Bcr-Abl inhibitors(Bcr-Abl tyrosine kinase inhibitors), PDGFR inhibitors(Platelet-derived growth factor receptor inhibitors), c-Kit inhibitors(Stem cell growth factor receptor inhibitors)

Therapeutic Areas

NeoplasmsImmune System DiseasesDigestive System Disorders+ [4]

Active Indication

Myelodysplastic SyndromesMyeloproliferative DisordersPh-Like Acute Lymphoblastic Leukemia+ [13]

Inactive Indication

Abdominal NeoplasmsAcral Lentiginous Malignant MelanomaAcute Myeloid Leukemia+ [57]

Originator Organization

Novartis Pharma AG

Active Organization

Teva Pharmaceuticals Europe BVNovartis Europharm Ltd.Accord Healthcare SLU

+ [5]

Inactive Organization

Novartis AGActavis Group PTC ehfKoanaa Healthcare GmbH

+ [7]

Drug Highest PhaseApproved

First Approval Date

US (10 May 2001),

Philadelphia chromosome positive chronic myelogenous leukemia

RegulationAccelerated Approval (US), Orphan Drug (US), Priority Review (CN), Orphan Drug (JP)

Structure

Molecular FormulaC30H35N7O4S

InChIKeyYLMAHDNUQAMNNX-UHFFFAOYSA-N

CAS Registry220127-57-1

679

Clinical Trials associated with Imatinib mesylate

NCT06119789 / Not yet recruitingPhase 2

The MATRIX Clinical Studies of Precision Cancer Therapy for Rare Cancers

Some rare cancers are hard-to-treat and patients have a poor prognosis. It is known that some of these patients have targetable molecular alterations, and some benefit from targeted drugs. However in many cases these drugs are not approved for the rare cancers.
In this study the aim is to do advanced molecular diagnostics to identify possible targets for therapy, and to treat accordingly.

Start Date01 Aug 2024

Sponsor / Collaborator

Oslo universitetssykehus HF

[+10]

NCT05493215 / RecruitingPhase 2IIT

A Phase 2 Study of Imatinib Therapeutic Drug Monitoring in Gastrointestinal Stromal Tumor

Imatinib can lead to long recurrence free survival in patients diagnosed with gastrointestinal stromal tumors (GIST); however side effects can significantly hinder quality of life for our patients. This study will use therapeutic drug monitoring to improve quality of life and symptoms and assess how many patients maintain therapeutic levels. Free drug levels and pharmokinetics of imatinib will also be monitored.

Start Date26 Mar 2024

Sponsor / Collaborator-

NCT06175702 / Not yet recruitingNot ApplicableIIT

Treatment Protocol for Newky Diagnosed Adult Ph-Chromosome Positive (BCR::ABL1) Acute Lymphoblastic Leukemia (LALPh2022)

The goal of this prospective, multicenter, open observational study is to assess the efficacy and safety of the treatment for acute lymphoblastic leukemia Ph' positive adult patients with approved combinations of chemotherapy and tyrosine kinase inhibitor (TKI).
Efficay refers to the rate of Complete Molecular Response (BCR::ABL1/ABL1 ratio 0.01%) in eah treatment arm. Safety refers to measurement of i) Adverse events (AEs) and serious adverse events (SAEs) according to standard clinical and laboratory tests (hematology and chemistry, physical examination, vital sign measurements, and diagnostic tests), ii) incidence and degree of cytopenias and iii) incidence and degree of infections.
Low-dose chemotherapy will be given together with the TKI imatinib to patients of all ages as induction to remission phase.
Consolidation treatment will continue with low-dose chemotherapy with imatinib if the patient fullfills both criteria: to show a measurable residual disease (MRD) value lower than 0,01% at 3 month of therapy, and not showing IKZF1plus genetics Those patients have any of these 2 conditions will be considered high-risk patients and will recieve consolidation treatment intensification with low-dose chemotherapy plus ponatinib as TKI and allogeneic stem cell transplantation (allo SCT). The remaining patients (standard-risk) will receive maintenance chemotherapy together with imatinib or ponatinib and will not be submitted to alloSCT.

