Form 8-K AGILE THERAPEUTICS INC For: Mar 15
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(D)
of the Securities Exchange Act of 1934
March 15, 2019
Date of report (Date of earliest event reported)
Agile Therapeutics, Inc.
(Exact name of registrant as specified in its charter)
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Delaware |
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001-36464 |
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23-2936302 |
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(State or other jurisdiction |
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(Commission |
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(IRS Employer |
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101 Poor Farm Road |
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08540 |
Registrant’s telephone number, including area code (609) 683-1880
(Former name or former address, if changed since last report)
Check the appropriate box below if the Form 8-K is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
o Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425).
o Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12).
o Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)).
o Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))
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 x
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. x
Item 8.01. Other Events.
Agile Therapeutics, Inc. (“Agile”) a women’s healthcare company, announced on March 15, 2019 that an abstract presenting data from two Phase 1 in vivo wear studies on the adhesion of Twirla® has been selected for a poster presentation during the 2nd Annual Formulation & Drug Delivery USA Congress being held March 18th – 19th, 2019 in San Diego, California. The poster, titled “Results of Two Phase 1 Clinical Trials on the Adhesion Profile of AG200-15, An Investigational Transdermal Contraceptive Delivery System,” is being presented by lead author Terrance Ocheltree, PhD. Dr. Ocheltree previously served as both an FDA Reviewer and as Director of the Division of New Drug Quality Assessment II at the FDA.
Copies of the press release and Agile’s poster are attached hereto as Exhibit 99.1 and Exhibit 99.2 respectively, and are hereby incorporated by reference herein.
Item 9.01. Financial Statements and Exhibits.
(d) Exhibits.
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Exhibit |
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Description |
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99.1 |
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99.2 |
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Agile Therapeutics, Inc. Poster Presentation to be available between March 18 -19, 2019. |
SIGNATURES
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.
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Agile Therapeutics, Inc. | |
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Dated: March 18, 2019 |
By: |
/s/ Alfred Altomari |
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Name: |
Alfred Altomari |
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Title: |
Chairman and Chief Executive Officer |
Agile Therapeutics to Present In Vivo Adhesion Data from Two Phase 1 Studies at the 2nd Annual Formulation & Drug Delivery USA Congress
PRINCETON, NJ, March 15, 2019 - Agile Therapeutics, Inc., (Nasdaq: AGRX), a women’s healthcare company, today announced that an abstract presenting data from two Phase 1 in vivo wear studies on the adhesion of Twirla® has been selected for a poster presentation during the 2nd Annual Formulation & Drug Delivery USA Congress being held March 18th – 19th, 2019 in San Diego, California. The poster, titled “Results of Two Phase 1 Clinical Trials on the Adhesion Profile of AG200-15, An Investigational Transdermal Contraceptive Delivery System,” will be presented by lead author Terrance Ocheltree, PhD. Dr. Ocheltree previously served as both an FDA Reviewer and as Director of the Division of New Drug Quality Assessment II at the FDA.
The adhesion profile of Twirla (AG200-15) was recently evaluated in two single-center studies. The company performed the first, a single-arm pilot wear study (ATI-CL26), to inform the design of the second, a crossover wear study (ATI-CL25) comparing Twirla to Xulane®, a marketed generic contraceptive patch. The poster presentation will include adhesion and safety data from both studies. The results of these studies support an acceptable in vivo adhesion profile for Twirla, and both patches were generally well tolerated.
About Twirla® (AG200-15)
Twirla (levonorgestrel/ethinyl estradiol transdermal system) or AG200-15 is an investigational low-dose, once-weekly combined hormonal contraceptive (“CHC”) patch that contains the active ingredients ethinyl estradiol (“EE”), a type of estrogen, and levonorgestrel (“LNG”), a type of progestin. Twirla is designed to be applied once weekly for three weeks, followed by a week without a patch. The Company has completed its Phase 3 clinical trials of Twirla and is pursuing regulatory approval in the U.S. Agile received a complete response letter (“CRL”) from the FDA in December 2017 relating to the New Drug Application (“NDA”) for Twirla. In the CRL, the FDA informed the Company that the product could not be approved in its present form. The Company plans to resubmit the Twirla NDA in the first half of 2019.
