June 2020 – Inspirna

RGENIX Presents Results from Preclinical Safety and Efficacy Studies of RGX-019 at the 2020 AACR Annual Meeting

New York, NY – June 22, 2020 – RGENIX, Inc., a clinical stage biopharmaceutical company developing first-in-class small molecule and antibody cancer therapeutics, announced today it is presenting an abstract on RGX-019, RGENIX’s pre-clinical antibody program in development. RGENIX’s abstract, “In Vivo Safety and Efficacy of RGX-019, a MerTK Targeting Monoclonal Antibody” was accepted for the 2020 American Association for Cancer Research (AACR) Annual Meeting, which this year was scheduled as two virtual meetings. The abstract results will be presented as a virtual poster presentation (LB-090) during the Late-Breaking Research: Immunology 1 session on June 22, by RGENIX’s Vice President of Research Dr. Isabel Kurth, who is senior author on the abstract.

MerTK is a member of the TAM family of receptor tyrosine kinases and is predominantly expressed on macrophages as well as on cancer cells from a number of solid and hematologic malignancies. The binding of ligands to MerTK on cancer cells activates signaling that increases proliferation, angiogenesis, and drug resistance. On immune-suppressive M2 macrophages, MerTK signaling promotes immune tolerance. Therefore, there is rationale to target MerTK both to suppress tumor growth and activate anti-tumor immunity.

RGX-019 is a novel humanized MerTK targeting monoclonal antibody with a unique mechanism of action. As outlined in the presentation, RGX-019 was found to bind with high affinity to human and monkey MerTK, without detectable binding to related TAM receptors AXL or Tyro. RGX-019’s unique mechanism drives MerTK degradation through receptor internalization and lysosomal trafficking, resulting in the elimination of MerTK from the surface of treated cells. In vitro, RGX-019 inhibited human cancer cell viability and induced immune-stimulatory cytokine expression in M2 macrophages, consistent with robust inhibition of MerTK signaling. RGX-019 treatment in vivo led to near complete elimination of MerTK from the surface of tumor cells, which was associated with anti-tumor efficacy in mouse xenograft models.

Importantly, RGX-019 demonstrated a favorable safety profile in a 28-day dose-range finding toxicology study in monkeys. Of note, retinal toxicity – a finding associated with other MerTK targeting approaches – was not observed at any dose of RGX-019. The results overall demonstrate that RGX-019 can potently target MerTK signaling on both cancer cells and immune-suppressive M2 macrophages with a novel mechanism, resulting in anti-tumor activity with a wide therapeutic window.

Masoud Tavazoie, M.D., Ph.D., and Chief Executive Officer of RGENIX, said, “The results presented today demonstrate the potential for RGX-019 to be a best-in-class MerTK inhibitor. Its unique characteristics have yielded a favorable safety and efficacy profile in animals that provides a solid foundation for further development of RGX-019. We are excited to move RGX-019 through further IND-enabling studies and ultimately into clinical development.”

About RGENIX

RGENIX, Inc., is a privately-held clinical-stage biopharmaceutical company focused on the discovery and development of novel cancer drugs that target key pathways in cancer progression. The company is pursuing several first-in-class drug candidates to treat cancers of high unmet need. RGENIX identifies novel cancer targets using a microRNA based target discovery platform originally developed by RGENIX’s scientific co-founders at The Rockefeller University and now exclusively licensed to RGENIX. The company brings together distinguished scientific founders, a seasoned Board, 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, 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.rgenix.com.

About RGX-019

RGX-019 is humanized monoclonal antibody that targets MerTK, a receptor kinase that mediates tumor growth as well as immune evasion. RGX-019 has a unique mechanism-of-action that results in degradation of MerTK in target cells, which is associated with in vivo anti-tumor activity. RGX-019 is currently in pre-clinical development. MerTK was revealed as a driver of metastatic cancer progression using a novel microRNA-based discovery platform developed by RGENIX’s scientific co-founders at The Rockefeller University.

