A Phase 1/2 Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of AMG 193 in Combination With IDE397 in Subjects With Advanced MTAP-null Solid Tumors

The main aims of this study are to evaluate the safety and tolerability, and to determine the maximum tolerated dose (MTD) or the recommended combination dose of AMG 193 in combination with IDE397 in adult participants with metastatic or locally advanced MTAP-null solid tumors, and to evaluate the preliminary anti-tumor activity of AMG 193 in combination with IDE397 in adult participants with metastatic or locally advanced MTAP-null Non-Small-Cell Lung Cancer (NSCLC).

开始日期2023-08-01

申办/合作机构

Amgen, Inc.

NCT04794699 / Recruiting临床1期

An Open Label, Phase 1, Treatment Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of IDE397 (MAT2A Inhibitor) In Adult Participants With Advanced Solid Tumors

This is a Phase 1, open-label, multicenter, dose escalation and expansion study of the safety, PK, PD, and preliminary anti-tumor activity of IDE397 as a single agent and in combination with other anticancer agents including taxanes (docetaxel, paclitaxel), or sacituzumab govitecan (SG), in adult patients with selected advanced or metastatic MTAP-deleted advanced solid tumors who are unresponsive to standard of care therapy. IDE397 is a small molecule inhibitor of methionine adenosyltransferase 2 alpha (MAT2A).

开始日期2021-04-14

申办/合作机构

IDEAYA Biosciences, Inc.

100 项与 IDE-397 相关的临床结果

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100 项与 IDE-397 相关的转化医学

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100 项与 IDE-397 相关的专利（医药）

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项与 IDE-397 相关的文献（医药）

2022-09-01·Current Opinion in Oncology

Targeting the methionine−methionine adenosyl transferase 2A−S-adenosyl methionine axis for cancer therapy

Review

作者: Yang, Yanzhong ; Buettner, Ralf ; Guo, Jiamin ; Rosen, Steven T.

Purpose of reviewIn this review, we summarize the biological roles of methionine, methionine adenosyl transferase 2A (MAT2A) and S-adenosyl methionine (SAM) in methylation reactions during tumorigenesis. Newly emerged inhibitors targeting the methionine−MAT2A−SAM axis will be discussed.Recent findingsSAM is the critical and global methyl-donor for methylation reactions regulating gene expression, and in mammalian cells, it is synthesized by MAT2A using methionine. Recent studies have validated methionine and MAT2A as metabolic dependencies of cancer cells because of their essential roles in SAM biosynthesis. MAT2A inhibition leads to synthetic lethality in methylthioadenosine-phosphorylase (MTAP)-deleted cancers, which accounts for 15% of all cancer types. Of note, remarkable progress has been made in developing inhibitors targeting the methionine−MAT2A−SAM axis, as the first-in-class MAT2A inhibitors AG-270 and IDE397 enter clinical trials to treat cancer.SummaryThe methionine−MAT2A−SAM axis plays an important role in tumorigenesis by providing SAM as a critical substrate for abnormal protein as well as DNA and RNA methylation in cancer cells. Targeting SAM biosynthesis through MAT2A inhibition has emerged as a novel and promising strategy for cancer therapy.

项与 IDE-397 相关的新闻（医药）

2024-11-04

·PRNewswire

IDEAYA Biosciences, Inc. Reports Third Quarter 2024 Financial Results and Provides Business Update

