On April 26, 2022 Janux Therapeutics, Inc. (Nasdaq: JANX) (Janux), a biopharmaceutical company developing a broad pipeline of novel immunotherapies by applying its proprietary technology to its Tumor Activated T Cell Engager (TRACTr) and Tumor Activated Immunomodulator (TRACIr) platforms, reported its upcoming presentation of preclinical data for the Company’s two lead TRACTr programs, PSMA-TRACTr (JANX007) and EGFR-TRACTr (JANX008), in separate poster presentations at the 18th Annual Protein & Antibody Engineering Summit (PEGS) Boston Conference & Expo, scheduled to take place May 2-6, 2022, virtually and in-person at the Hynes Convention Center in Boston, Massachusetts (Press release, Janux Therapeutics, APR 26, 2022, View Source [SID1234612988]).
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Janux’s TRACTr candidates are a novel class of T cell engagers (TCEs) designed to be highly potent, half-life extended anti-tumor therapeutics with enhanced safety features and the potential to overcome problems with existing TCE approaches for solid tumors, which have been limited to date by cytokine release syndrome (CRS), on-target healthy tissue toxicity, poor pharmacokinetics (PK) profiles, and dose-limited efficacy. JANX007 is a novel TRACTr therapeutic targeting prostate-specific membrane antigen (PSMA) for the treatment of metastatic castration-resistant prostate cancer (mCPRC), and JANX008 is a novel TRACTr therapeutic targeting epidermal growth factor receptor (EGFR) for the treatment of multiple solid cancers including, metastatic colorectal cancer (mCRC), squamous cell carcinoma of the head and neck (SCCHN), and non-small cell lung cancer (NSCLC). JANX007 and JANX008 are the first development programs to emerge from Janux’s TRACTr platform.
"The preclinical data to be presented for JANX007 and JANX008 at PEGS Boston is an important step forward for Janux’s proprietary TRACTr technology platform and our pipeline of next-generation immunotherapies," said David Campbell, Ph.D., President, and CEO of Janux. "These data display our TRACTr platform’s ability to circumvent common clinical limitations of existing TCE approaches and support our goal of delivering product candidates with potential for significantly reduced risk of toxic CRS responses, as well as reduced risk of on-target, healthy tissue toxicities. We look forward to advancing the IND submissions for both next-generation immunotherapies over the course of this year."
In a poster titled, "Preclinical Activity and Safety Profile of JANX007, a Novel PSMA-Targeting Tumor-Activated T Cell Engager for Treatment of Metastatic Castration-Resistant Prostate Cancer," Janux highlighted:
– JANX007 exhibits enhanced safety and PK properties relative to the PSMA-TCE.
– The critical safety feature of JANX007 is a tumor protease-cleavable, inhibitory peptide mask, which decreases JANX007 binding to human CD3 by >600x, restricting T cell activation to the tumor microenvironment (TME).
– In vitro, JANX007 exhibits up to 500x decrease in potency to activate T cells and induce T-cell mediated tumor cell killing relative to non-masked PSMA-TCE.
– In a repeat dose, GLP toxicity study in non-human primates (NHPs) JANX007 demonstrated an enhanced safety profile featuring a decrease in cytokine CRS-associated proinflammatory cytokines and no signs of healthy tissue toxicity with no-observed-adverse-effect-level (NOAEL) ≥ 1.5 mg/kg/dose IV bolus once-weekly (QW) x5.
– Albumin-binding domain extends the circulating half-life of JANX007 to ~120 hours in NHPs, relative to 2 hour half-life of non-masked TCE, supporting the TRACTr’s projected once weekly clinical dosing.
– GMP drug substance and drug product production has been completed to support a planned Phase 1 clinical trial.
– Cleavage-dependent activity, half-life extended PK, potential for superior safety, and manufacturability properties of JANX007 support its further development as an attractive mCRPC therapeutic.
– Janux plans to submit an investigational new drug (IND) application for JANX007 with the U.S. Food and Drug Administration (FDA) in the first half of 2022.
In a poster titled, "Preclinical Development of an EGFR-Targeted Tumor-Activated T Cell Engager with Enhanced Safety to Activity Multiple and Pharmacokinetics Profile," Janux highlighted:
– JANX008 exhibits enhanced safety and PK properties relative to the EGFR-TCE.
– The critical safety features of JANX008 are two tumor protease-cleavable peptide masks that inhibit EGFR and CD3 binding by >300x and >1,000x, respectively.
– Potent cleavage- and dose-dependent activity of JANX008 was demonstrated in multiple preclinical models, including EGFR antibody-resistant tumor and T cell co-culture assays, humanized mouse CRC model, and a fully human primary CRC tumor system with intact TME.
– Enhanced PK profile and high exposure of JANX008 were well tolerated in single dose and repeat dose NHP safety studies with limited CRS and healthy tissue toxicities with NOAEL ≥ 0.6 mg/kg/dose.
– GMP manufacturing has been completed to support a planned Phase 1 clinical trial.
– Preclinical data demonstrate key characteristics of JANX008 including cleavage-dependent activity, half-life extended PK, potential for superior safety, and manufacturability properties that could mitigate major limitations of TCEs and support JANX008 clinical development.
– Janux plans to submit an IND application for JANX008 with the FDA in the second half of 2022.
Details on Janux’s upcoming PEGS Boston presentations are as follows:
Poster: Preclinical Activity and Safety Profile of JANX007, a Novel PSMA-Targeting Tumor-Activated T Cell Engager for Treatment of Metastatic Castration-Resistant Prostate Cancer
Presenter: Shahram Salek-Ardakani, Ph.D. (Janux Chief Scientific Officer)
Poster Number: P078
Live Poster Sessions: May 2-5, 2022
Poster: Preclinical Development of an EGFR-Targeted Tumor-Activated T Cell Engager with Enhanced Safety to Activity Multiple and Pharmacokinetics Profile
Presenter: Shahram Salek-Ardakani, Ph.D. (Janux Chief Scientific Officer)
Poster Number: P079
Live Poster Sessions: May 2-5, 2022
The posters to be presented at PEGS Boston will be available beginning on May 2, 2022, on the "Scientific Publications" section of the Janux website at www.januxrx.com.