Investigation of the Radiotracer Uptake of [68Ga] MDM2/MDMX Peptide at Lesion Sites in Patients with Malignant Tumors, and Evaluation of the Capability of [68Ga] MDM2/MDMX Peptide to Detect Overexpression of MDM2/MDMX in Tumor Patients, Particularly Those with Recurrent or Advanced Disease.

开始日期2024-06-10

申办/合作机构

北京市肿瘤防治研究所

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100 项与 ATSP7041 相关的转化医学

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100 项与 ATSP7041 相关的专利（医药）

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项与 ATSP7041 相关的文献（医药）

2024-12-31·Journal of enzyme inhibition and medicinal chemistry

Searching for novel MDM2/MDMX dual inhibitors through a drug repurposing approach

Article

作者: Wen, Hongmei ; Li, Wei ; Hu, Wenshu ; Li, Keting ; Liu, Jian ; Chen, Wenxing ; Wang, Yingjie ; Wang, Bo

Disruption of p53-MDM2/MDMX interaction by smaller inhibitors is a promising therapeutic intervention gaining tremendous interest. However, no MDM2/MDMX inhibitors have been marketed so far. Drug repurposing is a validated, practical approach to drug discovery. In this regard, we employed structure-based virtual screening in a reservoir of marketed drugs and identified nintedanib as a new MDM2/MDMX dual inhibitor. The computational structure analysis and biochemical experiments uncover that nintedanib binds MDM2/MDMX similarly to RO2443, a dual MDM2/MDMX inhibitor. Furthermore, the mechanistic study reveals that nintedanib disrupts the physical interaction of p53-MDM2/MDMX, enabling the transcriptional activation of p53 and the subsequent cell cycle arrest and growth inhibition in p53^+/+ cancer cells. Lastly, structural minimisation of nintedanib yields H3 with the equivalent potency. In summary, this work provides a solid foundation for reshaping nintedanib as a valuable lead compound for the further design of MDM2/MDMX dual inhibitors.

2023-12-12·ACS nano

Targeted Polymersome Delivery of a Stapled Peptide for Drugging the Tumor Protein p53:BCL-2-Family Axis in Diffuse Large B-Cell Lymphoma

Article

作者: Kung, Andrew L. ; Ting, Jeffrey M. ; Tirrell, Matthew V. ; Watkins, Elyse A. ; LaBelle, James L. ; Thomas-Toth, Anika T. ; Hubbell, Jeffrey A. ; Kucera, Isadora M. ; Hawley, Katrina M. ; Raczy, Michal M. ; Leak, Logan B. ; Schnorenberg, Mathew R. ; Tian, Yu

Diffuse large B-cell lymphoma (DLBCL) remains a formidable diagnosis in need of new treatment paradigms. In this work, we elucidated an opportunity for therapeutic synergy in DLBCL by reactivating tumor protein p53 with a stapled peptide, ATSP-7041, thereby priming cells for apoptosis and enhancing their sensitivity to BCL-2 family modulation with a BH3-mimetic, ABT-263 (navitoclax). While this combination was highly effective at activating apoptosis in DLBCL in vitro, it was highly toxic in vivo, resulting in a prohibitively narrow therapeutic window. We, therefore, developed a targeted nanomedicine delivery platform to maintain the therapeutic potency of this combination while minimizing its toxicity via packaging and targeted delivery of a stapled peptide. We developed a CD19-targeted polymersome using block copolymers of poly(ethylene glycol) disulfide linked to poly(propylene sulfide) (PEG-SS-PPS) for ATSP-7041 delivery into DLBCL cells. Intracellular delivery was optimized in vitro and validated in vivo by using an aggressive human DLBCL xenograft model. Targeted delivery of ATSP-7041 unlocked the ability to systemically cotreat with ABT-263, resulting in delayed tumor growth, prolonged survival, and no overt toxicity. This work demonstrates a proof-of-concept for antigen-specific targeting of polymersome nanomedicines, targeted delivery of a stapled peptide in vivo, and synergistic dual intrinsic apoptotic therapy against DLBCL via direct p53 reactivation and BCL-2 family modulation.

