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Sienna Biopharmaceuticals Announces Its Topical, Non-Steroid TrkA Inhibitor SNA-120 (0.05%) Demonstrated Significant Impact on Psoriasis in Phase 2b Study and Plans to Initiate Phase 3 Psoriasis Trials

Posted on: December 6, 2018 | Posted in: Relationships & Accomplishments
Sienna Biopharmaceuticals Announces Its Topical, Non-Steroidal TrkA Inhibitor SNA-120 (0.05%)
Demonstrated Significant Impact on Psoriasis in Phase 2b Study and Plans to Initiate Phase 3 Psoriasis
Trials in Second Half of 2019
-- 27% of subjects achieved 75% reduction in PASI score (PASI 75) vs 13% with vehicle; 29% of subjects
achieved two-grade improvement on IGA and ‘clear’ or ‘almost clear’ skin vs 13% with vehicle
(statistically significant)
-- Subjects achieved 58% improvement in itch from baseline on the I-NRS vs 55% with vehicle (not
statistically significant)
-- SNA-120 was well tolerated with few treatment-related adverse events
-- Sienna also reported data from exploratory Phase 1/2 study of atopic dermatitis with SNA-125; Phase
2 study expected to begin second half 2019
-- Company will conduct conference call and webcast today at 8:15 am ET
WESTLAKE VILLAGE, Calif., Dec. 3, 2018 – Sienna Biopharmaceuticals, Inc. (NASDAQ:SNNA), a clinicalstage
medical dermatology and aesthetics company, today announced top-line results from a Phase 2b
study of SNA-120 (pegcantratinib), the Company’s lead drug candidate developed using its proprietary
Topical by Design™ platform. This Phase 2b study, in mild-to-moderate psoriasis patients with at least
moderate pruritus (itch), was designed to assess the efficacy and safety of SNA-120 on itch (primary
endpoint), as well as the underlying psoriasis (secondary endpoints). In this study, subjects treated with
SNA-120 (0.05%) achieved statistical significance, compared to vehicle, on important pre-specified
regulatory endpoints of psoriasis disease severity. Subjects treated with SNA-120 also experienced a
meaningful reduction in itch, although the result did not reach statistical significance against vehicle.
SNA-120 is a topical tropomyosin receptor kinase A (TrkA) inhibitor that blocks nerve growth factor (NGF)
signaling, which plays an important role in the pathogenesis of psoriasis and itch. SNA-120 was developed
using Sienna’s Topical by Design™ platform, which yields new chemical entities (NCEs) designed to deliver
high local drug concentration in the target tissue with minimal to no systemic exposure for patients.
Sienna’s multicenter, randomized, double-blind, vehicle-controlled Phase 2b study evaluated the safety
and efficacy of two doses (0.05% and 0.5%) of SNA-120 ointment in 208 male and female patients over
the age of 18 with mild-to-moderate psoriasis and with at least moderate itch. Subjects were randomized
into three groups and administered a high dose (0.5%) of SNA-120, a low dose (0.05%) of SNA-120 or
vehicle twice daily for 12 weeks.
The primary endpoint of the study was mean change from baseline to week eight on the Itch Numeric
Rating Scale (I-NRS). The I-NRS is an 11-point scale ranging from ‘no itch’ (0) to the ‘worst imaginable itch’
(10) that study participants used daily to report the intensity of their worst itch in the previous 24 hours.
Patients treated with SNA-120 (0.05%) experienced a mean 4.3 point (58%) reduction from baseline on
the I-NRS, compared to a mean 4.0 point (55%) reduction with vehicle (not statistically significant,
p=0.244). SNA-120 (0.5%) showed similar results.
On pre-specified, key secondary endpoints related to the clearance of psoriatic plaques, SNA-120 (0.05%)
demonstrated statistically significant and clinically meaningful improvements. Specifically, 27% of
subjects experienced a 75% reduction in their Psoriasis Area and Severity Index (PASI 75) score from
baseline, compared to 13% of subjects treated with vehicle (p=0.045). The study also included an
Investigator Global Assessment (IGA), in which 29% of patients achieved a two-grade improvement and
‘clear’ or ‘almost clear’ skin, compared to 13% of subjects treated with vehicle (p=0.036). Both the PASI
75 and IGA results remained statistically significant at 14 weeks, two weeks after discontinuation of
treatment. The high dose (0.5%) of SNA-120 did not show statistical significance on these study endpoints.