Start Date25 Dec 2023

Sponsor / Collaborator-

100 Clinical Results associated with Imatinib mesylate

100 Translational Medicine associated with Imatinib mesylate

100 Patents (Medical) associated with Imatinib mesylate

16,272

Literatures (Medical) associated with Imatinib mesylate

05 Jul 2106·Oncotarget

Inhibitor of Apoptosis Proteins (IAPs) are commonly dysregulated in GIST and can be pharmacologically targeted to enhance the pro-apoptotic activity of imatinib

Article

Author: Heinrich, Michael ; Corless, Christopher ; Bauer, Sebastian ; Reis, Anna-Carina ; Marino-Enriquez, Adrian ; Mühlenberg, Thomas ; Podleska, Lars Erik ; Fletcher, Jonathan Alfred ; Treckmann, Jürgen ; Falkenhorst, Johanna ; Grunewald, Susanne ; Schuler, Martin

Gastrointestinal stromal tumors (GIST) exhibit a strong oncogenic dependency on KIT and KIT inhibitors confer long lasting disease stabilization in the majority of patients. Nonetheless, KIT inhibition alone does not cure GIST as a subset of GIST cells evade apoptosis and eventually develop resistance. Inhibitors of Apoptosis Proteins (IAPs) may confer resistance to drug-induced apoptosis. We observed that the mRNA and protein of IAPs XIAP (BIRC4) and survivin (BIRC5) were highly expressed in primary GIST tumors and cell line models. Amplification of the respective gene loci (BIRC2, BIRC3, BIRC4, BIRC5) was detected in 47% of GIST studied by SNP arrays. Whole exome analyses revealed a mutation of SMAC(DIABLO) in a heavily pretreated patient. Both, survivin (rank 62-92/11.194 tested proteins) and XIAP (rank 106-557/11.194) were found to be essential proteins for survival in a synthetic lethality screen. Expression of XIAP and survivin decreased upon KIT inhibition and may play a role in KIT-regulated pro-survival signaling. SMAC-mimetic treatment with LCL161 and TL32711 reduced cIAP1 and XIAP expression. Survivin inhibitor YM155 lead to transcriptional repression of BIRC5/survivin (YM155) and induced apoptosis. Combinational treatment with KIT inhibitors (imatinib, regorafenib) enhanced the proapoptotic effect. These findings support the combination of KIT inhibition with IAP antagonists in GIST.

01 Dec 2024·Molecular biology reports

“Combination treatments of imatinib with astaxanthin and crocin efficiently ameliorate antioxidant status, inflammation and cell death progression in imatinib-resistant chronic myeloid leukemia cells”

Article

Author: Golestani, Amin ; Najafzadeh, Mahsa ; Sajjadi, Seyed Mehdi ; Sayadi, Mahtab ; Rahimi, Atefeh

BACKGROUND:

Imatinib resistance remains a major obstacle in the treatment of chronic myelogenous leukemia (CML). Crocin (CRC) and astaxanthin (ATX) are phytochemicals with anti-cancer properties.

AIMS:

This study aimed to explore the effects of combination treatment of Imatinib with CRC and ATX on Imatinib-resistant K562 (IR-K562) cells.

METHODS AND RESULTS:

After the establishment of IR-K562 cells, growth inhibitory activity was determined by the MTT assay. To test the regeneration potential, a colony formation assay was performed. Cell cycle analyses were examined by flow cytometry. Cell injury was evaluated by lactate dehydrogenase (LDH) leakage. Real-time PCR was applied to assess the expression of IL6, TNF-α, STAT3, BAD, CASP3, TP53, and Bcl-2 genes. Caspase-3 activity was determined by a colorimetric assay. Antioxidant activity was measured using a diphenylpicrylhydrazyl (DPPH) assay. After 48 h of treatment, ATX (IC₅₀ = 30µM) and CRC (IC₅₀ = 190µM) significantly inhibited cell proliferation and colony formation ability, induced G1 cell cycle arrest and cell injury, upregulated the expression of apoptosis-associated genes, and downregulated the expression of anti-apoptotic and inflammatory genes. The combination of IM with ATX and/or CRC synergistically reduced cell viability (combination index [CI] < 1).

CONCLUSION:

Our data suggest that IM shows better therapeutic efficacy at lower doses when combined with ATX and/or CRC.

01 Dec 2024·Cellular and molecular life sciences : CMLS

miR-181a plays the tumor-suppressor role in chronic myeloid leukemia CD34 + cells partially via SERPINE1

Article

Author: Zhou, Haixia ; Zhao, Yun ; Wang, Yu ; Li, Yuan-Yuan ; Ma, Wenjuan ; Zhang, Xiuyan ; Xue, Wen ; Li, Quanxue ; Chen, Pan ; Hu, Xiaohui

Abstract:

