Can you provide a brief overview of SPARK and the key reasons for the organization’s establishment in 2006?

Spark was initially established by my co-director Daria Mochly-Rosen, who is a professor of chemical and systems biology at Stanford University. In the early 2000s, Daria obtained promising research results which indicated that giving a drug at the time of a heart attack can reduce the gravity of the heart attack. Her aim was then to make this discovery available to patients, which proved to be a difficult process. There is a disconnect between the level of research we do in academia and the de-risked level of projects that investors are interested in. Daria approached big pharma companies to advance her project further but had no success. Then one of her graduate students suggested they establish a start-up company around this drug. They met with various venture capital groups for the next 18 months, while adding to their research and de-risking the project by implementing feedback from the industry. They eventually found a group of venture capitalists willing to lead in founding a company, KAI Pharmaceuticals.  

KAI was originally founded based on advancing the heart attack project, as well as Daria’s platform in protein kinase C (PKC) modulators. While these projects ultimately did not move forward, a third project based on a peptide therapeutic to treat patients with secondary hyperparathyroidism who have kidney failure and are on dialysis did move forward.  KAI was acquired by Amgen and the drug became FDA- and EMA-approved.

When Daria returned to Stanford after serving as the KAI Chief Science Officer, she was offered the position of Senior Associate Dean of Research at the medical school. She decided that this was a good way through which to address the disconnect between academic research and industry. This was the genesis of SPARK. Given our academic and industry experience, we understand the motivators at the academic institutions as well as in the commercial sector. We have benefited greatly from the local biotech ecosystem – SPARK has more than 100 volunteer collaborators, including healthcare investors biotech executives involved in trying to bring promising ideas to the table and get drugs commercialized and to the market.  

Since 2006, what has been the evolution of SPARK’s therapeutic focus areas?  

Initially, SPARK was focused on diagnostics as well as therapeutics. One of the main evolutions came when Stanford reapplied for an NIH  Clinical and Translation Science Award in 2012 and created a new program to focus exclusively on diagnostics. We now primarily focus on therapeutics and will only occasionally take on diagnostic projects.

In the therapeutic space, we were initially involved with small molecule development, which still remains a major focus of SPARK. Over the years, we have gradually added antibody therapeutics, protein therapeutics, vaccines, gene therapeutics and nucleic acid therapeutics to our portfolio, and we have moved all the way into genomically-modified stem cell therapies. The program is at a stage where we define therapeutics very broadly. Roughly 20% of what we do is in the oncology space and approximately a third of our work is in pediatric diseases. SPARK is a not-for-profit entity, and from the beginning we wanted to focus on undervalued therapeutics such as those for children and the developing world. Our selection criteria include the following: 1) the proposed product addresses a serious unmet medical need, 2) the approach is novel, and 3) the product is feasible for development and commercialization at scale.     

What are the drivers for SPARK’s areas of focus?

SPARK does not really consider financial return; our focus is on patient need. We are fortunate that as a nonprofit institution, we do not have to focus on commercial return, which is something the industry needs to keep in mind at all times. Thus, we can take on projects for very rare diseases or for the developing world that  traditional pharma might not be interested in. 

SPARK’s success rate of discoveries for commercial and in-clinic applications has continuously remained high. How does SPARK support its students and faculty to facilitate these rates?

We define success as either a hand-off to a commercial partner or bringing a project into the clinic ourselves. Through 2017, approximately 50% of the projects that came through SPARK were licensed to a commercial partner, and at least half of these projects were going into clinical studies. Another 10% of the projects were brought into the clinic at Stanford’s. Our aim is to continue to keep the success rate of projects above 50%.

A SPARK team is typically led by a faculty member and a graduate student or postdoctoral fellow, who will attend meetings and seminars and represent the team. We require that teams present a quarterly progress report on what they were trying to accomplish, what they successfully accomplished and what they still need help with. At these seminars, our advisors provide exceptional feedback and advice to help the projects continue to progress. We also have three project managers working with the teams to establish if the projects are on track and, if not, where guidance and assistance are needed.

What demands, in terms of new therapeutics, does SPARK see from a patient perspective?

From a patient perspective, there is still a significant amount of unmet need. SPARK has a number of projects, still in their early stages, looking at the unmet needs in the neurologic diseases and cancer space. We define unmet need fairly broadly, as there is no shortage of needs to be defined. Often, we will have basic researchers come in with novel discoveries that are fundamental to physiology and disease. We will then introduce them to clinicians to help brainstorm what the best therapeutic application would be. Sometimes, our investigators are physician scientists who look have identified specific targets tied to their clinical expertise.

Every two years, we teach a course on drug discovery and development for graduate students. During this course, we will select a therapeutic area to focus on and set a goal for the students to conceive of a therapeutic for an indication within the focus area. The students have to identify unmet needs and we will then select projects to further during the second quarter of the course. Approximately one third of these projects are licensed, which is not bad for an extracurricular student project.    

What are the key milestones for SPARK over the coming two to three years?

One key milestone is to establish a more robust funding strategy. Our current funding comes from the dean of our medical school, the Maternal and Child Health Research Institute, and various NIH grants and foundations; and we are very grateful for this support. Nonetheless, it is a yearly challenge to collect enough funding to support all of our projects. We have to start thinking about new models to fund new our novel therapeutics. For example, new drug development is almost exclusively in the realm of the for-profit sector, but there are potential therapies that will provide immense benefit to patients that are not going to be profitable. We want to continue to fund projects which are going to improve patient outcomes, even if they will not be taken up by the commercial sector. SPARK is very open to industry partnerships to advance our projects and programs, but we are not be able to take funding from commercial industry players with strings attached.   

We have established a global SPARK network with programs in Japan, Taiwan, Singapore, Australia, North and South America, Finland, Germany and Norway. The aim is to increase the collaboration between these various SPARK programs so that we become bigger than the sum of our parts and find more synergies. Bringing the global SPARK network together to be more efficient in what we are doing would be a major milestone for the program. We also have initiatives to apply new tools, such as machine learning, informatics, and ‘omics early in the process in the hope of improving efficiency and success rates in our drug discovery and development efforts.