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Prof. Suzie Chen and her colleagues at Rutgers University have recently discovered that the metabotropic glutamate receptor 1 (GRM1, mGluR1) plays a significant role in the development and growth of melanoma tumors.  They found that riluzole, the only drug approved by the U.S. FDA for the treatment of amyotrophic lateral sclerosis (ALS), which also blocks glutamate release from GRM1 cells, inhibits melanoma growth and proliferation both in vitro, in mouse xenograft models, and in limited human clinical trials in melanoma patients.  However, the clinical use of riluzole for ALS, and potentially for melanoma, is severely limited by variable CYP1A2-mediated first pass metabolism.  Fox Chase Chemical Diversity Center, Inc. has developed novel and innovative prodrug derivatives of riluzole which avoid CYP1A2 in vitro metabolism and are expected to provide more regular pharmacokinetics and exposure in patients, with a longer half-life, allowing for once daily oral dosing versus the current twice daily dosing that is required, and potentially greater patient compliance.  

The company has filed several PCT provisional U.S. patent applications on riluzole prodrugs, with additional composition of matter patent filings anticipated. Other than riluzole, there are no compounds that target the glutamate pathway for treatment of metastatic melanoma.  The company has raised more than $2.2 million specifically for this program since 2010, and is looking to raise an additional $3 million by the third quarter of 2015, in order to perform the required IND-enabling studies for an IND application and enter Phase I clinical trials at the Cancer Center of New Jersey

Technology Name: Reduction of Chemotherapy­Induced Myelosuppression (“Chemoprotection”)

Company Background

G1 Therapeutics (G1, or the Company) is a clinical-stage oncology company using a small molecule-based approach to attenuate multi-lineage bone marrow suppression due to chemotherapy. G1 was founded by Ned Sharpless, MD (Director, UNC Cancer Center), and Kwok-Kin Wong, MD, PhD (Director, Belfer Institute/DFCI/Harvard), to capitalize on their research into how certain cyclin-dependent kinases (CDKs) control the production of blood cells by hematopoietic stem and progenitor cells (HSPCs) in the bone marrow. The Company’s lead program, G1T28-1, is a highly potent and selective CDK4/6 inhibitor that is currently in Phase 1 clinical trials. G1 has assembled a team of accomplished drug discovery and development scientists with extensive experience in bringing innovative oncology drugs to market. The Company has 10 full-time employees and is based in Research Triangle Park, NC.

Technology Overview 

Bone marrow suppression (also known as myelosuppression) is a severe side effect of chemotherapy, resulting in the loss of red blood cells (anemia), white blood cells (neutropenia) and platelets (thrombocytopenia). Patients can experience fatigue due to anemia, infections due to neutropenia and bleeding due to thrombocytopenia. While oncologists expect chemotherapy to remain the standard treatment regimen for many kinds of tumors, the current treatments for myelosuppression have significant liabilities and shortcomings.

G1T28-1 induces a transient, reversible arrest of HSPCs, making them resistant to DNA damaging insults. Preclinical data has demonstrated that protecting the bone marrow from damage results in a quicker recovery of all blood lineages and mitigates bone marrow exhaustion. G1T28-1 has the potential to enhance anti-tumor efficacy by maintaining chemotherapy dose density and schedule, and to improve quality of life and to positively impact pharmacoeconomics by reducing transfusions, preventing hospital admissions due to infection, and attenuating the incidence of secondary hematological malignancies.

Market Potential

G1’s clinical candidate, G1T28-1, will enter the bone marrow supportive care market which includes growth factors (biologics) such as Neulasta, Epogen, Procrit, Neupogen, and Aranesp with combined 2013 sales of $8.4 billion in the United States alone. The Company has a target chemotherapy patient population of up to 300,000 per year in the US alone.

Competitive Advantage

G1's first-in-class chemoprotectant, G1T28-1, is differentiated from current treatments for myelosuppression because it protects all hematopoietic lineages: red cells, platelets, granulocytes and lymphocytes. While growth factors stimulate single-lineage bone marrow progenitor cells that have already been damaged by chemotherapy, G1T28-1 protects all hematopoietic stem and progenitor cells (HSPCs) before damage is done, potentially changing the treatment paradigm.