The formation of the BCR-ABL fusion gene drives human chronic myeloid leukemia (CML). The last 2 decades have witnessed that specific tyrosine kinase inhibitors (TKIs, e.g., imatinib mesylate, IM) against ABL1 improve disease treatment, although some patients still suffer from relapse and TKI resistance. Therefore, a better understanding of the molecular pathology of CML is still urgently needed. miR-181a-5p (miR-181a) acts as a tumor suppressor in CML; however, the molecular mechanism of miR-181a in CML stem/progenitor cells remains elusive. Herein, we showed that miR-181a inhibited the growth of CML CD34+ cells, including the quiescent subset, and sensitized them to IM treatment, while miR-181a inhibition by a sponge sequence collaborated with BCR-ABL to enhance the growth of normal CD34+ cells. Transcriptome data and biochemical analysis revealed that SERPINE1 was a bona fide and critical target of miR-181a, which deepened the understanding of the regulatory mechanism of SERPINE1. Genetic and pharmacological inhibition of SERPINE1 led to apoptosis mainly mediated by caspase-9 activation. The dual inhibition of SERPINE1 and BCR-ABL exhibited a significantly stronger inhibitory effect than a single agent. Taken together, this study demonstrates that a novel miR-181a/SERPINE1 axis modulates CML stem/progenitor cells, which likely provides an important approach to override TKI resistance.

268

News (Medical) associated with Imatinib mesylate

23 May 2024

·www.globenewswire.com

Cogent Biosciences Announces Positive Updated Lead-In Data from Ongoing Phase 3 PEAK Trial Evaluating Bezuclastinib in Combination with Sunitinib in Patients with Gastrointestinal Stromal Tumors (GIST) at ASCO Annual Meeting