2023-06-16·Biomolecules

Identification of the Stapled α-Helical Peptide ATSP-7041 as a Substrate and Strong Inhibitor of OATP1B1 In Vitro.

Article

作者: Saito, Yoshiro ; Demizu, Yosuke ; Misawa, Takashi ; Ishikawa, Rika ; Saito, Kosuke

ATSP-7041, a stapled α-helical peptide that inhibits murine double minute-2 (MDM2) and MDMX activities, is a promising modality targeting protein-protein interactions. As peptides of molecular weights over 1000 Da are not usually evaluated, data on the drug-drug interaction (DDI) potential of stapled α-helical peptides remain scarce. Here, we evaluate the interaction of ATSP-7041 with hepatic cytochrome P450s (CYPs; CYP1A2, CYP2C9, CYP2C19, CYP3A4, and CYP2D6) and transporters (organic anion transporting polypeptides (OATPs; OATP1B1 and OATP1B3), P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP)). ATSP-7041 demonstrated negligible metabolism in human liver S9 fraction and a limited inhibition of CYP activities in yeast microsomes or S9 fractions. On the contrary, a substantial uptake by OATPs in HEK 293 cells, a strong inhibition of OATP activities in the cells, and an inhibition of P-gp and BCRP activities in reversed membrane vesicles were observed for ATSP-7041. A recent report describes that ALRN-6924, an ATSP-7041 analog, inhibited OATP activities in vivo; therefore, we focused on the interaction between ATSP-7041 and OATP1B1 to demonstrate that ATSP-7041, as a higher molecular weight stapled peptide, is a substrate and strong inhibitor of OATP1B1 activity. Our findings demonstrated the possibility of transporter-mediated DDI potential by high molecular weight stapled peptides and the necessity of their evaluation for drug development.

项与 ATSP7041 相关的新闻（医药）

2023-06-30

·PRNewswire

Proteomics Collaborations: A Comprehensive Review (2010-2023) with Access to Headline, Upfront, Milestone & Royalty Data

