MTA-PRMT5

Bristol Myers Squibb and Ideaya Biosciences both released detailed snapshots of early-stage data for cancer drugs targeting solid tumors with a certain mutation known as MTAP deletion. There are no approved therapies specifically for MTAP deletions, though these tumors can be found in a wide range of cancer types, such as urothelial, lung, pancreatic and others. Either drug would allow patients an additional option if they end up resistant to other therapies like checkpoint inhibitors. While the companies are separately working to treat the same kinds of cancer mutations, their drugs act differently. Bristol Myers’ program, called BMS-986504, is a next-generation PRMT5 inhibitor that affects the binding of PRMT5 and MTA (the “PRMT5-MTA complex”) in an attempt to avoid off-target toxicity from earlier-in-class drugs. Ideaya’s therapy, codenamed IDE397, is a MAT2A inhibitor and is designed on the concept of synthetic lethality, where tumors with certain genetic aberrations become dependent on another cellular pathway. By blocking MAT2A, IDE397 can effectively treat patients with MTAP-deletion solid tumors, Ideaya says. Bristol Myers said Friday that, as of May 15, it enrolled 125 patients, 107 of whom were evaluable for efficacy. Of those patients, 21 achieved a partial response, good for an ORR of 20%. There were no complete responses, and the median duration of response was 4.8 months, with a median follow-up of 5.8 months. BMS measured seven different dose levels, but did not break down efficacy by each specific dose. The highest ORR came in mesothelioma, with three of seven patients achieving a partial response for 43%. Median duration of response was not reached. In NSCLC, six of 20 patients reached a partial response (30% ORR) with a median duration of response of 6.8 months. Pancreatic ductal adenocarcinoma had the lowest response rate, with three of 30 patients achieving partial response (10%). Treatment-related side effects were observed in 74% of the 125-patient sample, including 12% who saw grade 3 or higher adverse events. The most common side effects were nausea, vomiting, fatigue, diarrhea and decreased appetite. Additionally, 2% of patients discontinued treatment due to side effects. Ideaya’s data build on a July readout from an 18-patient sample. In the new dataset, there are 27 patients evaluable for efficacy as of an Aug. 22 cutoff. Nine of the 27 patients responded to the therapy, including one complete response and eight partial responses (33% ORR, down from 39% in July). Enrolled patients had either urothelial cancer, squamous NSCLC or adenocarcinoma NSCLC with MTAP deletions. The median duration of response is still immature, Ideaya said, as is median progression-free survival. The median duration of treatment has also not been reached. Treatment-related side effects were observed in 54% of patients, including 18% who saw grade 3 or higher adverse events (though none of those observed in more than 5% of patients). The most common side effects were peripheral neuropathy (none at grade 3 or higher), decreased appetite, blood creatinine increase, nausea, fatigue and asthenia. In addition to the monotherapy, Ideaya is also testing IDE397 with BMS-986504 and an experimental PRMT5 inhibitor from Amgen.

