Metastatic castration-resistant prostate cancer

SAN DIEGO, CA, USA I May 05, 2025 I Janux Therapeutics, Inc. (Nasdaq: JANX) (Janux), a clinical-stage 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 the initiation of Phase 1b expansion studies in the ongoing ENGAGER-PSMA-01 trial. ENGAGER-PSMA-01 is a first-in-human, open-label, multicenter Phase 1 clinical trial designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of JANX007 administered as monotherapy or in combination in adult patients with advanced metastatic castration-resistant prostate cancer (mCRPC). In December 2024, Janux reported positive interim clinical data from the Phase 1a dose escalation portion of the trial in 16 mCRPC patients with a median of four prior lines of therapy. At that time, the median radiographic progression-free survival (rPFS) reported was 7.4 months for all 16 patients.* As of April 21, 2025, updated results** have been achieved in the same 16 patients supporting the initiation of the Phase 1b expansion studies: *8/16 patients were noted as in-progress in the December 2024 reported results. **rPFS results based upon Kaplan-Meier estimate. In addition, Janux has selected a CRS-mitigation strategy to support the initiation of the Phase 1b expansion studies that is designed to maintain the CRS profile reported in December. The first Phase 1b expansion study will enroll taxane-naïve mCRPC patients and is designed to generate additional safety and efficacy data in this first and second line (1L/2L) patient population. This study will assess JANX007 monotherapy at two dose regimens (0.3/2/6mg and 0.3/2/9mg) with dosing administered once weekly or once every two weeks in mCRPC patients who have progressed on or after novel hormonal therapy (NHT). “Initiation of the taxane-naïve study marks an important step as we begin to evaluate JANX007 in earlier-line mCRPC patient populations,” said Zachariah McIver, D.O., Ph.D., Chief Medical Officer of Janux. “While therapeutic options for mCRPC have expanded, there remains a significant need for novel, non-chemotherapeutic approaches.” Janux plans to initiate three additional Phase 1b expansion studies, evaluating: “Improved efficacy and durability of responses has been observed by other prostate cancer drugs and TCEs when moving into earlier lines of therapy. There are also indications that safety with TCEs improve in earlier lines of therapy where disease burden is lower. We believe that these observations, coupled with the data seen in our Phase 1a dose escalation in later line patients, strongly support our decision to develop JANX007 in earlier lines of therapy,” said David Campbell, Ph.D., President and CEO of Janux. Additional data from JANX007 and JANX008 will be presented at future Janux events in the second half of 2025. Separately, Janux will host an R&D Day in mid-2025 highlighting product candidates identified from its preclinical pipeline to move into clinical trials. Janux’s TRACTr and TRACIr Pipeline Janux’s first clinical candidate, JANX007, is a TRACTr that targets prostate-specific membrane antigen (PSMA) and is being investigated in a Phase 1 clinical trial in adult patients with metastatic castration-resistant prostate cancer. Janux’s second clinical candidate, JANX008, is a TRACTr that targets epidermal growth factor receptor (EGFR) and is being studied in a Phase 1 clinical trial for the treatment of multiple solid cancers including colorectal carcinoma, squamous cell carcinoma of the head and neck, non-small cell lung cancer, renal cell carcinoma, small cell lung cancer, pancreatic ductal adenocarcinoma and triple-negative breast cancer. We are also generating a number of additional TRACTr and TRACIr programs for potential future development, some of which are at development candidate stage or later. We are currently assessing priorities in our preclinical pipeline. About Janux Therapeutics Janux is a clinical-stage biopharmaceutical company developing tumor-activated immunotherapies for cancer. Janux’s proprietary technology enabled the development of two distinct bispecific platforms: TRACTr and TRACIr. The goal of both platforms is to provide cancer patients with safe and effective therapeutics that direct and guide their immune system to eradicate tumors while minimizing safety concerns. Janux is currently developing a broad pipeline of TRACTr and TRACIr therapeutics directed at several targets to treat solid tumors. Janux has two TRACTr therapeutic candidates in clinical trials, the first targeting PSMA is in development for prostate cancer, and the second targeting EGFR is being developed for colorectal carcinoma, squamous cell carcinoma of the head and neck, non-small cell lung cancer, renal cell carcinoma, small cell lung cancer, pancreatic ductal adenocarcinoma and triple-negative breast cancer. For more information, please visit www.januxrx.com and follow us on LinkedIn. SOURCE: Janux Therapeutics

