Synaptic Bio, the First-Place winner of the Innovator’s Pitch Challenge at RESI Boston, is advancing a tetravalent bispecific antibody designed to improve both the efficacy and tolerability of cancer immunotherapy. In this interview, the team shares how SYB302 applies immune synapse biology to PD-1 therapy, its path toward the clinic, and the investor and partnering conversations sparked at RESI. 

Yotam Levin CEO and Co-Founder at Synaptic Bio

Caitlin Dolegowski Program Director, LSN

Caitlin Dolegowski (CD): Introduce Synaptic Bio and the unmet need you are addressing in cancer immunotherapy. 

Yotam Levin (YL): Synaptic Bio is a spinout from Dr. Adam Mor’s lab at Columbia University, building bispecific antibodies around the biology of the immune synapse, the interface where a T cell and a tumor cell engage. Our lead program, SYB302, pairs a next-generation PD-1 blocker with IL-25 neutralization in a single asset. Checkpoint inhibitors (ICIs) transformed oncology, but they leave a lot of patients behind. Roughly 800,000 people in the US are treated with ICIs each year, but an estimated 480,000 don’t respond. About half overall develop immune-related adverse events, an expected side effect of bolstering the immune system, and an estimated 140,000 patients have to stop therapy because of severe ones. So there are two problems: too few patients respond, and too many who do respond are forced off a drug that was working. We designed SYB302 to address both concerns.

CD: How does your tetravalent bispecific platform, including SYB302, leverage immune synapse biology to differentiate it from existing checkpoint therapies? 

YL: Today’s PD-1 antibodies mainly work by blocking PD-1 from binding its ligand. SYB302 adds a physical mechanism. Its PD-1 arms are long, and the molecule is larger than a standard antibody. That size pushes PD-1 out of the immune synapse so it can’t suppress the T cell. We have a cool movie on our website at www.synaptic-bio.com to show this. The tetravalent design adds a second mechanistic layer. IL-25 is a homodimer, so each IL-25 molecule can bridge two SYB302 antibodies. That clusters PD-1 on the T cell surface and drives its internalization and degradation. IL-25 is abundant in the tumor microenvironment, so the effect is strongest where we want it. IL-25 is also a driver of immune-related toxicity. Neutralizing this cytokine gives us a built-in safety brake. In preclinical models, including colon, melanoma, and bladder tumors, SYB302 showed stronger tumor control than anti-PD-1 with markedly less organ damage. A single antibody designed to improve both efficacy and tolerability – we have not seen any other antibody that does both.

CD: What are the most important scientific or development milestones over the next 12 to 18 months? 

YL: Our focus is moving SYB302 from a mature Development Candidate toward the clinic. The key milestones are:

1. Stable cell line and process: completing cell line development and defining the manufacturing process, targeted around month 9 after funding.

1. FDA engagement: a pre-IND meeting, targeted around month 12.

1. GMP and toxicology: starting GMP manufacturing and GLP toxicology, leading to an IND submission at about month 24.

In parallel, we’ll expand our preclinical data in colorectal cancer and other indication-specific models, characterize IL-25 as a potential patient-selection biomarker, and advance the manuscript describing the SYB302 data. Colorectal cancer, particularly the MSS subtype that responds poorly to current checkpoint inhibitors, is our lead indication. CRC is a very prevalent disease with few treatment options. As supported by the biology of IL-25, this tumor shows that having high levels of IL-25 correlates highly with poor overall survival.

CD: What did being named First Place winner of the Innovator’s Pitch Challenge at RESI Boston mean to your team? 

YL: It was a meaningful validation, especially coming from an audience of investors and industry experts who evaluate hundreds of stories a year. Our science comes from a university lab and takes a different approach to PD-1 biology, so it’s rewarding to see that message resonate with people who understand the field. It also reinforces our conviction that the next generation of checkpoint therapy needs to deliver both better efficacy and better tolerability.

Preparing for the pitch was fun, because we had to distill a 30 to 60-minute story into a mere six minutes. This forced substantial simplification on one hand, but it also required us to ensure a sophisticated audience gets what they came for – understanding the essence of what we do. The most critical listener in the audience was, of course, Professor Mor – the fact that he liked the presentation was yet another award.

CD: What aspects of the RESI experience, including the pitch, judge feedback, or partnering conversations, were most valuable? 

YL:

1. The pitch: We had to make multiple decisions on what to leave behind and not share. It’s like asking – of the 12 major value propositions of your assets, what are the one and a half that you really need to focus on?
2. Judge feedback: The judges were very insightful, despite the brevity of the presentation and lack of detail. One asked about breakdown of budgets and its assumptions, identifying some assumptions we’ve taken without showing them. I was happy we could answer the questions quickly without to use backup slides for an answer.
3. RESI Sessions: We really enjoyed the panels because they brought industry leaders and experienced investors. We could get a much better feel for what individual fund managers expect to see, how they differ from one another, how to overcome the overwhelming noise of hundreds of pitches and business plans, and whether or not there is a likely fit with certain parties. Meeting these investors in person instead of through email, Zoom, or networking apps made all the difference.

CD: Did RESI Boston lead to any meaningful investor, strategic partner, or scientific conversations that you expect to continue? 

YL: Yes. We had productive conversations with a few investors and potential strategic partners, and several are in the funnel. I can’t share specifics of course, but the interest has been in both SYB302 and the broader platform.

CD: What types of investors or strategic partners would be most valuable, and why should other early-stage companies consider the Innovator’s Pitch Challenge? 

YL: We’re looking for partners who understand the immuno-oncology landscape and can support a long development path. That includes biotech-focused venture investors for our seed financing, and strategic partners in oncology and immunology who see the value of a differentiated PD-1 backbone. For our lead asset, we prefer traditional seed funding; for our additional assets in Type2 inflammation we also foresee single-asset licensing, option-based co-development or a strategic investment. We think corporate VCs could be a natural fit, because they have deep scientific expertise but also an eye for market access. Our strongest asset is our science, data, and results – having experienced investors in our team would go a long way.