Canadian informatics firm Cyclica is making good  on a promise it made last year to make  a software-as-a-service version of  Ligand Express, its proprietary software for analyzing and  evaluating drug-protein interactions, available to the pharmaceutical market.

The company plans to begin beta testing the software product in the fourth quarter of this year with existing clients with a full launch scheduled for the first half of 2017,  Naheed Kurji, Cyclica's President and CEO, told GenomeWeb this week.  These clients will have  a chance to test the solution at a reduced price and  to provide feedback that will be used to improve it ahead of the launch. The company has also added new features to its software including a tool for determining the effects of drug compounds on protein activity.

“The real value out of all of this is [customers] can  keep  the data in house, they don't have  to disclose anything to us,” Steven Molinski, an application scientist at Cyclica, told GenomeWeb. Equally importantly “is the visualization and  the ability to really tailor the analysis to their needs,” he said.

Historically, Cyclica has provided services based on Ligand Express to customers seeking fresh candidates for their drug development pipelines. The software uses biological, chemical, and  protein structure data to identify small molecule candidates for possible development and  testing including opportunities for drug repurposing. Given a list of compounds, it looks at known  interactions between the test compounds and  proteins as well as interactions between similar compounds and proteins. It selects drug-protein interactions that are more  likely than  others and  uses them  as a template to explore much  larger sets of proteins for possible interactions. As it finds new interactions, the software selects those that will likely be good  candidates for research and development. Cyclica recently published a  validation study that showcases the efficacy of the software's proteome-docking capabilities using experimental data from kinase inhibitors.

The company targets small- to mid-cap pharmaceutical companies as well as academic institutions. These clients submit lists of molecules to Cyclica which performs the computational analysis internally and  reports the results back  to the client. But now it wants to make  those internal pipelines available to customers so that they can  search for those compounds on their own. Kurji told GenomeWeb last year that the company would offer the software under  an enterprise licensing model and  that it would also provide some additional speciality services to customers.

The company planned to launch the software as early as Q4 this year but decided to hold off on doing so in order  to lay some additional groundwork and  make  some improvements, Kurji told GenomeWeb. For one thing, it wanted to make  sure that the platform was secure and  that there would be no data leaks once it was accessed. To that end,  it tapped a Canadian data security company to assess Cyclica's security mechanisms, bridge gaps, and  put all the necessary components in place to ensure that hosted customer data would be safe. “When we agreed to take those necessary steps, we realized that's going to be a six-to-eight month  process,” he said.

The company also wanted to ensure that its intellectual property was protected prior to the launch, he said. At the end  of last year, it filed an international patent for the core  Ligand Express technology that covers the algorithms and  scripts that underlie the software. They also wanted to include newer applications that they were developing in the final product. If they had  launched the software earlier, they would not have  been able to include those features in the initial release, he said.

In the last year, the company has added two new capabilities to its platform, which it says were developed in response to customers' requests for more  information to be included in their results. Historically, “what  we've been doing is proteome docking,” Kurji explained. “We can  dock…a drug or ligand to every protein in the human body  [as well as] bacterial and  viral proteins. It's a lock-and-key approach where  the drug is the key and  we are trying to find the best lock.” The output is a list of candidate proteins for a given drug and  associated docking scores. Those scores are useful but customers wanted more  information, specifically, about the consequences of the drug-protein interactions. “This is really important because certain diseases require inhibition of proteins that are overexpressed whereas [in] other  diseases [we need] to turn on a protein and  make  it work better than it did before,” Kurji noted.

To that end,  Cyclica developed a tool called Switchx, which uses machine learning techniques to predict whether a protein will be turned on or off when  it interacts with a given drug compound. Specifically, Switchx predicts the most likely category for a compound — inhibitor or activator — by looking at how all drugs have  interacted with the protein, Molinski explained to GenomeWeb. It makes an initial prediction based on this data and  then  refines that prediction based on information about the binding properties of the interaction and  the consequences of those interactions, he said. According to Cyclica, it can  take  four to five months for scientists to run standard assays to determine the effects of drugs on proteins. With Switchx clients get results in minutes.

A second application that Cyclica has added to Ligand Express lets users identify alternative compounds that behave in similar ways to the drug molecules that they are interested in. The new tool that Cyclica has developed lets users generate proteome-binding profiles for compounds and then  compare them  to one another to identify those that are similar, Molinski said. It offers an alternative to traditional pharmacophore-based searching or mapping which identifiers biosimilars by looking at chemical structures, he said. “Instead of looking at just the structure of the drugs, we can see how each drug interacts with every protein in the human body  and  find similar drugs which act  in that way.”

Other applications available in Cyclica's software include a tool called Divex which can  be used to predict combinations of drugs that can  be used to treat  complex diseases such as AIDS or cancer.

With these tools “we can  really look at the whole picture [of] how a drug is interacting with every protein and  make  some conclusions on how this can  streamline or facilitate future drug discovery or drug repurposing and  development efforts,” Molinski said. “We can  prioritize [compounds] based on mechanism of therapeutic action … we can  provide you with a list of every protein that your new drug interacts with [and] we can  tell you how it will interact with these proteins.” Furthermore, “we can further enrich the data by using systems biology to map  these interactions on different disease pathways and  processes,” he said.

