Presentation Monday, June 4, 2018, at ASCO. RGX-104 is a small-molecule LXR agonist that modulates innate immunity via transcriptional activation of the ApoE gene. To read the abstract, please click here.
Author: inspirnastg
LXR/ApoE Pathway Identified as Key Regulator of Innate Immune Suppression in Cancer
FOR IMMEDIATE RELEASE
New York, NY – January 11, 2018– Rgenix, Inc., a clinical stage biopharmaceutical company developing first-in-class small molecule and antibody cancer therapeutics, announced today the publication of clinical and pre-clinical results by research collaborators at Rgenix and The Rockefeller University. The results of the collaboration, published in the January 11 online issue of Cell, reveal that the Liver-X Receptor/Apolipoprotein E (LXR/ApoE) pathway regulates anti-tumor immunity via effects on myeloid-derived suppressor cells (MDSCs).
MDSCs are an immunosuppressive cell population that have been found to be circulating at high levels in cancer patients who are also commonly found to be non-responders to immunotherapy. RGX-104 was able to deplete MDSCs both in cancer patients participating in the dose escalation portion of the Phase 1a/b trial and in mice. This resulted in robust activation of relevant T cell populations in both settings.
“We are pleased to have this opportunity to share our latest research results in Cell that illustrate the effects our first-in-class RGX-104 compound has on one of the key cells that are responsible for suppressing the immune response in cancer patients,” said Masoud Tavazoie, M.D., Ph.D., and Chief Executive Officer and co-founder of Rgenix. “We believe RGX-104 represents a novel strategy for stimulating anti-tumor immunity, and this data cements this belief and furthers our resolve to continue developing this compound both as monotherapy as well as in combination with checkpoint inhibitor therapy.”
Sohail Tavazoie, M.D., Ph.D., Leon Hess Associate Professor and Head of Elizabeth and Vincent Meyer Laboratory of Systems Cancer Biology at the Rockefeller University who was the senior-author of the study as well as co-founder of Rgenix, added: “The data our research has generated at this stage is exciting and supports our perspective that RGX-104 has the potential to modulate the immune response in a broad array of cancers. We will continue to progress in our research and our pursuit of unique treatments for patients affected by cancers with a high unmet medical need.”
The paper, titled “LXR/ApoE Activation Restricts Innate Immune Suppression in Cancer”, was published today and is available online.
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 A/S, Sofinnova Partners, and Alexandria Venture Investments. For more information, please visit www.rgenix.com.
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 clinical studies. 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. These combined effects result in suppression of tumor growth and metastasis in a broad array of animal tumor models. 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.
Rgenix is conducting a Phase 1a/b clinical trial of RGX-104 in patients with advanced solid malignancies and lymphoma—for more information about the clinical trial, please visit: https://clinicaltrials.gov/ct2/show/NCT02922764.
Media Contacts:
RooneyPartners
Marion Janic
212-223-4017
How Rgenix’s Liver X Agonist Could Help Overcome Checkpoint Resistance in Cancer. To read the full article, please click here.
Rgenix Inc. (New York, N.Y.) reported preliminary data from a Phase Ia/Ib trial showing that oral RGX-104 led to 4 cases of stable disease among 12 evaluable patients with advanced solid malignancies and lymphoma. To read the full article, please click here.
Preliminary Phase 1a/b data demonstrate RGX-104 modulates the innate immune system to stimulate T cell activation in a diverse group of heavily pre-treated patients with refractory solid cancers.
Phase 1 dose escalation continues, and future plans include initiation of an expansion component of the trial as monotherapy as well as in combination with a checkpoint inhibitor.
FOR IMMEDIATE RELEASE
New York, NY – October 29, 2017 – Rgenix, Inc., a clinical stage biopharmaceutical company developing first-in-class small molecule and antibody cancer therapeutics, announced today preliminary data from an ongoing Phase 1a/b clinical trial with its lead oral investigational agent, RGX-104. These data demonstrate immune-stimulatory activity in solid tumor patients with highly-refractory malignancies, including patients who have failed prior checkpoint inhibitors. Also presented were pre-clinical data establishing the immune-modulatory and anti-tumor effects of RGX-104. The company presented the data at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Philadelphia.
