HER4

81.8% ORR by BICR and 63.6% confirmed ORR by BICR at the 240 mg dose; 46.2% confirmed ORR in CNS Metastases 90.9% (n = 20/22) of patients with confirmed responses remained on study with a median duration of response not yet reached at time of analysis ArriVent to host virtual webinar on these interim analyses of Phase 1b data for firmonertinib in EGFR PACC mutant NSCLC on September 9, 2024 at 4:30 pm ET NEWTOWN SQUARE, Pa., Sept. 09, 2024 (GLOBE NEWSWIRE) -- ArriVent BioPharma, Inc. (Company or ArriVent) (Nasdaq: AVBP), a clinical-stage company dedicated to accelerating the global development of innovative biopharmaceutical therapeutics, today announced positive proof-of-concept randomized global Phase 1b FURTHER interim data for first-line firmonertinib monotherapy in patients with non-small cell lung cancer (NSCLC) harboring EGFR PACC mutations at a Presidential Symposium Presentation at the IASCLC 2024 annual World Conference on Lung Cancer (WCLC), in San Diego, California. ArriVent plans to host a virtual webinar on September 9, 2024 at 4:30 pm ET. To register for the event, please click here. “These compelling dose-dependent interim data are the first to demonstrate robust systemic and CNS anti-tumor activity for firmonertinib in a PACC mutant population,” said Bing Yao, Chairman and Chief Executive Officer of ArriVent. “We believe that the generally well-tolerated safety profile and response duration seen to date reinforce the therapeutic potential of firmonertinib to be an effective oral, chemotherapy-free treatment for this underserved patient population. Importantly, these data add to the clinical body of evidence supporting firmonertinib as a potentially effective option across EGFR mutation types and lines of non-small cell lung cancer therapy.” Dr. Xiuning Le, Associate Professor of Thoracic Head and Neck Medical Oncology at MD Anderson Cancer Center and the lead Principal Investigator added, “Treating lung cancer patients with EGFR uncommon mutation lung cancer, including PACC mutations and Exon 20 insertion mutations, remains a clinical challenge, as we need more potent and better tolerated EGFR inhibitors. These encouraging randomized data for firmonertinib suggest rapid and robust anti-tumor activity across PACC mutations which is similar to that observed for firmonertinib in exon 20 insertions. Moreover, the apparent high CNS activity points to firmonertinib as a promising potential new therapy for frontline patients with PACC mutations including those with CNS disease.” Presidential Symposium Presentation HighlightsCurrent standards of care have improved outcomes for classical EGFR mutations but have been less effective against uncommon EGFR mutation types including PACC and Exon 20 insertion mutations which represent approximately 12% and 9% of NSCLC EGFR mutations, respectively. Firmonertinib, an oral, once-daily, highly brain-penetrant EGFR inhibitor with broad activity across EGFR mutations, was evaluated for interim clinical proof-of-concept data in first-line EGFR PACC mutant NSCLC as part of the Phase 1b FURTHER trial. Select clinical activity and safety results from FURTHER interim data analysis include: First clinical dataset from an EGFR inhibitor being tested in a randomized defined population of EGFR PACC mutant NSCLCRobust systemic and central nervous system (CNS) responses across patients observed as of June 20, 2024 (data cut): 81.8% at 240mg and 47.8% at 160mg overall response rate (ORR) by blinded independent central review (BICR)63.6% and 34.8% confirmed ORR by BICR at 240mg and 160mg dose levels, respectively. One unconfirmed partial response pending confirmation at each of the 160mg and 240mg dose levels.Median duration of response had not yet been reached; 90.9% (n = 20/22) patients with confirmed responses remain on study46.2% (n = 6/13) CNS confirmed ORR by modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by BICR in first-line patients with brain metastases at baseline Generally well-tolerated with a profile consistent with prior firmonertinib data Most frequent treatment-related adverse events (TRAEs) were diarrhea, rash, dry skin, stomatitis, and hepatic enzyme elevationNo treatment discontinuation due to TRAEs was observed Firmonertinib showed promising dose-dependent activity in NSCLC patients across a broad range of EGFR PACC mutations in the first-line metastatic setting and includes CNS antitumor activity consistent with its high brain penetrance. About ArriVentArriVent is a clinical-stage biopharmaceutical company dedicated to the identification, development, and commercialization of differentiated medicines to address the unmet medical needs of patients with cancers. ArriVent seeks to utilize its team’s deep drug development experience to maximize the potential of its lead development candidate, firmonertinib, and advance a pipeline of novel therapeutics, such as next-generation antibody drug conjugates, through approval and commercialization. About FirmonertinibFirmonertinib (formerly furmonertinib) is an oral, highly brain-penetrant, and broadly active mutation-selective epidermal growth factor receptor (EGFR) inhibitor active against both classical