About Agile Therapeutics, Inc.
Agile Therapeutics is a forward-thinking women’s healthcare company dedicated to fulfilling the unmet health needs of today’s women. Our product candidates are designed to provide women with contraceptive options that offer freedom from taking a daily pill, without committing to a longer-acting method. Our lead product candidate, Twirla® (levonorgestrel/ethinyl estradiol transdermal system), also known as AG200-15, is an investigational low-dose, non-daily,
prescription contraceptive. Twirla is based on our proprietary transdermal patch technology, called Skinfusion®, which is designed to allow drug delivery through the skin. For more information, please visit the company website at www.agiletherapeutics.com. The Company may occasionally disseminate material, nonpublic information on the Company’s website.
Follow Agile on Linked In and Twitter: @AgileTher.
Xulane® is a registered trademark of Mylan N.V.
Forward-Looking Statements
Certain information contained in this press release includes “forward-looking statements”, within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, related to our regulatory submissions. We may, in some cases use terms such as “predicts,” “believes,” “potential,” “continue,” “anticipates,” “estimates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “likely,” “will,” “should” or other words that convey uncertainty of the future events or outcomes to identify these forward-looking statements. Our forward-looking statements are based on current beliefs and expectations of our management team that involve risks, potential changes in circumstances, assumptions, and uncertainties, including statements regarding our conclusion that Twirla has acceptable adhesion and our expectations about Twirla and the timing of our planned resubmission of the Twirla NDA. Any or all of the forward-looking statements may turn out to be wrong or be affected by inaccurate assumptions we might make or by known or unknown risks and uncertainties. These forward-looking statements are subject to risks and uncertainties including risks related to our available cash and our ability to obtain additional funding to fund our business plan without delay and to continue as a going concern, our ability to adequately and timely respond to the deficiencies in the second Twirla CRL issued by the FDA on December 21, 2017, the potential that the FDA determines that our data do not support resubmission or approval of Twirla NDA, including the conclusion that Twirla has acceptable adhesion, and requires us to conduct additional studies to address the concerns raised in the 2017 CRL, our ability to resubmit the Twirla NDA and obtain and maintain regulatory approval of our product candidates, and the labeling under any approval we may obtain, our third-party manufacturer, Corium International, Inc.’s (“Corium”) inability to complete any work or provide any data and other information necessary to support the resubmission and approval of our Twirla NDA, our ability along with Corium to complete successfully the scale-up of the commercial manufacturing process for Twirla, including the qualification and validation of equipment related to the expansion of Corium’s manufacturing facility and to pass a likely FDA pre-approval inspection, the performance and financial condition of Corium or any of the suppliers to our third-party manufacturer, the success and timing of our clinical trials or other studies, our ability to retain key employees, regulatory and legislative developments in the United States and foreign countries, and the other risks set forth in our filings with the U.S. Securities and Exchange Commission, including our Annual Report on Form 10-K and our Quarterly Reports on Form
10-Q. For all these reasons, actual results and developments could be materially different from those expressed in or implied by our forward-looking statements. You are cautioned not to place undue reliance on these forward-looking statements, which are made only as of the date of this press release. We undertake no obligation to publicly update such forward-looking statements to reflect subsequent events or circumstances.
SOURCE: Agile Therapeutics, Inc.