RGX-104 is a liver X receptor (LXR) agonist that upregulates the expression of the target gene, Apolipoprotein E (ApoE), triggering several downstream effects via ApoE receptors. In pre-clinical data presented today, treatment with RGX-104 in mouse models resulted in dual effects on myeloid-derived suppressor cells (MDSCs) and dendritic cells (DCs), both innate immune cells that play a central role in regulating anti-tumor immunity and response to checkpoint inhibitors. Innate immune activation with RGX-104, coupled with a reduction in tumor blood vessels, resulted in anti-tumor activity as a monotherapy as well as synergy with checkpoint inhibitors (CPI) in several drug-resistant mouse models. These data provide rationale for Rgenix’s ongoing Phase 1a/b trial of RGX-104 in advanced cancer patients and support evaluation of RGX-104 as both a monotherapy as well as in combination with CPIs.
As part of the ongoing Phase 1a/b clinical trial, 15 patients with a variety of solid tumors have been treated with escalating doses of RGX-104 monotherapy. Patients treated with RGX-104 had a median of six prior therapies with a range of 1-12, highlighting a population of patients with profoundly resistant disease.
Activation of the LXR-ApoE pathway with oral administration of RGX-104 was associated with immune-stimulatory activity in 9 of 10 evaluable patients. This was demonstrated by an increase (up to 11-fold) in activated circulating PD-1+CD8+ T cells during treatment. T cell activation was observed in patients who experienced modulation of the innate immune system during treatment. The effect of RGX-104 on the innate immune system consisted of both MDSC depletion (up to 95% decrease) as well as DC activation as indicated by induction of PD-L1 expression (up to 100% increase). In most cases these effects were observed within two weeks of treatment initiation and generally preceded the onset of T cell activation.
Safety data demonstrate good tolerability with on-target safety findings in the first three dosing cohorts. One patient experienced a DLT of grade 4 reversible neutropenia – a known potential effect of LXR agonism – that reversed within one week, allowing the patient to subsequently tolerate a 50% dose reduction. No MTD has been reached to date. Stable disease has been observed in 4 of 12 evaluable patients, including three who have failed prior checkpoint inhibitor therapy, for periods of at least 8 weeks.
“We are very pleased to see robust evidence of immune stimulation in such highly-pretreated patients,” said Roger Waltzman, MD, MBA, and Chief Medical Officer of Rgenix. “CPI therapy is now commonplace but only a minority of patients derive clinical benefit. We hope the effects of RGX-104 on modulating barriers to innate and adaptive immune function will enable a larger number of patients to benefit from this therapy. These preliminary results also highlight the potential for development of RGX-104 as a monotherapy.”
Rgenix plans to enroll subsequent dose-escalation cohorts of the RGX-104 monotherapy trial in Q4 2017. Additionally, Rgenix is planning to initiate the Phase 1b expansion component of the study, comprised of disease directed cohorts receiving RGX-104 monotherapy as well as cohorts receiving RGX-104 combined with a CPI, projected to begin in 1H 2018.
“These preliminary data establish RGX-104 as a potential first-in-class oral immunotherapy agent with broad immune-stimulatory activity and a unique dual mechanism targeting innate immunity,” said Masoud Tavazoie, MD, PhD, and Chief Executive Officer of Rgenix. “These results also further validate our discovery platform at Rgenix, as well as our pipeline of other drug candidates slated to begin entering clinical-stage development in 2018.”
The LXR-ApoE pathway was discovered as a cancer target using a microRNA (miRNA) based target discovery approach originally developed at The Rockefeller University and now exclusively licensed to Rgenix.
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 A/S, Sofinnova Partners, and Alexandria Venture Investments. For more information, please visit www.rgenix.com.
About RGX-104
RGX-104 is a potent small molecule agonist of the Liver X Receptor (LXR). 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 in tumor models. LXR activation also blocks the ability of tumors to recruit blood vessels. These combined effects result in suppression of tumor growth and metastasis in a broad array of pre-clinical models. 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. Rgenix is conducting a Phase 1a/b clinical trial of RGX-104 in patients with advanced solid malignancies and lymphoma—for more information about the clinical trial, please visit: https://clinicaltrials.gov/ct2/show/NCT02922764.
Media Contacts:
RooneyPartners
Marion Janic
212-223-4017
Preliminary Phase 1a/b data demonstrate RGX-104 modulates the innate immune system to stimulate T cell activation in a diverse group of heavily pre-treated patients with refractory solid cancers.
Phase 1 dose escalation continues, and future plans include initiation of an expansion component of the trial as monotherapy as well as in combination with a checkpoint inhibitor.
FOR IMMEDIATE RELEASE
New York, NY – October 29, 2017 – Rgenix, Inc., a clinical stage biopharmaceutical company developing first-in-class small molecule and antibody cancer therapeutics, announced today preliminary data from an ongoing Phase 1a/b clinical trial with its lead oral investigational agent, RGX-104. These data demonstrate immune-stimulatory activity in solid tumor patients with highly-refractory malignancies, including patients who have failed prior checkpoint inhibitors. Also presented were pre-clinical data establishing the immune-modulatory and anti-tumor effects of RGX-104. The company presented the data at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Philadelphia.
