Inspirna to Present Phase 1b RGX-202-01 Clinical Trial Data at the 2022 ESMO World Congress on Gastrointestinal Cancer

Inspirna, Inc., a clinical stage biopharmaceutical company developing first-in-class small molecule cancer therapeutics, announced today data from the ongoing Phase 1b clinical trial studying RGX-202-01 in combination with FOLFIRI and bevacizumab (FOLFIRI/BEV) in second-line advanced colorectal cancer (CRC) at the 2022 European Society for Medical Oncology (ESMO) World Congress on Gastrointestinal Cancer being held June 29 through July 2, 2022 in Barcelona, Spain.

"These clinical data continue to demonstrate the clear potential of RGX-202-01 to improve on the standard of care for patients with advanced or metastatic colorectal cancer, especially for those whose tumors harbor KRAS mutations," said Andrew Hendifar, M.D., Assistant Professor at Cedars-Sinai Medical Center and Principal Investigator on the study. "RGX-202-01 employs a novel mechanism by inhibiting the creatine transporter SLC6a8, which enables cells to generate ATP as well as other nucleotides by importing phospho-creatine (p-creatine). These results also show that KRAS mutant tumors are highly sensitive to the effects of SLC6a8 inhibition by RGX-202-01. The drug is also very well-tolerated, enabling a safe and effective combination therapy with FOLFIRI/BEV to provide further optionality for patients."

RGX-202-01 is an oral, potential first-in-class small molecule inhibitor of SLC6a8, a creatine transporter that drives colorectal cancer and certain other cancers' progression. It is currently being evaluated in a Phase 1b dose escalation and expansion study in combination with FOLFIRI/BEV in second-line, advanced or metastatic CRC. The primary endpoint of the study is to determine maximum tolerated dose (MTD), overall response rate (ORR), and treatment-emergent adverse events (TEAEs). In the dose escalation stage of the study, two dose levels of RGX-202-01 with FOLFIRI/BEV have been evaluated in patients with advanced or metastatic CRC who have progressed on available oxaliplatin based first line therapy. In the ongoing expansion stage, additional patients with CRC are being treated at the dose of 3000mg PO BID to provide further characterization of the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of the treatment.

Key findings to be presented at ESMO World Congress on Gastrointestinal Cancer:

• Previously reported data from the study (at ASCO 2022) as of a data cutoff of April 28, 2022 included 19 patients who were enrolled in the study, including eight total patients in the dose escalation stage treated with either 2400mg twice daily (BID) of RGX-202-01 plus FOLFIRI/BEV (n = 4) or 3000mg BID RGX-202-01 plus FOLFIRI/BEV (n = 4), and 11 patients treated in the expansion stage with 3000mg BID RGX-202-01 plus FOLFIRI/BEV.
• 17 patients were evaluable for response per RECIST v1.1 at data cutoff, of which 10 patients had KRAS mutant tumors and seven patients had KRAS wild-type tumors.
  • In the KRAS mutant population, five patients (50%) had confirmed partial responses (PR) and five patients (50%) had stable disease (SD).
  • In the KRAS wild-type population, one patient (14%) had an unconfirmed PR, five patients (71%) had SD, and one patient (14%) had progressive disease (PD).
  • Preliminary median progression-free survival (mPFS) was 11.8 months in the enrolled patients with KRAS mutant tumors.
  • Tumor regression was observed to deepen over time in patients with KRAS mutant tumors, with first radiographic achievement of PR appearing as late as 40 weeks post-treatment induction.
• Updates since April 28, 2022 (data cutoff date) through June 10, 2022:
  • Two patients with KRAS mutant tumors had follow up imaging: patient 102-3112 remains in PR status and patient 102-2407 now has SD.
  • Two patients with KRAS WT tumors had follow up imaging: patient 102-3121 remains in SD status and patient 103-3127 maintained SD radiographically but was declared clinical PD as per the Investigator.
  • The ORR remains unchanged (50% in KRAS mutant group, 14% in the KRAS WT group).
  • Two grade 3 TEAEs (neutropenia, pulmonary embolus) deemed unrelated to RGX-202-01.
  • No grade 4 or 5 TEAEs reported.

The poster is available at the Annals of Oncology website and https://inspirna.com/presentations-publications/.

Poster Presentation Details

Title: Phase 1b study of RGX-202-01, a first-in-class oral inhibitor of the SLC6a8/CKB pathway, in combination with FOLFIRI and bevacizumab (BEV) in second-line advanced colorectal cancer (CRC)

Date and time: July 1, 2022 at 10:30 ? 10:50am CEST and 4:30 ? 5pm CEST

Abstract Category: Clinical Colon Cancer

Abstract Subcategory: Metastatic Disease

Abstract ID: 291

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 two first-in-class small molecule drug candidates, RGX-202 and RGX-104. Inspirna's lead drug candidate RGX-202 is an orally-administered small molecule that targets the CKB/SLC6A8 pathway. This pathway becomes activated in the tumors of select patients with gastrointestinal cancers where it enables the generation of the energy molecule ATP in response to tumor hypoxia. RGX-202 is currently being tested in a Phase 1b clinical trial in combination with standard-of-care FOLFIRI and bevacizumab for the second line treatment of patients with advanced CRC. Inspirna is also developing a first in class small molecule that activates ApoE, RGX-104 (abequolixron), in high unmet medical need lung cancer settings and in advanced endometrial cancer in collaboration with Bristol-Myers Squibb.

Inspirna identifies novel cancer targets using its RNA-based target discovery platform, RNA-DRIVErtm, 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, Lepu Holdings Limited, Sixty Degree Capital, K2 HealthVentures, Oceanpine Capital, WuXi PharmaTech Healthcare Fund I, LP, Alexandria Venture Investments, LLC, Exor Seeds, and the Partnership Fund for New York City. For more information, please visit www.inspirna.com.