DUBLIN, June 30, 2023 /PRNewswire/ -- The "Global Proteomics Partnering Terms and Agreements 2010 to 2023" report has been added to ResearchAndMarkets.com's offering. The Global Proteomics Partnering Terms and Agreements 2010 to 2023 report provides an understanding and access to the proteomics partnering deals and agreements entered into by the world's leading healthcare companies. Trends in proteomics dealmaking in the biopharma industry since 2010 Access to headline, upfront, milestone and royalty data Access to over 600 proteomics deal records and contract documents where available The leading proteomics deals by value since 2010 Most active proteomics dealmakers since 2010 The leading proteomics partnering resources The Global Proteomics Partnering Terms and Agreements report provides an understanding and access to the proteomics partnering deals and agreements entered into by the world's leading healthcare companies. The report provides a detailed understanding and analysis of how and why companies enter proteomics partnering deals. The majority of deals are early development stage whereby the licensee obtains a right or an option right to license the licensors proteomics technology or product candidates. These deals tend to be multicomponent, starting with collaborative R&D, and commercialization of outcomes. Understanding the flexibility of a prospective partner's negotiated deals terms provides critical insight into the negotiation process in terms of what you can expect to achieve during the negotiation of terms. Whilst many smaller companies will be seeking details of the payments clauses, the devil is in the detail in terms of how payments are triggered - contract documents provide this insight where press releases and databases do not. This report contains links to online copies of actual proteomics deals and contract documents as submitted to the Securities Exchange Commission by companies and their partners. Contract documents provide the answers to numerous questions about a prospective partner's flexibility on a wide range of important issues, many of which will have a significant impact on each party's ability to derive value from the deal. Contract documents provide the answers to numerous questions about a prospective partner's flexibility on a wide range of important issues, many of which will have a significant impact on each party's ability to derive value from the deal. For example, analyzing actual company deals and agreements allows assessment of the following: What is actually granted by the agreement to the partner company? What exclusivity is granted? What are the precise rights granted or optioned? What is the payment structure for the deal? How are sales and payments audited? What is the deal term? How are the key terms of the agreement defined? How are IPRs handled and owned? Who is responsible for commercialization? Who is responsible for development, supply, and manufacture? How is confidentiality and publication managed? How are disputes to be resolved? Under what conditions can the deal be terminated? What happens when there is a change of ownership? What sublicensing and subcontracting provisions have been agreed? Which boilerplate clauses does the company insist upon? Which boilerplate clauses appear to differ from partner to partner or deal type to deal type? Which jurisdiction does the company insist upon for agreement law? The initial chapters of this report provide an orientation of proteomics dealmaking and business activities. Chapter 1 provides an introduction to the report, whilst chapter 2 provides an overview of the trends in proteomics dealmaking since 2010, including details of average headline, upfront, milestone and royalty terms. Chapter 3 provides a review of the leading proteomics deals since 2010. Deals are listed by headline value, signed by big pharma, most active proteomics dealmaking companies. Where the deal has an agreement contract published at the SEC a link provides online access to the contract. Chapter 4 provides a comprehensive listing of the top 25 most active companies in proteomics dealmaking with a brief summary followed by a comprehensive listing of proteomics deals, as well as contract documents available in the public domain. Where available, each deal title links via Weblink to an online version of the actual contract document, providing easy access to each contract document on demand. Chapter 5 provides a comprehensive and detailed review of proteomics partnering deals signed and announced since Jan 2010. Each deal title links via Weblink to an online version of the deal record and where available, the contract document, providing easy access to each contract document on demand. Chapter 6 provides a comprehensive and detailed review of proteomics partnering deals signed and announced since Jan 2010. Each deal title links via Weblink to an online version of the deal record and where available, the contract document, providing easy access to each contract document on demand. In addition, a comprehensive appendix is