A Phase I/IIa Study Evaluating the Safety and Tolerability of Intratumoral Administration of ORCA-010 in Treatment-Naïve Patients With Localized Prostate Cancer.

This open label, dose escalating study is a phase I/IIa first in man study designed to evaluate the safety and tolerability of intratumoral administration of a novel oncolytic adenovirus (ORCA-010) in treating diagnosed treatment naïve Patients with localized prostate cancer.

Start Date12 Nov 2019

Sponsor / Collaborator

ORCA Therapeutics BV

[+1]

100 Clinical Results associated with ORCA-010

100 Translational Medicine associated with ORCA-010

100 Patents (Medical) associated with ORCA-010

Literatures (Medical) associated with ORCA-010

17 Jul 2020·Clinical and experimental immunologyQ3 · MEDICINE

Oncolytic adenovirus ORCA-010 increases the type 1 T cell stimulatory capacity of melanoma-conditioned dendritic cells

Q3 · MEDICINE

Article

Author: de Gruijl, T D ; de Haan, H ; Eck van der Sluijs, J ; López González, M ; van de Ven, R ; van Beusechem, V W ; Dong, W

Summary:

Immune checkpoint blockade has resulted in durable responses in patients with metastatic melanoma, but only in a fraction of treated patients. For immune checkpoint inhibitors (ICI) to be effective, sufficient infiltration with tumor-reactive T cells is essential. Oncolytic viruses (OV) selectively replicate in and lyse tumor cells and so induce an immunogenic form of cell death, providing at once a source of tumor-associated (neo)antigens and of danger signals that together induce effective T cell immunity and tumor infiltration. Melanoma-associated suppression of dendritic cell (DC) differentiation effectively hampers OV- or immune checkpoint inhibitor (ICI)-induced anti-tumor immunity, due to a consequent inability to prime and attract anti-tumor effector T cells. Here, we set out to study the effect of ORCA-010, a clinical stage oncolytic adenovirus, on DC differentiation and functionality in the context of human melanoma. In melanoma and monocyte co-cultures, employing a panel of five melanoma cell lines with varying origins and oncogenic mutation status, we observed clear suppression of DC development with apparent skewing of monocyte differentiation to a more M2-macrophage-like state. We established the ability of ORCA-010 to productively infect and lyse the melanoma cells. Moreover, although ORCA-010 was unable to restore DC differentiation, it induced activation and an increased co-stimulatory capacity of monocyte-derived antigen-presenting cells. Their subsequent ability to prime effector T cells with a type I cytokine profile was significantly increased in an allogeneic mixed leukocyte reaction. Our findings suggest that ORCA-010 is a valuable immunotherapeutic agent for melanoma.

01 Oct 2014·Human gene therapyQ2 · MEDICINE

ORCA-010, a Novel Potency-Enhanced Oncolytic Adenovirus, Exerts Strong Antitumor Activity in Preclinical Models

Q2 · MEDICINE

Article

Author: Dong, Wenliang ; Meulenberg, Janneke J.M. ; Alemany, Ramon ; Au, Kam Y. ; van Beusechem, Victor W. ; van Ginkel, Jan-Willem H.

Improving the antitumor potency of current oncolytic adenoviruses represents one of the major challenges in development of these viruses for clinical use. We have generated an oncolytic adenovirus carrying the safety-enhancing E1AΔ24 deletion, the potency-enhancing T1 mutation, and the infectivity-enhancing fiber RGD modification. The results of in vitro cytotoxicity assays on 15 human cancer cell lines derived from different tumor types demonstrated that ORCA-010 is more potent than Ad5-Δ24RGD or ONYX-015. As ORCA-010 will initially be developed for the treatment of prostate cancer, selectivity experiments were performed using primary human prostate cells. ORCA-010 killed cancer cells more effectively than these primary human cells. In both primary prostate fibroblasts and epithelial cells, ORCA-010 was as safe as Ad5-Δ24RGD. Evaluation of ORCA-010 in in vivo xenograft tumor models in nude mice showed that ORCA-010 significantly inhibited growth of prostate, lung, and ovarian tumors and conferred prolonged survival of tumor-bearing animals. Furthermore, we observed a substantial increase in infectious viral particles in tumors injected with ORCA-010. The number of infectious viral particles increased after treatment and infectious particles remained present up to at least 4 weeks posttreatment. Intratumoral virus replication was associated with substantial necrosis and fibrosis. In conclusion, ORCA-010 is more potent than earlier generation oncolytic adenoviruses, without demonstrating increased toxicity. ORCA-010 exerted strong in vivo antitumor activity and is therefore a suitable candidate for clinical evaluation.

