Liraglutide

Indications:

 

  • As monotherapy or in combinations with other medicinal products for the treatment of type 2 diabetes
  • Weight management

Liraglutide:

  • Liraglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist also known as incretin mimetic
  • 97% similarity with human glucagon-like peptide-1
  • By binding to GLP-1 receptors, Liraglutide stimulates insulin secretion
  • Liraglutide inhibits glucagon production, inhibits gastric motility and stimulates the hypothalamic satiety center
  • Solution for injection in multi-dose disposable pre-filled pen (subcutaneous administration)
  • Originator - Victoza by Novo Nordisk
  • Off-patent

Key Facts

21,7 mln

Liraglutide packs were sold in 2021*

*MIDAS Data by IQVIA

6,1 bln

Total market in 2021 in USD*

*MIDAS Data by IQVIA

2009                2010

MA in Europe                                                            MA in USA

avva-tech

AVVA`s
Technology

AVVA’s Liraglutide API Technology was developed in cooperation between AVVA Pharmaceuticals Ltd (Cyprus), and the Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry (Russia).

Know-how and patent protected IP rights:

 

  • Recombinant plasmid DNA for fusion protein expression
  • E. coli strain
  • Recombinant fusion protein production method
  • Liraglutide production method

Main Technology Features:

 

  • Specific Kanamycin – resistant E. coli strain:
    • Reduced contamination risk
    • Does not require dedicated production
  • Increased protein yield: result of producing strain genetic construct
  • Reduced fermentation cycle
  • Scalable technology
  • Specific impurities lower detection limits
  • Optimized purification process

AVVA’s Technology Advantages and Completed Milestones

Advantage AVVA NOVO Nordisk AVVA’s Advantage
1 Strain-based technology E. coli S.cerevisiae More robust
technology, lower
possibility of target
protein
degradation
2 Reduced fermentation cycle ~8 hours ~5 days Faster production
cycle
3 Process nutrient demand less more Cost effective
4 Target protein yield up to 5.3 g/l - Generally higher than
S.cerevisie-based
technology
5 Impurity profile 2 identified impurities* 3 identified impurities* Higher purity
product

Completed Milestones:

  • check-list

    Specific E. coli strain creation

  • check-list

    Master bank and Working bank

  • check-list

    Similarity to originator

  • check-list

    Analytical method

  • check-list

    Manufacturing:

    • 25 Pilot batches: 20 L – reactor with protein yield up to 3.7 g/l
    • 5 Scale up batches: 100 L reactor with protein yield up to 5.3 g/l
*based on HPLC analysis

Established Similarity

AVVA`s Liraglutide VS Victoza

AVVA`s Liraglutide

graph1

Victoza

PIC 1
graph2

Pre-Clinical Study in db/db mice

Victoza (300 μg/kg) and AVVA’s Liraglutide (300 μg/kg) show similar decrease on blood glucose levels at 4, 24 and 48 hours after administration, p> 0.9*

*data analysis by LSD test

Victoza 300 μg/kg

Liraglutide AVVA 300 μg/kg

Control group

Additional studies performed for establishing similarity

  • Peptite mapping
  • N-terminal sequencing
  • Mass spectrometry
  • Biological activity
  • Isoelectric focusing
  • SEC HPLC

License Conditions

    License
Conditions
  • Exclusive rights within the Territory
  • Patent validity within the Territory
  • License Fee:
    • Territory based
  • Milestone Payments:
    • Upon signature
    • On Dossier disclosure
    • Upon successful tech transfer completion
    • Upon M.A. grant
  • Tech Transfer expenses:
    • Covered by the licensee
  • Time to market:
    • Within 5 years post successful tech transfer
  • Royalties:
    • For 15 years post commercialization
diabetes

Diabetes.
Overview

Diabetes is a chronic disease that occurs either when the pancreas does not produce enough insulin or when the body cannot effectively use the insulin it produces. Insulin is a hormone that regulates blood glucose.

Hyperglycaemia is common in uncontrolled diabetes and may lead to a number of acute and chronic complications

Health impact

 

  • Acute complications:
    • Hyperosmolar Hyperglycaemic State (HHS)
    • Diabetic ketoacidosis (DKA)

Chronic complications

 

  • These are long-term problems that can develop gradually, and can lead to serious damage if they go unchecked and untreated.
  • Retinopathy
  • Heart attack / Stroke
  • Nephropathy
  • Diabetic foot syndrome
  • Kidney failure

Diabetes Key Facts

mln
537

Adults are living with diabetes. This number is predicted to rise to 643 million by 2030 and 783 million by 2045.

sec
5

death every 5 seconds. 6.7 million deaths in 2021 from diabetes

%
95

Type 2 diabetes represents more than 95% of total cases