provided organized by Proteomics partnering company A-Z, deal type definitions and proteomics partnering agreements example. Each deal title links via Weblink to an online version of the deal record and where available, the contract document, providing easy access to each contract document on demand. The report also includes numerous tables and figures that illustrate the trends and activities in proteomics partnering and dealmaking since 2010. In conclusion, this report provides everything a prospective dealmaker needs to know about partnering in the research, development and commercialization of proteomics technologies and products. Key Topics Covered Executive Summary Chapter 1 - Introduction Chapter 2 - Trends in proteomics dealmaking 2.1. Introduction 2.2. Proteomics partnering over the years 2.3. Most active proteomics dealmakers 2.4. Proteomics partnering by deal type 2.5. Proteomics partnering by therapy area 2.6. Deal terms for proteomics partnering 2.6.1 Proteomics partnering headline values 2.6.2 Proteomics deal upfront payments 2.6.3 Proteomics deal milestone payments 2.6.4 Proteomics royalty rates Chapter 3 - Leading proteomics deals 3.1. Introduction 3.2. Top proteomics deals by value Chapter 4 - Most active proteomics dealmakers 4.1. Introduction 4.2. Most active proteomics dealmakers 4.3. Most active proteomics partnering company profiles Chapter 5 - Proteomics contracts dealmaking directory 5.1. Introduction 5.2. Proteomics contracts dealmaking directory Chapter 6 - Proteomics dealmaking by technology type Appendices Appendix 1 - Proteomics deals by company A-Z Appendix 2 - Proteomics deals by stage of development Appendix 3 - Proteomics deals by deal type Appendix 4 - Proteomics deals by therapy area Deal type definitions Companies Mentioned 3SBio 20/20 BioResponse 21st Century Biochemicals A*STAR Bioinformatics Institute A*STAR Genome Institute of Singapore A*STAR Institute of Microelectronics (IME) AB Analitica Abbvie Abcam Ablynx Abnova Abraxis BioScience Absorption Systems Abt Bio Pharma Solutions Academy for Medical Development & Collaboration Acceleron Pharma Acella Pharmaceuticals ACGT Activiomics ActivX Biosciences ADC Biotechnology Adeona Pharmaceuticals Adimab Aduro BioTech Advaita Advanced Biological Laboratories Advanced BioScience Laboratories Advanced Manufacturing Fund Advinus Therapeutics Aelan Cell Technologies Aestus Therapeutic AEterna Zentaris Affibody Affomix Affymetrix Agilent Technologies AGTC Aileron Therapeutics Ajinomoto AminoScience Alamar Biosciences Albumedix Alexion Pharmaceuticals Allergan Allozyne Almac Diagnostics Almac Group Almirall Alnylam Pharmaceuticals Althea Technologies Altus Pharmaceuticals Alzheimers Research UK Amarantus BioSciences Ambergen Ambrx American College of Cardiology American CryoStem American Health Assistance Foundation Amgen AmorChem Amplimmune Amunix Analytical Testing Laboratory AnaSpec Anchor Therapeutics Angel Biotechnology Anteo Diagnostics Anthera Pharmaceuticals Antigen Discovery Antitope Apeiron Biologics Applied Proteomics Arbor Vita Arbutus Arecor Ariadne Genomics ArmaGen Arrayit Artes Biotechnology Aspera Astellas Pharma AstraZeneca Asuragen ATUM Auburn University Aurigene Discovery Technologies Aushon BioSystems Autism Speaks Autogenesis Auven Therapeutics Avera Heart Hospital of South Dakota Avid Bioservices AvidBiotics Avila Therapeutics Avraham Pharmaceuticals Axil Scientific BaroFold Batavia Biosciences Baxter International Bayer Bayer CropScience Bayer Schering Pharma Baylor College of Medicine BellBrook Labs Bellus Health Berg BGI Americas BG Medicine Bicycle Therapeutics Bill and Melinda Gates Foundation Bio-Techne BioAtla Biocartis Biocius Life Sciences Biocrates Biodesix Bioeasy Diagnostica BioFocus Biogen Biognosys BioGrammatics Biomodels BioNova Cientifica Biopharm BioSante Pharmaceuticals BioSeek Bio Sidus Argentina BioSilta BioSystem Development Biotage Biotechnology and Biological Sciences Research Council (BBSRC) Biotechnology Value Fund Biotest bioVidria BioWa Bioyong BluePen Biomarkers Blue Sky Biotech Boehringer Ingelheim Boehringer Ingelheim Vetmedica BostonGene Bristol-Myers Squibb Bruker Bucher Biotec Bulldog Bio c-LEcta Caladrius Biosciences Caliber Biotherapeutics California Institute for Quantitative Biosciences (QB3) Calixar Cambridge Isotope Laboratories Cambridge Research Biochemicals Camino Partnership Cancer Research Technology Cancer Research UK Cangene Caprion Biosciences Caprion Proteomics Caprotec Bioanalytics For more information about this report visit About ResearchAndMarkets.com ResearchAndMarkets.com is the world's leading source for international market research reports and market data. We provide you with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends. Media Contact: Research and Markets Laura Wood, Senior Manager [email protected] For E.S.T Office Hours Call +1-917-300-0470 For U.S./CAN Toll Free Call +1-800-526-8630 For GMT Office Hours Call +353-1-416-8900 U.S. Fax: 646-607-1904 Fax (outside U.S.): +353-1-481-1716 Logo: SOURCE Research and Markets

