In an interview with PharmaShots, Dr. Ian Walters, CEO of Portage Biotech shared his views on the interim data from the P-II IT-01 trial evaluates the safety and efficacy of INT230-6 as both a monotherapy and in combination with pembrolizumab or ipilimumab in solid tumors

Shots:

• The P-II IT-01 trial evaluates the safety & efficacy of INT230-6 as monothx. & in combination with pembrolizumab or ipilimumab in patients with solid tumors
• The preliminary data demonstrated that combination therapy was well-tolerated with direct tumor-killing effects & generate abscopal responses from Ag presentation & immune activation
• The results from monothx. therapy showed 62% of patients alive across all tumor types & 78% survival with =50% of tumor dosed, patients alive (88%) in combination therapy @1yrs., m-OS (23.8mos.) in heavily pre-treated mixed sarcoma population compared to 4-6mos. in a historical patient population with similar prognostic features

Tuba: Highlight the important points of the poster presented at ASCO.

Ian: This data builds on the data we have from our 3 clinical programs. The IT-01 trial, which is being managed in collaboration with Bristol Myers Squibb and Merck showed that when INT230-6 (PORT-1) is injected into a tumor as a monotherapy or in combination with checkpoint inhibitors in solid tumors:

• Small to large tumors throughout the body can easily be treated for a short period of time and have long treatment-free intervals
• The technology allows for the drugs to stay in the tumor and the safety profile is well tolerated (safe)
• Shows direct tumor-killing benefits and immune activation
• This leads to a longer median overall survival (mOS) compared to historical controls of similar populations

Tuba: Discuss the MoA, RoA, and other specifications of INT230-6 (PORT-1).

Ian: INT230-6 (PORT-1) is an intratumoral amphiphilic formulation that delivers potent cancer-killing agents directly into almost any tumor. The technology allows for the drugs to get specifically into cancer cells and spare healthy ones. This route of administration aims to immediately reduce the cancer burden by directly killing the injected tumor and presenting the tumor antigens to the immune system. It also breaks down the cytokine wall and recruits immune cells to attack microscopic and metastatic disease (which weren't injected).

Used alone or in combination with checkpoint inhibitors, PORT-1 may lead to improved survival by delivering a greater amount of drug directly to the tumor without unwanted toxic side effects often seen with intravenous infusion. PORT-1 targets cancer cells to trigger a robust immune response not only at the site of the primary tumor but also systemically without exposing healthy tissue in the body to harsh medicines.

PORT-1's efficacy and safety profile have been demonstrated in interim data from a Phase 1/2 study for the treatment of refractory solid tumors. Data demonstrate that the technology allows for doses in excess of 3x the typical systemic dose to be administered safely and directly to the tumor being targeted. The increased potency halts cancer proliferation and initiates cell death in a way that stimulates the immune system to recognize cancer and fight distal tumors and unseen metastases.

Tuba: Discuss the company's strategy to target novel cancer treatment pathways and improve patients quality of life.

Ian: Portage's leadership team consists of I/O pioneers and former senior oncology leaders at Bristol Myers Squibb, each of whom has over 20 years of industry experience. Collectively, they offer a balance of R&D, clinical operations, business development, and financing acumen suitable for rapid business growth. 

• The transaction experienced and successful commercialization of numerous oncology blockbuster products of the senior management and advisory team enables Portage to source and focus on developing the most promising cancer therapeutics in high-value untapped markets. 
• Portage takes a hands-on approach to guide assets from the bench through human proof-of-concept, bringing critical insights to the process that help reduce risks and maximize value.
• Portage's current portfolio consists of five technology platforms initially yielding 10 candidates that uniquely target different cancer resistance pathways. Portage has helped 3 assets go from the bench into the clinic. Portage's flagship platform is its invariant natural killer T cell (iNKT) agonists, which include PORT-2 and PORT-3. Additional platforms include novel intratumoral formulations (PORT-1), nanolipogels (PORT-4), and virus-like particles (PORT-5).

Tuba: Can we have a glance at the IT-01 trial and what are the results of the study?