News (Medical) associated with ORCA-010

04 Nov 2024

·www.orca-therapeutics.nl

Prof. Dr. Tanja de Gruijl to Present Clinical Data on ORCA-010 at ESMO Immuno-Oncology Congress 2024

Amsterdam, Netherlands – November 2024 ORCA Therapeutics B.V., a Dutch biopharmaceutical company pioneering innovative oncolytic immunotherapies for cancer treatment, today announced that Professor Dr. Tanja de Gruijl will present clinical data from the company’s lead product ORCA-010 at the European Society for Medical Oncology Immuno-Oncology (ESMO IO) Congress in Geneva, Switzerland. The presentation, titled “ORCA-010 Oncolytic Therapy: Inducing Tumor-Specific Immune Responses and Activation of Tumor Microenvironment in Treatment-Naïve Prostate Cancer,” will highlight key immunological findings from ORCA’s Phase I/IIA clinical trial. Patients treated with ORCA-010 presented with immune infiltration highly associated with regions containing cancer cells, activation of the tumor microenvironment and the induction of systemic tumor-specific immune responses. Professor de Gruijl is a distinguished leader in tumor immunology, holding the position of Professor of Translational TumourImmunology and the Fenna Diemer Lindeboom Chair at Amsterdam University Medical Centers. With over 25 years of experience and more than 250 publications, her expertise spans from preclinical research to immune monitoring in clinical trials. Her groundbreaking work includes research on tumor-draining lymph nodes, immunological enhancement of oncolytic adenoviruses, and targeted immune cell therapies. Prof. de Gruijlserves on the board of directors of the Society for the Immunotherapy of Cancer (SITC) and is an associate editor for several prestigious journals in the field. ORCA-010 is a state-of-the-art oncolytic adenovirus therapy designed to specifically kill tumor cells, modify the tumor microenvironment while inducing systemic anti-tumor immune responses. The Phase I/IIA trial focuses on treatment-naïve, early-stage prostate cancer patients. Analyses suggest not only the potential to induce stabilization or decrease of PSA, but also impact on distant tumors, long-term immunological activation of the tumor microenvironment and induction of a systemic anti-tumor immune response. ORCA Therapeutics BV is a leader in immuno-oncology therapeutics, specializing in oncolytic viruses and innovative gene therapy approaches. The company is dedicated to translating cutting-edge scientific discoveries into effective therapeutic solutions, addressing unmet medical needs and improving patient outcomes globally. For more information about our mission and ongoing projects, visit www.orca-therapeutics.com Dr. Wenliang Dong, Ph.D., MBA CEO, ORCA Therapeutics BV Email: info@orca-therapeutics.com Website: www.orca-therapeutics.com

ImmunotherapyClinical Study

28 Oct 2024

·www.orca-therapeutics.nl

ORCA Therapeutics to Present Clinical Data on ORCA-010 at International Oncolytic Virus Conference

