Janux Therapeutics is a clinical-stage biopharmaceutical company developing new cancer immunotherapies. The company’s work centers on creating treatments designed to guide a patient’s immune system to eliminate tumors. This approach provides therapeutic options for various forms of cancer. Janux is advancing a pipeline of drug candidates into clinical trials to address unmet needs for people with late-stage cancers.
The TRACTr Technology Platform
A T-cell engager is a molecule that functions as a bridge, connecting a patient’s immune T-cells to cancer cells to facilitate their destruction. Janux developed a proprietary platform called the Tumor Activated T Cell Engager (TRACTr) to improve this concept. TRACTr molecules are designed to remain inactive until they reach a tumor’s microenvironment, a process called conditional activation. This technology is engineered to overcome some limitations of previous T-cell based treatments in solid tumors.
The TRACTr molecule has a domain that targets a specific protein on a tumor cell and a separate domain that binds to a protein called CD3 on T-cells. A feature of the design is a “masking” peptide that covers the T-cell binding domain. This mask is connected by a linker designed to be cut by proteases, enzymes that are more abundant around tumors than healthy tissues. This structure is intended to keep the molecule inert, preventing it from activating T-cells in non-cancerous areas.
Once the TRACTr molecule enters the tumor microenvironment, the high concentration of proteases cleaves the linker and removes the mask. This cleavage uncovers the T-cell binding domain, effectively switching the molecule “on” precisely at the cancer site. This activation allows the TRACTr to connect the T-cell to the tumor cell, directing the immune cell to attack the cancer. This targeted mechanism is also designed to improve the drug’s pharmacokinetics, allowing it to remain in circulation longer while inactive.
Addressing Safety in Cancer Immunotherapy
A challenge in cancer immunotherapy is managing treatment-related toxicities. Conventional T-cell engagers can activate the immune system throughout the body, not just at the tumor site. This systemic activation can lead to serious side effects, which have limited the effectiveness and application of these therapies, particularly against solid tumors.
A common and serious side effect is Cytokine Release Syndrome (CRS). CRS occurs when activated immune cells release a flood of inflammatory molecules called cytokines, causing widespread inflammation that can lead to fever, nausea, and in severe cases, life-threatening organ damage. Another issue is “on-target, off-tumor” toxicity, where the therapy attacks healthy cells that happen to express the same target protein as the cancer cells, just at lower levels.
Janux’s TRACTr platform was engineered to address these safety concerns. By keeping the T-cell engaging part of the molecule masked until it reaches the tumor, the technology aims to prevent widespread immune activation in healthy tissues. This localized activation is intended to reduce the risk of systemic CRS and minimize damage to healthy cells, allowing for safer administration and more effective dosing.
Clinical Development Pipeline
Janux is advancing several drug candidates from its TRACTr platform through clinical development. The company’s lead candidate is JANX007, which targets Prostate-Specific Membrane Antigen (PSMA), a protein highly expressed on prostate cancer cells. JANX007 is in Phase 1 clinical trials for patients with metastatic castration-resistant prostate cancer (mCRPC), a late-stage form of the disease. Early results from the trial have shown encouraging safety and efficacy.
Another candidate in the pipeline is JANX008, which targets the Epidermal Growth Factor Receptor (EGFR), a protein found on the surface of various solid tumor cells. The Phase 1 trial for JANX008 is enrolling patients with several types of cancer, including colorectal, lung, head and neck, and renal cell carcinoma. This trial aims to establish the drug’s safety, tolerability, and preliminary anti-tumor activity across these cancers.
The company is also developing JANX009, a drug candidate using a related platform to target PD-L1 and the CD28 receptor on T-cells. Janux also has a TRACTr in development targeting TROP2, a protein overexpressed in numerous cancers like breast, lung, and pancreatic cancer. These programs represent the company’s strategy to apply its technology to a wide range of cancer targets.
Corporate Collaborations and Partnerships
In December 2020, Janux announced a partnership with Merck to discover and develop TRACTr drug candidates for cancer. The agreement is focused on creating therapies for two cancer targets selected by Merck. This collaboration helps validate Janux’s technology and secures resources for development.
Under the terms of the collaboration, Janux is eligible to receive up to $500.5 million per target in upfront payments, milestone payments, and future royalties on commercialized products. Merck is responsible for funding the research and development activities. This arrangement provides Janux with non-dilutive funding and access to the expertise of a major pharmaceutical company.
This partnership serves as external validation of the TRACTr platform’s potential. For a clinical-stage company like Janux, collaborating with an established industry leader like Merck provides credibility and financial support. This allows the company to accelerate its partnered programs while also advancing its internal pipeline of drug candidates.