Author: jill

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. 

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. Shelley Force Aldred, CEO and co-founder of Rondo Therapeutics. Shelley is a serial founder and prominent figure in the antibody drug development space. 

More about Shelley:

Shelley earned a Ph.D. in genetics from Stanford where she worked on the human genome and ENCODE projects in the lab of Rick Myers. She spun her first company SwitchGear Genomics out of Stanford in 2006 with a grad school colleague who has since become her long-term business partner. After selling SwitchGear in 2013, Shelley shifted her focus from producing genomics tools to developing therapeutics: she helped build TeneoBio from the ground up, leading preclinical development of the company’s T-cell engager platform for treating liquid tumors, a platform that has generated $1.5 billion in upfront payments to date from multiple big pharmas. Shelley then moved on to start yet another company, Rondo Therapeutics, where she currently serves as CEO. There, she leads a team that develops innovative therapeutic antibodies for the treatment of solid tumors.

If you prefer listening, here’s a link to the recording!

Key takeaways:

1. The therapeutic window in immuno-oncology is narrow: tuning the immune system in the case of solid tumor treatment can be like playing with fire. To overcome this, Rondo has focused on using bispecific antibodies to find the ‘Goldilocks’ zone between efficacy and toxicity.

• Previously at Teneobio, Shelley spearheaded efforts in preclinical development of immune cell engaging antibodies for liquid tumors. However, the lessons they learned and the molecules they developed couldn’t make a dent in solid tumors. Wanting to attack this problem head-on, Shelley and her long-time colleague Nathan Trinklein made the decision to start Rondo Therapeutics. 
• One characteristic behavior of solid tumors that makes them particularly difficult to treat is their ability to trick the immune system into thinking they aren’t a threat. To combat this, Rondo is creating immuno-oncological therapies that can re-activate the immune cells that reside in the tumor microenvironment. 
• Rondo’s efforts have been focused on the development of bispecific antibodies which are Y-shaped molecules with two arms that each can grab on and bind to different substrates. Rondo engineers these antibodies so that one arm recognizes and binds to proteins on the tumor cells while the other arm grabs onto immune cells. This brings the cells into close proximity so that the immune cells can recognize and kill the cancer cells. 
• Shelley noted that other strategies such as checkpoint inhibitors and antibody drug conjugates often lack efficacy in solid tumors. In addition, CAR-T and other cell therapies have shown some promising preliminary results, but they can’t be administered in an off-the-shelf manner and are difficult to scale up.

Where we felt like we fit is as an off-the-shelf solution to driving tumor and immune cell engagement in a way that’s targeted specifically to the location of the tumor and isn’t body wide.

• However, modulating the immune response is no easy feat. If pushed too far, the immune cells can start to attack healthy cells and tissues elsewhere in the both. Rondo’s cutting-edge bispecific antibodies ‘thread the needle’ and strike a balance between sparing healthy cells and killing tumor cells. Shelley noted that Rondo has been making steady progress in preclinical development and plans to be in the clinic in 2025. 

I think within other kinds of immune cell-engaging bispecifics, what we have a reputation for and are really good at is tuning and finding the Goldilocks zone. So, we’re going to be best in class in terms of this therapeutic window.

2. The ability to pivot and change directions is critical; one of Shelley’s strengths is her ability to follow the science and rely on the advice of her team. 

• Being a founding member of three companies is quite an accomplishment. Shelley explained that joining a new company and growing it from the ground up is simultaneously an incredible opportunity and a ‘trial by fire.’ One of the advantages of working in a small start-up is the chance to take on roles that you might not otherwise have access to. 

[In a smaller company], you get to see more pieces than you would in a larger company. Inherently, when you’re in a group of only 10 or 20 people, there’s so much more visibility into what’s happening in other groups or in other people’s responsibility spheres. It’s really hard to get that in a larger company.

• Each member within a smaller team has more responsibility in guiding the company and achieving critical milestones. Early founders and employees have to wear a lot of different hats to solve problems and ultimately push the company forward.
• For example, Shelley noted that she had to spend a lot of time thinking not only about the science, but also about choosing the right targets and indications to pursue.

Part of that is staying humble and realizing you might not always be choosing the right targets on the first pass. We do high-throughput genomic space discovery, and so we always have a lot of targets in the mix; we have our lead program, but we also have backup programs. Particularly in this field, targets can go cold really quickly, depending on clinical results that are coming out from other companies.

• Shelley also emphasized the importance of finding those who are willing to ride the roller-coaster with you. Bringing in experts and team members with different strengths can help keep the company agile. There are many reasons why a pivot might be necessary, and it is important to be willing to follow the science and the market. 
• Even at Switchgear, the first company Shelley founded, an early pivot led to their eventual success and acquisition. In the initial view for the company, they anticipated having a small number of customers placing very large orders. However, it turned out that the market was asking that they have thousands of customers, each placing small orders through an e-commerce platform. By being willing to change their vision, the company ended up being extremely successful.

3. Your team is your most valuable resource, especially early on in company creation, and it’s important to surround yourself with a supportive community and a team you fully trust. 

