Gordian Biotechnology has released a preprint describing a scalable in vivo screening platform that tests genetic targets directly in living organisms across multiple tissues and disease contexts. The platform addresses a key drug discovery bottleneck by distinguishing genes that merely correlate with disease from those that causally drive it. The system combines pooled perturbation screens with single-cell sequencing and uses barcoded viral serotypes to deliver perturbations to specific tissues. A computational framework predicts physiological endpoints from transcriptomic data, enabling target prioritisation based on human patient datasets. The platform evaluates targets relevant to all major therapeutic modalities, including small molecules, antibodies and gene therapies. Gordian currently runs screening in heart, lung, liver, joint, kidney and adipose tissue, with a pipeline focused on cardio-renal-metabolic indications. The preprint is available on bioRxiv.

Gordian Bio inks obesity research collab with Pfizer. Companies seek new obesity targets using platform that enables thousands of genes to be screened simultaneously in living tissue. Longevity biotech Gordian Bio today announced a new research collaboration with pharma giant Pfizer aimed at speeding up the discovery of drug targets for obesity by studying them directly inside living fat tissue. The partnership is evocative of the rapidly evolving obesity therapeutics market, where drug developers are increasingly looking beyond first-generation GLP-1 therapies toward novel biological mechanisms that can deliver durable, long-term benefit. The non-exclusive agreement will leverage Gordian's in vivo mosaic screening platform, which allows hundreds of gene targets to be evaluated simultaneously in living tissue. As part of the collaboration, Gordian will carry out a large-scale screen of gene targets in key fat tissues that play an important role in metabolic disease but are difficult to study outside the body. The goal is to identify targets that meaningfully influence the behavior of fat cells (adipocytes), inflammation, insulin signaling, and other metabolic pathways relevant to obesity. But what are the implications for the company's broader mission to target chronic age-related diseases? Longevity.Technology: Founded on the premise that drug discovery must move closer to real human biology, Gordian has built a high-throughput in vivo screening platform capable of testing genetic perturbations directly in living systems. The company's collaboration with Pfizer reflects a growing industry interest in scalable, in vivo-first approaches that can rapidly prioritize targets across complex diseases. We sat down with Gordian CEO Francisco LePort to find out how the collaboration came together, why early stage in vivo interrogation is attracting increased attention, and how obesity fits into the company's longevity-focused strategy. LePort explains that the runaway success of GLP-1 drugs like Wegovy has driven significant interest in novel mechanisms of action - mechanisms that could either work alongside, or potentially follow, the GLP-1s. "People are looking for what comes next, post-GLP-1," he says. "One area of focus is things like obesogenic memory and other adipocyte-focused mechanisms that could be therapeutically relevant. We had met at several conferences earlier in 2025, including some that Pfizer hosted, where these topics were being discussed." Overcoming key limitations. Obesity and related metabolic disorders involve complex interactions across multiple tissues, and many target discovery efforts still rely on ex vivo systems or narrow, single-gene approaches, which can miss these interactions. Gordian's platform is designed to overcome those limitations by generating transcriptional and functional readouts for hundreds of genetic perturbations at once, all within intact, living tissue. According to LePort, Pfizer took an interest in the platform's ability to enable direct interrogation of genetic perturbations in adipocytes in vivo. "In particular, we can target visceral adipose tissue, which is biologically the most interesting fat depot, but also notoriously difficult to study ex vivo or in vitro," he explains. "Even beyond the general benefits of studying biology in vivo, that specific tissue presents a real challenge. So our ability to interrogate genetic perturbations in visceral adipose tissue in a living animal has been particularly interesting - not just to Pfizer, but to the field more broadly. That's really where the collaboration clicked." For Pfizer, the collaboration offers a way to prioritize obesity targets based on direct evidence from relevant tissue environments rather than proxy models. For Gordian, the work will also feed into its growing internal dataset on cardiometabolic disease. The resulting data are expected to expand the company's broader atlas of intervention effects, which is being built to support drug discovery across obesity and other cardio-renal-metabolic indications. This also links closely to the company's longevity focus. "Obesity really sits within the broader cardio-renal-metabolic space, and the industry has increasingly consolidated those indications - scientifically and organizationally - across major pharma companies," says LePort. "For chronic age-related diseases, roughly 50% of deaths - excluding accidents - fall within that combined indication space. Heart failure is the leading cause, but diabetes and many related diseases are also part of that cluster. So this has been a very natural and compelling area for us to move into." The benefit of Gordian's approach is that it can run in vivo screens across different tissues, such as heart, kidney and liver - and can draw inferences across systems. "We can identify obesity-specific targets, but we can also look for synergistic effects of individual perturbations across multiple organs," says LePort. "That's where we see the longer-term opportunity: identifying the next wave of multi-indication or multimorbidity therapeutics. That fits squarely within our broader longevity and age-related disease focus." While in vivo testing has always been the gold standard prior to clinical studies, the challenge has always been that it's slow, expensive and difficult to scale. "The industry has long wanted to accelerate this step, but it's lacked the tools to do so in a meaningful way," says LePort. "What we've built is a breakthrough that allows the in vivo validation step, which is traditionally slow and target-by-target, to be massively parallelized." Big pharma interest. According to LePort, several large pharma companies have approached Gordian with prioritized lists of hundreds of genes. "Historically, validating those targets in vivo could take years," he says. "With our platform, we can evaluate hundreds or even thousands of targets in a matter of months. That ability to rapidly prioritize targets in vivo has resonated strongly in our conversations with large players." In addition to Pfizer, LePort says the company has signed a second collaboration with "another major player," and gives a hint as to where the next partnership will be focused. "Our primary focus remains the cardio-renal-metabolic space - obesity, heart failure and chronic kidney disease in particular - and we have ongoing conversations across all three," he says. A key aspects of Gordian's platform is how quickly the company can translate it into new indication areas. "For example, a year ago we hadn't done any work in obesity," says LePort. "After conversations with a major pharma partner, we decided to focus on adipocytes and adipose tissue. We began that effort at the start of 2025, and by April we had successfully translated the platform, completed our first screens, and started identifying novel targets." "That four-month turnaround really illustrates the opportunity here. We've now translated the platform into five indication areas - adipose, liver, heart, lung and joint for osteoarthritis - and we're currently translating it into kidney, with first data expected in the next few months." Moving towards the clinic. In terms of Gordian's own internal pipeline, LePort confirms that osteoarthritis remains its most advanced program. "We have a development-candidate gene therapy that has successfully gone through FDA INTERACT, and we're now moving into clinical development," he says. "We're also developing a protein-based version of the same therapeutic as an injectable alternative to gene therapy. In parallel, we're exploring the animal health market, where a disease-modifying osteoarthritis therapy would also be first-in-class." "In cardio-renal-metabolic, we've run screens in obesity and heart failure and are now translating into kidney. We've identified promising targets and have small-molecule campaigns underway, with the goal of advancing development candidates over time." So, how long will it be before we see Gordian take one of its own programs into clinical trials? "We're still likely a couple of years away from entering the clinic with our osteoarthritis candidate, but we're firmly on that path now," says LePort.