Janux Therapeutics Profile
Janux Therapeutics, Inc. operates as a clinical-stage biopharmaceutical company.
The company is developing a broad pipeline of novel immunotherapies by applying its proprietary technology to its TRACTr and TRACIr platforms to better treat patients suffering from cancer.
The company’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.
The company uses its TRACTr platform technology to engineer product candidates designed to overcome these limitations. The company is developing a broad pipeline with lead programs targeting prostate-specific membrane antigen (PSMA), epidermal growth factor receptor (EGFR), and trophoblast cell surface antigen 2 (TROP2). In October 2022, the first patient was dosed with its PSMA-TRACTr (JANX007) in its first-in-human Phase 1 clinical trial in patients with prostate cancer and the company anticipates providing an interim clinical update from the trial in the second half of 2023. For the company’s EGFR-TRACTr (JANX008), it recently received the U.S. Food and Drug Administration (FDA) clearance of an Investigational New Drug application (IND). For the company’s TROP2-TRACTr, it expects to select a development candidate in 2023.
The company is also applying its proprietary technology to develop a TRACIr costimulatory bispecific product candidate (JANX009) against programmed death-ligand 1 (PD-L1) and Cluster of Differentiation 28 (CD28) designed to further enhance the anti-tumor activity of T cells, which has the potential to be used as a single-agent or in combination with its TRACTr pipeline and other modalities. The company expects to submit an IND for this product candidate in 2023.
TRACTr and TRACIr Platforms
The company’s proprietary TRACTr and TRACIr platforms offer the potential to expand the breadth of patients that can be treated with TCEs and non-TCE based immunomodulators while reducing the risk of life-threatening toxicities. Each of the company’s proprietary TRACTrs and TRACIrs are consisted of an antigen-binding domain, a T cell-binding domain, domain-optimized peptide masks, an albumin-binding domain, and cleavable peptide linkers. The mask is a peptide designed to bind to the tumor or T cell-binding domain. It inhibits the binding domain’s interaction with its target, thereby inhibiting the activation of T cells. The antigen and T cell-binding domains in the company’s TRACTr and TRACIr product candidates may be covalently attached to peptide masks that block binding and activity until they are removed. The company uses proprietary peptide linker sequences composed of tumor protease recognition sites to attach these masks to the antigen-binding domains in a way designed to make the masks highly sensitive to removal by tumor proteases but highly stable in the absence of these proteases. In addition, the company attaches an albumin-binding domain to one mask, which is designed to extend the half-life of its TRACTr and TRACIr product candidates until they become activated inside a tumor.
While the company’s TRACTr and TRACIr platforms are novel and unproven and its product candidates remain in the early clinical, preclinical or discovery stage.
Lead Programs
The company’s lead TRACTr product candidates are designed to target PSMA, EGFR, and TROP2. Each of these tumor targets is clinically validated and implicated in solid tumors with high prevalence, including metastatic castrate-resistant prostate cancer (mCRPC), colorectal cancer (CRC), renal cell carcinoma (RCC), squamous cell carcinoma of the head and neck (SCCHN), triple-negative breast cancer (TNBC), urothelial cancer (UC), and non-small cell lung cancer (NSCLC). The company is also applying its proprietary technology to develop a TRACIr costimulatory bispecific product candidate against PD-L1 and CD28 designed to further enhance the anti-tumor activity of T cells, which has the potential to be used as a single-agent or in combination with its TRACTr pipeline and other modalities.
In addition to the company’s wholly-owned pipeline programs, it has a strategic research collaboration with Merck Sharp & Dohme Corp. (Merck) to develop TRACTr product candidates directed against two cancer targets selected by Merck.
The company recently received FDA clearance of an IND to conduct a Phase 1 trial in patients with advanced solid tumors that overexpress EGFR, including CRC, RCC, SCCHN and NSCLC, to assess safety, tolerability, and pharmacokinetics. In addition, the company plans to evaluate additional opportunities where EGFR is overexpressed.
The company is developing its TROP2-TRACTr program to treat TROP2 overexpressing solid tumors, including TNBC, UC, and NSCLC. TROP2 is a cell surface glycoprotein overexpressed by many human carcinomas. In preclinical studies, the company showed that its TROP2-TRACTr had an over 6,500-fold reduced ability to activate T cells when it was masked compared to unmasked. In addition, the company demonstrated that its TROP2-TRACTr was well-tolerated in NHPs, substantially reduced cytokine release relative to the unmasked TCE, and had a prolonged half-life. The company expects to select a development candidate in 2023 for its TROP2-TRACTr.