SNA-120 was well-tolerated with no serious treatment-related adverse events. Treatment-related
adverse events were observed in two patients and included dermatitis (0.5% group) and pain and pruritus
(vehicle group). SNA-120 has now been tested in more than 500 patients and has been consistently well
tolerated with a safety profile that further validates Sienna’s Topical by Design™ platform
“These results, although not entirely as we expected, are very exciting. While we did not meet our primary
endpoint on pruritus, SNA-120 demonstrated statistically significant and clinically meaningful effects on
key secondary psoriasis endpoints that were greater than anticipated,” said Frederick C. Beddingfield III,
MD, PhD, President and Chief Executive Officer of Sienna Biopharmaceuticals. “In addition to its
significant effect on psoriatic plaques, SNA-120 reduced itch by 58%, although it did not separate from
vehicle. This may be partially due to the beneficial emollient effect of the vehicle and the inherent variability
in patient-reported assessments. Taken together, these results demonstrate the potential of
SNA-120 as a novel topical, non-steroidal treatment for psoriasis. Moving ahead, we plan to pursue a
psoriasis indication for SNA-120 with pruritus measured as a secondary endpoint. We expect to start our
Phase 3 studies for psoriasis in the second half of 2019.”
Local peripheral nerves in the skin play an important role in the pathogenesis of psoriasis, as the absence
of neural input has been shown to lead to plaque clearance. Plaques in psoriasis patients with associated
itch have elevated levels of NGF-immunoreactive keratinocytes and TrkA expression in innervating nerve
fibers. The NGF/TrkA signaling pathway is important in neurogenic inflammation and keratinocyte
hyperproliferation which contribute to psoriatic plaques, as well as itch.
“SNA-120 selectively targets the NGF-TrkA signaling pathway,” said Paul F. Lizzul, MD, PhD, Chief Medical
Officer of Sienna Biopharmaceuticals. “In our second Phase 2b study, we enrolled psoriasis patients with
at least moderate itch, which may be a proxy for elevated NGF/TrkA activation. We believe, based on our
evolving understanding of the importance of neurogenic inflammation in psoriasis, that enriching the
patient population in this study and specifically targeting the NGF-TrkA signaling pathway within the
plaque contributed to the observed effects of SNA-120, on both PASI 75 and composite IGA.”
“These are promising results for an innovative, non-steroidal, topical treatment for the large majority of
psoriasis patients who have mild-to-moderate disease but are not candidates for systemic therapies,” said
Alan Menter, Chair of dermatology at Baylor Scott & White, Dallas, Principle Faculty at Texas A&M
University Health Science Center, and a clinical professor of dermatology at the University of Texas
Southwestern Medical School. “Given the safety profile observed in this Phase 2 study, SNA-120 could
also potentially address the unmet need for treating sensitive areas such as the face and skin folds. If
these results are replicated in Phase 3 studies, this type of innovation could be of significant interest to
physicians and patients with mild-to-moderate psoriasis.”
SNA-125 Phase 1/2 Study in Atopic Dermatitis
Sienna also announced results from an exploratory Phase 1/2 study of its investigational new chemical
entity SNA-125, a JAK3/TrkA inhibitor being evaluated as a first-in-class topically administered
medication to treat atopic dermatitis. JAK3 inhibition blocks the signaling of key cytokines, resulting in
reduced severity of certain autoimmune and inflammatory diseases.
This early-stage randomized, double-blind, vehicle-controlled, intra-individual study, using a target
lesion model, was designed to evaluate the safety and efficacy of SNA-125 gel in 30 patients with atopic
dermatitis. The study compared a high dose (2%) and a low dose (0.2%) of SNA-125 with a vehicle and
an active control. Subjects were treated in the clinic once daily for 14 days, with each treatment
topically applied to a small and distinct area.
