On March 26, 2025, Sonnet BioTherapeutics Holdings, Inc. (the "Company") reported the positive findings from the first safety review of the expansion cohort in its Phase 1 SB101 clinical trial evaluating SON-1010, the Company’s proprietary version of recombinant human interleukin-12 ("rhIL-12") configured using genetic fusion to the Company’s Fully Human Albumin Binding ("FHAB") platform, in combination with trabectedin ("Yondelis") in adult patients with advanced leiomyosarcoma ("LMS") or liposarcoma ("LPS") (Press release, Sonnet BioTherapeutics, MAR 26, 2025, View Source [SID1234651472]).The expansion cohort builds on the successful completion of monotherapy dose escalation and assignment of the SON-1010 maximum tolerated ("MTD") dose of 1200 ng/kg.

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The SB101 Safety Review Committee ("SRC") met to evaluate the initial status of the patients in the expansion cohort, all of whom are receiving the SON-1010/trabectedin combination, as enrollment continues. After an average treatment of slightly over two months, one patient progressed and the other six are tolerating treatment. Adverse events ("AEs") considered to be related to either drug have all been mild or moderate, suggesting that the two drugs do not appear to be adversely impacting each other. The annual review including all 30 patients dosed to date showed that common AEs considered related to SON-1010 monotherapy or in combination included fatigue, fever, chills, and myalgia in 15% or more; moderate fatigue was the only related AE in 2 or more of the patients treated with trabectedin to date. Full enrollment of the combination cohort will provide an opportunity to evaluate statistical evidence of benefit in the response using the standard RECIST paradigm, which may also confirm synergy. Meanwhile, five of the six patients in the SON-1010 high-dose monotherapy group (83%) showed stable disease at 4 months and four continue on trial at 6 months with no new safety concerns. The partial response ("PR") in one of those patients persists, confirming the potential for benefit of SON-1010 monotherapy at the MTD in this small cohort. Overall, 13 of the 24 patients studied during SON-1010 dose escalation (54%) had evidence of monotherapy clinical benefit.

The primary outcome measures for the Phase 1 SB101 trial are the safety, tolerability, pharmacokinetics ("PK") and pharmacodynamics ("PD") of SON-1010 and to establish the MTD. The Company has treated 7 patients over 2 months on average and expects to enroll up to 18 patients with unresectable, metastatic LMS or LPS in this open-label, single-arm expansion cohort. Patients are being treated with SON-1010 in combination with the standard 21-day trabectedin cycles, alternating the dosing of the two drugs. Trabectedin, the first approved chemotherapeutic drug for advanced soft-tissue sarcomas ("STS") after failure of primary therapy, works by preventing tumor cells from proliferating but has also been shown to have pro-inflammatory immune effects in the tumor microenvironment ("TME") that may be enhanced by the IL-12 activity in SON-1010. Trabectedin is approved in 76 countries globally for the treatment of advanced STS as a single-agent, and in 69 countries for relapsed ovarian cancer in combination with doxorubicin HCl liposome injection.

On March 26, 2025 IDEAYA Biosciences, Inc. (Nasdaq: IDYA), a leading precision medicine oncology company, reported the publication of abstracts for an oral presentation in the New Drugs on the Horizon series, and three poster presentations on IDE275 (GSK959) at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, taking place April 25-30, 2025, in Chicago, Illinois (Press release, Ideaya Biosciences, MAR 26, 2025, View Source [SID1234651488]). IDE275 (GSK959), a potential best-in-class Werner Helicase (WRN) inhibitor, has demonstrated selective preclinical efficacy in the high microsatellite instability (MSI-H) solid tumor setting, and is advancing in a Phase 1 dose escalation trial in partnership with GSK.

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"IDE275 (GSK959) has a potential best-in-class profile and the preclinical data to be presented at AACR (Free AACR Whitepaper) 2025 with GSK highlights the molecule’s selectivity to treat MSI-H solid tumors and potential to be developed clinically as both a monotherapy agent and in combination with PD1," said Yujiro S. Hata, President and Chief Executive Officer, IDEAYA Biosciences. "MSI-H represents a meaningful biomarker-defined population with double-digit percent prevalence observed in multiple solid tumor types, including endometrial, colorectal, and gastric cancers. By binding uniquely to the helicase domain of WRN, IDE275 (GSK959) delivers potent and selective inhibition across MSI-H models," said Michael White, Ph.D., Chief Scientific Officer, IDEAYA Biosciences.

IDE275 (GSK959) was discovered through a collaboration between IDEAYA and GSK. Preclinical studies have demonstrated IDE275’s (GSK959) potential as a best-in-class WRN inhibitor, inducing single-agent tumor regressions in MSI-H patient-derived xenograft (PDX) and cell line-derived xenograft (CDX) models for endometrial, colorectal, and gastric cancers. Notably, MSI-H prevalence in these cancers has been reported at approximately 31%, 20%, and 19%, respectively, underscoring the significant patient population that could benefit from this therapeutic approach.

