Novel Science

ONCT-808

Publications - ROR1 Biology

ROR1: An Orphan Becomes Apparent (Thomas J Kipps, Blood. 2022 Oct 6;140(14):1583-1591)

The Onco-Embryonic Antigen ROR1 is Expressed by a Variety of Human Cancers (Suping Zhang , Liguang Chen, Jessica Wang-Rodriguez, Ling Zhang, Bing Cui, Wendy Frankel, Rongrong Wu, Thomas J Kipps, Am J Pathol. 2012 Dec;181(6):1903-10).

Publications - ROR1 as Target for Immunotherapy

Anti-ROR1 CAR-T Cells: Architecture and Performance (Daniel Andrés Osorio-Rodríguez, Bernardo Armando Camacho, César Ramírez-Segura Front Med (Lausanne). 2023; 10: 1121020).

Developing ROR1 Targeting CAR-T Cells Against Solid Tumors in Preclinical Studies (Boon Kiat Lee, Yuhua Wan, Zan Lynn Chin, Linyan Deng, Mo Deng, Tze Ming Leung, Jian Hua, Hua Zhang, Cancers (Basel). 2022 Jul 25;14(15):3618).

The WNT/ROR Pathway in Cancer: From Signaling to Therapeutic Intervention (Kerstin Menck, Saskia Heinrich, Cornelia Baden, Annalen Bleckmann, Cells. 2021 Jan 12;10(1):142).

Conference Presentations

S. Meinke 2022 EHA Poster Preclinical Evaluation of Zilovertamab-Based Anti-ROR1 Chimeric Antigen Receptors in NK and T Cells

Preclinical Evaluation of Anti-ROR1 CAR T-cells Employing a ROR1 Binding scFv Derived  From the Clinical Stage mAb Cirmtuzumab (Prussak et al.,  2020 ASCO-SITC Clinical Immuno-Oncology Symposium)

ONCT-534

Publications - Androgen Receptor as Target for Prostate Cancer Therapy

An Overview of Next-Generation Androgen Receptor-Targeted Therapeutics in Development for the Treatment of Prostate Cancer, (Michael L Mohler, Arunima Sikdar, Suriyan Ponnusamy, Dong-Jin Hwang, Yali He, Duane D Miller, Ramesh Narayanan, Int J Mol Sci. 2021 Feb 20;22(4):2124).

AR-V7 and Resistance to Enzalutamide and Abiraterone in Prostate Cancer, (Emmanuel S. Antonarakis, M.D., et al.; N Engl J Med 2014; 371:1028-1038).

Publications - DAARI / ONCT-534 Publications

Novel Selective Agents for the Degradation of Androgen Receptor Variants to Treat Castration-Resistant Prostate Cancer, (Ponnusamy S et al., Cancer Res. 2017 Nov 15;77(22):6282-6298. MID: 28978635).

New Generation of Selective Androgen Receptor Degraders: Our Initial Design, Synthesis, and Biological Evaluation of New Compounds with Enzalutamide-Resistant Prostate Cancer Activity Hwang DJ et al., (J Med Chem 2019 Jan 24;62(2):491-511. PMID: 30525603).

Orally Bioavailable Androgen Receptor Degrader, Potential Next-Generation Therapeutic for Enzalutamide-Resistant Prostate Cancer. (Ponnusamy S et al., Clin Cancer Res. 2019 Sep 3. PMID: 31481513)

Pyrazol-q-yl-Propanamides as Selective Androgen Receptor Degraders (SARDs) and Pan-Antagonists for the Treatment of Enzalutamide-Resistant Prostate Cancer. (He Y et al., J. Med. Chem. 2020 Nov 12. PMID: 33095584)

Conference Presentations

AACR-NCI-EORTC Molecular Targets and Cancer Therapuetics Conference Presentation_October 2021

Cellular Hormone Metabolism is Critical for Canonical Androgen Receptor Antagonist Activity (EORTC-NCI-AACR Molecular Targets and Cancer Therapeutics Symposium 2022)

