SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): December 3, 2018
SIENNA BIOPHARMACEUTICALS, INC.
(Exact name of registrant as specified in its charter)
(State or Other Jurisdiction of
Incorporation or Organization)
30699 Russell Ranch Road, Suite 140
Westlake Village, CA 91362
(Address of principal executive office, including Zip Code)
Registrants telephone number, including area code: (818) 629-2256
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):
Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
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Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).
Emerging growth company ☒
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|Item 8.01.|| |
On December 3, 2018, Sienna Biopharmaceuticals, Inc. (the Company) announced (i) top-line results from a Phase 2b study of SNA-120 for the treatment of itch and psoriasis and (ii) results from an exploratory Phase 1/2 study of SNA-125 for the treatment of atopic dermatitis. Additionally, the Company will be hosting a conference call for analysts and investors to discuss the top-line results utilizing the attached presentation (the Presentation). A copy of the press release and the Presentation are filed as Exhibits 99.1 and 99.2 to this Current Report on Form 8-K, respectively, and incorporated by reference herein.
|Item 9.01.|| |
Financial Statements and Exhibits.
|99.1||Press Release dated December 3, 2018.|
|99.2||Presentation dated December 3, 2018.|
Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
|SIENNA BIOPHARMACEUTICALS, INC.|
Date: December 3, 2018
|Name:||Timothy K. Andrews|
|Title:||General Counsel and Secretary|
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 clinical-stage medical dermatology and aesthetics company, today announced top-line results from a Phase 2b study of SNA-120 (pegcantratinib), the Companys 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 Siennas 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.
Siennas 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 Siennas 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 treatment-related 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 Companys website at Investors.SiennaBio.com. An archived version of the webcast will be available approximately two hours following the live call for 90 days.
About Siennas 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 Companys 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 Companys website at www.SiennaBio.com.
This press release contains forward-looking statements, including but not limited to statements by Siennas Executive Officers and Alan Mentor, M.D. regarding Siennas 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 Siennas expectations for additional data readouts for its clinical trials. Such forward-looking statements involve substantial risks and uncertainties that could cause Siennas 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, Siennas 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 Siennas 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 Siennas 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
Sienna Biopharmaceuticals, Inc.
30699 Russell Ranch Road, Suite 140, Westlake Village, CA 91362
Office 818-629-2256 | Fax 818-706-1214
SNA-120 Phase 2b Trial Top-Line Results December 3, 2018 March 2017 Exhibit 99.2
Forward Looking Statements This presentation contains forward-looking statements. All statements other than descriptions of historical facts contained in this presentation, including statements regarding future operational and financial results and positions, business strategy, prospective products, potential market, commercial opportunity and market share, availability and potential sources of funding, clinical trial results, product approvals and regulatory pathways, research and development costs, timing (including but not limited to clinical development and regulatory timelines), strategies for completion and likelihood of success for our business activities, and plans for future operations, are forward-looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. Because forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified and some of which are beyond our control, you should not rely on these forward-looking statements as predictions of future events. The events and circumstances reflected in our forward-looking statements may not be achieved or occur and actual results could differ materially from those projected in the forward-looking statements. Such risks and uncertainties include, among others, those inherent in the preclinical and clinical development process and the regulatory approval process; the risks and uncertainties in commercialization and gaining market acceptance; the risks associated with protecting and defending our patents or other proprietary rights; the risk that our proprietary rights may be insufficient to protect our product candidates; the risk that we will be unable to obtain necessary capital when needed on acceptable terms or at all; competition from other products or procedures; our reliance on third-parties to conduct our clinical and non-clinical trials; and our reliance on single-source third-party suppliers to manufacture clinical, non-clinical and any future commercial supplies of our product candidates. 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 our business in general, see our most recent Annual Report on Form 10-K filed with the Securities and Exchange Commission and our future current and periodic reports. Except as required by applicable law, we assume no obligation to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise.