As part of the collaboration, GSK is responsible for 80% of global research and development costs for IDE275 (GSK959), and IDEAYA is responsible for 20% of such costs. GSK holds a global, exclusive license to develop and commercialize IDE275 (GSK959). IDEAYA has the potential to earn a $10.0 million milestone payment upon initiation of Phase 1 clinical dose expansion. Additionally, IDEAYA is eligible to receive up to $465 million in future late-stage development and regulatory milestone payments. Upon commercialization, IDEAYA will be eligible to receive up to $475.0 million of commercial milestones, 50% of U.S. net profits and tiered royalties on global non-U.S. net sales of the IDE275 (GSK959) – ranging from high single-digit to sub-teen double-digit percentages, subject to certain customary reductions.

At AACR (Free AACR Whitepaper) 2025, IDEAYA will have 8 total presentations across 3 clinical and 2 pre-clinical programs. There will be 4 IDEAYA/GSK presentations of IDE275 (GSK959) and 4 additional presentations across the IDE397/MAT2A, IDE161/PARG, PRMT5, and KAT6/7 programs.

Details for the oral presentation are as follows:
Presenter: Dr. Yanhua Rao, GSK
Title: An innovative and reversible WRN helicase inhibitor, GSK4418959 (IDE275), emerges as a promising clinical candidate for MSI-H cancers
Session: New Drugs on the Horizon Session, Part 3 (DDT003)
Date and Time: Monday, April 28, 2025 at 10:40am CDT
Location: Room S406 (Vista Ballroom) – McCormick Place South (Level 4)

Poster presentation details are below:
Author: Rao, Y. et al.
Title: Patient selection, target engagement and pharmacodynamic markers of WRN inhibitor GSK4418959 (IDE275)
Poster Number: 6393/30
Session Title: Pharmacokinetics and Pharmacodynamics of Cancer Therapeutics
Date and Time: Tuesday, April 29, 2025 at 9:00am – 12:00pm CDT

Author: Lee, Y. et al.
Title: Preclinical Characterization of GSK4418959 (IDE275): A Potent, Selective, and Highly Efficacious WRN Inhibitor for MSI-H Tumors Across Multiple Cancer Types
Poster Number: 2913/20
Session Title: DNA Damage Response and Modulation of DNA Repair 1
Date and Time: Monday, April 28, 2025 at 2:00pm – 5:00pm CDT

Author: Taygerly, P. et al.
Title: Discovery of GSK4418959 (IDE275): A novel, non-covalent, reversible Werner Helicase inhibitor and a new potential therapeutic for the treatment of MSI-H cancers
Poster Number: 5750/50
Session Title: Drug Design, Synthesis, & Disposition
Date and Time: Tuesday, April 29, 2025 at 2:00pm CDT

Author: Gupta, M. et al.
Title: Dual KAT6/7 inhibition disrupts epigenetic programs that promote tumor evolution and adaptive drug resistance
Poster Number: 442/3
Session Title: Epigenetic Targets
Date and Time: Sunday, April 27, 2025 at 2:00pm – 5:00pm CDT

Author: Maskey, R. et al.
Title: PARG inhibition provokes a DNA damage-dependent innate immune reaction that enhances ICI-driven anti-tumor immunity
Poster Number: 2899/6
Session Title: DNA Damage Response and Modulation of DNA Repair 1
Date and Time: Monday, April 28, 2025 at 2:00pm – 5:00pm CDT

Author: Garbett, D. et al.
Title: The allosteric MAT2A inhibitor IDE397 uniquely exploits metabolic liabilities associated with MTAP deletion to perturb DNA replication and repair
Poster Number: 4268/25
Session Title: New and Emerging Cancer Drug Targets
Date and Time: Tuesday, April 29, 2025 at 9:00am – 12:00pm CDT

Author: Aubi, O. et al.
Title: The impact of metabolite kinetics on dysregulation of essential enzymes in cancers with MTAP deficiencies
Poster Number: 4504/15
Session Title: Proteomic Biomarkers and Therapeutics
Date and Time: Tuesday, April 29, 2025 at 9:00am – 12:00pm CDT

The oral presentation and posters will be available online at View Source following the presentations.

On March 26, 2024 Alphamab Oncology reported financial results for the full year ended December 31, 2024 and highlighted recent business progress (Press release, Alphamab, MAR 26, 2025, View Source,amounted%20to%20RMB%20159.46%20million. [SID1234654359]).

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Financial Summary

● For the year ended December 31, 2024, we recorded total revenue of RMB 640.08 million, a 192.58% year-on-year increase. Meanwhile, product revenue (attributed to the Company) amounted to RMB 159.46 million.

● For the year ended December 31, 2024, our R&D expenditure amounted to RMB 404.15 million, basically unchanged as compared with prior year.

● For the year ended December 31, 2024, we reached profitability for the first time on an annual basis, recording profit for the year of RMB 166.34 million.

● We have a healthy financial position, with cash reserves of RMB 1,571.47 million as of December 31, 2024.

Business Highlights

With multiple proprietary platforms, the Company has established a globally competitive and differentiated pipeline that includes antibody-drug conjugation (ADC), single domain antibody, and bispecific antibodies. Envafolimab, the world’s first subcutaneously injectable PD-(L)1 inhibitor, was approved by Chinese authorities in 2021, providing a safer and more convenient tumor immunotherapy for patients. Multiple assets are in phase III or pivotal clinical trials, and several other bispecific ADC new drug candidates are in preclinical development.

