BMS-986497 / Orum Therap, BMS - LARVOL DELTA

Study of BMS-986497 (ORM-6151) as a Monotherapy, in Double and Triple Combination With Azacitidine and Venetoclax in Participants With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome (clinicaltrials.gov) - P1 | N=105 | Recruiting | Sponsor: Bristol-Myers Squibb | N=35 ➔ 105

Enrollment change • Monotherapy • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

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

TRX-214-1002, An antibody drug conjugate (ADC) targeting CD33 with a novel GSPT1 molecular glue for treatment of acute myeloid leukemia (AACR 2025) - "However, clinical development of GSPT1 MGDs, such as CC-885 and CC-90009, has been hampered by off-target toxicities...The in vitro and in vivo pharmacology of TRX-214-1002 were compared with ORM-6151 (another GSPT1 MG degrader-based CD33 ADC) and Mylotarg...Collectively, TRX-214-1002 highlighted the noticeable GSPT1 degradability and enhanced antileukemic activity, particularly in TP53 mutated and venetoclax-resistant AML cell lines, along with significant antitumor activity superior to competitor ADCs. Our preclinical data suggest that TRX-214-1002 has the high potential to provide a novel treatment strategy for CD33 positive relapse/refractory AML patients."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Lung Cancer • Oncology • Solid Tumor • ATF3 • ATF4 • CD33 • FLT3 • GSPT1 • TP53

Study of BMS-986497 (ORM-6151) in Participants With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome (clinicaltrials.gov) - P1 | N=35 | Recruiting | Sponsor: Bristol-Myers Squibb | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Study of BMS-986497 (ORM-6151) in Participants With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome (clinicaltrials.gov) - P1 | N=35 | Not yet recruiting | Sponsor: Bristol-Myers Squibb

New P1 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Orum Therapeutics Announces Acquisition of ORM-6151 Program by Bristol Myers Squibb (Businesswire) - "Orum Therapeutics...announced that they have entered into a definitive agreement under which Bristol Myers Squibb has acquired Orum’s ORM-6151 program. ORM-6151 is a first-in-class, anti-CD33 antibody-enabled GSPT1 degrader that has received the FDA’s clearance for Phase 1 for the treatment of patients with acute myeloid leukemia or high-risk myelodysplastic syndromes....Under this transaction, Bristol Myers Squibb has acquired Orum’s ORM-6151 program for an upfront payment of $100 million, and Orum Therapeutics is eligible to receive milestone payments for a total deal value of $180 million. Further details were not disclosed."

IND • M&A • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

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

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

ORM-6151: A First-in-Class, Anti-CD33 Antibody-Enabled GSPT1 Degrader for AML (ASH 2022) - "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). The tumor growth inhibition correlated with the degree and duration of GSPT1 depletion and changes in 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 • Targeted Protein Degradation • CD33 • GSPT1

Orum Therapeutics Presents Positive Preclinical Data of ORM-6151, a First-in-Class, CD33-GSPT1 Dual-Precision Targeted Protein Degrader for AML, at ASH 2022 (Businesswire) - "Orum Therapeutics...today announced the presentation of positive preclinical data for ORM-6151, a first-in-class, anti-CD33 antibody-enabled GSPT1 degrader for acute myeloid leukemia (AML), at the 64th American Society of Hematology (ASH 2022)....The data show that ORM-6151 has picomolar potency and efficacy superior to clinically equivalent doses of CC-90009...in CD33-expressing cell lines and primary relapsed/refractory AML patient blasts. In a clinically relevant animal model of AML, a single treatment of ORM-6151 at doses as low as 1 mg/kg, compared to a clinically equivalent dose of CC-90009, demonstrated superior tumor growth inhibition and correlated with the degree and duration of GSPT1 depletion."

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

Orum Therapeutics Announces Presentation at ASH 2022 Annual Meeting (Businesswire) - "Orum Therapeutics...announced the presentation of preclinical data for ORM-6151, a first-in-class, anti-CD33 antibody-enabled GSPT1 degrader for acute myeloid leukemia (AML). The data will be presented at the 64th American Society of Hematology (ASH 2022) Annual Meeting & Exposition taking place December 10-13, in New Orleans."

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

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