Using 'semicon' simulation for drug discovery

Most of us have heard of simulation in semiconductors. However, using the technique in drug discovery/pharmaceuticals is indeed unique. The Cellworks Group Inc. (CWG) has managed to achieve this unique status by developing in silico based physiologically aligned predictive analysis platforms based on a systems biology approach.

These contain quantitative and dynamic maps of metabolic and cell signaling pathways, which are relevant to several diseases like cancer, inflammation, diabetes, CNS, infectious diseases, etc. The company was founded in June 2005, with corporate office in California, USA and the R&D team stationed in Bangalore, India.

Taher Abbasi, CEO & COO, CWG and Cellworks Research India Pvt Ltd, said that drug researchers can "simulate" these in silico platforms with various disease triggers, biological target inhibition/activation to represent functional drug action, patient sub-types with the overall objective to understand the disease physiology and treatment therapies in the context of a physiological view.

Simulation in pharma
Modeling and simulation have been used very successfully in fields such as aeronautics and semiconductors. However, their adaptability within the pharmaceutical domain has been anemic until now. Physiology simulation and modeling is crucial for identifying the issues early in the development cycle and in creating more efficacious and safer drugs.

Abbasi, a former Cadence employee, said: "Coming from the VLSI/chip industry, we are used to using automation technologies, especially simulation. One of our co-founders is Dr. Shireen Vali, who has a deep scientific background. We looked at how we could bring in the concept of simulation into drug discovery." The company has just crossed 65 members and is growing. "We have covered a pretty broad range of diseases and we have also brought together people who are experts in their respective fields."

Cellworks took the idea of simulation into drug discovery by looking at diseases, identifying the biological processes involved with a particular disease, and then looking at the biological players -- such as proteins, enzymes, etc., finally leading to building a unique dynamic map -- which is underlined by mathematics, he added. "As it is mathematics, it is similar to say, looking at transistors," he said.

Cellworks has an underlying computational engine, which is an OD (ordinary differential equations) solver, and solves those. The first layer is biology, the second -- mathematics, and the third -- semiconductors. Abbasi said: "Under the hood, we have put in the best practices of the semiconductor industry, especially, the automation part. This should handle pathways, runtime capacity and analysis capability to probe the system for data."

Cellworks' goal is crystal clear. Its mission is to be the infrastructure supplier to the pharmaceutical industry, by enabling the different components of this industry to carry out drug discovery. Besides this, Cellworks also aims to become the equivalent of Goggle Maps/Earth for understanding the human physiology, disease progression and predict the biological responses and therapeutic effects of drugs.

Huge market opportunity
So what is the market opportunity in this domain? As per Cellworks' estimate, the total available market (TAM) is said to be worth $1bn+ for collaborative R&D, disease platforms and in-house drug research. The pharmaceuticals and biotech industries spend over $51bn yearly on drug research.

The vast majority of this money goes into projects that have to be cancelled because of unanticipated side-effects, toxicity or lack of potency which is discovered in clinicals when very large expenses have already been incurred. Abbasi added, "We will and we can create and own the largest and most comprehensive IP of the dynamic physiological maps and computational infrastructure for the in silico analysis of cell physiology and disease pathology."

He pointed out that the only way to reduce costs and improve on the first time succession is to prototype a drug in a virtual environment -- similar to simulation in semiconductors/chip design. "The key is to first get the biology right, followed by the focus on chemistry, which is similar to frontend and backend in chip design," he noted. "Only then can you drive the in vitro and in vivo experiments through in silico."

Cellworks has already tasted early success. So far, it has created seven base disease platforms, which are physiologically validated. It is also working on live projects with initial customers, collaborators on these platforms. These platforms contain 100+ validated sub-pathways, which model over 10,000 reactions and 30,000 parameters.

The seven base disease platforms include: oncology platform (Glioma, Breast cancer), inflammation platform (RA and IBD), metabolic-syndrome platform (Diabetes II), skin (Pigmentation), pre-term endocrinology, infectious diseases, and neuro-degenerative disease platform (Parkinson's).

Cellworks has established strong active collaborations/partnerships in several areas. Notable being the UC Davis relationship in oncology, neuro-science, pharmacokinetics and inflammation; Cedar-Sinai/UCLA on pediatrics/pre-term delivery research, NIMHANS in Bangalore, for CNS work; UoH for oncology and Indian Institute of Sciences, Bangalore for heat shock proteins.

Cellworks has created a fast and scalable software platform for validation and analysis of disease platforms. The software platform allows it to simulate and verify at the subsystem level as well as at the disease level. It enables easy integration and re-use of models, intuitive debug and analysis of the platform. Next, it has a natural language processing system for enabling pathway analysis and validation.

Abassi added: "We are working with Orchid Chemicals on an arthritis project. We had real success regarding the usage of our technology in various R&D and production projects." Most of the R&D is done out of India, with only two people based in the US for marketing/sales.

Cellworks had done a small round of funding in January 2007 worth $1mn. Abbasi said, "We will do another round of funding in Q3-08 now that we have success stories and customers in place."