI") being jointly developed by AstraZeneca and HUTCHMED and commercialized by AstraZeneca. TAGRISSO is a third-generation, irreversible EGFR TKI.

About NSCLC and MET aberrations
Lung cancer is the leading cause of cancer death, accounting for about one-fifth of all cancer deaths.[1] Lung cancer is broadly split into NSCLC and small cell lung cancer, with 80-85% classified as NSCLC.[2] The majority of NSCLC patients (approximately 75%) are diagnosed with advanced disease, and approximately 10-15% of NSCLC patients in the US and Europe and up to 40-50% of patients in Asia have EGFR-mutated ("EGFRm") NSCLC.[3],[4],[5],[6],[7]

MET is a tyrosine kinase receptor that has an essential role in normal cell development. MET overexpression and/or amplification can lead to tumor growth and the metastatic progression of cancer cells, and is one of the mechanisms of de novo or acquired resistance to EGFR TKI for metastatic EGFRm NSCLC.[8],[9]

About ORPATHYS
ORPATHYS (savolitinib) is an oral, potent and highly selective MET TKI that has demonstrated clinical activity in advanced solid tumors. It blocks atypical activation of the MET receptor tyrosine kinase pathway that occurs because of mutations (such as exon 14 skipping alterations or other point mutations), gene amplification or protein overexpression.

ORPATHYS is approved in China and is marketed by AstraZeneca for the treatment of adult patients with locally advanced or metastatic NSCLC with MET exon 14 skipping alteration, representing the first selective MET inhibitor approved in China. ORPATHYS is also approved in China for the treatment of patients with locally advanced or metastatic EGFRm-positive non-squamous NSCLC with MET amplification after disease progression on EGFR tyrosine kinase inhibitor therapy, in combination with TAGRISSO.

It is currently under clinical development for multiple tumor types, including lung, kidney, and gastric cancers as a single treatment and in combination with other medicines.

About TAGRISSO
TAGRISSO (osimertinib) is a third-generation, irreversible EGFR-TKI with proven clinical activity in NSCLC, including against central nervous system (CNS) metastases. TAGRISSO (40mg and 80mg once-daily oral tablets) has been used to treat more than one million patients across its indications worldwide and AstraZeneca continues to explore TAGRISSO as a treatment for patients across multiple stages of EGFRm NSCLC.

There is an extensive body of evidence supporting the use of TAGRISSO in EGFRm NSCLC, and it is the only targeted therapy shown to improve patient outcomes across all stages of the disease.

In late-stage disease, TAGRISSO demonstrated improved outcomes as monotherapy in the FLAURA Phase III trial and in combination with chemotherapy in the FLAURA2 Phase III trial. TAGRISSO is also being investigated in this setting in combination with ORPATHYS (savolitinib) in the SAFFRON Phase III trial and in combination with DATROWAY (datopotamab deruxtecan or Dato-DXd) in the TROPION-Lung14 and TROPION-Lung15 Phase III trials.

TAGRISSO also showed improved outcomes in early-stage disease in the NeoADAURA and ADAURA Phase III trials and in locally advanced stages in the LAURA Phase III trial. As part of AstraZeneca’s ongoing commitment to treating patients as early as possible in lung cancer, TAGRISSO is also being investigated in the early-stage adjuvant resectable setting in the ADAURA2 Phase III trial.

About ORPATHYS and TAGRISSO Combination Development in EGFR-mutated NSCLC
Among patients who experience disease progression following treatment with a third-generation EGFR TKI, approximately 15-50% present with MET aberration, depending on the sample type, detection method and assay cut-off used. TAGRISSO is a third-generation, irreversible EGFR-TKI with proven clinical activity in NSCLC, including against central nervous system metastases. Treatment with ORPATHYS in combination with TAGRISSO has been studied extensively in these patients in the TATTON (NCT02143466) and SAVANNAH (NCT03778229) studies. The encouraging results led to the initiation of several Phase III trials in this setting including the SACHI trial in China (NCT05015608) and the global SAFFRON trial (NCT05261399), as well as the SANOVO trial in China (NCT05009836).

This combination represents a promising chemotherapy-free oral treatment strategy to address mechanisms of resistance in this advanced setting. Positive data from the SACHI randomized Phase III trial led to the filing of a third NDA in China. Strong data from the SAVANNAH single-arm Phase II study was recently presented at the European Lung Cancer Congress (ELCC) in March 2025 demonstrated high, clinically meaningful and durable ORR, with consistent safety results. The SAFFRON randomized Phase III trial is progressing. Following AstraZeneca’s consultation with the US Food and Drug Administration ("FDA"), we look forward to completing the SAFFRON trial as soon as possible to support potential US and other global registration filings.

SACHI: The SACHI China Phase III study evaluated the combination of ORPATHYS and TAGRISSO for the treatment of patients with EGFRm, MET-amplified locally advanced or metastatic NSCLC after progression on EGFR TKI compared to platinum-based doublet chemotherapy. Results were presented at the ASCO (Free ASCO Whitepaper) Annual Meeting in June 2025. Based on the data from the SACHI study, the combination of ORPATHYS and TAGRISSO received approval from the China NMPA for the treatment of patients with locally advanced or metastatic EGFR mutation-positive non-squamous NSCLC with MET amplification after disease progression on EGFR TKI therapy in June 2025.

SAFFRON: In 2023, ORPATHYS and TAGRISSO received Fast Track Designation from the US FDA in this setting. The global SAFFRON Phase III trial is currently ongoing to assess the ORPATHYS plus TAGRISSO combination versus platinum-based doublet chemotherapy in patients with EGFRm, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC following progression on treatment with TAGRISSO. Patients are being prospectively selected using the high MET level cut-off identified in SAVANNAH.