Olumacostat glasaretil (OG) / DRM01 MOA: Acetyl Coenzyme A Carboxylase Inhibito

Acne Vulgaris
Phase IIa Lesion Count
n=108 Inflammatory Non-inflammatory
Mean Number Mean Absolute % Change at Mean Number
(Wk 0) Change (Wk 12) 12 Wks (Wk 0)
Vehicle only 28.6 -13.3 -45.9 38.8
7.5% OG (BID) 29.7 -19.3 -63.9 40.9
p=0.0003 p=0.0032

Phase IIb % Change in No. Inflammatory Lesions

n=420 4 Wks Significance 12 Wks Significance
Vehicle only -26.7 N/A -40.0 N/A
4% OG (QD) ND ND ND "p<0.05"
4% OG (BID) ND ND ND ND
7.5% OD (QD) ND ND ND "p<0.05"
7.5% OD (BID) -33.7 p=0.107 -55.6 p=0.001

ND: Not Disclosed

Phase III Primary Endpoints

CLAREOS-1 (n=759) 1) Mean absolute change in acne lesion counts (inflammatory and non-inflamm
CLAREOS-2 (n=744) 2) Proportion of subjects who achieved ≥ 2-grade improvement and a grade o
Due Q118
Secondary Endpoints
1) Percent change in acne lesion counts (inflammatory and non-inflammatory
2) Proportion of subjects who achieved ≥ 2-grade improvement in the investig
yme A Carboxylase Inhibitor

t Investigator Global Assessment (IGA) Score

Non-inflammatory Score at Baseline Change in Score at 12 Wks (% of Patie
Mean Absolute % Change at 3 (Moderate) 4 (Severe) 1 Grade Grade
Change (Wk 12) 12 Wks Worsened Unchanged
-11.2 -28.8 52 3 1.8% 54.5%
-19.3 -48.1 47 6 0% 34%
p=0.0032 p=0.0025
Note: only ≥2 grade improvement deemed 'clinically m

% Change in No. Non-inflammatory Lesions % Patients w. ≥2 Grade IGA Improvem

4 Wks Significance 12 Wks Significance 4 Wks Significance
-16.5 N/A -28.7 N/A 2.3 N/A
ND ND ND "p<0.05" ND ND
ND ND ND ND ND ND
ND ND ND "p<0.05" ND ND
-22.7 p=0.283 -47.8 p<0.001 4.1 p=0.495

mmatory and non-inflammatory lesions) from baseline to Week 12

provement and a grade of 0 or 1 in the investigator global assessment of acne (IGA) from baseline to Week 12

ry and non-inflammatory lesions) from baseline to Week 12

provement in the investigator global assessment of acne (IGA) from baseline to Week 12
ssment (IGA) Score
Score at 12 Wks (% of Patients)
1 Grade 2+ Grade
Improvement Improvement
36.4% 7.3%
41.5% 24.5%
p=0.007
ovement deemed 'clinically meaningful'

s w. ≥2 Grade IGA Improvement

12 Wks Significance
9.8 N/A
ND ND
ND ND
ND p=0.06
25.9 p=0.004

) from baseline to Week 12

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4
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A significant DRM01 signal was present in sebaceous glands re
surrounding dermis. After 7 days of twice daily treatment with 7.
gel, levels of 41 sebum lipids were decreased (all statistically sig
differences; p<0.01)'. (Yorkshire pig model)

OG (6% w/w) in solvent mixture significantly reduced relative se

gland size when applied twice daily for 14 days (21.4 ± 12.7%),
21 days (16.5 ± 17.6%) or twice daily for 21 days (20.4 ± 10.1%
treatment, sebaceous glands were generally less lobular in appe
(Figure 4B-C). The ear sebaceous gland area for hamsters treat
gel (7.5% w/w) daily for three weeks was 15.3 ± 7.3% lower than
gel-treated animals (p <0.05).

In answer to the question ‘Can sebum reduction predict acne ou

evidence in the literature supports the answer of ‘Yes’. Acne out
appears to be highly dependent on sebum reduction not only wi
studies, but also across studies and multiple drug classes.

Sebum reduction of 30–50% would be required to achieve 50%

acne measures.
The inhibition of ACC, the rate-limiting enzyme of fatty acid de n
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