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NEW YORK--( BUSINESS WIRE )--Inspirna, Inc., a clinical stage biopharmaceutical company developing first-in-class cancer therapeutics, announced today that Chief Executive Officer Dr. Usman “Oz” Azam, M.D., will participate in a corporate presentation at the 42 nd Annual J.P. Morgan Healthcare Conference on Thursday, January 11, 2024 at 8:30am PT / 11:30am ET. About Inspirna Inspirna, Inc., is a privately-held clinical-stage biopharmaceutical company focused on the discovery and development of novel cancer drugs that target key pathways in cancers of high unmet need. The company is pursuing several first-in-class drug candidates. Inspirna’s lead drug candidate, ompenaclid (RGX-202), is an orally-administered small molecule that targets the CKB/SLC6A8 pathway. This pathway becomes activated in the tumors of select patients where it enables the generation of the energy molecule ATP in response to tumor hypoxia. Ompenaclid is currently being tested in multiple mid stage clinical trials in patients with advanced or metastatic RAS mutant colorectal cancer. Inspirna’s second clinical stage drug candidate, abequolixron (RGX-104), is an oral small molecule activator of LXR/APOE that inhibits angiogenesis and tumor myeloid derived suppressor cells to enhance the immune response against tumors. Abequolixron is currently being tested in a Phase 1b/2 clinical trial in patients with advanced or metastatic lung cancer in combination with docetaxel and endometrial cancer in combination with ipilimumab through a clinical collaboration with Bristol Myers Squibb. Inspirna identifies novel cancer targets using its microRNA-based target discovery platform, RNA-DRIVEr, which was originally developed by Inspirna’s scientific co-founders at The Rockefeller University and exclusively licensed to Inspirna. The Company brings together distinguished scientific founders, a seasoned board of directors, and a leadership team comprised of experienced drug developers. The Company is funded by leading biotechnology investors, including Novo Holdings A/S, Sofinnova Partners, Sands Capital, Vivo Capital, Lepu Holdings Limited, Sixty Degree Capital, Silicon Valley Bank, K2 HealthVentures, Oceanpine Capital, WuXi PharmaTech Healthcare Fund I, LP, Alexandria Venture Investments, LLC, Dreavent 6, Exor Seeds, and the Partnership Fund for New York City. For more information, please visit https://inspirna.com/ .

NEW YORK--( BUSINESS WIRE )--Inspirna, Inc., a clinical stage biopharmaceutical company developing first-in-class cancer therapeutics, announced today a licensing agreement with Merck KGaA, Darmstadt, Germany, for ompenaclid (RGX-202), a first-in-class oral inhibitor of the creatine transport channel SLC6A8, currently in development for RAS mutated (RASm) second-line (2L) advanced or metastatic colorectal cancer (mCRC) and SLC6a8 targeting follow-on compounds. “ We are excited to partner with Merck KGaA, Darmstadt, Germany, a leader in the oncology field with global drug development and commercial expertise in colorectal cancer specifically, to help bring our novel therapies to more patients in need,” said Dr. Usman “Oz” Azam, M.D., Chief Executive Officer of Inspirna. “ The data to date validates our belief in ompenaclid as a potential first-in-class therapy for advanced colorectal cancer and underscores the power of our proprietary target discovery platform RNA-DRIVEr™. We look forward to working closely with Merck KGaA, Darmstadt, Germany, as we continue to evaluate ompenaclid in a Phase 2 randomized controlled trial.” “ Over the past decade, the treatment paradigm for patients with RAS-mutated CRC, accounting for approximately 45% of second-line population, has not seen major innovation,” said Victoria Zazulina, M.D., Head, Development Unit, Oncology for the Healthcare business of Merck KGaA, Darmstadt, Germany. “ With our expertise in the treatment of CRC, and based on the encouraging early data for ompenaclid, this agreement with Inspirna offers the opportunity to advance a potential new first-in-class therapy that may improve outcomes for patients.” Under the terms of the license agreement, Merck KGaA, Darmstadt, Germany will receive an exclusive license to ompenaclid outside of the United States and an option to co-develop and co-promote ompenaclid in the US. Furthermore, the parties agreed to collaborate on Inspirna’s SLC6A8 follow-on compounds for which Inspirna will retain US co-development and co-commercialization rights. Inspirna will receive an upfront payment of $45 million. Upon the achievement of certain development and sales milestones for ompenaclid, Inspirna is eligible to receive milestone payments with tiered royalty rates in the low teens on net sales outside of the US. Inspirna is eligible to also receive development, regulatory and sales milestone payments for each follow-on compound targeting SLC6A8 along with up to double-digit royalties on net sales outside of the US. Inspirna most recently presented clinical data from the Phase 1b/2 study of ompenaclid