Our Core Product TSN1611 is an orally bioavailable KRAS G12D inhibitor. Designed to address the substantial unmet medical needs of patients with KRAS G12D-driven cancers — including lung, pancreatic, and colorectal malignancies, TSN1611 has demonstrated early clinical efficacy, along with a favorable safety and tolerability profile. TSN1611 is designed to block both the active (“on,” GTP-bound) and inactive (“off,” GDP-bound) states of the KRAS G12D protein. This dual-state inhibition allows TSN1611 to more effectively and durably shut down KRAS signaling, and potentially slow the development of drug resistance. The high selectivity of TSN1611 toward KRAS G12D protein also offers the advantages of a lower rate of adverse events in the clinical settings.

As monotherapy, TSN1611 has completed its phase 1 clinical trial in the United States and China and is currently in phase 2 development stage.  In combination therapy settings, we are conducting trials of TSN1611 in combination with cetuximab, GnP (Gemcitabine and nab-paclitaxel), or mFOLFOX6. 

TSN222 is a small molecule drug designed to leverage the power of the immune stimulation for cancer immunotherapy. It acts through a dual-function mechanism, distinguishing it from conventional immune agonists and their ADCs. TSN222 is engineered to provide sequential dual functionality by initially stimulating the STING pathway to activate the immune system, followed by the unleashing of the cytotoxic activity to kill tumor cells. TSN222's mechanism provides significant advantages in the treatment of various cancers, enabling the stimulation of the immune system followed by direct tumor cell killing. This offers the potential to overcome many limitations associated with traditional cancer therapies.

The compound is currently undergoing phase 1 clinical trial in China, showing favorable safety and early signs of efficacy in heavily pretreated patients, and profound modification of the immune profile of the tumors clinically. In addition, we are using TSN222 as a novel payload for our ADC drug candidates.

TSNA3339 is an EGFR-targeted antibody–drug conjugate designed to deliver a highly potent KRAS G12D inhibitor directly to tumor cells. Unlike conventional toxin-based ADCs, TSNA3339 uses a targeted KRAS G12D inhibitor as its payload, offering a differentiated approach to addressing key limitations of existing KRAS inhibitors, including acquired resistance and systemic toxicity. The ADC is enabled by our proprietary linker technology, which is specifically designed for highly hydrophobic payloads.

In extensive preclinical testing across engineered and tumor-derived KRAS-mutant cell lines, the payload demonstrated strong and selective activity against KRAS G12D-mutant cells, with minimal activity observed against wild-type KRAS, NRAS, HRAS, and other tested KRAS mutants. By combining EGFR-mediated tumor targeting with direct KRAS G12D pathway inhibition, TSNA3339 is designed to enable multi-point suppression of cancer growth signaling.

Through selective delivery of the KRAS G12D inhibitor to tumor cells, TSNA3339 has the potential to achieve deeper and more durable tumor suppression, delay or overcome KRAS inhibitor resistance, reduce gastrointestinal toxicity commonly associated with oral KRAS inhibitors, improve pharmacokinetic exposure through targeted delivery, and support broad combination therapy opportunities.

We are currently optimizing the antibody component of TSNA3339 and anticipate submitting an IND application in the first quarter of 2027.

At Tyligand Bioscience, our R&D strategy is built on the premise that overcoming advanced malignancies requires both direct oncogenic inhibition and the restoration of the host’s immune surveillance. By integrating our precision small-molecule program with our innovative ADC platforms, we are creating a "one-two punch" designed to eradicate tumors and prevent their recurrence.

TSNA1789 is a lead ADC candidate developed on our proprietary DATIA platform, utilizing TSN222 as its payload. Representing a new class of immune-stimulating ADCs, TSNA1789 incorporates both cytotoxic and immunostimulatory functions within a single molecule.

Our goal is to transform "cold" tumors-characterized by minimal immune cell infiltration-into "hot" tumors with active immune engagement. Ultimately, this establishes a tumor-specific adaptive immunity that efficiently recognizes and attacks malignancies. 

Unlike traditional ADCs that deliver purely cytotoxic payloads, this new class of ADCs releases immune agonists upon binding to tumor cell targets. This triggers a potent biological cascade:

• •   Activation: Stimulates interferon secretion and triggers cytokine and chemokine production.
• •   Recruitment: Activates myeloid cells, such as macrophages and dendritic cells, which in turn recruit adaptive T-cells.
• •   Sustained Response: Establishes a positive feedback loop of immune signaling, inducing long-term immune memory and building durable anti-tumor immunity.

This approach offers the potential to overcome therapeutic resistance and prevent tumor recurrence. We are currently advancing TSNA1789 through preclinical development and plan to submit an IND application in the second half of 2027.