Bezuclastinib + sunitinib combination therapy reached median progression free survival (mPFS) of 19.4-months and 33% ORR in subset of advanced GIST patients with one prior treatment Encouraging long-term safety and tolerability with combination bezuclastinib and sunitinib therapy in Part 1 PEAK Phase 3 guidance accelerated with enrollment completion now expected in 3Q 2024 Company announces new advanced GIST clinical trial sponsored by the Sarcoma Alliance for Research through Collaboration (SARC) and in collaboration with The Life Raft Group and Dana-Farber Cancer Institute WALTHAM, Mass. and BOULDER, Colo., May 23, 2024 (GLOBE NEWSWIRE) -- Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, today announced positive updated lead-in data from the company’s ongoing Phase 3 PEAK trial evaluating the selective and potent KIT mutant inhibitor, bezuclastinib, in combination with sunitinib, in patients with Gastrointestinal Stromal Tumors (GIST). The data will be presented in a poster presentation at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, IL on June 1. Cogent also announced today a new Phase 2 clinical trial of bezuclastinib plus sunitinib in later line GIST patients, sponsored by the Sarcoma Alliance for Research through Collaboration (SARC) and in collaboration with The Life Raft Group and Dana-Farber Cancer Institute. “These data presented today reinforce our excitement that the combination of bezuclastinib and sunitinib has the potential to become a new standard of care for advanced GIST patients,” said Andrew Robbins, President and Chief Executive Officer at Cogent Biosciences. “Coupled with the impressive clinical activity demonstrated by the combination, the addition of bezuclastinib to sunitinib continues to be generally well-tolerated with an encouraging safety profile. We are pleased to report that the pace of enrollment in PEAK is significantly ahead of schedule, and we now expect enrollment to complete in the third quarter of 2024.” “We are also excited today to announce a collaboration with SARC, The Life Raft Group and Dana-Farber on a new Phase 2 clinical trial assessing the potential benefit of bezuclastinib with sunitinib in later line GIST patients who are not eligible for the PEAK study and currently have very limited treatment options,” continued Mr. Robbins. “There is tremendous need for additional treatment options for GIST patients,” said Andrew Wagner M.D., Ph.D., Senior Physician, Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, and Associate Professor of Medicine, Harvard Medical School. “Today’s updated lead-in data from the bezuclastinib combination are very promising, and I remain excited about the ongoing PEAK trial. Additionally, with the announcement of this new study today, we have a clinical trial which allows us to explore the use of bezuclastinib with sunitinib in patients who are not eligible for the PEAK study.” PEAK Trial UpdatePEAK is a randomized, open-label, global, Phase 3 clinical trial evaluating bezuclastinib in combination with sunitinib vs sunitinib alone in GIST patients previously treated with imatinib. In the updated lead-in data being presented at ASCO, as of the cutoff date, April 1, 2024, the 42 patients in Part 1 have been on study for a median of 15.3 months. The median progression-free survival (mPFS) during treatment with bezuclastinib and sunitinib was 10.2 months in all patients. In a subset of second-line GIST patients with only prior imatinib, which most closely resembles patients currently enrolling in Part 2 of PEAK, the data demonstrate a mPFS of 19.4 months. In addition, the objective response rate (ORR) in all patients treated with bezuclastinib and sunitinib was 27.5% and in the subset of second-line patients the ORR was 33.3%, per investigator assessment. Combination treatment resulted in a disease control rate of 80% in all patients and 100% in patients with prior imatinib only. Safety DataAs of the data cutoff, the combination of bezuclastinib and sunitinib does not appear to add to the severity of adverse events known to be associated with sunitinib monotherapy and is well-tolerated. The majority of treatment-emergent adverse events (TEAEs) were low-grade and reversible. No additional serious adverse reactions or discontinuations due to TEAEs have been reported since the last presentation of data in November 2023. ASCO Poster DetailsTitle: Peak part 1 summary: A phase 3, randomized, open-label multicenter clinical study of bezuclastinib (CGT9486) and sunitinib combination versus sunitinib in patients with gastrointestinal stromal tumors (GIST)Session Type and Title: Poster Session – SarcomaSession Date and Time: June 1, 2024, 1:30 PM-4:30 PM CDT The poster will be available in the Posters and Publications portion of the Cogent website at approximately 8:00 AM ET on June 1. Phase 2 SARC TrialThe open label, single