and uncommon EGFR mutations, including PACC and exon 20 insertion mutations. In March 2021, firmonertinib was approved in China for first-line advanced non-small-cell lung cancer (NSCLC) with EGFR exon 19 deletion or L858R mutations and for patients with previously treated locally advanced or metastatic NSCLC with EGFR T790M mutation, otherwise known as EGFR classical mutations. Firmonertinib was granted U.S. Food and Drug Administration (FDA) Breakthrough Therapy Designation for the treatment of patients with previously untreated, locally advanced or metastatic non-squamous NSCLC with EGFR exon 20 insertion mutations. Firmonertinib was also granted FDA Orphan Drug Designation for the treatment of non-small cell lung cancer with epidermal growth factor receptor (EGFR) mutations or human epidermal growth factor receptor 2 (HER2) mutations or HER4 mutations. Firmonertinib is currently being studied in a global Phase 3 trial for first-line NSCLC patients with EGFR exon 20 insertion mutations (FURVENT; NCT05607550) and in a global Phase 1b study, which includes a cohort evaluating firmonertinib in patients with EGFR PACC mutations (FURTHER; NCT05364073). In addition, firmonertinib is also being studied in a clinical combination study targeting advanced or metastatic NSCLC patients with EGFR classical mutations, in partnership with Beijing InnoCare Pharma Tech Co., Ltd. About EGFR mutant NSCLCGlobally, lung cancer is the leading cause of cancer-related deaths among men and women. NSCLC is the predominant subtype of lung cancer, accounting for approximately 85% of all cases. Mutational activation of the EGFR is a frequent and early event in the development of NSCLC. EGFR mutations are divided into classical and uncommon. EGFR exon 20 insertion mutations are a group of uncommon EGFR mutations and constitute approximately 9% of all EGFR mutations. PACC mutations are another group of uncommon EGFR mutations and represent approximately 12% of all EGFR mutations. Patients with NSCLC whose tumors harbor uncommon EGFR mutations have significantly lower life expectancy with available therapies and represent an area of unmet medical need. Forward-Looking StatementsThis press release includes certain disclosures that contain “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 about us and our industry that involve substantial risks and uncertainties. All statements other than statements of historical facts contained in this press release, including statements regarding our future results of operations or financial condition, business strategy and plans, activity of firmonertinib compared to available therapies, anticipated clinical milestones, including proof of concept data for firmonertinib in patients with NSCLC EGFR PACC mutations, top-line pivotal Phase 3 data for firmonertinib in previously untreated NSCLC patients whose tumors contain EGFR exon 20 insertion mutations, and objectives of management for future operations, are forward-looking statements. In some cases, you can identify forward-looking statements because they contain words such as “anticipate,” “believe,” “contemplate,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” or “would” or the negative of these words or other similar terms or expressions. Forward-looking statements are based on ArriVent’s current expectations and are subject to inherent uncertainties, risks and assumptions that are difficult to predict. Factors that could cause actual results to differ include, but are not limited to, risks and uncertainties that are described more fully in the section titled “Risk Factors” in our annual report on Form 10-K for the fiscal year ended December 31, 2023, filed with the Securities and Exchange Commission on March 28, 2024 and our other filings with the Securities and Exchange Commission. Forward-looking statements contained in this press release are made as of this date, and ArriVent undertakes no duty to update such information except as required under applicable law. Contact:Joyce AllaireLifeSci Advisors, LLCjallaire@lifesciadvisors.com

Groups Develop Request for Proposals for Research Grants Focused on Lung Cancers Harboring HER2 Mutations and/or Other HER2 Alterations NEW YORK, Sept. 5, 2024 /PRNewswire/ -- The Lung Cancer Research Foundation (LCRF) is pleased to announce its collaboration with Bayer Pharmaceuticals to fund two research grants focused on innovative strategies to advance understanding and management of lung cancers harboring HER2 mutations and/or other HER2 alterations. This collaboration seeks to address important mechanistic questions and developmental therapeutics across the care continuum for HER2-mutant NSCLC, and has the potential to improve patient outcomes. "LCRF is delighted to collaborate with Bayer to identify and support outstanding lung cancer research projects that will help develop treatments for this specific set of lung cancers," says Kathryn O'Donnell, PhD, LCRF Scientific Advisory Board chair. "Expanding the treatment options available to patients affected by HER2 mutations or alterations is an important and exciting area in lung cancer research." "We are delighted to encourage and support groundbreaking research via this new LCRF initiative. This collaboration underscores our ongoing commitment to patients living with lung cancer, and our unwavering drive to advance precision oncology in disease areas with the highest unmet needs," said Abdelali Majdi, MD, Head of Global Medical Affairs Precision Oncology & Pipeline at Bayer's Pharmaceuticals Division. Lung cancer is responsible for more deaths worldwide than any other cancer, accounting for an estimated 130,180 deaths annually in the United States alone.1 Globally, there are approximately 1.8 million new cases of lung cancer every year and over 1.6 million deaths. 