On September 24, 2025 Daiichi Sankyo (TSE: 4568) and AstraZeneca’s (LSE/STO/Nasdaq: AZN) reported that supplemental Biologics License Application (sBLA) for ENHERTU (famtrastuzumab deruxtecan-nxki) in combination with pertuzumab has been accepted and granted Priority Review in the U.S. for the first-line treatment of adult patients with unresectable or metastatic HER2 positive breast cancer.

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ENHERTU is a specifically engineered HER2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca.

The U.S. Food and Drug Administration (FDA) grants Priority Review to applications for medicines that, if approved, would offer significant improvements over available treatment options by demonstrating safety or efficacy improvements, preventing serious conditions or enhancing patient compliance. The Priority Review follows receipt of Breakthrough Therapy Designation granted by the FDA for ENHERTU plus pertuzumab based on data from the DESTINY-Breast09 phase 3 trial in July 2025. The Prescription Drug User Fee Act (PDUFA) date, the FDA target action date for their regulatory decision, is January 23, 2026.

The sBLA is being reviewed under the Real-Time Oncology Review (RTOR) program, an initiative of the FDA designed to bring safe and effective cancer treatments to patients as early as possible. RTOR allows the FDA to review components of an application before submission of the complete application.

The sBLA is based on data from DESTINY-Breast09 presented as a special late-breaking oral session at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) (#ASCO25) Annual Meeting. In the trial, ENHERTU in combination with pertuzumab reduced the risk of disease progression or death by 44% versus taxane, trastuzumab and pertuzumab (THP) (hazard ratio [HR]: 0.56; 95% confidence interval [CI]: 0.44-0.71; 2 p<0.00001) as a first-line treatment for patients with HER2 positive metastatic breast cancer. Median progression-free survival (PFS) was 40.7 months (95% CI: 36.5-NC) with ENHERTU plus pertuzumab compared to 26.9 months (95% CI: 21.8-NC) for THP as assessed by blinded independent central review (BICR). The PFS benefit for ENHERTU plus pertuzumab versus THP was consistent across subgroups.

Confirmed objective response rate (ORR) with ENHERTU plus pertuzumab was 85.1% (95% CI: 81.2-88.5) versus 78.6% (95% CI: 74.1-82.5) with THP. There were 58 complete responses (CR) and 268 partial responses (PR) with ENHERTU plus pertuzumab compared to 33 CRs and 271 PRs with THP. Median duration of response (DOR) for ENHERTU plus pertuzumab exceeded three years (39.2 months) versus 26.4 months with THP.

"ENHERTU in combination with pertuzumab delayed disease progression for more than three years compared to around two years with current standard of care as a first-line treatment for patients with HER2 positive metastatic breast cancer," said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. "Receiving Priority Review moves us closer to offering ENHERTU to patients even earlier in the metastatic treatment pathway as a potential new first-line treatment option."

"The DESTINY-Breast09 trial showed that treating patients with HER2 positive metastatic breast cancer with ENHERTU in combination with pertuzumab until progression in the first-line setting produced a new landmark of more than 40 months for progression-free survival and nearly doubled the number of patients with no evidence of disease on imaging," said Susan Galbraith, MBBChir, PhD, Executive Vice President, Oncology Hematology R&D, AstraZeneca. "This marks the first major evolution in treatment in this firstline setting in more than a decade – a setting where a strong response is crucial, as up to one third of patients may not receive second-line therapy."

The safety profile of ENHERTU plus pertuzumab in DESTINY-Breast09 was consistent with the known profiles of each individual therapy with no new safety concerns identified. Grade 3 or higher treatment emergent adverse events (TEAEs) occurred in 54.9% of patients in the ENHERTU plus pertuzumab arm and 52.4% of patients in the THP arm. The most common grade 3 or higher TEAEs occurring in 5% or more of patients treated with ENHERTU plus pertuzumab were neutropenia (23.9%), hypokalemia (10.2%), anemia (8.4%), fatigue (7.9%), diarrhea (6.8%), thrombocytopenia (6.3%) and nausea (5.0%). Interstitial lung disease (ILD) or pneumonitis events occurred in 12.1% of patients treated with ENHERTU plus pertuzumab as determined by an independent adjudication committee. The majority of ILD or pneumonitis events were low grade (grade 1 [n=17; 4.5%] or grade 2 [n=27; 7.1%]). There were two grade 5 ILD events (0.5%) in the ENHERTU plus pertuzumab arm.