Enrollment in darovasertib + crizotinib 1L HLA-A2+ MUM potential Ph2/3 registration-enabling trial is ahead of schedule and has exceeded 150 patients Successful FDA Type C meeting and targeting initiation of Ph3 registration-enabling trial for darovasertib in neoadjuvant UM in H1 2025; Phase 2 neoadjuvant update with ~49% with >30% ocular tumor shrinkage & ~61% eyes preserved, and over 75 patients enrolled ENA 2024: Late-breaker oral presentation of IDE397 in MTAP-deletion UC and NSCLC with confirmed ORR by RECIST 1.1 of 40%, 38%, and 22%, in UC, SqNSCLC, and AdenoNSCLC, respectively; co-published IDE397 + AMG 193 preclinical combo data in MTAP-deletion IDE397 + AMG 193 combination study ongoing in MTAP-deletion solid tumors, and targeting expansion in MTAP-deletion NSCLC in late 2024 to early 2025 Targeting expansion of Phase 1/2 study of IDE397 in combination with Trodelvy® in MTAP-deletion UC in Q4 2024, and PR reported at ENA 2024 has confirmed by RECIST 1.1 Targeting Phase 1/2 expansion for IDE161 and FPI in combination with Merck's anti-PD-1 therapy KEYTRUDA® (pembrolizumab) in MSI-High and MSS EC in Q4 2024 IDE705 (GSK 101) Pol Theta Helicase Phase 1 dose escalation ongoing in HRD solid tumors Received IND clearance for IDE275 (GSK959) Werner Helicase development candidate ($7.0 million milestone) for Phase 1 trial in MSI-High solid tumors Targeting Development Candidate nomination for MTAP-deletion, KAT6 pathway and B7H3/PTK7 Topo-Payload Bispecific-ADC programs in Q4 2024 Targeting Investor R&D Day on Monday, December 16, to highlight IDEAYA's preclinical and clinical pipeline with leading KOL(s) and Pharma partner(s) $1.2 billion of cash, cash equivalents and marketable securities as of September 30, 2024, anticipated to fund operations into at least 2028; Completed an oversubscribed ~$302.4 million follow-on financing in July 2024 SOUTH SAN FRANCISCO, Calif., Nov. 4, 2024 /PRNewswire/ -- IDEAYA Biosciences, Inc. (Nasdaq: IDYA), a precision medicine oncology company committed to the discovery and development of targeted therapeutics, provided a business update, and announced financial results for the third quarter ended September 30, 2024. "This was a transformational quarter for IDEAYA, including completion of an oversubscribed ~$302.4 million follow-on financing, a late breaker oral presentation at ENA 2024 for IDE397 in heavily pre-treated MTAP-deletion urothelial and lung cancer patients, and a successful Type C meeting with the FDA to enable a potential registration-enabling trial for darovasertib in neoadjuvant uveal melanoma. Next, we received IND clearance for Werner Helicase inhibitor IDE275 with our partner GSK, representing our fifth potential first-in-class clinical program," said Yujiro S. Hata, Chief Executive Officer and Founder, IDEAYA Biosciences. "We continue to execute on our strategic vision to build a leading precision medicine oncology pipeline, and are on track to nominate our 6th, 7th, and 8th development candidate by year-end, including from our B7H3/PTK7 bi-specific topo-ADC, MTAP-deletion, and KAT6 pathway programs. We look forward to highlighting IDEAYA's potential first-in-class preclinical and clinical programs, and to continue to establish our scientific leadership in precision medicine oncology at our upcoming investor R&D day," said Michael White, Ph.D., Chief Scientific Officer, IDEAYA Biosciences. "This past quarter, we made significant progress on the darovasertib program, including being ahead of our enrollment targets for the first-line MUM potential registration-enabling trial, and a successful Type C meeting with the FDA to inform a potentially registration-enabling trial in the neoadjuvant uveal melanoma setting. Next, the clinical data update from ENA 2024, provides further clinical proof-of-concept for IDE397 at the RP2D in MTAP-deletion urothelial and lung cancer. We are excited to advance our broader IDE397 rational combination strategy, including target expansion with AMG 193 in MTAP-deletion NSCLC in late 2024 to early 2025, and target expansion with Trodelvy® (sacituzumab govitecan-hziy), Gilead's Trop-2 directed antibody-drug conjugate, in MTAP-deletion urothelial cancer in the fourth quarter. Lastly, we are targeting to select a monotherapy expansion dose for IDE161, and achieve FPI in combination with Keytruda in MSI-High and MSS endometrial cancer by year-end," added Darrin Beaupre, M.D., Ph.D., Chief Medical Officer, IDEAYA Biosciences. Summary of Q3 and Recent Key Developments Research and Clinical Development Darovasertib in 1L MUM and Neoadjuvant Uveal Melanoma (UM) Enrollment in darovasertib + crizotinib 1L HLA-A2+ MUM potential Ph2/3 registration-enabling trial is ahead of schedule and has exceeded 150 patients Positive interim Phase 2 results of darovasertib (IDE196) from the company-sponsored and investigator-sponsored trials (IST) were highlighted during an Investor Webcast in September 2024, and over 75 patients have been enrolled in company-sponsored trial. Following a successful Type C meeting with the U.S. Food and Drug Administration (FDA), IDEAYA is finalizing the Phase 3 registrational trial protocol and is targeting to initiate its potential registration-enabling trial in the first half of 2025. IDE397 in MTAP-Deletion Solid Tumors Phase 1 expansion results of IDE397 in 27 evaluable MTAP-deletion urothelial cancer (UC) and non-small cell lung cancer (NSCLC) patients were presented as a late-breaking oral presentation at the 36th EORTC-NCI-AACR Symposium (ENA 2024) in Barcelona, Spain. Additional preclinical data on the anti-tumor activity by combinatorial inhibition of IDE397 and clinical stage PRMT5 inhibitors AMG 193 and BMS-986504 in MTAP-deleted tumors were included in a poster presentation. Reported positive interim data from 18 evaluable MTAP-deletion UC and NSCLC patients and selected the move-forward Phase 2 expansion dose (RP2D) in an Investor Webcast in July 2024. Enrollment is ongoing in the IDE397 and AMG 193 Phase 1 dose escalation, and targeting expansion in NSCLC in late 2024 to early 2025. Ongoing Phase 1 trial evaluating IDE397 in combination with Trodelvy in MTAP-deletion UC; targeting combination expansion in the fourth quarter of 2024. The PR reported at ENA 2024 has confirmed by RECIST 1.1. IDE161 in Tumors with Homologous Recombination Deficiency Targeting Phase 1/2 monotherapy expansion for IDE161 PARG inhibitor in priority solid tumor type(s) in the fourth quarter of 2024. Targeting first-patient-in for the Phase 1 trial evaluating IDE161, IDEAYA's first-in-class potential PARG inhibitor, in combination with Merck's (known as MSD outside of the US and Canada) anti-PD-1 therapy, KEYTRUDA® (pembrolizumab), in MSI-High and MSS endometrial cancer (EC) in the fourth quarter of 2024. Preclinical data on IDE161 and antibody drug conjugate (ADC) combination rationale presented as a poster at ENA 2024. Received FDA IND clearance for IDE275 (GSK959), a potential first-in-class and best-in-class Werner Helicase inhibitor, for a Phase 1 trial in high microsatellite instability (MSI-High) tumors and earned a $7.0 million milestone from GSK. Targeting Development Candidate nomination for MTAP-deletion, KAT6 pathway and B7H3/PTK7 Topo-Payload Bispecific-ADC programs in the fourth quarter of 2024. IDEAYA is targeting to host a Virtual Investor R&D Day on Monday, December 16, 2024, to highlight IDEAYA's potential first-in-class preclinical and clinical pipeline with management, leading Key Opinion Leader(s) (KOLs), and Pharma partner(s). Corporate Development Raised gross proceeds of approximately $302.4 million in July 2024 through public offering, generating net proceeds of approximately $283.8 million. Appointed Douglas B. Snyder as Senior Vice President, General Counsel. Mr. Snyder brings over 25 years of legal experience with leading healthcare organizations, including GW Pharmaceuticals, Actelion Pharmaceuticals, Eisai, GSK, and the U.S. FDA. Clinical Programs and Upcoming Milestones Darovasertib (IDE196) Program in Tumors with GNAQ or GNA11 Mutations Darovasertib is a potent and selective protein kinase C (PKC) inhibitor being developed to broadly address primary and metastatic UM. Darovasertib is currently being evaluated in four ongoing clinical trials. The darovasertib and crizotinib combination in MUM has FDA Fast Track designation: IDE196-002 (NCT05987332) is a Phase 2/3 potentially registration-enabling clinical trial of darovasertib + crizotinib in first-line human leukocyte antigens (HLA)-A2*02:01 negative (-) MUM. Over 150 patients enrolled as of October 31, 2024. IDE196-001 (NCT03947385) is a Phase 1/2 clinical trial of darovasertib + crizotinib in which we are planning to enroll additional HLA-A2*02:01 positive (+) patients. Phase 2 trials of darovasertib as neoadjuvant / adjuvant therapy in primary UM: IDE196-009 (NCT05907954) is a company-sponsored Phase 2 trial evaluating darovasertib as neoadjuvant treatment of UM prior to primary interventional treatment of enucleation or radiation therapy, and as adjuvant therapy following the primary treatment. Over 75 patients enrolled as of October 31, 2024. NADOM (NCT05187884) is a Phase 2 neoadjuvant / adjuvant trial of darovasertib in ocular melanoma. This is an IST led by Anthony Joshua, MBBS, PhD, FRACP, Head Department of Medical Oncology, Kinghorn Cancer Centre, St. Vincent's Hospital in Sydney with additional participating sites in Melbourne, Australia. Positive interim efficacy data from both the company-sponsored and the IST trials were highlighted during an Investor webcast in September 2024: 31 enucleation and 18 plaque brachytherapy evaluable UM patients treated with darovasertib neoadjuvant therapy in Phase 2 company-sponsored and IST trials. ~59% (29 of 49) of patients with >20% ocular tumor shrinkage by product of diameters. ~49% (24 of 49) of patients with >30% ocular tumor shrinkage by product of diameters. ~61% (19 of 31) eye preservation rate observed. Evidence of predicted visual preservation observed by reducing the amount of radiation associated with plaque brachytherapy. Manageable AE profile observed from Phase 2 company-sponsored trial (n=38), including 11% grade 3 or higher AEs, and 5% serious AE rate. The discontinuation rate observed was 3%. The most common AEs observed included diarrhea, nausea, vomiting and fatigue. IDEAYA had a successful Type C meeting with the FDA to discuss the clinical trial design for a registration-enabling Phase 3 trial in neoadjuvant UM patients. The planned trial aims to enroll approximately 400 patients in two cohorts: cohort 1 of plaque brachytherapy eligible UM patients, and cohort 2 of enucleation eligible UM patients. Cohort 1 will be randomized to darovasertib followed by plaque brachytherapy versus plaque brachytherapy alone, and cohort 2 will be randomized with or without darovasertib as neoadjuvant therapy. The primary endpoint of the trial is planned to be time to vision loss and eye preservation rate for cohort 1 and 2, respectively. The secondary endpoint for the trial is no detriment to Event-Free-Survival (EFS). Discussions with the FDA are ongoing regarding surrogate and composite endpoints to support earlier approval scenarios. IDEAYA is currently finalizing the trial protocol and is targeting to initiate the potential Phase 3 registration-enabling study in the first half of 2025. IDE397 Program in Tumors with MTAP Deletion IDE397 is a potent and selective small molecule inhibitor targeting methionine adenosyltransferase 2 alpha (MAT2A) in patients having solid tumors with methylthioadenosine phosphorylase (MTAP) deletion. IDEAYA continues to evaluate IDE397 in two trials in select monotherapy indications and in high conviction clinical combinations: IDE397-001 (NCT04794699) is a Phase 1/2 treatment study with a monotherapy expansion in MTAP-deletion UC and NSCLC. The estimated U.S. MTAP-deletion annual incidence in UC and NSCLC is approximately 48,000 patients. Encouraging clinical activity at the 30 mg once-a-day Phase 2 monotherapy expansion dose was observed in the Phase 1 clinical trial evaluating IDE397 in heavily pre-treated MTAP-deletion UC and NSCLC patients presented at ENA 2024 in October 2024. The patients evaluated had a median of two to three prior lines-of-therapy, ranging from one to seven. The reported Phase 1 clinical expansion data was based on 27 evaluable MTAP-deletion patients, including 10 UC, nine adenocarcinoma (Adeno) NSCLC, and eight squamous (Sq) NSCLC patients at the expansion dose of 30 mg once-a-day of IDE397 : ~33% Overall Response Rate (ORR). One complete response (CR) and eight partial responses (PRs) by RECIST 1.1 evaluation out of 27 evaluable patients. Nine of nine responses have been confirmed by RECIST 1.1, including four UC patients, of which one was a CR, three squamous NSCLC patients, and two adenocarcinoma NSCLC patients. Two patients confirmed after the data cutoff date. In the earlier reported July 8, 2024, IDE397 webcast program update, five confirmed responses were reported out of 18 evaluable MTAP-deletion UC and NSCLC patients by RECIST 1.1. There were zero non-evaluable patients reported as of the data analysis. Confirmed ORR% by RECIST 1.1 by Solid Tumor Type: MTAP-deletion UC = 40% (4 of 10) confirmed ORR%; MTAP-deletion squamous NSCLC = ~38% (3 of 8) confirmed ORR%; MTAP-deletion adenocarcinoma NSCLC = ~22% (2 of 9) confirmed ORR%. Multiple confirmed partial responses by RECIST 1.1 harbor genetic co-alterations, including MTAP-deletion and KRAS G12D mutation in NSCLC, and MTAP-deletion and FGFR-TACC3 fusion in UC. ~93% Disease Control Rate (DCR). One CR, eight PRs, and 16 stable disease (SD) by RECIST 1.1 evaluation out of 27 evaluable patients. Preliminary durability assessment: 15 of 27 patients still on treatment. Seven of nine RECIST 1.1 responses remain on treatment. Median duration of treatment (DOT) has not been reached and is greater than 6.2 months and median time to response (TTR) is ~2.7 months. The median duration of response and median progression free survival data is still immature. Three UC patients on treatment greater than 250 days, four squamous NSCLC patients on treatment greater than 200 days, and three adenocarcinoma NSCLC patients on treatment greater than 200 days ~81% circulating tumor DNA (ctDNA) Molecular Response Rate (MRR). 