This is a Phase 1 first-in-human study of ORM-5029 in participants with HER2-expressing advanced solid tumors. The study consists of two parts: a Part 1 Dose Escalation and Part 2 Dose Expansion.

Start Date03 Oct 2022

Sponsor / Collaborator

Orum Therapeutics USA, Inc.

100 Clinical Results associated with ORM-5029

100 Translational Medicine associated with ORM-5029

100 Patents (Medical) associated with ORM-5029

Literatures (Medical) associated with ORM-5029

01 Nov 2024·PHARMACOLOGY & THERAPEUTICS

Powering up targeted protein degradation through active and passive tumour-targeting strategies: Current and future scopes

Review

Author: Lakshminarayanan, Kalaiarasu ; Vasanthakumari Thirumalaiswamy, Harashkumar ; Murugan, Dhanashree ; Rangasamy, Loganathan ; Thirumalaiswamy, Harashkumar Vasanthakumari ; Kandhasamy, Hariprasath ; Smith, Alexis R. ; Zheng, Guangrong ; Venkatesan, Janarthanan ; Zender, Boutheina ; Smith, Alexis R

Targeted protein degradation (TPD) has emerged as a prominent and vital strategy for therapeutic intervention of cancers and other diseases. One such approach involves the exploration of proteolysis targeting chimeras (PROTACs) for the selective elimination of disease-causing proteins through the innate ubiquitin-proteasome pathway. Due to the unprecedented achievements of various PROTAC molecules in clinical trials, researchers have moved towards other physiological protein degradation approaches for the targeted degradation of abnormal proteins, including lysosome-targeting chimeras (LYTACs), autophagy-targeting chimeras (AUTACs), autophagosome-tethering compounds (ATTECs), molecular glue degraders, and other derivatives for their precise mode of action. Despite numerous advantages, these molecules face challenges in solubility, permeability, bioavailability, and potential off-target or on-target off-tissue effects. Thus, an urgent need arises to direct the action of these degrader molecules specifically against cancer cells, leaving the proteins of non-cancerous cells intact. Recent advancements in TPD have led to innovative delivery methods that ensure the degraders are delivered in a cell- or tissue-specific manner to achieve cell/tissue-selective degradation of target proteins. Such receptor-specific active delivery or nano-based passive delivery of the PROTACs could be achieved by conjugating them with targeting ligands (antibodies, aptamers, peptides, or small molecule ligands) or nano-based carriers. These techniques help to achieve precise delivery of PROTAC payloads to the target sites. Notably, the successful entry of a Degrader Antibody Conjugate (DAC), ORM-5029, into a phase 1 clinical trial underscores the therapeutic potential of these conjugates, including LYTAC-antibody conjugates (LACs) and aptamer-based targeted protein degraders. Further, using bispecific antibody-based degraders (AbTACs) and delivering the PROTAC pre-fused with E3 ligases provides a solution for cell type-specific protein degradation. Here, we highlighted the current advancements and challenges associated with developing new tumour-specific protein degrader approaches and summarized their potential as single agents or combination therapeutics for cancer.

News (Medical) associated with ORM-5029

13 Sep 2024

·www.businesswire.com

Degrader-Antibody Conjugates 2024: Industry Analysis of Stakeholders, Technologies, Pipeline and Partnering - ResearchAndMarkets.com