ENHERTU is already approved in more than 85 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HER2 positive (immunohistochemistry [IHC] 3+ or in-situ hybridization (ISH)+) breast cancer who have received a prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial.

About DESTINY-Breast09

DESTINY-Breast09 is a global, multicenter, randomized, open-label, phase 3 trial evaluating the efficacy and safety of ENHERTU (5.4 mg/kg) either alone or in combination with pertuzumab versus standard of care THP as a first-line treatment in patients with HER2 positive metastatic breast cancer.

Patients were randomized 1:1:1 to receive either ENHERTU monotherapy with a pertuzumab matching placebo; ENHERTU in combination with pertuzumab; or THP. Randomization was stratified by prior treatment (de novo metastatic disease versus progression from early-stage disease), hormone receptor (HR) status and PIK3CA mutation status.

The primary endpoint of DESTINY-Breast09 is PFS as assessed by BICR in both the ENHERTU monotherapy and ENHERTU combination arms. Secondary endpoints include investigator-assessed PFS, overall survival, ORR, DOR, pharmacokinetics and safety. The investigational arm assessing ENHERTU monotherapy versus THP remains blinded to patients and investigators and will continue to the final PFS analysis.

DESTINY-Breast09 enrolled 1,157 patients across multiple sites in Africa, Asia, Europe, North America and South America. For more information about the trial, visit ClinicalTrials.gov.

About HER2 Positive Metastatic Breast Cancer

Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide.1 More than two million breast cancer cases were diagnosed in 2022, with more than 665,000 deaths globally.1 In the U.S., more than 300,000 cases of breast cancer are diagnosed annually with more than 42,000 deaths. 2 While survival rates are high for those diagnosed with early breast cancer, only about 30% of patients diagnosed with or progress to metastatic disease are expected to live five years following diagnosis.

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors including breast cancer.4 HER2 protein overexpression may occur as a result of HER2 gene amplification.5 Approximately one in five cases of breast cancer are considered HER2 positive.6 4 HER2 positive metastatic breast cancer is an aggressive disease driven by overexpression or amplification of HER2 that affects 15% to 20% of patients with metastatic breast cancer.7 Approximately 10,000 patients are treated each year in the first-line HER2 positive metastatic setting in the U.S.8 While HER2 targeted therapies have improved outcomes, prognosis remains poor with most patients experiencing disease progression within two years of first-line treatment with THP, which has been the standard of care for more than a decade.5,9,10,11 Further, approximately 25% to 30% of patients do not receive any treatment following first-line therapy due to discontinuation or death.

About ENHERTU

ENHERTU (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the U.S. only) is a HER2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, ENHERTU is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca’s ADC scientific platform. ENHERTU consists of a HER2 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

ENHERTU (5.4 mg/kg) is approved in more than 85 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HER2 positive (immunohistochemistry [IHC] 3+ or in-situ hybridization (ISH)+) breast cancer who have received a prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial.

ENHERTU (5.4 mg/kg) is approved in more than 85 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HER2 low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.

ENHERTU (5.4 mg/kg) is approved in more than 45 countries/regions for the treatment of adult patients with unresectable or metastatic hormone receptor (HR) positive, HER2 low (IHC 1+ or IHC 2+/ISH-) or HER2 ultralow (IHC 0 with membrane staining) breast cancer, as determined by a locally or regionally approved test, that have progressed on one or more endocrine therapies in the metastatic setting based on the results from the DESTINY-Breast06 trial.