arm Phase 2 trial sponsored by SARC and in collaboration with The Life Raft Group and Dana-Farber Cancer Institute is designed to evaluate the mPFS as well as the safety and tolerability of bezuclastinib plus sunitinib in 40 patients with GIST who have previously progressed on sunitinib. This trial will focus on later line patients, where limited treatment options are available. Additional details can be found on clinicaltrials.gov; Identifier NCT06208748. For more information about SARC or The Life Raft Group, please visit www.sarctrials.org or www.liferaftgroup.org. Bezuclastinib Clinical DevelopmentEnrollment continues in the Phase 3 registration-enabling PEAK study, which will include approximately 388 second-line, post imatinib GIST patients. Due to rapid enrollment, the Company now expects PEAK enrollment to be completed in the third quarter of 2024 with top-line results still expected by the end of 2025. Cogent remains on-track to complete enrollment in APEX in patients with advanced systemic mastocytosis (AdvSM) by the end of 2024 and report top-line results mid-2025 and complete enrollment in SUMMIT Part 2 in the second quarter of 2025 and report top-line results by the end of 2025. Upcoming Investor ConferenceCogent will participate in the Jefferies Global Healthcare Conference on Wednesday, June 5 at 2:30 p.m. ET. A live webcast will be available on the Investors & Media page of Cogent’s website at investors.cogentbio.com/events. A replay will be available approximately two hours after completion of the event and will be archived for up to 30 days. About Cogent Biosciences, Inc.Cogent Biosciences is a biotechnology company focused on developing precision therapies for genetically defined diseases. The most advanced clinical program, bezuclastinib, is a selective tyrosine kinase inhibitor that is designed to potently inhibit the KIT D816V mutation as well as other mutations in KIT exon 17. KIT D816V is responsible for driving systemic mastocytosis, a serious disease caused by unchecked proliferation of mast cells. Exon 17 mutations are also found in patients with advanced gastrointestinal stromal tumors (GIST), a type of cancer with strong dependence on oncogenic KIT signaling. In addition to bezuclastinib, the Cogent Research Team is developing a portfolio of novel targeted therapies to help patients fighting serious, genetically driven diseases initially targeting mutations in FGFR2, ErbB2 and PI3Kα. Cogent Biosciences is based in Waltham, MA and Boulder, CO. Visit our website for more information at www.cogentbio.com. Follow Cogent Biosciences on social media: X (formerly known as Twitter) and LinkedIn. Information that may be important to investors will be routinely posted on our website and X. Forward Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding the long-term safety and tolerability profile of the combination of bezuclastinib and sunitinib therapy, the potential for the combination of bezuclastinib and sunitinib to become a new standard of care for advanced GIST patients, the updated guidance that the Company now expects PEAK enrollment to be completed in the third quarter of 2024 with top-line results still expected by the end of 2025, the expectation that PEAK will include approximately 388 second-line post imatinib GIST patients, the expectation to complete enrollment in APEX by the end of 2024 and to report top-line results mid-2025 and the expectation to complete enrollment in SUMMIT Part 2 in the second quarter of 2025 and to report top-line results by the end of 2025. The use of words such as, but not limited to, "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "might," "plan," "potential," "predict," "project," "should," "target," "will," or "would" and similar words expressions are intended to identify forward-looking statements. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, our clinical results, the rate of enrollment in our clinical trials and other future conditions. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. We may not actually achieve the forecasts or milestones disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Such forward-looking statements are subject to a number of material risks and uncertainties including but not limited to those set forth under the caption "Risk Factors" in Cogent's most recent Quarterly Report on Form 10-Q filed with the SEC. Any forward-looking statement speaks only as of the date on which it was made. Neither we, nor our affiliates, advisors or representatives, undertake any obligation to publicly update or revise any forward-looking statement, whether as result of new information, future events or otherwise, except as required by law. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date hereof. Contact:Christi WaarichSenior Director, Investor Relationschristi.waarich@cogentbio.com617-830-1653

