ORM-5029 / Orum Therap - LARVOL DELTA

Discovery of novel, potent and orally active GSPT1 molecular glue degraders (AACR 2025) - "In fact, clinical proof of concept has been obtained with immunomodulatory drugs such as thalidomide, lenalidomide and pomalidomide, which degrade IKZF1/IKZF3...GSPT1 degrader antibody conjugates are now in clinical trials for breast cancer (ORM-5029) and AML (BMS-986497/ORM-6151)...These encouraging results have prompted us to explore a series of GSPT1 MGDs.In the present study, we describe the discovery of a series of novel, potent and orally active GSPT1 MGD targeting tumors with high GSPT1 expression...This compound demonstrates in vivo efficacy in CDX model with a favorable profile comparable to that of MRT-2359. In summary, a series of orally active GSPT1 degraders have been discovered with preclinical profile suitable for further development to manage cancers with high GSPT1 expression."

Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BCL6 • GSPT1 • IKZF1 • IKZF3 • STAT6 • VAV1

[IPO Alert][Orum Therapeutics] No Good News for Several Years After IPO [Google translation] (PRESS9) - "Orum therapeutics announced that it plans to transfer technology for ORM-5029, which was suspended due to toxicity issues in the low-dose phase 1 clinical trial, in 2026....In addition, Orom Therapeutics announced that it plans to transfer ORM-1023 and ORM-1153, which are still in the discovery stage, in 2026. It seems premature to discuss technology transfer when the substance has not been confirmed."

Commercial • Hematological Malignancies • HER2 Breast Cancer • Small Cell Lung Cancer

Orom Therapeutics, IPO Re-challenge… Demand Forecast Begins on the 17th of Next Month [Google translation] (News1 Korea) - "Orom Therapeutics dismissed the serious adverse events (SAEs) that occurred in participants in the phase 1 clinical trial of its flagship pipeline 'ORM-5209', which were identified during the initial listing process, as being limited to a specific project...'We officially reported the occurrence of the SAE to the U.S. Food and Drug Administration (FDA) on the 11th of last month, and received a partial clinical hold notification from the FDA in accordance with the procedure.'....'We believe that the ORM-5029 SAE is limited to the characteristics of the project. We believe that the possibility of a significant impact on the achievement of milestones in the existing technology transfer contract and the ongoing R&D project is limited.'"

Trial status • Trial suspension • Solid Tumor • HER-2

Study of ORM-5029 in Subjects with HER2-Expressing Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=87 | Active, not recruiting | Sponsor: Orum Therapeutics USA, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Orum Therapeutics invests 30 billion won in research funds for 3 types including ’ORM-5029’ [Google translation] (Medipana) - "It plans to raise the funds through a public offering on the KOSDAQ market in November. According to the Financial Supervisory Service's Electronic Disclosure System on the 7th, Orum Therapeutics plans to use approximately 30 billion won in funds for three projects under research and development, 'ORM-5029', 'ORM-1023', and 'ORM-1153', by 2026. Specifically, it plans to invest 11.3 billion won in 'ORM-5029', a metastatic breast cancer treatment, 9 billion won in 'ORM-1023', a small cell lung cancer treatment, and 9.8 billion won in 'ORM-1153', a blood cancer treatment....The plan is to procure funds for research and development through a KOSDAQ listing scheduled for November. According to the securities report submitted by Orum Therapeutics on the 2nd, the number of shares being offered through this KOSDAQ listing is 3 million, and the range of the desired public offering price per share is 30,000 to 36,000 won."

Financing • Breast Cancer • Hematological Malignancies • HER2 Breast Cancer • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Orum Therapeutics invests 30 billion won in research funds for 3 types including 'ORM-5029' [Google translation] (Medipana) - "The company's lead pipeline ORM-5029 is currently undergoing phase 1 clinical trials in the United States, and the company plans to transfer the asset technology after the phase 1 clinical trial is completed...'it is expected that a technology transfer contract can be signed in 2026.'....In addition, the company announced that it is planning an asset technology transfer for 'ORM-1153', which is currently in the preclinical stage, at the IND stage before entering phase 1 clinical trials in 2026, and an asset technology transfer for 'ORM-1023', which will also be conducted jointly with a partner at the IND stage before entering phase 1 clinical trials in 2026."

Licensing / partnership • New P1 trial • Trial status • Breast Cancer • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • HER-2

Powering up targeted protein degradation through active and passive tumour-targeting strategies: Current and future scopes. (PubMed, Pharmacol Ther) - "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."

Journal • Review • Oncology • Targeted Protein Degradation

ORM-5029: Discovery of an antibody drug conjugate with first-in-class molecular glue degrader warhead for treatment of HER2-positive breast cancer (ACS-Fall 2023) - P1 | "HER2-targeted ADCs, Kadcyla and Enhertu, have improved survival rates for patients with metastatic breast cancer, but additional therapies are needed due to dose-limiting toxicities and ultimate drug resistance. As a result, we nominated ORM-5029, composed of SMol006 conjugated to pertuzumab via a Val-Cit PABc linker (average degrader-to-antibody ratio ~4).ORM-5029 treatment in HER2-expressing cell lines showed 10 to 1000-fold greater potency compared to Enhertu and tumor growth delay at 3 mg/kg in the HER2-low, MDA-MB-453 triple negative breast cancer model (HER2 2+ by IHC). ORM-5029 is currently in clinical development (ClinicalTrials.gov Identifier: NCT05511844) as a potential first-in-class targeted protein degrader powered with ADC technology."

Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • Triple Negative Breast Cancer • GSPT1 • HER-2

A phase 1, first-in-human, open label, escalation and expansion study of ORM-5029, a highly potent GSPT1 degrader targeting HER2, in patients with HER2-expressing advanced solid tumors. (ASCO 2023) - P1 | "ORM-5029 is a first-in-class human epidermal growth factor receptor 2 (HER2)-targeted antibody-drug conjugate (ADC) comprised of SMol006, a highly potent GSPT1 degrader, conjugated to pertuzumab, a clinically validated antibody...ORM-5029 showed robust in vitro and in vivo efficacy in multiple HER2-expressing models with comparable activity to trastuzumab deruxtecan and strong activity in trastuzumab emtansine-refractory models...Escalation cohort 1 was completed without DLT; enrollment in cohort 2 began as of December 2022. Clinical trial information: NCT05511844."

Clinical • Metastases • P1 data • Breast Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • HER2 Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • GSPT1 • HER-2

Orum Therapeutic Announces ORM-5029 Phase 1 Clinical Trial Design Poster at ASCO [Google translation] (Yakup Shinmoon) - "Orum Therapeutic (CEO Lee Seung-joo) announced on the 2nd that it will post a poster for the Phase 1 clinical trial of ORM-5029 at the ASCO (American Society of Clinical Oncology)....The clinical trial, which began administering the first patient in October last year, aims to develop a breast cancer treatment that relapses or is refractory to existing HER2-targeted therapies such as Enhertu, and is aimed at more than 2 breast cancer patients."

Trial status • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

TPD2 Conjugates – Antibody-Enabled Dual Precision Targeted Protein Degraders (PEGS 2023) - "Two TPD² GSPT1 degraders in clinical/late preclinical testing, ORM-5029 for breast cancer and ORM-6151 for AML will be discussed. Furthermore, a second TPD² platform PROTAb used to deliver bifunctional degraders will also be highlighted."

Acute Myelogenous Leukemia • Breast Cancer • Hematological Disorders • Hematological Malignancies • Oncology • Solid Tumor • Targeted Protein Degradation • GSPT1

ORM-6151: A first-in-class CD33-antibody enabled GSPT1 degrader for AML (AACR 2023) - "We have previously shown in vitro and in vivo efficacy with a HER2-targeted TPD2 conjugate: ORM-5029...ORM-6151 treatment in CD33-expressing cell lines showed picomolar activity with 10-1000-fold greater potency compared to several GSPT1 degrader molecules, including CC-90009 or Mylotarg, and had robust activity in Mylotarg-resistant lines (AML193 and Kasumi6)...Tumor growth inhibition correlated with the degree and duration of GSPT1 depletion and changes in the expression of previously described integrated stress response biomarker genes. In summary, ORM-6151 is a promising, potential therapy for AML and currently in preclinical development as a first-in-class targeted protein degrader therapy with CD33-targeted delivery."

Acute Myelogenous Leukemia • Oncology • CD33 • GSPT1 • HER-2

Development of RNAscope multiplex-based assay for exploratory pharmacodynamic biomarkers assessment in breast cancer patients from Phase I clinical trial of ORM-5029, a potent GSPT1 degrader (AACR 2023) - P1 | "It delivers a highly potent and precise catalytic GSPT1 protein degrader molecule (SMol006) selectively to HER2-expressing tumor cells via conjugation to pertuzumab. The optimized protocol is currently being developed into RNAscope multiplex workflow using BT474 FFPE sections and tissue microarrays. In summary, RNAscope multiplex assay could be used as a method to determine pharmacodynamic response in HER2+ breast cancer patients treated with ORM-5029."

Clinical • P1 data • PK/PD data • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • ATF3 • DDIT3 • GSPT1 • HER-2

Orum Therapeutics Unveils New Program at AACR 2023, Highlighting Cbl-b Inhibitor-PD-1 Conjugate, and Presents New Data Supporting Clinical Development of Two GSPT1 Programs (Businesswire) - "Orum’s new program in immuno-oncology achieves simultaneous blockade of PD-1/PD-L1 pathway and delivery of a Cbl-b inhibitor using anti-PD-1-Cbl-bi conjugates and demonstrates enhanced T cell activation in vitro compared to anti-PD-1 alone, even in the presence of immunosuppressive factors....ORM-6151 shows superior tolerability and robust single-dose efficacy, both in vitro and in vivo compared to CC-90009 or Mylotarg™, suggesting the potential for an improved therapeutic option in AML that appropriately balances efficacy with safety and tolerability of a clinically validated GSPT1 degradation mechanism....Orum has identified pharmacodynamic biomarkers as predictors of efficacy to support clinical development of ORM-5029 in HER2-expressing solid tumors."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor

Orum Therapeutics Announces Three Presentations at AACR 2023 (Businesswire) - "Orum Therapeutics...announced that it will present new preclinical data for its ORM-5029, ORM-6151, and PD-1-Cbl-b programs in three separate presentations at the American Association for Cancer Research (AACR) Annual Meeting 2023....ORM-5029 is a potential first-in-class targeted protein degrader therapy currently in a Phase 1 clinical trial for HER2-expressing breast cancer. ORM-6151 is currently in the IND-enabling stage for CD33-positive hematologic malignancies, such as acute myeloid leukemia (AML)."