Contact:
Investor Relations
Agile Therapeutics
609-683-1880
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Results of Two Phase 1 Clinical Trials on the Adhesion Profile of AG200-15, An Investigational Transdermal Contraceptive Delivery System Terrance Ocheltree, PhDa, Janet Wittes, PhDb, Jessica Case, MPHb, Michael Tuley, PhDc, Irina Krause, MSc, Elizabeth I.O. Garner, MD, MPHd, Joseph Chiodo III, PharmDd aPharmTree Consultants, LLC, Libertyville, IL, USA; bStatistics Collaborative, Inc., Washington, DC, USA; cTKL Research Inc., Fair Lawn, NJ, USA; dAgile Therapeutics Inc., Princeton, NJ, USA INTRODUCTION • AG200-15 (Twirla®) is a transdermal contraceptive delivery system (TCDS) under investigation as a once-weekly prescription combined hormonal contraceptive patch (Figure 1) Figure 1. Schematic of the AG200-15 Contraceptive Patch (Not drawn to scale) RESULTS ATI-CL26 • • For ATI-CL26 the overall mean score for all 30 subjects was 0.08 (SD 0.26) (Table 4) Overall, 96.7% of subjects had a mean adhesion score < 1 (i.e., > 90% adhesion) and 100% of subjects had a mean adhesion score < 2 (i.e., > 75% adhesion) (Table 5) There were no complete detachments; 2 subjects had an adhesion score > 2 at any time point, these occurred on Day 6 and Day 7 of the study (Table 6) • Table 5. ATI-CL26 Adhesion > 90% and > 75% Table 4. ATI-CL26 Mean Adhesion Score • • AG200-15 delivers approximately 120 ug of levonorgestrel and 30 ug of ethinyl estradiol daily A 28-day cycle consists of consecutive administration of three 7-day patches followed by 7 days off-treatment We report two Phase 1 in-vivo, single center wear studies: a single-arm study (ATI-CL26) and a crossover study (ATI-CL25) comparing AG200-15 to Xulane®, a marketed generic TCDS combination hormonal contraceptive containing norelgestromin and ethinyl estradiol (Figure 2) Table 6. ATI-CL26 Adhesion Scores by Time Point • Figure 2. Schematic of Xulane Contraceptive Patch (Not drawn to scale) ATI-CL25 Top-Line • For ATI-CL25 the overall mean score for AG200-15 subjects was 0.14 (SD 0.28) and for Xulane was 0.39 (SD 0.40). Results for all time points are presented in (Table 7) The study met the non-inferiority criterion by demonstrating a mean difference of -0.25 and upper 95% confidence limit of -0.16 (Table 8 and Figure 3) STUDY DESIGN, MATERIAL, & METHODS ATI-CL26 was a 7-day, single-arm pilot study of AG200-15 ATI-CL25 subjects were randomized to wear AG200-15 or Xulane for Week 1; they then switched to the patch not initially worn for Week 2; only top-line results are presented for this study Both studies enrolled 18 - 35 year-old women with BMI < 35 kg/m2 who remained in the clinic for the duration of the studies. Patch adhesion was assessed daily by trained study site personnel using a five-point scale (Table 1) – Patch tracers held a transparent diagram over the patch and lifted areas were marked using a permanent marker – Patch graders (separate from the tracers) provided grading for the percentage of patch lifting – Each tracer and grader was blinded to any previous assessments • • • Table 7. ATI-CL25 Adhesion Scores by Time Point • • Table 1. Adhesion Scale Table 8. ATI-CL25 Mean Adhesion Scores Met • Subjects were allowed to conduct activities of daily living and were instructed not to attempt re-adhesion of patches that partially detached; no overlays, tape or other coverings were used The primary objective of ATI-CL26 was to evaluate the adhesion of AG200-15 over 7 days; descriptive statistics, including mean patch adhesion scores and number and percent of subjects with patch adhesion scores > 90% and > 