Seeing the power of AI in drug development

Today we announced our collaboration with Santen, a world leader in the development of innovative ophthalmology treatments. Scientists at twoXAR will use our proprietary computational drug discovery platform to discover, screen and prioritize novel drug candidates with potential application in glaucoma. Santen will then develop and commercialize drug candidates arising from the collaboration. This collaboration is an exciting example of how artificial intelligence-driven approaches can move beyond supporting existing hypotheses and lead the discovery of new drugs. Combining twoXAR’s unique capabilities with Santen’s experience in ophthalmic product development and commercialization… 

READ THE FULL POST AT MEDIUM.COM

Consider Your Biases

In the wake of Donald Trump’s victory over Hillary Clinton, pundits and politicians alike have wondered, “how did we not predict this?” Theories range from misrepresentative polling to journalistic bias to confirmation bias, fueled by the echo chambers of social media. These fervent debates about bias in politics had me reflecting on the role that bias plays in science and in R&D. Sampling bias, expectancy bias, publication bias… all hazards of the profession and yet science is held up against other disciplines as relatively bias-free by virtue of its data-centric approach.

Biopharma R&D has rapidly evolved over the last few years — it is more collaborative, demands greater speed to respond to competition, and challenges many notions of “conventional” drug discovery. In my reflections, I was curious whether this rapid evolution was a harbinger of biases not conventionally associated with science — and wanted to understand how we at twoXAR aim to stay aware and ahead of such biases.

READ THE FULL POST AT MEDIUM.COM

Augmenting Drug Discovery with Computer Science

The short-list for the annual Arthur C. Clarke Award was recently announced and it reminded me of a post we did last fall on augmentation vs. automation. Clarke is a British science fiction writer who is famous for being the co-screenplay writer (with Stanley Kubrick) of the 1968 film 2001: A Space Odyssey. He is also known for the so-called Clarke’s Laws, which are three ideas intended to guide consideration of future scientific developments.

  1. When a distinguished but elderly scientist states that something is possible, he is almost certainly right. When he states that something is impossible, he is very probably wrong.
  2. The only way of discovering the limits of the possible is to venture a little way past them into the impossible.
  3. Any sufficiently advanced technology is indistinguishable from magic.

These laws resonate here at twoXAR where every week we meet with biopharma research executives who tell us — usually right after we say something like, “using our platform you can evaluate tens of thousands of drug candidates and identify their possible MOAs, evaluate chemical similarity, and screen for clinical evidence in minutes” — that’s “impossible” or “magic”!

READ THE FULL POST AT MEDIUM.COM

Mission Possible: Software-driven Drug Discovery

Originally published at Life Science Leader Online.

In the 25-plus years since the modern Internet was launched we have seen virtually every industry evolve by leveraging the connected, global computing infrastructure we can now tap into any time, from anywhere. Today, advanced software programming tools like machine learning, massive data sets and cloud-based compute are making it easier than ever to rapidly launch and globally scale software-driven services without the capital expense that was once required.

The debate about whether or not software will eat drug discovery is not a new one and remains a topic that can raise voices. As a formally educated computer scientist and cofounder of a company focused on software-driven drug discovery, I come to the discussion with my own biases.

There is no shortage of software in today’s biopharma R&D organization. Cloud-based electronic data capture (EDC), laboratory information management systems (LIMS), process automation, and chemical informatics are just a few of the well-established tools that support R&D and have a meaningful impact. While software has become a …

Read the full piece at Life Science Leader Online.

What’s the difference between “software-led” and “using software”?

Ask an automotive engineer to improve passenger safety and they will invent features like seat belts, airbags and anti-lock brakes. Ask a software engineer to improve passenger safety and they will replace the driver with sensors and software.

The power of software-led projects goes beyond…

 READ THE FULL POST ON MEDIUM.COM.

A milestone worth celebrating

There have been a series of events that have defined the history of twoXAR. There was the lecture from Prof. Sirota on computational drug discovery that inspired me to invent. There was the encouragement from V. Paul Lee to patent my idea rather than publish an academic paper. There was the realization that Andrew M. Radin shared not only my name, but my passion for biotechnology and entrepreneurship.  There was that key moment while sailing the Charles River in the summer of 2014 when Andrew and I decided to launch this company.

More milestones followed. There was the day we received funds from our very first investor, Haya Al Ghanim. The email that told us we had been accepted to the StartX accelerator program at Stanford University. The phone call with Michigan State University’s Dr. Tim Collier where we learned our technology predicted in silico what he saw in the lab.

All along the way we’ve assembled an amazing team of scientists and engineers who continually push twoXAR’s technology forward, beyond my wildest imagination.

Today, I’m pleased to announce an exciting new milestone that will further shape our future. Andreessen Horowitz has led a $3.5M investment in twoXAR, along with the Stanford-StartX Fund and our visionary group of angel investors.

