First Patient Dosed in PRECIOUS-01 Study of PORT-3 for the Treatment of NY-ESO-1 Positive Solid Tumors

April 7, 2021

Portage Biotech Inc., a clinical-stage immuno-oncology company focused on the development of therapies and treatments targeting cancer treatment resistance, today announced that the first patient has been dosed in the Phase 1 portion of the PRECIOUS-01 open-label, dose-escalation and expansion clinical trial assessing the safety, tolerability, efficacy and dosing of PORT-3 in the treatment of cancer. 

PORT-3 is a nanoparticle co-formulation of the invariant natural killer T-cell (iNKT) agonist IMM60 and NY-ESO-1 immunogenic peptides developed for the treatment of NY-ESO-1 positive solid tumors.

“Today’s initiation of the PRECIOUS trial marks an important milestone in the clinical development of Portage’s iNKT agonists, including both PORT-2 and PORT-3,” said Dr. Ian Walters, chief executive officer of Portage Biotech. “Preclinical studies of both compounds have shown that treatment can lead to a broad reprogramming of the immune system. We are excited to begin first-in-human trials of PORT-3 to test the proof-of-concept of this approach. If the trial is successful with NY-ESO-1, it will open the door to a multitude of opportunities to design more formulations with other tumor-specific antigens.”

The trial is based on preclinical data for PORT-3, which was recently published in Frontiers in Immunology. The preclinical data demonstrated good tolerability and a strong cancer-specific B and T-cell response. Importantly, preclinical data also showed that co-formulation of other cancer antigen vaccines and iNKT agonists resulted in up to 2-5x increases in potency. This has the potential to increase the specificity of treatment, including targeting specific tumor markers, and increase the effectiveness of treatment. The phase 1 part of the trial is expected to enroll 15 patients.

“In the cancer treatment landscape, solid tumors represent an area of significant unmet need as many patients, including those with NY-ESO-1 positive tumors, have been unable to find an effective therapeutic solution,” said Dr. Jolanda de Vries, Professor at the Department of Tumor Immunology of Radboud University, Netherlands. “We are encouraged by the preclinical data for the PORT-3 iNKT agonists and are excited to explore how this novel co-formulation approach may offer a new treatment paradigm with the potential to target a broad array of solid tumor types in patients with few other options.”

The study is supported by a grant from the EU Horizon 2020 program. The trial is actively recruiting at Radboud University, Netherlands. For more information, please visit #NCT04751786.

About iNKT agonists PORT-2 and PORT-3

PORT-2 and PORT-3 contain small molecule agonists (IMM60) of invariant natural killer T-cells (iNKT cells) developed by Oxford University, which play an important role in anti-tumor immune responses. iNKT cells are a distinct class of T lymphocytes and recognize lipid antigens on the surface of the tumor. Our synthetic iNKT agonists are designed to optimally engage the T-cell receptor on the iNKT and facilitate its binding to dendritic cells, resulting in the secretion of a large amount of pro-inflammatory cytokines. This leads to the activation and expansion of important immune system components and primes and boosts an adaptive immune attack against cancer. We see that monotherapy treatment with iNKT agonists shows a heightened immune response and better cancer control in animal models that are resistant to PD-1 antibody treatment. Combination therapy with PD-1 antibodies is synergistic with iNKT agonists and restores sensitivity to PD-1 blockade. While treatment with iNKT agonists alone shows promising preclinical activity against cancer, data suggests that when an iNKT agonist is co-packaged with tumor-specific antigens, potency is increased by up to 5x. PORT-2 is a liposomal formulation of our IMM60 iNKT agonist while PORT-3 is a co-formulation of our IMM60 iNKT agonist with an NY-ESO-1 peptide vaccine, co-packaged into a nanoparticle.

About Portage Biotech Inc.

Portage is a clinical-stage immuno-oncology company advancing first-in-class therapies that target known checkpoint resistance pathways to improve long-term treatment response and quality of life in patients with evasive cancers. The Company’s access to next-generation technologies coupled with a deep understanding of biological mechanisms enables the identification of the most promising clinical therapies and product development strategies that accelerate these medicines through the translational pipeline.