Phase 3Phase 2Clinical ResultASCO

21 May 2024

·www.globenewswire.com

Aerovate Therapeutics Presents Baseline Data from the Phase 2b Portion of the IMPAHCT Trial at the American Thoracic Society 2024 International Conference

Baseline characteristics reflect a PAH population with significant disease Topline data from Phase 2b portion of IMPAHCT study to be released in June 2024 Enrollment into the Phase 3 portion of IMPAHCT continues at more than 120 sites globally WALTHAM, Mass., May 21, 2024 (GLOBE NEWSWIRE) -- Aerovate Therapeutics, Inc. (Nasdaq: AVTE), a clinical stage biopharmaceutical company focused on developing drugs that meaningfully improve the lives of patients with rare cardiopulmonary disease, today presented a poster outlining baseline characteristics from all patients enrolled in the dose-ranging Phase 2b portion of the Inhaled iMatinib Pulmonary Arterial Hypertension Clinical Trial (IMPAHCT) at the American Thoracic Society (ATS) 2024 International Conference taking place in San Diego, CA. IMPAHCT is a Phase 2b/Phase 3, randomized, double-blind, placebo-controlled, multinational trial evaluating the safety and efficacy of AV-101 in adults with pulmonary arterial hypertension (PAH). “These baseline characteristics reflect a patient population with significant disease despite treatment with two to three targeted PAH therapeutics. This underscores the unmet need for novel therapeutics with unique mechanisms of action that address the key drivers of PAH,” said Hunter Gillies, MBChB, Chief Medical Officer of Aerovate Therapeutics. “Coupled with our operationally seamless and adaptive IMPAHCT Phase 2b/Phase 3 trial design, we believe we are well positioned to move AV-101 forward efficiently through Phase 3 development without compromising the scientific rigor required to optimize the dose of a new investigational drug for patients.” The 202 adult patients in the Phase 2b portion of IMPAHCT are roughly split between World Health Organization functional classes II and III, with approximately 57% of patients on triple background therapy consisting of prostacyclins, endothelin receptor antagonists, and nitric oxide pathway targeting compounds. The baseline characteristics are similar to other recent studies in PAH for novel therapeutics and should support the ability to evaluate clear signals of efficacy, safety and tolerability of AV-101, a novel dry powder formulation of imatinib administered by inhalation. “We believe that we are at the beginning stages of a new era of therapeutics in PAH that have the potential to address the root cause of disease,” said Tim Noyes, Chief Executive Officer of Aerovate Therapeutics. “Our previous Phase 1 study in healthy adult volunteers demonstrated that direct delivery of lower doses of imatinib to the lung through dry powder inhalation resulted in lower systemic exposure than achieved with 400mg of oral imatinib with no serious adverse events reported. We are looking forward to providing our Phase 2b data in June and advancing AV-101 development to provide a novel antiproliferative treatment for patients with PAH who need more options.” Aerovate expects to present topline Phase 2b data in June and continue Phase 3 trial enrollment globally. A copy of the conference poster presentation will be available in the “Events & Presentations” section of Aerovate’s website at ir.aerovatetx.com. About PAHPAH is a rare, progressive orphan disease with unmet medical need that affects approximately 70,000 people in the United States and Europe. PAH can cause strain on the heart, leading to limitation of physical activity, heart failure and reduced life expectancy. About AV-101AV-101 is an investigational, proprietary dry powder inhaled formulation of the antiproliferative drug imatinib. Developed specifically for pulmonary arterial hypertension (PAH), AV-101 is designed to target cellular hyperproliferation and resistance to apoptosis, driven by improper signaling in cells of the distal pulmonary arteries. By targeting the proliferation and accumulation of cells in the arteries of the lungs, we believe AV-101 has the potential to provide meaningful improvements for patients beyond the capabilities of currently approved therapies. AV-101 is designed for delivery by an easy-to-use dry powder inhaler, directly into the lungs to maximize potential clinical benefit and limit systemic adverse effects. Phase 1 results published in ERJ Open Research showed that AV-101 delivered by dry powder inhalation was generally well-tolerated by healthy adult volunteers with no serious adverse events reported. Aerovate has completed enrollment in the Phase 2b portion of the IMPAHCT clinical trial and is currently enrolling patients in the Phase 3 portion to evaluate the safety and efficacy of AV-101 in adults with PAH. About the IMPAHCT TrialIMPAHCT (Inhaled iMatinib Pulmonary Arterial Hypertension Clinical Trial) is a multi-national, placebo-controlled Phase 2b/Phase 3 trial in adults with PAH that continuously enrolled patients from Phase 2b to Phase 3. The Phase 2b portion of the trial will evaluate three doses of AV-101 over 24 weeks, compared to placebo, to identify an optimal dose based on the primary endpoint, change in pulmonary vascular resistance (PVR), and safety, tolerability, and other clinical measures. The Phase 3 portion of the trial will compare patients taking the optimal dose of AV-101, selected from the Phase 2b data, to placebo. The primary endpoint of the Phase 3 portion of the trial will be change in six-minute walk distance (6MWD) over 24 weeks versus placebo. More information about this trial is available at https://clinicaltrials.gov/ct2/show/NCT05036135.About Aerovate Therapeutics, Inc.Aerovate is a clinical stage biopharmaceutical company focused on developing drugs that meaningfully improve the lives of patients with rare cardiopulmonary disease. Aerovate's initial focus is on advancing AV-101, its proprietary dry powder inhaled formulation of the drug imatinib for the treatment of patients with PAH. Learn more at aerovatetx.com or follow the Company on X (formerly known as Twitter) and LinkedIn. Available InformationAerovate announces material information to the public about the Company, its products and services, and other matters through a variety of means, including filings with the U.S. Securities and Exchange Commission (SEC), press releases, public conference calls, webcasts, the investor relations section of the Company website at ir.aerovatetx.com, and the Company’s X (formerly known as Twitter) account @AerovateTx in order to achieve broad, non-exclusionary distribution of information to the public and for complying with its disclosure obligations under Regulation FD. Cautionary Note Regarding Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements can be identified by words such as “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “future,” “goal,” “intend,” “look forward to,” “may,” “plan,” “potential,” “predict,” “project,” seek,” “strategy,” “should,” “target,” “will,” “would” and similar expressions regarding future periods. These forward-looking statements include, but are not limited to, statements regarding the baseline patient characteristics from the Phase 2b portion of the IMPAHCT trial and contribution of those characteristics to the evaluation of safety and efficacy measures; the clinical significance of similarities in baseline characteristics of patients in IMPAHCT as compared to prior-conducted trials, including third-party trials; our expectations regarding continuing patient enrollment for the Phase 3 portion of the IMPAHCT trial; therapeutic potential and clinical benefits of AV-101; and our anticipated timing for the release of topline data from the Phase 2b portion of the IMPAHCT trial. Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, those risks and uncertainties related to the therapeutic potential, safety and clinical benefits of AV-101; the timing associated with the identification and activation of clinical sites, patient enrollment, initiation, delivery of drug supply and continuation of our Phase 2b/Phase 3 trial of AV-101 in PAH patients; positive results from a clinical study may not necessarily be predictive of the results of future or ongoing clinical studies; regulatory developments in the United States and foreign countries; as well as those risks and uncertainties set forth more fully under the caption “Risk Factors” in our most recent Annual Report on Form 10-K filed with the SEC and subsequent filings with the SEC. We caution you not to place undue reliance on any forward-looking statements, which speak only as of the date they are made. We disclaim any obligation to publicly update or revise any such statements to reflect any change in expectations or in events, conditions or circumstances on which any such statements may be based, or that may affect the likelihood that actual results will differ from those set forth in the forward-looking statements. Any forward-looking statements contained in this press release represent our views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. Media ContactPeg Rusconipeg.rusconi@vergescientific.com Investor ContactIR@Aerovatetx.com

