Predix Pharmaceuticals’ proprietary 3-D modeling program (PREDICT) predicts and simulates the 3-D structure of G-protein coupled receptors (GPCR’s), a family of proteins that are involved in many major diseases and form the basis of leading drugs today.A company must be doing something right if the American Cystic Fibrosis Foundation provides it with $12.5 million in funding to research and develop an effective treatment for this debilitating genetic disease.
That company, Predix Pharmaceuticals Holdings Inc., founded in Israel in 2000, has won the confidence of the Cystic Fibrosis Foundation Therapeutics, Inc. (CFFT), the drug development affiliate of the Foundation.
“We have been extremely impressed with Predix’s drug discovery and development track record,” says Robert J. Beall, Ph.D., president and CEO of the CF Foundation and CFFT. “This agreement will enable us to work with a cutting-edge company to focus on promising research…We are confident that collaborating on these research programs will move us closer to finding an effective therapy to restore function to CF cells in patients with cystic fibrosis.”
Cystic fibrosis (CF) affects approximately 30,000 children and adults in the US alone. A defective gene causes the body to produce an abnormally thick, sticky mucus that clogs the lungs, leading to life-threatening lung infections, and obstructs the pancreas, causing difficulty absorbing food. The median life expectancy has improved from early childhood to the mid-30s today, but many individuals battle lung disease for years.
Why the vote of confidence in Predix? For one thing, the young company has a proprietary technology that has enabled it to develop a series of potential high-demand drugs – two of which are already in human clinical trials – all in the last two years. In fact, the Ramat Gan-based start-up is soon to become the first Israeli biotechnology company to float on the NASDAQ exchange.
The key to the company’s success is its proprietary 3-D modeling program (PREDICT) which predicts and simulates the 3-D structure of G-protein coupled receptors (GPCR’s), a family of proteins that are involved in many major diseases and form the basis of leading drugs today.
Two of the company’s GPCR-type drugs, now undergoing clinical trials, are aimed at treating depression and Alzheimer’s disease. A third drug for pulmonary hypertension is expected to enter clinical trials later this year.
“We have the first computer shortcut to GPCR drug discovery,” says Dr. Oren Becker, co-founder with Dr.Sylvia Noiman of Predix Pharmaceuticals. Professor Chaim Aviv, a pioneer of biotechnology in Israel, was also involved in the initial founding of the company, originally called. Bio-IT.
The shortcut has enabled the company to identify several compounds that are potential high-demand drugs.
Like bees to honey, the success has attracted investors who raised a total of $43 million in an oversubscribed private offering in January. Predix had already raised $27 million in an earlier round of financing, plus $10 million in the seed stage. The company’s computational division is in Israel; its headquarters in Woburn, Massachusetts, were set up in 2002. Predix has begun negotiating with various investment houses to conduct its initial public offering in the coming months according to a company value of between $160 million to $250 million.
“We are very excited with the results of our Phase I trials for the anti-anxiety, anti-depressant drug candidate. It will be developed as a drug with rapid onset of action and no sexual side effects,” says Woburn-based President and CEO of Predix, Michael Kaufman (MD, PhD.-Johns Hopkins; post-doc, Harvard).
Speed and efficiency are buzz words in the company. “Our goal is to drive one or two novel drug candidates into clinical testing each year. We did that in 2004 with both our anxiety and depression programs, and our compound for Alzheimer’s and other cognitive disorders,” says Becker, Chief Scientific Officer.
“Moving a drug from in-silico discovery, through optimization and into clinical trials in less than two years demonstrates the power of our platform,” says Becker. The company is already collaborating with one of the five largest pharmaceutical companies on one specific GPCR.”