Preclinical • Acute Myelogenous Leukemia • Breast Cancer • Hematological Malignancies • Leukemia • Oncology • Solid Tumor

"Tony Tolcher mentioned our first clinical molecule ORM-5029 at #ena2022. #tpd #adc https://t.co/wKw2fRgbZm" (@peterparkbio)

Clinical • Oncology

Orum Therapeutics Announces First Patient Dosed in Phase 1 Clinical Trial of ORM-5029 in Development to Treat HER2-Expressing Advanced Solid Tumors (Businesswire) - "Orum Therapeutics...announced that the first patient has been dosed with ORM-5029 in a Phase 1 clinical trial for patients with HER2-expressing advanced solid tumors. ORM-5029 is one of two lead programs from the company’s GSPT1 platform leveraging the Dual-Precision Targeted Protein Degradation (TPD²) approach, which is designed to leverage antibody drug conjugates (ADCs) to precisely deliver and target intracellular proteins for degradation leading to cancer cell death....The Phase 1 trial (ClinicalTrials.gov Identifier: NCT05511844) is an open label, multicenter, dose escalation and expansion study of ORM-5029 in patients with HER2-expressing advanced solid tumors who are not eligible for standard of care therapy."

Trial status • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

Study of ORM-5029 in Subjects With HER2-Expressing Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=87 | Recruiting | Sponsor: Orum Therapeutics USA, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Study of ORM-5029 in Subjects With HER2-Expressing Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=87 | Not yet recruiting | Sponsor: Orum Therapeutics USA, Inc.

New P1 trial • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

ORM-5029: A first-in-class targeted protein degradation therapy using antibody neodegrader conjugate (AnDC) for HER2-expressing breast cancer (AACR 2022) - "Given the comparable activity of both antibodies and frequent use of trastuzumab as the antibody domain of several ADCs, we selected pertuzumab as our targeting antibody...In the BT474 xenograft model, treatment with ORM-5029 demonstrated single-dose activity superior to Kadcyla, and comparable to Enhertu when given at an equivalent dose. In an HCC1569 xenograft model, tumor growth inhibition correlated with the degree and duration of GSPT1 depletion and changes in expression of previously described integrated stress response biomarker genes. ORM-5029 is currently in preclinical development as a potential first-in-class targeted protein degrader therapy with HER2-targeted delivery."

Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • GSPT1 • GSTP1 • HER-2

Orum Therapeutics Presents Preclinical Data at AACR 2022 Highlighting Novel Dual-Precision Targeted Protein Degrader, ORM-5029, Degrading GSPT1 (Businesswire) - "The data presented at AACR 2022 describes initial preclinical evaluation of potency, efficacy, and pharmacodynamic (PD) response of ORM-5029....ORM-5029 displays robust efficacy both in vitro and in vivo compared to other small molecule GSPT1 degraders and approved antibody drug conjugates (ADCs). ORM-5029 exhibits potent activity in HER2-low models both in vitro and in vivo."

Preclinical • Oncology • Solid Tumor

Orum Therapeutics to Present Preclinical Data for ORM-5029, a Novel Antibody Neodegrader Conjugate, at the AACR Annual Meeting 2022 (Businesswire) - "Orum Therapeutics...today announced that the Company will present preclinical data for ORM-5029 at the upcoming American Association for Cancer Research (AACR) Annual Meeting 2022 taking place April 8-13 virtually....Orum is developing ORM-5029 as a potential first-in-class targeted protein degrader therapy for HER2-expressing breast cancer."

Preclinical • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor

Orum Therapeutics Closes $84 Million Series B Financing to Advance Novel Targeted Protein Degrader Payloads into Clinical Trials for Cancer (Businesswire) - “Orum Therapeutics...announced the close of a $84 million Series B financing…Orum plans to use the proceeds to advance the Company’s lead therapeutic candidates into clinical trials…The lead therapeutic programs from Orum’s AnDC platform are ORM-5029 for the treatment of solid tumors and ORM-6151 for the treatment of hematological cancers. Each program employs a different antibody drug to specifically deliver Orum’s lead neoDegrader to tumor cells. The company plans to file Investigational New Drug (IND) applications for ORM-5029 and ORM-6151 in 2022 and 2023, respectively."

Financing • IND • Hematological Malignancies • Oncology • Solid Tumor