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Baseline characteristics

• In total, 18 subjects (face, n=9; scalp, n=9) were enrolled and completed the study (Table

1).

• The mean (standard deviation, SD) age of subjects was 66.4 (9.42 [range: 43‒83])

years.

• Subjects were White, predominantly male (83.3%) with Fitzpatrick skin type I‒III (94.4%)

and a mean (SD) baseline AK lesion count of 8.2 (2.43 [range: 6‒14]).

• Mean (SD) dose applied was 137 (44.9) mg among the combined subject group (~55%

of the full dose possible, 250 mg).

RESULTS

Regina Yavel,1 J. Scott Overcash,2 Jay Zhi,3 Eva Cutler,3 David Cutler,3 Jane Fang,3
1TKL Research Inc., Fair Lawn, NJ, USA; 2eStudySite, La Mesa, CA, USA; 3Athenex Inc., Buffalo, NY, USA

PHASE I MAXIMAL USE PHARMACOKINETIC STUDY OF TIRBANIBULIN OINTMENT 1% IN SUBJECTS WITH ACTINIC KERATOSIS

• The primary objective was to determine the PK of tirbanibulin ointment 1% under

maximal use conditions.

• Secondary objectives were to evaluate the safety and tolerability of tirbanibulin

ointment 1% and to determine the PK of tirbanibulin metabolites.

OBJECTIVES

• Writing support was provided by TFS S.L. 

• This study was sponsored by Athenex, Inc..

ACKNOWLEDGEMENTS

CONCLUSIONS

• Under maximal use conditions, low systemic exposure of tirbanibulin with

subnanomolar plasma concentrations for both parent drug and metabolites was

confirmed.

• Tirbanibulin ointment 1% for 5 days was well tolerated for the treatment of AK on

the face/balding scalp.

METHODS

Study design

• Subjects (aged ≥18 years) with ≥6 clinically typical, visible and discrete AK lesions on

25 cm2 of the face/balding scalp were enrolled in the study.

• Subjects self-applied sufficient tirbanibulin to cover the treatment area (25 cm2 area of

the face/balding scalp) from the 250 mg sachet once-daily for 5 consecutive days.

Subjects were instructed to avoid touching or wetting the treatment area for at least 12

hours after drug application.

Study evaluations

Pharmacokinetics

• PK blood sampling (for tirbanibulin and its inactive metabolites [KX2-5036 and KX2-

5163]) occurred on Days 1, 3 and 4 at 0 (pre-dose) and on Day 5 at 0, 2, 4, 6, 8, 10,

12, 16 and 24 hours post-the Day 5 application.

Safety

• Adverse events (AEs) were assessed.

• LSRs (erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation,

erosion/ulceration; scale of 0‒3 [absent‒severe]) were evaluated on Days 1, 6, 8, 15

and 29; and LSR composite scores were calculated as the sum of all individual LSR

scores at each visit with the possible range of 0–18.

• Tirbanibulin is a synthetic, highly selective, novel inhibitor of tubulin polymerisation and

Src kinase signalling developed as a first-in-class topical formulation for the treatment of

actinic keratosis (AK)1.

• In Phase I/II studies, tirbanibulin was minimally absorbed and systemic exposure was

low when applied topically.

• Previous Phase I and II studies showed that tirbanibulin ointment 1% for 5 days was

effective against AK lesions on the forearm, face and scalp. Local skin reactions (LSRs)

were mostly transient and mild-to-moderate in severity, and tirbanibulin was well

tolerated.2,3 These studies supported the further development of the 5-day clinical

regimen of tirbanibulin ointment 1% in treating AK on the face/scalp.

• Results from two Phase III studies (KX01-AK-003/KX01-AK-004), demonstrated that

tirbanibulin ointment 1% self-administered once-daily for 5 days resulted in higher rates

of complete lesion clearance at Day 57 compared with placebo (KX01-AK-003: 44% vs.

5%, P<0.0001; KX01-AK-004: 54% vs. 13%, P<0.0001) and was well tolerated,

potentially making it a valuable new addition to AK treatment4 (See EADO 2020 Poster

#35).

• Here, we present results from a Phase I, open-label, uncontrolled, non-randomised,

maximal use pharmacokinetic (PK) study (KX01-AK-007) evaluating the systemic

exposure and safety of tirbanibulin ointment 1% (5 days) applied to the face/balding

scalp of adults with AK.

SYNOPSIS

Safety

Adverse events

• Four subjects (face, n=1; scalp, n =3) experienced a total of 5 treatment-emergent AEs 

(TEAEs); all were unrelated to treatment.

