Pear Biotech Bench to Business: insights on identifying new cancer targets, building a discovery pipeline, and growing as a CEO with Kevin Parker

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. 

How 3 PearX founders raised $3M+ each

Early-stage company building poses a unique set of challenges, and we’ve created what we believe to be the best accelerator out there for pre-seed founders. PearX is our exclusive, small batch, 14 week program. PearX alums have extremely high likelihood of startup success. In fact, 90% of our companies go on to raise a successful round from top tier investors and have cumulatively raised $2B in venture capital.

But don’t take our word for it – we spoke with 3 recent PearX alums about their experiences going through PearX, and what sets it apart from other programs:

Bobyard (PearX S23):

Bobyard automates the construction takeoff process with CV and NLP models to make cost estimates 10x faster while eliminating mistakes. After Demo Day, Bobyard raised a $3.5M round from Primary.

EarthXYZ (PearX S23):

EarthXYZ makes imaging hardware & analytics software to create & process the highest resolution hyperspectral data, using ML & genAI to deliver insights. They’re in the final stages of closing a sizable round; the only capital before this was their PearX check. 

Advex (PearX S23):

Advex works on synthetic data for vision, solving the biggest bottleneck for applied machine learning. After Demo Day, Advex raised $3M from Construct Capital, Emerson Collective, and Pear.

Answers have been edited for clarity and brevity. 

What did you learn from PearX? 

Bobyard: I learned what good looks like. I’m a solo founder and a first-time founder. I didn’t know how fast a team could move until I entered PearX. The structure of the cohort, working with companies that are in similar places as you, pushes you to go further. 

I also learned how important it is to deeply understand your customer and the value prop of your product. Ajay and Sean constantly pushed me to dive deeper into the customer psyche, discovering where my product could be worth a lot more.

Earth XYZ: During the accelerator, we nailed down customer discovery, understanding what our customers want from our technology and ironing out what we needed to build. After Demo Day, we got a ton of new customers — we juggled between supporting the customers while continuing to build on the technical side. 

Advex: During PearX, we went from having a potential customer to really fleshing out what our V0 was going to look like. We closed a real paying customer and since then, we’ve closed several more customers, raised the seed round, and grown our team to 5 people. 

What sets the Pear team apart? 

Bobyard: They have all bases covered. Pear knows the problems that most startups deal with, regardless of the vertical or the industry. 

Pear’s an order of magnitude smaller than the other accelerator programs out there, which means you get more than twice the attention, and you get support from a partner for each of the major categories. 

Earth XYZ: When I talk about Pear, the first thing that comes to mind is resources. I’ve heard friends who have gone through other accelerators where they receive a random firehose of generalistic knowledge. At Pear, I talked to dedicated partners 1:1 on specific strategies. 

How has Pear helped your company the most? 

Bobyard: I’d never fundraised before. Demo Day is a really special experience, but without structure and guidance towards preparing your presentation, it’s very difficult to pull off. 

The next thing is hiring. It’s pretty difficult to convince someone that’s better than you to work for you, but hiring a great team is so important to the company. I worked with Nate after the accelerator to hire the first founding engineers at Bobyard, and all of them turned out to be amazing. He helped me with the job descriptions, the interview rounds, what we should look for… it’s a lot of knowledge that accrues over many years of hiring for startups. 

Advex: As we’re now a seed stage company, we’ve really been leveraging the hiring help from Pear and it’s been a huge help. They’ve helped us understand how the job description should evolve over time, ensuring that we’re hiring the right person that we need for whatever the business needs are at the time. 

Describe Pear in 3 words:

Bobyard: 

Home— I spent all my waking hours in the Pear office during PearX. 

Support— the team believed in my vision and took a chance on me. 

Family— I work out of the Pear SF office now, and every day I see people from the Pear team. 

Advex: 

Grounding— they’ve helped us understand why our customers are reacting the way they are, given their previous experience. 

