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Andrew A. Radin and Andrew M. Radin, Co-Founders, twoXAR
In an unusual but fruitful coincidence, two of Pharm Exec’s 2016 Emerging Pharma Leaders happen to be named Andrew Radin. No relation; only their middle initials are different. Nevertheless, that shared surname proved the spark for a singular mission: to build a new company, twoXAR (two times Andrew Radin or “two czar”), dedicated to advancing a new approach to drug discovery using the advanced data processing and deep knowledge analytical powers of software-based comput ational biology rather than traditional chemistry. twoXAR can chart a course to early-stage candidate discovery faster, and at significantly lower cost, than the “sift, test and verify” methods that have set the standard of R&D practice for decades.
“The easiest thing we’ve done so far is giving our company a name-literally, it says you don’t get one Andrew Radin but two,” co-founder and CEO Andrew A. Radin (above left), 43, told Pharm Exec. The first encounter came when the younger of the two co-founders, 31-year-old Chief Business Officer Andrew M. Radin (above right), asked if he could buy Andrew A.’s Internet domain name. The answer from the older of the two was a rather testy “no,” but in the course of Andrew M.’s courtship via email they discovered both were seeking ways to leverage their academic backgrounds into something more tangible than a shelf full of published peer-review papers.
Andrew A., who comes from a family with a history of engagement in social causes, also had a track record in leading engineering teams at data mining start-ups prior to launching twoXAR. One of them, Locationary Inc., was bought by Apple in 2013. Radin’s equity in the company allowed for some time off to use his computer science skills to create something with broader social value. This led him to a graduate-level program in bioinformatics at Stanford University. “Ironically, the relentless pursuit of practicality common to everyone who does tech in the Valley took me off the ‘publish or perish’ pedestal. It convinced me that a stronger focus on commercial imperatives-like filing a patent-could best fulfill my humanitarian impulse to show how technology can change the world. When I discussed putting my ideas about applying computer informatics to drug discovery into a research paper, the response out here was instantaneous: ‘you’re not going to publish this, you’re going to patent it.’”
Andrew M., a biochemistry and economics major at the University of California/San Diego, already possessed the entrepreneurial gene, having started a web development business while still in high school in Thousand Oaks, Calif.-just a short walk from the HQ of Amgen, the first successful big biotech. “I like to build things,” he says, which persuaded him to enroll in MIT’s MBA program at the Sloan School of Business.
Other mutual interests like travel in China kept the online conversation going between the two, leading finally to a face-to-face encounter during one of Andrew M.’s MIT field trips to Silicon Valley. “We clicked around his passion to bring meds to patients faster by applying big data to biology, and my interest in turning that passion into a real business-even better, one that disrupts.” At a later meeting back at MIT, both agreed on an enterprise mission: tackle a market challenge-the lagging pace and poor productivity of conventional early-stage drug discovery-and solve it, in a way that changes the world for the better and is both profitable and beneficial to patients.”
Andrew A.’s Stanford work, on algorithms created specifically to predict the most viable disease-to-candidate drugs, joined to Andrew M.’s investment banking and commercial build-out skills, led them to contacts with the local VC community, which, in turn, provided the seed capital for twoXAR. The company was incorporated in 2014 with 10 employees and the two men as principal shareholders, headquartered in Palo Alto.
An early, influential backer of twoXAR was the Valley’s flagship VC, Andreessen-Horowitz, whose belief in the power of technology to change the way entire industries do business was summarized in a 2011 Wall Street Journal op-ed, “Why Software is Eating the World.” The Radin duo captured this sentiment in their own follow-on investor pitch: “Software Eats Bio.” This won them $3.4 million in financing from Andreessen Horowitz’s Bio Fund and Stanford University’s StartX Fund. This has led to research collaborations with Stanford University Medical School, on rare disease applications in dermatology; Icahn School of Medicine at Mount Sinai, on diabetic nephropathy; and the University of Chicago, on atherosclerosis. Earlier this year, twoXAR snagged its first private-sector partner, Vium LLC, another Silicon Valley start-up using informatics to enhance the accuracy and reproducibility of in-vivo testing for preclinical drug candidates.
Embedded in the twoXAR business model is a strong contrarian streak. Drug companies instinctively associate computer software with a service-a non-essential but “nice to have” support tool. Wrong, say the two Radins. Their approach puts the cloud squarely in the service of investigatory biology, with a patent-pending, customized software-trademarked DUMA-that can roam unbiased through billions of data points associated with a specific disease indication to tease out trends and abnormalities and render predictive assessments of likely drug candidates, at a rate 175,000 times faster than conventional screening methods. Better targeting and faster timing carries a tangible payoff by adding more certainty to those early-stage markers, which helps de-risk the odds for failures at the costly later stages of development. It might be a stretch to reference such capabilities as discovery R&D on a disk, but it definitely breaches the standard software-as-a-service (SaaS) process model, which few big pharma now regard as strategic.
So far, the DUMA software has been run-tested on 55 therapy areas and conditions, including autoimmune disorders, cancer, neurological impairments, and metabolic disease. In June, twoXAR announced the results of a joint screening program with its partner Vium, for important new indications in rheumatoid arthritis. “Our data established preliminary in-vivo efficacy for 10 separate drug candidates that could be repurposed to treat various aspects of this debilitating condition. It further validates software-driven approaches in rapidly identifying new drug candidates,” the company said in a statement. Four other programs are now underway to accomplish the same thing, in other diseases, at the preclinical stage.
Yun Fang, assistant professor at the University of Chicago’s Department of Medicine, signed on to work with twoXAR after he saw the initial results on rheumatoid arthritis. “I was curious to explore how their in-silico approach would tackle atherosclerosis,” he said. “In the short time we’ve been working together, the twoXAR team has generated a dozen strong hypotheses around unique candidates that my lab will evaluate through in-vivo models.”
While the biopharma world itself remains hesitant about the idea of letting software lead discovery, both Radins insist that the big players will eventually come around. For example, there is an emerging interest in purchasing the IP or licensing compounds that the twoXAR DUMA software identifies as a new or novel disease target. Ultimately, the Radins tell Pharm Exec all this validation work could put twoXAR in a position to identify promising drug candidates, de-risk the opportunities through preclinical studies and progress them to the clinic through industry partnerships. “Long-term, our aim is to become a full product innovator, not just a leader in process engineering,” CEO Radin said.
What kind of leadership is required to move a new enterprise like twoXAR forward, from an idea to an institution? Andrew A. sums it up in a single word. Grit. “For nearly all start-ups, the odds are against you. It was particularly hard for us because of the alien complexity of the subject matter-computational biology. The standard response to our pitch would begin with the admonition ‘don’t talk mathematics to me,’ followed by the conclusion ‘what I don’t understand, I can’t evaluate, so I have to take a pass.’
“We had to break this fatal connection, and we did it by replacing the math with an of-this-world vision, using accessible story telling that linked the technology to a result that held meaning to them, which is the pathway to getting a drug primed for approval. We took the time to answer questions, listen carefully to objections, psychoanalyze the fears, and emphasize a specific result. I’d say this is a set of actions that apply to any new business-and I guarantee you will hear ‘no’ 80 times before you get the first ‘yes.’”
Adds Andrew M.: “Don’t forget the tactical side when you are building a business from scratch-we are used to doing everything, and it’s not just coding and meeting investors. The story of a start-up begins every morning when you remind yourself to do things like take out the trash. That’s what keeps you grounded.”
- William Looney