We will use these funds to grow our team, form new partnerships and further progress our drug candidates through preclinical studies. We are honored and pleased to have Andreessen Horowitz support our efforts. In addition to their investment, the team at Andreessen Horowitz, including our General Partner Vijay Pande, have signed up to help us with everything from recruiting to business development. It gives us great satisfaction to know we have a world-class organization standing behind us.

There are many more milestones, to be revealed on the road ahead. We look forward to sharing with you our success and discoveries along the way.

Let’s Augment, Not Automate

“Any sufficiently advanced technology is indistinguishable from magic.”

Science writer and futurist Arthur C. Clarke’s poignant “third law” only becomes more relevant as technological innovation accelerates and disciplines like computer science, data science and life science converge.

As we have been out in the field demonstrating the power of our technology platform to our collaborators, it has been interesting to hear their reactions when we tell them how it can
evaluate tens of thousands of drug candidates and identify their possible MOAs, evaluate chemical similarity, and screen for clinical evidence in minutes. These responses cover the gamut from, “Wow, this is going to revolutionize drug discovery!” to “this is magic, I don’t believe computers can do this…”

However, whether we are talking to the converted or the skeptical, as we get deeper into conversations about how our technology works, we come into agreement that using advanced data science techniques to analyze data about drug candidates is not magic. In fact, we’re doing what scientific researchers have always done – analyze data that arises from experiments. What’s different is that advances in statistical methods, our proprietary algorithms, and secure cloud computing enable us to do this orders of magnitude faster than by hand or with the naked eye.

The speed of our technology combined with the massive quantities of data that it processes, is simply enhancing the work that our collaborators have been doing in the lab for years. We believe that the most interesting and powerful new discoveries will arise at the intersection of open-minded life scientists combining their deep expertise with unbiased software.

Technologies like ours are meant to augment* the work of life scientists and help them accelerate drug discovery and fill clinical pipelines while leading society to a more robust and streamlined scientific process. Although DUMA might sound futuristic, today it is enabling therapeutic researchers to better leverage the value of their data and do it more rapidly than ever before.

Don’t believe the magic? Contact me and we’ll get a trial started to show you the science.

 

*Sidenote: I have been particularly interested in this interaction between humans and machines, which led me to a class at MIT called The [Technological] Singularity and Related Topics. One of those major topics was whether or not machines (including software) will replace aspects of society. One of my professors Erik Brynjolfsson, author of The Second Machine Age: stated that “We are racing with machines – let’s augment, not automate.”And we definitely share that view here at twoXAR.

Balancing Transparency and Protecting IP

The recent Theranos news has brought to mind the difficult balance between full technical transparency and protecting company IP. As co-founder of a company that has developed a technology that we believe will transform the drug discovery industry, I have struggled with how to best support our claims while protecting our trade secrets.

Early in our company history we thought about moving right from our computational drug predictions into animal studies without involving third parties. At the time, it seemed like the right idea. We could move quickly, reduce uncertainties and produce results in an efficient manner. We learned, however, that without anyone to validate our claims, it was difficult to develop the partnerships and raise the capital required to run these experiments.

Given these hurdles, we decided to  pursue a collaboration-based model. Today, we are working with scientists in academic and commercial biopharma labs who can validate our predictions independently without having any knowledge of our predictive algorithms. We do this by making computational predictions that are then compared to physical experiments made by our collaborators in the wet lab. As we continue to show that our computational predictions match the results they are generating independently in the wet lab, we build confidence in our technology while keeping our secret sauce under wraps.

While we feel that we’ve struck an appropriate balance for where we are today, we continue to think through the best ways to provide the right level of transparency for others to evaluate our claims. For us as scientists, it is important to have the feedback and input of the drug development community. We believe that it’s going to take more than just us to bring this new technology to market – we rely on our collaborators and partners to work with us in this regard.

We want to radically change the process of drug discovery, but, at the end of the day, we want to make sure we are able to do it without sacrificing our commitment to safety and efficacy through rigorous scientific validation.

Riding the Wave of Data Science and Biomed Convergence

In 1993, I decided that I wanted to launch a biotech company.* Since then, my friends and I have brainstormed biotech-driven solutions in toothpaste, paint, energy, and medicine.

22 years later I have realized this dream. The path was by no means direct.  But despite my sometimes seemingly random education and career path, I have found myself at the nucleolus of bioinnovation: the intersection of data science and biomedicine. Fortunately, my timing was impeccable.  Technology is rapidly changing the rules for the life sciences and, like the many industries that it has already touched, software is finally enabling business models in the life sciences to scale to new heights.

I have posted previously about how biopharmas are shifting the burden of innovation to venture investors and startups and how, even at the POTUS-level, that data science is being recognized as the future of life science and healthcare.

More and more, we are seeing exciting examples of how biopharma companies are embracing big data, or at least confirming to the world that they need it, and how investors and startups are diving in to fill the gap.

Big pharma buys into big data

We were recently invited to speak at an internal Sanofi symposium called Convergence of Science, Technology, & Data Sciences – Impact on Pharma. We presented alongside leaders in the space including: Isaac Kohane (Co-Director of Harvard Medical School’s Biomedical Informatics Department), Vikram Bajaj (Chief Scientist, Google Life Sciences), and Avi Ma’ayan (Professor, Pharmacology and Systems Therapeutics at Mount Sinai).