Commercial Product

KN035 (Envafolimab)

KN035, an innovative anti-tumor immunotherapy drug, is the first subcutaneously injectable PD-(L)1 inhibitor worldwide, the first immunotherapy drug aimed at cross-tumor indications in China and the first domestically produced PD-L1 drug. KN035 offers advantages in effectiveness, safety, convenience and compliance, particularly suitable for frail, elderly patients and those with adverse reactions to intravenous infusions, while significantly reducing the use of healthcare resources.

Events during the Reporting Period

● In January 2024, Envafolimab obtained the market approval by the Pharmaceutical Administration Bureau of the Macau Special Administrative Region of the People’s Republic of China for the treatment of non-metastatic advanced microsatellite instability-high (MSI-H) or non-mismatch-repair deficiency (dMMR) advanced solid tumors.

● In January 2024, Alphamab Oncology and 3D Medicines entered into a license agreement with Glenmark Pharmaceuticals Ltd. (Glenmark) for the subcutaneous injection PD-L1 antibody drug KN035, pursuant to which, Glenmark was granted exclusive licensing interests in clinical development and commercialization of oncology indications of KN035 (the "Field") in India, Asia Pacific (except Singapore, Thailand, Malaysia), the Middle East and Africa, Russia, Commonwealth of Independent States and Latin America (the "Territory"). Glenmark shall bear its own costs and expenses related to the development and commercialization of KN035 in the Field in the Territory. Jiangsu Alphamab retains the exclusive right to produce KN035 for any purpose either inside or outside the Territory.

● In March 2024, Envafolimab was included in the 2024 edition of the "Chinese Expert Consensus on the Use of Immune Checkpoint Inhibitors in Perioperative Treatment of Advanced Gastric Cancer" published by the Gastric Cancer Committee of the Chinese Anti-Cancer Association. Envafolimab has been highly recommended by 16 latest domestic authoritative guidelines and consensus recommendations in 2024.

● In August 2024, Envafolimab was granted breakthrough therapy designation by the Center for Drug Evaluation (CDE) of the National Medical Products Administration of China (NMPA) for the treatment of patients with unresectable or metastatic solid tumors with high tumor mutation burden (TMB-H) who have failed prior standard treatment and no satisfactory alternative treatment.

● In September 2024, the supplementary application for production site, scale and process changes of KN035 successfully passed the GMP compliance inspection, and we received Pharmaceutical GMP Compliance Inspection Certificate in December 2024.

Clinical Product Pipeline

KN026

KN026 is a HER2 heterodimeric bispecific antibody (BsAb) that can simultaneously bind two non-overlapping epitopes of HER2, leading to HER2 signal blockade. KN026 has demonstrated better tumor inhibition in HER2-positive tumor cell lines compared with Trastuzumab and Pertuzumab in combination. Additionally, KN026 has also shown inhibitory effect on tumor cells with Trastuzumab-resistant cell lines. The results of multiple clinical studies in different stages showed that KN026 has significant anti-tumor activities, even in heavily pretreated patients with HER2-positive BC and GC, including those with prior anti-HER2 treatment. KN026 in combination with chemotherapy for the treatment of patients with HER2-positive GC (including GEJ) who have failed first-line standard treatment was granted breakthrough therapy designation by the Center for Drug Evaluation (CDE) of the National Medical Products Administration of China (NMPA).

Events during the Reporting Period

● The phase III clinical trial of KN026 combined with chemotherapy as second-line and later-line treatment of HER2-positive GC/GEJ is undergoing smoothly.

● The phase III clinical trial of KN026 combined with albumin-bound Docetaxel HB1801 as first-line treatment of HER2-positive recurrent and metastatic BC is undergoing smoothly.

● In October 2024, a phase III clinical trial of KN026 in combination with albumin-bound Docetaxel HB1801 was approved by CDE as neoadjuvant treatment for HER2-positive early or locally advanced BC, and the first patient was successfully dosed in December 2024.

Events after the Reporting Period

● In January 2025, the results of phase II clinical trial of KN026 in combination with docetaxel as first-line treatment for HER2-positive recurrent or metastatic BC were published in Cancer Communications.

● In March 2025, the results of phase II clinical trial of KN026 in combination with KN046 for the treatment of advanced HER2-positive solid tumors (excluding BC) were published in Signal Transduction and Targeted Therapy.

JSKN003

JSKN003 is a bispecific ADC developed based on KN026 using the proprietary Glycan-specific conjugation platform. JSKN003 can bind HER2 on the surface of tumor cells and release topoisomerase I inhibitors (TOPIi) through cellular endocytosis, thereby exerting anti-tumor effects. Compared with its ADC counterparts, JSKN003 demonstrated better serum stability and stronger bystander effect, which effectively expands the therapeutic window. Results of multiple clinical studies at various stages of JSKN003 in China and Australia have demonstrated favorable safety profile, with promising efficacy of JSKN003 in heavily pretreated patients with advanced solid tumors, especially in patients with platinum-resistant ovarian cancer (PROC), HER2-expressing BC, or high HER2-expressing solid tumors.