Predix has good reason to focus on G-Protein Coupled Receptors, a superfamily of proteins, which are primary drug targets today. Embedded in membranes, they facilitate “chat-cell talk,” communication between the cell and its environment. Passing signals across the cell membrane, they signal a second messenger system to respond. The receptors are involved in a wide variety of body systems and processes and control the physiology of all the major organs in the body. Scientists have identified 800 different human G-PCRs-400 for taste, and 400 for other life functions. They are involved in major diseases?hypertension, cardiac dysfunction, depression, anxiety, asthma, obesity, inflammation, and pain. G-PCR’s account for nearly 50% of all drugs on the market, and 30% of the top 50 best-selling drugs.
“It is all about getting the right key in the right lock,” explains Dr. Sylvia Noiman, co-founder and general manager of Predix Pharmaceuticals, Israel. Noiman earned her Ph.D. in Molecular Biology at Tel Aviv University, and post-Doctorate at the Weizmann Institute of Science, after earning an MBA in parallel with a Masters in Science at TAU. An entrepreneur, as well as a scientist, Noiman had been been looking for cutting edge technology for drug development when she met Becker.
Co-founder Becker earned his Ph.D. in Theoretical Chemical Physics, wrote a highly praised textbook in the field and has been a Visiting Professor at Harvard.
The first lock Predix is fixing is a faulty GPCR protein that causes anxiety, depression, ADHD, and other similar maladies because it has a malfunctioning key. Initially, it is concentrating on a serotonim-based compound for anxiety.
“Hormones and other molecules (neurotransmitters and peptides) that are expressed in the brain and transmitted to the blood interact with GPCR which is the gateway in the membrane, on the periphery of the cell. If the fit of the key is correct, the hormone binds with the GPCR which then sends out signals that cascade in the cell. If the key is not working properly, there may be too much signaling or other problem which brings on illness,” explains Dr. Noiman.
The key is in a database of two million compounds. “We are looking for the best key to interact with the lock,” says Noiman. Filtering to a library of 150,000 compounds, Predix computational scientists screen out the best 100 compounds to test with the 3-D modeling technology.
“Our approach allows us to compete with companies with far greater resources because we focus on making fewer compounds, but with the right properties,” said Becker. “We are the first to do rational screening rather than random screening which is used throughout the industry.”
“We try to do screening in less than one year, screening that would take five years in a lab,” says Dr.Yael Marantz, Senior Director, Computational Drug Discovery. Marantz was tapped for a key position at the start-up as soon as she finished her doctorate in computational chemistry at TAU.
She is eager to show a dynamic 3-dimensional image of the GPCR structure, a meshy protein characterized by seven tubular helixes. “We look for a hole, a pocket, a place to dock.”
Maranz says that they are not just looking for a “hit.” “Our goal is to find the best drug candidate – one that is more active, that does not decompose, has more metabolic stability, does not interact with other receptors, and has no side effects.”
Predix’s compound for anxiety scored high on the simulation test-stable with no side effects. Phase II trials are underway.
Another medical need, Predix is targeting is cardiac arrhythmia, caused when insufficient oxygen gets to the heart. Expensive defibrillators and ineffective drugs with side effects are not good medical solutions. The Israeli scientists have discovered an ion channel directed compound, which it is optimizing, and expects to reach pre-clinical testing within a year.
With seven drugs in the pipeline (including drug candidates for cancer and inflammation) Predix is setting a new pace in drug discovery. Its edge: “We put the computer up front,” says Noiman.
Now the company will be setting its sights on developing a treatment for cystic fibrosis as well, by using its proprietary PREDICT technology to model the structure of a defective ion channel that ultimately leads to the symptoms of CF. Once the exact site of the channel is identified, Predix plans to use its computational drug discovery capabilities to discover a drug that restores proper functioning to the channel in patients with CF.
“Our technology has enabled us to advance two compounds from discovery into the clinic in less than two years,” notes Chen Schor, chief business officer of Predix Pharmaceuticals. “We are excited about applying our drug discovery and optimization technology… for the benefit of patients with cystic fibrosis.”
“This agreement is a perfect fit for Predix strategically and enables us to use our proven technology and discovery capabilities to help people battling this critical life-threatening disease,” adds co-founder Becker.