EXECUTIVE INTERVIEW - Nuritas Pharma: Life Changing Peptide Drug Discoveries for a Changing World

Peptides are the major signaling molecules in the human body (most bodily functions communicate via peptides) and as a result have both significant therapeutic potential and the highest probability of clinical success compared to other modalities. While there are now about 60 approved peptide drugs, we believe the landscape of opportunity is vast and largely unexplored. Enabled by artificial intelligence, our scientists are able to interrogate vast numbers of peptides and identify first-in-class therapeutics that meet or surpass industry standards, overcoming previous peptide delivery challenges.

Drug Development & Delivery recently interviewed Nora Khaldi, PhD, Founder and Chief Executive Officer of Nuritas, to discuss the company’s innovative approach to accelerating the discovery of novel therapeutic peptides that address unmet patient needs in multiple disease areas.

Q: The category of infectious disease is now on everyone’s minds with the challenges we face in global pandemics. How does your platform help address the challenges we are facing today and in the future?

A: Peptides have long demonstrated exceptional utility against a host of microorganisms, with drugs like Vancomycin remaining one of the last effective bulwarks against antibiotic-resistant bacterial species. Using AI to take the serendipity out of drug discovery in this space should enable a rapid, systematic response to the global challenge of infectious disease opening the possibility of bringing many diseases that have historically been economically unattractive to drug developers (eg, tropical diseases or diseases endemic to developing nations) into the frame for real, concerted development efforts.

We’re excited by two opportunities that we believe Nuritas can offer to address these significant challenges. The first is rapid response. Our KRAS work is a great example of the power of Nuritas’ AI platform to identify peptides in a matter of months that may be able to serve as therapeutic options for development against a known target. The same strategy can be applied to target new bacterial, fungal, and viral challenges as they arise.

As a proof of concept in the anti-infective space, we identified peptides that kill bacteria, yeast, and molds by creating predictors to address each microbial subtype; identifying more than 20 such peptides from the millions searched in our database. The selected peptides offer exceptional potency and highly specific activity to each targeted microbial type. In fact, data on one of our patented antimicrobials was published in September 2019 in the peer-reviewed journal Frontiers of Microbiology. We also have compelling data on other compounds that have anti-fungal properties.

Our success to date in the infectious disease space represents just the tip of the iceberg, and by channeling the power of our AI platform to address the unique challenges in bacterial resistance and the frightening task of tackling unknown bacteria, viruses, and fungi, Nuritas will realize its mission of delivering life-changing drug discoveries to people around the globe.

Q: In this era of remarkable new technologies like CRISPR, stem cell and regenerative medicine, and organ bioprinting, why has Nuritas chosen to focus on peptides for drug discovery?

A: Peptides are the major signaling molecules in the human body (most bodily functions communicate via peptides) and as a result, have both significant therapeutic potential and the highest probability of clinical success compared to other modalities. While there are now about 60 approved peptide drugs, we believe that the landscape of opportunity is vast and largely unexplored. From a bioactivity standpoint, peptides offer a “goldilocks” solution that neither small molecules nor large biologics can offer:

-Peptides have broader reach than small molecules because they can engage with a huge target population that small molecules cannot. For example, peptide-peptide and protein-protein interactions (PPIs) are key to most cellular processes, and small molecules have limited ability to interfere with PPIs in a meaningful way – they are simply too small. Additionally, many proteins have broad shallow binding sites or are unstructured, which makes them much more suited to binding peptides than small molecules.

-Peptides are a more attractive modality than biologics because peptides can enter cells and interact with intracellular targets (approx. 75% of all known druggable targets) – while biologics (antibodies) are too big to get into cells.

-Peptides are safer than small molecules because they are generally exquisitely specific for their target and display far fewer off-target or side effects. Additionally, they are less likely to generate an immune response than large biologics.

-Peptides are easier and less expensive to manufacture than large biologics, cell therapies, or gene therapies

Q: What is Nuritas’ approach to peptide drug discovery?

A: Enabled by the Nuritas AI platform, Nuritas scientists can interrogate vast numbers of peptides and identify first-in-class therapeutics that meet or surpass industry standards – specifically, unmodified peptides with demonstrated potency, cell penetration (if needed), lengthy half-life, and other characteristics necessary for successful development.

Q: There are many companies using AI to enable drug discovery. How is your AI platform different?

A: Unlike most other AI platforms, Nuritas has a legacy benefit that exceeds many other companies in the space. Our machine-learning infrastructure and algorithms have been trained on proprietary data generated throughout the past 5 years.

The company has built a large collection of plant, animal, and marine proteomes, analyzing them using mass spectrometry and using the resulting data to train our AI. This process has given us what is arguably one of the largest natural peptide databases in the world (both pure peptides and peptide networks). In addition, we have generated large quantities of proprietary assay data on peptide performance in a wide variety of cell-based bioassays, in vivo animal models, and human clinical studies. The human clinical data derives from studies conducted with GRAS peptide networks that we have been able to rapidly get into the clinic. As much of the biological “low-hanging fruit” in the target landscape has been picked, our ability to generate validated bioactivity predictions even in low data environments addresses the biopharma industry’s huge appetite for novelty and allows development against previously considered “undruggable” targets.

In contrast to other AI drug discovery companies, Nuritas can uniquely provide evidence of its powerful discovery capabilities in PeptAIde^TM, an anti-inflammatory to support exercise recovery, discovered by AI, marketed by BASF, and backed by human clinical data. Additionally, we are developing a broad proprietary biopharma pipeline, with the most advanced programs in fibrosis and cancer. Our fibrosis program is built on a novel target that is implicated in the major pathophysiologies of NASH (steatosis, inflammation, and fibrosis) and which has the potential for broader anti-fibrotic use. Next in the pipeline is a program targeting oncology indications driven by the previously undruggable KRAS G12D mutation.

Q: Do you have plans to develop your own products, or are you focused on commercialization through partnerships?

A: Both. One of the benefits of the AI platform is the ability to rapidly generate multiple discovery programs, at a pace that none but the largest pharma companies could hope to develop themselves. The prolific nature of the platform allows us to choose only the best of the best to advance and affords us the luxury of being able to design the best path forward for each program. For instance, with the KRAS peptide, we may be able to quickly demonstrate proof of concept internally using in vitro and PDX models, enabling rapid advancement for our own pipeline, perhaps retaining US rights and partnering ex-US.

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