Lichen Planus;   Information was received on 03MAR2020 from an Investigator.  A 29-year-old male was diagnosed with lichen planus after the administration of all the three doses of the blinded study drug.  Study drug administration dates:  06MAY2019: Dose 1 20MAY2019: Dose 2 03JUN2019: Dose 3  On 06MAY2019, the subject received the first dose of the blinded study drug. After two weeks, on 20MAY2019, he received the second dose, and on 03JUN2019, he received his last dose of the study drug.   On 22NOV2019, 172 days after the last dose, he presented to the clinic with chief complaints of rash and red bumps on his hands, forearms, and shins ongoing since two weeks. Rash was located on his wrist, going up to his arms and shoulders. His bumps were somewhat itchy and resembled bug bites. Rashes appeared as blisters and flaky spots. No one else in his house had a rash or similar bumps. He denied fever, pets in the home, history of eczema or asthma. On the same day, his vital sign measurement showed a body mass index (BMI) of 35.8 kg/m2, blood pressure was 118/79 mmHg, temperature was 97.4 F, heart rate was 87 beats per minute and oxygen saturation was 97 %. Physical examination revealed skin with multiple scattered erythematous papules on the dorsal hands, volar wrists, forearms and anterior lower legs. He was administered dexamethasone sodium phosphate Injection Solution and Depo-medrol (methylprednisolone acetate) injection. He was also advised to start triamcinolone acetonide external cream for topical application and Zyrtec, and to follow up if the symptoms persist or worsen.  On 09DEC2019, he came for follow up visit with continued red and itchy bumps on his wrists, forearms and shins. He had been using topical triamcinolone as prescribed without any improvement. He denied fever, chest pain, shortness of breath or any family member with similar symptoms. The rash was not always bothersome or itchy, but it did not improve. He was advised to continue using triamcinolone for two weeks, followed by interruption for a week and then restart as required. He was encouraged to continue good skin care.  On 16DEC2019, he presented again for a follow-up due to a persistent rash. Despite oral, injection, and topical steroids, there was not much improvement. Physical examination revealed 1 mm to 10 mm round to linear red papules, vesicles, and scaly patches on volar wrists, forearms, shoulders, and shins. A shave biopsy of a right arm lesion confirmed lichen planus. Microscopic examination revealed acanthosis, hyperkeratosis, and hypergranulosis. Sub-epidermal vesicle formation was present associated with underlying acute and chronic in?ammation which obscured the dermal-epidermal junction. There was no evidence of malignancy.   Medical history included environmental and seasonal allergies and wisdom tooth extraction. Also had a positive history of blistering sunburns and denied history of psoriasis and eczema. There was no personal or family history of skin cancer.  Family history included non-Hodgkin's lymphoma (maternal grandmother) and rheumatoid arthritis (maternal grandfather).  Outcome: The subject had not recovered at the time of report.   The Investigator assessed the event lichen planus to be possibly related to therapy with study drug.  Medical Monitor assessed the event as unexpected and possibly related to study product administration. It is not possible to exclude causality at this time due to the event being reported post-enrolment in the study, even though the immuno-stimulatory effect of CPG is transient as demonstrated by clinical studies. The subject last received study product about six months prior to the onset of the event. Though the etiology of lichen planus is currently unknown, no cases have been reported in other clinical studies involving higher doses of CPG 7909 when used as monotherapy, in combination with anti-cancer therapies or as vaccine adjuvants. Thus, there is currently no known association between CPG 7909 and lichen planus.  The case was reviewed by the Board on 09MAR2020: The Physician indicated the diagnosis might be possible related, even given the time lapse.  Company Assessment: The Company assessed the event as possibly related.  The six-month timespan between blinded study drug exposure makes causality unlikely especially with the known transient immuno-stimulatory effect of CPG; however, causality is unable to be definitely excluded at this time.  Analysis of Similar Events: Case involves a 29-year-old male who was diagnosed with lichen planus 172 days after receiving the last dose of blinded study product.  The subject received all 3 doses of the blinded study drug with the last dose being on03JUN2019.  On 22NOV2019, he presented to the clinic complaining of a rash of red bumps on his hands, forearms, and shins for two weeks.  Nobody else in the household complained of similar systems.  Physical examination revealed skin with multiple scattered erythematous papules on the dorsal hands, volar wrists, forearms, and anterior lower legs.  Medical history included environmental and seasonal allergies and denied history of psoriasis and eczema.  The subject was administered a corticosteroid injection, along with topical treatment and Zyrtec.  On 09DEC2019, he returned for follow-up visit with without any improvement.  He was advised to continue using triamcinolone for two weeks, followed by interruption for a week, and then restart as required.  On 16DEC2019, he presented again for follow-up due to no improvement.  Physical examination revealed 1 mm to 10 mm round to linear red papules, vesicles, and scaly patches on volar wrists, forearms, shoulders, and shins. A shave biopsy of a right arm lesion confirmed lichen planus. Microscopic examination revealed acanthosis, hyperkeratosis, and hypergranulosis.  Sub-epidermal vesicle formation was present associated with underlying acute and chronic in?ammation which obscured the dermal-epidermal junction. There was no evidence of malignancy.  The subject was not recovered at the time of this report.    A search concerning similar events was performed on 16MAR2020.  The following Preferred Terms (PT) in relationship with AV7909 were searched in the Database: o     Lichen planus o     Rash  The search yielded the following expedited reports: none   RISK/BENEFIT STATEMENT: There is no change to the risk/benefit profile for this study/product as a result of this individual report/event(s).; Sender's Comments: The Company assessed the event as possibly related.  The six-month timespan between blinded study drug exposure makes causality unlikely especially with the known transient immuno-stimulatory effect of CPG; however, causality is unable to be definitely excluded at this time.  Analysis of Similar Events: Case involves a 29-year-old male who was diagnosed with lichen planus 172 days after receiving the last dose of blinded study product.  The subject received all 3 doses of the blinded study drug with the last dose being on03JUN2019.  On 22NOV2019, he presented to the clinic complaining of a rash of red bumps on his hands, forearms, and shins for two weeks.  Nobody else in the household complained of similar systems.  Physical examination revealed skin with multiple scattered erythematous papules on the dorsal hands, volar wrists, forearms, and anterior lower legs.  Medical history included environmental and seasonal allergies and denied history of psoriasis and eczema.  The subject was administered a corticosteroid injection, along with topical treatment and Zyrtec.  On 09DEC2019, he returned for follow-up visit with without any improvement.  He was advised to continue using triamcinolone for two weeks, followed by interruption for a week, and then restart as required.  On 16DEC2019, he presented again for follow-up due to no improvement.  Physical examination revealed 1 mm to 10 mm round to linear red papules, vesicles, and scaly patches on volar wrists, forearms, shoulders, and shins. A shave biopsy of a right arm lesion confirmed lichen planus. Microscopic examination revealed acanthosis, hyperkeratosis, and hypergranulosis.  Sub-epidermal vesicle formation was present associated with underlying acute and chronic in?ammation which obscured the dermal-epidermal junction. There was no evidence of malignancy.  The subject was not recovered at the time of this report.    A search concerning similar events was performed on 16MAR2020.  The following Preferred Terms (PT) in relationship with AV7909 were searched in the Database: o     Lichen planus o     Rash  The search yielded the following expedited reports: none   RISK/BENEFIT STATEMENT: There is no change to the risk/benefit profile for this study/product as a result of this individual report/event(s).