Multi-target bacterial gene therapy for chronic wounds and cancer

Abstract

Complex diseases like chronic wounds and cancers are multi-factorial. Unfortunately, existing treatments are unable to address multiple biologic targets. Aurealis' platform and gene therapy products are uniquely suited to address those needs. Aurealis' 4-in-1 products can be deployed directly at the site of the disease, delivering multiple therapeutic factors-cytokines, chemokines, growth factors, antibody fragments...-adapted to a specific indication. This allows very high efficacy, a clear regulatory pathway-multiple factors in one API-and substantially lower manufacturing costs versus other treatment types such as CART or viral vectors. In this poster we show the development and high clinical efficacy of this approach for chronic wounds-such as diabetic foot ulcers-and preclinical data for ovarian and peritoneal cancer. Host: Lactococcus cremoris non-pathogenic, transient and with immune-activating properties.

Full text

AUREALIS THERAPEUTICS • Multi-target cell and gene therapies for unmet medical needs • www.aurealistherapeutics.com
Complex diseases like chronic wounds and cancers are mul-factorial. Unfortunately, exisng treatments are unable to address mulple biologic targets. Aurealis’ plaorm and gene therapy products are uniquely suit-
ed to address those needs. Aurealis’ 4-in-1 products can be deployed directly at the site of the disease, delivering mulple therapeuc factors - cytokines, chemokines, growth factors, anbody fragments... - adapted
to a specic indicaon. This allows very high ecacy, a clear regulatory pathway - mulple factors in one API - and substanally lower manufacturing costs versus other treatment types such as CAR-T or viral vectors.
In this poster we show the development and high clinical ecacy of this approach for chronic wounds - such as diabec foot ulcers - and preclinical data for ovarian and peritoneal cancer.
Host: Lactococcus cremoris
non-pathogenic, transient and
with immune-acvang properes.
Constructs: Making use of procaryoc genec elements to
design operons consisng of an inducible promoter (Reg),
signal sequences (SS), internal ribosome binding sites (RBS),
the human target genes and a terminator (T).
AUP-16 FOR CHRONIC WOUNDS AUP-55 FOR ONCOLOGY
CONSTRUCT
MANUFACTURING
The modular design of Aurealis’ plaorm and gene therapy products makes them an ideal system to approach complex mul-factorial diseases such as chronic wounds and cancer. The proof of concept and posive
Phase 1 clinical trial results by Aurealis helps to pave the way for a new generaon of mul-factor gene therapies for unmet medical needs.
PHASE 1 CLINICAL TRIAL
GMP manufacturing for clinical trials in a sterile, single-use closed
system to ensure a monosepc product.
CONSTRUCT
Igor Mierau1, Haritha Samaranayake1, Jere Kurkipuro1, Wesley Smith1, Hanna-Riikka Kärkkäinen1, Mirka Tikkanen1, Laurent Décory1,
Thomas Wirth1, Juha Yrjänheikki1
1 Aurealis Therapeucs
MULTI-TARGET BACTERIAL GENE THERAPY
FOR CHRONIC WOUNDS AND CANCER
MODE OF ACTION
ACTIVATION OF
INNATE IMMUNE SYSTEM
TARGET 1:
ACTIVATION OF
ADAPTIVE IMMUNE SYSTEM
TARGET 2:
BLOCKING OF
ANGIOGENESIS
TARGET 3:
DIRECT TUMOR CELL
KILLING EFFECT
TARGET 4:
PRE-CLINICAL STUDY
CONCLUSIONS
Cytokine armed Lactococcus cremoris AUP-55 enables mulmodal acon. Treatment with AUP-55
suggests an-tumor acvity as a single therapeuc enty for the treatment of ovarian cancer and
peritoneal carcinomatosis.
In the ID8 model, treatment was started 14 days aer tumor
implantaon. Most untreated mice were terminated due to the
disease progress. Treatment with AUP-55 resulted in 91.3 %
survival and lower tumor load during the study duraon of 81
days compared to the 0 % survival and massively increased tu-
mor load in untreated mice.
All AUP-55 treatments were well tolerated. In the pathology
post-mortem, all untreated animals had typical ndings for ovar-
ian cancer, such as ascites and high number of tumor nodules
present in abdominal cavity, liver, spleen, kidney and pancreas.
In the group treated with AUP-55 there were no macroscopic
tumor deposits detected.
Intratumoral
injecon
Metastasis
AUP-55
For injecon
AUP-55 enables complete survival in interperitoneal mouse ovarian cancer model ID8.
Model: interperitoneally implanted ID8-Luc-mCH-Puro. TD1 murine ovarian carcinoma
model in female albino C57BI/6 mice.
Treatment: AUP-55 = mIL18-mGM-CSF
MODE OF ACTION
Best in class ecacy:
• 83% of the paents who received the
lead therapeuc dose reached complete
healing.
• >30% wound size reducon in rst 2
weeks treatment vs. >17% wound size
increase in 2 weeks run-in period with
SOC
• Median me to heal: 6.7 weeks / 65 days.
• No recurrence of healed wounds aer 12
months follow-up.
• No Dose Liming Toxicity, no systemic
or local safety nor tolerability issues.
Vehicle (5% Dextrose / 0.9 % NaCl)
AUP5591m-C#3
BLI = Bioluminescent Imaging
Before treatment
Wound 10 weeks old
End of treatment
6 weeks
2 weeks aer
end of treatment
4 weeks aer
end of treatment
EXAMPLE: Cohort 2,
low dose 2.5E+06 cfu/
cm2 3 mes per week
for 6 weeks
SUMMARY
INTRODUCTION
OVARIAN AND PERITONEAL CANCERDIABETIC FOOT ULCER
AUP-55
Stable disease in AUP-55 and 100% survival (tumor exists but does
not grow/kill). Treatment started on day 14 and ended on day 39.
Vehicle
All vehicle treated mice died
before Day 45.