17 of 21 patients with 50% or greater ctDNA reduction, and ~33% (7 of 21) with deep 90% or greater ctDNA reduction. All MRs (17 of 17) were rapid occurring at the first ctDNA sample analysis. There were several quality control failures of patient samples that led to unavailability for MR analysis Favorable adverse event (AE) profile. Approximately 18% grade 3 or higher drug-related AEs and no drug-related serious adverse events (SAEs) observed at the IDE397 30mg once-a-day expansion dose. No drug-related AEs leading to discontinuations were observed. We anticipate that the favorable AE profile and dosing convenience of a 30 mg once-a-day tablet has the potential to enable long-term dosing and combination development, including with MTA-cooperative PRMT5 inhibitors and topoisomerase payload antibody drug conjugates (ADCs) Over 35 global clinical trial sites activated in the U.S., Canada, Europe and Asia Pasic to enable rapid enrollment. Targeting development of IDE397 registrational plan in MTAP-deletion solid tumors in 2025. Phase 1/2 trial of IDE397 and AMG 193 in MTAP-Deletion NSCLC (Amgen-sponsored study, NCT05975073) Preclinical poster presentation on the antitumor activity by combinatorial inhibition of MAT2A and PRMT5 in MTAP-deleted tumors presented at ENA 2024. Enrollment is ongoing in the IDE397 and AMG193 Phase 1 dose escalation. Targeting expansion in NSCLC in late 2024 to early 2025. Phase 1 trial of IDE397 and Trodelvy in MTAP-deletion UC (IDEAYA-sponsored, NCT04794699) evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy is ongoing. Reported the first preliminary clinical case study of the IDE397 and Trodelvy combination in MTAP-deletion UC at ENA 2024, including a PR by RECIST 1.1 in a patient case report with a genetic co-alteration of MTAP-deletion and a FGFR3-TACC3 fusion, and rapid and deep first-evaluation molecular responses with ctDNA reduction of greater than 95% observed. The PR reported at ENA 2024 has now confirmed by RECIST 1.1. Targeting to initiate the IDE397 and Trodelvy Phase 1/2 combination expansion in MTAP-deletion UC in Q4 2024. Pursuant to the clinical study collaboration and supply agreement, IDEAYA and Gilead retain the commercial rights to their respective compounds, including with respect to use as a monotherapy or combination agent. IDEAYA is the study sponsor and Gilead will provide the supply of Trodelvy to IDEAYA. IDE397 monotherapy or in combination with Trodelvy has not been approved by any regulatory agency and the efficacy and safety of this combination has not been established. IDE161 Program in Tumors with Homologous Recombination Deficiency IDE161 is a potential first-in-class inhibitor of poly(ADP-ribose) glycohydrolase (PARG), a novel, mechanistically distinct target in the same clinically validated biological pathway as poly(ADP-ribose) polymerase (PARP). IDE161 received two FDA Fast Track designations in platinum-resistant advanced or metastatic ovarian cancer patients having tumors with BRCA1/2 mutations, and in pretreated advanced or metastatic HR+, Her2-, BRACA1/2 mutant breast cancer. IDE161 is currently being evaluated in IDE161-001 (NCT05787587), a Phase 1 trial of IDE161 monotherapy in solid tumors with homologous recombination deficiency (HRD) and in the planned combination with Merck's anti-PD-1 therapy, KEYTRUDA® (pembrolizumab) in microsatellite instability high (MSI-High) and microsatellite stable (MSS) endometrial cancer. Selection of an initial Phase 1/2 IDE161 monotherapy expansion dose in priority solid tumors type(s) is targeted in the fourth quarter of 2024. Separately, a first-patient-in for IDE161 in combination with KEYTRUDA is targeted in the fourth quarter of 2024. KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. In addition, preclinical results on IDE161 and ADC combination rationale were presented as a poster at ENA 2024. GSK-Partnered Programs IDE705 (GSK101) Program in Tumors with HRD IDE705 (GSK101) is a potential first-in-class small molecule inhibitor of Pol Theta Helicase being developed as a combination treatment with niraparib for advanced solid tumors with HRD. The dose escalation portion of the GSK-sponsored Phase 1/2 clinical trial to evaluate GSK101 in combination with niraparib, the GSK small molecule inhibitor of PARP, for patients having solid tumors with BRCA or other HR mutations, or with HRD is currently ongoing. Upon initiation of the Phase 1 dose expansion, IDEAYA will be eligible to receive a $10.0 million milestone payment, with the collaboration having potential further aggregate later-stage development and regulatory milestones of up to $465.0 million. GSK is responsible for all research and development costs for the program. Upon commercialization, IDEAYA will be eligible to receive up to $475 million of commercial milestones, and tiered royalties on global net sales of GSK101 – ranging from high single-digit to sub-teen double-digit percentages, subject to certain customary reductions. IDE275 (GSK959) Program in Tumors with MSI-High IDE275 (GSK959) is a potential first-in-class Werner helicase inhibitor that received FDA IND clearance for a Phase 1 trial in October 2024. The GSK-sponsored Phase 1 trial will evaluate IDE275 (GSK959) in patients having MSI-High tumors, as a monotherapy and in combination with a PD-1 inhibitor. IDEAYA earned a $7 million milestone payment for the IND clearance and has the potential to earn up to an additional $10.0 million upon initiation of Phase 1 clinical dose expansion. In addition, IDEAYA is entitled to receive up to $465.0 million in further later-stage development and regulatory milestones. GSK is responsible for 80% of global research and development costs and IDEAYA is responsible for 20% of such costs. Upon commercialization, IDEAYA will be eligible to receive up to $475 million of commercial milestones, 50% of U.S. net profits and tiered royalties on global non-U.S. net sales of the Werner Helicase inhibitor development candidate (DC) – ranging from high single-digit to sub-teen double-digit percentages, subject to certain customary reductions. B7H3/PTK7 Topo-Payload BsADC Program IDEAYA entered into an option and license agreement for a potential first-in-class B7H3/PTK7 Topo-Payload BsADC program with Biocytogen in July 2024. The agreement grants IDEAYA an option for an exclusive worldwide license from Biocytogen for a potential first-in-class B7H3/PTK7 Topo-Payload BsADC program. B7H3/PTK7 has been found to be co-expressed in multiple solid tumor types, including double-digit percent prevalence in lung, colorectal, and head and neck cancers, among others. Based on preclinical data, the potential first-in-class B7H3/PTK7 Topo-Payload BsADC program has the potential to be developed as a monotherapy agent and used in combination with multiple programs in IDEAYA's pipeline targeting DDR-based therapies, including the PARG inhibitor IDE161. A development candidate nomination for the B7H3/PTK7 Topo-Payload BsADC program is targeted in the fourth quarter of 2024. Next-Generation Precision Medicine Pipeline Programs Early preclinical research programs focused on pharmacological inhibition of several new targets for patients with solid tumors characterized by defined biomarkers based on genetic mutations and/or molecular signatures are ongoing. These programs have the potential for discovery and development of first-in-class or best-in-class therapeutics with multiple wholly owned DC nominations targeted in the fourth quarter of 2024, including in MTAP-deletion solid tumors indications to enable a potential wholly-owned clinical combination with IDE397, and separately a DC nomination in the lysine acetyltransferase 6 (KAT6) pathway. Financial Results As of September 30, 2024, IDEAYA had cash, cash equivalents and marketable securities totaling $1.2 billion. This compared to cash, cash equivalents and marketable securities of $952.7 million as of June 30, 2024. The increase was primarily attributable to $283.8 million in net proceeds from the underwritten public offering of common stock and pre-funded warrants to purchase common stock in July 2024, partially offset by net cash used in operations. Research and development (R&D) expenses for the three months ended September 30, 2024 totaled $57.2 million compared to $54.5 million for the three months ended June 30, 2024. The increase was primarily due to clinical trial and outside services expenses. General and administrative (G&A) expenses for the three months ended September 30, 2024 totaled $9.7 million compared to $10.4 million for the three months ended June 30, 2024. The decrease was primarily due to stock-based compensation expense. The net loss for the three months ended September 30, 2024 was $51.8 million compared to the net loss of $52.8 million for the three months ended June 30, 2024. Total stock compensation expense for the three months ended September 30, 2024 was $9.2 million compared to $9.7 million for the three months ended June 30, 2024. About IDEAYA Biosciences IDEAYA is a precision medicine oncology company committed to the discovery and development of targeted therapeutics for patient populations selected using molecular diagnostics. IDEAYA's approach integrates capabilities in identifying and validating translational biomarkers with drug discovery to select patient populations most likely to benefit from its targeted therapies. IDEAYA is applying its research and drug discovery capabilities to synthetic lethality – which represents an emerging class of precision medicine targets. IDEAYA's updated corporate presentation is available on its website, at its Investor Relations page: . Forward-Looking Statements This press release contains forward-looking statements, including, but not limited to, statements related to (i) the timing, content and venue of clinical program updates, (ii) the timing of expansion of Phase 1/2 trial of IDE397 in combination with Trodelvy® in MTAP-deletion UC, (iii) the timing of expansion of Phase 1 trial of IDE397 in combination with AMG 193 in NSCLC, (iv) the timing of finalization of Phase 3 registration trial protocol and initiation of trial for darovasertib, (v) the timing of a first-patient-in in the IDE161 and KEYTRUDA combination study, (vi) the timing of DC nominations for MTAP-deletion, KAT6 pathway and B7H3/PTK7 Topo-Payload Bispecific-ADC programs, (vii) the timing of designation of next generation development candidates, (viii) the extent to which IDEAYA's existing cash, cash equivalents, and marketable securities will fund its planned operations, (ix) the estimate of patient populations, (x) additional clinical combinations, and (xi) the receipt of development and regulatory milestones. Such forward-looking statements involve substantial risks and uncertainties that could cause IDEAYA's preclinical and clinical development programs, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainties inherent in the drug development process, including IDEAYA's programs' early stage of development, the process of designing and conducting preclinical and clinical trials, the regulatory approval processes, the timing of regulatory filings, the challenges associated with manufacturing drug products, IDEAYA's ability to successfully establish, protect and defend its intellectual property, and other matters that could affect the sufficiency of existing cash to fund operations. IDEAYA undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of IDEAYA in general, see IDEAYA's Annual Report on Form 10-K dated February 20, 2024 and any current and periodic reports filed with the U.S. Securities and Exchange Commission. Investor and Media Contact IDEAYA Biosciences Andres Ruiz Briseno SVP, Head of Finance and Investor Relations [email protected] SOURCE IDEAYA Biosciences, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床2期临床1期临床结果财报快速通道