Events during the Reporting Period

● In April 2024, the results of the dose-escalation stage of the phase I clinical trial of JSKN003 conducted in Australia were presented at the 2024 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, which demonstrated favorable tolerability and safety profile of JSKN003 in patients with advanced/metastatic solid tumors who received prior multi-line treatment. The occurrence of hematologic toxicity was very low among common treatment-related adverse events (TRAEs) of all grades and no TRAE led to death or treatment discontinuation. The results also demonstrated encouraging preliminary anti-tumor activity.

● In June 2024, data from a phase I clinical trial of JSKN003 conducted in China were presented for the first time at the 2024 Annual Meeting of American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper). The results showed that the ORR was 51.1% in all efficacy evaluable patients across HER2 low and HER2 positive populations, of which 28 patients who received prior anti-HER2 the ORR was 57.1%, and 21 patients who received prior anti-HER2 ADC the ORR was 57.1%. The results still showed efficacy signals in patients with previous anti-HER2 ADC treatment.

● In September 2024, clinical data from two studies on JSKN003 for the treatment of PROC and HER2-positive (IHC 3+) advanced solid tumors (excluding BC) were presented at the 2024 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress. The results have demonstrated favorable tolerability and safety profile, with promising efficacy of JSKN003 in heavily pretreated patients with PROC or HER2-positive solid tumors.

● In September 2024, the Company entered a licensing agreement with JMT-Bio Technology Co., Ltd. (JMT-Bio), a wholly-owned subsidiary of CSPC Pharmaceutical Group Co., Ltd. (CSPC) (stock code: 1093.HK), pursuant to which, JMT-Bio was granted the exclusive license and sublicense rights to develop, sell, offer for sale and commercialize JSKN003, for the treatment of tumor-related indications (the "Field") in mainland China (excluding Hong Kong, Macau or Taiwan) (the "Territory") and become the sole marketing authorization holder for JSKN003 for the Field in the Territory. Alphamab retains the sole right to supply JSKN003. According to the licensing agreement, Alphamab is entitled to receive upfront payment and milestone payments of up to RMB3.08 billion in total, and a double-digit percentage of royalties on net product sales of JSKN003.

● In December 2024, JSKN003 received approval from CDE to initiate a phase III clinical trial to compare the efficacy of JSKN003 versus investigator-selected chemotherapy for the treatment of platinum-resistant recurrent epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer, and the first patient was successfully dosed in February 2025.

● The phase III clinical trial of JSKN003 for the treatment of unresectable locally advanced or metastatic HER2-low expressing BC is undergoing smoothly.

● Multiple exploratory phase II clinical studies of JSKN003 are currently being conducted.

Events after the Reporting Period

● In February 2025, JSKN003 received approval from CDE to initiate a phase III clinical trial to compare the efficacy and safety of JSKN003 versus trastuzumab emtansine (T-DM1) for the treatment of HER2-positive advanced BC, and the first patient was successfully dosed in the same month.

● In March 2025, JSKN003 was granted breakthrough therapy designation by CDE. The designation is for the treatment of platinum-resistant recurrent epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer, not restricted to HER2 expression levels.

JSKN016

JSKN016 is a bispecific ADC simultaneously targeting HER3 (Human epidermal growth factor receptor 3) and TROP2 (Trophoblast cell surface antigen 2), which is developed with proprietary single-domain antibody platform and Glycan-specific conjugation platform. TROP2 and HER3 are overexpressed in multiple solid tumors. JSKN016 exerts tumor cell-killing activity through dual binding to both antigens, coupled with endocytosis and bystander effects, demonstrating superior efficacy compared to monospecific TROP2 or HER3 ADCs. Furthermore, JSKN016 shows enhanced ability to overcome drug resistance caused by tumor heterogeneity.

Events during the Reporting Period

● In March 2024, JSKN016 received approval from CDE to initiate a phase I clinical trial for the treatment of advanced malignant solid tumors and the first patient was successfully dosed in May 2024. JSKN016 has demonstrated preliminary antitumor activity and a favorable safety profile across multiple solid tumor types, supporting its advancement to the next phase of clinical study.

Events after the Reporting Period

● The phase II clinical trial of JSKN016 monotherapy in multiple subgroups of lung cancer to evaluate efficacy, safety, and dose optimization is currently being conducted.

● The cohort expansion phase clinical trial of JSKN016 monotherapy for the treatment of non-HER2-positive BC is currently being conducted.

● In March 2025, IND application for JSKN016 combined with chemotherapy/immunotherapy /tyrosine kinase inhibitors (TKI) as first-line and later-line treatment of multiple subgroups of non-small cell lung cancer (NSCLC) was approved by CDE.

● In March 2025, IND application for JSKN016 combined with chemotherapy/immunotherapy as first-line and later-line treatment of multiple subgroups of non-HER2-positive BC was approved by CDE.

JSKN033

JSKN033 is a proprietary high-concentration co-formulation consisting of ADC and immune checkpoint inhibitor, independently developed by the Company, which can be administered subcutaneously. JSKN033 is the world’s first subcutaneous injectable ADC for clinical trials. By combining immunotherapy (KN035) and ADC (JSKN003), JSKN033 is anticipated to significantly enhance efficacy while leading to improved safety and convenience.