New preclinical data on PRMT5-MTA inhibitor program will also be presented NEW YORK, NY, USA I October 23, 2024 I Schrödinger (Nasdaq: SDGR) today announced new preclinical data on SGR-3515, its investigational Wee1/Myt1 inhibitor, during a poster session at the 36th EORTC-NCI-AACR Symposium (ENA 2024). The data demonstrate that in preclinical models, treatment with SGR-3515 results in synergistic anti-tumor activity that leads to deeper and more durable responses compared to inhibitors that target only Wee1 or Myt1. The preclinical data also show that SGR-3515 has a favorable pharmacological profile and dosing schedule that supports evaluating intermittent dosing in patients. Wee1 and Myt1 kinases regulate the cell cycle and DNA damage response, allowing time for DNA repair before cell division takes place. Concurrent loss of function or inhibition of Wee1 and Myt1 confers selective vulnerability in cancer cells, a mechanism referred to as synthetic lethality, which has become an emerging therapeutic strategy for a range of cancers. A Phase 1 dose-escalation study of SGR-3515 in patients with advanced solid tumors is ongoing in the U.S. and Canada, and initial data from the clinical study is expected in the second half of 2025. Schrödinger will also present preclinical data from its PRMT5-MTA program during a poster session on October 25. Schrödinger scientists have identified a novel series of selective, potent PRMT5-MTA inhibitors and are optimizing lead compounds for use in peripheral and brain tumors. “We are pleased to share these encouraging preclinical data on SGR-3515, a potential best-in-class treatment for patients with a broad range of solid tumors, including uterine and ovarian cancers, two patient populations with high unmet need,” stated Karen Akinsanya, Ph.D., president of R&D therapeutics at Schrödinger. “We also look forward to presenting preclinical data on the discovery of a novel series of compounds for our PRMT5-MTA inhibitor program. These programs highlight how we are deploying our computational platform at scale to discover highly optimized molecules to address diseases with significant medical need, and we believe the future of our therapeutics portfolio is very promising.” SGR-3515 Data at ENA 2024 The presentation (Abstract # 147), “Discovery of SGR-3515, a first-in-class Wee1/Myt1 inhibitor with differentiated pharmacological properties in xenograft tumor models,” includes preclinical data demonstrating superior anti-tumor activity of SGR-3515 compared to inhibitors of Wee1 or Myt1 alone due to strong target engagement of both Wee1 and Myt1. The data show that SGR-3515 is a more potent co-inhibitor of both Wee1 and Myt1 than previously disclosed inhibitors of either target. These data are consistent with prior preclinical observations demonstrating that SGR-3515 has a unique and differentiated pharmacological profile that supports evaluating an intermittent dosing schedule of three days on and 11 days off, as well as five days on and nine days off, which maintained anti-tumor activity while allowing recovery from any mechanism-based hematological toxicity in preclinical models. The preclinical data also demonstrate superior kinase selectivity and in vitro cell potency of SGR-3515 across a broad cell line panel compared to other known Wee1 and Myt1 inhibitors. These new data suggest that SGR-3515 is significantly more selective than existing compounds with low potential for drug-drug interaction. PRMT5-MTA Data at ENA 2024 Additionally, Schrödinger will present new preclinical data on its PRMT5-MTA inhibitor program at a poster session during the meeting on October 25 from 9:00 a.m. – 3:00 p.m. CEST. The presentation (Abstract # 372), “Discovery of a highly MTA-synergistic series of PRMT5 inhibitors for the treatment of MTAP-deficient tumors by virtual screening technology,” will include preclinical data on the discovery of highly selective PRMT5-MTA inhibitors. The poster will describe how Schrödinger’s virtual screening platform facilitated the identification of structurally distinct chemical matter with a high degree of MTA-synergy for compounds within a novel chemical series in vitro and in cellular contexts. Schrödinger has identified a novel series of selective, potent PRMT5-MTA inhibitors that did not show major off-target liabilities such as