Amsterdam, The Netherlands – October 2024 ORCA Therapeutics B.V., a Dutch biopharmaceutical company pioneering innovative oncolytic neo-adjuvant immunotherapies for cancer treatment, today announced that Prof. Dr. Victor van Beusechem will present new clinical data from the company’s lead product ORCA-010 at the International Oncolytic Virus Conference (IOVC) in Rotterdam. The presentation, titled “Oncolytic adenovirus ORCA-010 activates the tumor immune microenvironment and induces systemic tumor-specific T cell responses in patients with newly-diagnosed prostate cancer,” will highlight key findings from the ongoing Phase I/IIA clinical trial. Post-treatment analyses of radical prostatectomy specimens revealed notably low tumor presence in two patients compared to typical observations in untreated prostates and other treated patients in the study, suggesting potential treatment effect. This observation is further supported by one-year follow-up prostate biopsies in patients who did not undergo prostatectomy. Additionally, all other patients demonstrated evidence of an ongoing anti-tumor immune response in the prostate. “We are pleased to share these important clinical insights about ORCA-010’s mechanism of action in prostate cancer,” said Prof. Dr. van Beusechem. “The post-treatment tissue analyses provide interesting observations regarding ORCA-010’s effects on the tumor microenvironment and its ability to generate systemic tumor-specific T cell responses. These findings support the continued development of ORCA-010 as a potential new treatment option for prostate cancer patients.” About ORCA-010 ORCA-010 is a state-of-the-art oncolytic adenovirus therapy designed to modify the tumor microenvironment while inducing anti-tumor immune responses. The ongoing Phase I/IIA trial focuses on treatment-naïve, early-stage prostate cancer patients. Initial analyses suggest immunological activity in the tumor microenvironment, supporting ORCA-010’s continued investigation as a potential treatment approach for prostate cancer. About ORCA Therapeutics BV ORCA Therapeutics BV is a leader in potent neo-adjuvant immuno-oncology therapeutics, specializing in oncolytic viruses and innovative gene therapy approaches. The company is dedicated to translating cutting-edge scientific discoveries into effective therapeutic solutions, addressing unmet medical needs and improving patient outcomes globally. For more information about our mission and ongoing projects, visit http://www.orca-therapeutics.com Media Contact Dr. Wenliang Dong, Ph.D., MBA CEO, ORCA Therapeutics BV Email: info@orca-therapeutics.com Website: www.orca-therapeutics.com

Clinical StudyImmunotherapy

23 Sep 2024

·www.orca-therapeutics.nl

ORCA Therapeutics Secures €2 Million in Financing to Advance Oncolytic Immunotherapy Development

Amsterdam, The Netherlands – 23 September 2024 ORCA Therapeutics B.V., a Dutch biopharmaceutical company pioneering innovative oncolytic immunotherapies for cancer treatment, today announced the successful completion of a €2 million financing round led by existing shareholders. This strategic investment will accelerate the clinical development of the company’s lead product, ORCA-010, for early-stage prostate cancer. “This funding is a pivotal milestone in our mission to transform cancer treatment through oncolytic immunotherapy,” said Dr. Wenliang Dong, CEO of ORCA Therapeutics. “The continued support from our investors validates the potential of our technology and will enable us to expedite the clinical development of ORCA-010, bringing new hope to cancer patients.” ORCA-010 is a state-of-the-art oncolytic adenovirus therapy at the forefront of cancer treatment innovation. This potent immunotherapy is designed to achieve optimal tumor destruction while simultaneously fostering an immunostimulatory tumor microenvironment. The ongoing Phase I/IIA trial of ORCA-010 focuses on treatment-naïve, early-stage prostate cancer patients. Interim clinical analyses have demonstrated: ORCA-010’s promising efficacy Consistent and long term activation of the tumor microenvironment Induction of systemic anti-tumor immune responses These compelling results position ORCA-010 for continued development in prostate cancer treatment and potentially other indications. ORCA Therapeutics BV is a leader in immuno-oncology therapeutics, specializing in oncolytic viruses and innovative gene therapy approaches. The company is dedicated to translating cutting-edge scientific discoveries into effective therapeutic solutions, addressing unmet medical needs and improving patient outcomes globally. For more information about our mission and ongoing projects, visit www.orca-therapeutics.com Dr. Wenliang Dong, Ph.D., MBA CEO, ORCA Therapeutics BV Email: info@orca-therapeutics.com Website: www.orca-therapeutics.com

ImmunotherapyClinical StudyGene Therapy

100 Deals associated with ORCA-010

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Adenocarcinoma of prostate	Phase 2	CA	ORCA Therapeutics BV	12 Nov 2019
Localized Prostate Carcinoma	Phase 2	CA	ORCA Therapeutics BV	12 Nov 2019
Prostatic Cancer	Phase 2	CA	ORCA Therapeutics BV	01 Nov 2019

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04097002 (ESMO_IO2024) Manual	Phase 1/2	Prostatic Cancer First line	12	ORCA-010	hzyxycmwel(qgfbhlggnz) = uwfkcqwnfx lkqcesjscn (xhhsobkhbs ) View more	Positive	12 Dec 2024

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

ORCA-010

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation