Results: Rapid and Effective In conclusion, BPX-01 2% minocycline topical gel resulted in rapid improvement and better outcomes than vehicle control in the treatment of moderate- to-severe non-nodular inflammatory acne vulgaris. This treatment may provide an effective new option with a favorable safety profile and potential for high patient compliance. This work was sponsored by BioPharmX; all investigators were active participants in the trial. BPX-01 is limited by federal or US law to investigational use only. Introduction A reduction of 25% in the number of inflammatory lesions is considered clinically important and is recognized by patients as an indicator of an effective treatment. Because this milestone was reached within two weeks of treatment with BPX -01, it has the potential to result in optimal treatment compliance and improved patient satisfaction. The rapid rate of improvement (43% after four weeks) outpaced that observed in a separate clinical trial with oral minocycline for acne in which improvement exceeding 40% required 12 weeks of treatment,4 with much lower systemic exposure. Additionally, BPX-01 2% resulted in 58.5% reduction in lesions with consistent trends toward improvement in IGA, PGI, and satisfaction scores. The medication was well tolerated with good safety profile and was largely undetectable in blood plasma, hence no systemic side effects are anticipated. 1Mount Sinai St Luke’s, New York NY; 2Del Rosso Dermatology Research Center, Las Vegas NV; 3ACRC Trials/Innovative Dermatology, Plano, TX; 4Image Dermatology, Montclair, NJ; 5Dermatology Consulting Services, High Point, NC; 6International Clinical Research-Tennessee, Murfreesboro, TN; 7International Clinical Research, Sanford, FL; 8DS Research, Louisville, KY; 9Tennessee Clinical Research Center, Nashville, TN; 10Skin Research Institute, Coral Gables, FL; 11Austin Institute for Clinical Research, Heatherwilde, TX; 12Progressive Clinical Research, San Antonio, TX; 13MedaPhase, Newnan, GA; 14Medical & Cosmetic Dermatology, Santa Monica, CA; 15Premier Clinical Research, Spokane, WA; 16BioPharmX, Menlo Park, CA Methods This phase 2b study was intended to describe the safety and efficacy of topical minocycline in the treatment of inflammatory acne vulgaris. Acne affects up to 50 million Americans annually.1 It can be caused by sebaceous gland hyperactivity, abnormal keratinocyte desquamation, and bacteria-related local inflammatory changes.2,3 Comedones and inflammatory papules, pustules and nodules are sites of proliferation for Propionibacterium acnes bacteria. BPX-01 topical minocycline gel The study medication: BPX-01 is the first completely solubilized minocycline gel for topical use. It is intended for the treatment of non-nodular, moderate-to-severe inflammatory acne vulgaris in patients nine years of age and older. Its preliminary safety and efficacy profile have been demonstrated in extensive preclinical testing and a phase 2a study: Strong Efficacy » Stabilizes & solubilizes minocycline » Delivered directly to pilosebaceous unit » Targeted penetration Strong Safety Profile » Low dose: 1% and 2% minocycline » Minimizes side effects » Low systemic exposure » Rapidly absorbing » Non-staining » Non-oily » Non-fluorescing » Very high patient satisfaction in clinical trials Positive Patient Experience Primary Endpoint Achieved: Reduction in P. acnes colonies Change from Baseline at 4 weeks Mean (Log10) Percentage BPX-01 Minocycline (n=17) -1.04 -90.9% Vehicle (n=7) -0.46 -65.3% » No drug-related adverse events » No detectable plasma minocycline » No cutaneous toxicity » 100% patient satisfaction R E S U LT S Favorable Secondary and Safety Endpoints » Randomized, double-blind, vehicle-controlled, dose-ranging study in 226 patients with moderate-to-severe acne » 12-week study evaluating 3 arms: BPX-01 1% , BPX-01 2%, vehicle » Conducted at 15 U.S. sites » Patients ages 9 to 40, IGA* of 3 or 4, 20-60 non-nodular inflammatory lesions 1. Bickers DR, Lim HW, Margolis D, Weinstock MA, Goodman C, Faulkner E, et al. The burden of skin diseases: 2004 a joint project of the American Academy of Dermatology Association and the Society for Investigative Dermatology. J Am Acad Dermatol. 2006;55:490-500. 2. Gollnick H, Cunliffe W, Berson D, Dreno B, Finlay A, Leyden JJ, et al. Management of acne: a report from a Global Alliance to Improve Outcomes in Acne. J Am Acad Dermatol. 2003;49(1 Suppl):S1-37. 3. Weiss JS. Acne: evolving concepts of pathogenesis need to guide therapeutic developments. J Drugs Dermatol. 2013; 12: s66. 4. Torok HM. Extended-release formulation of minocycline in the treatment of moderate-to- severe acne vulgaris in patients over the age of 12 years. J Clin Aesthet Dermatol. 