Resident Company Q&A: Neutrolis

October 26, 2021

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As we continue to highlight the groundbreaking work of LabCentral resident and alumni biotech companies, here’s a snapshot of  Neutrolis, Inc., a preclinical-stage resident organization that develops therapies to combat the "dark side of DNA.” We spoke with Toby Fox, PhD, Co-founder and CEO, to learn more about the company’s focus and activities.

What prompted the founding of Neutrolis, and how did the company get started?

Neutrolis is focused on Neutrophil Extracellular Traps (NETs), an innate immune mechanism that was discovered by Dr. Arturo Zychlinsky in 2004 at the Max Planck Institute for Infection Biology in Berlin. My colleague and Neutrolis Co-founder, Abdul Hakkim R, PhD, and I were the first two PhD students to work on NETs in the lab of Dr. Zychlinsky. Our early academic careers were completely focused on NETs biology and related etiologies.

In 2017, I was a principal investigator in Germany and my lab gained novel insights into the homeostasis of NETs, while Hakkim was building his first biotech startup in Boston. At a family visit, we decided to use our know-how to develop a therapy against NETs. With support from our early stage investors, including Prefix Capital and First Rice Capital, and a Golden Ticket to LabCentral from Bristol Myers Squibb, we launched Neutrolis.

Neutrolis focuses on the “dark side of DNA.” Can you explain what this means?

DNA is known for its beneficial properties as a carrier of our genetic information. However, when DNA gains exposure to the extracellular space, it can take on an interesting pathological function. Specifically, neutrophils, the most abundant immune cell in the body, expel their long chromatin fibers (DNA wrapped around histone protein) into the extracellular space to form NETs.

Balance between NETs exposure and clearance is pivotal for immune homeostasis. NETs, which developed evolutionarily as a “bio-bandage” on skin wounds to prevent infection, also form within our body under pathological conditions. Accumulation of NETs in the body can exacerbate systemic immune response, trigger hyperinflammation and blood clotting (thrombosis), and cause irreversible end-organ damage and death.

How does your exDNASE Platform address this, and how is it different from treatments on the market today?

Our proprietary exDNASE™ platform is based on the discovery of naturally occurring enzymes that degrade the chromatin fibers that form NETs. The platform powers the rapid development of natural and engineered enzyme analogs that are optimized for therapeutic use including activity, bioavailability, tissue specificity and minimized immunogenicity, in order to address significant unmet acute and chronic medical needs.

How (and when) do you envision these therapies impacting treatment for patients?

We envision our therapies being a significant addition to clinicians' armamentarium for managing both acute and chronic conditions where NETs play a critical role by assisting the body in returning to homeostasis. NET-related pathologies arise when extracellular chromatin persists in the body as a result of either excessive NET formation or impaired degradation capability.

Importantly, we have the ability to leverage both genetics and biomarkers in order to target patients who are likely to respond to our therapies. We expect that our therapies will be used to quickly assist or prevent the accumulation of NETs in the body. NTR-441, our lead therapy, has entered clinical development earlier this year.

Are there certain diseases/conditions that you expect to target initially?

We are initially investigating NTR-441 in COVID-19. We should have more announcements about additional clinical programs over the next few months.

As a biotech startup, how has LabCentral helped you to operate, grow or accelerate?

Neutrolis won a series of “Golden Tickets” from Pfizer and Bristol Myers Squibb, which gave us initial access to LabCentral and covered costs for lab space over the last three years. The company has greatly benefited from the well-managed LabCentral environment, which provides administrative support, laboratory  infrastructure and equipment, and access to a network of partners in pharmaceutical industry and venture capital. In addition, the great ecosystem and community at LabCentral has allowed Neutrolis to grow and thrive.

What’s next for Neutrolis this year and beyond?

We recently completed a Series A financing round, and we’re looking forward to the clinical development of our lead asset, NTR-441, and follow-on programs.