Flexible — helping us get what we need, whether it’s product or hiring. 

Friendly— they help us think about the past and the future, working on improving at all times and making good decisions moving forward. 

Any advice for early-stage founders? 

Bobyard: You should apply. When you do apply, don’t force yourself to be a founder you are not or a company you are not. Build conviction on the thing you’re building. 

Earth XYZ: If you’re a founder like me with deep tech, hard tech, or non-traditional software based companies, don’t be turned away from applying to PearX. Beyond software, Pear has a ton of expertise, and partners bring in their own network and resources. Early-stage building is company-agnostic in many ways, and the Pear team has a deep bench of expertise. 


Applications for PearX are due Wednesday, May 1. Apply today!

Welcoming Ana Leyva to the team!

Pear is thrilled to welcome Ana Leyva to our go-to-market team! Ana’s journey is a testament to her passion for the startup ecosystem, with past roles at tech unicorns Box, ServiceTitan, and Vanta. We’re so excited to have her onboard as part of our GTM team, offering her first-hand experience as a seasoned operator. 

In her short time with us, Ana has already supported over 30 Pear companies, strategizing with them on all things GTM. This includes many critical steps of sales like: nailing ICP, prospecting, customer discovery, messaging, and more. 

A Bay Area native, Ana is a first-generation college graduate from Princeton University and holds an MBA/MA in Education from Stanford. After graduating from Princeton, she joined Box pre-IPO at Series E. At Box, she was hooked on startup culture, especially the GTM and commercial arms. Following Box, she was an early sales hire at ServiceTitan and then, while at Stanford GSB, worked with Vanta to hone their early sales motion. Following business school, Ana became a founder and CEO herself with her ed-tech startup Lelu. Ana embodies the entrepreneurial spirit that Pear champions. 

“From early on, I saw both Mar and Pejman champion founders in a way that was genuine and authentic. That authenticity and commitment to being helpful is the backbone of Pear’s culture and makes it stand out in the sea of VCs.”

Ana was a Pear Fellow while at Stanford GSB, and we’re so excited to have her with us full time. She hosts Winning Wednesdays, a bi-weekly webinar series on GTM topics, and will continue to build out Pear’s GTM programming. 
Interested in connecting with Ana? Email her at ana@pear.vc.

Debunking common myths: what technical founders need to know about sales

As a technical founder, you’re no stranger to challenging assumptions and pushing boundaries. Yet, when it comes to sales, many technical founders fall prey to common myths and misconceptions about sales that can hinder their startup’s growth. Let’s debunk these myths and uncover the truth about sales:

1. Myth: A Good Product Will Sell Itself, so I don’t need to worry about sales: Especially from a technical point of view, it’s easy to believe that if you’ve built a great product, customers will come flocking. While a strong product is undoubtedly essential, it’s not enough to guarantee success. In reality, ideas are cheap, and execution is critical. Competitors will inevitably emerge, and without a solid sales strategy, your product will get lost in the noise– even if it’s better than the alternatives. Early sales are crucial for validating your idea, learning how to talk about it and gaining traction in the market. 

2. Myth: I Can’t Sell Because I’m Not “Salesy”: Many technical founders shy away from sales, believing it’s a skill reserved for natural-born salespeople. However, this couldn’t be further from the truth. In Geoffrey Moore’s “Crossing the Chasm,” he highlights the importance of early sales to tech enthusiasts – a group that technical founders are uniquely positioned to identify with and sell to. Your deep understanding of the product and its technical intricacies can be a powerful asset in connecting with early adopters. Sales isn’t about being pushy or overly charismatic; it’s about building relationships and solving problems. 

3. Myth: Sales Is a Necessary Evil: Some technical founders view sales as a necessary evil – something to be delegated while they focus on building a product-centered company. However, the best businesses understand that success lies in being customer-centric from the get-go. Sales and technical teams should work hand in hand throughout the lifetime of the company, both driven by a shared commitment to delivering value to customers. Interweaving the shared success of both teams early on fosters collaboration and ensures that the customer remains at the heart of every decision. Ultimately, the most successful companies recognize and appreciate the unique contributions that both technical and sales teams bring to the table.