Media Contact:

RooneyPartners
Jeanene Timberlake
646-770-8858
jtimberlake@rooneyco.com

RGENIX Presents Biomarker and Efficacy Results from Phase 1 Dose Escalation Cohorts of RGX-104 at the 2020 AACR Annual Meeting

New York, NY – June 22, 2020 – RGENIX, Inc., a clinical stage biopharmaceutical company developing first-in-class small molecule and antibody cancer therapeutics, announced today it is presenting an abstract on RGX-104, RGENIX’s lead therapy in development. RGENIX’s abstract, “Correlative analysis of pharmacokinetics and pharmacodynamics of RGX-104, a first-in-class Liver-X-Receptor (LXR) agonist, and clinical outcomes in patients with advanced solid tumors” was accepted for the 2020 American Association for Cancer Research (AACR) Annual Meeting, which this year was scheduled as two virtual meetings. The abstract results will be presented as a virtual poster presentation (#LB-133/7) in the Late-Breaking Research: Clinical Research 1 session on June 22, by clinical investigator Dr. Monica Mita, Co-Director, Experimental Therapeutics Program, Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, who is lead author on the study.

RGX-104 is a small-molecule LXR agonist that modulates innate immunity via transcriptional activation of the ApoE gene. RGX-104 inhibits tumor angiogenesis and depletes myeloid derived suppressor cells (MDSC), thereby activating cytotoxic T-lymphocytes. MDSCs are associated with resistance to both checkpoint inhibitors (CPI) and chemotherapy, providing a rationale for combination therapy with RGX-104.

For the dose escalation stage of the Phase 1 study, RGX-104 was tested as a monotherapy or in combination with either nivolumab, ipilimumab, or docetaxel in heavily pre-treated patients with refractory or relapsed solid tumors, including patients who had progression on prior checkpoint inhibitors (CPI). As outlined in the presentation, objective clinical activity was observed in all treatment arms, including the monotherapy arm, with partial responses achieved in patients with NSCLC, SCLC, melanoma, SCCHN, and endometrial cancer.

Of note, in the combination arms, a 28.6% objective response rate was observed in all evaluable patients who had previously progressed on CPI, with 4 of 14 evaluable patients achieving PRs. Responses included ongoing durable PRs – some exceeding 11 months – in CPI refractory/resistant patients whose tumors were PD-L1 low/negative.

Importantly, clinical activity across all treatment arms was associated with RGX-104 related pharmacodynamic effects, including ApoE activation, MDSC depletion, and CD8 T cell activation with associated induction of IFNg. Robust ApoE induction was achieved with BID dosing of RGX-104 and was correlated with the magnitude of MDSC depletion. Additionally, in comparison to PD-L1 positive tumors, PD-L1 negative tumors were found to have significantly lower baseline (pre-treatment) levels of ApoE, a feature associated with higher likelihood of clinical benefit to RGX-104. The data demonstrate that MDSC depletion via ApoE induction with RGX-104 can overcome resistance to CPI or chemotherapy, resulting in durable clinical activity.

As a result, RGX-104 is being evaluated in combination with the front-line standard-of-care regimen of pembrolizumab plus carboplatin/pemetrexed in a phase 1b/2 study currently enrolling patients with advanced non-squamous non-small cell lung cancer (NSCLC) whose tumors are PD-L1 negative. RGX-104 is also being evaluated in combination with docetaxel in a phase 1b/2 expansion study that has begun enrolling patients with relapsed/refractory extensive stage small-cell lung cancer (ES-SCLC) or high grade-neuroendocrine tumors (HG-NET).

Monica Mita, M.D., principal investigator from Cedars-Sinai Medical Center and lead author and presenter of the poster, said, “These exciting results provide clinical validation of the novel MDSC-targeting mechanism of RGX-104. The durable clinical responses observed in patients who have previously progressed on checkpoint inhibitors are very promising.”

Masoud Tavazoie, M.D., Ph.D., and Chief Executive Officer of RGENIX, said, “We are very encouraged by the results presented today as they demonstrate that our first-in-class drug candidate RGX-104 can robustly target MDSCs, a key drug resistance mechanism, to provide durable clinical benefit to patients. The findings further strengthen the foundation for our ongoing Phase 1b/2 studies. We look forward to sharing results from these ongoing studies.”

About RGENIX

About RGX-104

RGX-104 is an orally-administered potent small molecule agonist of the Liver X Receptor (LXR) that is currently being evaluated in a Phase 1b/2 clinical study. Activation of the LXR-ApoE pathway by RGX-104 stimulates the innate immune response in cancer via depletion of myeloid-derived suppressor cells and activation of dendritic cells, leading to stimulation of T cells and anti-tumor immunity. LXR activation also blocks the ability of tumors to recruit blood vessels. The LXR-ApoE pathway was originally identified as a cancer target using a novel microRNA-based discovery platform developed by RGENIX’s scientific co-founders at The Rockefeller University.

Media Contact:

RooneyPartners
Jeanene Timberlake
646-770-8858
jtimberlake@rooneyco.com