2 The last ten to fifteen years have seen accelerated clinical trials and regulatory approvals of targeted therapies for non-small cell lung cancer (NSCLC) in part due to advances in molecular profiling of tumors. Many of these targeted therapies are directed against oncogenic drivers. The HER family of tyrosine kinases include HER1 (epidermal growth factor receptor [EGFR] or ERBB1), HER2 (HER2/neu or ERBB2), HER3, and HER4. EGFR mutations were one of the first oncogenic drivers that were successfully targeted with the use of tyrosine kinase inhibitors. Despite substantial progress in this area, available treatments are generally not curative, and resistance invariably develops. Twenty years ago, HER2 mutations were also identified as potential oncogenic drivers in lung cancer. Activating mutations of HER2 (mostly exon 20 insertions, such as HER2 YVMA) occur in up to 4% of NSCLC. Until recently, developing effective HER2-targeted therapies for lung cancer has been a challenge. Immunotherapeutic strategies have not been successful in the treatment of lung cancers with genomic alterations such as HER2 mutations. It is of vital importance that there is a better understanding of the mechanism of tumor response and resistance. Moreover, given that therapeutic options available to date are not curative, there is a need for novel approaches to treat HER2-mutant lung cancers. The LCRF | Bayer Lung Cancer Research Award will focus on the science behind HER2 alterations as oncogenic drivers of malignancy and/or the development of novel therapeutic approaches for patients with tumors harboring HER2 mutations and/or other HER2 alterations. To be notified when the Request for Proposals is open for submissions, go to LCRF.org/HER2-RFP. To learn more about LCRF and its grants program, visit . About the Lung Cancer Research Foundation (LCRF) The Lung Cancer Research Foundation® (LCRF) is the leading nonprofit organization focused on funding innovative, high-reward research with the potential to extend survival and improve quality of life for people with lung cancer. LCRF's mission is to improve lung cancer outcomes by funding research for the prevention, diagnosis, treatment, and cure of lung cancer. To date, LCRF has funded 419 research grants, totaling nearly $44 million, the highest amount provided by a nonprofit organization dedicated to funding lung cancer research. For more information, visit lcrf.org. Contact: Sheila Sullivan Sr. Director, Marketing & Communications, LCRF [email protected] 1 American Cancer Society. Cancer Facts & Figures 2022. Atlanta: American Cancer Society; 2022 2 Babar L, Modi P, Anjum F. Lung Cancer Screening. [Updated 2023 Jul 24]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: Accessed: June 2024. SOURCE Lung Cancer Research Foundation

In recent days, the long-standing patent dispute between Pfizer and AZ has finally come to an end. According to Reuters, US District Judge Matthew Kennelly dismissed the jury's decision that AZ's lung cancer drug Tagrisso (osimertinib) had infringed Pfizer's anti-cancer drug Nerlynx (neratinib) patent and should pay $107.5 million in damages. The judge ruled that Pfizer's two patents were invalid.   In the reversal of this patent lawsuit, neratinib, as a human epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), can irreversibly bind to EGFR (HER1), HER2, and HER4, inhibiting the phosphorylation of the receptor and blocking downstream signal transduction, thereby inhibiting the proliferation, survival, and migration of cancer cells and improving the tumor microenvironment.   Pfizer acquired Wyeth for $68 billion in 2009 and included neratinib in its product line. In 2011, Puma Biotechnology obtained a license from Pfizer for neratinib and took full responsibility for the global development and commercialization of the drug. In July 2017, the US Food and Drug Administration (FDA) approved neratinib for reducing the risk of recurrence in early-stage HER2-positive breast cancer. In 2020, the FDA further approved neratinib in combination with capecitabine for the treatment of adult patients with advanced or metastatic HER2-positive breast cancer who had received two or more prior therapies. With this indication's approval, neratinib's application range has expanded from early-stage breast cancer patients to patients with advanced or metastatic breast cancer.   