Agenda SNA-120 Phase 2b Executive Summary Study Design Demographics Top-Line Results Primary Endpoint Key Secondary Endpoints Safety and Tolerability Q&A Topical by Design™ Mechanism of Action of SNA-120
These data were not entirely as we would have expected We began this study with data suggesting we had a pruritus drug with a positive impact on psoriasis We now have data indicating we have a potential psoriasis drug with a positive impact on pruritus We had a substantial 58% reduction on itch in the primary endpoint, but it was not statistically different from Vehicle However, we had a substantial and statistically significant response on the two key psoriasis regulatory endpoints, PASI 751 and the composite IGA2, that was much stronger than we had expected The lower dose (0.05%) performed consistently better than the higher dose (0.5%) SNA-120 Phase 2b Trial Executive Summary PASI 75 = reduction of ≥ 75% in Psoriasis Area Severity Index score from baseline at Week 12 Composite IGA = proportion of subjects categorized as ‘clear’ or ‘almost clear’ on the Investigator Global Assessment and a minimum two-grade improvement from baseline at Week 12
We now have data in 500+ subjects treated with SNA-120, demonstrating that it is well tolerated and has an acceptable safety profile, and further validating our Topical by Design™ platform We intend to have an End-of-Phase 2 meeting with the FDA and then begin Phase 3 trials for psoriasis in 2H19 We believe the commercial opportunity is now significantly larger SNA-120 Phase 2b Trial Executive Summary (cont’d)
Multicenter, randomized, double-blind, Vehicle-controlled study Enrolled 208 subjects over the age of 18 with mild-to-moderate psoriasis and at least moderate itch Treated each subject twice daily for 12 weeks with either SNA-120 (0.05% or 0.5% ointment) or Vehicle Primary endpoint: Change in previous week’s mean daily scores in pruritus recorded on the I-NRS1 from baseline to Week 8 Key secondary regulatory endpoints: Proportion of subjects categorized as ‘clear’ or ‘almost clear’ on the IGA and a minimum two-grade improvement from baseline at Week 12 PASI 75: response defined as a reduction of ≥ 75% from baseline at Week 12 SNA-120 Phase 2b Study Design I-NRS = Itch Numeric Rating Scale
Refined population in this study: Included only itchy subjects with at least moderate itch (> 5 on the I-NRS) Excluded severe psoriasis subjects Longer treatment duration: 12 weeks (instead of 8 weeks) Only two SNA-120 doses: High (0.5%) and low (0.05%) concentrations from previous study I-NRS daily diary as primary itch measure (instead of itch VAS1) Important Changes from Previous Phase 2b Study VAS = Visual Analog Scale
Characteristic SNA-120 (0.05%) n=70 SNA-120 (0.5%) n=69 Vehicle n=69 Age (years) mean (SD1) 49.5 (15.3) 53.8 (13.4) 49.7 (14.5) Male, n (%) 35 (50.0) 34 (49.3) 29 (42.0) Race, n (%) Asian Black/African American White Other 3 (4.3) 4 (5.7) 59 (84.3) 4 (5.7) 4 (5.8) 4 (5.8) 59 (85.5) 2 (2.8) 4 (5.8) 1 (1.4) 62 (89.9) 2 (2.9) I-NRS weekly mean (SD) 7.34 (1.31) 7.41(1.24) 7.37 (1.31) BSA2 mean (SD) 6.03 (3.94) 5.66 (3.73) 5.48 (3.76) IGA 2-mild n (%) IGA 3-moderate n (%) 13 (18.6) 57 (81.4) 13 (18.8) 56 (81.2) 13 (18.8) 56 (81.2) PASI mean (SD) 6.49 (5.43) 5.94 (4.40) 5.98 (5.41) Demographics SD = standard deviation BSA = body surface area
Treatment Group Baseline Week 1 Week 8 (Primary) Week 12 (EoT1) SNA-120 (0.05%) Mean (SD) CFB2 (SD) p value vs Vehicle 7.3 (1.31) 5.7 (1.53) -1.6 (1.51) p=0.212 3.0 (1.96) -4.3 (2.41) p=0.244 2.6 (2.10) -4.6 (2.44) p=0.231 SNA-120 (0.5%) Mean (SD) CFB (SD) p value vs Vehicle 7.4 (1.24) 5.8 (1.63) -1.6 (1.43) p=0.423 3.8 (2.24) -3.7 (2.34) p=0.499 3.5 (2.5) -3.9 (2.61) p=0.384 Vehicle Mean (SD) CFB (SD) 7.4 (1.39) 6.0 (1.78) -1.3 (1.53) 3.4(2.63) -4.0 (2.57) 3.0 (2.56) -4.3 (2.60) Primary Endpoint: Significant reduction (58%) in mean I-NRS from baseline, but not differentiated from vehicle EoT = end of treatment CFB = change from baseline