DUBLIN--( BUSINESS WIRE )--The "Degrader-Antibody Conjugates 2024: A Landscape Analysis of Stakeholders, Technologies, Pipeline and Partnering from an Industry Perspective" report has been added to ResearchAndMarkets.com's offering. This report provides you with a landscape description and analysis of degrader-antibody conjugate (DAC) stakeholders, platform technologies, development and discovery pipelines and partnering deals from an industry perspective as of September 2024. The emerging novel drug modality of degrader-antibody conjugates represents the convergence of the existing technologies of antibody-drug conjugation and targeted protein degradation with the goal of combining the strengths and avoiding the limitations of both technologies. DACs combine the specificity of antibodies with the efficiency of degraders of difficult to drug protein targets. Degrader-antibody conjugates provide plenty of opportunities for ADC companies to use a novel payload to improve efficacy and the therapeutic window and for targeted protein degradation (TPD) companies to improve cell-specificity, half-life and drug-like properties. The two main uses for Degrader-Antibody Conjugate therapy are: Intracellular Targeted Protein Degradation Extracellular Targeted Protein Degradation The report brings you up-to-date with information about and analysis of: Stakeholders in the field, by company profiles of DAC activities at pharmaceutical and TPD technology companies; DAC technologies using PROTAC and molecular glue for proteasomal degradation for intracellular TPD; Proteins-of-interest for intracellular degradation; E3 ligases used for intracellular degradation; DAC technologies using broadly acting degraders for extracellular TPD; DAC technologies with lysosomal pathway degraders; Clinical and non-clinical development pipeline of DACs; Profiles of clinical stage DACs; DAC discovery pipeline; Preclinical proof-of-concept of DAC conjugate technologies and constructs; Partnering activities (acquisition, licensing, collaborations) The original concept of degrader-antibody conjugates defines DACs as tumor-targeted antibodies chemically conjugated to proteolysis-targeting chimera (PROTACs). PROTACs are large heterobifunctional small molecules with one part binding to the intracellular protein of interest (PoI), e.g. Bruton's Tyrosine Kinase (BTK), via a linker to a second part which binds to an E3 ligase that ubiquitylates the PoI, resulting in proteasomal degradation in the cytosol. The majority of DAC discovery programs rely on this concept, but DAC using a molecular glue instead of a PROTAC are also being pursued and even are the first in clinical evaluation. Molecular glue-type small molecules act as an glue that enhances the interaction between an E3 ligase and a PoI, leading to its ubiquitylation and proteasomal degradation. PROTACs are easier to design than glues given their independent binding sites to the E3 ligase and the PoI. However, they are generally large molecules that can be challenging to develop, whereas glues are typically smaller and more "drug-like". The scope of degrader-antibody conjugates is currently being expanded into the extracellular space for degradation of membrane bound and soluble proteins. Extracellular targeted protein degradation involves bispecific biologics or small molecules that recruit the PoI, either membrane-bound or secreted (soluble), to a degradation machinery. Degradation may occur through a transmembrane E3 ligase, or a cytokine receptor or via a membrane bound recycling receptor for transport of the PoI to the lysosome, which is the typical pathway for the degradation of extracellular proteins. Key Topics Covered: 1 Executive Summary 2 Introduction 3 Analysis of Stakeholders in Degrader-Antibody Conjugate R&D 3.1 Pharmaceutical Companies 3.2 Technology Companies 4 Analysis of Degrader-Antibody Conjugate Technologies 4.1 Overview of Degrader-Antibody Conjugate Technologies 4.2 Degrader-Antibody Conjugates with Molecular Glue-type Degraders 4.3 Degrader-Antibody Conjugates with PROTAC-type Degraders 4.4 Degrader-Antibody Conjugates with Broadly Acting Degraders 4.5 Degrader-Antibody Conjugates with Lysosomal Pathway Degraders 5 Analysis of Degrader-Antibody Conjugate Research & Development 5.1 Clinical & Nonclinical Development Pipeline of Degrader-Antibody Conjugates 5.1.1 Profile of ORM-6151 5.1.2 Profile of ORM-5029 5.2 Pipeline of Discovery Stage Degrader-Antibody Conjugate Programs 5.3 Preclinical Proof-of-Concept of Degrader-Antibody Conjugate Technologies and Constructs 6 Analysis of Partnering in the Field of Degrader-Antibody Conjugate Partnering 6.1 Acquisition 6.2 Licensing 6.3 Discovery Collaborations 7 Profiles of Companies with Degrader-Antibody Conjugate R&D 7.1 Pharmaceutical Companies Bristol Myers Squibb CSPC Pharmaceutical Group Debiopharm Eisai GlaxoSmithKline Merck KGaA Merck & Co. (MSD) Novartis Pfizer Pierre Fabre Roche Vertex Pharmaceuticals 7.2 Technology Companies C4 Therapeutics Crossfire Oncology Cullgen EpiBiologics Firefly Bio InduPro Lycia Therapeutics NanoMedSyn NIBEC Nurix Therapeutics Orum Therapeutics Prelude Therapeutics Ubix Therapeutics VectorY Therapeutics 8 Profiles of Degrader-Antibody Conjugate Technologies AMFA CELMoD ADC Degraducer DELigase EpiTAC EPriL LYTAC & GELYTAC PROTAB PROxAb REULR TORPEDO TPD2 uSMITE VecTron For more information about this report visit https://www.researchandmarkets.com/r/aj64k4 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.

ADC

16 Jul 2024

·pipelinereview.com

Orum Therapeutics Announces a Global, Multi-Target License and Option Agreement with Vertex for the Use of Orum’s TPD²® Technology to Develop Novel Degrader-Antibody Conjugates