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Technical founders must challenge traditional myths about the sales profession and recognize the pivotal role that sales will play in their startup’s success. A great product is just the beginning – it’s how you sell it that sets you apart. Embrace sales as a strategic imperative, leverage your technical expertise to connect with early adopters, and build a customer-centric organization from day one. By doing so, you’ll pave the way for sustainable growth and lasting success.

Want to know more about leading GTM as a technical founder? Check out our additional resources for technical founders here

Welcoming Hannah Berke to Pear!

We’re excited to announce that Hannah Berke joined Pear a few months ago as part of our Community + Operations team! A seasoned community leader, we can’t wait to have her on board, especially after our recent Pear Studio SF expansion. 

Born and raised in Chattanooga, Tennessee, Hannah was introduced to the Bay Area as an undergraduate at Stanford. As an undergrad, Hannah worked in technology integration and strategic communications at Amazon and MongoDB. She was also deeply involved in university life, serving in a number of different university offices, including the Board of Trustees, and community groups. “I learned the impact that a strong community can have on someone’s success— and that I was super passionate about creating those types of environments for people.” 

Hannah first encountered Pear through a classmate and friend who participated in PearX. She’d been hooked on startup culture ever since arriving at Stanford, and Pear’s founder-first approach stood out among VCs— “the mentality of giving before getting”. At Pear, Hannah now supports this goal, creating the community support founders need to build the best companies possible. 

“Mar and Pejman’s vision for a best-in-class ecosystem and community of tech builders is amazing, and I’m honored I get to be a part of bringing it to life.”

We’re thrilled to have Hannah on board. You can reach her at hannah@pear.vc.

Minimum Fundable Team: how early team shapes seed fundraising

My role at Pear is to directly support pre-seed founders that participate in PearX with their hiring needs. PearX is our hands-on, 14-week bootcamp designed to position founders to raise seed rounds from top tier investors. We’re experts at helping companies raise this capital; over 90% of PearX companies go on to raise capital from top investors.

We have found, that at early stage, the four largest themes driving an investor’s decision to invest in a company are:

  • Market
  • Product
  • Traction
  • Team

To successfully raise capital, you need all four to be great OR one or two to be exceptional

However, at pre-seed in particular, markets are difficult to size and product or traction are often still too early to measure with a high degree of conviction. For these reasons, investors will often place an outsized emphasis on the quality and completeness of the team when making an investment decision.

At Pear, we refer to the completeness of a team at this stage as Minimum Fundable Team or MFT.

Prior to raising a pre-seed or seed round, founders should ensure their MFT is a competitive advantage. We suggest that all founders ask the following three simple questions to determine the completeness of their team prior to raising:

1. Is someone on the team a deep subject matter expert with the market or product you’re building?
2. Has someone on the team built a successful product from zero? 
3. Do you have the right mix of skills across the team required to ship a quality product quickly? 

If the answer to any of the questions above is no, what steps need to be taken to fill in any gaps to achieve MFT? 

We believe that hiring is one of the best ways to do this quickly. 

One of the advantages of joining PearX is that helping founders achieve MFT is a core part of our offering. Over the last 12 months, I have worked with 30 different teams and helped fill over 25 roles. Each of these hires have played a critical role in helping those teams reach MFT and close a successful round of funding. 

If you take away one learning from this article, it’s that hiring plays one of the most critical roles in early stage fundraising. Founders who achieve MFT prior to fundraising will have a higher likelihood of success compared to those who don’t.