Events during the Reporting Period

● In March 2024, the first patient has been successfully dosed in Australia in the phase I/II clinical study of JSKN033 for the treatment of HER2-expressing advanced or metastatic solid tumors. The dose escalation phase has been completed until now.

● In November 2024, the research updates of the first-in-human phase I/II clinical trial of JSKN033 for the treatment of HER2-expressing advanced or metastatic solid tumors, have been presented for the first time as a poster in the Late-Breaking Abstract session at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper). JSKN033 presented a favorable safety profile and encouraging anti-cancer activity in heavily treated patients.

● In December 2024, JSKN033 received approval from CDE to initiate a phase I/II clinical trial in Chinese patients with advanced metastatic malignant tumors and the first patient was successfully dosed in January 2025. This study has previously been included in the "Pilot Program for Optimizing the Review and Approval of Clinical Trials for Innovative Drugs".

KN046

KN046, a bispecific antibody (BsAb) immune checkpoint inhibitor, composed of a fusion of CTLA-4 and PD-L1 single domain antibody, engineered to target the tumor microenvironment with high PD-L1 expression. Multiple clinical trials of KN046 at different stages covering different types of tumors including non-small cell lung cancer (NSCLC) have been conducted in China, the United States and Australia.

Events during the Reporting Period

● In February 2024, the results of the phase II clinical trial of KN046 in combination with nab-paclitaxel as first-line treatment for advanced triple-negative breast cancer were published in Nature Communications.

● In March 2024, the results of the phase II clinical trial of KN046 in combination with chemotherapy as first-line treatment for metastatic NSCLC were published in Cell Reports Medicine.

● In August 2024, the results of phase Ib clinical trial of KN046 in combination with chemotherapy and palliative radiotherapy as first-line treatment for advanced esophageal squamous cell carcinoma were published in Cancer Immunology, Immunotherapy.

● In September 2024, we completed OS final analysis for a phase III clinical trial of KN046 for the treatment of advanced squamous NSCLC (sq NSCLC).

● In December 2024, the results of the phase II clinical trial of KN046 in combination with Axitinib as first-line treatment for advanced NSCLC were presented at the European Society for Medical Oncology Immuno-Oncology (ESMO IO) Congress 2024.

Events after the Reporting Period

● In February 2025, the results of phase II clinical trial of KN046 in combination with lenvatinib for the treatment of advanced unresectable or metastatic hepatocellular carcinoma were published in Nature Communications.

Early-stage R&D

Leveraging proprietary platform technologies including glycan-specific conjugation, linker-payload, dual-payload conjugation, and bispecific antibodies, the Company has developed globally competitive new drugs such as ADCs and bispecific antibodies. The bispecific ADCs (BADC) and dual-drug conjugates (BADDC) developed by the Company, not only improve tumor targeting but also address heterogeneity and resistance issues, offering new strategies for cancer treatment. Currently multiple innovative bispecific ADC new drug candidates are in preclinical development and will be advanced into clinical trials sequentially.

● In June 2024, Jiangsu Alphamab entered into a research and collaboration agreement with ArriVent BioPharma, Inc. to use Jiangsu Alphamab’s proprietary linker-payload (Alphatecan) and glycan-specific conjugation platforms to discover and develop novel bispecific ADCs.

Manufacturing Facilities

The Company’s manufacturing facility was constructed in compliance with Good Manufacturing Practice (GMP) standards of the National Medical Products Administration of China (NMPA), the U.S. Food and Drug Administration (FDA), and the European Medicines Agency (EMA). The production lines are equipped with world-class equipment capable of meeting the large-scale manufacturing needs for a variety of biologics, including ADCs, both in the clinical and commercial stages. In 2024, the Company further expanded its production capacity by constructing the new suite dedicated to ADC drugs, which will be put into operation soon.

Other Highlights

● In November 2024, the Company was granted "2024 Top 100 Chinese Pharmaceutical Innovative Enterprises"and"2024 China Pharmaceutical Innovative Enterprise Bispecific Antibody Track Top5"by Healthcare Executive, a specialized magazine focusing on the pharmaceutical industry.

● In November 2024, the Company was granted "2024 Top 100 Brand Influence of Chinese Pharmaceutical Enterprise" by the China Health Culture Association, the China Hospital Association, and the National Health Commission of the People’s Republic of China Health TV Channel (CHTV) at the 2024 Healthy China Communication Conference.

For more information, please refer to the Company’s Annual Results Announcement for the Year Ended December 31, 2024 published on the Hong Kong Stock Exchange and the Company’s official website.