The company plans to submit an IND in 2023 to conduct a Phase 1 trial in patients with advanced solid tumors to assess safety, tolerability, and pharmacokinetics.
TRACTr Programs
The company is building a broad portfolio of TRACTr programs led by its PSMA, EGFR, and TROP2 targeted TRACTrs.
PSMA-TRACTr (JANX007)
The company’s PSMA-TRACTr is designed to target PSMA, a protein expressed in prostate cancer tumors and the vasculature of other tumors. The company’s PSMA-TRACTr is designed to generate potent anti-tumor activity in mCRPC patients by enabling the delivery of higher concentrations of active drugs to tumors than traditional TCEs. The company’s PSMA-TRACTr product candidate has the potential to deliver therapeutic benefits to patients while minimizing severe adverse events (SAEs), including the prevention of dose-limiting cytokine release syndrome (CRS). In October 2022, the first patient was dosed with JANX007 in its first-in-human Phase 1 clinical trial in patients with prostate cancer and it anticipates providing an interim clinical update from the trial in the second half of 2023.
EGFR-TRACTr (JANX008)
The company’s EGFR-TRACTr is designed to target EGFR, a well-validated target that is overexpressed in many cancer types with multiple approved mAbs, including ERBITUX, marketed by Eli Lilly and Merck KGaA, for the treatment of CRC and SCCHN, and VECTIBIX, marketed by Amgen and Takeda, for the treatment of CRC.
The company’s EGFR-TRACTr is designed to generate potent anti-tumor activity by enabling the delivery of higher concentrations of active drug to tumors than traditional TCEs. The company’s EGFR-TRACTr product candidate has the potential to deliver therapeutic benefits to patients while minimizing SAEs, including the prevention of dose-limiting CRS. The company recently received FDA clearance of an IND that it submitted for JANX008.
The company is developing its EGFR-TRACTr product candidate for the treatment of metastatic CRC, RCC, SCCHN and NSCLC. The company has shown in preclinical studies that its EGFR-TRACTr had an 8,500-fold reduced ability to activate T cells when it is masked compared to when it is unmasked. In addition, the company demonstrated that its EGFR-TRACTr was well-tolerated in NHPs, substantially reduced cytokine release relative to the unmasked TCE, and had a prolonged half-life.
TROP2-TRACTr
The company’s TROP2-TRACTr is designed to target TROP2, a clinically validated anti-tumor target for which there is a recently approved anti-TROP2 antibody-drug conjugate (ADC), sacituzumab govitecan, marketed as TRODELVY by Gilead. TRODELVY has been approved to treat metastatic TNBC and UC. The company’s TROP2-TRACTr is designed to generate potent anti-tumor activity, initially in TNBC patients, by enabling the delivery of higher concentrations of active drug to tumors than traditional TCEs. The company’s TROP2-TRACTr has the potential to deliver therapeutic benefits to patients while minimizing SAEs, including the prevention of dose-limiting CRS. The company’s TROP2-TRACTr has the potential to deliver the potent anti-tumor activity of a TCE to patients who have tumors that overexpress TROP2 while also providing increased safety and dosing convenience. The company plans to select a TROP2-TRACTr development candidate in 2023.
TRACIr Program
The company is also applying its proprietary technology to its TRACIr platform, with its first program being a tumor-activated PD-L1xCD28 T cell costimulatory bispecific.
PD-L1xCD28 Costimulatory Bispecific (JANX009)
The company’s PD-L1xCD28 costimulatory bispecific program is designed to amplify existing T cell anti-tumor responses and TRACTr activity through a dual mechanism of blocking tumor-expressed immunosuppressive signaling and activating T cell costimulatory signaling. The company’s bispecific molecule is designed to bind to immunosuppressive PD-L1 on tumor cells and to the CD28 costimulatory receptor on T cells. The company’s technology’s potential to convert the inhibitory checkpoint signal into an immune activation signal via costimulation could stimulate further anti-tumor activity. Like checkpoint inhibitors, the company’s costimulatory program could be combined with a variety of classes of therapeutics, including chemotherapeutics, as well as other immunotherapies. The company has shown that the use of this bispecific led to potent T cell-directed tumor cell killing in cell assays in which a checkpoint inhibitor was ineffective. In addition, the company’s costimulatory program enhanced the potency of tumor cell killing when combined with a TCE. The company plans to submit an IND for its PD-L1xCD28-TRACIr in 2023.
Research Collaboration with Merck Sharp & Dohme Corp.
