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…
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.
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.
- 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.
- The only way of discovering the limits of the possible is to venture a little way past them into the impossible.
- 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”!
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 …
“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.
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.
Our first session at Stanford University’s StartX accelerator is coming to a close. It’s the perfect time to collect my thoughts on the top 10 things I learned at StartX these past months.
- Startups are hard
- Medical startups are even harder
- There’s torrential chaos behind every success story
- You know more than you think you know
- You know less than you think you know
- Evaluating the advice you receive is critical
- People will help you if you ask
- Grit is more valuable than intellect
- Grit without intellect is suicide
- There is always a way through
1. Startups are hard
A big part of the StartX experience is to share your stories with fellow founders. One of the key things you learn right away is that everyone, regardless of stage of funding and business, has big problems to solve. Funding. Customers. Traction. Recruiting. Competition. All of these things are amplified when you have limited resources and climbing uphill. Every day we are exposed to some of the brightest people on the planet, and I assure you, it’s hard for them too.
2. Medical startups are even harder
Having helped build three different consumer based internet startups, I was blissfully unaware of the extra burden that comes with a medical based startup. In consumer you build and deliver with no delay, and immediately get feedback on your work. Iterations are fast because you are directly connected to the end user. In the medical world you build and test, build and test, and then do some more building and testing. Despite shaving years of the drug discovery process, it will take quite some time before any of our work makes it into a human being. It’s why medical companies stay in StartX for two sessions, while other companies stay for one.
3. There’s torrential chaos behind every success story
The StartX community includes many serial entrepreneurs who share their stories. The outside world is exposed to the big exits, the signed deals and the brand-name VC investments. What the world doesn’t hear about is the twists and turns of deals gone bad, employees who need to be dismissed, or investors who push entrepreneurs in the wrong direction. The craziest story I’ve heard at StartX is from an entrepreneur who built a successful company only to have an unscrupulous contractor drain the bank account and walk away with all the cash.
4. You know more than you think you know
I was surprised to find how helpful I could be to other StartX companies. While I’m yet to be a part of a billion-dollar exit, my role as CTO in my prior startups gave me more experience and wisdom that I had previously recognized. Every StartX founder has deep expertise or experience in a wide array of disciplines. Some of the best advice we’ve gotten to date, on pitching and selling, has come from other founders in the session with us.
5. You know less than you think you know
Every day the StartX community fills another gap in our knowledge. We speculate on the future and what we think it will take to conclude a successful scientific experiment, close a deal, or raise money. The community here offers their shared experience and allows us to think about things we had never considered before. What we’ve learned about working deals in the pharmaceutical space has been pure gold.
6. Evaluating the advice you receive is critical
StartX puts you in front of people who advise you all the time. Sometimes this advice is solicited by us, other times we receive it without asking. What we find is that often the experts disagree on what is our best path forward. We need to decide which mentors we think are best aligned with our world, and which are off the mark. The process of choosing which advice to follow is often more important that getting the advice itself. In retrospect, we realize we have sometimes received misaligned or mistimed advice from highly successful people. It’s sometimes tough to filter that advice given the high-profiles of those who advise us.
7. People will help you if you ask
There is a culture of mutual assistance at StartX. Part of being a founder in the community is actively helping others while being open about asking for help yourself. We quickly learned this applies outside of the walls of StartX as well. We’ve received help from world-renowned professors, CEOs of billion dollar companies, and scientific leaders from around the world – simply by asking – often with nothing expected in return.
8. Grit is more valuable than intellect
We are exposed to over fifty companies here at StartX. The ones we see making the most progress are those that take multiple hits on the chin and keep moving. Startups are about endless mini-failures that can wear down anyone without resolve. The mental attitude that backs up a culture of perseverance is a key factor behind those that make it and those that evaporate.
9. Grit without intellect is suicide
It’s a challenge to put a pencil in one of my ears and pull it out of the other. That doesn’t mean it’s a challenge worth pursuing. Part of accepting mentorship is being able to admit that your plans aren’t going to work. It’s sometimes tough to let go of what your heart says to do and listen to your head.
10. There is always a way through
We admire our peer companies that hit what seems like an impenetrable wall, only to wiggle and worm and find a way to get through. We’ve learned that every challenge has a solution as long as you are signed up to find it. Sometimes you need to grit your teeth and climb the mountain. Sometimes the fastest path is to hike around the mountain. In very special cases you can eliminate the mountain all together,
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!
We recently had an article written about us over at Medtech Boston, how fun! Click the link to learn more: https://medtechboston.medstro.com/twoxar/
From the White House to medical education data science is being recognized as the future of life science and healthcare.
President Obama recently appointed Dr. DJ Patil (fellow USCD Alum!) as U.S. Chief Data Scientist. In his memo: Unleashing the Power of Data to Serve the American People Dr. Patil states, “The vast majority of existing data has been generated in the past few years, and today’s explosive pace of data growth is set to continue. In this setting, data science — the ability to extract knowledge and insights from large and complex data sets — is fundamentally important.” One of Dr. Patil’s priority areas is the Precision Medicine Initiative President Obama announced in January, which is great to see that medical data is recognized as a strong national interest. But a focus on data science isn’t just seen at a national policy level, it continues to permeate in startups, medical school, and biopharma.
Last Friday Andrew and I attended the MIT Sloan Bioinnovations Conference – He spoke on the Big Data, Policy, and Personalized Medicine panel with several other companies noted here and naturally, the conversation focused on the power of computation in this space and whether or not our vision of “Star Trek Medicine” (as one audience member put it) was soon to come. During the rest of the conference, topics ranged from Policy to Biomedical Research to Financial Engineering to Education and I was excited that a common theme that ran through each of the sessions was data science and how it’s changing the medical landscape.
One example includes Jaime Heywood’s ALS Therapy Development Institute/PatientsLikeMe who used mathematical algorithms to determine that ½ of the animal studies they were attempting to reproduce (n=50) of an ALS drug could not even possibly have been statistically significant prompting more rigorous studies. When describing how they initially approached this, Jaime stated very matter-of-factly, “This can be done with math.” The power of data science in the life science and healthcare space is also being recognized in medical education. Dr. Jeffrey Flier, dean of Harvard Medical School, states in a recent WSJ piece: “There is palpable excitement at the interface of biology, psychology, engineering, sensor technology, computation and therapeutics… …The opportunities are immense and consequential.”
I’ve heard similar sentiment from senior executives at biopharmaceutical companies that I have spoken to – that the future of drug discovery resides in the data (whether biological, chemical, clinical or otherwise) and the surrounding analytics that can reveal hidden insights. However, industry professionals also express that it’s not yet apparent how the data sciences will transform the industry – that is where startups have room to show them how.
The shift in the recognition of the importance of data science is clear and being seen across the spectrum of public and private sector in the medical space. At twoXAR, we are excited to be a part of enabling society to reach Star Trek heights in medicine faster, cheaper, and ultimately more accurate.