[L-R] Cartography Biosciences co-founders Howard Chang, MD, PhD, of Stanford University; Kevin Parker, PhD, the company’s CEO; and Ansu Satpathy, MD, PhD. Cartography is working to create the first-ever comprehensive atlas of antigens that can serve as targets for cancer immunotherapies—making them more precise and thus, it reasons, more effective. [Cartography Biosciences]

Like Ptolemy, whose pioneering map of the earth was referenced for more than a millennium, Cartography Biosciences aims to blaze a trail in mapping of a different sort.

The developer of precision therapeutics is working to create the first-ever comprehensive atlas of antigens that can serve as targets for cancer immunotherapies—making them more precise and thus, it reasons, more effective.

Cartography says it can accelerate that task with the $57 million in combined seed and Series A financing it received over the summer. Proceeds from the financing are intended toward advancing the company’s pipeline of therapeutics designed to broaden the reach of next-generation cancer therapies, as well as conducting discovery programs to identify novel, best-in-class target antigens across cancer indications.

The company isn’t saying much about the size or focus of that pipeline, or the targets it has identified. And it isn’t quantifying beyond “multiple” what targets it has found.

“We already have and expect to have more targets than we ourselves can pursue,” Cartography CEO Kevin Parker, PhD, told GEN Edge. Cartography plans to partner with other companies what it cannot develop in-house.

Parker did say, however, that Cartography is interested in both liquid and solid tumors: “We’re going after where there’s unmet need for patients.”

“I think the field as a whole is kind of an infancy here because it’s the new way of mapping and classifying cancers, but we’re excited to really push this forward, and be a leader in this space,” Parker said.

Cartography aims to map out a cell-by-cell atlas that identifies optimal antigens for cancer immunotherapies by predicting both efficacy and off-target effects for binders against a given target. To do that, the company has developed a platform intended to create detailed annotations of cell profiles by combining computational and experimental techniques—including single-cell genomics, proteomics—with high-throughput binder discovery methods.

“We’ve really made a lot of progress here,” Parker said. “We have an understanding of every cell type in the body, what’s expressed where across hundreds of different cell types in the body. We’ve pored over millions of cells across thousands of samples from cancerous and healthy tissue already, and many, many more to come that are in process over the course of the next set of years.”

Different approach

By studying antigen expression, Cartography’s platform differs from past approaches to precision immuno-oncology, which have been based on histology or genetic mutations.

“If you think about how immunotherapies work, there’s basically two parts: the drug part and the targeting part. The drug part can be a T cell, it can be an antibody drug conjugate. Then, you target it with the receptor antibody. The way that that drug knows where to go in the body is where the antibody binds, and that’s basically what antigen the antibody is directed against,” Parker explained. “Essentially, the question of how things become precise is based on where the antigen is expressed. And that’s really why you have to profile cancers by antigen expression.”

Cartography, he continued, works to improve the effectiveness of immunotherapies so that they find targets faster, and kill more tumor cells when targets are found.

“A lot of the immunotherapy we have that have had some mixed successes and some toxicity. You can imagine, basically throwing a dart at a dartboard and hit the tumor. And sometimes you hit it and sometimes you don’t,” Parker said. “Because of that, you’ve got two problems: Both the patient has toxicities but also you can’t ramp up the efficacy because you’re limited by those toxicities.”

“If you can actually go and every time you throw the dart it hits the patient’s tumor, you’re very precise there, and you can basically ramp up efficacy and the potency of that drug. And you minimize the side effects,” Parker added. “You get both of those two things together, efficacy and toxicity, and that’s how you get that drug to be really precise and really potent for that patient.”

While the company has set its sights on fighting cancer, Parker said, “We’re thinking about other areas down the road. There’s autoimmune possibilities, there’s other aspects you can imagine. But there’s a lot to oncology, and we’re really focused there for now.”

Beyond the usual suspects

One area where Cartography hopes to play a key role is finding targets beyond the usual suspects in immuno-oncology, such as CD19, CD20, CD22, and BCMA.

“All of those were identified in cancer decades ago, and we keep going back to them and keep trying to engineer little tweaks here and there. But we haven’t invested in the tools to find new antigens to go after, so that’s really bottlenecked the field,” Parker observed. “It’s limited the success of the therapies that we have, and also limited the patients we can treat, because they only represent a few percent of the patient population.”

[Estimates for response rates have ranged from 12.48% as of 2018, according to a study published in JAMA Network Open, to between 20% and 50% according to Johns Hopkins Medicine, which adds that only “15%-20% of patients achieve durable results.”]