hERG inhibition in preclinical studies and may be suitable for use in combinations across tumor types. About Schrödinger Schrödinger is transforming the way therapeutics and materials are discovered. Schrödinger has pioneered a physics-based computational platform that enables discovery of high-quality, novel molecules for drug development and materials applications more rapidly and at lower cost compared to traditional methods. The computational platform is licensed by biopharmaceutical and industrial companies, academic institutions, and government laboratories around the world. Schrödinger’s multidisciplinary drug discovery team also leverages the software platform to advance a portfolio of collaborative and proprietary programs to address unmet medical needs. Founded in 1990, Schrödinger has approximately 850 employees and is engaged with customers and collaborators in more than 70 countries. To learn more, visit www.schrodinger.com , follow us on LinkedIn , or visit our blog, Extrapolations.com . SOURCE: Schrödinger

Results Illustrate Depth and Diversity of Amgen's Targeted Therapies Across Tumor Types THOUSAND OAKS, Calif., Sept. 13, 2024 /PRNewswire/ -- Amgen (NASDAQ: AMGN) today announced the presentation of new data across its broad oncology pipeline and portfolio at the European Society for Medical Oncology (ESMO) Congress 2024, taking place Sept. 13-17 in Barcelona. The abstracts showcase data from Amgen-sponsored and investigator-sponsored studies for colorectal, lung, prostate and gastric cancers using molecularly targeted modalities. "The breadth of these data reflects our strategy to advance diverse modalities for difficult-to-treat cancers," said Jay Bradner, M.D., executive vice president, Research and Development, and chief scientific officer at Amgen. "These ESMO results underscore our leadership in oncology, contributing significant advancements with both investigational and established therapies. Guided by a deep understanding of cancer biology and leveraging incisive therapeutics, we can target dominant drivers of disease with unprecedented precision." Key presentations include: First findings from the Phase 1b study of LUMAKRAS® plus Vectibix® in combination with FOLFIRI in first-line patients with KRAS G12C-mutated metastatic colorectal cancer (mCRC). Phase 1 dose escalation and initial dose expansion data from AMG 193 selected for a presidential symposium session. First-in-human study of xaluritamig in men with metastatic castration-resistant prostate cancer (mCRPC). For more information on the Amgen abstracts, see below. Abstracts and Presentation Times: Amgen Sponsored Abstracts LUMAKRAS® (sotorasib) plus Vectibix® (panitumumab) Sotorasib (soto) + panitumumab (pani) and FOLFIRI in the first line (1L) setting for KRAS-G12C mutated metastatic colorectal cancer (mCRC): Safety and efficacy from the phase 1b CodeBreaK 101 study Abstract #505O, Proffered Paper Oral Session: 2, Madrid Auditorium – Hall 2, Sunday, September 15 from 3:05 - 3:15 p.m. CEST AMG 193 Phase 1 dose escalation and initial dose expansion results of AMG 193, an MTA-cooperative PRMT5 inhibitor, in patients (pts) with MTAP-deleted solid tumors Abstract #3482, Proffered Paper Oral Session: Presidential Symposium III: Eyes to the Future, Barcelona Auditorium – Hall 2, Monday, September 16 from 16:30 – 18:15 p.m. CEST Xaluritamig C irculating tumor cell (CTC) enumeration and overall survival (OS) in men with metastatic castration-resistant prostate cancer (mCRPC) treated with xaluritamig Abstract #1610P, Poster, September 15 Xaluritamig, a STEAP1 x CD3 XmAb 2+1 immune therapy, in patients with metastatic castration-resistant prostate cancer (mCRPC): Initial results from dose expansion cohorts in a Phase 1 study Abstract #1598P, Poster, September 15 LUMAKRAS® (sotorasib) for NSCLC Sotorasib long-term clinical outcomes in pre-treated KRAS G12C-mutated advanced NSCLC: pooled analysis from the CodeBreaK clinical trials Abstract #1305P, Poster, September 14 Clinical characteristics and therapeutic sequences of KRAS G12C advanced Non-Small Cell Lung Cancer (aNSCLC) patients (pts) treated by sotorasib in the French post-marketing authorization early access (post-MA EA) Abstract #1307P, Poster, September 14 Bemarituzumab Fibroblast growth factor receptor 2 isoform IIIb (FGFR2b) protein overexpression