• One subject in the scalp-treated group experienced a treatment-related TEAE (mild skin 

dryness; resolved spontaneously).

• There were no serious AEs, severe AEs, deaths or TEAEs leading to study 

discontinuation.

Local skin reactions

• LSRs on the treatment area were mostly transient, all were mild-to-moderate erythema 

and flaking/scaling that peaked around Day 8 (mean [SD] composite score: 3.4 [1.76]) 

before resolving or returning to baseline.

Table 1. Subject demographics and baseline characteristics

Face (n=9) Scalp (n=9) Combined (n=18)

Mean Age (SD), years 71.1 (6.92) 61.8 (9.58) 66.4 (9.42)

Gender: Female, n (%) 3 (33.3) 0 3 (16.7)

Male, n (%) 6 (66.7) 9 (100) 15 (83.3)

Race: White, n (%) 9 (100) 9 (100) 18 (100)

Ethnicity, n (%)

Hispanic or Latino 0 2 (22.2) 2 (11.1)

Not Hispanic or Latino 9 (100) 7 (77.8) 16 (88.9)

Fitzpatrick Skin Type,a n (%)

I 2 (22.2) 2 (22.2) 4 (22.2)

II 2 (22.2) 2 (22.2) 4 (22.2)

III 5 (55.6) 4 (44.4) 9 (50.0)

IV 0 1 (11.1) 1 (5.6)

Mean (SD) Baseline AK lesion count 8.4 (2.46) 7.9 (2.52) 8.2 (2.43)

40th Annual Fall Clinical Dermatology Conference, October 29 - November 1, 2020

Figure 1. (A) Mean trough plasma concentrations of tirbanibulin at Days 1, 3, 4 and 5; 

(B) Individual plasma concentrations of tirbanibulin with overall mean on Day 5 post-

dose

aType I: always burns easily, never tans; Type II: always burns easily, tans minimally; Type III: burns moderately, tans gradually; Type IV: burns minimally, always 

tans well. AK, actinic keratosis; SD, standard deviation.

Pharmacokinetics

Tirbanibulin

• Using an LC-MS/MS bioanalytical assay (lower limit of quantification [LLOQ] of 0.01 

ng/mL), all subjects had measurable but low concentrations of tirbanibulin at troughs 

(Figure 1).

• By the observed Ctrough plateau, the pre-dose concentration Ctrough data demonstrated that 

steady-state was achieved following the third dose (72 hours) of once-daily, 5 days of 

dosing.

• On Day 5, mean (SD) Cmax was 0.258 (0.231) ng/mL (0.598 nM), median tmax was 6.91 h, 

and mean (SD) AUC0-24h was 4.09 (3.15) ng∙h/mL (Table 2).

Tirbanibulin metabolites

• For the majority of subjects, plasma concentrations for the main tirbanibulin metabolites 

KX2-5036 (n=14/18) and KX2-5163 (n=13/18) were below the LLOQ of 0.05 ng/mL.

REFERENCES

1. Smolinksi, MP, et al. J Med Chem. 2018;61:4707-4719; 2. DuBois J, et al. Phase I study of tirbanibulin ointment 1%, a novel Src phosphorylation and tubulin

polymerization inhibitor, in subjects with actinic keratosis. Poster presented at the 6th Annual Practical Symposium, Beaver Creek, CO, USA, August 8–11, 2019; 3.

DuBois J, et al. Phase II study of tirbanibulin ointment 1%, a novel Src phosphorylation and tubulin polymerization inhibitor, for actinic keratosis. Poster presented

at the 6th Annual Practical Symposium, Beaver Creek, CO, USA, August 8–11, 2019; 4. Blauvelt A, et al. Tirbanibulin ointment 1% for actinic keratosis(AK):

Results from two Phase 3 studies with 1-year follow-up. Poster presented at the Maui Derm Virtual Congress, June 24-27, 2020

Table 2. Tirbanibulin plasma PK parameters following 5 days of consecutive topical 

dosing
Face (n=9) Scalp (n=9) Combined (n=18)

Mean (SD)

Cmax (ng/mL) 0.340 (0.297) 0.176 (0.102) 0.258 (0.231)

tmax
a (h) 6.0 (2.0, 9.8) 7.8 (2.0, 10.0) 6.91 (2.0, 10.0)

AUC0-24 (h*ng/mL) 5.0 (3.9) 3.18 (1.92) 4.09 (3.15)

aFor tmax, median (min, max) are reported. AUC0-24, area under the curve from 0-24 hours; Cmax, maximum plasma concentration; PK, pharmacokinetic; tmax, time 

of maximum concentration.

A

B