PearX: join the ranks of elite founders

The most elite founders walk through walls to build category-defining companies. They are unique individuals, who don’t come by very often. Having seeded and helped build companies like DoorDash, Dropbox, Vanta, Aurora Solar, Gusto, Guardant Health and Affinity from their earliest days, we know what these founders look like and what they need. We have developed PearX to partner and support the very best entrepreneurs at the very beginning of their journey to help them get to the next stage. 

We believe small cohorts of less than 20 teams give PearX companies a disproportionate advantage. As a result, 90% of our PearX alums go on to secure funding following our Demo Day. Pear’s unparalleled resources lead to these unrivaled results. Here are some of the things we offer to each PearX company.

  • Capital to build your company, your way: We invest between $250k and $2M in all PearX companies. We know that some founders only need a small amount of capital to ideate and other teams are in more cost-intensive verticals that require more funding. All companies are unique so we’ll work with you. 
  • Founder to founder: Work 1:1 with a partner who has been in your shoes and knows your industry. Our team has started and sold 10 companies to the likes of Cisco, Instacart, Plaid, and Zynga.
  • Join the best community: Entrepreneurship doesn’t have to be a lonely journey. Joining PearX means joining a community of like-minded founders. We kick off each cohort with Camp Pear: a 3-day retreat for the entire cohort to come together, learn key company building tactics, and get to know one another. Not only will you work alongside your PearX batch for 14+ weeks, but you’ll also have the wider PearX alumni network to lean on. 
  • Access Pear Studio: Everyone in PearX receives dedicated office space in Pear Studio SF, our 30,000 square foot state-of-the-art office space with standing desks, conference rooms, phone booths, and more. This space is completely free to you for the first 12 months.
  • Build a scalable sales motion: Our go-to-market team, Pepe and Ana, will guide you through the critical steps of sales: nailing ICP, prospecting, customer discovery, messaging, and more. 
  • Recruit the best talent: Our dedicated PearX Recruiter, Nate, will find your founding engineer, co-founder, or whatever critical hire your team needs. In the last two cohorts, Nate has hired 25 people for our PearX companies. Nate leads the full cycle of recruiting for your team – from sourcing to closing candidates. This is an unprecedented level of support for an accelerator, but that’s how much we believe that hiring impacts company building. Last batch, Nate hired an average of two people per PearX company.
  • Fundraise strategically: We help you raise additional capital when you’re ready. From perfecting the story and creating a pitch deck to creating a target investor list and negotiating and closing your round. In fact, 90% of companies that go through PearX raise capital from institutional investors.

Are you interested in joining our PearX S24 cohort? We’re actively looking for our next batch of founders, and we’d love to hear from you. Please apply at pear.vc/pearx!

Pear Biotech Bench to Business: insights on tackling solid tumors and navigating company creation with Shelley Force Aldred

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. 

Pear portfolio company BioAge Labs announces oversubscribed $170M Series D financing

Last week, Pear portfolio company BioAge Labs announced its $170M Series D round led by Sofinnova Investments, with participation from a strong syndicate of new investors including Longitude Capital, RA Capital, OrbiMed Advisors, RTW Investments, Eli Lilly, and Amgen, among others, in addition to many existing investors. 

To mark this occasion, we wanted to share more about Pear’s partnership with BioAge Labs and its co-founders, Kristen Fortney (CEO) and Eric Morgen (COO). 

Pear’s founders, Pejman and Mar, first met Kristen in 2015 through an introduction by another company founder associated with the Stanford Genome Technology Center. At that time, Kristen was a postdoc at Stanford in Professor Stuart Kim’s lab, where she studied the genetics of extreme human longevity. At the time, Kristen had published extensively in the space of genetics and longevity, but the company was merely an idea. She was pondering the question: could we use genetic information and new machine learning techniques to develop a therapy discovery platform for longevity? Kristen’s vision at the time was just as clear as it is today. 

That year, Pear invested in BioAge’s initial seed financing, and we have gone on to successively back BioAge at every subsequent round, including the Series D. 

As it’s not common for a seed-stage focused firm like ours to invest up until the Series D round, why have we continued to support BioAge?

