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Chen compared Synthetic Design Lab\'s ADCs to riding a bike, as opposed to engineered T cells, which are more like riding a horse.\n Just a few years ago, Daniel Chen, M.D., Ph.D., was spending his spare time in his backyard, sketching out designs for new antibody-drug conjugates (ADCs) with a friend. Now, he’s sharing with the world the result of those complicated doodles: a biotech startup with a focus on “smart” cancer drugs.On the Sunday of the American Association for Cancer Research (AACR) annual meeting in San Diego, Chen officially unveiled Synthetic Design Lab, a Bay Area biotech with a platform for engineering ADCs that can adapt as the cancer they are fighting does.“It really is a smart drug in the sense that I originally thought of it as a nanobot,” Chen told Fierce Biotech on the sidelines of the conference. The goal is to move away from target-centered drug design, Chen explained, and toward the creation of therapeutics that can work across broad patient populations. In an oral presentation at the AACR event, Chen shared preclinical data from ADCs built to attack multiple myeloma and lymphoma targets that showed more than 80 times greater in vivo potency in mouse models and human cells than GSK’s ADC Blenrep.SDL’s platform, Synthbody, can craft ADCs with up to four arms and six to 12 binding sites, he told Fierce, allowing a single drug candidate to pursue many different targets on the surface of cancer cells that might individually be quite rare.“When you start to summate them, you actually start to create something that\'s really good,” Chen said. And because the ADC has so many binding sites, a single molecule can be designed to bind to cancer cells in different ways as the disease morphs to avoid the drug.“Essentially, it adapts,” Chen explained. “I spent so much of my career on biomarkers and diagnostics, [finding the] right drug for the right patient, but this kind of blows that up.”Chen’s dream of SDL first started taking shape during his 12 and a half years at Genentech, where he rose through the ranks to eventually become global head of cancer immunotherapy development.“It was really during my time at Genentech where I became convinced that we can\'t just focus on continuing to discover the next breakthrough,” Chen said, namechecking the likes of PD-1, HER2 and GLP-1. Instead, he wanted to push into creating new drug modalities entirely. Chen left Genentech in 2018 for a three-year stint as chief medical officer at IGM Biosciences, which has since been acquired by Concentra, in order to bolster his resume with experience from a small biotech startup.Now he’s putting that experience to use with SDL, which he told Fierce is already well-financed with $20 million in seed funding but could stand to raise more soon. A cash infusion could come in the form of a standard series A, he said, or through a pharma partnership.Partnerships will also be a key part of SDL’s eventual pipeline, Chen added, which he envisages including a mix of wholly owned and partnered assets.“When you have such a fundamental platform—like [how] we\'re making smart drugs—we do what we\'re going to do best, and the rest of it should be partnered down,” Chen said. For SDL, that means focusing on ADCs while letting partners take the lead in other promising potential applications, like neuroscience. Other companies interested in these “smart” drugs will have no choice but to choose SDL, he said. While a similar approach is well-established in cell therapy, like Senti Bio\'s synthetic biology platform, Chen isn’t aware of any other biotech doing what SDL is doing. When it comes to adaptable cancer therapies, Chen explained that he prefers using ADCs over T cells for the superior control they allow.“T cells are like riding a horse, because they have a mind of their own,” he told Fierce. ADCs, however, are like a bicycle—“it only does what you built it to do.”In terms of testing its ADCs in humans, the biotech is “running as fast as we can to take drugs into the clinic,” Chen said. “What we don\'t know yet is which one we want to take.” An engineer at heart SDL’s ADCs are essentially designed to have logic gates, where the chemotherapy payload is only delivered if the right combination of binding sites is activated. The ADC gets its flexibility from the fact that this can be triggered in multiple different ways, depending on how the molecule is designed.“Our platform is a fundamentally different way of thinking about how to target a cancer cell,\" Ramesh Baliga, Ph.D., SDL’s co-founder and chief scientific officer, said in an April 19 release. \"By controlling the geometry and biophysics of the targeting architecture itself, we can generate capabilities and emergent properties that simply aren\'t possible with conventional IgG-based formats.”It was Baliga who sat with Chen in the latter’s backyard during SDL’s early days, drawing potential ADCs by hand before sending them out to contract research organizations to be synthesized.“The first few sequences we sent off completely failed,” Chen recalled. “When you\'re doing something new, you have to have thick skin, and you have to problem solve.”Chen views SDL as a full-circle moment from his undergraduate days at Massachusetts Institute of Technology, where students are known as “engineers.” While there, he seriously considered a career in physics, before ultimately becoming the only one of his friends to pursue medicine.Still, physics looms large in his conception of biotech today, he told Fierce.“Back in the early 1900s there were all these fundamental physics breakthroughs that led to Nobel Prizes, like the photovoltaic effect,” he said, referring to Albert Einstein\'s award for explaining how solar cells convert sunlight into electricity. “At some point, you make enough fundamental discoveries where you could actually now move beyond discovery into design and engineering.”For physics, those century-old discoveries led to groundbreaking technologies like radios, telephones or solar panels. With SDL, he said, he wants to do the same for biology.“That was the fundamental piece—can we actually move to engineering?” Chen said. “Can we design an approach that would allow us to start building things that we never would have conceived would be possible before?”With SDL, he’s excited to find out. And he’s also excited to no longer have to keep his fledgling company a secret.