Aurealis Pipeline: Multi-Target Bacterial Gene Therapy for Chronic Wounds and Cancer

Aurealis Therapeutics develops multi-target cell and gene therapies using its modular bacterial platform based on genetically engineered Lactococcus cremoris. Products from our platform produce multiple therapeutic proteins simultaneously in the diseased tissue, the only company globally to achieve three-protein expression in bacteria. Pipeline spans chronic wounds (Phase 2 completed), oncology (preclinical), and inflammation (discovery).

OUR PRODUCT PIPELINE IS ORGANIZED AROUND THREE THERAPY AREAS:

Lead product: AUP-16

Our Phase 1 clinical study in Diabetic Foot Ulcer (DFU) patients was completed with excellent results. The DIAMEND AUP-16 Phase 2 DFU clinical study was completed in December 2025, showing the complete wound closure rate was tripled versus placebo, in wounds that had not healed for more than three months. Global Phase 3 study preparation is ongoing.

 Clinical trials in Venous Leg Ulcer (VLU) and Pressure Ulcer (PU) will follow.

Lead candidate: AUP-55

We have obtained pre-clinical results in ovarian cancer and other secondary peritoneal carcinomatosis. Our first abstract was accepted and published at ASCO website.

3. INFLAMMATION

Lead candidate: AUP-60

At discovery stage.

Aurealis Therapeutics development pipeline

Indication

With our established platform, creating customized new products with desired 2-3 human therapeutic proteins can be developed in six to ten weeks.

Why Chronic Wounds Resist Conventional Treatment

There is no effective treatment that can hit multiple targets as one product.

We believe that when treating complex diseases like chronic inflammation and cancer, one needs to hit multiple targets to be disease-modifying. Very few companies or products can claim to truly target multiple biological targets. With our 4-in-1 technology, we can.

The wound healing process, for example, involves multiple steps: inflammation, proliferation, angiogenesis, and epithelialization. This process occurs naturally in normal circumstances. However, in chronic non-healing wounds, this process is impaired — wounds remain in the inflammation stage. To successfully restart wound healing in chronic non-healing wounds, it is essential to activate different biologic targets.

AUREALIS THERAPEUTICS 4-IN-1 PRODUCT AUP-16

Diagram showing Aurealis Therapeutics’ multi-target wound healing approach: reducing inflammation through immune cells, promoting fibroblast proliferation, improving angiogenesis through endothelium, and accelerating epithelial remodeling

Even though many different treatments exist today – traditional or moist wound dressings, negative pressure wound therapy, cell and tissue-based products, skin substitutes, and growth factors – most existing products only tackle one target with a single mode of action.

That is why we created Aurealis Therapeutics 4-in-1 platform.

How the Aurealis Bacterial Gene Therapy Platform Works

Illustration of the Aurealis Therapeutics Technology Platform

A synthetic biology, cell and gene therapy platform based on modified food-grade lactic acid bacteria. These bacteria are genetically modified to include 90 copies of a plasmid, allowing them to synthesize multiple human therapeutic proteins, acting as millions of bioreactors in the body.

We are the only company in the world to have genetically engineered bacteria expressing three human therapeutic proteins.

This novel cell and gene therapy platform is backed by pre-clinical and clinical results in wide-ranging applications from diabetic foot ulcers, other non-healing wounds, oncology and inflammatory diseases.

Illustration of the Aurealis Therapeutics Technology Platform

A synthetic biology, cell and gene therapy platform based on modified food-grade lactic acid bacteria. These bacteria are genetically modified to include 90 copies of a plasmid, allowing them to synthesize multiple human therapeutic proteins, acting as millions of bioreactors in the body.

We are the only company in the world to have genetically engineered bacteria expressing three human therapeutic proteins.

This novel cell and gene therapy platform is backed by pre-clinical and clinical results in wide-ranging applications from diabetic foot ulcers, other non-healing wounds, oncology and inflammatory diseases.

Our Bacterial Gene Therapeutic Areas

CHRONIC WOUNDS

AUP-16 is our lead clinical asset for chronic wounds.

ONCOLOGY

AUP-55 is our lead pre-clinical asset in oncology.