2023-02-21

·PipelineReview

Aileron Therapeutics Announces Termination of Phase 1b Breast Cancer Chemoprotection Trial and Exploration of Strategic Alternatives

BOSTON, MA, USA I February 21, 2023 I Aileron Therapeutics (Nasdaq: ALRN) today announced that a review of initial data from its Phase 1b chemoprotection trial of ALRN-6924 in patients with p53-mutated breast cancer showed that patients in the trial experienced severe neutropenia (Grade 4) and alopecia. The primary endpoint of the Phase 1b open-label trial, which was evaluating ALRN-6924 in patients with breast cancer receiving neoadjuvant or adjuvant treatment with docetaxel, doxorubicin, and cyclophosphamide, or “TAC” chemotherapy, was duration and incidence of severe neutropenia in cycle 1. Incidence of chemotherapy-induced alopecia (hair loss) was a secondary endpoint. Based on these findings, Aileron has decided to terminate the Phase 1b breast cancer trial and further development of ALRN-6924. Aileron also announced that it is exploring a range of strategic alternatives to maximize shareholder value. The company has engaged Ladenburg Thalmann & Co., Inc. to act as a strategic advisor for this process. Strategic alternatives that are being evaluated may include, but are not limited to, an acquisition, a merger, a business combination, a sale of assets or other transactions. There is no set timetable for this process and there can be no assurance that this process will result in Aileron pursuing a transaction or that any transaction, if pursued, will be completed on attractive terms. Aileron does not intend to comment further on this process unless or until its Board of Directors has approved a definitive course of action or it is determined that other disclosure is appropriate. Aileron has determined to reduce its remaining workforce from 9 to 3 full-time employees in the coming weeks. The company plans to retain the remaining employees to assist in executing the strategic alternatives review process. “We are very disappointed by these initial findings from our breast cancer trial, given the significant unmet need of cancer patients who must endure a wide range of chemotherapy-induced side effects and given the activity we had observed in our clinical trial in small cell lung cancer patients receiving topotecan chemotherapy. I would like to extend a heartfelt thanks to our patients, investigators and clinical trial staff and scientific advisors, as well as all others who have supported this trial and our efforts to advance ALRN-6924 as a chemoprotective agent. I would also like to thank our talented and truly dedicated Aileron team who have worked so diligently to advance ALRN-6924,” said Manuel Aivado, M.D., Ph.D., President and Chief Executive Officer at Aileron Therapeutics. “We certainly hoped for a much different outcome for patients, but it is imperative that we now shift our focus toward conserving our resources as we explore strategic alternatives to maximize shareholder value.” About ALRN-6924 ALRN-6924 is an MDM2/MDMX inhibitor that leverages Aileron’s proprietary peptide drug technology. Aileron originally initiated development of ALRN-6924 as an anti-cancer agent to restore p53-dependent tumor suppression in p53 wild-type tumors, evaluating ALRN-6924 as an anti-cancer agent in 196 patients in multiple clinical trials, including a single-agent Phase 1 trial in solid tumor and lymphoma patients [1]; a single-agent Phase 2a trial for the treatment of peripheral T-cell lymphoma (PTCL) [2]; a single-agent and Ara-C-combination Phase 1/1b trial for the treatment of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) [3]; and a Phase 2a combination trial of ALRN-6924 and palbociclib in patients with tumors harboring MDM2 amplifications [4]. In these trials, ALRN-6924 was generally well-tolerated, with evidence of single-agent anti-tumor activity including complete and partial responses. Aileron has also conducted three clinical trials of ALRN-6924 as a chemoprotective agent in p53-mutated small cell lung cancer [5], non-small cell lung cancer, and breast cancer. Aileron has a strong intellectual property portfolio in the U.S. and internationally and maintains exclusive worldwide rights to ALRN-6924 as well as the company’s proprietary peptide drug technology. The company is based in Boston, Mass. Visit aileronrx.com to learn more. References [1] M. N. Saleh et al., Phase 1 Trial of ALRN-6924, a Dual Inhibitor of MDMX and MDM2, in Patients with Solid Tumors and Lymphomas Bearing Wild-type TP53. Clin Cancer Res 27 , 5236-5247 (2021). [2] A. R. Shustov et al., Preliminary Results of Stapled Peptide ALRN-6924, a Dual Inhibitor of MDMX and MDM2, in Two Phase IIa Dose Expansion Cohorts in Relapsed/Refractory TP53 Wild-Type Peripheral T-Cell Lymphoma. Blood 132 , 1623-1623 (2018). [3] D. A. Sallman et al., Phase 1/1b Study of the ALRN-6924 As Monotherapy or in Combination with Cytarabine for the Treatment of Relapsed/Refractory AML and Advanced MDS with TP53 Wild-Type. Blood 132 , 4066-4066 (2018). [4] F. Meric-Bernstam et al., A phase IIa clinical trial combining ALRN-6924 and palbociclib for treatment of patients with tumors harboring wild-type p53 and MDM2 amplification or MDM2/CDK4 co-amplification. Annals of Oncology 30 , v179-v180 (2019). [5] Z. Andric et al., “A phase Ib/II study of the dual MDMX/MDM2 inhibitor, ALRN-6924, for the prevention of chemotherapy-induced myelosuppression.” Annals of Oncology 32 , S1166 (2021) SOURCE: Aileron Therapeutics

