Positive Preclinical Proof-of-Concept Results For Liver Cancer Candidate, TXR-311

In September 2016, we announced a collaboration with the Asian Liver Center at Stanford University School of Medicine (the Asian Liver Center). The goal of this collaboration was to identify new drug candidates targeting hepatocellular carcinoma (HCC, the major form of adult liver cancer). Today, we announced a lead candidate, TXR-311, that has shown positive results in cell-based assays. I wanted to share a bit more background on liver cancer and details on why these results are exciting.

HCC is a primary cancer of the liver that tends to occur in patients with… 

READ THE FULL POST AT MEDIUM.COM

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

Inspiration from the TEDMED Stage

As with many of my fellow Americans, I have been reflecting about events that have been highlighted in 2016 in the media. Racial strife, gun violence and a polarizing political environment were repeated themes throughout the year. Over dinners and social events, the conversations with friends and family have been morose at times, as many are wondering if society is taking a turn for the worse.

I’m here to tell you that isn’t the case — there is a dedicated group of talented individuals working quietly to make the world a better place.

As a recent speaker at TEDMED 2016, I was fortunate enough to meet dozens of these inspiring pioneers and watch them on stage answering a question…

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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.

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.

Top 10 Things I Learned at StartX This Summer

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.

  1. Startups are hard
  2. Medical startups are even harder
  3. There’s torrential chaos behind every success story
  4. You know more than you think you know
  5. You know less than you think you know
  6. Evaluating the advice you receive is critical
  7. People will help you if you ask
  8. Grit is more valuable than intellect
  9. Grit without intellect is suicide
  10. 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,

Validating DUMA Independently

When independent scientific validation happens with new technologies it is an exciting time for both researcher and validator.

Some time ago we used our DUMA drug discovery platform to find new potential drug treatments for Parkinson’s disease. After processing over 25,000 drugs with our system, we identified a handful of promising candidates for further study. We noticed one of our highest ranked predictions was currently under study at an NIH Udall Center of Excellence in Parkinson’s Disease Research at Michigan State University.

We decided to be good citizens to the research community and provide our findings to the research team at Michigan State University. We prepared a 5-page PDF that summarized our computational prediction. When DUMA highly ranks a drug for efficacy it also provides the supporting evidence it used to make that prediction. This can include:

  • Calculated proteins of significant interest in the disease state,
  • How the drug interacts with those proteins or their binding neighbors,
  • Drugs with similar molecular substructures that have similar effects, and
  • Protective evidence found in clinical medical records.

We emailed our report to Dr. Tim Collier and figured that was the end of it. Much to our surprise we found ourselves on a phone call the next day with Tim and his colleague Dr. Katrina Paumier. Tim told us that we had independently validated work that had been going on for years.

As part of the review of the report, Tim and Katrina asked a number of questions on how we came up with the prediction we presented. We explained a bit about DUMA and how quickly it can be used to screen large databases of drugs and make predictions within a few minutes. They told us they had another promising drug under study and asked us to run it through DUMA. We returned the results on this new drug right away. It turned out this second candidate was highly predicted by DUMA to be effective in treating Parkinson’s disease. Once again our evidence matched their data, independently validating that they were on the right track with their second candidate.

Finally, Tim asked us to run one more drug through our system. He didn’t tell us much about this particular molecule, and we let DUMA process the data we collected on it. The prediction ranked this candidate relatively lower. We informed Tim that our system gave a low to moderate indication of efficacy, and supplied the evidence that DUMA had made to assign this ranking. This once again matched his own data about the compound.

Our work with Michigan State University continues today. We are working with Tim on providing new, novel compounds for further study. We have collaborated on combining the power of the DUMA drug discovery system with the expertise in Parkinson’s research labs.