Revere Pharma Announces Publication of Research that Elaborates Role of Rac1 in Prostate Cancer

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Research conducted by Dr. Erik Goka and published in Molecular Cancer Therapeutics demonstrates that Rac1 inhibition can attenuate the growth and survival of prostate cancer cells

Boston, Mass. — Revere Pharmaceuticals, an emerging biopharmaceutical company developing small molecule drugs targeting key signaling proteins to treat cancer and other disease, announced the publication of research results demonstrating the central role of Rac1 signaling in the growth and survival of prostate cancer cells.  The article, titled “Hormone dependent prostate cancers are dependent on Rac signaling for growth and survival,” is based on research conducted by Erik Goka, PhD, the company’s head of biology, and published in Molecular Cancer Therapeutics, a peer-reviewed publication of the American Association of Cancer Research. The research was conducted under the direction of Dr. Marc Lippman, a preeminent cancer researcher at Georgetown University, who is a member of Revere’s board of directors.

“Dr. Goka’s recently published work demonstrates the pivotal role of Rac1 signaling in castrate resistant prostate cancer and the promise of targeting Rac1 to advance the treatment of this disease,” said Jedd Levine, MD, Chief Medical Officer Revere Pharmaceuticals.

The published research demonstrated that Rac1 dysregulation resulted in cancer-driving mechanisms of enhanced cellular proliferation, motility and viability in prostate cancer. Moreover, the work revealed a link between Rac1 signaling and androgen receptor gene expression, indicating a potential role for Rac1 inhibition in combination with conventional androgen receptor antagonists. 

This paper builds upon a substantial body of Rac1 research published by a research team headed by Drs. Goka and Lippman.   Over the last several years, this team has elucidated the mechanism by which Rac1 activation promotes the growth of multiple tumor types.  They further showed that pharmacologic inhibition of Rac1 effectively inhibited tumor growth in vivo.  Key findings from recent publications include the following:

  • “Rac Signaling Drives Clear Cell Renal Carcinoma Tumor Growth by Priming the Tumor Microenviornment for an Angiogenic Switch” Mol. Cancer Ther. (2020).

In this study, a Rac1 inhibitor was found to suppress the pro-angiogenic growth factors VEGF, TSP-1 and CXCL16, block angiogenesis and inhibit CC renal carcinoma growth in vivo. 

  • “Rac1b Overexpression Confers Resistance to Chemotherapy Treatment in Colorectal Cancer” Mol. Cancer Ther. (2019). 

Rac1b, a constitutively active splice variant of Rac1, was found to be overexpressed in colorectal cancer with the highest levels in metastatic disease.  Furthermore, Rac1b was shown to activate the pro-survival NF-kB pathway which leads to resistance to standard-of-care chemotherapy (5-FU and Oxaliplatin). Rac1 inhibition was found to sensitize colorectal cancer to chemotherapy.

  • “Loss of the E3 ubiquitin ligase HACE1 results in enhanced Rac1 signaling contributing to breast cancer progression” Oncogene (2015). 

The authors showed for the first time the role of HACE1 in breast cancer progression and why it correlates to poor patient outcomes.  HACE1 was found to reduce levels of activated Rac1 by targeting (GTP-bound) Rac1 for ubiquitin mediated protein degradation.

“It is exciting to be a part of this important research that expands our understanding of the role of Rac1 signaling in cancer progression,” said Dr. Goka, Revere Senior Director of Biology and lead author of the study.  “I look forward to translating these findings into new medicines to treat patients with the Revere team.” 

About Rho GTPases

Rho GTPases are a diverse group of signaling proteins, including Rac1 and Cdc42, which serve as molecular ‘on-off’ switches because of their ability to bind to the guanosine triphosphate (GTP) nucleotide and hydrolyze it to guanosine diphosphate (GDP).  Activity of these proteins switch between the inactive GDP-bound form and the active GTP-bound form which recruits other downstream effector proteins to promote many critical cancer processes, including cell growth, migration, invasion, and angiogenesis. Dysregulation of Rac1 or Cdc42 is implicated in multiple cancer types including lung, breast, prostate, colorectal, and gastric cancer and is commonly associated with resistance to chemotherapy and other targeted cancer therapeutics.  Rho GTPase dysregulation has also been implicated in chronic kidney disease and viral infections such as SARS CoV2.

About Revere Pharmaceuticals

Revere Pharmaceuticals is a biopharmaceutical company developing small molecule drugs targeting the Ras-homologous (Rho) family GTPases, molecular switches that are central to cancer progression and other disease processes. Based on a deep understanding of how to balance the active and inactive forms of the GTPase, the company has built a pipeline of novel small molecules that target Rac1, select Rac1 variants and CDC42. The company is headquartered in Boston, Massachusetts. For more information, please visit www.reverepharma.com.

Revere Pharmaceuticals Announces Asset Purchase Agreement to Acquire All Assets of Geneyus LLC

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Revere becomes the leader in developing drugs targeting Rho GTPases with consolidation of key assets pertaining to Rac1, including a drug discovery platform and promising preclinical programs

Boston, Mass. — Revere Pharmaceuticals, an emerging biopharmaceutical company developing small molecule drugs targeting the Ras-homologous (Rho) family GTPases, announced the  completion of an Asset Purchase Agreement to acquire all the assets of Geneyus LLC, a company focused on the Rho GTPase Rac1. Key assets include the Rho GTPase drug discovery platform built by Geneyus, several preclinical programs including GYS32661, and other novel Rac1 inhibitors. In addition, two key individuals from Geneyus will join Revere, Marc Lippman, MD as Board Director and Erik Goka, PhD as Senior Director of Biology.