临床1期临床2期临床结果

2023-02-21

·GlobeNewswire-Health Care

Aileron Therapeutics Announces Termination of Phase 1b Breast Cancer Chemoprotection Trial and Exploration of Strategic Alternatives

BOSTON, Feb. 21, 2023 (GLOBE NEWSWIRE) -- Aileron Therapeutics (Nasdaq: ALRN) today announced that a review of initial data from its Phase 1b chemoprotection trial of ALRN-6924 in patients with p53-mutated breast cancer showed that patients in the trial experienced severe neutropenia (Grade 4) and alopecia. The primary endpoint of the Phase 1b open-label trial, which was evaluating ALRN-6924 in patients with breast cancer receiving neoadjuvant or adjuvant treatment with docetaxel, doxorubicin, and cyclophosphamide, or “TAC” chemotherapy, was duration and incidence of severe neutropenia in cycle 1. Incidence of chemotherapy-induced alopecia (hair loss) was a secondary endpoint. Based on these findings, Aileron has decided to terminate the Phase 1b breast cancer trial and further development of ALRN-6924. Aileron also announced that it is exploring a range of strategic alternatives to maximize shareholder value. The company has engaged Ladenburg Thalmann & Co., Inc. to act as a strategic advisor for this process. Strategic alternatives that are being evaluated may include, but are not limited to, an acquisition, a merger, a business combination, a sale of assets or other transactions. There is no set timetable for this process and there can be no assurance that this process will result in Aileron pursuing a transaction or that any transaction, if pursued, will be completed on attractive terms. Aileron does not intend to comment further on this process unless or until its Board of Directors has approved a definitive course of action or it is determined that other disclosure is appropriate. Aileron has determined to reduce its remaining workforce from 9 to 3 full-time employees in the coming weeks. The company plans to retain the remaining employees to assist in executing the strategic alternatives review process. “We are very disappointed by these initial findings from our breast cancer trial, given the significant unmet need of cancer patients who must endure a wide range of chemotherapy-induced side effects and given the activity we had observed in our clinical trial in small cell lung cancer patients receiving topotecan chemotherapy. I would like to extend a heartfelt thanks to our patients, investigators and clinical trial staff and scientific advisors, as well as all others who have supported this trial and our efforts to advance ALRN-6924 as a chemoprotective agent. I would also like to thank our talented and truly dedicated Aileron team who have worked so diligently to advance ALRN-6924,” said Manuel Aivado, M.D., Ph.D., President and Chief Executive Officer at Aileron Therapeutics. “We certainly hoped for a much different outcome for patients, but it is imperative that we now shift our focus toward conserving our resources as we explore strategic alternatives to maximize shareholder value.” About ALRN-6924 ALRN-6924 is an MDM2/MDMX inhibitor that leverages Aileron’s proprietary peptide drug technology. Aileron originally initiated development of ALRN-6924 as an anti-cancer agent to restore p53-dependent tumor suppression in p53 wild-type tumors, evaluating ALRN-6924 as an anti-cancer agent in 196 patients in multiple clinical trials, including a single-agent Phase 1 trial in solid tumor and lymphoma patients [1]; a single-agent Phase 2a trial for the treatment of peripheral T-cell lymphoma (PTCL) [2]; a