Osimertinib is the third-generation EGFR-TKI developed by AstraZeneca, which was approved by the FDA in November 2015 for the treatment of non-small cell lung cancer (NSCLC) patients with the T790M gene mutation as a second-line treatment. Currently, osimertinib has been approved for several indications in the NSCLC field. As the market leader of the third-generation EGFR-TKI, osimertinib's sales have continued to rise, reaching $5.799 billion in 2023 and becoming AstraZeneca's flagship product.   In 2021, Pfizer's subsidiary Wyeth and Puma Biotechnology filed a lawsuit against AstraZeneca, accusing osimertinib of infringing on their two key patents. One of the patents, "Patent 314," involves a method for treating NSCLC patients who are resistant to gefitinib and/or erlotinib with an EGFR inhibitor that covalently binds to cysteine 773 of the protein. The other is Wyeth's "Patent 162," which protects the use of these irreversible inhibitors to treat NSCLC patients who are resistant to gefitinib or erlotinib and carry a specific T790M mutation in the EGFR protein.   In May 2023, a federal jury in Delaware ruled that AstraZeneca had indeed infringed on Pfizer's patent and awarded $107.5 million in damages. Despite AstraZeneca's argument that Pfizer's patent was invalid, the jury did not adopt it. In response to this result, AstraZeneca filed an "additional defense."   In the latest ruling, the judge pointed out that two of Pfizer's patents were invalid because they lacked an effective written description of their invention, and that ordinary scientists in the field could not reproduce them based on these descriptions. Therefore, AstraZeneca has won the patent lawsuit. However, there are still many challenges ahead for Osimertinib.   At present, lung cancer has become the second most common type of cancer globally, according to statistics from the World Health Organization's International Agency for Research on Cancer (IARC), with lung cancer accounting for 11.1% of all cancer cases worldwide in 2020. Among lung cancer patients, non-small cell lung cancer (NSCLC) accounts for 85% of the total, while small cell lung cancer (SCLC) accounts for the remaining 15%. Epidermal growth factor receptor (EGFR) is one of the most important oncogenic driver genes in NSCLC, and studies have shown that the incidence rate of EGFR mutations in metastatic NSCLC patients is about 30%. In China, the proportion of EGFR mutations among NSCLC patients is about 51%.   To date, three generations of EGFR tyrosine kinase inhibitors (EGFR-TKI) have been approved for marketing worldwide. The first and second generation EGFR-TKIs mainly target patients with the EGFR ex19del mutation and the EGFR 21L858R mutation. However, the third-generation drugs are not only effective against these sensitive mutations, but also against the T790M resistance mutation that arises after treatment with the first and second-generation TKIs.   Osimertinib, an EGFR-TKI that is already on the market, has seen consistent sales growth since its launch, becoming an important revenue driver for AstraZeneca. However, despite the huge market potential of the third-generation EGFR-TKIs, the competition is extremely fierce, with seven similar products approved globally and six approved in the domestic market.   Moreover, the compound patent for Osimertinib in China (CN103702990) will expire in July 2032. Given the huge potential of Osimertinib in the domestic market for imported anti-cancer drugs, Jiangsu Wanbangshenghua Pharmaceutical Group has submitted an application for the approval of a biosimilar and successfully obtained approval.   In the field of innovative drugs, Jiangsu Haosen Pharmaceutical's Ametinib and Aileris Pharmaceutical's Fumetinib have been approved for marketing by the National Medical Products Administration (NMPA). Meanwhile, Oseacon's Limertinib, Johnson & Johnson's Lanresertinib, Tongyuan Pharmaceutical's TY-9591, and Aisen Pharmaceutical's Aivetinib have also submitted marketing applications or have entered the III phase clinical trial stage in China. In addition to the competition from similar products, osimertinib is also facing the challenge of dual antibody drugs. Recently, Johnson & Johnson's EGFR/C-MET dual antibody Amivantamab, combined with the third-generation EGFR-TKI Lartruvo (A+L), achieved the primary endpoint of progression-free survival (PFS) in a direct comparison clinical trial with osimertinib monotherapy for the first-line treatment of EGFR-mutated advanced NSCLC. The study results showed that compared with osimertinib, the A+L group significantly reduced the risk of PFS by 30% (HR, 0.70; 95% CI, 0.58-0.85; P<0.001), with a median PFS of 23.7 months (compared with 16.6 months), and an objective response rate (ORR) of 86% (compared with 85%). In terms of overall survival (OS), the median OS for the A+L group could not be estimated (HR, 0.77), while the OS for the osimertinib group was 37.3 months (HR, 0.77). The OS reached a statistically significant endpoint, indicating that A+L may become a new standard for the first-line treatment of EGFR-mutated NSCLC.   Faced with the dual pressure of generic drugs and innovative drugs, AstraZeneca's osimertinib is facing a severe competitive situation. Nevertheless, the victory in the patent lawsuit has saved AstraZeneca up to $107 million in potential compensation.