Peer-Reviewed Publications and Clinical Evidence

Peer-Reviewed Journal Articles
November 2024
Multi-target gene therapy AUP1602-C to improve healing and quality of life for diabetic foot ulcer patients: a phase I, open-label, dose-finding study
Therapeutic Advances in Endocrinology and Metabolism
Schindler C, Mikosiński J, Mikosiński P, Kärkkäinen H-R, Sanio M, Kurkipuro J, Mierau I, Smith W, Vartiainen A, Décory L, Weber D, Wirth T, Yrjänheikki J, Schellong S, Samaranayake H
DOI 10.1177/20420188241294134
Access article
February 2022
Four in one—Combination therapy using live Lactococcus lactis expressing three therapeutic proteins for the treatment of chronic non-healing wounds
PLOS ONE
Kurkipuro J, Mierau I, Wirth T, Samaranayake H, Smith W, Kärkkäinen H-R, Tikkanen M, Yrjänheikki J
DOI 10.1371/journal.pone.0264775
Access article
May 2026
Results of Phase-2 Randomized Controlled "DIAMEND" Study with Multi-targeting Cell & Gene Therapy AUP1602-C in Chronic Neuro-Ischemic Diabetic Foot Ulcers Oral Presentation
EWMA Conference Bremen 2026 — European Wound Management Association
Piaggesi A (presenter), on behalf of Aurealis Therapeutics
DOI 10.13140/RG.2.2.18401.06240
Access presentation
April 2026
Final results of Phase-2 Randomized Controlled "DIAMEND" Study In Chronic Diabetic Foot Ulcer With Topical Multi-Target Cell & Gene Therapy AUP1602-C Poster
SAWC Spring Charlotte 2026 — Symposium on Advanced Wound Care
Piaggesi A, Mikosiński J, Iacopi E, Lammers D, Kosch C, Pańczak K, Grobelna M, Monami M, Scatena A, Malka M, Meloni M, Schindler C, Sanio M, Kurkipuro J, Kärkkäinen H-R, Piiroinen M, Mierau I, Décory L, Yrjänheikki J, Samaranayake H
DOI 10.13140/RG.2.2.27244.32642
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March 2025
A randomized controlled Phase 2 trial to evaluate multi-factorial gene therapy AUP1602-C in the management of non-healing Diabetic Foot Ulcer Abstract & E-Poster
EWMA Conference Barcelona 2025 — European Wound Management Association
Piaggesi A, Mikosiński J, Iacopi E, Lammers D, Kosch C, Pańczak K, Grobelna M, Monami M, Scatena A, Malka M, Meloni M, Schindler C, Sanio M, Kurkipuro J, Kärkkäinen H-R, Piiroinen M, Mierau I, Décory L, Yrjänheikki J, Samaranayake H
November 2023
A Markov model to determine the cost-effectiveness of a multi-targeting bacterial gene therapy (AUP-16) at healing a Diabetic Foot Ulcer when compared to the current standard of care Abstract & Poster
ISPOR Health Economic Conference 2023
Basskin L, Décory L, Samaranayake H, Kurkipuro J, Smith W, Mierau I, Kärkkäinen H-R, Tikkanen M, Yrjänheikki J, Apelqvist J
October 2023
4-in-1 live biotherapeutic Gene Therapy Medicinal Product (GTMP) accelerates healing of Diabetic Foot Ulcers (DFUs): a first-in-human, phase 1 clinical study Oral Presentation
EWMA Conference Milan 2023 — European Wound Management Association
Schindler C, Mikosiński J, Schellong S, Samaranayake H, Kärkkrinen H-R, Tikkanen M, Kurkipuro J, Mierau I, Smith W, Décory L, Weber D, Wirth T, Yrjänheikki J
October 2023
Multi-target bacterial gene therapy for chronic wounds and cancer Poster
14th International Symposium on Lactic Acid Bacteria
Mierau I, Samaranayake H, Kurkipuro J, Smith W, Kärkkäinen H-R, Tikkanen M, Décory L, Wirth T, Yrjänheikki J
May 2023
Effect of multi-targeting bacterial gene therapy on tumour regression and survival in mouse models of ovarian and intraperitoneal cancer Abstract
Journal of Clinical Oncology — ASCO Annual Meeting 2023
Samaranayake H, Kurkipuro J, Smith W, Mierau I, Kärkkäinen H-R, Tikkanen M, Décory L, Wirth T, Yrjänheikki J
DOI 10.1200/JCO.2023.41.16_suppl.e17550
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December 2017
Therapeutic use of Lactococcus lactis bacteria to produce proteins locally in diseased tissues of chronic wounds Poster
EWMA Conference Krakow 2018 — European Wound Management Association
Weber D, Samaranayake H, Mierau I, Smith W, Kärkkäinen H-R, Kurkipuro J, Yrjänheikki J, Wirth T

Frequently Asked Questions

01. What is bacterial gene therapy for chronic wounds?

Bacterial gene therapy for chronic wounds uses, non-pathogenic lactic acid bacteria applied directly to a wound, genetically engineered to continuously produce and release human therapeutic proteins at the site of injury. Rather than delivering a fixed drug dose, the living bacteria act as millions of nanoscale bioreactors, secreting growth factors and cytokines exactly where the wound needs them. Aurealis Therapeutics pioneered this approach using Lactococcus cremoris, a food-grade bacterium engineered to produce three therapeutic proteins simultaneously, delivering combination biological therapy as a single product.

