PowerPoint Presentation


Sarecycline Demonstrates Narrow-spectrum Antibacterial Activity and Anti-inflammatory

Effect in Animal Models
Christopher Bunick1, James Del Rosso2, Stephen Tyring3, Michael Draper4, Jodi L. Johnson5, Ayman Grada6

1Department of Dermatology, Yale University School of Medicine, New Haven, CT, USA, 2JDR Dermatology Research LLC/Thomas Dermatology, Las Vegas and Henderson, Nevada, USA 3University of Texas Health Science Center, Department 

of Dermatology & Center for Clinical Studies, Houston, TX, USA, 4Paratek Pharmaceuticals, Inc.(at the time of the study), Boston, -Massachusetts, USA, 5Departments of Dermatology and Pathology, Feinberg School of Medicine, Northwestern 

University, USA,  6R&D and Medical Affairs, Almirall (US), Exton, Pennsylvania, USA

Poster accepted for Winter Clinical Dermatology meeting  2021.

Introduction

Methods

Results - Table 1. Efficacy of sarecycline and 

comparators against S. aureus and E. coli in mice

Results - Table 2. Efficacy of sarecycline and 

doxycycline against S. aureus tissue infection

Results - Table 3. Anti-inflammatory effect of sarecycline and 

comparators in rat footpad model

Antibacterial S. aureus RN450-1 E. coli PBS1478

agent
MIC 

(mg/mL)

PD50
(mg/kg)

MIC (mg/mL)
PD50

(mg/kg)

Sarecycline < 0.06 0.25 4 > 40

Doxycycline < 0.06 0.3 0.5 5.72

Minocycline < 0.06 0.03 1 6.95

Murine systemic infection model at 48 h post-infection.

Agent MIC (mg/mL) ED50 (mg/kg)

Sarecycline < 0.06 8.23

Doxycycline < 0.06 8.31

➢ Sarecycline demonstrated in vivo efficacy against S. aureus but not E. coli in animal models of infection, in agreement with the narrower-spectrum of activity observed in in vitro studies.  

➢ Sarecycline showed anti-inflammatory effect comparable to doxycycline and minocycline in the rat footpad edema model. 

Discussion 

Compound Mean % inflammation compared to untreated controls

150 

mg/kg

100 

mg/kg

75 

mg/kg

50 

mg/kg

25 

mg/kg

10 

mg/kg

5 

mg/kg

1 

mg/kg

Sarecycline 25.8 53.1 55.7 52 59 65.2 77.8 103.3

Doxycycline - 36 67.6 - - - - -

Minocycline - 20.5 53.9 32.9 47.2 - - -

Carrageenan-induced rat footpad edema model

➢ Sarecycline is the first narrow-spectrum tetracycline-class antibiotic to be 

developed for the treatment of acne vulgaris.

▪ Sarecycline is an FDA-approved tetracycline-class oral antibiotic specifically 

developed for the treatment of moderate-to-severe acne vulgaris.

▪ In vitro studies demonstrated a narrow-spectrum antibacterial activity, targeting 

clinically relevant Gram-positive bacteria while showing reduced activity against 

Gram-negative bacteria commonly found in the human gastrointestinal tract.

▪ Here we report results of In vivo antibacterial and anti-inflammatory studies in 

mouse and rat models.

In vivo antibacterial activity

Table 1. A murine systemic (intraperitoneal) infection model was utilized to assess the 

in vivo efficacies of sarecycline, doxycycline, and minocycline against S. aureus

RN450-1 and E. coli PBS1478.

Table 2. A murine neutropenic thigh wound infection model was utilized to represent a 

tissue-based infection to assess the comparative efficacies of sarecycline and 

doxycycline against S. aureus RN450-1.

Anti-inflammatory effect In vivo

Table 3. To evaluate the anti-inflammatory effects of sarecycline, a carrageenan-

induced rat footpad edema model was utilized. Male, Sprague Dawley rats were 

intraperitoneally injected with saline, sarecycline, or a positive control (doxycycline or 

minocycline) and inflammation was determined as change in paw volume. Percent 

inflammation was calculated as 100 x [(post paw volume at 3 hours – pre paw volume 

at 0 hours)/pre paw volume at 0 hours].

Conclusions

Murine neutropenic thigh wound infection model to represent tissue-based infection with S. aureus RN450-1.

References

Zhanel G, et al. Microbiological Profile of Sarecycline, a Novel Targeted Spectrum Tetracycline 

for the Treatment of Acne Vulgaris. Antimicrob Agents Chemother: 2018 Dec;63(1):e01297-18.

Carrageenan-induced rat footpad edema model experiments performed by Paratek 

Pharmaceuticals. Data on file with Almirall.

➢ The reduced activity of sarecycline against bacteria commonly found in 

the gut suggests reduced risk of antibiotic resistance within the GI tract 

microbiome.

➢ Sarecycline proved effective against S. aureus (G+ Bacteria) in both 

systemic and tissue-based infection models in mice.  However, low 

efficacy was demonstrated vs. E.coli  (G- enteric bacteria).

➢ The anti-inflammatory effect of sarecycline in rats is similar to doxycycline 

and minocycline, and in agreement with sarecycline being efficacious for 

inflammatory moderate-to-severe acne lesions in humans.

MIC – minimum inhibitory concentration; PD50 – protective dose required to achieve 50% survival

MIC – minimum inhibitory concentration; ED50 – effective dose required to achieve a 50%, or 2-log10,   

reduction in bacterial burden

Corresponding email:Grada@bu.edu