“With our shared belief in targeting Rho GTPases for treating cancer and other diseases, we are very pleased to join forces with Geneyus” said Bob Silverman, President and CEO of Revere.   “We are especially happy to welcome Drs. Marc Lippman and Erik Goka to the Revere team, and together we have a unique opportunity to develop first-in-class drugs for unmet patient needs.”

Together with Revere’s expert medicinal chemistry and in silico models, the Rho GTPase drug discovery platform will allow the company to systematically identify inhibitors of Rac1 and its genomic variants and CDC42.  Key to the platform is the cascade of biochemical and cell based assays to rapidly assess compound activity and selectivity against specific GTPase targets. 

In the non-cash transaction, Geneyus shareholders received equity in Revere. Other terms of the transaction were not disclosed.

About Rho GTPases

Rho GTPases are a diverse group of signaling proteins, including Rac1 and CDC42 characterized by their ability to bind to the guanosine triphosphate (GTP) nucleotide and hydrolyze it to guanosine diphosphate (GDP).  Activity of these proteins switch between the inactive GDP-bound form and the active GTP-bound form which recruits other downstream effector proteins to promote many critical cancer processes, including cell growth, migration, invasion, and angiogenesis. Dysregulation of Rac1 or Cdc42 is implicated in multiple cancer types including lung, breast, prostate, colorectal, and gastric cancer and is commonly associated with resistance to chemotherapy and other targeted cancer therapeutics.  Rho GTPase dysregulation has also been implicated in chronic kidney disease and viral infections such as SARS CoV2.

About Revere Pharmaceuticals

Revere Pharmaceuticals is a biopharmaceutical company developing small molecule drugs targeting the Ras-homologous (Rho) family GTPases, molecular switches that are central to cancer progression and other disease processes. Based on a deep understanding of how to balance the active and inactive forms of the GTPase, the company has built a pipeline of novel small molecules that target Rac1, select Rac1 variants and CDC42. The company is headquartered in Boston, Massachusetts. For more information, please visit www.reverepharma.com.

Revere Pharmaceuticals Expands Board of Directors to Include Marc Lippman, MD

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Renown cancer researcher and biotech veteran brings expertise in developing novel cancer therapeutics in emerging biotech companies

Boston, Mass. — Revere Pharmaceuticals, an emerging biopharmaceutical company developing small molecule drugs targeting the Ras-homologous (Rho) family GTPases, announced today that in connection with Revere’s Asset and Purchase Agreement with Geneyus, Marc Lippman, MD, MACP, FRCP has joined its Board of Directors. Dr. Lippman, a world renown cancer researcher and professor in the departments of oncology and medicine at Georgetown University Medical Center, co-Founded Geneyus in 20xx.  Dr. Lippman also bring a wealth of experience building emerging biotech companies having served on the Board of Directors of Seattle Genetics since 2000.

“We are thrilled and fortunate to have Marc join our Board of Directors,” says Bob Silverman, CEO of Revere. “As an exceptional world-class scientist and clinician with over 20 years of experience as a director of a major biotech company, Marc brings important depth and breadth to our company.”

“Rac1 is an underappreciated oncology target,” said Dr. Lippman. “I launched Geneyus based on the potential of Rac1 inhibition to address the unmet needs of many distinct cancer patient populations, and I look forward to working with the Revere team to realize the promise of targeting these important molecular switches.”

Dr. Marc Lippman is a recognized leader in breast cancer research and is currently professor in the departments of oncology and medicine at Georgetown University Medical Center.  He has served as director of the Georgetown Lombardi Comprehensive Cancer Center. An accomplished researcher, Dr.  Lippman is widely known for his work in the investigation and treatment of breast cancer, and he previously led the medical breast cancer section of the medicine branch at the National Cancer Institute. Throughout his career, Lippman has garnered many honors including a Clinical Investigator Award from the American Federation for Clinical Research, the Transatlantic Medal and Lecture from the British Endocrine Societies, the Astwood Award from the Endocrine Society, the Bernard Fisher Award from the University of Pittsburgh, the Rosenthal Award from the American Association for Cancer Research, and the Brinker Award for Basic Science from the Komen Foundation.

Dr. Lippman is author of many chapters and books, including a textbook on breast disease.  He has also published over 400 peer-reviewed articles and is editor-in-chief of Breast Cancer Research and Treatment.

About Revere Pharmaceuticals

Revere Pharmaceuticals is a biopharmaceutical company developing small molecule drugs targeting the Ras-homologous (Rho) family GTPases, molecular switches that are central to cancer progression and other disease processes. Based on a deep understanding of how to balance the active and inactive forms of the GTPase, the company has built a pipeline of novel small molecules that target Rac1, select Rac1 variants and CDC42. The company is headquartered in Boston, Massachusetts. For more information, please visit www.reverepharma.com.