Financial Overview

Since inception, G1 has raised over $5 million from non-dilutive sources and closed a Series A financing of $12.5M in October 2013. The Company is currently seeking a $15M Series B for conducting a Phase 1b/2a trial to demonstrate reduction of chemotherapy-induced myelosuppression in cancer patients.

Intellectual Property

G1 has broad freedom to operate for its novel compounds and their methods of use. G1 has five issued composition-of-matter US patents covering compounds (including G1T28-1) related to the Company’s first proprietary scaffold. Additionally, G1 has multiple pending applications for composition-of-matter and methods-of-use on all three of its novel kinase inhibitor scaffolds.  

Commercialization Strategy

G1 is focused on developing G1T28-1, for chemoprotection. The Company plans to first demonstrate early proof of concept of bone marrow protection in a rapid and straightforward clinical trial in patients with small cell lung cancer.  Following this trial, G1 plans to conduct additional Phase 2 trials to demonstrate efficacy in other cancer types.

Additionally, there has been heightened interest in drugs that target CDK4/6 as antineoplastic agents. The Company is currently in active discussion with several potential partners for G1’s proprietary CDK4/6 inhibitors used as antineoplastics.

Pipeline Products

G1 Therapeutics is advancing a portfolio of proprietary drug candidates for both antineoplastic and chemoprotection indications.  The Company’s lead program, G1T28-1 is currently in Phase 1 clinical testing.  PK/PD data from this trial will inform dose and schedule for Phase 1b/2a trials in cancer patients that are planned for Q2 2015.  In addition, G1 has back-up/follow-on compounds for both chemoprotection (G1T30-1) and antineoplastic use (G1T38-1).

Management Team

·   CEO Mark Velleca MD, PhD was instrumental in founding, building, and leading CGI Pharmaceuticals. He forged a major drug discovery/development collaboration with Genentech and an acquisition of the company by Gilead.

·   CMO Raj Malik MD is an oncologist with more than 20 years of drug development experience in academics (University of Virginia), large pharma (BMS), and small biotech (Agennix).

·   CBO Greg Mossinghoff, MBA has extensive operational, financial, and deal-making experience in small biotech and big pharma. As President of Inspire (from inception through IPO), he established significant corporate partnerships.

·   CSO Jay Strum PhD brings more than 20 years of drug discovery experience to G1. He was a key leader of programs in cancer and metabolic diseases at GSK that led to marketed therapeutics such as Tykerb.

Technology Name: Small molecule CDK8/19 inhibitor

Company Background

The mission of Senex Biotechnology is to develop novel therapeutics for the treatment of cancer and other major diseases by targeting key disease-promoting pathways induced by cellular damage and aging, and by identifying and attacking novel cancer-specific molecular targets. Founded by Dr. Igor Roninson, on the basis of discoveries in his laboratory in 2002, the company is located in Columbia, SC, and currently supports three scientists.  Senex has won a series of grants, including two Phase II SBIR grants, and concluded a strategic licensing agreement with a foreign pharmaceutical company in 2014. Senex has identified several novel targets and generated first-in-class small molecules against three of these targets. The drug for the most advanced program is about a year from clinical trials.

Technology Overview 

Senex’s most advanced program targets CDK8/19, a transcription-regulating oncogenic kinase. CDK8/19 inhibition has multiple anti-cancer effects at the molecular level, including the inhibition of oncogenic transcription factors, as well as stimulating immune surveillance by NK cells. The lead molecule, Senexin B, is fully optimized and exceptionally selective for CDK8/19. It is orally available, non-toxic, and extremely potent in numerous in vivo studies: Senexin B directly suppresses prostate and breast tumor growth, exhibits strong synergistic effects with several widely used drugs, and has anti-metastatic activity in several cancer types.

Market Potential

Senex will initially develop Senexin B for treatment of metastatic castration-resistant prostate cancer (mCRPC), the second leading cause of cancer related death in the United States. Over 29,000 people die from prostate cancer every year; 1 out of every 36 men will die from prostate cancer.  Median survival for mCRPC is less than 2 years.  Although several new drugs have recently been approved, resistance to these drugs develops within several months so there is a large unmet need.  Senexin B acts against those cancers that do not respond to any class of androgen receptor inhibitors, including cancers that are resistant to the newly approved drugs Xtandi and Zytiga.