Narayanan SUO 2022 Poster Dual-Action Androgen Receptor Inhibitors (DAARI)

Zilovertamab

Publications

 Outcomes in 370 patients with mantle cell lymphoma treated with ibrutinib: a pooled analysis from three open-label studies (Rule et al, Br J Haem 2017) 

Cirmtuzumab inhibits ibrutinib-resistant, Wnt5a-induced Rac1 activation and proliferation in mantle cell  lymphoma (Yu et al., Oncotarget 2018)

Phase 1 Trial: Cirmtuzumab Inhibits ROR1 Signaling and Stemness Signatures in Patients with Chronic Lymphocytic Leukemia (Choi et al, Cell Stem Cell, 2018)

Inhibition of chemotherapy resistant breast cancer stem cells by a ROR1 specific antibody (Zhang et al.,  PNAS 2019)

Ovarian Cancer Stem Cells Express ROR1, Which Can Be Targeted  for Anti-Cancer-Stem-Cell  Therapy (Zhang et al., PNAS 2014)

Conference Presentations

Phase 1/2 Study of Zilovertamab and Ibrutinib in Mantle Cell Lymphoma (MCL), Chronic Lymphocytic Leukemia (CLL), or Marginal Zone Lymphoma (MZL) ) (Lee et al., ASH 2022 Annual Meeting).

Study ZILO-301 A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Zilovertamab Plus Ibrutinib vs. Ibrutinib in Patients with Relapsed or Refractory Mantle Cell Lymphoma (EHA 2022, S. Yazji)

Phase 1/2 Study of Zilovertamab (formerly Cirmtuzumab) and Ibrutinib in Mantel Cell Lymphoma (MCL) or Chronic Lymphocytic Leukemia (CLL) (Lee et al., ASCO 2022 Annual Meeting)

Lee 2021 ASH Poster Zilovertamab + Ibrutinib for MCL

Lee 2021 ASH Presentation Zilovertamab + Ibrutinib for MCL

Phase 1/2 Study of Cirmtuzumab and Ibrutinib in Mantle Cell Lymphoma (MCL) or Chronic Lymphocytic Leukemia (CLL)

Phase 1/2 Study of Cirmtuzumab and Ibrutinib in Mantle Cell Lymphoma (MCL) or Chronic Lymphocytic Leukemia (CLL) - VIDEO

A Phase 1b Trial of Cirmtuzumab and Paclitaxel in Locally Advanced/Unresectable or Metastatic Her2 Negative Breast Cancer (Shatsky et al., AACR 2021 Virtual Annual Meeting)

Inhibition of Ovarian and Endometrial Cancer Cell Proliferation by an Anti-ROR1 Monoclonal Antibody (Liu et al., AACR 2021 Virtual Annual Meeting)

Cirmtuzumab, an Anti-ROR1 Antibody, in Combination with Ibrutinib: Clinical Activity in Mantle Cell Lymphoma (MCL) or Chronic Lymphocytic Leukemia (CLL) from a Phase 1/2 Study (Lee et al., ASH 2020 Virtual Annual Meeting)

 Clinical Activity of Cirmtuzumab, an Anti-ROR1 Antibody, in Combination with Ibrutinib; Interim Results of a Phase 1b/2 Study in Mantle Cell Lymphoma (MCL) or Chronic Lymphocytic Leukemia (CLL) (Lee et al., ASCO 2020 Virtual Annual Meeting)

Cirmtuzumab, a ROR1 Targeted Mab, Reverses Cancer Stemness, and Its Combination with Ibrutinib Is Safe  and Effective: Planned Analysis of the CIRLL Phase 1/2 Trial for CLL and MCL (Choi et al,. ASH Annual  Meeting 2019)

 A Phase 1b Trial of Cirmtuzumab and Paclitaxel in Locally Advanced /Unresectable or Metastatic Her2  Negative Breast Cancer (Shatsky et al., San Antonio Breast Cancer Symposium 2019)