ENHERTU (5.4 mg/kg) is approved in more than 60 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations, as detected by a locally or regionally approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 and/or DESTINY-Lung05 trials. Continued approval in China and 5 the U.S. for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

ENHERTU (6.4 mg/kg) is approved in more than 70 countries/regions worldwide for the treatment of adult patients with locally advanced or metastatic HER2 positive (IHC 3+ or IHC 2+/ISH+) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01, DESTINY-Gastric02 and/or DESTINY-Gastric06 trials. Continued approval in China for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

ENHERTU (5.4 mg/kg) is approved in more than 10 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HER2 positive (IHC 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options based on efficacy results from the DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02 trials. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

About the ENHERTU Clinical Development Program

A comprehensive global clinical development program is underway evaluating the efficacy and safety of ENHERTU as a monotherapy or in combination or sequentially with other cancer medicines across multiple HER2 targetable cancers.

(Press release, Daiichi Sankyo, SEP 24, 2025, View Source [SID1234665029])

On September 24, 2025 Lantheus Holdings, Inc. (NASDAQ: LNTH) and GE HealthCare (NASDAQ: GEHC) reported an exclusive licensing agreement for GE HealthCare to develop, manufacture, and commercialize Lantheus’ piflufolastat F18 (PYLARIFY in U.S. market) in Japan for prostate cancer diagnostics and companion diagnostic use. PYLARIFY is used for positron emission tomography (PET) imaging of prostate-specific membrane antigen (PSMA) positive lesions in men with prostate cancer.

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The agreement includes the transfer of regulatory dossiers, manufacturing competencies and technical support to enable GE HealthCare to drive clinical development in Japan, towards potential regulatory submissions and commercial launch. GE HealthCare will draw on its extensive manufacturing network and R&D expertise following its acquisition in March 2025 of Nihon Medi-Physics Co., Ltd. (NMP), a leading radiopharmaceutical company in Japan.

Prostate cancer is the fourth most common cancer worldwide, with Japan recording the third highest number of cases in the world in 2022, after the U.S. and China.1

"This partnership is expected to meaningfully extend the reach of our diagnostic imaging agent in key international markets," said Brian Markison, CEO of Lantheus. "GE HealthCare and NMP’s deep regional expertise will enable us to advance the detection and care of prostate cancer and drive significant impact in an important market."

"Bringing targeted PET imaging agents to new geographies supports Lantheus’ Purpose to Find, Fight and Follow disease to deliver better patient outcomes," added Jean-Claude Provost, Chief Science Officer at Lantheus. "By aligning with GE HealthCare, we’re addressing a critical clinical need in Japan, and helping to lay the foundation for a more personalized approach to prostate cancer detection, diagnosis and monitoring."

"This collaboration represents a strategic advancement for GE HealthCare as we expand our pipeline of radiopharmaceuticals and continue to deliver on our commitment to improving patient access to innovative diagnostics," said Kevin O’Neill, President & CEO of the Pharmaceutical Diagnostics (PDx) segment of GE HealthCare and President of NMP. "Working alongside Lantheus gives us access to one of the best-in-class PET imaging agents that is already approved in the U.S. and in Europe, and if approved locally, could provide clinicians and their patients with a powerful new option for detecting and monitoring prostate cancer."

Under the terms of the agreement, GE HealthCare will pay Lantheus an upfront license fee, development milestones and tiered royalties based on product sales in Japan. The companies will also establish a Joint Steering Committee to oversee development and commercialization activities.

Piflufolastat F 18 (also known as 18F-DCFPyL, PYLARIFY or PYLCLARI) was FDA-approved in 2021 and is marketed as PYLARIFY. PYLARIFY has made a profound impact on the lives of patients battling prostate cancer and is the number one utilized PSMA PET imaging agent in the U.S. It is a proven diagnostic backed by real-world experience, including in over 500,000 scans across 48 states. In 2023, it was approved in the European Union and is marketed there as PYLCLARI. The European rights were licensed to Curium from Progenics Pharmaceuticals, Inc., a Lantheus company.

