Prostate specific membrane antigen tumour activated T-cell engager therapy (Janux Therapeutics/Merck & Co)

Recently presented positive Phase 1 clinical trial data for PSMA-TRACTr JANX007 in mCRPC and for EGFR-TRACTr JANX008 in solid tumors Enrollment ongoing for JANX007 and JANX008 Update on JANX007 data and doses selected for expansion cohorts is anticipated in 2H 2024 $344.0 million in year-end cash, cash equivalents, and short-term investments In March, further strengthened balance sheet with approximately $320.2 million net proceeds from underwritten offering 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 reported financial results for the fourth quarter and full year ended December 31, 2023, and provided a business update. “2023 was a critical year for Janux as we tested the potential power of our TRACTr platform in the clinic. We believe the data recently presented from both of our clinical programs displays the profound impact we can have on patients through our tumor-activated approach. We are excited to be helping cancer patients who need novel therapies and with our substantial cash runway we feel well-positioned to execute on our clinical plan,” said David Campbell, Ph.D., President and CEO of Janux. RECENT BUSINESS HIGHLIGHTS AND FUTURE MILESTONES: Presented positive updated interim Phase 1 clinical trial data for PSMA-TRACTr JANX007 in prostate cancer in February 2024. As of February 12, 2024: Increasing depth of PSA declines and RECIST responses at higher doses were observed, while a favorable safety pro maintained. 83% (5/6) of subjects achieved PSA50 declines with first step dose ≥ 0.2mg. 56% (10/18) of subjects achieved PSA50 declines with first dose ≥ 0.1mg. No CRS > Grade 2 observed in heavily pre-treated late stage mCRPC population. Majority of non-CRS treatment-related adverse events (TRAEs) were Grade 1 or 2. Low incidence of Grade 3 TRAEs, and no Grade 4 or 5 events were observed. JANX007 has been administered at doses up to 3mg, significantly exceeding the anticipated maximum tolerable dose for the parental T cell engager, while the maximum tolerable dose for the TRACTr has not yet been established. Also presented positive interim Phase 1 clinical trial data for EGFR-TRACTr JANX008 in solid tumors. As of February 12, 2024: A subject with NSCLC achieved a RECIST PR maintained through 18-weeks with 100% target lung lesion reduction and elimination of liver metastasis with no CRS or TRAEs. No CRS greater than Grade 1 observed in any cohort. Majority of non-CRS TRAEs were Grade 1 or 2. No treatment-related SAEs or DLTs have been observed. Net proceeds of approximately $320.2 million (after deducting underwriting discounts, commissions and other estimated offering expenses) raised in an underwritten offering of common stock and pre-funded warrants in March 2024. Janux plans to deploy these funds to expand development of clinical programs, advance additional preclinical programs and extend corporate runway. JANX007 continues to enroll in the first-in-human Phase 1 clinical trial in mCRPC (NCT05519449). JANX008 continues to enroll in the first-in-human Phase 1 clinical trial in advanced or metastatic solid tumors (NCT05783622). Co-founder Dr. Tommy DiRaimondo promoted to Chief Scientific Officer. Tommy was instrumental in successfully transitioning Janux’s PSMA-TRACTr and EGFR-TRACTr programs from research into clinical trials. Tommy continues to manage the internal and external research operations and plays an integral role in managing the IP, discovery, creation, optimization and expansion of Janux’s preclinical pipeline. An update on JANX007 data and doses selected for expansion cohorts is anticipated in the second half of 2024. FOURTH QUARTER AND FULL YEAR 2023 FINANCIAL RESULTS: Cash and cash equivalents and short-term investments: As of December 31, 2023, Janux reported cash and cash equivalents and short-term investments of $344.0 million compared to $327.0 million at December 31, 2022. Research and development expenses: Research and development expenses were $12.2 million for the quarter and $54.9 million for the year ended December 31, 2023, compared to $15.4 million and $53.4 million for the same quarter and year in 2022. General and administrative expenses: General and administrative expenses were $6.4 million for the quarter and $26.1 million for the year ended December 31, 2023, compared to $5.7 million and $22.3 million for the same quarter and year in 2022. Net loss: Net loss was $11.8 million for the quarter and $58.3 million for the year ended December 31, 2023, compared to $16.1 million and $63.1 million for the same quarter and year in 2022. Janux’s TRACTr and TRACIr Pipeline Janux’s first clinical candidate, JANX007, is a TRACTr that targets PSMA and is being investigated in a Phase 1 clinical trial in adult subjects with metastatic castration-resistant prostate cancer (mCRPC). Janux’s second clinical candidate, JANX008, is a TRACTr that targets EGFR and is being studied in a Phase 1 clinical trial for the treatment of multiple solid cancers including colorectal cancer, squamous cell carcinoma of the head and neck, non-small cell lung cancer, and renal cell carcinoma. 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: Tumor Activated T Cell Engagers (TRACTr) and Tumor Activated Immunomodulators (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, lung, head and neck, and renal cancers. For more information, please visit 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, expectations regarding the use of Janux’s platform technologies to generate novel product candidates and the strength of Janux’s balance sheet and the adequacy of cash on hand. 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 . 