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Company Background

Modulation Therapeutics is an early discovery and research startup company, which has been spun out of the Moffitt Cancer Center as part of their initiative to commercialize the research being conducted at the research facility. Modulation is dedicated to the development of novel peptidomimetic drugs for multiple myeloma (MM) and other cancers that home to bone. The company is currently focused on development of its lead candidate, MTI-101, a novel drug with a first-in-class mechanism of action.

Technology Overview 

MTI-101 is a cyclic peptidomimetic  that binds  CD44 and induces an agonistic signal leading to toxic increases in the levels of intracellular Ca2+ that trigger cell necrosis in MM cells. Recent evidence indicates that metastatic tumors rewire their Ca2+ circuitry. We propose that rewiring of Ca2+ signaling renders tumor cells vulnerable to Ca2+ overload. The in vivo efficacy of Modulation’s lead compound, MTI-101, has been demonstrated as a single agent and in combination with the proteasome inhibitor bortezomib using two independent MM in vivo models that considers the tumor microenvironment.  Importantly, MTI-101 shows increased activity in primary MM specimens obtained from patients who have relapsed on therapy; a finding that has been used to develop predictive biomarkers to be further explored in early phase clinical trials.

Intellectual Property

Modulation Therapeutics has licensed MTI-101 and several analogs from the Moffitt Cancer Center. The composition of matter and use patent was filed in 2012. Additional filed patents include coverage of analogs, combination strategies as well as biomarkers of response.

Market Potential

Multiple Myeloma is a disease that initially responds to therapy. However, inevitably all patients will relapse with disease that is refractory to standard of care agents. Thus novel treatment strategies are required to improve patient outcome. The market for MM is very large, and with improved diagnosis/detection combined with an aging population, is projected to exceed $10 billion worldwide by 2018.

Competitive Advantage

There are no drugs on the market or in development that would provide direct competition to Modulation’s lead candidate, MTI-101.

• MTI-101 induces necrotic cell death in myeloma cells and thus does not require the apoptotic machinery to induce cell death.
• Inhibits osteoclast formation and function and augments differentiation of osteoblasts using in vitro cultures and demonstrates decreased myeloma induced lytic bone lesions in vivo. MTI-101 uniquely targets the both the tumor and the bone marrow niche.
• Shows increased ex-vivo activity in specimens obtained from patients relapsing on therapy.

The crucial unmet need in myeloma is for drugs effective in patients that have relapsed on existing therapies. Modulation Therapeutics is well positioned to develop MTI-101 for the treatment of drug refractory myeloma.

Financial Overview

Modulation is an early-stage, pre-clinical research organization and has not generated any company revenues to date, nor have they developed any revenue projects beyond understanding the potential size of the market opportunity.

The company has raised over $1.7 million to date through a combination of research grants, foundation investments, and local commercialization debt.

Commercialization Strategy

Modulation is looking to raise $3 million to build and fund the infrastructure and partnerships required to plan, manage, execute, and document the IND-enabling studies to include the IND application and approval process. Modulation expects to complete the IND approval process within 18 months of receiving the required funding. Currently, Modulation has been able to advance the development of MT-101 through initial PK studies.

Pipeline Products

The initial focus for Modulation is on MTI-101 for the treatment of MM. Additional indications currently being validated are EGFR driven lung cancer, metastatic prostate and breast cancer. Targeting antibody conjugation strategies are in development and the patent has been filed for this strategy. Moreover a peptoid-peptide library is currently in development for covering additional chemical space surrounding MTI-101.

Management Team

• Co-founder and CSO Lori Hazlehurst, PhD is an expert in defining strategies to target the tumor microenvironment and is the co-inventor of multiple patents, including MTI-101.
• Director of Synthetic Chemistry Mark McLaughlin, PhD is an experienced synthetic organic and peptide chemist with more than 100 publications, is a co-inventor of MTI-101, and a senior member of the Moffitt Cancer Center.
• Board Member William Dalton, MD, PhD is the current CEO of M2GEN and former CEO of the Moffitt Cancer Center.
• Board Member Anne Cress, PhD is a professor of Cellular & Molecular Medicine at the University of Arizona, and Deputy Dean of Research.

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.

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.