In December 2020, the company entered into a research collaboration and exclusive license agreement with Merck to develop TRACTr product candidates distinct from those in its internally developed pipeline. Merck had the right to select up to two collaboration targets related to next-generation TCE immunotherapies for cancer treatment, both of which have been selected. Merck received an exclusive worldwide license for each selected target and intellectual property from the collaboration.
License Agreement with WuXi Biologics (Hong Kong) Limited
In April 2021, the company entered into a cell line license agreement (Cell Line License Agreement) with WuXi Biologics (Hong Kong) Limited (WuXi Biologics), pursuant to which it received a non-exclusive, worldwide, sublicensable license under certain of WuXi Biologics’ patent rights, know-how and biological materials (WuXi Biologics Licensed Technology), to use the WuXi Biologics Licensed Technology to make, use, sell, offer for sale and import certain therapeutic products produced through the use of the cell line licensed by WuXi Biologics under the Cell Line License Agreement (WuXi Biologics Licensed Product). Specifically, the WuXi Biologics Licensed Technology is used to manufacture a component of the company’s PSMA-TRACTr and EGFR-TRACTr product candidates.
Strategy
The key elements of the company’s strategy are to advance its lead TRACTr programs through clinical development; broaden its portfolio of TRACTr product candidates; expand its internal pipeline into logical classes of therapeutics beyond TCEs; and selectively evaluate opportunities to maximize the potential of its programs in partnership with leading biopharmaceutical companies.
Intellectual Property
The company owns the patents and patent applications relating to its TRACTr and TRACIr platform technologies.
As of February 15, 2023, the company owned 16 pending U.S. provisional and non-provisional patent applications, two U.S. patents, 12 pending patent applications filed under the Patent Cooperation Treaty (PCT) and 16 foreign patent applications. Specifically, the company has one U.S. non-provisional patent application and five foreign patent applications directed to compositions of its TRACTr and TRACIr platform technologies that are applicable across its product candidates for its PSMA-TRACTr (JANX007), EGFR-TRACTr (JANX008), and costimulatory bispecific (JANX009) and its TROP2-TRACTr program. The company also has two PCT patent applications, one U.S. patent, one U.S. non-provisional patent application, five foreign patent applications that cover compositions and applications of various components and aspects of its TRACTr and TRACIr platform technologies and have general applicability across various product candidates. The company has one PCT patent application that covers compositions and applications of components of its TRACTr platform technology that has generally applicability to TRACTr product candidates. The company further has one U.S. patent, two U.S. provisional patent applications, two PCT patent applications, one U.S. non-provisional patent application, and two foreign patent applications specific to JANX007, two U.S. provisional patent applications, two PCT patent applications, and two foreign patent applications specific to its TROP2-TRACTr program, two U.S. provisional patent applications, three PCT applications, and two foreign patent applications specific to JANX008, and one U.S. provisional patent application and one PCT patent application specific to JANX009. In addition, the company has six U.S. non-provisional patent applications and one PCT patent application relating to compositions of its other proprietary antibodies, compounds, technology, inventions, improvements, and other aspects of its technology that are not under active development. Any patents that issue from these pending patent applications are expected to expire between 2038 and 2043, absent any patent term adjustments or extensions.
Research and Development
The company’s research and development expenses were $53.4 million for the year ended December 31, 2022.
Competition
With respect to the company’s lead PSMA-TRACTr, it is aware of other competing PSMA-targeting clinical-stage therapeutics, which include, but are not limited to: T cell engagers from Amgen, Abbvie/Calibr, Crescendo Biologics, Johnson and Johnson, Lava Therapeutics and Regeneron; T cell immunomodulators from Regeneron; antibody-drug conjugates from Ambrx; CAR T cell therapies from Gilead/Tmunity Therapeutics; and radiopharmaceuticals from Novartis, Point Biopharma, Telix and Bayer.
With respect to the company’s EGFR-TRACTr, it faces competition from several targeted therapies approved by the FDA to treat CRC, including, but not limited to, Roche’s bevacizumab, Amgen’s panitumumab, Eli Lilly/Merck KGaA’s cetuximab, Bayer’s regorafenib, and Eli Lilly’s ramucirumab.
The company is developing a pipeline of TRACTr and other protease-activated therapeutics that face increasing competition from other biologic prodrug developers, which include, but are not limited to, Adagene, BioAtla, Chugai Pharmaceutical Co./Roche Holding AG, CytomX Therapeutics, Harpoon Therapeutics, Merck & Co., Sanofi, and Xilio Therapeutics.
History
Janux Therapeutics, Inc. was founded in 2017. The company was incorporated under the laws of the state of Delaware in 2017.