and biomarker overlap in patients with advanced gastric or gastroesophageal junction cancer (GC/GEJC) Abstract #1420P, Poster, September 16 Investigator Sponsored Studies Vectibix® (panitumumab) **mRNA profiling as a biomarker of prognosis and response to first-line treatment in metastatic colorectal cancer: discovery and validation of a gene expression signature in three randomized trials Abstract #581P, Poster, September 16 Circulating tumor DNA driving anti-EGFR rechallenge therapy in metastatic colorectal cancer: the RASINTRO prospective multicenter study Abstract #517P, Poster, September 16 Prospective validation of the metastatic colon cancer score (mCCS) in patients with RAS wild-type metastatic colorectal cancer treated with first-line panitumumab plus FOLFIRI/FOLFOX: Final results of the non-interventional study VALIDATE Abstract #585P, Poster, September 16 About LUMAKRAS®/LUMYKRAS® (sotorasib) LUMAKRAS received accelerated approval from the U.S. Food and Drug Administration (FDA) on May 28, 2021. The U.S. FDA completed its review of Amgen's supplemental New Drug Application (sNDA) seeking full approval of LUMAKRAS ® on December 26, 2023, which resulted in a complete response letter. In addition, the FDA concluded that the dose comparison postmarketing requirement (PMR) issued at the time of LUMAKRAS accelerated approval, to compare the safety and efficacy of LUMAKRAS 960 mg daily dose versus a lower daily dose, has been fulfilled. 960 mg once-daily is the indicated dose for patients with KRAS G12C-mutated NSCLC under accelerated approval. The U.S. FDA also issued a new PMR for an additional confirmatory study to support full approval that will be completed no later than February 2028. About Metastatic Colorectal Cancer and the KRAS G12C Mutation Colorectal cancer (CRC) is the second leading cause of cancer deaths worldwide, comprising 10% of all cancer diagnoses.1 It is also the third most commonly diagnosed cancer globally.2 KRAS mutations are among the most common genetic alterations in colorectal cancers, with the KRAS G12C mutation present in approximately 3-5% of colorectal cancers.3-5 About Advanced Non-Small Cell Lung Cancer and the KRAS G12C Mutation Lung cancer is the leading cause of cancer-related deaths worldwide, and it accounts for more deaths worldwide than colon cancer, breast cancer and prostate cancer combined.6 KRAS G12C is the most common KRAS mutation in NSCLC.7 About 13% of patients with non-squamous NSCLC harbor the KRAS G12C mutation.8 About CodeBreaK The CodeBreaK clinical development program for Amgen's drug sotorasib is designed to study patients with an advanced solid tumor with the KRAS G12C mutation and address the longstanding unmet medical need for these cancers. Amgen also has several Phase 1b studies investigating sotorasib monotherapy and sotorasib combination therapy across various advanced solid tumors (CodeBreaK 101) open for enrollment.9 A Phase 2 randomized study evaluating sotorasib in patients with stage IV KRAS G12C-mutated NSCLC in need of first-line treatment is ongoing (CodeBreaK 201).10 A Phase 3 study of LUMAKRAS plus carboplatin and pemetrexed as front-line therapy in KRAS G12C-mutant, programmed death-ligand 1 (PD-L1) negative advanced NSCLC is enrolling patients (CodeBreaK 202). A Phase 3 study of LUMAKRAS in combination with Vectibix and FOLFIRI in first-line KRAS G12C–mutated CRC is also enrolling patients (CodeBreak-301). LUMAKRAS® (sotorasib) U.S. Indication LUMAKRAS is indicated for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least one prior systemic therapy. This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). LUMAKRAS® (sotorasib) Important U.S. Safety Information Hepatotoxicity LUMAKRAS can cause hepatotoxicity, which may lead to drug-induced liver injury and hepatitis. Among 357 patients who received LUMAKRAS in CodeBreaK 100, hepatotoxicity occurred in 1.7% (all grades) and 1.4% (Grade 3). A total of 18% of patients who received LUMAKRAS had increased alanine aminotransferase (ALT)/increased aspartate aminotransferase (AST); 6% were Grade 3 and 0.6% were Grade 4. In addition to dose interruption or reduction, 5% of patients received corticosteroids for the treatment of hepatotoxicity. Monitor liver function tests (ALT, AST and total bilirubin) prior to the start of LUMAKRAS every 3 weeks for the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop transaminase and/or bilirubin elevations. Withhold, reduce or permanently discontinue LUMAKRAS based on severity of adverse reaction. Interstitial Lung Disease (ILD)/Pneumonitis LUMAKRAS can cause ILD/pneumonitis that can be fatal. Among 357 patients who received LUMAKRAS in CodeBreaK 100, ILD/pneumonitis occurred in 0.8% of patients, all cases were Grade 3 or 4 at onset, and 1 case was fatal. LUMAKRAS was discontinued due to ILD/pneumonitis in 0.6% of patients. Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold LUMAKRAS in patients with suspected ILD/pneumonitis and permanently discontinue LUMAKRAS if no other potential causes of ILD/pneumonitis are identified. Most Common Adverse Reactions The most common adverse reactions occurring in ≥ 20% were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity and cough. Drug Interactions Advise patients to inform their healthcare provider of all concomitant medications, including prescription medicines, over-the-counter drugs, vitamins, dietary and herbal products. Inform patients to avoid proton pump inhibitors and H2 receptor antagonists while taking LUMAKRAS. If coadministration with an acid-reducing agent cannot be avoided, inform patients to take LUMAKRAS 4 hours before or 10 hours after a locally acting antacid. Please see LUMAKRAS full Prescribing Information. About Vectibix® (panitumumab) Vectibix is the first and only fully human monoclonal anti-EGFR antibody approved by the FDA for the treatment of mCRC. Vectibix was approved in the U.S. in September 2006 as a monotherapy for the treatment of patients with EGFR-expressing mCRC after disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy. In May 2014, the FDA approved Vectibix for use in combination with FOLFOX as first-line treatment in patients with wild-type KRAS (exon 2) mCRC. With this approval, Vectibix became the first-and-only biologic therapy indicated for use with FOLFOX, one of the most commonly used chemotherapy regimens, in the first-line treatment of mCRC for patients with wild-type KRAS mCRC. In June 2017, the FDA approved a refined indication for Vectibix for use in patients with wild-type RAS (defined as wild-type in both KRAS and NRAS as determined by an FDA-approved test for this use) mCRC. INDICATION AND LIMITATION OF USE Vectibix® is indicated for the treatment of patients with wild-type RAS (defined as wild-type in both KRAS and NRAS as determined by an FDA-approved test for this use) metastatic colorectal cancer (mCRC): as first-line therapy in combination with FOLFOX, and as monotherapy following disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy. Limitation of Use: Vectibix® is not indicated for the treatment of patients with RAS mutant mCRC or for whom RAS mutation status is unknown. IMPORTANT SAFETY INFORMATION BOXED WARNING: DERMATOLOGIC TOXICITY Dermatologic Toxicity: Dermatologic toxicities occurred in 90% of patients and were severe (NCI-CTC grade 3 and higher) in 15% of patients receiving Vectibix monotherapy [see Dosage and Administration (2.3), Warnings and Precautions (5.1), and Adverse Reactions (6.1)]. In Study 20020408, dermatologic toxicities occurred in 90% of patients and were severe (NCI-CTC grade 3 and higher) in 15% of patients with mCRC receiving Vectibix®. The clinical manifestations included, but were not limited to, acneiform dermatitis, pruritus, erythema, rash, skin exfoliation, paronychia, dry skin, and skin fissures. Monitor patients who develop dermatologic or soft tissue toxicities while receiving Vectibix® for the development of inflammatory or infectious sequelae. Life-threatening and fatal infectious complications including necrotizing fasciitis, abscesses, and sepsis have been observed in patients treated with Vectibix®. Life-threatening and fatal bullous mucocutaneous disease with blisters, erosions, and skin sloughing has also been observed in patients treated with Vectibix®. It could not be determined whether these mucocutaneous adverse reactions were directly related to EGFR inhibition or to idiosyncratic immune- related effects (e.g., Stevens Johnson syndrome or toxic epidermal necrolysis). Withhold or discontinue Vectibix® for dermatologic or soft tissue toxicity associated with severe or life-threatening inflammatory or infectious complications. Dose modifications for Vectibix® concerning dermatologic toxicity are provided in the product labeling. Vectibix® is not indicated for the treatment of patients with colorectal cancer that harbor somatic RAS mutations in exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146) of either KRAS or NRAS and hereafter is referred to as "RAS." Retrospective subset analyses across several randomized clinical trials were conducted to investigate the role of RAS mutations on the clinical effects of anti-EGFR-directed monoclonal antibodies (panitumumab or cetuximab). Anti-EGFR antibodies in patients with tumors containing RAS mutations resulted in exposing those patients to anti-EGFR related adverse reactions without clinical benefit from these agents. Additionally, in Study 20050203, 272 patients with RAS-mutant mCRC tumors received Vectibix® in combination with FOLFOX and 276 patients received FOLFOX alone. In an exploratory subgroup analysis, OS was shorter (HR = 1.21, 95% CI: 1.01-1.45) in patients with RAS-mutant mCRC who received Vectibix® and FOLFOX versus FOLFOX alone. Progressively decreasing serum magnesium levels leading to severe (grade 3-4) hypomagnesemia occurred in up to 7% (in Study 20080763) of patients across clinical trials. Monitor patients for hypomagnesemia and hypocalcemia prior to initiating Vectibix® treatment, periodically during Vectibix® treatment, and for up to 8 weeks after the completion of treatment. Other electrolyte disturbances, including hypokalemia, have also been observed. Replete magnesium and other electrolytes as appropriate. In Study 20020408, 4% of patients experienced infusion reactions and 1% of patients experienced severe infusion reactions (NCI-CTC grade 3-4). Infusion reactions, manifesting as fever, chills, dyspnea, bronchospasm, and hypotension, can occur following Vectibix® administration. Fatal infusion reactions occurred in postmarketing experience. Terminate the infusion for severe infusion reactions. Severe diarrhea and dehydration, leading to acute renal failure and other complications, have been observed in patients treated with Vectibix® in combination with chemotherapy. Fatal and nonfatal cases of interstitial lung disease (ILD) (1%) and pulmonary fibrosis have been observed in patients treated with Vectibix®. Pulmonary fibrosis occurred in less than 1% (2/1467) of patients enrolled in clinical studies of Vectibix®. In the event of acute onset or worsening of pulmonary symptoms interrupt Vectibix® therapy. Discontinue Vectibix® therapy if ILD is confirmed. In patients with a history of interstitial pneumonitis or pulmonary fibrosis, or evidence of interstitial pneumonitis or pulmonary fibrosis, the benefits of therapy with Vectibix® versus the risk of pulmonary complications must be carefully considered. Exposure to sunlight can exacerbate dermatologic toxicity. Advise patients to wear sunscreen and hats and limit sun exposure while receiving Vectibix®. Keratitis and ulcerative keratitis, known risk factors for corneal perforation, have been reported with Vectibix® use. Monitor for evidence of keratitis or ulcerative keratitis. Interrupt or discontinue Vectibix® for acute or worsening keratitis. In an interim analysis of an open-label, multicenter, randomized clinical trial in the first-line setting in patients with mCRC, the addition of Vectibix® to the combination of bevacizumab and chemotherapy resulted in decreased OS and increased incidence of NCI-CTC grade 3-5 (87% vs 72%) adverse reactions. NCI-CTC grade 3-4 adverse reactions occurring at a higher rate in Vectibix®-treated patients included rash/acneiform dermatitis (26% vs 1%), diarrhea (23% vs 12%), dehydration (16% vs 5%), primarily occurring in patients with diarrhea, hypokalemia (10% vs 4%), stomatitis/mucositis (4% vs < 1%), and hypomagnesemia (4% vs 0). NCI-CTC grade 3-5 pulmonary embolism occurred at a higher rate in Vectibix®-treated patients (7% vs 3%) and included fatal events in three (< 1%) Vectibix®-treated patients. As a result of the toxicities experienced, patients randomized to Vectibix®, bevacizumab, and chemotherapy received a lower mean relative dose intensity of each chemotherapeutic agent (oxaliplatin, irinotecan, bolus 5-FU, and/or infusional 5-FU) over the first 24 weeks on study compared with those randomized to bevacizumab and chemotherapy. Vectibix® can cause fetal harm when administered to a pregnant woman. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment, and for at least 2 months after the last dose of Vectibix®. In monotherapy, the most commonly reported adverse reactions (≥ 20%) in patients with Vectibix® were skin rash with variable presentations, paronychia, fatigue, nausea, and diarrhea. The most commonly reported adverse reactions (≥ 20%) with Vectibix® + FOLFOX were diarrhea, stomatitis, mucosal inflammation, asthenia, paronychia, anorexia, hypomagnesemia, hypokalemia, rash, acneiform dermatitis, pruritus, and dry skin. The most common serious adverse reactions (≥ 2% difference between treatment arms) were diarrhea and dehydration. To see the Vectibix® Prescribing Information, including Boxed Warning visit . About Amgen Amgen discovers, develops, manufactures and delivers innovative medicines to help millions of patients in their fight against some of the world's toughest diseases. More than 40 years ago, Amgen helped to establish the biotechnology industry and remains on the cutting-edge of innovation, using technology and human genetic data to push beyond what's known today. Amgen is advancing a broad and deep pipeline that builds on its existing portfolio of medicines to treat cancer, heart disease, osteoporosis, inflammatory diseases and rare diseases. In 2024, Amgen was named one of the "World's Most Innovative Companies" by Fast Company and one of "America's Best Large Employers" by Forbes, among other external recognitions. Amgen is one of the 30 companies that comprise the Dow Jones Industrial Average®, and it is also part of the Nasdaq-100 Index®, which includes the largest and most innovative non-financial companies listed on the Nasdaq Stock Market based on market capitalization. For more information, visit Amgen.com and follow Amgen on X, LinkedIn, Instagram, TikTok, YouTube and Threads. Amgen Forward-Looking Statements This news release contains forward-looking statements that are based on the current expectations and beliefs of Amgen. 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The scientific information discussed in this news release related to our product candidates is preliminary and investigative. Such product candidates are not approved by the U.S. Food and Drug Administration, and no conclusions can or should be drawn regarding the safety or effectiveness of the product candidates. Further, any scientific information discussed in this news release relating to new indications for our products is preliminary and investigative and is not part of the labeling approved by the U.S. Food and Drug Administration for the products. The products are not approved for the investigational use(s) discussed in this news release, and no conclusions can or should be drawn regarding the safety or effectiveness of the products for these uses. CONTACT: Amgen, Thousand Oaks Elissa Snook, 609-251-1407 (media) Justin Claeys, 805-313-9775 (investors) References Rawla, P, et al. Gastroenterology Review. 2019;14(2):89-103. World Health Organization. 2022 Statistics. Available at: . Accessed on May 17, 2024. Neumann J, et al. Frequency and type of KRAS mutations in routine diagnostic analysis of metastatic colorectal cancer. Pathol Res Pract. 2009;205(12):858-862. Jones RP, et al. Specific mutations in KRAS codon 12 are associated with worse overall survival in patients with advanced and recurrent colorectal cancer. Br J Cancer. 2017;116(7):923-929. Wiesweg M, et al. Impact of RAS mutation subtype on clinical outcome-a cross-entity comparison of patients with advanced non-small cell lung cancer and colorectal cancer. Oncogene. 2019;38(16):2953-2966. Sung H, et al. CA Cancer J Clin. 2021;71:209-249. Arbour KC, et al. Effects of Co-occurring Genomic Alterations on Outcomes in Patients with KRAS-Mutant Non-Small Cell Lung Cancer. Clin Cancer Res. 2018;24:334-340. Nassar AF, et al. Distribution of KRASG12C Somatic Mutations across Race, Sex, and Cancer Type. N Engl J. Med. 2021;384:185-187. ClinicalTrials.gov. CodeBreaK 101. Available at: . Accessed on May 7, 2024. ClinicalTrials.gov. CodeBreaK 201. Available at: . Accessed on May 7, 2024. **These data are a combined analysis of three studies, one of which was not Amgen supported. SOURCE Amgen WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED