LTZ Therapeutics Wins FDA IND Clearance for LTZ-232, a Myeloid Engager Bispecific Targeting EpCAM-Positive Colorectal Cancer

LTZ Therapeutics announced today that the FDA has cleared its Investigational New Drug (IND) application for LTZ-232, a first-in-class bispecific antibody designed to activate tumor-associated macrophages (TAMs) to recognize and phagocytose EpCAM-positive solid tumor cells, with an initial focus on advanced metastatic colorectal cancer (mCRC).¹ The company expects to initiate a phase 1, open-label, multicenter dose-escalation study in Q4 2026. LTZ-232 is the second asset from LTZ's Universal Myeloid Cell Engager (U-MCE) platform to receive IND clearance, following LTZ-301 in hematologic malignancies — marking a strategic expansion of myeloid-engaging immunotherapy into one of the most immunologically resistant solid tumor indications.

Why Is colorectal cancer such a challenging target for immunotherapy?

The majority of colorectal cancers are classified as immunologically cold tumors — characterized by low T-cell infiltration, high myeloid cell content, and a profoundly immunosuppressive tumor microenvironment (TME) that renders conventional PD-1/PD-L1 checkpoint inhibitors largely ineffective.² Approximately 95% of mCRC cases are microsatellite-stable (MSS), lacking the high tumor mutational burden that drives immunotherapy sensitivity in the minority of MSI-H tumors. In the MSS setting, response rates to standard checkpoint inhibitors have historically fallen below 5%, leaving patients reliant on chemotherapy, anti-VEGF antibodies, and targeted agents that provide only incremental survival benefit in later lines of therapy.³

This immunosuppressive biology is driven in part by tumor-associated macrophages — among the most abundant immune cell populations in the CRC tumor microenvironment — which in the tumor context typically adopt an immunosuppressive, pro-tumorigenic phenotype rather than an anti-tumor effector function.⁴ LTZ's strategy is to co-opt these same macrophages as effectors, reprogramming them through bispecific antibody-mediated engagement to phagocytose and eliminate tumor cells rather than supporting tumor growth.

How does LTZ-232 work?

LTZ-232 is a bispecific antibody engineered through LTZ's U-MCE platform to simultaneously bind EpCAM on tumor cells and an activating receptor on monocytes and macrophages, forming a bridge that drives myeloid-mediated phagocytosis of EpCAM-positive cancer cells.¹ EpCAM is a cell-surface epithelial cell adhesion molecule expressed at high levels across the majority of colorectal cancers and a range of other solid tumors — including gastric, pancreatic, lung, and breast cancers — making it an attractive pan-solid-tumor target for EpCAM-positive indications.⁵

The approach is mechanistically distinct from the dominant T-cell engager (TCE) paradigm that has driven most bispecific antibody development in oncology. Rather than recruiting CD3-expressing cytotoxic T cells — which are scarce in cold tumor microenvironments — LTZ-232 targets the myeloid compartment, which is abundantly represented even in immunotherapy-resistant tumors. Preclinical studies of LTZ-232 demonstrated potent pharmacological activity across in vitro and in vivo models, supported by a favorable safety profile, providing the data package underpinning the IND filing.¹

"Advanced metastatic colorectal cancer remains a significant unmet need in oncology, particularly since it's typically an immunologically cold tumor microenvironment, limiting the effectiveness of many existing immunotherapies," said William Grossman, MD, PhD, chief medical officer of LTZ. "Our differentiated and novel approach is designed to redirect myeloid cells to drive anti-tumor activity in these challenging tumor microenvironment settings. We believe LTZ-232 has the potential to expand the reach of immunotherapy into cold solid tumors, and that we can meaningfully improve patients' lives."¹

How does LTZ-232 fit within LTZ's broader platform strategy?

LTZ-232 is the second IND-cleared asset from LTZ's U-MCE platform, which is built on reverse translational science and a deep focus on TME myeloid biology. The platform's first asset, LTZ-301, is a bispecific antibody targeting CD79b-positive B-cell malignancies — redirecting monocytes and macrophages to deplete malignant B cells in hematologic tumors resistant to CD19- or CD20-directed therapies — and is currently in early clinical development.¹

As noted in BioPharm International's coverage of LTZ's $38 million financing in May 2026, "macrophages are among the most prevalent immune cell populations within the TME across hematologic and solid tumors" — and by enhancing their phagocytic activity rather than bypassing them, LTZ's platform is designed to harness resident myeloid biology rather than fight it. Beyond oncology, the U-MCE platform is also being explored in autoimmune disease, and LTZ holds a strategic collaboration with Eli Lilly for myeloid engager development in autoimmune indications, announced in July 2025.¹

The IND clearance of LTZ-232 also follows the company's $38 million financing closed in April 2026 — providing the runway to advance both LTZ-301 and LTZ-232 through early clinical development simultaneously. LTZ has headquarters in Redwood City, California and operations in Shenzhen, China.

"Advancing LTZ-232 into the clinic represents another significant milestone for LTZ, as it highlights the therapeutic potential of our U-MCE Platform for broad disease areas beyond our initial program," said Robert Li, PhD, founder and CEO of LTZ. "We are excited to initiate our second first-in-class myeloid engager immunotherapy, delivering novel therapeutic options for patients."¹

References

1. LTZ Therapeutics Announces FDA Clearance of IND Application for LTZ-232 to Treat Advanced Metastatic Colorectal Cancer and Other Solid Tumors. (2026 Jul 7). Business Wire. https://www.businesswire.com/news/home/20260707252962/en/LTZ-Therapeutics-Announces-FDA-Clearance-of-IND-Application-for-LTZ-232-to-Treat-Advanced-Metastatic-Colorectal-Cancer-and-Other-Solid-Tumors
2. Andac-Aktas AB, Calibasi-Kocal G. (2025 Oct. 29). Immunological characterization of colorectal cancer: tumor microenvironment, cellular players, and immunotherapeutic opportunities. Front Mol Biosci. https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2025.1687556/full
3. Gilson A, Tan V, Koessler T, et al. (2025 Jun 24). Immune checkpoint inhibitors for metastatic colorectal cancer: a systematic review. Cancers (Basel). https://pubmed.ncbi.nlm.nih.gov/40647424/
4. Bied M, Ho WW, Ginhoux F, Blériot C. (2023 Jul 10). Roles of macrophages in tumor development: a spatiotemporal perspective. Cell Mol Immunol. https://www.nature.com/articles/s41423-023-01061-6
5. Golubovskaya V, Sienkiewicz J, Sun J, et al. (2023 May 22). mRNA-lipid nanoparticle delivery of humanized EpCAM-CD3 bispecific antibody significantly blocks colorectal cancer tumor growth. Cancers (Basel). https://pubmed.ncbi.nlm.nih.gov/37345198/