Month: May 2024

Here at Pear, we specialize in backing companies at the pre-seed and seed stages, and we work closely with our founders to bring their breakthrough ideas, technologies, and businesses from 0 to 1. Because we are passionate about the journey from bench to business, we created this series to share stories from leaders in biotech and academia and to highlight the real-world impact of emerging life sciences research and technologies. This post was written by Pear PhD Fellow Sarah Jones.

Today, we’re excited to share insights from our discussion with Dr. Kevin Parker, CEO and co-founder of Cartography Biosciences. Kevin is a first-time founder working to identify new cancer immunotherapy targets and to make precision cancer treatment a reality. 

More about Kevin:

After receiving his bachelor’s degree in human development and regenerative medicine from Harvard, Kevin completed his PhD in just over four years in the lab of Prof. Howard Chang at Stanford. As a trailblazer and successful technical founder, Kevin has also been named to the Forbes 30 under 30 healthcare list and Endpoints 20 under 40 in biopharma. His scientific interests span immuno-oncology, genetics, precision medicine, and single-cell characterization methods. In 2020, he made the decision to take his work in the Chang lab from academia to industry and officially started Cartography Biosciences. 

If you prefer listening, here is the recording:

Key takeaways:

1. Most immuno-oncology drug discovery programs are focused on the exact same targets. Instead of racing toward these well-known targets, Kevin Parker and his team at Cartography are working to create a platform that unlocks new targets. 

• During his PhD training, Kevin realized that he was most passionate about working on projects that could have a direct impact on the lives of patients. While working in Prof. Howard Chang’s lab, he had the chance to join a collaborative project with Prof. Carl June’s lab at the University of Pennsylvania. 
• The goal of that project, which was published in the esteemed scientific journal Cell, was to understand why CD19-directed chimeric antigen receptor (CAR) T cell treatments for cancer had high rates of neurotoxicity. Essentially, CAR T cells are immune cells that have been modified to specifically target and kill cancer cells. However, CD19-targeted CAR T cell therapies can have negative effects on the brain and cause neurotoxicity.
• The team utilized a technology called single-cell RNA sequencing, or sc-RNAseq, to characterize the gene expression of individual cells in the brain. Ultimately, they were able to gain insight into CD19 expression and better understand what caused the neurotoxicity. 

That initial project where we looked at single-cell sequencing of the human brain made us appreciate how complex it was to really understand target biology and how important it was to be able to use tools like single-cell genomics to understand cell expression across the genome. Some of these ideas ended up percolating into the realization that we didn’t just need to be able to understand existing targets better, but we needed to find new targets that had better specificity.

• While cancer immunotherapies can be transformative for certain subsets of patients, the rate at which we are discovering new targets–and thus expanding the range of patients we can treat effectively–has slowed dramatically. In other words, we’re seeing a whole lot of new hammers being made, but not a lot of nails.
• The growing immuno-oncology landscape is now ripe with companies and pipelines that look increasingly similar to one another. 

Companies are competing against the same targets and the same patients, which is great for those patients, but it leaves a lot of patients behind.

• New target identification is not a simple task, but Kevin and his team have made it their mission to find novel ways of killing cancer cells and sparing healthy cells.
• To do this, they are mapping out every single cell in the healthy body and every cell in a patient’s tumor. They believe that this in-house data set holds the keys to unlocking new biological targets that are only found on cancer cells. 

The way that we do that is by building up this data set that encompasses effectively every major cell type across the body and every cell in a patient’s tumor so that you can go and kind of line up the genomic profiles of every single one of these populations and say, ‘okay, these are the cells I’m trying to target.’ Now, we can look at this from a data-driven, ground-up computational approach and [find] the most specific way to target them.’

2. Platform-based companies must strike a balance between building a strong platform and focusing on the advancement of a lead program or drug candidate. 

• Inherently baked into Cartography’s approach is a huge amount of data generation and analysis. Much like finding a needle in a haystack, new targets have to be identified and carefully characterized across all the healthy cells in the body to ensure drugs won’t have nasty, off-target effects. 
• For the first couple of years after the company’s creation, efforts were centered primarily around building up a robust data set that could feed their pipeline and serve as the basis for multiple lead programs. 

Now that we have [a strong data set], we found some targets that are really compelling, and we can focus on building those out in our pipeline.