single-agent and Ara-C-combination Phase 1/1b trial for the treatment of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) [3]; and a Phase 2a combination trial of ALRN-6924 and palbociclib in patients with tumors harboring MDM2 amplifications [4]. In these trials, ALRN-6924 was generally well-tolerated, with evidence of single-agent anti-tumor activity including complete and partial responses. Aileron has also conducted three clinical trials of ALRN-6924 as a chemoprotective agent in p53-mutated small cell lung cancer [5], non-small cell lung cancer, and breast cancer. Aileron has a strong intellectual property portfolio in the U.S. and internationally and maintains exclusive worldwide rights to ALRN-6924 as well as the company’s proprietary peptide drug technology. The company is based in Boston, Mass. Visit aileronrx.com to learn more. Forward-Looking Statements Statements in this press release about Aileron’s future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements about the potential of ALRN-6924, the Company’s future operations, the exploration of strategic alternatives and the outcome of such exploration. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including whether Aileron’s cash resources will be sufficient to fund its continuing operations for the period anticipated or with respect to the matters anticipated; whether the Company will identify a strategic transaction to pursue and whether such a transaction may be consummated on favorable terms, on a timely basis or at all; whether results obtained in clinical trials would be indicative of results that could be obtained in future clinical trials; and other factors discussed in the “Risk Factors” section of Aileron’s annual report on Form 10-K for the year ended December 31, 2021, filed on March 28, 2022, and quarterly report on Form 10-Q for the quarter ended September 30, 2022, filed on November 1, 2022, and risks described in other filings that Aileron may make with the Securities and Exchange Commission. Any forward-looking statements contained in this press release speak only as of the date hereof, and Aileron specifically disclaims any obligation to update any forward-looking statement, whether because of new information, future events or otherwise. Contact: Liz Melone lmelone@aileronrx.com References [1] M. N. Saleh et al., Phase 1 Trial of ALRN-6924, a Dual Inhibitor of MDMX and MDM2, in Patients with Solid Tumors and Lymphomas Bearing Wild-type TP53. Clin Cancer Res 27, 5236-5247 (2021). [2] A. R. Shustov et al., Preliminary Results of Stapled Peptide ALRN-6924, a Dual Inhibitor of MDMX and MDM2, in Two Phase IIa Dose Expansion Cohorts in Relapsed/Refractory TP53 Wild-Type Peripheral T-Cell Lymphoma. Blood 132, 1623-1623 (2018). [3] D. A. Sallman et al., Phase 1/1b Study of the ALRN-6924 As Monotherapy or in Combination with Cytarabine for the Treatment of Relapsed/Refractory AML and Advanced MDS with TP53 Wild-Type. Blood 132, 4066-4066 (2018). [4] F. Meric-Bernstam et al., A phase IIa clinical trial combining ALRN-6924 and palbociclib for treatment of patients with tumors harboring wild-type p53 and MDM2 amplification or MDM2/CDK4 co-amplification. Annals of Oncology 30, v179-v180 (2019). [5] Z. Andric et al., “A phase Ib/II study of the dual MDMX/MDM2 inhibitor, ALRN-6924, for the prevention of chemotherapy-induced myelosuppression.” Annals of Oncology 32, S1166 (2021)

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100 项与 ATSP7041 相关的药物交易

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