On March 26, 2025 Exelixis, Inc. (Nasdaq: EXEL) reported that the U.S. Food and Drug Administration (FDA) has approved CABOMETYX (cabozantinib) for the treatment of 1) adult and pediatric patients 12 years of age and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated pancreatic neuroendocrine tumors (pNET); and 2) adult and pediatric patients 12 years of age and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated extra-pancreatic NET (epNET) (Press release, Exelixis, MAR 26, 2025, View Source [SID1234651457]). NET are heterogeneous tumors that arise from the neuroendocrine cells of the digestive tract and other organs, such as the lung and pancreas. Most patients with advanced disease face a poor prognosis.1,2,3,4

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"The characteristics of NET vary widely from patient to patient, and very few treatment options have demonstrated the ability to improve outcomes across such a heterogeneous population," said Jennifer Chan, M.D., M.P.H., study chair for the CABINET trial, Clinical Director of the Gastrointestinal Cancer Center and Director of the Program in Carcinoid and Neuroendocrine Tumors at Dana-Farber Cancer Institute. "It was encouraging to see that cabozantinib resulted in significant delays in disease progression in the CABINET trial—regardless of primary tumor site and grade. This FDA approval marks a meaningful advancement, which may establish an important new treatment option for patients, without limitations based on somatostatin receptor expression and functional status."

The FDA approval—adding to five previous approvals for CABOMETYX—is based on results from CABINET, a phase 3 pivotal trial evaluating CABOMETYX compared with placebo in two cohorts of patients with previously treated NET: advanced pNET and advanced epNET. Final progression-free survival results were presented at the 2024 European Society for Medical Oncology Congress and published in The New England Journal of Medicine. In January 2025, the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology for Neuroendocrine and Adrenal Tumors were updated to include cabozantinib as a category 1 preferred regimen for the majority of well-differentiated advanced NET following specific treatments, and as a category 2A preferred regimen for other forms of advanced NET, depending on tumor grade and different requirements for prior therapy.

"As a company committed to improving the standard of care for people living with advanced, difficult-to-treat cancers, we are proud to bring CABOMETYX to patients with previously treated advanced neuroendocrine tumors," said Amy Peterson, M.D., Executive Vice President, Product Development & Medical Affairs, and Chief Medical Officer, Exelixis. "I would like to extend our sincere gratitude to the Alliance for Clinical Trials in Oncology for conducting the CABINET trial, to the FDA for their collaboration on the review of this application and to all the patients and physicians who participated in this important study. Looking forward, we are doubling down on our commitment to the NET community as we prepare to initiate our STELLAR-311 pivotal trial examining zanzalintinib versus everolimus in the first half of 2025."

The safety profile of CABOMETYX observed in each CABINET cohort was consistent with its known safety profile. No new safety signals were identified; however, the incidence of hypertension, regardless of treatment arm, was higher in NET patients compared to other approved tumor types. A majority of patients treated with CABOMETYX required dose modifications or reductions to manage adverse events.

"As a person who has lived with neuroendocrine tumors for over 14 years—and who has met many patients and caregivers in that time—I know that there are many challenges that come with this diagnosis, including the need to closely monitor the disease and adapt your treatment approach if faced with progression," said Cindy Lovelace, co-founder of The Healing NET Foundation. "As very few targeted therapies have been approved for advanced NET in recent years, I am excited that CABOMETYX brings new hope to the patients in our community who have been in need of effective new treatment options."

About CABINET (Alliance A021602)
CABINET (Randomized, Double-Blinded Phase III Study of CABozantinib versus Placebo In Patients with Advanced NEuroendocrine Tumors After Progression on Prior Therapy) is sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health, and is being led and conducted by the NCI-funded Alliance for Clinical Trials in Oncology with participation from the NCI-funded National Clinical Trials Network as part of Exelixis’ collaboration through a Cooperative Research and Development Agreement with the NCI’s Cancer Therapy Evaluation Program.

CABINET is a multicenter, randomized, double-blinded, placebo-controlled phase 3 pivotal trial that had enrolled a total of 298 patients in the U.S at the time of the final analysis. Patients were randomized 2:1 to cabozantinib (60 mg) or placebo in two separately powered cohorts (pNET, n=99; epNET, n=199). The epNET cohort included patients with the following primary tumor sites: gastrointestinal (GI) tract, lung, unknown primary sites and other organs. Each cohort was randomized separately and had its own statistical analysis plan. Patients must have had measurable disease per RECIST 1.1 criteria and must have experienced disease progression or intolerance after at least one U.S. FDA-approved line of prior systemic therapy other than somatostatin analogs. The primary endpoint in each cohort was PFS per RECIST 1.1 by blinded independent central review. Secondary endpoints included overall survival, objective response rate and safety. More information about this trial is available at ClinicalTrials.gov.

About NET
NET are cancers that begin in the specialized cells of the body’s neuroendocrine system.1 These cells have traits of both hormone-producing endocrine cells and nerve cells.1 In 2024, the estimated prevalence of NET in the U.S. was more than 380,000 people.5 It is estimated that 161,000 to 192,000 people are living with unresectable, locally advanced or metastatic NET.5 The number of people diagnosed with NET has been increasing in recent decades.6 Functional NET release peptide hormones that can cause debilitating symptoms, like diarrhea, hypertension and flushing which may require focused treatment, while symptoms of non-functional NET are related primarily to tumor growth.7,8,9,10,11 Most NET take years to develop and grow slowly, but eventually all patients with advanced or metastatic NET will develop refractory and progressing disease.12,13

