NVUS 2018 Annual Report

Figure 1: Mean Passive Opening Pressures in Gerbil and Mice at Baseline, Immediately after Propellant, and at 5 and 10 Minutes after Surfactant Administration (Experiment 1)

* p<0.05 for surfactant treatment (each timepoint and animal group) compared to baseline and following propellant administration. In a study of experimentally induced AOM in chinchillas, the use of the early formulation was associated with a marked reduction in the severity and duration of AOM. Furthermore, quantitative cultures of middle ear fluid showed dramatic decreases in bacterial colonization with intranasal treatment alone (i.e., no antibiotics were administered in this study). Based on these findings, Novus believes that resolution of MEE may occur significantly earlier with treatment. The data suggest that restoration of ET function and ventilation of the middle ear is beneficial in resolving bacterial AOM. Prior to licensing rights to the surfactant program, the inventors treated nine humans who had various OM and ETD conditions. This human experience was captured as case studies and reported to the FDA. Based on these case studies, in conjunction with the preclinical animal data, Novus believes that a product of this type may have utility in the treatment and prevention of OM and ETD in children and adults. Novus is currently conducting four clinical trials to explore the safety, tolerability, and potential efficacy of OP0201. following a single intranasal dose of OP0201 in 16 healthy adults. The randomized, double-blind, placebo- controlled, cross-over trial will explore the effect of a 20 mg dose of OP0201 on ET function. Assessment of ET function will be captured using continuous tympanic impedance while subjects are exposed to changes in atmospheric pressure produced in a hyperbaric/hypobaric chamber. The single center study will be conducted in Germany. Additional information about the study can be found at clinicaltrials.gov using the identifier NCT03828149. x Study OP0201-C- ³& - ´ LV D SKDVH FOLQLFDO WULDO GHVLJQHG WR HYDOXDWH VDIHW\ WROHUDELOLW\ DQG (7 IXQFWLRQ ³& - ´ LV D SKDVH FOLQLFDO WULDO GHVL gned to evaluate safety and tolerability of daily intranasal administration of OP0201 over 14 consecutive days in 30 healthy adults. The randomized, double-blind, placebo-controlled, parallel-group, dose-escalation trial includes a 30 mg per day dose (Cohort A) and 60 mg per day dose (Cohort B) of OP0201. The study is being conducted at a single phase 1 unit in the U.S. Additional information about the study can be found at clinicaltrials.gov using the identifier NCT03748758. pain over a 60-minute observation period following a single intranasal dose of OP0201 in 24 adults with acute otitis media. The randomized, double-blind, placebo-controlled, parallel-group trial will explore the effects of a 20 mg intranasal dose of OP0201. Assessment of pain relief will be captured utilizing a Visual Analog Scale (VAS), Numeric Rating Scale (NRS-11), Patient Global Impression of Change (PGIC), and Clinical Global Impressions Scale: Global Improvement (CGI-I). The multicenter study was conducted in the U.S. Additional information about the study can be found at clinicaltrials.gov using the identifier NCT03766373. x Study OP0201-C- ³& - ´ L s a phase 1 clinical trial designed to evaluate safety, tolerability, and relief of ear x Study OP0201-C-

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