2024-11-03

·药明康德

“癌症之王”疾病控制率达80%的共价抑制剂；使淀粉样蛋白几乎全部清除的阿尔茨海默病疗法…… | 一周盘点

▎药明康德内容团队编辑本期看点 1. KRAS G12D共价小分子抑制剂RMC-9805用于经治胰腺导管腺癌（PDAC）患者的早期临床结果亮眼，客观缓解率（ORR）达30%，疾病控制率（DCR）为80%。 2. 潜在“first-in-class”合成致死疗法IDE397在一项1期临床试验中展现积极结果，在甲硫腺苷磷酸化酶（MTAP）缺失的尿路上皮癌（UC）和非小细胞肺癌（NSCLC）患者中的DCR为93%。 3. 罗氏（Roche）用于治疗阿尔茨海默病的在研抗体trontinemab在一项1b/2a期临床试验中，使大多数接受较高剂量的患者大脑中的淀粉样蛋白斑块在28周时几乎全部清除。药明康德内容团队整理 RMC-9805：公布1/1b期临床试验数据 Revolution Medicines公司公布了其小分子抑制剂RMC-9805在经治胰腺导管腺癌患者中的初步积极数据。RMC-9805是一款潜在“first-in-class”的口服KRAS G12D突变选择性共价抑制剂。RMC-9805通过和KRAS G12D以及与伴侣蛋白cyclophilin A蛋白之间形成稳定的高亲和力三复合物，能够破坏KRAS G12D（ON）与RAF激酶等下游效应物的相互作用，抑制KRAS G12D（ON）的下游信号传导。在一项多中心、开放标签、剂量递增和剂量扩展的1/1b期研究RMC-9805-001中，截至2024年9月2日的数据，在推荐的2期剂量（每日一次1200 mg和每日两次600 mg）下，至少接受14周RMC-9805治疗患者的ORR达30%（n=12），DCR为80%（n=32）。此外，RMC-9805显示出良好的安全性特征，并在不同剂量水平上普遍展现良好的耐受性。在每日服用1200 mg RMC-9805的患者中（n=99），超过10%的最常见治疗相关不良事件（TRAEs），包括胃肠道相关毒性（如恶心、腹泻和呕吐）以及轻微皮疹，主要为1级且持续时间有限。 ▲RMC-9805展现初步治疗PDAC的效果（图片来源：参考资料[2]） IDE397：公布1期临床试验数据 IDEAYA Biosciences公司公布了其在研疗法IDE397在MTAP缺失的尿路上皮癌和非小细胞肺癌患者中进行的1期临床试验扩展数据。IDE397是一款潜在“first-in-class”甲硫氨酸腺苷转移酶2α（MAT2A）小分子抑制剂。MTAP缺失的肿瘤因为肿瘤代谢途径的变化对它尤其敏感。MTAP缺失患者群体估计占所有实体瘤的15%，包括大约15%的非小细胞肺癌、28%的食道癌、26%的膀胱癌、和10%的胃癌患者。此次公布的数据显示，在27名可评估患者中，1例患者获得完全缓解（CR），8例患者获得部分缓解（PR）。这9例患者的缓解均已通过RECIST 1.1评估确认，包括4例UC患者（其中1例为CR）和5例NSCLC患者。此外，16例患者疾病稳定。在27名可评估患者中，疾病控制率约为93%。 ▲IDE397的1期临床试验扩展数据（图片来源：IDEAYA Biosciences公司官网） Trontinemab：公布1b/2a期临床试验数据罗氏公布了其在研抗体trontinemab用以治疗轻度至中度阿尔茨海默病（AD）患者的1b/2a期试验积极结果。Trontinemab是一款运用罗氏大脑穿梭（brain shuttle）技术的靶向淀粉样蛋白单克隆抗体。它将靶向淀粉样蛋白的单克隆抗体与可以和转铁蛋白受体相结合的蛋白域融合，可以有效协助抗体穿越血脑屏障，在用药3-6个月后可以快速有效地清除大脑中的淀粉样蛋白沉积。此次公布的结果显示，两种较高剂量（1.8 mg/kg与3.6 mg/kg）的trontinemab在第12周时便导致患者大脑淀粉样蛋白水平迅速且显著地降低。在28周时，大多数接受较高剂量的患者大脑中的淀粉样蛋白斑块几乎全部清除。此外，trontinemab不仅降低了淀粉样蛋白水平，还降低了阿尔茨海默病的其他生物标志物的水平，包括脑脊液当中的总tau蛋白与pTau181等。研究人员认为总体上trontinemab具有良好的安全性，并指出观察到的水肿/渗出相关的淀粉样蛋白相关成像异常（ARIA-E）病例数量非常有限。 ▲在28周时，大部分接受高剂量抗体治疗患者的大脑淀粉样蛋白斑块几乎全部清除（图片来源：参考资料[5]） IDE275（GSK959）：IND申请获得FDA许可 IDEAYA Biosciences公司宣布其候选小分子IDE275（GSK959）向美国FDA递交的IND申请已获批准，将启动1期临床试验。IDE275是一种由IDEAYA与GSK合作发现的潜在“first-in-class”的小分子Werner解旋酶（WRN）抑制剂。在临床前研究中，IDE275在微卫星不稳定性高（MSI-H）生物标志物背景下展示了强烈的选择性合成致死效应，包括在源自结直肠、子宫内膜和胃癌的MSI-H细胞异体移植模型（CDX）和患者异体移植模型（PDX）中，IDE275单药治疗诱导了肿瘤消退。预计IDE275的1期临床试验将于2024年第四季度启动。GSK是IND申请的赞助方，并计划在1期临床试验中将IDE275作为单药以及与PD-1抑制剂联用治疗MSI-H肿瘤患者。 NM32：启动1期临床试验 Numab Therapeutics宣布启动其靶向受体酪氨酸激酶样孤儿受体1（ROR1）和T细胞受体相关抗原CD3的新一代三特异性免疫肿瘤治疗药物NM32的1期临床试验。NM32是潜在“first-in-class”ROR1靶向半衰期增强型T细胞接合器。ROR1是一种肿瘤相关抗原，在实体瘤和血液恶性肿瘤中广泛表达。NM32的分子量较小，与较大的免疫球蛋白G分子（目前CD3接合器的标准形式）相比，能够更有效地渗透肿瘤。NM32的第三个结合部分以血清白蛋白为靶点，延长了半衰期，方便实现两周一次的给药频率。 CNP-106：1b/2a期临床试验完成首例患者给药 COUR Pharmaceuticals公司宣布，其用于治疗全身性重症肌无力（gMG）患者的候选疗法CNP-106的1b/2a期概念验证临床试验已完成首例患者给药。CNP-106是一种使用可生物降解的纳米颗粒封装乙酰胆碱受体（AChR）的产品。gMG主要由体内产生的抗AChR抗体引起。这些抗体会阻断或破坏控制肌肉收缩的重要神经递质乙酰胆碱的神经信号传递给AChR，导致肌肉无法正常收缩。随着病情的发展，gMG可能会引发更严重的健康问题，比如肌无力危象、胸腺肿瘤、甲状腺功能异常以及其他自身免疫性疾病。CNP-106旨在下调或抑制针对AChR的T细胞和抗体水平，从而帮助改善患者的肌肉功能。 BBO-10203：1期临床试验完成首例患者给药 BridgeBio Oncology Therapeutics公司宣布，其用于治疗晚期实体瘤的候选小分子BBO-10203的1期临床试验已完成首例患者给药。BBO-10203是一种潜在“first-in-class”、口服生物可利用的RAS：PI3Kα断路器（breaker）。BBO-10203不直接抑制PI3Kα的催化活性，而是通过选择性地共价结合到PI3Kα的RAS结合域（RBD），阻断RAS和PI3Kα之间的相互作用，从而抑制RAS驱动肿瘤中的PI3Kα-AKT信号传导。这种选择性抑制不受限于PI3Kα和RAS的突变状态。在临床前模型中，即使在个位数纳摩尔浓度下也能完全抑制RAS驱动的pAKT信号。此外，在接受BBO-10203治疗的临床前动物模型中未观察到高血糖现象。BBO-10203有望为患有RAS和PI3Kα驱动的恶性肿瘤患者提供具有临床意义的治疗选择。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料（可上下滑动查看） [1] Revolution Medicines Presents Initial Data from RMC-9805 Monotherapy Study in Patients with Advanced Pancreatic Ductal Adenocarcinoma. Retrieved October 25, 2024 from https://ir.revmed.com/news-releases/news-release-details/revolution-medicines-presents-initial-data-rmc-9805-monotherapy [2] Pancreatic Cancer Update. Retrieved October 25, 2024 from https://ir.revmed.com/static-files/87b6dcb4-94c9-4e79-9d8c-d21f2bb7aaaf [3] IDEAYA Announces Positive Interim Phase 1 Expansion Data of IDE397 in MTAP-Deletion Urothelial and Lung Cancer as Late-Breaker Oral Presentation at EORTC-NCI-AACR 2024. Retrieved October 25, 2024, from https://www.prnewswire.com/news-releases/ideaya-announces-positive-interim-phase-1-expansion-data-of-ide397-in-mtap-deletion-urothelial-and-lung-cancer-as-late-breaker-oral-presentation-at-eortc-nci-aacr-2024-302286733.html [4] IDEAYA Biosciences Announces IND-Clearance for Werner Helicase Development Candidate IDE275 (GSK959) for a Phase 1 Study in MSI-High Solid Tumors. Retrieved October 25, 2024, from https://www.prnewswire.com/news-releases/ideaya-biosciences-announces-ind-clearance-for-werner-helicase-development-candidate-ide275-gsk959-for-a-phase-1-study-in-msi-high-solid-tumors-302287911.html [5] LATEST INTERIM RESULTS FROM THE BRAINSHUTTLE™ AD STUDY, A PHASE IB/IIA STUDY OF TRONTINEMAB IN PEOPLE WITH ALZHEIMER’S DISEASE. Retrieved October 30, 2024 from https://medically.roche.com/global/en/neuroscience/ctad-2024/medical-material/CTAD-2024-presentation-kulic-latest-interim-results-from-brainshuttle-ad-study-pdf.html [6] Numab Therapeutics Announces Initiation of Phase 1 Clinical Study of NM32 Program in Patients with Solid Tumors. Retrieved November 1, 2024, from https://www.globenewswire.com/news-release/2024/10/30/2971606/0/en/Numab-Therapeutics-Announces-Initiation-of-Phase-1-Clinical-Study-of-NM32-Program-in-Patients-with-Solid-Tumors.html [7] COUR Pharmaceuticals Doses First Patient in Phase 1b/2a Clinical Trial Evaluating CNP-106 in Generalized Myasthenia Gravis. Retrieved November 1, 2024, from https://www.globenewswire.com/news-release/2024/10/30/2971607/0/en/COUR-Pharmaceuticals-Doses-First-Patient-in-Phase-1b-2a-Clinical-Trial-Evaluating-CNP-106-in-Generalized-Myasthenia-Gravis.html [8] BridgeBio Oncology Therapeutics (BBOT) Announces First Patient Dosed with First-in-Class BBO-10203, a RAS:PI3Kα Breaker, in the Phase 1 BREAKER-101 Trial for Advanced Solid Tumors. Retrieved November 1, 2024, from https://www.businesswire.com/news/home/20241030409443/en/BridgeBio-Oncology-Therapeutics-BBOT-Announces-First-Patient-Dosed-with-First-in-Class-BBO-10203-a-RASPI3K%CE%B1-Breaker-in-the-Phase-1-BREAKER-101-Trial-for-Advanced-Solid-Tumors/ [9] Thetis Pharmaceuticals Announces Positive Initial Results From Phase 1a Study of TP-317 in Healthy Subjects. Retrieved November 1, 2024, from https://www.businesswire.com/news/home/20241031890209/en/Thetis-Pharmaceuticals-Announces-Positive-Initial-Results-From-Phase-1a-Study-of-TP-317-in-Healthy-Subjects [10] AiCuris Initiates First-in-Human Phase 1 Trial with Antiviral Agent AIC468 to Address BK Virus Infections in Kidney Transplant Recipients. Retrieved November 1, 2024, from https://www.aicuris.com/index.php/fuseaction/download/lrn_file/20241031_aicuris-pr_aic468-fpi_final.pdf [11] Disc Medicine Presents Positive Data from SAD Cohorts of a Phase 1b Trial in Patients with Chronic Kidney Disease (CKD) and Anemia at the 2024 American Society of Nephrology (ASN) Kidney Week. Retrieved November 1, 2024, from https://www.globenewswire.com/news-release/2024/10/25/2969602/0/en/Disc-Medicine-Presents-Positive-Data-from-SAD-Cohorts-of-a-Phase-1b-Trial-in-Patients-with-Chronic-Kidney-Disease-CKD-and-Anemia-at-the-2024-American-Society-of-Nephrology-ASN-Kidn.html [12] Jubilant Therapeutics Inc. announces First Patient Dosing in Global Clinical Trials for JBI-802, a CoREST Inhibitor and JBI-778, a PRMT5 Inhibitor. Retrieved November 1, 2024, from https://www.prnewswire.com/news-releases/jubilant-therapeutics-inc-announces-first-patient-dosing-in-global-clinical-trials-for-jbi-802-a-corest-inhibitor-and-jbi-778-a-prmt5-inhibitor-302287204.html [13] Maze Therapeutics Reports Positive First-in-Human Data from Phase 1 Healthy Volunteer Clinical Trial Evaluating MZE829 as a Potential Treatment for APOL1 Kidney Disease (AKD). Retrieved November 1, 2024, from https://mazetx.com/maze-therapeutics-reports-positive-first-in-human-data-from-phase-1-healthy-volunteer-clinical-trial-evaluating-mze829-as-a-potential-treatment-for-apol1-kidney-disease-akd/ [14] Kymera Therapeutics Announces Dosing of First Participant in Phase 1 Clinical Trial of KT-621, a First-in-Class Oral STAT6 Degrader, for the Treatment of TH2 Immuno-Inflammatory Diseases. Retrieved November 1, 2024, from https://investors.kymeratx.com/news-releases/news-release-details/kymera-therapeutics-announces-dosing-first-participant-phase-1 [15] NAYA Biosciences Announces Initiation of Phase 1/2a Clinical Trial for its GPC3-targeted NK Engager Bispecific Antibody in Patients with Hepatocellular Carcinoma. Retrieved November 1, 2024, from https://www.globenewswire.com/news-release/2024/10/24/2968749/0/en/NAYA-Biosciences-Announces-Initiation-of-Phase-1-2a-Clinical-Trial-for-its-GPC3-targeted-NK-Engager-Bispecific-Antibody-in-Patients-with-Hepatocellular-Carcinoma.html [16] Praxis Bioresearch Obtains FDA Clearance On the IND Application for Its Lead Candidate PRX-P4-003 In Alzheimer’s Disease Apathy. Retrieved November 1, 2024, from https://www.globenewswire.com/news-release/2024/10/29/2970716/0/en/Praxis-Bioresearch-Obtains-FDA-Clearance-On-the-IND-Application-for-Its-Lead-Candidate-PRX-P4-003-In-Alzheimer-s-Disease-Apathy.html [17] Nektar Announces Publication in Nature Communications of Results from Phase 1b Studies of Rezpegaldesleukin in Two Inflammatory Skin Diseases. Retrieved November 1, 2024, from https://www.prnewswire.com/news-releases/nektar-announces-publication-in-nature-communications-of-results-from-phase-1b-studies-of-rezpegaldesleukin-in-two-inflammatory-skin-diseases-302289469.html [18] Aro Biotherapeutics Announces Start of First in Human Study with ABX1100, a Novel First in Class Centyrin-siRNA Conjugate in Development for Pompe Disease. Retrieved November 1, 2024, from https://www.arobiotx.com/aro-bio-announces-start-of-first-in-human-study-with-abx1100 [19] Bitterroot Bio Completes Enrollment in Phase 1 First-in-Human Study of BRB-002 in Healthy Volunteers. Retrieved November 1, 2024, from https://brbio.com/bitterroot-bio-completes-enrollment-in-phase-1-first-in-human-study-of-brb-002-in-healthy-volunteers/ [20] ProMIS Neurosciences Presents Positive Data from PMN310 Phase1a Clinical Trial at the 17th Clinical Trials on Alzheimer’s Disease Conference. Retrieved November 1, 2024, from https://www.globenewswire.com/news-release/2024/10/30/2971622/0/en/ProMIS-Neurosciences-Presents-Positive-Data-from-PMN310-Phase1a-Clinical-Trial-at-the-17th-Clinical-Trials-on-Alzheimer-s-Disease-Conference.html [21] Alterome Therapeutics Announces First Patient Dosed in Phase 1 Study of ALTA2618 in AKT1 E17K-mutant solid tumors (AKTive-001). Retrieved November 1, 2024, from https://www.businesswire.com/news/home/20241030626999/en/Alterome-Therapeutics-Announces-First-Patient-Dosed-in-Phase-1-Study-of-ALTA2618-in-AKT1-E17K-mutant-solid-tumors-AKTive-001 [22] Ajax Therapeutics Announces First Patient Dosed in Phase 1 Clinical Trial Evaluating AJ1-11095, a First-in-Class Type II JAK2 inhibitor, for the Treatment of Myelofibrosis. Retrieved November 1, 2024, from https://www.ajaxtherapeutics.com/ajax-therapeutics/ajax-therapeutics-announces-first-patient-dosed-in-phase-1-clinical-trial-evaluating-aj1-11095-a-first-in-class-type-ii-jak2-inhibitor-for-the-treatment-of-myelofibrosis/ [23] KITHER BIOTECH ANNOUNCES PHASE 1 CLINICAL STUDY OF KIT2014, A NOVEL INHALED PEPTIDE THERAPY FOR CYSTIC FIBROSIS. Retrieved November 1, 2024, from https://www.prnewswire.com/news-releases/kither-biotech-announces-phase-1-clinical-study-of-kit2014-a-novel-inhaled-peptide-therapy-for-cystic-fibrosis-302290900.html [24] Medera Announces Completion of Cohort A and Initiation of Dosing in Cohort B of MUSIC-HFpEF, a Phase 1/2a Clinical Trial Evaluating First-In-Human Gene Therapy SRD-002 for Heart Failure with Preserved Ejection Fraction. Retrieved November 1, 2024, from https://www.prnewswire.com/news-releases/medera-announces-completion-of-cohort-a-and-initiation-of-dosing-in-cohort-b-of-music-hfpef-a-phase-12a-clinical-trial-evaluating-first-in-human-gene-therapy-srd-002-for-heart-failure-with-preserved-ejection-fraction-302285414.html [25] Lexeo Therapeutics Announces Positive Interim Data for LX1001, First-Ever Gene Therapy to Impact the Underlying Genetic Cause of APOE4-Associated Alzheimer’s Disease, at the Clinical Trials on Alzheimer’s Disease (CTAD) Conference. Retrieved November 1, 2024, from https://ir.lexeotx.com/news-releases/news-release-details/lexeo-therapeutics-announces-positive-interim-data-lx1001-first [26] NKGen Biotech Presents Phase 1/2a Troculeucel Data in Alzheimer’s Disease at the 17th Annual Clinical Trials on Alzheimer’s Disease (CTAD) Conference. Retrieved November 1, 2024, from https://www.globenewswire.com/news-release/2024/10/29/2970775/0/en/NKGen-Biotech-Presents-Phase-1-2a-Troculeucel-Data-in-Alzheimer-s-Disease-at-the-17th-Annual-Clinical-Trials-on-Alzheimer-s-Disease-CTAD-Conference.html [27] Regeneration Biomedical Presents Data on First Cohort from an Ongoing Phase I Clinical Trial of Stem Cell Therapy Delivered Directly into the Brains of Patients with Alzheimer’s Disease. Retrieved November 1, 2024, from https://www.globenewswire.com/news-release/2024/10/29/2970530/0/en/Regeneration-Biomedical-Presents-Data-on-First-Cohort-from-an-Ongoing-Phase-I-Clinical-Trial-of-Stem-Cell-Therapy-Delivered-Directly-into-the-Brains-of-Patients-with-Alzheimer-s-Di.html [28] AIMDBIO，TOP1 'FGFR3 ADC' “美国 1 期 IND 批准”. Retrieved November 1, 2024, from http://www.biospectator.com/view/news_view.php?varAtcId=23469 [29] Bexion Pharmaceuticals, Inc. Announces Publication of Phase 1 Data for BXQ-350 in Advanced Solid Tumors. Retrieved November 1, 2024, from https://www.prnewswire.com/news-releases/bexion-pharmaceuticals-inc-announces-publication-of-phase-1-data-for-bxq-350-in-advanced-solid-tumors-302293463.html [30] JCR Pharmaceuticals Initiates First Dosing in Phase I Clinical Trial of JR-441 for Mucopolysaccharidosis Type IIIA. Retrieved November 1, 2024, from https://www.businesswire.com/news/home/20241031198164/en/JCR-Pharmaceuticals-Initiates-First-Dosing-in-Phase-I-Clinical-Trial-of-JR-441-for-Mucopolysaccharidosis-Type-IIIA 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