75% were assessed The primary objective of ATI-CL25 was to evaluate the adhesion of AG200-15 patch over 7 days/168 hours compared to the 7-day adhesion of the Xulane TCDS; AG200-15 would be considered statistically non-inferior to Xulane if the upper 95% confidence limit (95% CL) of the mean difference in adhesion scores was below +0.15 All analyses used the worst score carried forward method, such that the highest adhesion score for a subject using the five-point scale assessed at any time point after baseline is used for the subsequent time points until a higher score is assessed for that subject * One subject is excluded from the primary endpoint mean calculation because her data cannot be analyzed using a paired t-test • Figure 3. ATI-CL25 Non-inferiority Scale (Not drawn to scale) • • Safety ATI-CL26 SUBJECT DISPOSITION & DEMOGRAPHICS • ATI-CL26 screened 54 subjects; thirty subjects were randomized into the study and received study drug, all subjects completed the study – The mean age of the subjects was 28.3 years of age; the mean weight was 69.0 kg, and the mean BMI was 26.7 kg/m2. Further baseline information is available in (Table 2) Table 2. ATI-CL26 Demographics ATI-CL25 • Overall, 14/30 (46.7%) of the subjects experienced at least one TEAE (Table 9) All adverse events were mild except one subject reported an event that was considered moderate in severity (fatigue) Two adverse events were considered unrelated to study drug (skin discoloration and acne), the remainder were considered possibly related by the investigator There were no TEAEs that led to study-drug discontinuation, no SAEs, and no deaths during the course of the study • Overall, 49/83 (59.0%) of the subjects experienced at least one TEAE, 32/81 (39.5%) and 36/81 (44.4%) of subjects for the AG200-15 and Xulane treatment periods, respectively (Table 10) There were no TEAEs that led to study-drug discontinuation, no SAEs, and no deaths during the course of the study • • • Table 10. ATI-CL25 Adverse Events (occurring in over 2% of subjects in either treatment period) • Table 9. ATI-CL26 Adverse Events 8 (26.7%) 3 (10.0%) • ATI-CL25 screened 135 subjects; 83 subjects were randomized into the study and received study drug, 79 subjects completed the study, and 77 subjects were included in the per protocol analysis population (two subjects were excluded from the analysis for a protocol violation) – Overall, the mean age was 27.3 years of age; the mean weight was 68.3 kg, and the mean BMI was 26.2 kg/m2. Further baseline information is available in (Table 3) Table 3. ATI-CL25 Demographics Note: Adverse events are coded using MedDRA and are sorted by decreasing SOC frequency. Subjects are counted once for each system organ class. Adverse events are analyzed based on the treatment last applied prior to the onset of the AE. Note: Adverse events are coded using MedDRA and are sorted by decreasing SOC frequency. Subjects are counted once for each system organ class. A TEAE is an adverse event with an onset date on or after the first patch application through Day 8 (day of final study visit). CONCLUSION Overall, the ATI-CL26 and ATI-CL25 studies support an acceptable in-vivo adhesion profile of AG200-15 In ATI-CL25, AG200-15 demonstrated non-inferiority compared to Xulane since the upper 95% CL was -0.16 which was below the prespecified +0.15 NI criterion Both TCDS were generally well-tolerated • • • Parameter Subjects (N=83) Age (years), mean (SD) 27.3 (4.8) Weight (kg), mean (SD) 68.3 (10.8) Height (cm), mean (SD) 161.4 (5.9) BMI (kg/m2), mean (SD) 26.2 (3.9) Race, n (%) White Black or African American Other 