Phase 1b expansion study initiated in taxane-naïve mCRPC patients Updated data from Phase 1a dose escalation support initiation of Phase 1b dose expansion Updates on JANX007 and JANX008 expected in the second half of 2025 Janux to host R&D Day in mid-2025 highlighting preclinical pipeline progression to the clinic SAN DIEGO--(BUSINESS WIRE)-- Janux Therapeutics, Inc. (Nasdaq: JANX) (Janux), a clinical-stage 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 the initiation of Phase 1b expansion studies in the ongoing ENGAGER-PSMA-01 trial. ENGAGER-PSMA-01 is a first-in-human, open-label, multicenter Phase 1 clinical trial designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of JANX007 administered as monotherapy or in combination in adult patients with advanced metastatic castration-resistant prostate cancer (mCRPC). In December 2024, Janux reported positive interim clinical data from the Phase 1a dose escalation portion of the trial in 16 mCRPC patients with a median of four prior lines of therapy. At that time, the median radiographic progression-free survival (rPFS) reported was 7.4 months for all 16 patients.* As of April 21, 2025, updated results** have been achieved in the same 16 patients supporting the initiation of the Phase 1b expansion studies: Median rPFS of 7.5 months (n=16) Median rPFS of 7.9 months for patients treated at 6mg and 9mg target doses (n=9) 6-month rPFS of 65% (n=16) 6-month rPFS of 78% for patients treated at 6mg and 9mg target doses (n=9) Safety data remained consistent with the December 2024 data disclosure (n=16) *8/16 patients were noted as in-progress in the December 2024 reported results. **rPFS results based upon Kaplan-Meier estimate. In addition, Janux has selected a CRS-mitigation strategy to support the initiation of the Phase 1b expansion studies that is designed to maintain the CRS profile reported in December. The first Phase 1b expansion study will enroll taxane-naïve mCRPC patients and is designed to generate additional safety and efficacy data in this first and second line (1L/2L) patient population. This study will assess JANX007 monotherapy at two dose regimens (0.3/2/6mg and 0.3/2/9mg) with dosing administered once weekly or once every two weeks in mCRPC patients who have progressed on or after novel hormonal therapy (NHT). “Initiation of the taxane-naïve study marks an important step as we begin to evaluate JANX007 in earlier-line mCRPC patient populations,” said Zachariah McIver, D.O., Ph.D., Chief Medical Officer of Janux. “While therapeutic options for mCRPC have expanded, there remains a significant need for novel, non-chemotherapeutic approaches.” Janux plans to initiate three additional Phase 1b expansion studies, evaluating: JANX007 in combination with an androgen receptor inhibitor in taxane-experienced mCRPC patients JANX007 monotherapy in PARP inhibitor-resistant mCRPC patients JANX007 monotherapy in NHT- and taxane-experienced mCRPC patients designed to support OPTIMUS dose selection for registrational studies “Improved efficacy and durability of responses has been observed by other prostate cancer drugs and TCEs when moving into earlier lines of therapy. There are also indications that safety with TCEs improve in earlier lines of therapy where disease burden is lower. We believe that these observations, coupled with the data seen in our Phase 1a dose escalation in later line patients, strongly support our decision to develop JANX007 in earlier lines of therapy,” said David Campbell, Ph.D., President and CEO of Janux. Additional data from JANX007 and JANX008 will be presented at future Janux events in the second half of 2025. Separately, Janux will host an R&D Day in mid-2025 highlighting product candidates identified from its preclinical pipeline to move into clinical trials. Janux’s TRACTr and TRACIr Pipeline Janux’s first clinical candidate, JANX007, is a TRACTr that targets prostate-specific membrane antigen (PSMA) and is being investigated in a Phase 1 clinical trial in adult patients with metastatic castration-resistant prostate cancer. Janux’s second clinical candidate, JANX008, is a TRACTr that targets epidermal growth factor receptor (EGFR) and is being studied in a Phase 1 clinical trial for the treatment of multiple solid cancers including colorectal carcinoma, squamous cell carcinoma of the head and neck, non-small cell lung cancer, renal cell carcinoma, small cell lung cancer, pancreatic ductal adenocarcinoma and triple-negative breast cancer. We are also generating a number of additional TRACTr and TRACIr programs for potential future development, some of which are at development candidate stage or later. We are currently assessing priorities in our preclinical pipeline. About Janux Therapeutics Janux is a clinical-stage biopharmaceutical company developing tumor-activated immunotherapies for cancer. Janux’s proprietary technology enabled the development of two distinct bispecific platforms: TRACTr and TRACIr. The goal of both platforms is to provide cancer patients with safe and effective therapeutics that direct and guide their immune system to eradicate tumors while minimizing safety concerns. Janux is currently developing a broad pipeline of TRACTr and TRACIr therapeutics directed at several targets to treat solid tumors. Janux has two TRACTr therapeutic candidates in clinical trials, the first targeting PSMA is in development for prostate cancer, and the second targeting EGFR is being developed for colorectal carcinoma, squamous cell carcinoma of the head and neck, non-small cell lung cancer, renal cell carcinoma, small cell lung cancer, pancreatic ductal adenocarcinoma and triple-negative breast cancer. For more information, please visit www.januxrx.com and follow us on LinkedIn. 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, expectations regarding the timing, scope and results of Janux’s development activities, including its ongoing and planned preclinical studies and clinical trials, the timing of and plans for regulatory filings, the potential benefits of Janux’s product candidates and platform technologies, the timing of future data releases, and expectations regarding the use of Janux’s platform technologies to generate novel product candidates. 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, the risks related to geopolitical events, including international tariffs, global economic, financial, and healthcare system disruptions and the current and potential future negative impacts to Janux’s business operations and development activities, 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. Investors: Andy Meyer Janux Therapeutics ameyer@januxrx.com (202) 215-2579 Media: Jessica Yingling, Ph.D. Little Dog Communications Inc. jessica@litldog.com (858) 344-8091