临床2期临床1期

2024-10-30

·PRNewswire

AMGEN REPORTS THIRD QUARTER 2024 FINANCIAL RESULTS

THOUSAND OAKS, Calif., Oct. 30, 2024 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced financial results for the third quarter of 2024. "Strong growth in sales and earnings this quarter reflects the momentum we're building throughout our business. We continue to invest heavily in our rapidly advancing pipeline, with a focus on delivering innovative therapies across our core therapeutic areas," said Robert A. Bradway, chairman and chief executive officer. Key results include: For the third quarter, total revenues increased 23% to $8.5 billion in comparison to the third quarter of 2023. Product sales grew 24%, driven by 29% volume growth, partially offset by 2% lower net selling price. Excluding sales from our Horizon Therapeutics (Horizon) acquisition, product sales grew 8%, driven by volume growth of 12%. Ten products delivered at least double-digit sales growth in the third quarter, including Repatha® (evolocumab), TEZSPIRE® (tezepelumab-ekko), BLINCYTO® (blinatumomab), EVENITY® (romosozumab-aqqg), and TAVNEOS® (avacopan). Our performance included $1.2 billion of sales from our rare disease products, driven by several first-in-class, early-in-lifecycle medicines, including TEPEZZA® (teprotumumab-trbw), KRYSTEXXA® (pegloticase), UPLIZNA® (inebilizumab-cdon), and TAVNEOS® (avacopan). GAAP earnings per share (EPS) increased 62% from $3.22 to $5.22, driven by mark-to-market gains on our BeiGene, Ltd. (BeiGene) equity investment and higher revenues, partially offset by higher operating expenses, including amortization expense from Horizon-acquired assets and incremental expenses from Horizon. GAAP operating income remained relatively unchanged at $2.0 billion, and GAAP operating margin decreased 5.8 percentage points to 25.1%. Non-GAAP EPS increased 13% from $4.96 to $5.58, driven by higher revenues, partially offset by higher operating expenses, including incremental expenses from Horizon, and interest expense. Non-GAAP operating income increased from $3.4 billion to $4.0 billion, and non-GAAP operating margin decreased 2.4 percentage points to 49.6%. The Company generated $3.3 billion of free cash flow in the third quarter of 2024 versus $2.5 billion in the third quarter of 2023, driven by business performance and timing of working capital items, partially offset by lower interest income. References in this release to "non-GAAP" measures, measures presented "on a non-GAAP basis" and "free cash flow" (computed by subtracting capital expenditures from operating cash flow) refer to non-GAAP financial measures. Adjustments to the most directly comparable GAAP financial measures and other items are presented on the attached reconciliations. Refer to Non-GAAP Financial Measures below for further discussion. Product Sales Performance General Medicine Repatha® (evolocumab) sales increased 40% year-over-year to $567 million in the third quarter, driven by 41% volume growth and 8% favorable changes to estimated sales deductions, partially offset by 10% lower net selling price. EVENITY® (romosozumab-aqqg) sales increased 30% year-over-year to $399 million in the third quarter, driven by volume growth. Prolia® (denosumab) sales increased 6% year-over-year to $1.0 billion in the third quarter, driven by 9% volume growth, partially offset by lower inventory levels. Oncology BLINCYTO® (blinatumomab) sales increased 49% year-over-year to $327 million in the third quarter, primarily driven by volume growth. Vectibix® (panitumumab) sales increased 12% year-over-year to $282 million in the third quarter, primarily driven by volume growth. KYPROLIS® (carfilzomib) sales increased 8% year-over-year to $378 million in the third quarter, primarily driven by volume growth outside the U.S. LUMAKRAS®/LUMYKRAS™ (sotorasib) sales increased 88% year-over-year to $98 million in the third quarter, driven by volume growth and favorable changes to estimated sales deductions. XGEVA® (denosumab) sales increased 4% year-over-year to $541 million in the third quarter, driven by higher net selling price. Nplate® (romiplostim) sales increased 9% year-over-year to $456 million in the third quarter. U.S. government orders were $128 million in Q3'24 compared to $142 million in Q3'23. Excluding these U.S. government orders, Nplate sales grew 18% year-over-year in the third quarter, driven by 14% volume growth and higher net selling price. IMDELLTRA™ (tarlatamab-dlle) generated $36 million of sales in the third quarter. Sales increased 200% quarter-over-quarter, driven by volume growth. IMDELLTRA is the first and only FDA-approved bispecific T-cell engager (BiTE ®) therapy for the treatment of extensive-stage small cell lung cancer (ES-SCLC). MVASI® (bevacizumab-awwb) sales decreased 8% year-over-year to $195 million in the third quarter. Going forward, we expect continued sales erosion driven by competition. Inflammation TEZSPIRE® (tezepelumab-ekko) sales increased 67% year-over-year to $269 million in the third quarter, driven by volume growth. Otezla® (apremilast) sales decreased 1% year-over-year to $564 million in the third quarter, primarily driven by 7% lower net selling price, partially offset by 5% volume growth. Enbrel® (etanercept) sales decreased 20% year-over-year to $825 million in the third quarter, primarily driven by 13% unfavorable changes to estimated sales deductions and 12% lower net selling price. Going forward, we expect continued declining net selling price and relatively flat volumes. AMJEVITA®/AMGEVITA™ (adalimumab) sales increased 9% year-over-year to $166 million in the third quarter. Rare Disease Except for TAVNEOS®, the products listed below were added through the acquisition of Horizon on Oct. 6, 2023. TEPEZZA® (teprotumumab-trbw) generated $488 million of sales in the third quarter. TEPEZZA is the first and only FDA-approved treatment for thyroid eye disease (TED). KRYSTEXXA® (pegloticase) generated $310 million of sales in the third quarter. KRYSTEXXA is the first and only FDA-approved treatment for chronic refractory gout. UPLIZNA® (inebilizumab-cdon) generated $106 million of sales in the third quarter. UPLIZNA is used to treat adults with neuromyelitis optica spectrum disorder. TAVNEOS® (avacopan) generated $80 million of sales in the third quarter. Sales increased 116% year-over-year, primarily driven by volume growth. TAVNEOS is a first-in-class treatment for severe active anti-neutrophil cytoplasmic autoantibody-associated vasculitis (ANCA-associated vasculitis). Ultra-Rare products, which consist of RAVICTI® (glycerol phenylbutyrate), PROCYSBI® (cysteamine bitartrate), ACTIMMUNE® (interferon gamma-1b), QUINSAIR® (levofloxacin) and BUPHENYL® (sodium phenylbutyrate), generated $188 million of sales in the third quarter. Established Products Our established products, which consist of EPOGEN® (epoetin alfa), Aranesp® (darbepoetin alfa), Parsabiv® (etelcalcetide) and Neulasta® (pegfilgrastim), generated $550 million of sales. Sales decreased 7% year-over-year for the third quarter, driven by volume declines. In the aggregate, we expect the year-over-year volume declines for this portfolio of products to continue. Product Sales Detail by Product and Geographic Region Operating Expense, Operating Margin and Tax Rate Analysis On a GAAP basis for the third quarter: Total Operating Expenses increased 32% year-over-year. Cost of Sales as a percentage of product sales increased 13.0 percentage points driven by higher amortization expense from Horizon acquisition-related assets and, to a lesser extent, higher royalties and profit share. Research & Development (R&D) expenses increased 34% driven by higher spend in later-stage clinical programs, marketed product support, and research and early pipeline, including Horizon-acquired programs. Selling, General & Administrative (SG&A) expenses increased 20% primarily driven by commercial expenses related to Horizon-acquired products. Other operating expenses consisted primarily of an impairment charge associated with an IPR&D asset and changes in the fair values of contingent consideration liabilities, both related to our Teneobio, Inc. acquisition from 2021. Operating Margin as a percentage of product sales decreased 5.8 percentage points year-over-year to 25.1%. Tax Rate decreased 2.4 percentage points year-over-year primarily due to the change in earnings mix as a result of the inclusion of the Horizon business, partially offset by quarter-to-date 2024 unrealized gains on our strategic equity investments, primarily BeiGene. On a non-GAAP basis for the third quarter: Total Operating Expenses increased 27% year-over-year. Cost of Sales as a percentage of product sales increased 0.4 percentage points driven by higher royalties and profit share, partially offset by lower manufacturing costs and changes in sales mix. R&D expenses increased 35% driven by higher spend in later-stage clinical programs, marketed product support, and research and early pipeline, including Horizon-acquired programs. SG&A expenses increased 21%, primarily driven by commercial expenses related to Horizon-acquired products. Operating Margin as a percentage of product sales decreased 2.4 percentage points year-over-year to 49.6%. Tax Rate decreased 2.7 percentage points year-over-year primarily due to the change in earnings mix as a result of the inclusion of the Horizon business. Cash Flow and Balance Sheet The Company generated $3.3 billion of free cash flow in the third quarter of 2024 versus $2.5 billion in the third quarter of 2023, driven by business performance and timing of working capital items, partially offset by lower interest income. The Company's third quarter 2024 dividend of $2.25 per share was declared on August 2, 2024, and was paid on September 6, 2024, to all stockholders of record as of August 16, 2024, representing a 6% increase from this same period in 2023. During the third quarter, the Company reduced principal debt outstanding by $2.5 billion. Year-to-date, the Company has reduced principal debt outstanding by $4.5 billion. Cash and investments totaled $9.0 billion and debt outstanding totaled $60.4 billion as of September 30, 2024. 2024 Guidance For the full year 2024, the Company now expects: Total revenues in the range of $33.0 billion to $33.8 billion. On a GAAP basis, EPS in the range of $8.71 to $9.56, and a tax rate in the range of 9.0% to 10.5%. On a non-GAAP basis, EPS in the range of $19.20 to $20.00, and a tax rate in the range of 14.0% to 15.0%. Capital expenditures to be approximately $1.3 billion. Share repurchases not to exceed $500 million. Third Quarter Product and Pipeline Update The Company provided the following updates on selected product and pipeline programs: General Medicine MariTide (maridebart cafraglutide, AMG 133) MariTide is a multispecific molecule that inhibits the gastric inhibitory polypeptide receptor (GIPR) and activates the glucagon like peptide 1 (GLP-1) receptor. A Phase 2 study of MariTide is ongoing in adults who are living with overweight or obesity, with or without Type 2 diabetes mellitus. Topline data are anticipated in late 2024. Planning for a broad Phase 3 program across multiple indications remains on track. A Phase 2 study investigating MariTide was initiated for the treatment of Type 2 diabetes in patients with and without obesity. AMG 513 A Phase 1 study of AMG 513 was initiated and is enrolling patients living with obesity. Olpasiran (AMG 890) Olpasiran is a potentially best-in-class small interfering ribonucleic acid (siRNA) molecule that reduces lipoprotein(a) (Lp(a)) synthesis in the liver. The Ocean(a)-Outcomes trial, a Phase 3 cardiovascular outcomes study, is ongoing in patients with atherosclerotic cardiovascular disease and elevated Lp(a). Repatha EVOLVE-MI, a Phase 4 study of Repatha administered within 10 days of an acute myocardial infarction to reduce the risk of cardiovascular (CV) events, is ongoing. VESALIUS-CV, a Phase 3 CV outcomes study of Repatha, is ongoing in patients at high CV risk without prior myocardial infarction or stroke. In September data were presented from: a sub-analysis of the FOURIER trial demonstrating that patients with obesity (BMI >35) are at an increased risk of CV events. Repatha treatment of patients with obesity resulted in a reduction in the composite endpoint of CV death, myocardial infarction, stroke, hospitalization for unstable angina or coronary revascularization at 3 years [HR 0.71 (0.59-0.86), and Absolute Risk Reduction = 5.65%] the SLICE-CEA study, the first randomized trial of Repatha in patients with asymptomatic severe high-risk carotid artery stenosis. The study demonstrated that 6 months of Repatha treatment led to significant reductions in lipid rich necrotic core (LRNC) volume (p=0.017) and its components, intraplaque hemorrhage (IPH) (p=0.037) and lipid volume (p=0.023) in the carotid vessels, as assessed by MRI. Oncology IMDELLTRA IMDELLTRA is a first-in-class delta-like ligand 3 (DLL3) targeting BiTE® (bispecific T-cell engager) molecule. The Company is advancing a comprehensive global clinical development program across extensive-stage and limited-stage small cell lung cancer (SCLC): DeLLphi-304, a Phase 3 study comparing IMDELLTRA with standard of care chemotherapy in second-line extensive-stage small cell lung cancer (ES-SCLC), is ongoing. DeLLphi-305, a Phase 3 study comparing IMDELLTRA and durvalumab with durvalumab alone, is enrolling patients with first-line ES-SCLC. DeLLphi-306, a Phase 3 study comparing IMDELLTRA with placebo following concurrent chemoradiation therapy, is enrolling patients with limited-stage SCLC. DeLLphi-308, a Phase 1b study evaluating subcutaneous tarlatamab, was initiated in patients with second line or later ES-SCLC. DeLLphi-303, a Phase 1b study of IMDELLTRA in combination with a programmed cell death protein ligand-1 (PD-L1) inhibitor +/- carboplatin and etoposide, is ongoing in patients with first-line ES-SCLC. DeLLphi-302, a Phase 1b study