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. Janux Therapeutics, Inc. Condensed Balance Sheets (in thousands) December 31, Assets 2023 2022 Current assets: Cash and cash equivalents $ 19,205 $ 51,426 Short-term investments 324,823 275,590 Prepaid expenses and other current assets 5,213 5,423 Total current assets 349,241 332,439 Restricted cash 816 816 Property and equipment, net 7,003 7,086 Operating lease right-of-use assets 20,838 22,279 Other long-term assets 2,509 1,390 Total assets $ 380,407 $ 364,010 Liabilities and Stockholders’ Equity Current liabilities: Accounts payable $ 2,424 $ 2,159 Accrued expenses 7,387 8,179 Current portion of deferred revenue 1,705 5,406 Current portion of operating lease liabilities 1,517 763 Total current liabilities 13,033 16,507 Deferred revenue, net of current portion — 2,221 Operating lease liabilities, net of current portion 23,025 24,542 Total liabilities 36,058 43,270 Total stockholders’ equity 344,349 320,740 Total liabilities and stockholders’ equity $ 380,407 $ 364,010 Janux Therapeutics, Inc. Condensed Statements of Operations and Comprehensive Loss (in thousands, except share and per share data) Three Months Ended December 31, Year Ended December 31, 2023 2022 2023 2022 Collaboration revenue $ 2,461 $ 2,845 $ 8,083 $ 8,612 Operating expenses: Research and development 12,241 15,434 54,922 53,441 General and administrative 6,357 5,677 26,140 22,262 Total operating expenses 18,598 21,111 81,062 75,703 Loss from operations (16,137 ) (18,266 ) (72,979 ) (67,091 ) Total other income 4,379 2,201 14,686 4,032 Net loss $ (11,758 ) $ (16,065 ) $ (58,293 ) $ (63,059 ) Other comprehensive gain (loss): Unrealized gain (loss) on available-for-sale securities, net 1,840 742 2,200 (1,265 ) Comprehensive loss $ (9,918 ) $ (15,323 ) $ (56,093 ) $ (64,324 ) Net loss per common share, basic and diluted $ (0.25 ) $ (0.39 ) $ (1.32 ) $ (1.52 ) Weighted-average shares of common stock outstanding, basic and diluted 46,683,613 41,584,195 44,016,283 41,469,631

The promise of therapies that activate and redirect T cells to attack tumors has been stymied by lack of efficacy or unacceptable toxicity. Such therapies have also had a hard time treating solid tumors. Janux Therapeutics’ technology is designed to overcome those limitations. Interim Phase 1 data for two programs are lending validation to the biotech’s approach. The results are early and more testing is needed. But one analyst says the data so far indicate that Janux’s lead program has blockbuster potential. Shares of Janux more than doubled at the market open Tuesday. The biotech’s share price continued its climb throughout the day before closing at $49.75, a 229% increase over Monday’s closing price. The company is now using the rise in stock price as an opportunity to raise about $175 million through a stock offering. Janux’s drugs belong to a class of therapies called T cell engagers. With one part that binds to a target on a T cell and another part that binds to a target on a tumor, the therapy brings the two cells together so the immune cell can kill the cancer cell. One challenge for T cell engagers is that toxicity develops when these systemically circulating therapies hit targets that are also found on healthy tissue. San Diego-based Janux calls its platform Tumor Activated T Cell Engager, or TRACTr. This technology designs a T cell engager with a “mask” that inhibits activation of the immune cell in healthy tissue. These masks stay in place with peptide linkers removable only by enzymes found at the site of a tumor. Each therapy also includes a component that extends its half-life. Janux therapy JANX007 is in development for metastatic castration-resistant prostate cancer. In updated Phase 1a results reported late Monday for the prostate cancer therapy, as of Feb. 12 cutoff date, 14 of the 18 participants who received the starting dose of 0.1 mg achieved PSA30 declines, which means at least a 30% decline in blood levels of the prostate specific antigen (PSA) that is elevated in men with prostate cancer. At a starting step dose of 0.2 mg, all six subjects achieved PSA declines of 30% and five of six achieved 50% declines. The higher dose 0.2 mg drove a deeper and more durable response, including one patient who achieved 90% decline in PSA. This response was achieved without compromising safety. T cell engagers can spark a complication called cytokine release syndrome. Janux said no cases of this complication higher than Grade 2 were observed in the Phase 1a trial. William Blair analyst Matt Phipps acknowledged the small number of patients in the study. But in a research note, he said the Janux therapy’s level of activity is “clearly significant and above relevant benchmarks in such heavily pretreated patients.” He added that tests of how the drug moves throughout the body detected the cleaved half-life extension domain but did not detect the active T cell engager in the periphery, a finding that has been consistent across treatment groups. “We believe this is a key data point validating the TRACTr platform and the ability to achieve cleavage of the molecule across patients,” Phipps said. The results increase this program’s chances of success, Phipps added. If it’s approved, the firm estimates peak sales could reach $1.5 billion in patients whose metastatic prostate cancer does not respond to chemotherapy. If JANX007 can move into earlier lines of treatment, this therapy offers multi-blockbuster potential, he said. Janux also reported preliminary data for JANX0008, which is being tested in heavily pretreated patients whose solid tumors express high levels of a protein called EGFR. This Phase 1a study includes patients with colorectal cancer, squamous cell carcinoma of the head and neck, non-small cell lung cancer (NSCLC), and renal cell carcinoma. As of Feb. 12, Janux said 11 participants across all four tumor types have been enrolled. In one patient whose NSCLC was treated with JANX0008, Janux reported a confirmed partial response with 100% reduction of the target lung lesion and elimination of liver metastasis. No cytokine release syndrome or treatment related adverse effects were reported. In addition, one patient with renal cell carcinoma experienced a 12% reduction in size of a large cancerous mass as well as significant clinical benefit. This patient experienced cytokine release syndrome classified as Grade 1. Janux is continuing dose optimization of the prostate cancer therapy, which is expected to have its next data update in the second half of this year. Dose escalation and optimization is also continuing for the test of the solid tumor therapy. Public domain image via the National Cancer Institute