Ian: The IT-01 trial is evaluating the safety and efficacy of INT230-6 (PORT-1) as both a monotherapy and in combination with pembrolizumab or ipilimumab in heavily pretreated solid tumor patients.

Data thus far have shown that both INT230-6 (PORT-1) monotherapy and combination therapy are well-tolerated with direct tumor-killing effects and generate responses in un-injected tumors likely from antigen presentation and immune activation. The data for PORT-1 as monotherapy demonstrated an estimated 62% of patients alive at one year across all tumor types. An exploratory analysis of patients who received =50% of the tumor dosed (higher dose) had an estimated 78% one-year survival.

Preliminary estimates for patients who received the pembrolizumab combination indicate approximately 88% were alive at one year. The estimated median overall survival (mOS) was approximately 23.8 months in a heavily pre-treated mixed sarcoma population compared to 4-6 month expected mOS in a historical patient population with similar prognostic features.

Tuba: What are the other indications in which you are evaluating INT230-6?

Ian: PORT-1 is currently being tested in multiple Phase 2 cohorts in combination with pembrolizumab in pancreatic, non-MSI colorectal cancer, gall bladder, and squamous cell cancer and combination with ipilimumab in sarcoma, liver, and breast cancers. Additional tumor types can be enrolled and treated with PORT-1 monotherapy. There is a second trial named the INVINCIBLE study that is a randomized Phase 2 trial to evaluate this drug as a monotherapy in breast cancer subjects before surgical resection, which is the first drug to be used in this way. Additional data readouts for these studies are anticipated over the next 12-18 months.

Tuba: Can you discuss the company's recent progress and near-term goals?

Ian: In April 2021, we dosed the first patient in the PRECIOUS Phase 1 study of PORT-3, our iNKT antagonist (IMM60) co-packaged with NY-ESO-1 immunogenic peptides. In August, we commenced Phase 1/2 clinical trials of PORT-2, a liposomal formulation of IMM60, both as a monotherapy and in combination with standard of care (Keytruda) in melanoma and NSCLC.

Pulling from the newly secured $26.5 million gross proceeds from our recent public offering, we're able to accelerate development activities and provide two years of capital runway, enough to complete Phase 1 and Phase 2 clinical trials for all three clinical assets. We're also on a trajectory to achieve numerous milestones across our pipeline including preparing the next leads to start human testing.

Tuba: As per your pipeline, you have collaborated with multiple companies. Are you open to more collaboration in the future?

Ian: We are certainly open to more collaboration in the future. It is a priority for us to continue to build relationships with prospective collaborators, including potential big pharma partners, as we continue to build out our clinical pipeline to accelerate the entry of first-in-class cancer treatments to market.

Tuba: What are your long-term goals, where do you expect the growth of the company in a long run?

Ian: Our long-term goal is to advance new therapeutic opportunities for people with cancer who currently have limited or no treatment options. To do this, we plan to progress our existing technology platforms and grow our product engine with additional platforms over the coming months and years.

Ultimately, we hope that our programs can make a significant impact on the cancer treatment landscape and can help overcome resistance to current therapies. We are continually pursuing innovative opportunities to increase the success of both monotherapies and combination treatments.

Tuba: Are you expecting BTD, FTD from global regulatory authorities for your therapies?

Ian: We are leveraging strong data (both preclinical and clinical) across all of our platforms to progress through clinical development and work toward approval as quickly as possible. We are pleased that the FDA recognized the potential of PORT-1 (INT230-6) and has granted it fast track designation (FTD) for the treatment of triple-negative breast cancer. There are still many other cancers that we are studying, and that have limited therapeutic options. Hopefully, we will see this change in our lifetime. 

Source: Technology Networks

About Author: Dr. Ian Walters is the CEO of Portage Biotech & has received his M.D. from the Albert Einstein College of Medicine and an MBA from the Wharton School of The University of Pennsylvania. Ian has ~20yrs. of leadership and expertise in oncology/immunology drug for the treatment of severe diseases. Prior to Portage, Ian spent 7yrs. at BMS

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