of IMDELLTRA in combination with AMG 404 in patients with second-line or later SCLC, is complete. AMG 404 is an anti-programmed cell death protein 1 (PD1) monoclonal antibody. DeLLpro-300, a Phase 1b study of IMDELLTRA in patients with previously treated de novo or treatment-emergent neuroendocrine prostate cancer, is complete. In September, data were presented from: DeLLphi-301, a Phase 2 study of IMDELLTRA where extended follow-up data demonstrated sustained anti-cancer activity and a manageable safety profile in patients with ES-SCLC previously treated with platinum-based chemotherapy. Among 100 patients treated with the 10 mg dose level, the median duration of response was 9.7 months (95% CI, 6.9‒NE) and the median overall survival was 15.2 months. No new safety concerns were identified. DeLLphi-303, a Phase 1b study of IMDELLTRA combined with a PD-L1 inhibitor as first-line ES-SCLC maintenance therapy. With a median follow-up of 10.0 months (range 1.4 - 20.4), IMDELLTRA in combination with a PD-L1 inhibitor, demonstrated a manageable safety profile with durable disease control [median duration of disease control: 9.3 months (95% CI: 5.6–not estimable)] and notable survival outcomes [median PFS 5.6 months (95% CI: 3.6–9.0), 9-month Kaplan-Meier estimate for OS of 88.9%]. BLINCYTO Golden Gate, a Phase 3 study of BLINCYTO alternating with low-intensity chemotherapy, continues to enroll older adult patients with newly diagnosed Philadelphia chromosome (Ph)-negative B-cell precursor acute lymphoblastic leukemia (B-ALL). A Phase 1/2 study of subcutaneous blinatumomab has completed enrollment in the dose-expansion and optimization phase in adult patients with relapsed or refractory Ph-negative B-ALL. The Company is planning to advance blinatumomab subcutaneous administration to a potentially registration-enabling Phase 2 portion of this study with initiation in H2 2025. Xaluritamig (AMG 509) Xaluritamig is a first-in-class bispecific T-cell engager targeting six-transmembrane epithelial antigen of prostate 1 (STEAP1). The Company will initiate a Phase 3 study in post-taxane metastatic castrate resistant prostate cancer (mCRPC) in fourth quarter of 2024. A Phase 1 monotherapy dose-expansion study of xaluritamig is ongoing in patients with mCRPC and has completed enrollment of patients in a reduced monitoring after treatment administration cohort. A fully outpatient treatment cohort continues to enroll patients to further improve administration convenience. A Phase 1 combination of xaluritamig with enzalutamide or abiraterone continues to enroll patients with mCRPC in dose-escalation and dose-expansion respectively. A Phase 1b study evaluating neoadjuvant xaluritamig therapy prior to radical prostatectomy was initiated in patients with newly diagnosed localized intermediate or high–risk prostate cancer. A Phase 1b study was initiated and is now enrolling patients to evaluate xaluritamig in patients with high-risk nonmetastatic hormone-sensitive prostate cancer after definitive therapy. In September results were presented from: a Phase 1 dose exploration cohort evaluating xaluritamig monotherapy in patients with mCRPC where with a median follow-up of 27.9 months, the median OS was 17.7 months across all cohorts. An encouraging PSA90 rate (45.1%) was also observed in high-dose cohorts, and presence of PSA90 response was associated with survival (p = 0.0044), potentially serving as an early indicator for benefit in these patients. a Phase 1 dose-expansion cohort evaluating xaluritamig monotherapy using multiple dosing regimens in patients with mCRPC demonstrated that the 1.5 mg Q2W target dosing regimen is the most favorable efficacy and safety profile and will be the recommended Phase 3 dose and schedule. AMG 193 AMG 193 is a first-in-class small molecule methylthioadenosine (MTA)-cooperative protein arginine methyltransferase 5 (PRMT5) inhibitor. A Phase 1/1b/2 study of AMG 193 continues to enroll patients with advanced methylthioadenosine phosphorylase (MTAP)-null solid tumors in the dose-expansion portion of the study. A Phase 1b study of AMG 193 alone or in combination with other therapies is enrolling patients with advanced MTAP-null thoracic malignancies. A Phase 1b study of AMG 193 in combination with other therapies in advanced MTAP-null gastrointestinal, biliary tract, and pancreatic cancers is enrolling patients. A Phase 1/2 study of AMG 193 in combination with IDE397, an investigational methionine adenosyltransferase 2A (MAT2A) inhibitor, continues to enroll patients with advanced MTAP-null solid tumors. A Phase 2 study evaluating the efficacy, safety, tolerability, and pharmacokinetics of AMG 193 was initiated in patients with MTAP-null previously treated advanced non-small cell lung cancer (NSCLC). In September, data were presented from a Phase 1 dose-escalation and initial dose-expansion study of AMG 193 in patients with MTAP-null solid tumors. The data demonstrated monotherapy activity and an acceptable safety profile. These data open opportunities to explore both monotherapy and combination therapy development strategies. Bemarituzumab Bemarituzumab is a first-in-class fibroblast growth factor receptor 2b (FGFR2b) targeting monoclonal antibody. FORTITUDE-101, a Phase 3 study of bemarituzumab plus chemotherapy, is ongoing in patients with first-line gastric cancer. FORTITUDE-102, a Phase 1b/3 study of bemarituzumab plus chemotherapy and nivolumab in patients with first-line gastric cancer, has completed enrollment of the Phase 3 portion of the study. FORTITUDE-103, a Phase 1b/2 study of bemarituzumab plus oral chemotherapy regimens with or without nivolumab, continues to enroll patients in first-line gastric cancer. FORTITUDE-301, a Phase 1b/2 basket study of bemarituzumab monotherapy, is ongoing in patients with solid tumors with FGFR2b overexpression. Nplate The primary analysis of a Phase 3 study of Nplate as supportive care in chemotherapy-induced thrombocytopenia in gastrointestinal malignancies is complete. The Company continues to follow patients through a planned final analysis in H1 2025. Data presentation at a medical congress is anticipated in mid-2025. LUMAKRAS/LUMYKRAS CodeBreaK 202, a Phase 3 study of LUMAKRAS plus chemotherapy vs. pembrolizumab plus chemotherapy, is enrolling patients with first-line KRAS G12C–mutated and programmed PD-L1 negative advanced NSCLC. Regulatory review by the European Medicines Agency (EMA) of the CodeBreaK 200 Phase 3 study of adults with previously treated locally advanced or metastatic KRAS G12C–mutated NSCLC along with data from the Phase 2 dose-comparison substudy is ongoing. The U.S Food and Drug Administration (FDA) extended the Prescription Drug User Fee Act (PDUFA) date for the Phase 3 CodeBreaK 300 study of LUMAKRAS plus Vectibix vs. investigator's choice of therapy in KRAS G12C–mutated metastatic colorectal cancer (CRC) from October 17, 2024, to January 17, 2025, to allow time for review of recently submitted supplemental data. CodeBreaK 301, a Phase 3 study of LUMAKRAS in combination with Vectibix and FOLFIRI, is enrolling patients with first-line KRAS G12C–mutated CRC. Inflammation TEZSPIRE The Company is planning to initiate Phase 3 studies in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) and a BEC ≥ 150 cells/µl or greater. Study initiation is anticipated in H1 2025. A Phase 3 study of TEZSPIRE is ongoing in patients with chronic rhinosinusitis with nasal polyps. Data readout is anticipated in H2 2024. A Phase 3 study of TEZSPIRE continues to enroll patients with eosinophilic esophagitis. In severe asthma, the WAYFINDER Phase 3b study and the PASSAGE Phase 4 real-world effectiveness study are fully enrolled. The SUNRISE Phase 3 study continues to enroll patients. Rocatinlimab (AMG 451/KHK4083) Rocatinlimab is a first-in-class T-cell rebalancing monoclonal antibody targeting the OX40 receptor. The eight study ROCKET Phase 3 program continues to enroll patients with moderate-to-severe atopic dermatitis (AD). To date, over 3,200 patients have been enrolled in the ROCKET program, with six studies having completed enrollment. In September, the Company reported results from the Phase 3 HORIZON study (part of the ROCKET program), evaluating rocatinlimab monotherapy vs. placebo in adults with moderate-to-severe AD. The study met its co-primary endpoints and all key secondary endpoints, achieving statistical significance versus placebo at week 24. 32.8% of patients in the rocatinlimab group achieved ≥ 75% reduction from baseline in Eczema Area and Severity Index score (EASI-75), compared to 13.7% placebo treated (19.1% difference, p<0.001). 19.3% of patients in the rocatinlimab group achieved a Validated Investigator's Global Assessment for Atopic Dermatitis (vIGA-ADTM) score of 0 (clear) or 1 (almost clear) with a ≥ 2-point reduction from baseline, compared to 6.6% in placebo (12.8% difference, p<0.001). In the U.S., a more stringent scoring method was used (revised Investigator's Global Assessment, or rIGA) where 16.4% of patients in the rocatinlimab group achieved a score of 0 (clear) or 1 (almost clear) with a ≥ 2-point reduction from baseline, compared to 4.9% in placebo (11.5% difference, p<0.001). Safety findings were consistent with those seen in the Phase 2b AD study. Additional key data readouts from the ROCKET Phase 3 program are expected in late 2024 through H2 2025: ROCKET SHUTTLE is a 24-week study evaluating rocatinlimab in combination with topical corticosteroids and/or topical calcineurin inhibitors in adult patients with moderate-to-severe AD. Data readout is anticipated in late 2024 to early 2025. ROCKET IGNITE is a 24-week study evaluating rocatinlimab monotherapy in adult patients with moderate-to-severe AD. Data readout is anticipated in late 2024 to early 2025. ROCKET ASCEND is a study evaluating rocatinlimab maintenance therapy in adult and adolescent patients with moderate-to-severe AD. Data readout is anticipated in H2 2025. ROCKET ASTRO is a 52-week study evaluating rocatinlimab in adolescent patients with moderate-to-severe AD. Data readout is anticipated in H2 2025. A Phase 2 study of rocatinlimab is enrolling patients with moderate-to-severe asthma. A Phase 3 study of rocatinlimab is enrolling patients with prurigo nodularis. Otezla In September data were presented from: a Phase 3 study of Japanese patients with Palmoplantar Pustulosis (PPP) demonstrating maintained or increased efficacy (compared with the week 16 primary analysis) and no new safety signals with 52 weeks of Otezla treatment. the DISCREET moderate-to-severe genital psoriasis study demonstrating that improvements in disease severity, symptoms, and quality of life with Otezla treatment were maintained at week 32. No new safety signals were observed. the FOREMOST study of patients with oligoarticular psoriatic arthritis, where Otezla demonstrated sustained benefits in skin, joint, fatigue, and pain symptoms through 48-weeks. Blinatumomab Blinatumomab is a bispecific T-cell engager (BiTE) molecule targeting CD19. A Phase 2 study of blinatumomab was initiated in patients with autoimmune disease with an initial focus on systemic lupus erythematosus (SLE) with nephritis. Inebilizumab Inebilizumab is a monoclonal antibody targeting CD19. A Phase 2 study of inebilizumab was initiated in patients with autoimmune disease with an initial focus on SLE with nephritis. Efavaleukin alfa (AMG 592) Efavaleukin alfa is an interleukin 2 (IL 2) mutein Fc fusion protein. A Phase 2b study of efavaleukin alfa in patients with ulcerative colitis was terminated due to the study meeting a prespecified futility threshold, and not related to safety concerns. Ordesekimab (AMG 714/PRV-015) Ordesekimab is a monoclonal antibody that binds interleukin-15. A Phase 2b study of ordesekimab is ongoing in patients with nonresponsive celiac disease. AMG 104 (AZD8630) AMG 104 is an inhaled anti-thymic stromal lymphopoietin (TSLP) fragment antigen-binding (Fab). A Phase 2 study was initiated in patients with asthma. Rare Disease TAVNEOS A Phase 3, open-label study of TAVNEOS in combination with Rituximab or a cyclophosphamide-containing regimen, is enrolling patients from 6 years to < 18 years of age with active ANCA-associated vasculitis (Granulomatosis with Polyangiitis (GPA) / Microscopic Polyangiitis (MPA)). TEPEZZA In September, TEPEZZA was approved for the treatment of active Thyroid Eye Disease (TED) by Japan's Ministry of Health, Labour and Welfare (MHLW). Regulatory review in multiple additional geographies continues. A Phase 3 study of TEPEZZA in Japan continues to enroll patients with chronic or low clinical activity score TED. A Phase 3 study evaluating the subcutaneous route of administration of teprotumumab is enrolling patients with TED. KRYSTEXXA Data from the AGILE study evaluating the safety, tolerability, and efficacy of KRYSTEXXA administered with a shorter infusion duration in patients with uncontrolled gout receiving methotrexate as co-administration will be presented at the American College of Rheumatology Convergence (ACR) in November. UPLIZNA The Company recently presented results of the Phase 3 MINT clinical study evaluating the efficacy and safety of UPLIZNA for the treatment of generalized myasthenia gravis (gMG). UPLIZNA demonstrated a clinically meaningful and statistically significant Myasthenia Gravis Activities of Daily Living (MG-ADL) score improvement after two doses compared to placebo at Week 26: -4.2 overall improvement, -1.9 placebo adjusted (p < 0.0001, primary endpoint). In the acetylcholine receptor autoantibody-positive (AChR+) population, UPLIZNA demonstrated a clinically meaningful and statistically significant MG-ADL score improvement compared to placebo at Week 26: -4.2 overall improvement, -1.8 placebo adjusted (p = 0.0015, secondary endpoint). In the muscle-specific kinase autoantibody-positive (MuSK+) population, UPLIZNA demonstrated a clinically meaningful and statistically significant MG-ADL score improvement compared to placebo at Week 26: -3.9 overall improvement, -2.2 placebo adjusted (p = 0.0297, secondary endpoint). UPLIZNA demonstrated a statistically significant Quantitative Myasthenia Gravis (QMG) score improvement after two doses compared to placebo at week 26: -4.8 overall improvement, -2.5 placebo adjusted (p = 0.0002, secondary endpoint). In the AChR+ population, UPLIZNA demonstrated a clinically meaningful and statistically significant QMG score improvement compared to placebo at week 26: -4.4 overall improvement, -2.5 placebo adjusted (p = 0.0011, secondary endpoint). In the MuSK+ population, the mean change from baseline in QMG score at Week 26 showed a trend favoring UPLIZNA but was not statistically significant (-5.2 for UPLIZNA and -3.0 for placebo, difference -2.3, p=0.1326). Patients who entered the study taking corticosteroids were tapered down starting at Week 4 to prednisone 5 mg per day by Week 24. The overall safety results during the placebo-controlled period of the study were consistent with the known safety profile of UPLIZNA. 