• To overcome the technical challenges associated with new target identification, Kevin noted that access to high-quality primary viable tissue samples has been critical for them. However, it can take time to build necessary agreements and collaborations to gain access to these types of samples.  
• Kevin also acknowledged the value in balancing pipeline generation with platform development. While Cartography may be particularly adept at identifying new targets, it is also important to build programs around the targets they have the most confidence in.

We’ve got to build a pipeline if we believe in our targets, which we do… There’s this tradeoff between wanting to give [the platform] enough freedom to explore and make those serendipitous discoveries that we might not otherwise make, and wanting to actually do something with it and build a pipeline out of it.

• When identifying new targets and making decisions about which to pursue, it is also important to consider what patients will benefit most and what indications you are likely to have success in. 
• Hypothetically, Kevin explained that there’s no clear cut way to decide between a target that hits 60% of patients 40% well and a target that hits 40% of patients 60% well. 

There’s no right answer to that. It’s something that every company has to wrestle with and figure out for themselves. For us, the general approach is to first pick an indication where we want to make a difference and where we think we can make a difference.

3. It is becoming increasingly common to see companies leverage both wet and dry lab approaches to increase the pace of scientific discovery. One of Cartography’s distinct advantages is its ‘dampness,’ or its blurred lines between its wet and dry lab efforts.

• Kevin shared that one of his main priorities as CEO is bringing in people who can play in both worlds and conduct research in both the wet and dry lab. They have a certain level of ‘dampness.’
• Instead of having a wet lab team focused only on biology and a dry lab team focused only on computation, it’s important to allow both teams to interface and work closely with one another. 

We’ve actually been merging those teams closer over time… Because there is a lot [of overlap] between them, they have to work together, sync their timelines, and work together as a group.”

• It’s no secret that an early-stage technical founder has to wear a lot of hats and fulfill many different roles. Hiring is one crucial job that comes into play extremely early on. 
• Many employees specialize either in wet lab techniques like single-cell sequencing or in dry lab computation; however, Kevin notes that he specifically looks for scientists who have a breadth of training and experience and can operate at multiple levels in the discovery process. 
• This helps to create a feedback loop and speed up the overall rate of target identification. Though, making good hires is often easier said than done and is more of an art than a science. 

The major thing that I try to look for and think about is to understand what the person that I’m talking to is trying to solve for… To what extent are they solving for a salary or a job title? Do they only want to manage people or do bench science? Of course they want to grow in their career, but their goal should be to make the company successful irrespective of what it is [they] need to do or need to change.

4. Though a lack of previous experience can be challenging, being a technical founder can be a very rewarding experience. 

• Many aspects of company-building can be daunting to new founders, particularly technical founders. Getting your PhD doesn’t necessarily prepare you for the numerous roles and responsibilities a CEO and founder must fulfill. 
• However, in the early days, Kevin explained that the ability to dig deep, ask questions, and interface with the science is incredibly important in deciding how the company should move forward. 

I think that [being a technical founder] gives you an ability to really understand what is working and what isn’t working… You can only really do that as well as you possibly can if you can understand the technical details and can go into the weeds there.

• One thing that helps keep Kevin grounded is the fact that most CEOs are first-time CEOs: even people who have worked in industry for 15-20 years most likely haven’t been a CEO either. 
• This point was solidified for Kevin when he went to a conference and was in a room full of other founders. They were asked to raise their hands if they were first-time CEOs, and about two thirds of the audience’s hands went up. 
• Even though it might seem like an uphill battle, it can be helpful to surround yourself with other CEOs who might be one or two steps ahead of you in their career who can provide advice and mentorship. 

I feel very fortunate to be able to go on the journey. I think that being a technical founder gives you a lot of advantages. It also gives you a lot to learn.

Advice for early-stage founders: 

• Hiring good people quickly becomes job #1 as an early-stage CEO. 
• As you go through the hiring process, take the time to understand what someone’s goals and mindset are. It’s important to find alignment and find people willing to put the company’s priorities first.
• Don’t forget that most CEOs are first-time CEOs.
• While you might wear a lot of different hats in the very early days, it is important to grow into the CEO role and learn to manage and lead your team.
• Build your network intentionally and thoughtfully.
• Find yourself a personal advisory board of people who have walked in your shoes – other CEOs a few steps ahead who can provide invaluable insight and mentorship.