“There’s a problem of our field’s pipeline; we’re massively concentrated on a few targets,” Parker lamented. “1) we need better targets. And 2) people aren’t doing this. People aren’t building the tools out because it’s hard. There’s a lot of infrastructure, a lot of analysis methods. You need to be able to get samples. But the field isn’t working on finding better targets, so somebody’s got to do it.”

“That’s why we felt like we needed to start there. If we’re going to make better therapies, we need to start with that first platform, to identify the right antigens to go after,” Parker said.

He says Cartography’s ability to build molecular and computational tools in-house will make the company stand out in antigen discovery.

Antigen mapping vs. cancer

Two recent studies have reported on new antigen mapping approaches developed with cancer fighting in mind.

On Monday, a team led by Polly M. Fordyce, PhD, an Institute scholar at Stanford University’s Sarafan ChEM-H (Chemistry, Engineering, and Medicine for Human Health), published a study in Nature Methods detailing their new method designed to faster and more accurately predict which antigens will generate a strong immune response, and thus help develop more effective cancer immunotherapies. In February, researchers at Lund University in Sweden published findings in PNAS about their approach to mapping the whole cell surface tumor antigen landscape in patients, designed to enabling direct analysis of all accessible cell surface tumor antigens in tumor tissue.

Cartography aims to commercialize technology developed by Parker and two co-founders. As a PhD student at Stanford, Parker worked in the lab of Howard Chang, MD, PhD, carrying out research focused on functional genomics, computational biology, and immunology. Chang’s lab collaborated with the lab of Ansu Satpathy, MD, PhD, who joined Parker and Chang in establishing the company at the end of 2014.

Both Chang’s and Satpathy’s labs partnered with other researchers at Stanford as well as the University of Pennsylvania, where the Stanford investigators worked with research teams led by Joseph A. Fraietta, PhD, and CAR-T pioneer Carl June, MD. June leads Cartography’s Scientific Advisory Board, whose members include Fraietta as well as Emma Lundberg, PhD, of Stanford, and Angela Shen, MD, MBA, of Mass General Brigham.

Cartography’s founding scientific team includes:

  • Caleb Lareau, PhD, who leads the company’s Platform Technologies group, which develops and applies new methods aimed at accelerating next-generation antigen discovery.
  • Maxwell Mumbach, PhD, a former colleague of Parker’s from the Chang lab who heads the company’s Discovery team, which focused on multi-omic profiling of patient samples and validation of surface antigens on primary tissue.
  • Jeffrey Verboon, who leads the Computational Biology group, which offers computational support and applies genomic and multi-omic analyses to identify new target antigens.

“At the end of the day, we feel like we have a good approach, a good tool set, and there’s a lot of potential here,” Parker said. “I was very motivated by the science and the potential for impact.  This was the thing that we needed to do as a field. And that was very motivating to get the company off the ground.”

Navigation appellation

How did Cartography get its navigation-based appellation?

“We’re really excited about understanding how to make precision immunotherapies and precision therapies. And the way that we’re approaching this is, if you want to make them precise, you got to know what’s expressed where. And in order to know what’s expressed where, you want to basically profile everything,” Parker said.

“It’s like treading a course, taking the things that are currently unknown unknowns and making them known and helping you navigate throughout that,” he continued. “That was the play for all of the mapping and cartography and atlasing.”

Parker said Cartography needed “about a few months” to put together its Series A financing, drawing upon some existing relationships with investors as well as a partner it liked in venture capital firm 8VC, which led the round.

The decline in the market over the past year “did push us to want to be a bit quicker” in raising and closing on the financing,” Parker said: “Sometimes, you can think, Well let’s just keep it open, maybe we’ll keep talking to people. But once we really found partners we liked and raised the money that we wanted to raise—actually a little bit more—then we were, ‘Let’s get this, move on, start building.’”

In addition to 8VC, Cartography also enjoyed what it called “strong” participation from two existing investors—Andreessen Horowitz (a16z), which led the company’s seed financing, and another seed investor, Wing VC.

Joining them in the Series A round were six new investors: Catalio Capital Management, ARTIS Ventures, Alexandria Venture Investments, AME Cloud Ventures, the Cancer Research Institute, and Gaingels, a syndicate of LGBTQIA+ investors and their allies, who have committed to advancing diversity of leadership through venture capital investment.

With financing secured, Cartography plans to expand its workforce, now at just over 30 people.

“We’ll probably add another 10, maybe 20 or so people over the next 12-18 months,” Parker said. “We have a lot of early R&D focus, some BD [business development], a lot of antibody engineering, immunology, and some genomics and computational biology as well.

“We’ve got a great team that has largely put us in a good position to get the things done that we want to get done,” he added. “We’ll bring other people in when there’s a really exceptional person who’s exactly right and really motivated to help the company.”