52-week data from the AChR+ cohort and from AChR+ and MuSK+ patients in the open-label period of the study will be presented at a future date. Planning for regulatory submissions for gMG is underway. In August, the FDA granted Breakthrough Therapy Designation for UPLIZNA in the treatment of Immunoglobulin G4-related diseases (IgG4-RD) based upon data from the Phase 3 MITIGATE study. Regulatory filing activities for IgG4-RD are underway. MITIGATE results will be presented at ACR in November. Dazodalibep Dazodalibep is a fusion protein that inhibits CD40L. Two Phase 3 studies of dazodalibep in Sjögren's disease are enrolling patients. The first study is in patients with moderate-to-severe systemic disease activity, and the second study is in patients with moderate-to-severe symptomatic burden and low systemic disease activity. Daxdilimab Daxdilimab is a fully human monoclonal antibody targeting immunoglobulin-like transcript 7 (ILT7). A Phase 2 study of daxdilimab is ongoing in patients with moderate-to-severe active primary discoid lupus erythematosus refractory to standard of care. A Phase 2 study of daxdilimab is ongoing in patients with dermatomyositis and antisynthetase inflammatory myositis. Fipaxalparant Fipaxalparant is a lysophosphatidic acid receptor 1 (LPAR1) antagonist. A Phase 2 study of fipaxalparant in patients with idiopathic pulmonary fibrosis is complete. The study did not meet any of the primary or secondary endpoints. Development of fipaxalparant in this indication will be discontinued. A Phase 2 study of fipaxalparant has completed enrollment of patients with diffuse cutaneous systemic sclerosis. Biosimilars In August, the FDA approved PAVBLUTM (aflibercept-ayyh) (ABP 938), a biosimilar candidate to EYLEA® (aflibercept), for the treatment of retinal conditions, including neovascular age-related macular degeneration (wet AMD), macular edema following retinal vein occlusion, diabetic macular edema, and diabetic retinopathy. A randomized, double-blind pharmacokinetic similarity study of ABP 206 compared with OPDIVO® (nivolumab) is enrolling patients with resected stage III or stage IV melanoma in the adjuvant setting. A randomized, double-blind comparative clinical study of ABP 206 compared with OPDIVO is enrolling patients with treatment-naïve unresectable or metastatic melanoma. A randomized, double-blind combined pharmacokinetic/comparative clinical study of ABP 234 compared to KEYTRUDA® (pembrolizumab) is enrolling patients with advanced or metastatic non-squamous non-small cell lung cancer. TEZSPIRE is being developed in collaboration with AstraZeneca. AMG 104 is being developed in collaboration with AstraZeneca. Rocatinlimab, formerly AMG 451/KHK4083, is being developed in collaboration with Kyowa Kirin. Ordesekimab, formerly AMG 714 and also known as PRV-015, is being developed in collaboration with Provention Bio, a Sanofi Company. For the purposes of the collaboration, Provention Bio conducts a clinical trial and leads certain development and regulatory activities for the program. Xaluritamig, formerly AMG 509, is being developed pursuant to a research collaboration with Xencor, Inc. IDE397 is an investigational MAT2A inhibitor from IDEAYA Biosciences. EYLEA is a registered trademark of Regeneron Pharmaceuticals, Inc. OPDIVO is a registered trademark of Bristol-Myers Squibb Company. KEYTRUDA is a registered trademark of Merck & Co., Inc. Non-GAAP Financial Measures In this news release, management has presented its operating results for the third quarters of 2024 and 2023, in accordance with U.S. Generally Accepted Accounting Principles (GAAP) and on a non-GAAP basis. In addition, management has presented its full year 2024 EPS and tax guidance in accordance with GAAP and on a non-GAAP basis. These non-GAAP financial measures are computed by excluding certain items related to acquisitions, divestitures, restructuring and certain other items from the related GAAP financial measures. Management has presented Free Cash Flow (FCF), which is a non-GAAP financial measure, for the third quarters of 2024 and 2023. FCF is computed by subtracting capital expenditures from operating cash flow, each as determined in accordance with GAAP. The Company believes that its presentation of non-GAAP financial measures provides useful supplementary information to and facilitates additional analysis by investors. The Company uses certain non-GAAP financial measures to enhance an investor's overall understanding of the financial performance and prospects for the future of the Company's normal and recurring business activities by facilitating comparisons of results of normal and recurring business operations among current, past and future periods. The Company believes that FCF provides a further measure of the Company's liquidity. The Company uses the non-GAAP financial measures set forth in the news release in connection with its own budgeting and financial planning internally to evaluate the performance of the business, including to allocate resources and to evaluate results relative to incentive compensation targets. The non-GAAP financial measures are in addition to, not a substitute for, or superior to, measures of financial performance prepared in accordance with GAAP. 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.  Forward-Looking Statements This news release contains forward-looking statements that are based on the current expectations and beliefs of Amgen. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including any statements on the outcome, benefits and synergies of collaborations, or potential collaborations, with any other company (including BeiGene, Ltd. or Kyowa Kirin Co., Ltd.), the performance of Otezla® (apremilast) (including anticipated Otezla sales growth and the timing of non-GAAP EPS accretion), our acquisitions of Teneobio, Inc., ChemoCentryx, Inc., or Horizon (including the prospective performance and outlook of Horizon's business, performance and opportunities and any potential strategic benefits, synergies or opportunities expected as a result of such acquisition, and any projected impacts from the Horizon acquisition on our acquisition-related expenses going forward), as well as estimates of revenues, operating margins, capital expenditures, cash, other financial metrics, expected legal, arbitration, political, regulatory or clinical results or practices, customer and prescriber patterns or practices, reimbursement activities and outcomes, effects of pandemics or other widespread health problems on our business, outcomes, progress, and other such estimates and results. Forward-looking statements involve significant risks and uncertainties, including those discussed below and more fully described in the Securities and Exchange Commission reports filed by Amgen, including our most recent annual report on Form 10-K and any subsequent periodic reports on Form 10-Q and current reports on Form 8-K. Unless otherwise noted, Amgen is providing this information as of the date of this news release and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise. No forward-looking statement can be guaranteed and actual results may differ materially from those we project. Our results may be affected by our ability to successfully market both new and existing products domestically and internationally, clinical and regulatory developments involving current and future products, sales growth of recently launched products, competition from other products including biosimilars, difficulties or delays in manufacturing our products and global economic conditions. In addition, sales of our products are affected by pricing pressure, political and public scrutiny and reimbursement policies imposed by third-party payers, including governments, private insurance plans and managed care providers and may be affected by regulatory, clinical and guideline developments and domestic and international trends toward managed care and healthcare cost containment. Furthermore, our research, testing, pricing, marketing and other operations are subject to extensive regulation by domestic and foreign government regulatory authorities. We or others could identify safety, side effects or manufacturing problems with our products, including our devices, after they are on the market. Our business may be impacted by government investigations, litigation and product liability claims. In addition, our business may be impacted by the adoption of new tax legislation or exposure to additional tax liabilities. If we fail to meet the compliance obligations in the corporate integrity agreement between us and the U.S. government, we could become subject to significant sanctions. Further, while we routinely obtain patents for our products and technology, the protection offered by our patents and patent applications may be challenged, invalidated or circumvented by our competitors, or we may fail to prevail in present and future intellectual property litigation. We perform a substantial amount of our commercial manufacturing activities at a few key facilities, including in Puerto Rico, and also depend on third parties for a portion of our manufacturing activities, and limits on supply may constrain sales of certain of our current products and product candidate development. An outbreak of disease or similar public health threat, such as COVID-19, and the public and governmental effort to mitigate against the spread of such disease, could have a significant adverse effect on the supply of materials for our manufacturing activities, the distribution of our products, the commercialization of our product candidates, and our clinical trial operations, and any such events may have a material adverse effect on our product development, product sales, business and results of operations. We rely on collaborations with third parties for the development of some of our product candidates and for the commercialization and sales of some of our commercial products. In addition, we compete with other companies with respect to many of our marketed products as well as for the discovery and development of new products. Discovery or identification of new product candidates or development of new indications for existing products cannot be guaranteed and movement from concept to product is uncertain; consequently, there can be no guarantee that any particular product candidate or development of a new indication for an existing product will be successful and become a commercial product. Further, some raw materials, medical devices and component parts for our products are supplied by sole third-party suppliers. Certain of our distributors, customers and payers have substantial purchasing leverage in their dealings with us. The discovery of significant problems with a product similar to one of our products that implicate an entire class of products could have a material adverse effect on sales of the affected products and on our business and results of operations. Our efforts to collaborate with or acquire other companies, products or technology, and to integrate the operations of companies or to support the products or technology we have acquired, may not be successful. There can be no guarantee that we will be able to realize any of the strategic benefits, synergies or opportunities arising from the Horizon acquisition, and such benefits, synergies or opportunities may take longer to realize than expected. We may not be able to successfully integrate Horizon, and such integration may take longer, be more difficult or cost more than expected. A breakdown, cyberattack or information security breach of our information technology systems could compromise the confidentiality, integrity and availability of our systems and our data. Our stock price is volatile and may be affected by a number of events. Our business and operations may be negatively affected by the failure, or perceived failure, of achieving our environmental, social and governance objectives. The effects of global climate change and related natural disasters could negatively affect our business and operations. Global economic conditions may magnify certain risks that affect our business. Our business performance could affect or limit the ability of our Board of Directors to declare a dividend or our ability to pay a dividend or repurchase our common stock. We may not be able to access the capital and credit markets on terms that are favorable to us, or at all. CONTACT: Amgen, Thousand Oaks Elissa Snook, 609-251-1407 (media) Justin Claeys, 805-313-9775 (investors) Our GAAP diluted EPS guidance does not include the effect of GAAP adjustments triggered by events that may occur subsequent to this press release such as acquisitions, asset impairments, litigation, changes in fair value of our contingent consideration obligations and changes in fair value of our equity investments. SOURCE Amgen WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床1期临床2期临床结果上市批准临床3期