Significant unmet need and large market opportunity in obesity and metabolic disease

The company’s lead drug program, azelaprag, addresses obesity and metabolic diseases. A staggering 40% of American adults are considered obese, and many suffer from a host of comorbidities including diabetes, heart disease, and stroke.

One of the most exciting recent medical advances has been the remarkable success of GLP-1 receptor agonist drugs in achieving dramatic weight loss in such patients, while still being generally safe and well tolerated.

With this drug class expected to eventually exceed $150 billion in sales annually, the top two developers, Eli Lilly and Novo Nordisk, have catapulted to become the first and second largest pharma companies by market capitalization (~$740B and $550B, respectively, as of mid-Feb. 2024). 

As impressive as GLP-1 drugs are, one downside is that they can result in suboptimal body composition, in that they lead to the loss of both fat and muscle. BioAge’s preclinical studies have shown that azelaprag, which is a first-in-class oral apelin receptor agonist, can enhance body composition when combined with a GLP-1 drug. In a Phase 1b study sponsored by BioAge, azelaprag prevented muscle deterioration and promoted muscle metabolism in healthy older volunteers at bedrest.

A second limitation is that oral GLP-1 drugs have so far lagged behind the injectable versions in efficacy. Of course, most patients would strongly prefer orally dosed medications over injectables. In BioAge’s preclinical studies, azelaprag combined with a GLP-1 drug has been shown to double the weight loss achieved by the GLP-1 drug alone. Because it can be orally administered and has been well tolerated, azelaprag in combination with an oral GLP-1 drug may help to close this efficacy gap.

Human-first target discovery platform enabled by multi-omic analysis of aging human cohorts 

BioAge didn’t initially begin with a focus on a lead therapeutic asset in obesity. In fact, BioAge started as a target discovery company within the longevity space, with the ambitious goal of understanding the biology of human aging in an effort to extend human lifespan and healthspan. 

Although the longevity field has recently attracted much attention and investment, not all therapeutic strategies pursued have been equally scientifically rigorous. Many approaches rely on attempting to translate into humans tantalizing life extension or rejuvenation effects obtained in model organisms with very short lifespans like nematodes and mice.

But the biology of aging differs dramatically across species, and BioAge’s unique strategy was to partner with special biobanks that collected and stored blood from cohorts of people from middle age until death and that retained associated health records. By deploying multi-omics (primarily proteomics) and AI to interrogate the factors correlating with healthy human aging, the company generated unique insights into particular therapeutic targets of interest. 

From this platform, one of the strongest targets that emerged was the peptide that azelaprag is designed to mimic – apelin. Exercise stimulates release of apelin from skeletal muscle into the blood, and in BioAge’s cohorts, middle-aged people with more apelin signaling were living longer, with better muscle function, and better brain function. Correspondingly, in mice, azelaprag protected elderly mice from muscle atrophy & preserved function in vivo

Strong leadership team, advisors, and partners

As one might imagine, the team at BioAge has grown and matured substantially since inception in 2015. The leadership team today has world-class experience across biopharma. And in pursuing its Phase 2 study of azelaprag in combination with Eli Lilly’s GLP-1/GIP drug tirzepatide (Zepbound), BioAge will receive support from Eli Lilly’s Chorus organization, including the supply of tirzepatide and clinical trial design and execution expertise.  

It’s certainly uncommon for a postdoc straight out of the lab to lead a therapeutics company until a Phase 2 clinical study. But as Kristen relayed during a fireside chat at our Pear office, she learned a lot about what she needed to know on the job progressively over time, and she was not afraid to surround herself with experts specializing in the many functional domains required to take a drug program from a target to the clinic. 

This dedication to continual self-improvement and learning has been a hallmark of the many strong founders that we are fortunate to back at Pear. We are grateful that Kristen is helping to guide the next generation of such founders as part of our Pear Biotech Industry Advisory Council.