About PYLARIFY (piflufolastat F 18) Injection
PYLARIFY (piflufolastat F 18) injection (also known as 18F-DCFPyL or PYLCLARI) is a fluorinated small molecule PSMA-targeted PET imaging agent that enables visualization of lymph nodes, bone and soft tissue metastases to determine the presence or absence of recurrent and/or metastatic prostate cancer. For men with prostate cancer, PYLARIFY PET combines the accuracy of PET imaging, the precision of PSMA targeting and the clarity of an F 18 radioisotope for superior diagnostic performance. The recommended PYLARIFY dose is 333 MBq (9 mCi) with an acceptable range of 296 MBq to 370 MBq (8 mCi to 10 mCi), administered as a bolus intravenous injection.

PYLARIFY (piflufolastat F 18) Injection in the U.S.

Indication

PYLARIFY (piflufolastat F 18) Injection is a radioactive diagnostic agent indicated for positron emission tomography (PET) of prostate-specific membrane antigen (PSMA) positive lesions in men with prostate cancer:

with suspected metastasis who are candidates for initial definitive therapy.
with suspected recurrence based on elevated serum prostate-specific antigen (PSA) level.

Important Safety Information

Contraindications
None.

Warnings and Precautions

Risk of Image Misinterpretation
Imaging interpretation errors can occur with PYLARIFY imaging. A negative image does not rule out the presence of prostate cancer and a positive image does not confirm the presence of prostate cancer. The performance of PYLARIFY for imaging of patients with biochemical evidence of recurrence of prostate cancer seems to be affected by serum PSA levels. The performance of PYLARIFY for imaging of metastatic pelvic lymph nodes prior to initial definitive therapy seems to be affected by risk factors such as Gleason score and tumor stage. PYLARIFY uptake is not specific for prostate cancer and may occur with other types of cancer as well as non-malignant processes and in normal tissues. Clinical correlation, which may include histopathological evaluation of the suspected prostate cancer site, is recommended.

Hypersensitivity Reactions
Monitor patients for hypersensitivity reactions, particularly patients with a history of allergy to other drugs and foods. Reactions may be delayed. Always have trained staff and resuscitation equipment available.

Radiation Risks
Diagnostic radiopharmaceuticals, including PYLARIFY, expose patients to radiation. Radiation exposure is associated with a dose-dependent increased risk of cancer. Ensure safe handling and preparation procedures to protect patients and health care workers from unintentional radiation exposure. Advise patients to hydrate before and after administration and to void frequently after administration.

Adverse Reactions
The most frequently reported adverse reactions were headaches, dysgeusia and fatigue, occurring at rate of ≤2% during clinical studies with PYLARIFY. In addition, a delayed hypersensitivity reaction was reported in one patient (0.2%) with a history of allergic reactions.

Drug interactions
Androgen deprivation therapy (ADT) and other therapies targeting the androgen pathway, such as androgen receptor antagonists, may result in changes in uptake of PYLARIFY in prostate cancer. The effect of these therapies on performance of PYLARIFY PET has not been established.

To report suspected adverse reactions for PYLARIFY, call 1-800-362-2668 or contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Please read the accompanying full Prescribing Information also available at PYLARIFY.com.

(Press release, Lantheus, SEP 24, 2025, View Source [SID1234662958])

On September 24, 2025 ITM Isotope Technologies Munich SE (ITM), a leading radiopharmaceutical biotech company, and TerThera BV, a leading provider of GMP-grade Terbium-161, reported a supply agreement for non-carrier-added (n.c.a.) Terbium-161 (Tb-161), a novel medical radioisotope with distinct chemical properties and emerging potential in radiopharmaceutical therapy. Under the terms of the agreement, TerThera will supply Good Manufacturing Practice (GMP)-compliant n.c.a. Tb-161 to ITM to support the development of its Terbium-based pipeline candidates, complementing ITM’s established manufacturing capabilities in cooperation with the Paul Scherrer Institute (PSI).