In this study, SNA-125 was well tolerated and showed no safety signals in both healthy subjects and
patients with atopic dermatitis, with no serious adverse events reported. The most common treatmentrelated
adverse events were pain and pruritus. Similar small reductions in clinical scores of target
lesions were observed for both SNA-125 and vehicle; however, certain histological and biomarker
changes indicated a modest drug effect with SNA-125. The Company plans to initiate a Phase 2 study
with SNA-125 in atopic dermatitis in the second half of 2019.
Conference Call and Webcast
Sienna will host a conference call today, December 3, at 8:15 a.m. Eastern Time to discuss the SNA-120
Phase 2b trial results. Callers should dial in approximately 10 minutes prior to the start of the call. No
reservation is necessary to participate on the call. The phone number to join the conference call is +1
(877) 376-9929 (toll-free in the United States and Canada) or +1 (629) 228-0733 (international). The
conference identification number for the live call is 6081337.
The call will be webcast live and can be accessed through the Investor Relations section of the Company’s
website at An archived version of the webcast will be available approximately
two hours following the live call for 90 days.
About Sienna’s Topical by Design™ Platform
Topical by Design™ is an innovative platform, designed to enable the topical application of potent active
pharmaceuticals against known biologic targets while minimizing exposure to the systemic circulation,
thereby addressing the tolerability trade-offs that often make therapies unsuitable for use in larger
segments of the population with less severe disease. Topical by Design™ applies a scientific design process
to transform molecules into NCEs by stabily linking a short polyethylene glycol (PEG) polymer to a
pharmacologically active molecule. Applying this technology, we have created a pipeline of drug
candidates with unique pharmacological profiles to manage a variety of chronic inflammatory and immunologic conditions. Applications for the Topical by Design™ platform are currently being explored
with SNA-120 for use in psoriasis, and SNA-125 for use in atopic dermatitis, psoriasis and pruritus.
About Sienna Biopharmaceuticals
Sienna Biopharmaceuticals, Inc. is a clinical-stage biopharmaceutical company focused on bringing
innovations in biotechnology to the discovery, development and commercialization of first-in-class,
targeted, topical products in medical dermatology and aesthetics. The Company’s objective is to develop
a unique, diversified, multi-asset pipeline of topical therapies that enhance the health, appearance and
quality of life of dermatology and aesthetics patients. Sienna is led by a management team with extensive
experience in product development and commercialization at several leading dermatology, aesthetics and
biotechnology companies.
For more information, visit the Company’s website at
Forward-Looking Statements
This press release contains forward-looking statements, including but not limited to statements by
Sienna’s Executive Officers and Alan Mentor, M.D. regarding Sienna’s expectations for SNA-120, including
the potential for SNA-120 to be an effective treatment for psoriasis and the initiation of Phase 3 clinical
trials, as well as Sienna’s expectations for additional data readouts for its clinical trials. Such forwardlooking
statements involve substantial risks and uncertainties that could cause Sienna’s clinical
development programs, future results, performance, or achievements to differ significantly from those
expressed or implied by the forward-looking statements. Such risks and uncertainties include, among
others, the uncertainties inherent in the pharmaceutical drug and medical device development processes,
including the clinical development process, regulatory approval processes, the timing of regulatory filings,
the challenges associated with manufacturing pharmaceutical drug and medical device products, Sienna’s
ability to successfully protect and defend its intellectual property, and other matters that could affect the
sufficiency of existing cash to fund operations and the availability or commercial potential of Sienna’s drug
candidates. Sienna undertakes no obligation to update or revise any forward-looking statements. For a
further description of the risks and uncertainties that could cause actual results to differ from those
expressed in these forward-looking statements, as well as risks relating to the business of the Company
in general, see Sienna’s most recent Annual Report on Form 10-K and any subsequent current and periodic
reports filed with the Securities and Exchange Commission.
Caroline Van Hove
Crystal Muilenburg
Sean Andrews