Advances in precision medicine have revolutionized the way scientists target disease, with genomics and proteomics leading the way. However, the role of lipid biology in disease progression has gone largely unexplored — until now.
Lime Therapeutics, a pioneer in lipid-focused drug discovery, is breaking new ground with its novel LipidSense™ platform. This cutting-edge tool enables real-time tracking of lipid metabolism, hunting for dysfunctions and related targets for drug discovery.
With a growing body of research linking dysfunctional lipid metabolism to many forms of cancer, cardiometabolic diseases, lysosomal storage diseases and neurodegenerative disorders, Lime Therapeutics (derived from LIpid Medicines), is positioning itself at the forefront of this intriguing field.
In recognition of the promise of their approach, Lime Therapeutics received an XSeed Award in 2022 for its work to target lipid metabolism in disease processes. The XSeed Award provides critical funding to translate scientific discoveries into commercially successful drug therapies to winning New York City minority- and women-led life science and healthcare startups working on novel drug development projects.
Cure checked in with Shardule Shah, PhD, MBA, co-founder and CEO of Lime Therapeutics, to get an update on ongoing work and next steps in its research and development.
This interview has been edited for length and clarity.
Cure: What is the mission of Lime Therapeutics?
Shardule: The mission of Lime Therapeutics is to create precision medicines for diseases with dysfunctional lipid biology. We combine engineering and biology to solve a very large unmet need.
When you think of lipids, you may think of high cholesterol or obesity. But lipid biology has a role in other diseases as well. Efforts to hunt for lipid-mediated targets and create novel therapies have remained elusive due to lack of technology.
We are at the cusp of a new frontier in biology where the understanding of how lipids play a role in disease biology is just beginning to be clarified. We see ourselves being at the front of the wave, so people can understand that lipids play such an important role in many diseases.
Cure: How does LipidSense work?
Shardule: LipidSense is a combination of our nanotechnology-based lysosomal lipid monitoring platform, in vivo CRISPR screening against lipid-processing targets, and functional genomics for target validation in vitro and in vivo. The therapeutic opportunities we are exploring have the potential to touch the lives of millions of people with cancer, metabolic diseases, and neurodegenerative disorders.
Cure: Can you tell us about the project for which you won the XSeed Award?
Shardule: The work my co-founders had done shed light on the interaction that lipids play in the disease biology of Alzheimer's, Parkinson's and frontotemporal dementia. At the root of our application, our technology helped us to learn how to find new medicines to stop the dysfunctional lipid biology process occurring in these age-related neurodegenerative diseases.
Since then, we have continued with that part of the story to some degree. The company has primarily shifted to focusing on cancer therapeutics. Up to 90 percent of our current focus is the idea that lipids play a very large role in various forms of cancer. We have positioned our technology to find new drugs that can block lipids from having a negative effect in cancer.
Cure: Can you give an example of how altered lipid metabolism affects particular cancers?
Shardule: Our lead program is in hepatocellular carcinoma, a form of liver cancer. Utilizing our discovery platform, we identified an enzyme which interacts with lipids. Hepatocellular carcinoma cells use this lipid-mediated enzyme to prevent themselves from succumbing to a form of cancer cell death called ferroptosis.
We are now developing our own novel medicines to inhibit this novel target. We're identifying our lead series and will then be moving to lead optimization, followed by nomination of a development candidate by mid-2026.
Cure: How did Lime Therapeutics benefit from winning an XSeed Award?
Shardule: I can say without equivocation that the XSeed Award helped to put us on the New York City biotechnology map. It was our first connection to Deerfield, to the New York City Economic Development Corporation and to the Empire State Development organization.
Being at an incredibly early stage of our idea at that point, having the XSeed Award as validation has meant so much to Lime Therapeutics. When we make pitches to investors, the XSeed Award logo is visible on our slide deck. People recognize the award if they're in the New York area or if not, they know who Deerfield is.
Cure: In what ways has Lime Therapeutics participated in the New York City biotech ecosystem?
Shardule: There are so many programs that are available at different hospitals and universities, and we have engaged in many of them. There are too many to list, but examples include the Endless Frontier Labs run by New York University, the Advanced Science Research Consortium at City University of New York and ELabNYC.
Cure: Do you have any advice for entrepreneurs looking to launch a startup?
Shardule: For people who are just starting out, I would say to pressure test your idea with a diverse group of stakeholders before you fully launch it. This group could include anybody from venture capital groups to clinicians and patient advocacy groups. You'll want to ensure that your idea can be translated into a business.
If we're specifically talking about drug development, it's important to generate a drug that clinicians would prescribe if it's approved and that the market would buy. Connect the dots early on so you know that if you're going to take the leap and give up whatever safer job you might have, it's for the right reasons. While your game plan may change, it's incredibly important to know how you're going to bring whatever you're developing to patients.
Finally, seek out the advice and guidance of people who have done this before or who are experts in their respective areas. Expand your network by talking to people about what you're doing and getting them interested in what you're building. I firmly believe that in New York City, which is so small in geography compared to other areas, there are many opportunities to build up those kinds of relationships.
Cure: Who else is involved in this work?
Shardule: The other members of the XSeed Award-winning team include Prakrit Jena, PhD, co-founder and CTO, and Daniel Heller, PhD, co-founder at Lime and a faculty member at Memorial Sloan Kettering Cancer Center and Weill Cornell Medicine.