Competitive Advantage

CDK8/19, Senex’s primary target, belongs to the CDK family, but unlike better-known CDKs, CDK8/19 does not mediate cell cycle progression, and is not required by normal cells under homeostatic conditions. As a consequence Senexin B is extremely well tolerated. Senex is the only company to describe selective CDK8/19 inhibitors in a peer-reviewed article. Based on the known poster presentations and published patent applications, CDK8/19 inhibitors have been recently developed by Selvita (Poland), Bayer Pharma, and CNIO (Spain). Based on the available information, none of the competitors’ compounds appear to be as selective as Senex’s CDK8/19 inhibitors, and no comparable in vivo studies have been reported.

Financial Overview

Senex has received over $2.8 million in NIH funding and over $3.5 million from other sources, including angel investors, licensees, charitable foundations and the DOD. Senex is seeking $10 million to fund additional pre-clinical and clinical studies through proof-of-concept in castration-resistant prostate cancer.  The plans for this study have been developed with a NCI-designated cancer center.

Intellectual Property

The key issued patents for Senex’s CDK8/19-related IP are US patents 8,598,344 protecting the composition-of-matter of its CDK8/19 inhibitors and 8,592,147 protecting the general screening method for identifying inhibitors of transcriptional pathways including those regulated by CDK8/19. Senex also has several pending utility patent applications protecting other novel applications of CDK8/19 inhibitors that Senex and its collaborators have discovered.

Commercialization Strategy

Senexin B has been licensed to a foreign pharmaceutical company for minor markets. Marketing rights for all major markets are retained by Senex. The licensee will provide Senex with GMP manufactured Senexin B, the results of FDA acceptable preclinical safety studies, and clinical trials that will be conducted to international GCP standards. Senex will receive milestone payments and royalties from sales of drugs in the licensee’s minor markets. These results will enable Senex to partner with a major pharmaceutical company to perform additional clinical trials and to market the drug.  Anticipated milestone payments will fund other programs in Senex’s pipeline.

Pipeline Products

Senex also has programs targeting CDK3 and COPZ1. Senex has identified CDK3 as a cancer-specific target and is optimizing the first CDK3-selective small molecule inhibitors. COPZ1 is a component of the vesicle-coating complex and Senex has discovered the first COPZ1-targeting small molecules. COPZ1 inhibition should kill most types of tumor cells, including dormant cells and cancer stem cells, which are resistant to conventional therapy.

Management Team

• President and CSO Igor Roninson is the founder of Senex and the inventor on 41 issued US patents.
• CEO Lawrence Friedhoff has a long history of successful and rapid FDA approval of new drugs, including two blockbusters, one of which is Aricept, the main drug used to treat Alzheimer’s disease.
• Karthik Gopalakrishnan brings several years of experience in business development and negotiation skills to Senex.  He has successfully concluded business transactions with several pharmaceutical companies.

Robin Medical, Inc., has developed and commercialized a wide range of medical devices since its formation in 1997. The ultimate goal of its newest cryopreservation technology is to collect biopsy tissue samples that retain the cells’ viability, the in-vivo biochemical profile, and the tissue ultrastructure by using differential freezing profile that keeps part of the sample frozen (for biomarker analysis) and part unfrozen (for histology analysis). The cryogenic apparatus is either built into a cryobiopsy needle (CyroBx™)  to enable in-situ freezing of the tissue, or in a disposable sample holder (the CryoTray™) that maintains differential cryo temperature profile of samples acquired by any biopsy device.

The CryoBx™ will initially address the market of breast vacuum-assisted biopsy (VAB), estimated at $300 million, as a competitive VAB device with tissue cryopreservation. We then plan to address the much larger market of biopsy devices for internal organs that require thinner biopsy needles. In parallel, the company plans to complete the development of the CryoTray™tissue holder, to conduct clinical studies and to release it to market for use in any biopsy procedure.  A pending U.S. patent application for the cryogenic biopsy device and method awaits USPTO Office Action; a provision patent application covering the innovation of the CryoTray™ has been recently filed. Robin Medical has raised $15 million since its formation in 1997. The company looks for phase I investment of $1.5 million and intends to to apply for an SBIR Phase IIB (bridge) grant. The raised funds will be used to continue the development and clinical testing of the devices and to commercialize the biopsy cryopreservation line of products.