-PSMA-TRACTr (JANX007) and EGFR-TRACTr (JANX008) exhibit enhanced safety and PK properties relative to unmasked TCE-
-Enhanced PK profile and high exposure of TRACTrs were well tolerated in NHP safety studies with limited healthy tissue toxicities and cytokine release syndrome-
-Data highlight potential of Janux’s TRACTr technology platform to support clinical development–
-Company remains on-track to submit IND filings for JANX007 in 1H 2022 and JANX008 in 2H 2022-
SAN DIEGO–(BUSINESS WIRE)–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, today announced 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.
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.
About Janux Therapeutics
Janux Therapeutics is an innovative biopharmaceutical company developing next-generation therapeutics based on applying its proprietary technology to its Tumor Activated T Cell Engager (TRACTr) and Tumor Activated Immunomodulator (TRACIr) platforms to better treat patients suffering from cancer. Janux’s initial focus is on developing a novel class of T cell engagers (TCEs), and its lead product candidates are designed to target clinically validated drug targets. While TCE therapeutics have displayed potent anti-tumor activity in hematological cancers, developing TCEs to treat solid tumors have faced challenges due to the limitations of prior TCE technologies, namely (i) overactivation of the immune system leading to cytokine release syndrome, (ii) on-target, healthy tissue toxicities, and (iii) poor pharmacokinetics leading to short half-life. Janux is using its TRACTr platform technology to engineer product candidates designed to overcome these limitations by offering accuracy, stability, activity, modularity, and manufacturability. Janux is developing a broad pipeline with lead TRACTr programs targeting prostate-specific membrane antigen (PSMA), epidermal growth factor receptor (EGFR), and trophoblast cell surface antigen 2 (TROP2), and its lead TRACIr program targeting PD-L1xCD28, with all of its programs currently in the IND-enabling or discovery stage. For more information, please visit www.januxrx.com.
Forward-Looking Statements
This news release contains certain forward-looking statements that involve risks and uncertainties that could cause actual results to be materially different from historical results or from any future results expressed or implied by such forward-looking statements. Such forward-looking statements include statements regarding, among other things, Janux’s ability to bring new treatments to cancer patients in need, the progress and expected timing of Janux’s drug development programs, and the expected timing for our regulatory filings and initiation of our clinical trials. Factors that may cause actual results to differ materially include the risk that compounds that appear promising in early research do not demonstrate safety and/or efficacy in later preclinical studies or clinical trials, the risk that Janux may not obtain approval to market its product candidates, uncertainties associated with performing clinical trials, regulatory filings and applications, risks associated with reliance on third parties to successfully conduct clinical trials, the risks associated with reliance on outside financing to meet capital requirements, and other risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs. You are urged to consider statements that include the words “may,” “will,” “would,” “could,” “should,” “believes,” “estimates,” “projects,” “promise,” “potential,” “expects,” “plans,” “anticipates,” “intends,” “continues,” “designed,” “goal,” or the negative of those words or other comparable words to be uncertain and forward-looking. For a further list and description of the risks and uncertainties Janux faces, please refer to Janux’s periodic and other filings with the Securities and Exchange Commission, which are available at www.sec.gov. Such forward-looking statements are current only as of the date they are made, and Janux assumes no obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.
Contacts
Media:
Jessica Yingling, Ph.D.
Little Dog Communications Inc.
jessica@litldog.com
(858) 344-8091
Investors:
Christina Tartaglia
Stern Investor Relations, Inc.
christina@sternir.com
(212) 362-1200