1. Madam Therapeutics Next generation antibiotics to fight global anti-microbial resistance
November 2017

2. Scientific background

3. SAAPs synthetic Antimicrobial Antibiofilm Peptides
MadamTx has access to a family of SAAPs – lead SAAP-148
IP exclusively licenced from LUMC, national phase entered summer 2016
Mechanism of action different from current antibiotics, inspired by natural defense peptide LL37
24 amino acids
Very rapid bacterial killing
The peptides kill the bacteria from the outside unlike traditional antibiotics
Highly effective in in-vitro (lab) and in animal models
Active against very broad spectrum of pathogens
Gram+ and Gram- bacteria
Planktonic and Biofilm residing bacteria, including “persister” cells,
Replicating and dormant bacteria
Multi- and PAN resistant bacteria
Robust against bacterial resistance development
Favorable safety profile
Have shown potential beyond topical use

4. How do our SAAPs work? α-helices integrate
into the cell membrane as pentamers, causing a hole in the membrane
Cytoplasm leaks from the bacteria which are consequently killed

5. Killing in minutes rather than hours or days
“Time to kill” assay
Killing of S. aureus JAR after 0.5 – 120 min exposure.
Results are expressed as mean number of CFU (colony forming units) per ml with standard deviations of three replicates

6. SAAP-148 is robust to resistance development in Gram+ and Gram- bacteria
No increase in MIC after 20 serial passages in sub- inhibitory concentrations of SAAP-148
Results are expressed as fold change in MIC (Minimal Inhibitory Concentration)

7. Powerful dose-response relationship
SAAP148 formulated in hypromellose was highly effective in eradicating
MRSA and A. baumannii from wounded skin in a “Tape strip mice infection model”.

8. Our peptides are best in class
LC99.9% is the lowest concentration of the peptide that in vitro kills 99.9% of the bacteria within 1 hr

9. Planning of clinical studies
2017
2018
2019
2020
2021
2021
Today
Peptide production & preparation for AD trial
2017
12/4/2017
6/29/2018
Atopic Dermatitis exploratory phase I/IIa trial
7/2/2018
018
Preparation of peptide production for DFU trial
150 days
5/31/2018
11/30/2018
Peptide production & preparation DFU trial
110 days
11/30/2018
2/28/2020
Diabetic Foot Ulcer phase I study
132 days
3/2/2020
12/31/2020
Diabetic Foot Ulcer phase IIa study
326 days
1/1/2021
9/30/2021
219 days
Step 1
Step 2
195 days