Phase 2Clinical ResultPhase 1Phase 3

16 May 2024

·www.globenewswire.com

Novartis highlights pioneering innovation in CML with data from Scemblix® Phase III ASC4FIRST study in newly diagnosed patients at ASCO and EHA

Primary results of the Scemblix® ASC4FIRST pivotal Phase III study in first-line Ph+ CML-CP supporting third US FDA Breakthrough Therapy designation, to be detailed in the ASCO Press Program and the EHA Plenary Session Latest data from the Kisqali®* NATALEE trial, including efficacy endpoints for patients with node-negative stage II and III HR+/HER2- early breast cancer New radioligand therapy portfolio data supporting overall platform leadership and ongoing expansion in research infrastructure and supply capabilities May 15, 2024 – Novartis will present data from more than 60 abstracts, including investigator-initiated trials at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting and the European Hematology Association (EHA) 2024 Hybrid Congress. The primary results from ASC4FIRST, a pivotal Phase III study of Scemblix® (asciminib) versus standard of care tyrosine kinase inhibitors (imatinib, nilotinib, dasatinib, and bosutinib) in newly diagnosed patients with Philadelphia chromosome positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP) will be shared at the ASCO official Press Program and at the EHA Plenary Session. “Despite progress, people with CML continue to struggle to find treatment that is both efficacious and tolerable for them at diagnosis and beyond. We look forward to sharing the primary analysis from the pivotal Phase III ASC4FIRST trial, which builds on our over 20-year legacy to transform care for people diagnosed with CML,” said Jeff Legos, Executive Vice President, Global Head of Oncology, Novartis. “With these promising data, a new analysis of the NATALEE trial in patients with node-negative early breast cancer and additional updates from our RLT portfolio, we further our efforts to reimagine medicine for those with cancer in partnership with the scientific community.” Key highlights of data accepted by ASCO include: At the ASCO Annual Meeting, Novartis will also address health equity at the company’s booth on the meeting floor, with the More Than Just Words virtual reality experience. Meeting attendees will have the opportunity to immerse themselves in scenarios inspired by real-life microaggressions Black patients face due to bias in care, and explore resources co-created with leading multidisciplinary experts to help foster productive, nonbiased conversations about breast cancer risk, diagnosis, and care. Key highlights of data accepted by EHA include: Novartis is an innovative medicines company. Every day, we work to reimagine medicine to improve and extend people’s lives so that patients, healthcare professionals and societies are empowered in the face of serious disease. Our medicines reach more than 250 million people worldwide. The content above comes from the network. if any infringement, please contact us to modify.

ASCOBreakthrough TherapyClinical Result

100 Deals associated with Imatinib mesylate

External Link

KEGG	Wiki	ATC	Drug Bank
D01441	Imatinib mesylate	L01XE01	DB00619

R&D Status

Approved

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Myelodysplastic Syndromes	EU	Accord Healthcare SLU	30 Jun 2013
Myelodysplastic Syndromes	IS	Accord Healthcare SLU	30 Jun 2013
Myelodysplastic Syndromes	LI	Accord Healthcare SLU	30 Jun 2013
Myelodysplastic Syndromes	NO	Accord Healthcare SLU	30 Jun 2013
Myeloproliferative Disorders	EU	Teva Pharmaceuticals Europe BV	07 Jan 2013
Myeloproliferative Disorders	IS	Teva Pharmaceuticals Europe BV	07 Jan 2013
Myeloproliferative Disorders	LI	Teva Pharmaceuticals Europe BV	07 Jan 2013
Myeloproliferative Disorders	NO	Teva Pharmaceuticals Europe BV	07 Jan 2013
Ph-Like Acute Lymphoblastic Leukemia	EU	Teva Pharmaceuticals Europe BV	07 Jan 2013
Ph-Like Acute Lymphoblastic Leukemia	IS	Teva Pharmaceuticals Europe BV	07 Jan 2013
Ph-Like Acute Lymphoblastic Leukemia	LI	Teva Pharmaceuticals Europe BV	07 Jan 2013
Ph-Like Acute Lymphoblastic Leukemia	NO	Teva Pharmaceuticals Europe BV	07 Jan 2013
Philadelphia Chromosome Positive Leukemia	EU	Teva Pharmaceuticals Europe BV	07 Jan 2013
Philadelphia Chromosome Positive Leukemia	IS	Teva Pharmaceuticals Europe BV	07 Jan 2013
Philadelphia Chromosome Positive Leukemia	LI	Teva Pharmaceuticals Europe BV	07 Jan 2013
Philadelphia Chromosome Positive Leukemia	NO	Teva Pharmaceuticals Europe BV	07 Jan 2013
Acute Lymphoblastic Leukemia	US	Novartis Pharmaceuticals Corp.	19 Oct 2006
Systemic Mastocytosis	US	Novartis Pharmaceuticals Corp.	19 Oct 2006
Gastrointestinal Stromal Tumors	US	Novartis Pharmaceuticals Corp.	01 Feb 2002
Chronic Eosinophilic Leukemia	EU	Novartis Europharm Ltd.	07 Nov 2001

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Neurofibrosarcoma	Phase 3	DE	Novartis Pharma AG	01 May 2006
Pulmonary Arterial Hypertension	Phase 3	US	Novartis Pharma AG	01 Apr 2006
Pulmonary Arterial Hypertension	Phase 3	AT	Novartis Pharma AG	01 Apr 2006
Pulmonary Arterial Hypertension	Phase 3	DE	Novartis Pharma AG	01 Apr 2006
Pulmonary Arterial Hypertension	Phase 3	GB	Novartis Pharma AG	01 Apr 2006
Glioblastoma Multiforme	Phase 3	DE	Novartis Pharmaceuticals Corp.	01 Oct 2004
Chronic phase chronic myeloid leukemia	Phase 3	FR	Novartis AG	01 Sep 2003
Metastatic Gastrointestinal Stromal Tumor	Phase 3	US	National Cancer Institute	01 Dec 2000
Metastatic Gastrointestinal Stromal Tumor	Phase 3	CA	National Cancer Institute	01 Dec 2000
Metastatic Gastrointestinal Stromal Tumor	Phase 3	PR	National Cancer Institute	01 Dec 2000