Treatment Group Week 8 Week 12 PASI 50 SNA-120 (0.05%) proportion of subjects p value vs Vehicle 30 (49.2%) p=0.130 32 (54.2%) p=0.057 SNA-120 (0.5%) proportion of subjects p value vs Vehicle 20 (31.7%) p=0.636 25 (41.7%) p=0.562 Vehicle proportion of subjects 23 (35.9%) 22 (36.7%) PASI 75 SNA-120 (0.05%) proportion of subjects p value vs Vehicle 15 (24.6%) p=0.063 16 (27.1%) p=0.045* SNA-120 (0.5%) proportion of subjects p value vs Vehicle 6 (9.5%) p=0.614 6 (10.0%) p=0.590 Vehicle proportion of subjects 8 (12.5%) 8 (13.3%) Secondary Endpoints: PASI 50 and PASI 75 27% of subjects achieved PASI 75 with SNA-120 (0.05%) * statistically significant
Treatment Group Week 8 Week 12 IGA ≥ 2-grade and ‘Clear’/‘Almost Clear’ SNA-120 (0.05%) proportion of subjects p value vs Vehicle 10 (16.4%) p=0.518 17 (28.8%) p=0.036* SNA-120 (0.5%) proportion of subjects p value vs Vehicle 2 (3.2%) p=0.053 3 (5.0%) p=0.119 Vehicle proportion of subjects 8 (12.5%) 8 (13.3%) Secondary Endpoint: IGA 29% of subjects achieved 2-grade improvement and ‘Clear’ or ‘Almost Clear’ on IGA with SNA-120 (0.05%) * statistically significant
Treatment-related AEs were observed in only 2 subjects and included dermatitis (0.5% group) and pain and pruritus (Vehicle group) Most common AEs (≥ 2 subjects) in any group were nasopharyngitis, nausea, diarrhea, cellulitis and urinary tract infection Majority of TEAEs2 were mild to moderate There were 6 serious AEs in 3 subjects, but none were considered drug related SNA-120 was well-tolerated with no serious treatment-related AEs1 AEs = adverse events TEAEs = treatment-emergent adverse events We now have data in 500+ subjects treated with SNA-120, demonstrating that it is well tolerated and has an acceptable safety profile, and further validating our Topical by Design™ platform
7.5 million Total psoriasis patient population1 6.0 million Mild-to moderate psoriasis patients1 $500-$950/month Price range for 60-gram tube of current topical psoriasis therapies3 American Academy of Dermatology. Skin conditions by the numbers. Accessed November 2018. Pruritus in Chronic Plaque Psoriasis. G Stinco. Acta Dermatovenerol Croat. 2014;22(2):122-8. Includes Protopic, Elidel, Enstilar, Taclonex, Dovonex and Calcitriol. Large Market Opportunity for SNA-120 in United States Additional opportunity for other indications and/or populations, including other inflammatory diseases 4.8 million Psoriasis patients impacted by pruritus2 80% 80%
Regulated as a drug pursuant to a new drug application (NDA) regulatory pathway Regulated as a Class II medical device under 510(k) marketing clearance pathway TrkA = tropomyosin receptor kinase A JAK3 = Janus kinase 3 Top-line acne data for 1064 nm and 810 nm did not show statistical significance on primary and secondary endpoints. Top-line acne data for 755 nm are expected in 4Q18. Technology Platform Research Pre-clinical Phase 1 Phase 2 Phase 3 Anticipated Milestones Topical by Design™ Initiate Phase 3 trials in 2H19 Initiate Phase 2 trial in 2H19 Continued Progression to Phase 2 Technology Platform Research Pre-clinical Proof-of-Concept Pivotal Anticipated Milestones Topical Photoparticle Therapy™5 Top-line data in 4Q18 Top-line data in 1Q19 SNA-1201: TrkA3 inhibitor (psoriasis and pruritus) SNA-1251: JAK3/TrkA inhibitor (psoriasis and pruritus) SNA-0012 (unwanted light-pigmented hair reduction – 1064 nm) SNA-1251: JAK34/TrkA inhibitor (atopic dermatitis and pruritus) SNA-0012 (unwanted light-pigmented hair reduction – 810 nm and 755 nm) Sienna’s Diversified Topical Pipeline