Pear Biotech Industry Advisory Council

For these reasons, we remain excited to support BioAge Labs. We eagerly anticipate the results of its mid-stage clinical trials of azelaprag in obesity, as well as the development of additional programs nominated from its unique human aging target discovery platform. 

Pear Biotech Bench to Business: insights on the past, present, and future of synthetic biology with Dr. Jim Collins

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 Partner Eddie and Pear PhD Fellow Sarah Jones.

Today, we’re excited to share insights from our discussion with Dr. Jim Collins, Termeer Professor of Medical Engineering and Science at MIT. Jim is a member of the Harvard MIT Health Sciences Technology faculty, a founder of the Wyss Institute for Biologically Inspired Engineering at Harvard, and a member of the Broad Institute of MIT. His work has been recognized with numerous awards and honors over the course of his career, such as the MacArthur “Genius” Award and the Dickson Prize in Medicine.

Hailed as one of the key pioneers of synthetic biology, Dr. Collins has not only published numerous high-profile academic papers, but also has a track record of success as a founder and as an entrepreneur, co-founding companies such as Synlogic, Senti Biosciences, Sherlock Biosciences, Cellarity, and Phare Bio. If all that wasn’t enough, he’s even thrown the first pitch at a Boston Red Sox game. We were lucky to sit down and chat with Jim about his experiences and his perspective on the future of synthetic biology. 

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

Key takeaways:

1. At its conception, synthetic biology was simply a ‘bottom-up’ approach to molecular biology utilized by collaborative, interdisciplinary scientists. 

  • In the late 90’s, Jim’s focus in biology began to shift: rather than continuing to explore biology at the whole organism or tissue level, he found himself more excited about molecular-scale biology. After speaking with some bioengineering faculty members at Boston University who were interested in his background in physics and engineering, Jim was quickly invited to join the department. From there, his interest in designing and engineering natural networks and biological processes flourished. 
  • At that time, however, bioengineers weren’t yet able to reverse engineer biological systems and exert precise control at the molecular scale. He asked, 

Could we take a bottom-up approach to molecular biology? Could we build circuits from the ground up as ways to both test our physical and mathematical notions and also to create biotech capabilities?

  • Though it didn’t start out as a quest to launch a new scientific field, Jim’s work contributed heavily to what would become the foundation of synthetic biology. He noted the value in bringing together scientists with diverse backgrounds to work on the same problems; for example, neuroscience had greatly benefitted from the introduction of mathematical models to describe complex neural systems. In a similar way, physicists, mathematicians, and molecular biologists began to find themselves interested in the same sorts of complex biological questions that could not be answered by any one discipline alone. 
  • Jim also acknowledged that in the early days, the tools to engineer gene networks and molecular pathways did not exist, yet his team could envision a future in which gene networks could be described and designed using elegant mathematical models and a modular set of biological tools. This goal helped to propel synthetic biology into existence.

2. The ability to program genetic circuits marked the beginning of synthetic biology and allowed efforts within the field to quickly progress. 

  • One notable 1995 publication in Science authored by Lucy Shapiro and Harley McAdams that was titled ‘Circuit simulation of genetic networks’ helped to shape Jim’s efforts in programming genetic circuits. The paper explored parallels between electrical circuits and genetic circuits and used mathematical modeling to accurately describe the bacteriophage lambda lysis-lysogeny decision circuit. In this circuit, bacteriophages that have infected bacteria cells must decide whether they are going to kill the cell or remain dormant, sparing the cell’s life.
  • Such work helped to bridge the gap between bioengineering and molecular biology at a time when many bioengineers felt largely excluded from the world of molecular biology.
  • To prove that genetic engineering was possible, the Collins lab worked to develop a genetic toggle switch in the form of a synthetic, bi-stable regulatory genetic network that could be switched ‘on’ or ‘off’ by applying heat or a particular chemical stimuli. This is significant because researchers could now add well-defined genetic networks to cells in order to precisely control their behavior or output.
  • This work by Gardner et al. was published in 2000 in the prestigious scientific journal, Nature and was titled “Construction of a genetic toggle switch in Escherichia coli.” Interestingly, in the same issue of Nature, work by Mike Elowitz’s lab at Caltech also outlined the development of a synthetic gene circuit in E. coli. Their system, dubbed the ‘Repressilator,’ was also a regulatory network in which three feedback loops could oscillate over time and change the status of the cells. Basically, it was three genes in a ring where gene A could inhibit gene B, which could inhibit gene C, which could then inhibit gene A, creating an oscillatory network. 
  • This critical body of work and scientific discovery both demonstrated that genetic engineering was possible and highlighted tools and methods that could be used to modulate molecular systems. 