100 项与 IDE-397 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
食管癌	临床2期	-	IDEAYA Biosciences, Inc.	2023-05-30
非小细胞肺癌	临床2期	-	IDEAYA Biosciences, Inc.	2023-05-30
甲硫腺苷磷酸化酶缺失实体瘤	临床2期	-	IDEAYA Biosciences, Inc.	-
晚期恶性实体瘤	临床1期	韩国	IDEAYA Biosciences, Inc.	2021-04-14
晚期恶性实体瘤	临床1期	法国	IDEAYA Biosciences, Inc.	2021-04-14
晚期恶性实体瘤	临床1期	澳大利亚	IDEAYA Biosciences, Inc.	2021-04-14
晚期恶性实体瘤	临床1期	德国	IDEAYA Biosciences, Inc.	2021-04-14
晚期恶性实体瘤	临床1期	中国台湾	IDEAYA Biosciences, Inc.	2021-04-14
晚期恶性实体瘤	临床1期	西班牙	IDEAYA Biosciences, Inc.	2021-04-14
晚期恶性实体瘤	临床1期	美国	IDEAYA Biosciences, Inc.	2021-04-14

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04794699 (PRNewswire) 人工标引	临床2期	甲硫腺苷磷酸化酶缺失实体瘤	27	IDE397 30mg once-a-day	(選襯膚繭壓壓夢簾壓顧) = 構獵襯壓鏇壓襯繭膚構襯積簾顧廠鹹廠範膚鏇 (鑰製選窪築齋築憲範衊 ) 更多	积极	2024-10-25
				IDE397 30mg once-a-day (MTAP-deletion UC)	(選襯膚繭壓壓夢簾壓顧) = 蓋鬱積壓鬱壓餘遞遞膚襯積簾顧廠鹹廠範膚鏇 (鑰製選窪築齋築憲範衊 )