RGX-104 is a liver X receptor (LXR) agonist that upregulates the expression of the target gene, Apolipoprotein E (ApoE), triggering several downstream effects via ApoE receptors. In pre-clinical data presented today, treatment with RGX-104 in mouse models resulted in dual effects on myeloid-derived suppressor cells (MDSCs) and dendritic cells (DCs), both innate immune cells that play a central role in regulating anti-tumor immunity and response to checkpoint inhibitors. Innate immune activation with RGX-104, coupled with a reduction in tumor blood vessels, resulted in anti-tumor activity as a monotherapy as well as synergy with checkpoint inhibitors (CPI) in several drug-resistant mouse models. These data provide rationale for Rgenix’s ongoing Phase 1a/b trial of RGX-104 in advanced cancer patients and support evaluation of RGX-104 as both a monotherapy as well as in combination with CPIs.
As part of the ongoing Phase 1a/b clinical trial, 15 patients with a variety of solid tumors have been treated with escalating doses of RGX-104 monotherapy. Patients treated with RGX-104 had a median of six prior therapies with a range of 1-12, highlighting a population of patients with profoundly resistant disease.
Activation of the LXR-ApoE pathway with oral administration of RGX-104 was associated with immune-stimulatory activity in 9 of 10 evaluable patients. This was demonstrated by an increase (up to 11-fold) in activated circulating PD-1+CD8+ T cells during treatment. T cell activation was observed in patients who experienced modulation of the innate immune system during treatment. The effect of RGX-104 on the innate immune system consisted of both MDSC depletion (up to 95% decrease) as well as DC activation as indicated by induction of PD-L1 expression (up to 100% increase). In most cases these effects were observed within two weeks of treatment initiation and generally preceded the onset of T cell activation.
Safety data demonstrate good tolerability with on-target safety findings in the first three dosing cohorts. One patient experienced a DLT of grade 4 reversible neutropenia – a known potential effect of LXR agonism – that reversed within one week, allowing the patient to subsequently tolerate a 50% dose reduction. No MTD has been reached to date. Stable disease has been observed in 4 of 12 evaluable patients, including three who have failed prior checkpoint inhibitor therapy, for periods of at least 8 weeks.
“We are very pleased to see robust evidence of immune stimulation in such highly-pretreated patients,” said Roger Waltzman, MD, MBA, and Chief Medical Officer of Rgenix. “CPI therapy is now commonplace but only a minority of patients derive clinical benefit. We hope the effects of RGX-104 on modulating barriers to innate and adaptive immune function will enable a larger number of patients to benefit from this therapy. These preliminary results also highlight the potential for development of RGX-104 as a monotherapy.”
Rgenix plans to enroll subsequent dose-escalation cohorts of the RGX-104 monotherapy trial in Q4 2017. Additionally, Rgenix is planning to initiate the Phase 1b expansion component of the study, comprised of disease directed cohorts receiving RGX-104 monotherapy as well as cohorts receiving RGX-104 combined with a CPI, projected to begin in 1H 2018.
“These preliminary data establish RGX-104 as a potential first-in-class oral immunotherapy agent with broad immune-stimulatory activity and a unique dual mechanism targeting innate immunity,” said Masoud Tavazoie, MD, PhD, and Chief Executive Officer of Rgenix. “These results also further validate our discovery platform at Rgenix, as well as our pipeline of other drug candidates slated to begin entering clinical-stage development in 2018.”
The LXR-ApoE pathway was discovered as a cancer target using a microRNA (miRNA) based target discovery approach originally developed at The Rockefeller University and now exclusively licensed to Rgenix.
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 A/S, Sofinnova Partners, and Alexandria Venture Investments. For more information, please visit www.rgenix.com.
About RGX-104
RGX-104 is a potent small molecule agonist of the Liver X Receptor (LXR). 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 in tumor models. LXR activation also blocks the ability of tumors to recruit blood vessels. These combined effects result in suppression of tumor growth and metastasis in a broad array of pre-clinical models. 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. Rgenix is conducting a Phase 1a/b clinical trial of RGX-104 in patients with advanced solid malignancies and lymphoma—for more information about the clinical trial, please visit: https://clinicaltrials.gov/ct2/show/NCT02922764.
New York, NY – October 26, 2017 – Rgenix, Inc., a clinical stage biopharmaceutical company developing first-in-class small molecule and antibody cancer therapeutics, announced today that Dr. Monica Mita of Cedars-Sinai Medical Center and Principal Investigator of the RGX-104-001 study, will present at the 2017 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics. The conference is scheduled to take place from Thursday, October 26 to Monday, October 30 in Philadelphia.