26 (31.3%) 52 (62.7%) 5 (6.0%) Ethnicity, n (%) Hispanic or Latino Not Hispanic or Latino 22 (26.5%) 61 (73.5%) System Organ Class/Preferred Term AG200-15 (N=30) Any adverse events 14 (46.7%) Nervous system disorders Headache 8 (26.7%) Gastrointestinal disorders Vomiting Abdominal pain Nausea 5 (16.7%) 2 (6.7%) 1 (3.3%) Skin and subcutaneous tissue disorders Acne Hives Skin discoloration 3 (10.0%) 1 (3.3%) 1 (3.3%) 1 (3.3%) Reproductive system and breast disorders Menstrual cramps 2 (6.7%) 2 (6.7%) General disorders and administration site conditions Fatigue 1 (3.3%) 1 (3.3%) System Organ Class/Preferred Term AG200-15 (N=81) Xulane (N=81) Any adverse events 32 (39.5%) 36 (44.4%) Skin and subcutaneous tissue disorders Eczema Pruritus Rash 11 (13.6%) 3 (3.7%) 3 (3.7%) 4 (4.9%) 8 (9.9%) 2 (2.5%) 2 (2.5%) 1 (1.2%) Reproductive system and breast disorders Breast tenderness Metrorrhagia 8 (9.9%) 4 (4.9%) 3 (3.7%) 8 (9.9%) 3 (3.7%) 3 (3.7%) Respiratory, thoracic and mediastinal disorders Nasal congestion 0 0 5 (6.2%) 2 (2.5%) General disorders and administration site conditions Administration site rash 2 (2.5%) 2 (2.5%) 3 (3.7%) 1 (1.2%) Parameter AG200-15 (N=30) Age (years), mean (SD) 28.3 (5.2) Weight (kg), mean (SD) 69.0 (10.1) Height (cm), mean (SD) 160.8 (4.6) BMI (kg/m2), mean (SD) 26.7 (3.9) Race, n (%) White Black or African American Other 10 (33.3%) 18 (60.0%) 2 (6.7%) Ethnicity, n (%) Hispanic or Latino Not Hispanic or Latino 13 (43.3%) 17 (56.7%) noninferiority inferiority Mean difference = -0.25-0.16+0.15 (Primary Endpoint)Upper 95% Confidence Limit0NI Criterion (observed) AG200-15 (N = 77*) Xulane (N = 77) Difference (AG200-15 – Xulane) Mean (SD) Mean (SD) Mean (SE) One-sided upper 95% CL Non-inferiority Criteria Per Protocol population 0.14 (0.28) 0.39 (0.40) - 0.25 (0.05) - 0.16 YES Score Adhesion 0 > 90% adhered (essentially no lift off the skin) 1 > 75% to < 90% adhered (some edges only lifting off the skin) 2 > 50% to < 75% adhered (less than one-half of the patch lifting off the skin) 3 > 0% to < 50% adhered (not detached, but greater than one-half of the patch lifting off the skin without falling off) 4 0 % adhered (patch detached; completely off the skin) AG200-15 (N=78) Xulane (N=77) Time Point (hours) 0 n (%) 1 n (%) 2 n (%) 3 n (%) 4 n (%) 0 n (%) 1 n (%) 2 n (%) 3 n (%) 4 n (%) 24 77 (99) 1 (1) 0 0 0 72 (94) 5 (6) 0 0 0 48 75 (96) 3 (4) 0 0 0 69 (90) 7 (9) 1 (1) 0 0 72 72 (92) 6 (8) 0 0 0 64 (83) 12 (16) 1 (1) 0 0 96 68 (87) 9 (12) 1 (1) 0 0 51 (66) 24 (31) 2 (3) 0 0 120 63 (81) 14 (18) 1 (1) 0 0 38 (49) 35 (45) 4 (5) 0 0 144 60 (77) 17 (22) 1 (1) 0 0 34 (44) 35 (45) 8 (10) 0 0 168 58 (74) 19 (24) 1 (1) 0 0 29 (38) 37 (48) 11 (14) 0 0 Xulane Dimensions Total Patch Area (same as active drug matrix area) 14 cm2 Total Patch Diameter 4 cm Total Patch Thickness <1mm Time Point (hours) N 0 n (%) 1 n (%) 2 n (%) 3 n (%) 4 n (%) Mean (SD) 24 30 30 (100.0) 0 0 0 0 0 (0) 48 30 29 (96.7) 1 (3.3) 0 0 0 0.03 (0.18) 72 30 29 (96.7) 1 (3.3) 0 0 0 0.03 (0.18) 96 30 29 (96.7) 1 (3.3) 0 0 0 0.03 (0.18) 120 30 29 (96.7) 0 1 (3.3) 0 0 0.07 (0.37) 144 30 27 (90.0) 1 (3.3) 2 (6.7) 0 0 0.17 (0.53) 168 30 25 (83.3) 3 (10.0) 2 (6.7) 0 0 0.23 (0.57) Peripheral Laminate Region AG200-15 (N=30) n (%) Subjects with mean adhesion score < 1 (>90% adhesion) 29 (96.7) Subjects with mean adhesion score < 2 (>75% adhesion) 30 (100) N Mean (SD) Overall 30 0.08 (0.26) Active Matrix Region AG200-15 Dimensions Total Patch Area 28.0 cm2 Active Drug Matrix Area 15.0 cm² Total Patch Diameter 5.97 cm Drug Matrix Diameter 4.37 cm Peripheral Adhesive Width 0.80 cm Total Patch Thickness <1 mm