Orum to receive a $15 million upfront payment and up to $310 million in potential option fees and milestone payments per target plus tiered royalties BOSTON, MA, USA & DAEJEON, South Korea I July 16, 2024 I Orum Therapeutics (“Orum” or the “Company”), a clinical-stage private biotechnology company pioneering the field of degrader-antibody conjugates (DACs), today announced a global, multi-target license and option agreement whereby it granted Vertex Pharmaceuticals (“Vertex”) (Nasdaq: VRTX) rights to conduct research using Orum’s Dual-Precision Targeted Protein Degradation (TPD² ® ) technology for the discovery of novel targeted conditioning agents for use with gene editing. Following the research period for each target, Vertex will have the option to obtain a worldwide, exclusive license to research, develop, manufacture, and commercialize DACs developed with Orum’s TPD² technology for that target. Under the terms of this agreement, Orum will receive an upfront payment of $15 million and is eligible to receive additional option payments and milestones potentially totaling up to $310 million per target for up to three targets, as well as tiered royalties on potential future global annual net sales. Vertex is responsible for all research, development, and commercialization. “Vertex is a leader in discovering and developing innovative medicines, including being the first to receive FDA approval of a CRISPR/Cas9 gene-edited therapy, and we are pleased they’ve selected Orum’s TPD² technology to discover novel targeted conditioning agents,” said Sung Joo Lee, Ph.D., CEO and founder of Orum Therapeutics. “This agreement with Vertex creates the potential to treat patients in a novel indication space with our leading targeted protein degradation approach for an exciting new therapeutic class of degrader-antibody conjugates.” About Vertex Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious diseases. The company has approved medicines that treat the underlying causes of multiple chronic, life-shortening genetic diseases — cystic fibrosis, sickle cell disease and transfusion-dependent beta thalassemia — and continues to advance clinical and research programs in these diseases. Vertex also has a robust clinical pipeline of investigational therapies across a range of modalities in other serious diseases where it has deep insight into causal human biology, including acute and neuropathic pain, APOL1-mediated kidney disease, IgA nephropathy, autosomal dominant polycystic kidney disease, type 1 diabetes, myotonic dystrophy type 1 and alpha-1 antitrypsin deficiency. Vertex was founded in 1989 and has its global headquarters in Boston, with international headquarters in London. Additionally, the company has research and development sites and commercial offices in North America, Europe, Australia, Latin America and the Middle East. Vertex is consistently recognized as one of the industry’s top places to work, including 14 consecutive years on Science magazine’s Top Employers list and one of Fortune’s 100 Best Companies to Work For. For company updates and to learn more about Vertex’s history of innovation, visit www.vrtx.com or follow us on LinkedIn , Facebook , Instagram , YouTube and Twitter/X . About Orum’s TPD² Approach Orum’s unique Dual-Precision Targeted Protein Degradation (TPD²) approach builds novel targeted protein degraders combined with the precise tumor cell delivery mechanisms of antibodies to generate innovative, first-in-class, tumor-selective TPDs for the treatment of cancer. Orum has developed new molecular glue degrader payloads to specifically degrade an intracellular target protein within cancer cells via the E3 ubiquitin ligase pathway. Conjugated to antibodies, the payloads are designed to be delivered specifically to cancer cells and degrade the intracellular target protein and cause tumor cell death. About Orum Therapeutics Orum Therapeutics is a private, clinical-stage biotech pioneering the development of cell-specific, targeted protein degraders (TPD² ® ) and stabilizers (TPS²™) with the precision of antibody targeting to improve cancer treatment for more patients. The lead therapeutic candidate from the TPD² GSPT1 platform, ORM-5029, is in clinical development for the treatment of HER2-expressing solid tumors. The TPS² approach uses proprietary Cbl-b inhibitor payloads conjugated to immune cell- or tumor cell-targeting antibodies. Orum is located in Lexington, MA, US, and Daejeon, South Korea. For more info, visit www.orumrx.com . SOURCE: Orum Therapeutics

License out/in

16 Jul 2024

·www.fiercebiotech.com

Vertex mines for more gene editing riches with $15M Orum licensing deal

In return for its technology, Orum will receive an upfront payment of $15 million from Vertex, with the potential to earn close to $1 billion more. Vertex struck gold with the licensing of CRISPR Therapeutics’ sickle cell gene editing therapy in 2017. With that med now approved as Casgevy, Vertex is looking to extend its claim in gene editing therapy through a small licensing deal with South Korea's Orum. The pharma will license Orum’s degrader-antibody conjugate technology for $15 million upfront plus $310 million per target in milestones plus royalties on future sales. The deal includes three targets. Vertex will be responsible for all research, development and commercialization efforts as part of the deal. Vertex will conduct research using the South Korean biotech’s protein degraders to identify new conditioning agents. Conditioning agents are used in treatments to prepare patients for a more intense and disruptive therapy, like gene therapy, to improve the chance of success and make it less likely the patient experiences adverse side effects. Orum’s approach, which the firm calls Dual-Precision Targeted Protein Degradation, involves linking tumor-targeting antibodies with proteins called molecular glue degraders, which latch onto target proteins and recruit enzymes to destroy them. Eliminating the right proteins in the tumor cells leads to cell death. The biotech's lead candidate using this technique is ORM-5029, which is currently in clinical development for the treatment of HER2-expressing solid tumors. Orum had another deal with a much larger, though still modest, upfront payment late last year, when Bristol Myers Squibb picked up the company’s phase 1 blood cancer treatment for $100 million.

License out/inGene TherapyPhase 1

100 Deals associated with ORM-5029

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
HER2 Positive Breast Cancer	Phase 1	US	Orum Therapeutics USA, Inc.	03 Oct 2022
HER2 Positive Solid Tumors	Phase 1	US	Orum Therapeutics USA, Inc.	03 Oct 2022

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