• It’s not a coincidence that Shelley found herself working alongside Nathan Trinklein at three of her companies – Switchgear, Teneobio, and Rondo. After running operations at Switchgear and overseeing its acquisition, the pair found themselves wanting to transition to therapeutics to get closer to patients and into a bigger market. 

Company building is a heavy lift, and being able to do that with someone with great capability that I trust deeply has increased my enjoyment of doing this quite a bit. But I also think it’s increased our likelihood of success at every step: we both have deep respect for each other and enough confidence that we just push on each other all the time. I mean, there’s constant pressure testing of ideas and conclusions. And I think what comes out the other side is always better than it would have been if only one of our brains was attacking it.

• Another important relationship that needs to be established early on is between the founding team and the investor syndicate. Ideally, early-stage companies will have the opportunity to choose investors that support their long-term vision for the company – though the funding environment will likely determine exactly how much of a choice a founder has.
• At Rondo, Shelley prioritized investors who were deeply versed in therapeutics and understood the relevant risks and timelines for milestones. Biotech tends to move at a slower pace, and finding firms that understand this can make a huge difference in the long run.

I am grateful for my current funding syndicate at Rondo… they are all really experienced therapeutics investors, and this is important because it means they have realistic expectations about what we’re going to be able to achieve on what timelines and what amount of capital this is going to take. It also means that their deep expertise and their networks help support us quite a bit.

4. It’s not a secret that starting a company is hard, but Shelley highlights a few ways she stays motivated. Explaining that she prioritizes bringing high quality talent into her companies, she says it’s a good thing to ‘feel a little bit stupid, at least once a day.’ Being challenged to do better and learn more is one of her favorite things about the job. 

• Looking back over the summation of her experience as an operator, CEO, and co-founder, Shelley acknowledged that she grew and learned a lot about herself, “realizing with the exquisite mix of joy and pain that is starting a company, it was indeed the right place for me.” 
• Her motivation comes from keeping herself always on the steep phase of the learning curve. Instead of focusing on what she doesn’t know or isn’t able to do, she pushes herself to learn constantly from her team and to bring in people who are experts in their roles. 
• Not only does Shelley spend a lot of time recruiting and finding good employees, she also spends a considerable amount of time finding community within the broader biotech ecosystem to help keep her motivated.

We all fight different battles in our professional careers… and my network of other entrepreneurs has kept me afloat during a fundraising process when you’ve gotten a 50th no and you’re not sure you can get up and do it again. Talking to someone who’s been there and says, ‘I know you can get up to pitch number 51,’ is really important.

• Shelley also explained the importance of finding people with shared experiences who can support you. While she enjoys challenging herself and pushing her limits, she also gives credit to her network and support system for keeping her grounded. For example, she regularly meets with her group of women biotech CEOs, and she’s found a sisterhood of women through her HiPower women’s group where she serves as an executive member.

These groups of women have been life-saving, sanity-saving in 100 different ways: primarily because they know exactly what it feels like to operate in shoes just like mine. So whatever battles you are fighting, finding people who have fought similar battles is really important.

5. Not all technical founders make great, long-term CEOs. However, with commitment to leadership development and a willingness to learn on the go, Shelley has shown that it’s possible to grow into the role and successfully lead a company.

• Depending on the company structure, size, sector, and investor preference, there are a number of reasons founder-CEOs may not stay at the helm of their company long-term. However, Shelley has shown that technical founders, with the right experiences and mindset, can be effective leaders. 
• While Shelley did admit to having a propensity for leadership growing up, she has made the conscious decision to invest in her own development: she reads countless books, has an executive coach, a therapist, and a willingness to apologize for her mistakes. Her humility and compassion also foster a positive team culture at Rondo. 

What I’ve tried to do is own those mistakes, apologize, … and do better later. I think that people are really wonderful and supportive when you say, ‘you’re in a learning process, you can have some compassion for me, as I’m learning to be a better leader. Just like I will have compassion for you.’ It’s like you’re learning to do your job better, and it’s really opened the gates to excellent feedback.

• Before stepping into her role as CEO, Shelley gained invaluable experience in operational positions as a founding team member of Switchgear and Teneobio. When asked about her decision to take the CEO role at Rondo, Shelley explained that she had always known she wanted to get a chance at the job and put herself in a position to take that opportunity. 
• When it comes to particular skills that have helped her to be an effective CEO, she explains that her strength isn’t in one particular area she excels at; instead, she is a jack of all trades.

I’m not off the charts in any one particular area, I think my advantage is that I’m good at a lot of things. So like I said, I’m a good scientist, I’m a good operator, I’m good at managing finances, I have a pretty natural sense of managing people, and I can kind of put all these things together. I think I also am good at synthesizing information that I get from a lot of different places, I’m willing to make hard decisions, and I have a pretty high risk tolerance.

Getting to know Shelley:

In her free time, Shelley likes to travel and is a voracious reader, with a particular affinity for mystery or detective novels or historical fiction. One thing people are surprised to learn about her is that she can drive a boat much better than she can drive a car because she grew up water skiing and boating regularly with her family. 

Some advice she would give someone looking to follow in her career footsteps would be to create your own opportunities and to not waste time being miserable in your work. She noted that even in your best jobs, not every day will be a good one. However, she said if you regularly wake up and dread going to work, it’s okay to look for something else.