NIH Innovation Zone 2024: Talus Bio pioneers breakthroughs in ‘undruggable’ transcription factors

Talus Bio’s collaborative and innovative approach to unlocking the therapeutic potential of targeting transcription factors for cancer and other diseases is putting them at the forefront of the biotech industry. Tackling the challenge of “undruggable” targets, Talus Bio is working to solve some of the most historically difficult science and medicine in the industry and provide patients with life-saving solutions.

Talus Bio was one of the companies supported by the National Institutes of Health (NIH) SEED program chosen to present on the NIH Innovation Zone Stage at the 2024 BIO International Convention. Bio.News interviewed Talus Bio about their work and their vision for next-generation technology and early-stage drug discovery in the years to come.

Q: Talus Bio has said that “nothing is undruggable,” stating that you are “unlocking transcription factor therapeutics for cancer and beyond.” How can patients better understand the breadth of the work you are doing and how might it affect them in the future?

At Talus Bio, we believe that no target is “undruggable”, and our mission is to unlock the therapeutic potential of inhibiting transcription factors (TFs) that cause cancer and other diseases. Transcription factors are some of the most challenging targets but also the targets most desperately in need of effective drug molecules. For patients, this means that our innovative approach could lead to new treatments for diseases where we know the cause, but currently lack effective therapies.

Transcription factors are proteins that bind to specific DNA sequences, controlling which genes are on or off at any given time. Hundreds of these TFs are responsible for controlling the approximately 20,000 genes in our genome. Errors in TF activity frequently result in the underlying pathology across many types of diseases.

Unfortunately, many TFs are considered “undruggable” because they lack suitable binding sites for traditional small molecule drugs. Their dynamic and complex interactions within the cell make them difficult targets for drug development, and the artificial systems traditionally used in early-stage discovery don’t capture this biology faithfully.

Talus Bio’s TF-Scan platform enables us for the first time to measure the activity of these TFs at scale within live, unmodified human cells. This illuminates how TFs interact with the genome in real time to allow us to identify new molecules to block disease-causing TFs.

Q: Why are transcription factor-linked diseases such an important area of research and development for Talus Bio?

Broadly speaking, people think about two main factors in disease: genetic factors and environmental factors. When we say that diseases are caused by both genetic and environmental factors, we mean that both our inherited genes and our lifestyle/environment play crucial roles. Transcription factors are responsible for responding to environmental signals by controlling gene expression, ensuring that our body can adapt and respond to different challenges.

You could think of transcription factors as managers in a factory. The factory (the cells in your body) needs to produce different products (proteins) based on current demands (environmental factors). The managers (transcription factors) receive information about what is needed (e.g., more proteins to deal with stress or fight infection) and then instruct the workers (genes) to start or stop production accordingly.

For example, if someone has a gene that predisposes them to high cholesterol, eating a diet high in saturated fats (an environmental factor) can activate TFs that turn on genes related to cholesterol production, increasing their risk of heart disease. Conversely, a healthy diet and regular exercise can influence TFs in a way that helps keep cholesterol levels in check, even in someone with a genetic predisposition.

Q: Talus Bio takes a multidisciplinary approach to research, combining things like data collection with machine learning, and bringing together a team with a wide spectrum of scientific expertise and experience. Why is this approach so key to solving the problems Talus Bio is tackling?

At Talus Bio, we are addressing some of the most challenging problems in drug discovery. Our multidisciplinary approach is crucial for several reasons:

1. Complexity of TFs: TFs are difficult to drug due to their intrinsic disorder and complex interactions. Combining expertise from biochemistry, proteomics, cell biology, and data science allows us to effectively study TFs in their native context, for the first time, at scale.
2. Data: Our TF-Scan platform generates vast amounts of complex data collected on highly sophisticated instrumentation. Machine learning models are essential for processing this data, interpreting the results, identifying patterns, and guiding drug discovery.
3. Collaboration: Unlocking these targets with the TF-Scan technology requires cutting-edge innovations from multiple scientific disciplines that don’t ordinarily interact. We’ve built a unique, diverse group of scientists at Talus Bio that can not only scale this technology but also deploy it to tackle diseases with high unmet clinical need.

Q: Can you talk about the technology Talus Bio is spearheading, as well as the clinical pipeline that you have in development?

Our flagship technology, TF-Scan, is a cutting-edge platform designed to quantify the activity of all TFs simultaneously in live human cells, thus enabling comprehensive profiling of TF activity in real-time. The key components of TF-Scan are:

• Live Cell Testing: Unlike traditional methods that rely on in vitro models, TF-Scan tests drug candidates in live, unmodified human cells, therefore providing a more accurate representation of cellular processes.
• High Throughput: This platform leverages robotic, plate-based cell processing and next-gen mass spectrometry to analyze thousands of TF interactions in a single experiment.
• Machine Learning Integration: Our proprietary machine learning models analyze the data generated by TF-Scan, identifying actionable insights and guiding the next steps in drug discovery and development.
• Scalability: TF-Scan is designed to handle large datasets efficiently. This enabled rapid exploration of chemical space and accelerates the identification of potential drug candidates.

These integrations allow us to translate complex data into actionable steps for drug development, enhancing the efficiency and precision of the discovery process.

Our primary focus is on developing compounds that modulate the activity of oncogenic TFs (relating to tumor formation). We have made significant progress in developing a treatment for chordoma, a rare bone cancer. Our lead compound has demonstrated promising results in in vivo mouse studies, and we are advancing towards Investigational New Drug (IND)-enabling studies.

We partner with pharmaceutical and biotech companies to leverage our TF-Scan technology for the development of more potent and selective TF-targeted drugs. These collaborations help us extend the reach and impact of our platform, and therefore facilitate the discovery of novel therapeutics.

Q: What is the future of Talus Bio and how can potential strategic partners best develop a relationship with you in the coming months and years?

At Talus Bio, our vision is that by bringing next-generation technology (proteomics and machine learning) to early-stage drug discovery, we can unlock new therapeutics modalities previously inaccessible by traditional technologies. We’re starting in the realm of transcription factors, by leveraging our TF-Scan technology.

In the coming years, we’re focused on developing our platform in several areas:

• Scale: We plan to further scale our TF-Scan platform, improving its automation to increase throughput and reduce costs. This will enable us to process many more samples and generate a vast amount of data, which we then leverage to power our machine learning (ML) and artificial intelligence (AI) algorithms.
• ML and AI: We plan to enhance our ML and AI capabilities to further refine our data analysis and predictive models and leverage our rapidly growing unique dataset. This will improve the accuracy and efficiency of our drug discovery process.
• Broader Applications: We aim to extend the applications of TF-Scan beyond oncology to other therapeutic areas where TFs play a crucial role, such as autoimmune diseases, fibroproliferative diseases, neurological disorders, and cardiometabolic conditions.

Using our platform, we will also continue to progress our internal and partnered pipeline.

• Advancing Lead Compounds: We are focused on advancing our lead compounds through preclinical and clinical stages. This includes completing IND-enabling studies and initiating first-in-human trials for our most promising candidates.
• New Drug Candidates: By leveraging our platform’s capabilities, we will continue to discover and develop new drug candidates targeting various TFs implicated in a wide range of diseases.
• Collaborations with Pharma and Biotech: We aim to deepen our collaborations with pharmaceutical and biotech companies. These partnerships will help us co-develop novel therapeutics, share expertise, and accelerate the drug development process.

Learn more about the NIH Small business Education and Entrepreneurial Development (SEED) funding at seed.nih.gov.