NET can develop in any part of the body, but most commonly start in the GI tract or in the lungs, where they have historically been referred to as carcinoid tumors and are more recently called epNET.1 The five-year survival rates for advanced GI and lung NET tumors are 68% and 55%, respectively.2,3 NET can also start in the pancreas, where they tend to be more aggressive, with a five-year survival rate of only 23% for advanced disease.1,4 For advanced NET patients, treatment options include somatostatin analogs, chemotherapy, molecular targeted therapy and peptide-receptor radionuclide therapy.14

About CABOMETYX (cabozantinib)
In the U.S., CABOMETYX tablets are approved as monotherapy for the treatment of patients with advanced renal cell carcinoma (RCC) and in combination with nivolumab as a first-line treatment for patients with advanced RCC; for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib; for adult and pediatric patients 12 years of age and older with locally advanced or metastatic differentiated thyroid cancer (DTC) that has progressed following prior VEGFR-targeted therapy and who are radioactive iodine-refractory or ineligible; for the treatment of adult and pediatric patients 12 years of age and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated pancreatic neuroendocrine tumors (pNET); and adult and pediatric patients 12 years of age and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated extra-pancreatic NET (epNET). CABOMETYX tablets have also received regulatory approvals in over 65 countries outside the U.S. and Japan, including the European Union. In 2016, Exelixis granted Ipsen Pharma SAS exclusive rights for the commercialization and further clinical development of cabozantinib outside of the U.S. and Japan. In 2017, Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited for the commercialization and further clinical development of cabozantinib for all future indications in Japan. Exelixis holds the exclusive rights to develop and commercialize cabozantinib in the U.S.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hemorrhage: CABOMETYX can cause severe and fatal hemorrhages. The incidence of Grade 3-5 hemorrhagic events was 5% in CABOMETYX patients in RCC, HCC, and DTC studies. Discontinue CABOMETYX for Grade 3-4 hemorrhage and before surgery. Do not administer to patients who have a recent history of hemorrhage, including hemoptysis, hematemesis, or melena.

Perforations and Fistulas: Fistulas, including fatal cases, and gastrointestinal (GI) perforations, including fatal cases, each occurred in 1% of CABOMETYX patients. Monitor for signs and symptoms, and discontinue CABOMETYX in patients with Grade 4 fistulas or GI perforation.

Thrombotic Events: CABOMETYX can cause arterial or venous thromboembolic event. Venous thromboembolism occurred in 7% (including 4% pulmonary embolism) and arterial thromboembolism in 2% of CABOMETYX patients. Fatal thrombotic events have occurred. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or serious arterial or venous thromboembolic events.

Hypertension and Hypertensive Crisis: CABOMETYX can cause hypertension, including hypertensive crisis. Hypertension was reported in 37% (16% Grade 3 and <1% Grade 4) of CABOMETYX patients. In CABINET (n=195), hypertension occurred in 65% (26% Grade 3) of CABOMETYX patients. Do not initiate CABOMETYX in patients with uncontrolled hypertension. Monitor blood pressure regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled; when controlled, resume at a reduced dose. Permanently discontinue CABOMETYX for severe hypertension that cannot be controlled with antihypertensive therapy or for hypertensive crisis.

Diarrhea: CABOMETYX can cause diarrhea and it occurred in 62% (10% Grade 3) of treated patients. Monitor and manage patients using antidiarrheals as indicated. Withhold CABOMETYX until improvement to ≤ Grade 1; resume at a reduced dose.

Palmar-Plantar Erythrodysesthesia (PPE): CABOMETYX can cause PPE and it occurred in 45% of treated patients (13% Grade 3). Withhold CABOMETYX until PPE resolves or decreases to Grade 1 and resume at a reduced dose for intolerable Grade 2 PPE or Grade 3 PPE.

Hepatotoxicity: CABOMETYX in combination with nivolumab in RCC can cause hepatic toxicity with higher frequencies of Grades 3 and 4 ALT and AST elevations compared to CABOMETYX alone. With the combination of CABOMETYX and nivolumab, Grades 3 and 4 increased ALT or AST were seen in 11% of patients. Monitor liver enzymes before initiation of treatment and periodically. Consider more frequent monitoring as compared to when the drugs are administered as single agents. Consider withholding CABOMETYX and/or nivolumab, initiating corticosteroid therapy, and/or permanently discontinuing the combination for severe or life-threatening hepatotoxicity.

Adrenal Insufficiency: CABOMETYX in combination with nivolumab can cause primary or secondary adrenal insufficiency. Adrenal insufficiency occurred in 4.7% (15/320) of patients with RCC who received CABOMETYX with nivolumab, including Grade 3 (2.2%), and Grade 2 (1.9%) adverse reactions. Withhold CABOMETYX and/or nivolumab and resume CABOMETYX at a reduced dose depending on severity.

Proteinuria: Proteinuria was observed in 8% of CABOMETYX patients. Monitor urine protein regularly during CABOMETYX treatment. For Grade 2 or 3 proteinuria, withhold CABOMETYX until improvement to ≤ Grade 1 proteinuria; resume CABOMETYX at a reduced dose. Discontinue CABOMETYX in patients who develop nephrotic syndrome.