Cyclica has completed a number of projects in recent months one of which was submitted by Naturalis, a Canadian nutraceutical company that tapped Cyclica to find natural molecules that are similar to known  anesthetics that could be used to treat  acute alcoholic hangovers. “The results that Cyclica have  provided us have  opened completely new opportunities of R&D for my company, and have  saved us almost a year of R&D — and  with that a lot of money,” Arun Anand,  Naturalis co- founder and  president, said in a statement. He also told GenomeWeb that he and  a colleague have submitted a paper for peer-reviewed publication that describes compounds that Cyclica's software identified as likely candidates. Naturalis is now exploring partnership opportunities with pharmaceutical companies to develop compounds identified by Cyclica's analysis into commercial products.

Another  client is a non-profit organization called Cures Within Reach that supports research efforts to repurpose US Food  and  Drug Administration-approved drugs and  devices to provide safe and affordable treatments for common and  rare disorders that currently do not have  effective treatments. Cyclica worked  on a pilot project with Cures Within Reach and  Tulane University that aimed to asses five currently approved drugs for possible use in treating idiopathic pulmonary fibrosis (IPF), a chronic and  fatal lung disease that affects the elderly. Cyclica used its software to evaluate the interactions between the drug compounds and  proteins and  to assess the effects of the drugs on proteins. It identified three  potential candidates that could be potentially work as treatments for IPF.

Kurji said that the researchers have  since validated the compounds in vitro and  are preparing to publish a paper describing their results. The partners are now working together to see how Cyclica's software can  be used with the Cures Within Reach network  to move  forward  with multiple undisclosed projects, Kurji said. GenomeWeb reached out to one of the Tulane researchers for additional details about the past project but did not receive a response as of press time.

Cyclica is currently in talks with 14 other  unnamed companies that are interested in running their compounds through its platform. The company is also working on another agreement with a research group  at the University of Toronto  that is working on a small molecule therapeutic for  X- linked myotubular myopathy, a genetic muscular disease that affects 1 in 50,000 males and  is always fatal. It also has projects with researchers at other  institutions who are studying rare genetic conditions among other  conditions.

“One of our unique value propositions is that we are able to address the rare orphan disease space … [but] we have  multiple focus points,” Kurji said. For example, the company is working with at least one pharmaceutical company based in Canada that is developing a new cancer therapy. “Whether its target identification, reprioritization, drug repurposing or adverse effect  elucidation, that's our sweet spot,” he said. Competition comes from older firms such as NuMedii and  newer  players like TwoXar who are also building a business around using computational tools to match compounds to diseases.

But Kurji believes that one of the things that sets Cyclica's solution apart is that it takes advantage of a much  wider pool of data than  its competitor's offerings. Some of those solutions select compounds by looking only at known  and  well-supported disease targets. “Once  we get outside those [roughly] 1,500  disease targets to the orphan diseases or the rare diseases, machine learning technologies typically have  a harder time because the quantum relevance and  the quality of the datasets that they are looking at taper off,” he said. Cyclica on the other  hand  provides a “proteome- wide view of how a drug interacts with all aspects of human biology.”

Beyond the life sciences, Cyclica has accepted projects from the consumer packaged goods market. One client in that space tapped Cyclica to identify a compound in a skin cream product that caused some adverse side effects in a subset of the population. Cyclica was able to identify the offending compound in the product and  has signed a longer term agreement with the unnamed company, Kurji said.

Although it plans to offer Ligand Express under  a subscription model, Cyclica will continue to take on projects for companies who prefer  to access services as needed rather  than  purchase software. For first-time users, the company offers an introductory price of roughly $25,000 for the first five compounds. After that,  it charges between $10,000 and  $20,000 per compound, depending on factors such as the size of the compound and  the nature of the project, but those numbers are flexible. “We have  a framework in place but we are nimble enough that we are able to be amenable to the needs of that customer,” Kurji said.

Following the launch of the software next year, Cyclica expects that initially, about 25 percent of its revenues will come from sales of its SaaS, while 75 percent will come from projects; however, it expects those numbers to flip by 2019 with about 75 percent of revenues coming from software sales and  25 percent coming from projects, Kurji said.

To date, Cyclica has raised about C$3.1  million — about $2.4 million — from investors. The company plans to raise between C$5 million to C$7 million in a new round  planned for the fourth quarter of this year, Kurji said.

It has also hired a number of application scientists, including Molinski, whose role, in part,  is to test components of the product internally before the company rolls them  out and  to run analyses for customers who submit projects and  transition them  to the subscription-based version of software. The company has also hired Andreas Windemuth as senior vice president and  chief scientist who will be responsible for current and future development of Ligand Express.

Cyclica plans to open a new office in California in the near  future.  This is in addition to its headquarters in Toronto  and  existing offices in Connecticut and  Massachusetts.