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


EHA2024	Not Applicable	undetectable minimal residual disease (UMRD) \| BCR-ABL transcript	100	Imatinib	ciforffvyi(vcjnlwgmbi) = lbovjggziq fovpdgnbtt (tprysyzqfo, 94 - 100) View more	Positive	14 May 2024
INFINITY (EHA2024)	Not Applicable	Philadelphia chromosome positive chronic myelogenous leukemia First line	984	Imatinib	utuseztzom(nbxirwkeuz) = jcuedvktmw uxmouexlhi (bxarvgyvnc ) View more	Positive	14 May 2024
				Nilotinib	utuseztzom(nbxirwkeuz) = labogydwlz uxmouexlhi (bxarvgyvnc ) View more
NCT00367861 (BFR14, ESMO_SRC2024) Manual	Phase 3	Gastrointestinal Stromal Tumors	135	imatinib (Treatment discontinuation and restart at progression + after 1 year)	qxpkvrdqze(zgsepyopxf) = PFS was significantly improved in the CONT vs STOP arms in the three randomization periods. (p<0.001) wocibduyzv (eiyumkogor ) View more	Negative	14 Mar 2024
				imatinib (Continuation of treatment until progression + after 1 year)
ASCO_GI2024 Manual	Not Applicable	Gastrointestinal Stromal Tumors Neoadjuvant	137	Imatinib	cwgglyqgoo(oaznvfhczg) = sthhwsfagl ppucwjvoyd (tbgdbcqvox ) View more	Positive	18 Jan 2024
ASCO_GI2024	Not Applicable	Gastrointestinal Stromal Tumors First line	91	imatinib	szvrqfxvoe(uaeumlmyvh) = guatpfpxzc gvkpgrkrvj (vzxsqxpdjn ) View more	-	18 Jan 2024
				imatinib	szvrqfxvoe(uaeumlmyvh) = lmnjdnaoqo gvkpgrkrvj (vzxsqxpdjn ) View more
ASC4MORE (ASH2023)	Not Applicable	Add-on	84	ASC 40 mg add-on to IMA	clmwsfxcys(eradlqnqnh) = njanakmwri pysxhrvtpg (tpxynggbvy ) View more	-	11 Dec 2023
				ASC 60 mg add-on to IMA	clmwsfxcys(eradlqnqnh) = itbadhztll pysxhrvtpg (tpxynggbvy ) View more
ASH2023	Not Applicable	Chronic phase chronic myeloid leukemia First line	1,277	Imatinib	mdrgpgujst(sadtkpeumn) = ddouwupjks lxdjpftqkc (ozlkdmbljv )	-	10 Dec 2023
				2nd Generation TKIs	mdrgpgujst(sadtkpeumn) = mcptjftoef lxdjpftqkc (ozlkdmbljv )
ASH2023	Not Applicable	ALK-positive anaplastic large cell lymphoma	6	Imatinib	qzqnqcytth(zqifymycnh) = krlzotavuu qmqfskdope (fahyfmxeds )	-	09 Dec 2023
NCT05245968 (CHAPTER-GIST-101, ESMO2023) Manual	Phase 1	Gastrointestinal Stromal Tumors Second line	12	Pimitespib + Imatinib	aqanimufjb(njlobnqpmt) = vhasgsezzf xxltechrjf (ohmcgoshox ) View more	Positive	21 Oct 2023
NCT03891901 (CTgov)	Phase 2	Tuberculosis	24	Rifabutin+Imatinib+Isoniazid (Cohort 1a: Imatinib (50 mg) + Rifabutin + Isoniazid)	jtoblxcfxx(ogukrntkfn) = hzfxjoinlq qpfwuadlql (vmibpjcbeg, kcwuqwaein - ryzwwfagxa) View more	-	28 Sep 2023
				Rifabutin+Imatinib+Isoniazid (Cohort 1b: Imatinib (100 mg) + Rifabutin + Isoniazid)	jtoblxcfxx(ogukrntkfn) = scqtagcvzw qpfwuadlql (vmibpjcbeg, pfdfzujbxo - nxmeutjyqq) View more

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