Focus: First-in-class enzymatic therapies targeting neutrophil extracellular traps (NETs) in autoimmune and inflammatory disease

Problem: NETs — DNA webs expelled by neutrophils — drive tissue damage in lupus, RA, and dozens of inflammatory conditions; all current therapies suppress the entire immune system rather than targeting NETs directly

Approach: exDNASE platform engineers analogs of DNASE1L3, the natural enzyme responsible for degrading extracellular chromatin (the structural backbone of NETs); albumin fusion for SC dosing and extended half-life

Lead Assets: NTR-1011 — DNASE1L3-albumin fusion (Phase 1a complete in HVs; Phase 1b in SLE/RA mid-2026); NTR-641 — next-gen DNASE1L3 analog (IND-enabling); L304 — topical DNase for dry eye disease (preclinical)

Backing: ~$45M total raised; investors include Morningside Group, Prefix Capital, PBJ Capital

Leadership: Anthony Aiudi, PharmD, MBA (CEO) — biotech executive with M&A track record; Toby Fox, Ph.D. (Co-Founder, CSO) — NETs field pioneer

Neutrolis is building an entirely new therapeutic class around neutrophil extracellular traps — the sticky webs of DNA and proteins that neutrophils expel as part of the innate immune response. In healthy people, these NETs get cleaned up by natural enzymes. In autoimmune disease, they accumulate, driving chronic inflammation and tissue damage across organs. Genetic deficiency in DNASE1L3 — the enzyme responsible for degrading NETs — is directly linked to early-onset lupus, providing the human genetic validation for Neutrolis’s approach.

The company’s exDNASE platform engineers optimized analogs of DNASE1L3, fused to human serum albumin for stability and subcutaneous delivery. Earlier proof-of-concept with NTR-441 showed rapid clinical improvement in a teenager with severe treatment-refractory lupus and DNASE1L3 deficiency — presented at ACR 2025 as a late-breaking oral. NTR-1011, the optimized lead candidate, has now cleared Phase 1a with clean safety and is headed into patient studies.

NTR-1011 — DNASE1L3-Albumin Fusion in SLE and Rheumatoid Arthritis

First-in-class DNASE1L3 fusion protein optimized for SC delivery. Phase 1a (LIBERATE-I, NCT07237659) completed: 48 healthy volunteers, favorable safety/tolerability, no immunogenicity, predictable PK with robust SC bioavailability. Phase 1b basket trial in moderate-to-severe SLE and RA planned mid-2026.

NTR-641 — Next-Generation DNASE1L3 Analog

Next-generation DNASE1L3 analog from the exDNASE platform with further optimized properties. IND-enabling studies underway. Indication TBD — platform designed to expand across NET-mediated diseases.

L304 — Topical DNase for Dry Eye Disease

Topical DNase enzyme targeting NETs on the ocular surface for dry eye disease. Licensed IP from University of Illinois Chicago (Dec 2024). NETs have been implicated in corneal surface inflammation and DED pathology.

Company	Approach	Stage	Differentiator
Neutrolis	DNASE1L3 fusion protein (enzymatic NET degradation)	Phase 1	First-in-class NET enzyme; non-immunosuppressive; SC delivery; human genetic validation
Citryll	Anti-citrullinated histone antibody (CIT-013)	Phase 2	Blocks NET formation; €85M Series B; J&J/Forbion/Novartis backed
AstraZeneca	Anifrolumab (anti-IFNAR1)	Commercial	Approved for SLE; targets type I interferon pathway; immunosuppressive
GSK	Belimumab (anti-BLyS)	Commercial	First SLE biologic; B-cell targeting; immunosuppressive
Resolve Therapeutics	RNase-Fc fusion (RSLV-132)	Phase 2	Targets RNA in immune complexes; related but distinct mechanism from NET degradation

The global lupus therapeutics market exceeded $3B in 2024 and the RA market surpasses $25B, yet both remain dominated by broad immunosuppressants with significant infection risk. NETs have emerged as a validated upstream driver of autoimmune pathology — implicated not just in SLE and RA but in vasculitis, ANCA-associated disease, thrombosis, and even dry eye. A non-immunosuppressive therapy that clears NETs without compromising adaptive immunity would represent the first mechanistic shift in autoimmune treatment in decades.

The unlock: Autoimmune disease treatment has been stuck in the same paradigm for decades: suppress the immune system broadly and accept the infection risk. NETs are emerging as a root cause of tissue damage in lupus and RA — not a downstream effect, but the actual machinery of organ injury. If enzymatic NET degradation works in patients, it opens a treatment modality that addresses disease at its source without the immunosuppressive tradeoff. That’s not an incremental improvement — it’s a paradigm change.

For investors: Neutrolis is lean (~$45M raised) with a first-in-class asset that just cleared the Phase 1a safety gate. The Phase 1b data in SLE and RA patients (mid-2026 start, data likely 2027) is the binary event. The human genetic proof is the strongest possible preclinical signal — DNASE1L3 loss causes lupus, and compassionate-use DNASE1L3 replacement showed rapid clinical improvement. If patient data corroborates, this is a Series B / partnership inflection point. The risk is whether enzymatic NET degradation translates to clinical benefit in a genetically heterogeneous patient population.

For pharma BD: Any immunology franchise watching the NETs space should be engaging Neutrolis now. Citryll’s €85M raise (J&J, Novartis, Forbion) validated the commercial thesis around NET-targeting in autoimmune disease — but Citryll blocks NET formation while Neutrolis degrades existing NETs. These are potentially complementary, not competitive. The window to partner before patient data is closing.

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