in combination with FOLFIRI and bevacizumab at the European Society for Medical Oncology (ESMO) Congress in October 2023. Results as of the September 18, 2023 data cutoff showed encouraging efficacy and safety data, including a median progression-free survival of 10.2 months and median overall survival of 19.1 months across all 41 patients with 2L RASm mCRC. Of the 30 evaluable patients for response, the objective response rate was 37%, with 11 partial responses. Ompenaclid was well-tolerated, with no dose-limiting toxicities observed in the dose-escalation cohort and combination safety profile comparable to FOLFIRI plus bevacizumab backbone treatment. Inspirna has initiated a Phase 2 double-blind randomized controlled trial in 2L RAS mutant advanced or metastatic mCRC comparing ompenaclid versus placebo plus FOLFIRI and bevacizumab. About Inspirna Inspirna, Inc., is a privately-held clinical-stage biopharmaceutical company focused on the discovery and development of novel cancer drugs that target key pathways in cancers of high unmet need. The company is pursuing several first-in-class drug candidates. Inspirna’s lead drug candidate, ompenaclid (RGX-202), is an orally-administered small molecule that targets the CKB/SLC6A8 pathway. This pathway becomes activated in the tumors of select patients where it enables the generation of the energy molecule ATP in response to tumor hypoxia. Ompenaclid is currently being tested in multiple mid stage clinical trials in patients with advanced or metastatic RAS mutant colorectal cancer. Inspirna’s second clinical stage drug candidate, abequolixron (RGX-104), is an oral small molecule activator of LXR/APOE that inhibits angiogenesis and tumor myeloid derived suppressor cells to enhance the immune response against tumors. Abequolixron is currently being tested in a Phase 1b/2 clinical trial in patients with advanced or metastatic lung cancer in combination with docetaxel and endometrial cancer in combination with ipilimumab through a clinical collaboration with Bristol Myers Squibb. Inspirna identifies novel cancer targets using its microRNA-based target discovery platform, RNA-DRIVEr, which was originally developed by Inspirna’s scientific co-founders at The Rockefeller University and exclusively licensed to Inspirna. The Company brings together distinguished scientific founders, a seasoned board of directors, and a leadership team comprised of experienced drug developers. The Company is funded by leading biotechnology investors, including Novo Holdings A/S, Sofinnova Partners, Sands Capital, Vivo Capital, Lepu Holdings Limited, Sixty Degree Capital, Silicon Valley Bank, K2 HealthVentures, Oceanpine Capital, WuXi PharmaTech Healthcare Fund I, LP, Alexandria Venture Investments, LLC, Dreavent 6, Exor Seeds, and the Partnership Fund for New York City. For more information, please visit https://inspirna.com/ .

Encouraging efficacy and safety data for ompenaclid (RGX-202) in combination with FOLFIRI/BEV supports further development in second-line advanced or metastatic CRC NEW YORK--(BUSINESS WIRE)-- Inspirna, Inc., a clinical stage biopharmaceutical company developing first-in-class cancer therapeutics, announced today data from the ongoing Phase 1b/2 study of ompenaclid (RGX-202) in combination with FOLFIRI and bevacizumab (BEV) in RAS-mutated (RASm) advanced or metastatic colorectal cancer (CRC) presented at the European Society for Medical Oncology (ESMO) Congress 2023 being held October 20-24, 2023 in Madrid, Spain. “We are excited to share the clinical data being presented at ESMO, further demonstrating the clear potential of ompenaclid to improve on the standard-of-care for advanced CRC, especially for the approximately 40-45% of CRC patients whose tumors harbor a RAS mutation,” said Andrew Hendifar, M.D., Assistant Professor of Medicine at Cedars-Sinai Medical Center and Principal Investigator on the study. “Encouraging efficacy was observed in patients with RASm second-line metastatic CRC with a response rate exceeding that expected with the standard-of-care regimen FOLFIR/BEV alone. At the evaluated dose levels, ompenaclid plus FOLFIRI/BEV was also well tolerated and induced potent inhibition of SLC6A8, consistent with preclinical and previously presented Phase 1 data.” Ompenaclid is a first-in-class oral inhibitor of the creatine transport channel SLC6A8, a novel target that is enriched under hypoxic conditions and provides tumor cells with an additional energy source. Ompenaclid triggers tumor regressions in CRC patients by inducing apoptosis of tumor cells. The Phase 1b/2 study of ompenaclid in combination with FOLFIRI/BEV in second-line (2L) advanced or metastatic CRC patients has completed enrollment, with an ongoing follow up period. The primary endpoint of the study is to determine maximum tolerated dose (MTD), objective response rate (ORR), and treatment-emergent adverse events (TEAEs). In the dose escalation stage of the study, two dose levels of ompenaclid with FOLFIRI/BEV have been evaluated in patients with CRC with disease progression after a