Amunix is leveraging precision protein engineering to enable the promise of T cell engagers (TCEs) in solid tumors. CAR-Ts and the TCE, blinatumomab, demonstrate that redirecting T cells can induce prolonged responses and potential cures. But to date, T cell engagers have limitations due to significant toxicity and immunogenicity. Amunix has developed a platform to overcome these limitations.
The Amunix Solution: XPATs
XTENylated Protease-Activated T Cell Engagers
Amunix has designed the XPAT (XTENylated Protease-Activated T Cell Engager) platform using its longstanding and validated XTEN technology as a mask for TCEs. When combined with our proprietary protease release sites, we can selectively unleash the potent activity of TCEs in the tumor by taking advantage of the high protease activity in the tumor microenvironment. XTEN is an ideal masking device because it can not only extend half-life, but has been demonstrated to have low immunogenicity (>200 patients treated with XTENylated products to-date with no anti-drug antibodies influencing activity).
XPATs Enable Localized Tumor Killing, Limiting Activity in Healthy Tissue Expressing the Target Antigen
XPATs are Produced as Single Polypeptides
XTEN technology brings the precision of recombinant protein engineering to polymer chemistry. XTEN protein polymers, similar to chemical polymers, have undefined structures (random coil) and use a limited number of specific amino acids, while utilizing recombinant protein expression to achieve defined length and sequence. XTENs are designed for minimal immunogenicity and can be recombinantly fused to therapeutic proteins, such as TCEs, cytokines, and checkpoint inhibitors, to increase their in vivo half-life and mask their activity.
XPATs Leverage Multiple Mechanisms to Widen Therapeutic Window
Key Benefits of XPAT Technology
- Improvement of therapeutic index: On-target, off-tumor toxicity of TCEs is often dose-limiting, thus preventing TCEs from achieving therapeutic levels. The mask also has the potential to limit cytokine release syndrome (CRS) and systemic immune activation.
- Expansion of target universe: Tumor exclusive targets are exceptionally rare. Tumor-specific unmasking enables selection of targets with broader expression patterns.
- Validated technology: XTENylated drugs have been dosed in greater than 200 patients with minimal immunogenicity. Human proof of concept of prodrug and protease activation was achieved with Sanofi’s BIVV001, a novel, long-acting Factor VIII.
- Tunability of mask: XTEN length and number, as well as protease release site specificity, can be tuned to optimize therapeutic index and PK.
- Modularity of platform: Universal masks are broadly applicable to different tumor targeting domains (e.g. scFv, VHH, Fab).
- Enhanced efficacy potential: The current XPAT active moiety is a small dual scFv format, which brings T cell and tumor cell into close proximity and enables greater tumor penetration.
Amunix’s robust technology platforms have been validated through multiple collaborations with leading biopharmaceutical companies including Celgene, Genentech, Janssen, Roche, Bioverativ, and Baxter.