Frankly, I was pleasantly surprised to experience how open to innovation large pharma companies like Sanofi are; I was also excited by how enthusiastically they embraced the opportunity to explore how data science-driven approaches can augment the drug development process from discovery to clinical trials.

As #databio nerds, we were stoked by the interesting approaches others in the computational biology space were taking; from the business side, we were equally pleased to hear a very clear message best summarized by a quote from the former NIH Director and Sanofi President of R&D, Elias Zerhouni: “Big Data and the way we approach it is going to be determinant for the long-term success as an R&D Organization.

And this sentiment is being echoed throughout the industry:

“We have to build a data-analytics capability that we don’t have today. We’re also going to have to create partnerships and think about different types of people that we need to bring into our company so that we can take full advantage of that part of healthcare.”Joe Jimenez, CEO, Novartis

“Data will also help more efficiently develop medicines and better define which patients will most benefit.”  – Geno Germano, Group President, Global Innovative Pharma Business, Pfizer

“The [combined] role of health care and technology is going to be critical”Alex Gorsky, CEO, Johnson & Johnson

 An example of pharma action in this space recently is the doubling down on genomics. A number of large biopharma companies have publically announced their efforts to utilize big genomic data in both companion diagnostic and new drug development.

“Dramatic breakthroughs in understanding how the human genome functions are still in their infancy in terms of how they can be applied to drug discovery, but we can see their potential to transform the process. This is not an incremental change. We are aiming for transformative outcomes that could improve our ability to bring innovative and more effective new medicines to patients.”Lon Cardon, Senior Vice President of Alternative Discovery and Development at GSK

“The acquisition of Bina is a significant step for Roche to enable the promise of personalized healthcare by delivering the highest quality genomic data possible.”Dan Zabrowski, Head of Roche Sequencing

 Where there’s scale, there is VC…

a16z’s recent podcast, When Bio Meets Computer Science, discusses “how everything changes when software eats biology” and captures why life science businesses can now scale.

“These new startups have potential to have the kind of economics profile and the kind of financing needs of a software startup as compared to a pharma startup?

These new startups remind me a lot of software startups in 2005 when we see cloud computing start to realize. That’s sort of what we are starting to see now and because they have software at their heart, either literally or in terms of how they think about things, that they are organizing themselves in a cloud-like biology way, this would be very much on the Moore’s Law curve of things. And in a sense you could use this differentiate traditional biotech from this new crop of companies. That traditional biotech is governed by Eroom’s Law and these are governed much more by Moore’s Law”

Life science investors have questioned the value of platform companies in the recent past but the venture community is starting to warm up to them. VC’s recognize that the life science investment model of betting the farm on a potential billion dollar drug (unicorn drugs, anyone?) with a binary outcome is dying. Computation-driven platform companies coupled with the established CRO industry enable life science companies to look and act much more like software companies yielding stepwise, milestone-driven returns and valuations, with much smaller investments and shorter runways.

In a recent post on YC’s move in to the biotech realm, Atlas’ Bruce Booth commented:

“Although the math may be different, virtual biotechs doing drug discovery today are leveraging a similar trend: remove the heavy fixed costs of building out your own laboratory, purchasing expensive lab equipment, and then having to “feed” the system, and move to a lower cost virtual model of renting lab capabilities via a global network of CROs and collaborators. Others have already commented about the decreasing cost of DNA sequencing… but same holds for other aspects of drug discovery, like computer-aided drug design and structural biology. It’s easier to start a scientifically credible biotech today than ever before, and entrepreneurs can make real progress in validating a thesis on seed capital.”

Some examples of investments in the data science-driven drug development space today include Data Collective’s investments in Mousera and Atomwise and Atlas Venture Life Science’s investments in Nimbus Therapeutics and Numerate.

Software has enabled these dreams to become reality

I wish I was prescient enough in 1993 to have predicted the role of technology in transforming biopharma. Honestly, I was really just a kid eager to learn about biology and technology and explore the potential futuristic and off-the-wall applications. Applications that at the time seemed wacky, but today are becoming a reality.

At twoXAR, we use data science to accelerate the identification and validation of drug candidates for complex diseases. I hadn’t thought that this was possible until Andrew introduced me to the DUMA platform and demonstrated how, in minutes, we can identify new treatments for a disease. Since then we’ve translated our in silico results to the physical world and continue to do so through a growing list of exciting collaborations with commercial and academic discovery organizations.

Over the last 12 months, I have heard a variety of reactions to the speed and scalability that computational biology enables (and to the fact that both twoXAR founders are named Andrew Radin).  But, it’s clear that as software continues to penetrate all industries it will also keep altering the landscape of drug discovery and the life sciences. And, it’s refreshing to see executives and investors acknowledge the power of computation-based approaches and how they speed up discovery and validation of therapies and enable a new era of software-like scalability in the biopharmaceutical industry.

 

*feel free to ask me why!