first-line oxaliplatin-containing regimen. “There is a high unmet need for a safe and effective pan-RASm treatment in the advanced or metastatic CRC setting, and these data continue to show the potential of ompenaclid as a novel therapy that can improve upon the current standard-of-care,” said Dr. Usman “Oz” Azam, M.D., Chief Executive Officer of Inspirna. “In addition to fully enrolling this Phase 1b/2 study, we are excited to announce that we have begun enrollment in a randomized controlled trial in the same indication and expect to have interim efficacy data in the second half of 2024.” Inspirna hosted a virtual KOL panel on Sunday, October 22, 2023, with Andrew Hendifar, M.D., to discuss these clinical data. The event replay may be accessed by registering at . Key findings presented at ESMO Congress 2023: As of September 18, 2023, 50 patients in the dose escalation/expansion cohorts received either 2400mg twice daily (BID) of ompenaclid plus FOLFIRI/BEV (n = 27) or 3000mg BID ompenaclid plus FOLFIRI/BEV (n = 23). 39 patients were evaluable for RECIST 1.1 response if they completed at least one treatment cycle and had at least one follow-up on treatment scan. 41 patients had RASm CRC. ORR was 37% including 8 confirmed partial responses (PR) and 3 unconfirmed PRs (all 3 patients are ongoing) in the 30 evaluable patients. Median progression-free survival (mPFS) was 10.2 months, and median overall survival (mOS) was 19.1 months across all 41 patients in the intention to treat population. 9 patients (all evaluable) had RAS-wildtype (RAS-wt) CRC. ORR was 22%, including 1 confirmed PR and 1 unconfirmed PRs. mPFS was 7.5 months and mOS was 14.5 months. Across safety-evaluable patients (n = 48), ompenaclid was well-tolerated, and its safety pro combination was similar to FOLFIRI/BEV alone, demonstrating its potential to be added to standard-of-care treatments. The most common Grade ≤2 TEAEs were diarrhea (58%) and nausea (52%), frequent Grade ≥3 TEAEs were neutropenia (18%), diarrhea (13%), fatigue (10%) and abdominal pain (10%). At both doses, systemic exposure was comparable and resulted in up to a 48x increase in urine creatine, suggesting robust SLC6A8 target inhibition. No DLTs were observed in the dose escalation cohort, and MTD was not reached. The abstract is published in the ESMO Congress 2023 Abstract Book, a supplement to the official ESMO journal, Annals of Oncology. The poster is available at the Annals of Oncology website and . Poster Presentation Details Title: Phase 1b/2 study of ompenaclid (RGX-202-01), a first-in-class oral inhibitor of the creatine transporter SLC6A8, in combination with FOLFIRI and bevacizumab (BEV) in RAS mutated (RASm) second-line (2L) advanced/metastatic colorectal cancer (mCRC) Presenter: Andrew Hendifar, M.D., Assistant Professor of Medicine at Cedars-Sinai Medical Center and Study Principal Investigator Onsite Poster Display Date: Sunday, October 22, 2023 at 9:00 AM CEST Presentation Number: 646P About Inspirna Inspirna, Inc., is a privately-held clinical-stage biopharmaceutical company focused on the discovery and development of novel cancer drugs that target key pathways in cancers of high unmet need. The company is pursuing several first-in-class drug candidates. Inspirna’s lead drug candidate, ompenaclid (RGX-202), is an orally-administered small molecule that targets the CKB/SLC6A8 pathway. This pathway becomes activated in the tumors of select patients where it enables the generation of the energy molecule ATP in response to tumor hypoxia. Ompenaclid is currently being tested in a Phase 1b/2 clinical trial in combination with standard-of-care FOLFIRI and bevacizumab for the second line treatment of patients with advanced or metastatic RAS mutant colorectal cancer. Inspirna’s second clinical stage drug candidate, abequolixron (RGX-104), is an oral small molecule activator of LXR/APOE that inhibits angiogenesis and tumor myeloid derived suppressor cells to enhance the immune response against tumors. Abequolixron is currently being tested in a Phase 1b/2 clinical trial in patients with advanced or metastatic lung cancer in combination with docetaxel and endometrial cancer in combination with ipilimumab through a clinical collaboration with Bristol Myers Squibb. Inspirna identifies novel cancer targets using its microRNA-based target discovery platform, RNA-DRIVEr, which was originally developed by Inspirna’s scientific co-founders at The Rockefeller University and exclusively licensed to Inspirna. The Company brings together distinguished scientific founders, a seasoned board of directors, and a leadership team comprised of experienced drug developers. The Company is funded by leading biotechnology investors, including Novo Holdings A/S, Sofinnova Partners, Sands Capital, Vivo Capital, Lepu Holdings Limited, Sixty Degree Capital, Silicon Valley Bank, K2 HealthVentures, Oceanpine Capital, WuXi PharmaTech Healthcare Fund I, LP, Alexandria Venture Investments, LLC, Dreavent 6, Exor Seeds, and the Partnership Fund for New York City. For more information, please visit .