Chronic wounds such as Diabetic Foot Ulcers fail to heal because diabetes simultaneously disrupts all four stages of normal wound healing are disrupted — inflammation resolution, tissue proliferation, angiogenesis, and epithelialization — trapping the wound in a persistent, destructive inflammatory state. Macrophages remain locked in a pro-inflammatory M1 phenotype instead of converting to regenerative M2, new blood vessel formation is suppressed, and fibroblast activity is impaired [1]. Because the dysfunction is multi-factorial, single-target treatments cannot restart the healing cascade on their own. Between 1–2% of the population in developed countries suffer from chronic wounds at any given time [2], and diabetic foot ulcers account for more than 60% of all non-traumatic lower-limb amputations [1].

References:

  1. doi:10.1371/journal.pone.0264775
  2. doi:10.1186/s13643-016-0400-8

The Aurealis Therapeutics platform is a modular synthetic biology cell and gene therapy platform based on Lactococcus cremoris — a non-pathogenic, food-grade lactic acid bacterium — genetically engineered to produce and release multiple human therapeutic proteins simultaneously at the disease site. It is the only platform in the world to have genetically engineered bacteria expressing three human therapeutic proteins simultaneously (for example h-CSF-1, h-FGF-2 and h-IL-4 in the case of AUP-16). Using an established bacterial backbone, a new customized product expressing 2–3 target proteins can be built in approximately six to ten weeks, making the platform applicable across chronic wounds, oncology, and inflammation.

Each bacterium is engineered to carry approximately 90 copies of a multi-gene expression plasmid, turning every cell into a nanoscale bioreactor that continuously synthesizes and secretes multiple human proteins directly in the wound. The high plasmid copy number amplifies protein output per cell, and because production happens locally, therapeutic concentrations are sustained at the site of action without systemic exposure. All proteins produced are accepted by regulators as a single Active Pharmaceutical Ingredient (API), avoiding the complexity of a traditional multi-drug combination.

Lactococcus cremoris has centuries of safe use in food fermentation, carries Qualified Presumption of Safety (QPS) status from EFSA and GRAS status from the FDA, and produces no endotoxins — making it inherently safer than gram-negative bacterial vectors or viral gene therapy vectors. Because the bacteria produce therapeutic proteins locally and continuously, they achieve sustained high concentrations at the wound without systemic side effects or the rapid degradation associated with single-dose protein application. Fermentation-based manufacturing of lactic acid bacteria is well established at industrial scale, enabling low cost of goods, a critical factor for broad patient access.

References:

  1. doi:10.1371/journal.pone.0264775

In the completed Phase 1 study, 67% of patients with non-healing diabetic foot ulcers achieved complete wound closure at 20 weeks with recommended Phase 2 dose, up to 83% at the end of the study, with zero recurrences during 12 months of follow-up [1]. In the Phase 2 DIAMEND randomized controlled trial (64 patients, 10 sites across Germany, Italy, and Poland), AUP-16 administered twice weekly achieved a complete wound closure rate of 64% versus 20% in the placebo group (+44%, p < 0.05, Per Protocol population) and 60% versus 24% (+36%, p < 0.05, Intention-to-Treat population), both in patients with chronic DFUs of more than three months’ duration. No serious adverse reactions or safety concerns related to AUP-16 were observed [2]. Final DIAMEND results were presented by Prof. Alberto Piaggesi at the EWMA 2026 conference in Bremen, May 2026.

References:

  1. doi:10.1177/20420188241294134 
  2. doi:10.13140/RG.2.2.18401.06240 

The Aurealis Therapeutics technology platform is supported by peer-reviewed journal articles, clinical study publications, and conference presentations at leading medical societies including EWMA and ASCO. 

The full and up-to-date publication list is available at: aurealistherapeutics.com/pipeline-and-science/#publications.

Single-target treatments — including growth factor products, wound dressings, negative pressure therapy, and skin substitutes — each address only one aspect of the wound healing process, leaving the other disrupted pathways untreated [1]. Aurealis Therapeutics’ 4-in-1 platform simultaneously targets chronic inflammation (via IL-4-driven M2 macrophage conversion), angiogenesis and granulation tissue formation (via FGF-2), and immune microenvironment remodeling (via CSF-1) — all delivered as a single API [1, 2]. The clinical impact of this approach was demonstrated directly in the DIAMEND Phase 2 trial: AUP-16 achieved a 3.2-fold higher complete wound closure rate than placebo plus standard of care [3].

References:

  1. doi:10.1371/journal.pone.0264775
  2. doi:10.1177/20420188241294134
  3. Aurealis Therapeutics. DIAMEND Phase 2 results press release. December 4, 2025. aurealistherapeutics.com