• Sustainability
  • DE&I
  • Pandemic
  • Finance
  • Legal
  • Technology
  • Regulatory
  • Global
  • Pricing
  • Strategy
  • R&D/Clinical Trials
  • Opinion
  • Executive Roundtable
  • Sales & Marketing
  • Executive Profiles
  • Leadership
  • Market Access
  • Patient Engagement
  • Supply Chain
  • Industry Trends

Non-Gene Edited Therapeutics: Q&A with Jeffrey Erickson, Vice President of Business Development at Triumvira

Feature
Article

Erickson discusses his work developing unique, targeted autologous and allogeneic T cell therapeutics.

Jeffrey Erickson

Jeffrey Erickson
Vice president of business
development
Triumvira

Jeffrey Erickson serves as vice president of business development at Triumvira. He recently spoke with Pharmaceutical Executive about the company’s work developing non-gene edited therapeutics and recent advancements made in the field.

Pharmaceutical Executive: Can you describe your work with solid tumor cell therapy?
Jeffrey Erickson: Triumvira is developing unique, targeted autologous and allogeneic T cell therapeutics that co-opt the natural biology of T cells to treat a broad range of patients with cancer. T cells have the ability to eliminate tumors by using their T cell receptor (TCR) to identify cell surface markers known as cancer antigens, or tumor-associated antigens. Upon binding to an antigen, the TCR catalyzes a highly complex signaling cascade that leads to T cell activation, proliferation, and tumor cell killing. In cancer patients, T cells frequently fail to either recognize or effectively engage cancer cells. At Triumvira, we are developing the TAC platform, which leverages our proprietary T cell Antigen Coupler, a multi-domain chimeric molecule that works directly with the TCR to help a T cell better recognize and attack cancer cells. TAC can redirect T cells to any tumor antigen of choice, enabling selective tumor recognition with broad applicability across tumor types. This non-gene edited strategy is designed to retain the T cell’s natural control and internal feedback mechanisms, which leads to a low, controlled release of cytokines (as seen in normal T cells) and signals the T cell to stop cell killing once the tumor cell is eliminated, potentially reducing the risk of side effects and prolonging functional T cell persistence. We are currently enrolling patients in a Phase 1 dose escalation trial for our lead program TAC101-CLDN18.2, which is focused on patients with solid tumors expressing a novel tumor marker, Claudin 18.2.

PE: What is the benefit of producing non-gene edited therapeutics?
Erickson: The development of gene-edited cell therapies typically requires iPSCs as the cell source as gene edits in an autologous or donor-derived product would exceed the allowable culture period that can ensure sufficient T cell viability and functionality. However, iPSCs-derived cell banks and products have their own challenges, mainly related to ensuring the quality and consistent properties of cell products over time and across multiple product batches. Therefore, the CMC and regulatory hurdles are steep and, ultimately, having enough drug supply on hand is less certain. In addition, gene-edited cell products are subject to much more rigor (time-consuming and expensive) safety assessments (preclinically and clinically) as each of the genetic alternations poses its own risk for introducing unwanted changes, for example, render the product itself oncogenic. Thus, the long-term consequences of multiple edits are still not known. Finally, gene edits are introduced based on a hypothesis assuming it will only cause the desired outcome. However, T cell (immune cell) biology is quite complex whereby various receptors/effector molecules can have multiple functions and affect multiple processes. Therefore, gene edits in immune cells may also detrimentally affect functions that are therapeutically advantageous. In contrast, non-gene edited therapeutics stay free of these risks and challenges. Rather, they follow the KIS, Keep It Simple, principle as much as possible and attempt to harness and build on the natural programming of immune cells.

Note: Not all non-gene edited products are equal, e.g. CAR-T vs TAC-T. CAR-Ts, although not viewed as gene-edited T cells, do alter the natural way of T cell activation by completely bypassing the natural TCR function. This itself causes insufficiencies mainly attributed to tonic signaling, a lack of autoregulation and, consequently, CAR-related toxicities and premature exhaustion that has been seen in the use of CARs. In contrast, TAC functions entirely through the endogenous TCR and preclinically demonstrated superior efficacy and safety vs CAR.

PE: What successes have you seen with this approach?
Erickson: Working with independent pharma and biotechnology companies, as well as contract services organizations, we have conducted multiple preclinical studies of our TAC platform in different liquid and solid tumor models. Preclinical data reveals TAC’s ability to induce more efficient anti-tumor responses than other treatments, such as chimeric antigen receptors (CARs) and other active agents. In several preclinical TAC vs CAR head-to-head comparisons featuring various antigen binders (BCMA, HER2, CLDN18.2), TAC proved to provide stronger, more durable, and potentially safer anti-tumor responses. In a first-in-human trial for our initial lead program targeting patients with HER2+ solid tumors, we were able to demonstrate a favorable safety and tolerability profile, as well as encouraging disease control and response rates in a highly pre-treated patient population with greatly advanced cancers. Specifically, in a subsection of heavily pre-treated gastric cancer patients with HER2+ tumors, we saw a disease control rate of 86% and an overall response rate of 29%. The side effects associated with the TAC-based cell therapy were quite favorable relative to currently approved CAR-T therapies, with no ICU admissions following treatment, no neurotoxicity observed and low rates of cytokine release syndrome. Developing a novel, chemotherapy-sparing treatment regimen, especially for patients with gastric and gastroesophageal cancers, is of significant interest to key opinion leaders and treating physicians, and we believe these results show promise for the TAC platform as a potentially exciting, new approach to developing both autologous and allogeneic cell therapies targeting solid tumors.

PE: How would you describe your company’s pipeline?
Erickson: Currently, Triumvira is focusing on enrolling patients in a Phase 1 dose escalation trial for our lead program TAC101-CLDN18.2. The trial is enrolling patients with solid tumors expressing a novel tumor marker, Claudin 18.2, which is overexpressed in a variety of cancer types including gastric, gastroesophageal, pancreatic, ovarian, and non-small-cell lung cancer. We dosed our first patient earlier this year and, pending the outcome of this study, are planning to begin enrolling patients in a Phase 2 dose expansion arm in 2025. Our early-stage pre-clinical pipeline consists of additional TAC-based autologous therapies targeting novel tumor markers including GPC3 and GUCY2C. We also have an allogeneic, or “off the shelf” platform based on gamma delta T cells, with the lead allogeneic program being also focused on Claudin 18.2.

Related Videos
2023-07-12_Video Teaser_PE Podcast_Reproductive Health_Elizabeth Garner, Chief Scientific Officer, Ferring Pharmaceuticals_Meg Rivers
Related Content