3. To expand the repertoire of synthetic biology, Jim has co-founded two companies, Synlogic and Senti Biosciences, that are aimed at targeting the gut microbiome and engineering the mammalian system.

  • While initial excitement for synthetic biology applications centered on biofuel generation, the small scale bioreactors were never a match for fossil fuel companies. The paradigm in synthetic biology started shifting away from biofuel generation in the early 2000s to focus on the microbiome and its role in human disease. 
  • As local venture capitalists approached Jim and asked about what could actually be done with synthetic biology, it became clear to Jim that there were two main directions he could pursue. 

One was…an opportunity to create a picks and shovels company in synthetic biology. So, coming to create additional components or capacity to address a broad range of indications and applications, be it biofuels, industrial applications, therapeutics. The second was that you could engineer microbes to be living therapeutics, and in some cases, living diagnostics.

  • Jim partnered with Tim Lu, his former student and eventual coworker at MIT, to start Synlogic. One early direction of Synlogic was tackling a rare genetic metabolic disorder, phenylketonuria (PKU), that causes the amino acid phenylalanine to build up in the body. The idea was that they could engineer a microbe that could break down this byproduct and thereby eliminate the negative effects of the disease. This approach relied on the ability of the synthetic biologist to directly harness and control cell behavior via genetic engineering. 
  • Synlogic is also working on enzymes that produce therapeutic molecules instead of degrading toxic ones. The company now has efforts in inflammatory bowel disease and Lyme disease and has partnered with Roche to advance its pipeline. 
  • By around 2015, synthetic biology had continued to grow as an academic discipline and had moved beyond microbes to mammalian cells. Jim had since moved his lab from Boston University to MIT, and it wasn’t long before he was once again collaborating with Tim Lu, this time to apply synthetic biology in a mammalian system. This marked the start of Senti Biosciences, a company aimed at creating ‘smart medicines’ using genetic circuits.

We began to consider the possibility that we could do a mammalian version of Synlogic. Could we begin to really advance the development of human cell therapy and gene therapy using synthetic genes and gene circuits to create smart medicines? Having therapeutics that could sense their environment, sense the disease state or sense the disease target and produce therapeutics in a meaningful, decision-making way… was an exciting notion.

4. Historically, a lack of support from the venture community and insufficient infrastructure have been challenges for the diagnostics space.

  • Another company Jim helped start, Sherlock Biosciences, also leverages synthetic biology but operates in the diagnostic space. Although the diagnostic space is a notoriously challenging one, Sherlock was founded with the goal of combining approaches from synthetic biology and CRISPR technology to develop next-generation molecular diagnostics for at-home tests.
  • While many of the companies started right before the COVID-19 pandemic ultimately didn’t make it long-term, the team at Sherlock was able to quickly pivot and develop a CRISPR-based COVID-19 diagnostic that gained FDA-approval in May 2020. Notably, this test was the very first FDA-approved CRISPR product. 
  • Jim explained that the difficulties facing a company trying to operate in the diagnostics space are twofold:
    • (1) there is a lack of infrastructure for things like at-home testing, point-of-care testing, or nucleic acid tests
    • (2) there is a general lack of support for diagnostic companies in the venture community
  • Diagnostics companies are essentially valued as a multiple of revenue. In contrast, therapeutic companies can be valued based on projections 10-20 years in the future without the requirement of existing revenue. Combine this with the fact that wins tend to be much larger in the therapeutics space, diagnostic discovery and development have largely been set to the side. 
  • While COVID-19 did help to bring interest to the sector, funding and infrastructure continue to limit breakthroughs in diagnostics. 

5. Desperate for new antibiotics: a combination of synthetic biology, Machine Learning (ML) and in silico modeling has so far been fruitful.

  • With a challenging funding landscape, antibiotics have also been long-neglected by VC and industry. Despite this, Jim’s team was able to secure funding through The Audacious Project, a philanthropic effort put together by TED to support their work in antibiotic discovery. The funded project involved developing deep learning based models that could both discover and design novel antibiotics against some of the world’s nastiest pathogens. In fact, the team found success when they discovered a very powerful antibiotic called halicin. 
  • Recently published in Nature, an article by the Collins lab highlights their continued efforts in the “Discovery of a structural class of antibiotics using explainable deep learning.” 
  • Jim stressed the urgency for new antibiotic development: the pipeline has been drying up, but the demand has only increased. Acquired antibiotic resistance is also a significant problem that hasn’t yet been resolved.
  • As new, powerful antibiotics are developed, they become the last-line of defense against the worst, most deadly pathogens. However, drugs used as a last-line of defense don’t make it off the shelves very often: this means that there is less financial motivation to develop particularly potent antibiotics. To address this, Jim noted that we are going to need a new financial model to sufficiently support research in this space.

6. Past the hype cycle: the synthetic biology of tomorrow.

  • The field has experienced its fair share of ups and downs. In speaking with Jim, it’s clear that the roller coaster of high expectations and disappointing failures has not diminished his excitement about the future of synthetic biology. 
  • In 2004, the initial hype cycle was centered on biofuels and their potential to replace fossil fuels. Unrealistic expectations combined with the high cost of biofuel production led to disappointment; people began to question whether or not synthetic biology could deliver. 
  • In the second hype cycle, bold claims and an attitude that synbio could solve every problem in the world led to yet another massive let-down and shift in attitude towards the field. 

I think the markets haven’t kept pace with the public statements that are being made by some of the high priests in the field. And that’s a shame. I do think synthetic biology will emerge as one of the dominant technologies of this century. Our ability to engineer biology gives us capabilities that can address many of the big challenges that we have. But it’s still going to take a lot of time, it’s still very hard to engineer biology, and biology is not yet an engineering discipline.

  • Successes in areas where biology still outcompetes chemistry have helped to put some points back on the board for synthetic biology. Increasing utilization in therapeutic development has leveraged the efficiency of biological systems and will help to pave the way for the next way of discoveries in the field. 
  • Technologies like cell-free systems also have Jim excited about the future of synthetic biology. 

Get to know Jim Collins: 

Early career and developing a passion for science: 

  • Jim comes from a family of engineers and mathematicians and has always found himself wanting to do science. Jim explained that when he was four years old, his dad was a part of a team that designed an altimeter for Apollo 11. 
  • Another seminal event that influenced Jim’s decision to become a scientist was the decline of his grandfather’s health after a series of strokes left him hemiplegic. After watching someone he loved not receive the care or have treatment options that could restore function, Jim was inspired to pursue biomedical engineering. 
  • Once he realized that he could interface with clinicians, entrepreneurs, and policy-makers as a professor, he realized that was the path for him.

Advice for early-stage founders:

  • Find a strong business team early on to help find market fit and to guide the development of your final product. Young scientists are not trained to be good CEO’s, and it’s often challenging to navigate these decisions if you don’t have the experience.
  • Make sure your strategy has a real market pull and is differentiated from other approaches.