H2020 funded ‘PRECIOUS’ clinical trial has kicked off since February 2021

Rotterdam, 10th March 2021,

PRECIOUS has successfully recruited the first patient for Phase-1 clinical trials

Despite the delay caused by the ongoing COVID-19 pandemic, we are proud to announce that the Phase 1 clinical study to investigate the safety and efficacy of nanovaccines composed of PLGA particles that contain tumour antigen and adjuvant. This study will be conducted in RUMC with the support of the CRO team from CATO-SMS over a period of 1 year. Being a first-in-human trial, a safety dose-finding pilot cohort of 18 patients in 3 dose level groups of 6 patients will be recruited amongst advance lung-, bladder-, prostate-, and ovarian- cancer patients whose tumours express NY-ESO-1.

One of the main PIs supervising the study, Prof. dr. J. de Vries shares her enthusiasm about the trial and its possible outcomes.  “We are very pleased to be able to start the clinical trial to test the toxicity and tolerability of Precious-01. A very dedicated group of international scientists and GMP experts have made this possible. And now the time has come, the trial is open for inclusion! We hope to be able to present the first results of this innovative approach to cancer soon!”

PRECIOUS will revolutionise cancer treatment

The PRECIOUS consortium is coordinated by Prof. dr. Carl Figdor, senior professor in Experimental Immunology of the Tumour Immunology Department of the Radboud University Medical Center, the Netherlands. An international multi-disciplinary consortium of 11 partners, in which 5 leading academic institutes, 4 cutting-edge biotech companies and 2 excellent service providers have joined forces to advance the treatment of cancer using an innovative immunotherapeutic nanomedicine, has received an €8.3 million Horizon 2020 grant (grant agreement No 686089). The project kicked off in May 2016 and will last a duration of 60 months.

Novel treatment strategies for cancer are highly needed

The PRECIOUS (Scaling-up immunomodulating nanomedicines for multimodal precision cancer immunotherapy) project is working towards establishing a platform for the development of new medicines that contain immunomodulating components acting at multiple levels. ‘These novel medicines will act as a ‘two-sided knife’ by boosting the immune system, and at the same time attacking the immunosuppressive microenvironment that characterises the tumour site ‘, says Prof. dr. C. Figdor. Nanoparticles offer the optimal platform for a combinational immunotherapy, as they are able to encapsulate immunomodulators in biodegradable particles. Currently, immunomodulating nanomedicines are not used to their full potential due to is challenging manufacturing requirements. PRECIOUS is developing a manufacturing process at industrial scale for immunomodulating nanomedicines to test the potential of these nanoparticle-based immunotherapies in the clinic. To ensure that these novel treatment strategies will reach patients, the development of a marketing and commercialisation strategy for these novel medicines is an important part of the project. Together, PRECIOUS will realise a major improvement in cancer therapy to provide cancer patients with enhanced quality of life.

About the consortium

The consortium consists of academic experts in the field from 5 leading institutes (RadboudUMC, University of Konstanz, Institute of Macromolecular Chemistry ASCR, University of Oxford and Fondazione IRCCS Istituto Nazionale dei Tumori) with outstanding track records in the fields of immunotherapy, tumour immunology, preclinical drug development and clinical trials. In addition, it includes cutting-edge biotech companies that will enable project results to be translated to the clinic. Evonik Operations GmbH is the lead manufacturer of PLGA-based particles and will bring in invaluable expertise on manufacturing of nanomedicines. iTeos Therapeutics will develop and provide novel immunomodulators that target the tumour micro-environment. iOx Therapeutics and Oncoarendi Therapeutics will contribute their promising, novel immunomodulators (iNKT and ARG inhibitors respectively) to be part of the immunomodulating nanomedicine platform. SMS-oncology will support the clinical development path with their broad knowledge on clinical trial design and implementation. ttopstart, involved in developing the business cases of many leading cancer therapies and diagnostic tests, will be responsible for the business aspects of PRECIOUS by ensuring a strong exploitation strategy and tight project management. The combined expertise will allow the PRECIOUS consortium to truly perform translational research towards benefit of the most important stakeholder, cancer patients in need of novel treatment strategies.

Contact To learn more about the project, visit the EC website or the project website