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"Driving innovation across isotopes, targeting molecules and cancer indications keeps ITM at the forefront of the rapidly evolving radiopharmaceutical industry," said Dr. Andrew Cavey, CEO of ITM. "We see strong potential in Terbium-161 as a critical new isotope for targeted radiopharmaceutical therapy, and our partnership with TerThera will allow us to advance its use in our pipeline. With supply of Terbium-161, we are well-positioned to harness its radiation properties to deliver meaningful advances for people living with cancer."

Currently, Tb-161-based radiopharmaceuticals are being clinically investigated for various types of cancers. Tb-161 is gaining attention in the radiopharmaceutical field for its unique emission profile. Like Lu-177, it emits medium-range beta particles and has a similar half-life. However, Tb-161 also emits low-energy Auger and internal conversion electrons, delivering highly localized radiation that can effectively target isolated cancer cells and micro-metastases with minimal off-target effects.

"As industry interest in Terbium-161 grows, a safe and sustainable supply of this radionuclide is crucial to support the development of new treatment options and strategies and we see this as our core mission," added Philippe van Overeem, CEO of TerThera. "ITM is a true innovator in the dynamic radiopharmaceutical field and we look forward to supplying them with our GMP-grade Terbium-161 as they advance their pipeline candidates and make progress in bringing the benefit of this valuable isotope to patients."

(Press release, ITM Isotopen Technologien Munchen, SEP 24, 2025, View Source [SID1234661163])

On September 24, 2025 Akari Therapeutics, Plc (Nasdaq: AKTX), an oncology biotechnology company developing novel payload antibody drug conjugates (ADCs), reported key preclinical data demonstrating the potential of its novel antibody drug conjugate (ADC) spliceosome modulating payload, PH1, for the treatment of tumors fueled by alternative splicing-drivers, such as the Androgen Receptor splice variant 7 (AR-V7) in prostate cancer (Press release, Akari Therapeutics, SEP 24, 2025, View Source [SID1234656230]).

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AR-V7 is a key driver for progression of metastatic castration resistant prostate cancer (mCRPC). During progression of hormone-sensitive prostate cancer, many patients fail to respond to current first-line therapies known as Androgen Receptor Pathway Inhibitors (ARPIs), which include enzalutamide (Xtandi, $6B/annual sales), apalutamide (Erleada, $3B/annual sales) and darolutamide (Nubeqa, $1.6B/annual sales). Importantly, as patients lose ARPI response, their tumors transform and significantly increase in AR-V7 expression. As a result, there is an increasing and significant unmet need for targeted therapy options in ARPI-resistant hormone refractory patients, where there are currently limited options such as traditional chemotherapy like taxanes.

As referenced in the Company’s recent patent filing, preclinical data demonstrated that Akari’s ADC payloadPH1 is able to suppress the expression levels of the AR-V7 receptor in a hormone-refractory mCRPC model called 22Rv1. As a control, ARPIs had no effect on AR-V7 receptor expression in these experiments, which was expected given the refractory nature of these prostate cancer cell lines.

Surprisingly, in a different model, of hormone-sensitive LnCAP cells that express high levels of normal Androgen Receptor (i.e. ARPI sensitive) and lack AR-V7, PH1 demonstrated a benefit as a single agent, and additive effect when combined with either Xtandi or Erleada. The Company believes this combined efficacy data may potentially lead to the development of robust first-line combination regimens of Xtandi or Erleada with a PH1 payload conjugated ADC (PH1 ADC) to target prostate cancer that is sensitive to ARPIs. As progression is often linked to AR-V7 expression, and PH1 reduces AR-V7 expression, it is hypothesized that the combination of ARPI plus PH1 ADCs may slow the development of resistance and AR-V7-driven tumor progression which typically occurs after patients progress on Xtandi or Erleada. Akari has plans to test this hypothesis using PH1 ADCs against different prostate cancer targets in future research.