2013;6[7]:19–22. Poster presented at the 2017 Fall Clinical Dermatology Conference®; Las Vegas, NV; October 12-15, 2017. Primary Endpoint: Absolute mean change in number of inflammatory lesions from baseline at week 12EN D P O IN T S Secondary Endpoint: Proportion of subjects with at least a two-grade reduction in IGA* to clear or almost clear (0 or 1) at week 12 S T U D Y D E S IG N » Minocycline plasma concentrations » Safety – adverse events » Cutaneous tolerance » Patient satisfaction » Non-inflammatory lesion reduction * Investigator Global Assessment; based on scale of 0 (clear) to 4 (severe) E X P L O R A T O R Y / S A F E T Y BPX-01 1% BPX-01 2% Vehicle Subjects per arm 73 72 74 Absolute mean change in inflammatory lesions at week 12 - 15.5 - 15.4 - 11.2 p-value 0.0543 0.0352 Percent reduction in inflammatory lesions 54.4% 58.5% 43.8% p-value 0.0765 0.0256 15% » Primary endpoint: Absolute mean change in number of inflammatory lesions from baseline at week 12 » The above analysis reflects the intent to treat (ITT) population of 219 Rapid Rate of Improvement in BPX-01 2% Arm: Key Takeaways » > 25% reduction in lesions at week 2 with both doses » A 25% improvement is considered meaningful to patients » Reaching a 25% improvement within 2 weeks may lead to patient compliance and satisfaction with treatment » 43.3% reduction in lesions at week 4 with 2% dose » 58.5% reduction in lesions at week 12 with 2% dose Week 12 59% Clear Trend in IGA Reduction for 2% Treatment Arm BPX-01 1% BPX-01 2% Vehicle Subjects per arm 73 72 74 Proportion with ≥ two- grade reduction and clear or almost clear 20.5% 25.0% 17.6% p-value (vs vehicle) >0.9999 0.5445 » Secondary Endpoint*: 25% of subjects in the 2% arm demonstrated at least a two- grade reduction in IGA to clear or almost clear (0 or 1) » 7.4% separation between 2% dose and vehicle informs sample size for confirmatory phase 3 trials 7.4% Demonstrated Rapid Lesion Reduction Reduction in Inflammatory Lesions Safety Endpoint: Systemic Exposure » Treatment-related adverse events occurred in 0.4% of subjects » Generally safe and well tolerated in this study » No serious treatment-related adverse events » No photosensitivity or post- inflammation hyperpigmentation was reported » No staining and/or skin discoloration was reported Would you consider using again? Yes / No 86% of subjects would use BPX-01 2% again BPX-01 1% BPX-01 2% Vehicle Baseline BLOQ BLOQ BLOQ Week 4 BLOQ BLOQ BLOQ Week 12 BLOQ BLOQ* BLOQ *One subject measured 42 ng/ml at 12 weeks; no AEs BLOQ=Below Limit of Quantification (10 ng/mL) » Minocycline was undetectable in the plasma of 99.5% of subjects. » Further support for no anticipated systemic side effects » Highly sensitive assay with LLoQ for minocycline of 10 ng/mL in plasma Yes NoPositive Patient Experience: BPX-01 2% Shows Potential for High Patient Compliance P e rc e n ta g e R e d u ct io n v s. B a se li n e * Study was not powered for this endpoint Week 2 >25% Week 4 43% Onset of Benefit: BPX-01 vs. Oral Minocycline ER 0.0% -43.3% -49.5% -58.5% -70% -60% -50% -40% -30% -20% -10% 0% Baseline Week 4 Week 8 Week 12 BPX-01 2% 0.0% -31.6% -39.9% -44.5% -70% -60% -50% -40% -30% -20% -10% 0% Baseline Week 4 Week 8 Week 12 Oral Minocycline ER *See Reference #4 below. The results of two phase 3 studies were combined for comparison. P e rc e n ta g e L e si o n R e d u ct io n vs . B a se li n e » Not conducted as a head-to-head trial. While recognizing that these trial data cannot be directly compared, BPX-01 may demonstrate a more rapid rate of improvement when compared to clinical data available for oral ER minocycline.* » BPX-01 may demonstrate a greater percentage of reduction in inflammatory lesions at all time points. 79% 1 2 3 4 5 (most favorable) Ease of use and application Scale of 1-5 79% of subjects thought BPX-01 2% was easy to use and apply Andrew Alexis,1 James Del Rosso,2 Seemal R. Desai,3 Jeanine Downie,4 Zoe Diana Draelos,5 Christina Feser,6 Rion Forconi,7 Joseph Fowler,8 Michael Gold,9 Joely Kaufman-Janette,10 Edward Lain,11 Mark Lee,12 Mark Ling,13 Ava Shamban,14 William Werschler,15 AnnaMarie Daniels16 Rapid Improvement with BPX-01 Minocycline Topical Gel in the Treatment of Moderate-to-Severe Inflammatory Acne Vulgaris: a Randomized, Double-Blind, Vehicle-Controlled Study -70% -60% -50% -40% -30% -20% -10% 0% Baseline Week 4 Week 8 Week 12 BPX-01 1% BPX-01 2% Vehicle Baseline 0.0% 0.0% 0.0% Week 2 -32.8% -27.6% -25.7% Week 4 -39.7% -43.3% -25.3% Week 8 -50.5% -49.5% -38.7% Week 12 -54.4% -58.5% -43.8% Adverse Events Baseline Week 2 Week 4 Week 8 Week 12 25% Reduction FC17PosterBioPharmXRapidImprovementAlexis.pdf