OXFORD, UK I May 1, 2025 I Blue Earth Therapeutics today announced further progress in development of its radiohybrid, lutetium-labelled, PSMA targeted, investigational radioligand therapy, with enrolment of the first two patients in a Phase 2 clinical trial. The primary measure of efficacy in the study will be the proportion of patients achieving a ≥50% reduction in PSA levels, as well as assessing radiographic progression-free survival and patient safety (NCT05413850). The study is testing multiple dosing regimens that focus on delivering higher radiation doses when tumor burden is usually highest, at the beginning of treatment. This approach contrasts to pivotal studies of earlier radioligand therapies where the same dose was administered in every cycle 2 regardless of tumor burden. The study design aligns with the US FDA Project Optimus initiative where the goal is that drug developers optimize dosing early in a product’s development to deliver the best possible benefit risk profile. Loading doses will be delivered by either a) giving a higher dose in the first two treatment cycles, or b) shortening the time between administration of the first three doses to three weeks from the usual six weeks. The study is also designed to test the clinical benefit of administration of high total doses of administered radioactivity, up to 60GBq. The Phase 1 data confirmed a high ratio of uptake in tumor tissues vs. uptake in healthy tissues such as kidneys and salivary glands 1 . David Gauden DPhil, CEO of Blue Earth Therapeutics said, “This is an important step forward in the development of Lutetium ( 177 Lu) rhPSMA-10.1 injection and builds on the strong data seen in the Phase 1 clinical trial. Commencement of treatment of patients at full intended therapeutic dosing levels provides a great opportunity to assess the benefit this therapy can bring to patients. With up to 20 sites enrolling patients, we expect to see first results from the study early next year. We are grateful to the physicians and patients of Biogenix Molecular in Florida, who have just recruited the first patients for the study.” About metastatic prostate cancer In 2025 it is estimated that there will be 50,055 new cases of metastatic prostate cancer in the United States (de novo diagnoses plus recurrence from earlier stage diagnoses). 3 Five-year survival for newly diagnosed metastatic prostate cancer is low, 36.6%. 4 While death rates from prostate cancer have declined over the past three decades 4 , there is still considerable room to improve patient outcomes. About Radiohybrid Prostate–Specific Membrane Antigen (rhPSMA) rhPSMA compounds are referred to as radiohybrid (“rh”), as each molecule possesses four distinct domains. The first consists of a Prostate–Specific Membrane Antigen–targeted receptor ligand. It is attached to two labelling moieties which may be radiolabelled with diagnostic isotopes such as 18F or 68Ga for PET imaging, or with therapeutic isotopes such as 177Lu or 225Ac for radioligand therapy, all of which are joined together by a modifiable linker which can be used to modulate important pharmacokinetic characteristics. Radiohybrid PSMA offers the potential for targeted treatment for men with prostate cancer and originated at the Technical University of Munich, Germany. Blue Earth Diagnostics acquired exclusive worldwide rights to rhPSMA diagnostic imaging technology from Scintomics GmbH in 2018, and therapeutic rights in 2020, and has sublicensed the therapeutic application to its sister company Blue Earth Therapeutics. About Blue Earth Therapeutics Blue Earth Therapeutics is a clinical stage company dedicated to advancing next-generation targeted radiotherapeutics to treat patients who have cancer and has been incubated within the Bracco family of companies. Other investors joined with Bracco in a $76.5M Series A financing round in 2024. With proven management expertise across the spectrum of radiopharmaceutical and oncology drug development, as well as biotechnology start–up experience, the Company aims to innovate and improve upon current technologies and rapidly advance new targeted therapies for serious diseases. Blue Earth Therapeutics has an emerging pipeline initially focused on prostate cancer. For more information, please visit: https://www.blueearththerapeutics.com . About Bracco Imaging Bracco Imaging S.p.A., part of the Bracco Group, is a world–leading diagnostic imaging provider. Headquartered in Milan, Italy, Bracco Imaging develops, manufactures and markets diagnostic imaging agents and solutions. It offers a product and solution portfolio for all key diagnostic imaging modalities: X–ray imaging (including Computed Tomography–CT, Interventional Radiology, and Cardiac Catheterization), Magnetic Resonance Imaging (MRI), Contrast Enhanced Ultrasound (CEUS), and Nuclear Medicine through radioactive tracers and novel PET imaging agents to inform clinical management and guide care for cancer patients in areas of unmet medical need. Our continually evolving portfolio is completed by a range of medical devices, advanced administration systems and dose–management software. In 2019 Bracco Imaging enriched its product portfolio by expanding the range of oncology nuclear imaging solutions in the urology segment and other specialties with the acquisition of Blue Earth Diagnostics. In 2021, Bracco Imaging established Blue Earth Therapeutics as a separate, cutting–edge biotechnology vehicle to develop radiopharmaceutical therapies. Visit: www.braccoimaging.com . SOURCE: Blue Earth Therapeutics