On October 5, 2022 Lyell Immunopharma, Inc. (Nasdaq: LYEL), a clinical-stage T-cell reprogramming company dedicated to developing curative cell therapies for patients with solid tumors, reported that five abstracts highlighting preclinical data on its product candidates and new genetic and epigenetic reprogramming technologies were accepted for presentation at the 37th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) taking place in Boston, Nov. 8 – Nov. 12, 2022 (Press release, Lyell Immunopharma, OCT 5, 2022, View Source [SID1234621719]). The new preclinical data includes an abstract describing the effects of c-Jun overexpression in combination with NR4A3 gene knockout to enhance the functional activity of ROR1 CAR T cells. The combination of these two genetic reprogramming technologies is being incorporated in Lyell’s new product candidate, LYL119, a second generation investigational ROR1 targeting CAR T-cell therapy.

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"Our presence at SITC (Free SITC Whitepaper) includes presentations of new preclinical data from both existing and new reprogramming technologies being deployed in our growing pipeline of therapeutic candidates for solid tumors," stated Dr. Gary Lee, chief scientific officer at Lyell. "We look forward to sharing these preclinical findings on the potential of Lyell’s reprogramming technologies that are designed to address primary barriers to successful adoptive cell therapy in solid tumors in order to improve clinical responses in patients."

All the presentations describe preclinical data demonstrating that genetic and epigenetic reprogramming can ameliorate T cell exhaustion and enhance stem-like qualities and potency of T cells in various modalities, including CAR T cells, tumor-infiltrating lymphocytes (TILs) and T-cell receptor (TCR) T cells. Two presentations will feature preclinical data from LYL845, Lyell’s autologous TIL product candidate enhanced with Epi-R reprogramming technology, designed to create products with higher proportions of stem-like T cells. Lyell will also present preclinical data from its new genetic reprogramming technology designed to further limit T cell exhaustion, as well as data on its new epigenetic reprogramming technology, Stim-R, designed to generate a more potent T cell product by controlling delivery of activation molecules during T cell production.

Details on the five poster presentations are below:

NR4A3 gene editing and c-Jun overexpression synergize to limit exhaustion and enhance functional activity of ROR1 CAR T cells in vitro and in vivo

Category: Cellular therapies – Chimeric Antigen Receptors
Presentation Date, Time & Location: Thursday, Nov. 10, Poster Hall
Abstract No.: 243
Engineering potent CAR T-cell therapies by controlling T-cell activation signaling parameters using the Stim-R technology, a programmable synthetic cell-signaling platform

Category: Cellular Therapies – Chimeric Antigen Receptors
Presentation Date, Time & Location: Friday, Nov. 11, Poster Hall
Abstract No.: 252
The Epi-R technology produces a polyclonal TIL product (LYL845) with diverse tumor-reactive clones that have stem-like qualities and anti-tumor function

Category: Cellular therapies – Non-CAR adoptive cell therapies
Presentation Date, Time & Location: Friday, Nov. 11, Poster Hall
Abstract No.: 340
The Epi-R technology produces a polyclonal TIL product (LYL845) with a greater expansion success rate across hot and cold tumors, improved product phenotype, and maintenance of TCR diversity

Category: Cellular therapies – Non-CAR adoptive cell therapies
Presentation Date, Time & Location: Friday, Nov. 11, Poster Hall
Abstract No.: 370
Increased potency and functional persistence in vitro of a next-generation NY-ESO-1-specific TCR therapy incorporating Gen-R genetic reprogramming technology

Category: Cellular therapies – Non-CAR Adoptive Cell therapies
Presentation Date, Time & Location: Friday, Nov. 11, Poster Hall
Abstract No.: 232