In conversation with Alistair Duncan
As a co-founder, president and CEO of closely held viDA Therapeutics, a tissue repair company, Alistair Duncan has developed an affinity for doing biotech startups. From 1998 to 2008, he was president and CEO of Chromos Molecular Systems, where he was also a co-founder and director. He followed that up with Agrisoma Biosciences, a company building a high performance crop seeds business for the development of new genetically modified crops for renewable fuels, where he was a co-founder, director, and served as interim CFO. In his early career, Mr. Duncan was a principal with the Ernst & Young Corporate Finance and International Life Sciences Group, where he provided high technology and life sciences companies with corporate advisory services in strategic planning, valuations, financing, divestitures, and mergers and acquisitions. In this interview with BioTuesdays.com, Mr. Duncan discusses viDA’s novel technology platform and its goals for 2014.
Can you give me a brief history of viDA?
We were spun out from the University of British Columbia in 2008 to develop proprietary first-in-class therapeutics based on our recent discovery of a new mechanism of action for a well-characterized protease target, Granzyme B. To date, we have raised over $6-million in equity financing with the last round led by the Business Development Bank of Canada’s venture arm, BDC Venture Capital.
What are granzymes and what role do they play in the body?
There are five members of the granzyme family: granzyme A, B, H, K and M. Granzymes are serine proteases that historically were believed to be only released by cytoplasmic granules within cytotoxic T cells and natural killer cells.
This strictly intracellular role was to eliminate unwanted cells by inducing cell death. Granzyme B (GzmB) is now emerging as a key target for drug development, given recent discoveries of its extracellular actions, providing a clear distinction from GzmB’s intracellular role in apoptosis. It has now been shown that extracellular GzmB actively participates in degradation of key components of the body’s extracellular matrix (ECM), which acts as a scaffold for cell binding and provides essential structural integrity for proper function of tissues and organs. GzmB can also release growth factors from the ECM that drive inflammation and fibrosis.
How do granzymes impact tissue repair?
GzmB is capable of degrading key ECM substrates, including fibronectin, vitronectin and decorin. It is the degradation of the ECM that impedes tissue repair and remodeling, which results in the loss of tissue tensile strength, cellular damage and vascular dysfunction. For example, excessive degradation of decorin by GzmB during tissue repair impairs collagen fibrillogenesis and remodeling. GzmB can also impact tissue repair through the processing of cytokines, such as IL-1α into a more pro-inflammatory fragment and/or by releasing growth factors such as TGFb and VEGF into the extracellular milieu, which can contribute to inflammation, pathologic angiogenesis and fibrosis, depending on the context.
What’s the IP behind your inhibitor technology?
We have filed and have pending a number of patents on families of new chemical entities that have been designed, with high specificity, to bind to the active site of GzmB in order to prevent the proteolytic activity of extracellular GzmB. These highly soluble new chemical entities have molecular weights of between 400 and 550 Daltons and have IC50s in the picomolar and low nanomolar range. We are also developing a suite of proprietary monoclonal antibodies against GzmB.
What diseases can your technology treat?
An abundance of data has emerged in the literature demonstrating a link between elevated levels of GzmB in the extracellular milieu and increased severity of many chronic diseases of inflammation and/or aging, including autoimmune, cardiovascular, dermatological, musculoskeletal, neuroinflammation and respiratory. Both immune and non-immune cells express GzmB. In addition, GzmB is not naturally inhibited in the extracellular milieu. As such, levels of GzmB and resulting extracellular matrix protein degradation tend to increase substantially in disease states without any apparent restraint.
What’s the company’s development pathway?
To date, we have demonstrated, in models of vascular and skin injury, that inhibition of extracellular GzmB promotes tissue repair by preventing the degradation of keyextracellular matrix proteins that are essential for wound repair and tissue remodeling. Therefore, our initial focus is to advance the lead program in skin injury repair through clinical trials, beginning with the filing of an IND in 2015, with the objective of exhibiting the clinical benefit of topical administration of an extracellular GzmB inhibitor in the area of dermatology.
Dermatology offers both an economical and a timeline advantage to move our lead program into a clinical pathway and it provides the opportunity to explore several tissue injury conditions, including orphan indications.
In parallel with the advancement of our dermatology program into the clinic, we will continue developing our granzyme technology platform through our drug discovery program, generating small molecule and biological inhibitors. These innovative inhibitors will have specific properties allowing for different modes of administration to address different indications.
What are your goals for 2014?
To advance our first-in-class GzmB inhibitor program in tissue repair in dermatology, we plan to complete pre-IND studies, demonstrating efficacy and lead optimization, and also select our initial clinical indication for skin injury repair. We also plan to expand our library of proprietary inhibitors, including second-generation small molecules and additional biologics. Another goal is to create collaborations for multiple disease targets, including impaired tissue repair, autoimmune, inflammation, fibrosis, anti-aging. We also are targeting another equity raise in the third quarter this year to establish a financial foundation to support Phase 1 trials and advancement of other programs.