Osteonecrosis of the Jaw (ONJ): CABOMETYX can cause ONJ and it occurred in <1% of treated patients. Perform an oral examination prior to CABOMETYX initiation and periodically during treatment. Advise patients regarding good oral hygiene practices. Withhold CABOMETYX for at least 3 weeks prior to scheduled dental surgery or invasive dental procedures. Withhold CABOMETYX for development of ONJ until complete resolution; resume at a reduced dose.

Impaired Wound Healing: CABOMETYX can cause impaired wound healing. Withhold CABOMETYX for at least 3 weeks prior to elective surgery. Do not administer for at least 2 weeks after major surgery and until adequate wound healing. The safety of resumption of CABOMETYX after resolution of wound healing complications has not been established.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): CABOMETYX can cause RPLS. Perform evaluation for RPLS and diagnose by characteristic finding on MRI any patient presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.

Thyroid Dysfunction: CABOMETYX can cause thyroid dysfunction, primarily hypothyroidism, and it occurred in 19% of treated patients (0.4% Grade 3). Assess for signs of thyroid dysfunction prior to the initiation of CABOMETYX and monitor for signs and symptoms during treatment.

Hypocalcemia: CABOMETYX can cause hypocalcemia, with the highest incidence in DTC patients. Based on the safety population, hypocalcemia occurred in 13% of CABOMETYX patients (2% Grade 3 and 1% Grade 4).

Monitor blood calcium levels and replace calcium as necessary during treatment. Withhold and resume CABOMETYX at a reduced dose upon recovery or permanently discontinue CABOMETYX depending on severity.

Embryo-Fetal Toxicity: CABOMETYX can cause fetal harm. Advise pregnant women of the potential risk to a fetus and advise females of reproductive potential to use effective contraception during treatment with CABOMETYX and for 4 months after the last dose.

ADVERSE REACTIONS

The most common (≥20%) adverse reactions are:

CABOMETYX as a single agent: diarrhea, fatigue, PPE, decreased appetite, hypertension, nausea, vomiting, weight decreased, and constipation.

CABOMETYX in combination with nivolumab: diarrhea, fatigue, hepatotoxicity, PPE, stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain, decreased appetite, nausea, dysgeusia, abdominal pain, cough, and upper respiratory tract infection.

DRUG INTERACTIONS

Strong CYP3A4 Inhibitors: If coadministration with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage. Avoid grapefruit or grapefruit juice.

Strong or Moderate CYP3A4 Inducers: If coadministration with strong or moderate CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage. Avoid St. John’s wort.

USE IN SPECIFIC POPULATIONS

Lactation: Advise women not to breastfeed during CABOMETYX treatment and for 4 months after the final dose.

Hepatic Impairment: In patients with moderate hepatic impairment, reduce the CABOMETYX dosage. Avoid CABOMETYX in patients with severe hepatic impairment.

Pediatric Use: Physeal widening has been observed in children with open growth plates when treated with CABOMETYX. Physeal and longitudinal growth monitoring is recommended in children (12 years and older) with open growth plates. Consider interrupting or discontinuing CABOMETYX if abnormalities occur. The safety and effectiveness of CABOMETYX in pediatric patients less than 12 years of age have not been established.

Please see accompanying full Prescribing Information View Source

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatch or call 1-800-FDA-1088.

On March 26, 2025 ImCheck Therapeuticsannounced reported updated results from its ongoing open-label, randomized Phase I/II study EVICTION at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025 in Chicago, Illinois, USA (Press release, ImCheck Therapeutics, MAR 26, 2025, View Source [SID1234651473]). The poster presentation will provide efficacy, safety, pharmacodynamics and dose selection data on the novel γ9δ2 T-cell activator, ICT01, in combination with azacitidine and venetoclax for the treatment of patients with newly diagnosed AML.

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Details of the poster presentation at AACR (Free AACR Whitepaper) 2025 are:

Late-breaking abstract title: "γ9δ2 T-cell (γδTC) activation and azacitidine-venetoclax (AV) for older/unfit adults with newly diagnosed (ND) acute myeloid leukemia (AML) induces high rates of complete remission (CR): Preliminary efficacy, safety, pharmacodynamics (PD) and dose selection of ICT01 in the phase 1 study EVICTION"

Session: Phase 0 and Phase I Clinical Trials

Abstract number: CT024

Presenter: Abhishek Maiti, University of Texas MD Anderson Cancer Center

Authors:Abhishek Maiti, Pierre Peterlin, Daniel Morillo, Jose-Miguel Torregrosa-Diaz, Matthew Ulrickson, Agustin Penedo, Aude De Gassart, Elisabeth Wieduwild, Emmanuel Valentin, Maelle Mairesse, Patrick Brune, Katrien Lemmens, Stephan Braun, Daniel Olive, Naval G. Daver, Sylvain Garciaz, Pierre-Yves Dumas

Date: Monday, April 28, 2025

Time: 9:00 am- 12:00 pm EST

Location: Poster Section 49 / Poster Board Number: 3

The AACR (Free AACR Whitepaper) poster presentation will provide an update on the data in AML patients most recently presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting 2024 showing that ICT01 administered in combination with azacitidine and venetoclax demonstrated promising efficacy without compromising safety.

The AACR (Free AACR Whitepaper) poster will be available on ImCheck’s corporate website after the poster sessions have been opened.