Abizer Gaslightwala, President and Chief Executive Officer of Akari Therapeutics commented, "We believe these compelling preclinical data support the rationale for Akari to develop a novel ADC with our PH1 spliceosome-modulating payload targeting prostate cancer either alone or in partnership with potential partners. Our goal is to develop the first ADC therapeutic in prostate cancer, either as a first-line combination therapy with ARPIs or a second-line therapy post ARPI failures in tumors driven by AR-V7. We are excited to continue to advance this novel spliceosome modulating payload to drive robust anti-cancer biological mechanisms to treat difficult alternative splicing-driven tumors, for which there are currently no effective treatment options today."

The Company plans to present the preclinical data at an upcoming scientific conference.

On September 24, 2025 Summit Therapeutics Inc. (NASDAQ: SMMT) ("Summit," "we," or the "Company") reported that data from the Phase III HARMONi-6 trial, conducted in China and sponsored by our partner, Akeso, Inc. (HKEX Code: 9926.HK), featuring the novel, potential first-in-class investigational bispecific antibody, ivonescimab, will be featured as part of the Presidential Symposium at the European Society for Medical Oncology 2025 Congress (ESMO 2025) which takes place from October 17–21, 2025, in Berlin, Germany (Press release, Summit Therapeutics, SEP 24, 2025, View Source [SID1234656211]). The presentation will take place on Sunday, October 19 during the Presidential Symposium from 4:30pm – 6:30pm CET (10:30am – 12:30pm EDT).

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HARMONi-6 is evaluating ivonescimab in combination with platinum-based chemotherapy compared with tislelizumab, a PD-1 inhibitor, in combination with platinum-based chemotherapy in patients with locally advanced or metastatic squamous non-small cell lung cancer (NSCLC) irrespective of PD-L1 expression. HARMONi-6 is a single region, multi-center, Phase III study conducted in China sponsored by Akeso with all relevant data exclusively generated, managed, and analyzed by Akeso.

On April 23, 2025, Akeso announced, via a press release, topline results from HARMONi-6. At a prespecified interim analysis conducted by an Independent Data Monitoring Committee, ivonescimab plus chemotherapy demonstrated a statistically significant and clinically meaningful improvement in PFS by blinded independent central radiology review committee (BICR) compared to tislelizumab plus chemotherapy. The PFS benefit was demonstrated in patients with either PD-L1-positive or PD-L1-negative tumors. Akeso noted that no new safety signals were identified in this Phase III study. Prior to HARMONi-6, there were no known Phase III clinical trials in NSCLC which have shown a statistically significant improvement compared to PD-(L)1 inhibitor therapy in combination with chemotherapy in a head-to-head setting.

The trial results will be presented by Dr. Shun Lu, MD, PhD, Chief of Shanghai Lung Cancer Center at Shanghai Chest Hospital, Professor of Medicine at Shanghai Jiaotong University, and associate editor for Journal of Thoracic Oncology, Lung Cancer, and editor for The Oncologist.

Summit is currently enrolling patients in the HARMONi-3 study. HARMONi-3 is a multiregional Phase III clinical trial sponsored by Summit which is intended to evaluate ivonescimab combined with chemotherapy compared to pembrolizumab, an anti-PD-1 antibody, combined with chemotherapy in patients with first-line metastatic, squamous and non-squamous NSCLC. HARMONi-3 is currently enrolling patients globally and is conducted with registrational intent for the United States and other regions within Summit’s license territories.

About the ESMO (Free ESMO Whitepaper) 2025 Presidential Symposium Presentation

Presidential Symposium Presentation
Presentation Title: Phase III Study of Ivonescimab plus chemotherapy versus Tislelizumab plus chemotherapy as First-line Treatment for advanced squamous non-small cell lung cancer (HARMONi-6)
Presenter: Dr. Shun Lu, MD, PhD, Chief of Shanghai Lung Cancer Center at Shanghai Chest Hospital
ESMO Presentation No.: Presidential Symposium 2, #3035
Session Date & Time: Sunday, October 19, 2025, 4:30pm – 6:30pm CET (10:30am – 12:30pm ET)

About Ivonescimab

Ivonescimab, known as SMT112 in Summit’s license territories, North America, South America, Europe, the Middle East, Africa, and Japan, and as AK112 in China and Australia, is a novel, potential first-in-class investigational bispecific antibody combining the effects of immunotherapy via a blockade of PD-1 with the anti-angiogenesis effects associated with blocking VEGF into a single molecule. Ivonescimab displays unique cooperative binding to each of its intended targets with multifold higher affinity to PD-1 when in the presence of VEGF.