The details of Rgenix’s presentation are as follows:
Event: AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics: Discovery, Biology, and Clinical Applications
Date: October 29, 2017
Time: 12:30 P.M. – 4:00 P.M. EST
Description: Poster B001, “A phase 1 trial of RGX-104, a first-in-class immunotherapy targeting the liver-X nuclear hormone receptor (LXR), in patients with refractory malignancies”
Location: Hall E, Pennsylvania Convention Center, 1101 Arch St, Philadelphia, PA 19107
Dr. Mita will present data from the Phase 1 trial of RGX-104, a first-in-class investigational immunotherapy.
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 A/S, Sofinnova Partners, and Alexandria Venture Investments. For more information, please visit www.rgenix.com.
About RGX-104
RGX-104 is a potent small molecule agonist of the Liver X Receptor (LXR). 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 in tumor models. LXR activation also blocks the ability of tumors to recruit blood vessels. These combined effects result in suppression of tumor growth and metastasis in a broad array of pre-clinical models. 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.
Rgenix is conducting a Phase 1a/b clinical trial of RGX-104 in patients with advanced solid malignancies and lymphoma—for more information about the clinical trial, please visit: https://clinicaltrials.gov/ct2/show/NCT02922764.
Media Contacts:
RooneyPartners
Marion Janic
212-223-4017
It’s an exciting time to be in the biotech and pharmaceutical industries. To read the full piece, please click here.
Rgenix CEO Masoud Tavazoie was recently interviewed for an article in The Pharma Letter. To read the full piece, please click here.
For Immediate Release
New York, NY – April 27, 2017 – Rgenix, Inc., a clinical stage biopharmaceutical company developing first-in-class small molecule and antibody cancer therapeutics, announced today the appointment of Roger Waltzman, M.D., M.B.A. as its Chief Medical Officer. Dr. Waltzman brings more than 20 years of experience in oncology across the entire new drug development and approval process, including serving in various executive roles at Novartis for nearly a decade.
In his role, he will oversee clinical development at Rgenix, including clinical trial design and the new drug application process with regulators. He will also support Rgenix’s goals of providing a meaningful response for cancer patients lacking effective therapies by overseeing the patient experience.
“Dr. Waltzman has an extraordinary background in oncology, which is our focus at Rgenix, and his expertise will be crucial as we progress with the clinical development of our lead therapy, RGX-104, and our other drug candidates in development,” said Masoud Tavazoie, M.D., Ph.D., Chief Executive Officer and co-founder of Rgenix. “We look forward to his contributions to our work at Rgenix as we develop novel treatments for patients who suffer from cancer types with a high, unmet need.”
“Rgenix has innovation at its core, and I’m pleased to be joining an organization that is looking to fill a gap in oncology that could benefit hundreds of thousands of patients. I look forward to collaborating with the Rgenix team on its therapies and clinical developments as it looks to drive positive change in the industry,” said Dr. Waltzman.
Prior to Rgenix, Dr. Waltzman worked at Novartis in both Medical Affairs and Clinical Development roles. In oncology, he successfully filed an sNDA as the Clinical Development Head for Tasigna/Glivec and led the successful development and MAA/NDA filing of Jakavi/Jakafi, in collaboration with Incyte. His last position at Novartis was as Global Development Head for anti-malarials, where he continued Phase 2 development of two novel anti-malarials and facilitated a cost-saving Collaboration Agreement with the Bill and Melinda Gates Foundation and Medicines for Malaria Venture.
His most recent position was with Jaguar Animal Health and Napo Pharmaceuticals in San Francisco where he was the Chief Scientific Officer and Chief Medical Officer, leading the development of a first-in-class, FDA-approved botanical as a novel anti-diarrheal.
Dr. Waltzman received his medical degree from Brown University School of Medicine and his MBA from Columbia Business School. He completed his residency in Internal Medicine at Harvard’s Beth Israel Hospital, and his fellowship in hematology/oncology at Memorial Sloan-Kettering Cancer Center. He has been a member of the board of directors of GoDocGo and the Brown Medical Alumni Association since 2015.
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. Using a miRNA based target discovery platform developed by Rgenix’s founders at The Rockefeller University, the company is pursuing several first-in-class drug candidates to treat cancers of high unmet need. 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 A/S, Sofinnova Partners, and Alexandria Venture Investments. For more information, please visit www.rgenix.com.
Media Contacts:
RooneyPartners
Marion Janic
212-223-4017