This could differentiate ivonescimab as there is potentially higher expression (presence) of both PD-1 and VEGF in tumor tissue and the tumor microenvironment (TME) as compared to normal tissue in the body. Ivonescimab’s tetravalent structure (four binding sites) enables higher avidity (accumulated strength of multiple binding interactions) in the TME (Zhong, et al, SITC (Free SITC Whitepaper), 2023). This tetravalent structure, the intentional novel design of the molecule, and bringing these two targets into a single bispecific antibody with cooperative binding qualities have the potential to direct ivonescimab to the tumor tissue versus healthy tissue. The intent of this design, together with a half-life of 6 to 7 days after the first dose (Zhong, et al, SITC (Free SITC Whitepaper), 2023), is to improve upon previously established efficacy thresholds, in addition to side effects and safety profiles associated with these targets.

Ivonescimab was engineered by Akeso Inc. (HKEX Code: 9926.HK) and is currently engaged in multiple Phase III clinical trials. Over 2,800 patients have been treated with ivonescimab in clinical studies globally.

Summit began its clinical development of ivonescimab in non-small cell lung cancer (NSCLC), commencing enrollment in 2023 in two multiregional Phase III clinical trials, HARMONi and HARMONi-3. Additionally, in early 2025, the Company began enrolling patients in the United States for HARMONi-7.

HARMONi is a Phase III clinical trial which intends to evaluate ivonescimab combined with chemotherapy compared to placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who have progressed after treatment with a 3rd generation EGFR TKI (e.g., osimertinib).

HARMONi-3 is a Phase III clinical trial which is intended to evaluate ivonescimab combined with chemotherapy compared to pembrolizumab combined with chemotherapy in patients with first-line metastatic, squamous or non-squamous NSCLC, irrespective of PD-L1 expression.

HARMONi-7 is a Phase III clinical trial which is intended to evaluate ivonescimab monotherapy compared to pembrolizumab monotherapy in patients with first-line metastatic NSCLC whose tumors have high PD-L1 expression.

In addition, Akeso has recently had positive read-outs in three single-region (China), randomized Phase III clinical trials for ivonescimab in NSCLC: HARMONi-A, HARMONi-2, and HARMONi-6.

HARMONi-A was a Phase III clinical trial which evaluated ivonescimab combined with chemotherapy compared to placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who have progressed after treatment with an EGFR TKI.

HARMONi-2 is a Phase III clinical trial evaluating monotherapy ivonescimab against monotherapy pembrolizumab in patients with locally advanced or metastatic NSCLC whose tumors have positive PD-L1 expression.

HARMONi-6 is a Phase III clinical trial evaluating ivonescimab in combination with platinum-based chemotherapy compared with tislelizumab, an anti-PD-1 antibody, in combination with platinum-based chemotherapy in patients with locally advanced or metastatic squamous NSCLC, irrespective of PD-L1 expression.

Akeso is actively conducting multiple Phase III clinical studies in settings outside of NSCLC, including biliary tract cancer, colorectal cancer, breast cancer, pancreatic cancer, small cell lung cancer, and head and neck cancer.

Ivonescimab is an investigational therapy that is not approved by any regulatory authority in Summit’s license territories, including the United States and Europe. Ivonescimab was initially approved for marketing authorization in China in May 2024. Ivonescimab was granted Fast Track designation by the US Food & Drug Administration (FDA) for the HARMONi clinical trial setting.