— Current sleep apnea diagnosis

— Clinically signi�cant ear disorder within 6 weeks prior to Screening

— Pregnancy/breastfeeding

— Craniofacial anomaly

— Disorder with decreased mucociliary clearance or higher viscosity of the mucus

— Employees of Sponsor or Investigator

— Met any of the following criteria prior to Screening (time prior to screening):

▪ Tympanostomy tube placement (within 1 year)

▪ Upper respiratory tract infection or pharyngitis, allergy or sinus condition or gastroesophageal re�uxdisease (within 6 weeks)

▪ Tobacco/nicotine use (within 48 weeks)

▪ Symptomatic herpes zoster infection (within 12 weeks)

▪ Malignancy (within 5 years; skin cancer within 3 years; breast cancer within 10 years)

▪ Receipt of live vaccine (within 30 days)

▪ Use of medication (either topically or systemically) for ear or nose disorder (within 12 weeks)

▪ Use of medication with anticholinergic side effects (within 6 weeks) or vasoconstrictive properties(within 2 weeks)

▪ Regular alcohol consumption (within 24 weeks)

Treatment

Table 1. Dose Cohorts and Dose Regimens

Cohort Dose Regimen

Cohort Dose Allocation Subjects

Per Day Total Dose (mg)

Cumulative Total Dose (mg)

OP0201 (n) Placebo (n) Total (N)

A2 sprays per nostril

TID x 14 daysOP0201 (30 mg)a

Placebob OP0201 (420 mg)a

Placebob 12 3 15

B4 sprays per nostril

TID x 14 daysOP0201 (60 mg)a

Placebob OP0201 (840 mg)a

Placebob 12 3 15

a2.5 mg per spray. bHFA-134a propellant only. TID=three times a day.

Endpoints◦ Primary Endpoint

— Safety and tolerability of OP0201

Study Assessments◦ Safety and tolerability assessments include adverse events (AEs), otoscopy, tympanometry, nasal

and epipharynx endoscopy, UPSIT olfactory test, audiology pure-tone hearing test, triplicate 12-leadelectrocardiogram (ECG), physical examination, vital signs, and clinical laboratory tests

— Pretreatment AEs are de�ned as AEs that occur prior to administration of the �rst dose of study drug onDay 1 but after obtaining informed consent

— Treatment-emergent adverse events (TEAEs) are de�ned as AEs that �rst occur or worsen in severity after administration of study drug

— Relationship to study medication is evaluated by the Investigator

Statistical Analyses◦ Analysis Populations

— Entered Analysis Set: All screened subjects who provided informed consent, including subjects who failedscreening

— Safety Analysis Set: All subjects who were assigned to a study treatment arm and received at least 1 dose of either OP0201 or placebo

◦ Software

— All analyses, summaries, and listings performed using SAS software (Version 9.4 or higher; SAS Institute,Cary, NC, USA)

RESULTS

Subjects◦ A total of 101 subjects were screened and a total of 30 subjects were enrolled (15 into each Cohort). All

enrolled subjects completed the study

◦ Subject demographics and baseline characteristics are shown in Table 2

Table 2. Subject Demographics and Characteristics (Safety Analysis Set)

Demographic/Characteristic OP0201 30 mgn=12

OP0201 60 mgn=12

Placebon=6

OverallN=30

Sex, n (%) Male Female

6 (20.0)6 (20.0)

10 (33.3)2 (6.7)

2 (6.7)4 (13.3)

18 (60.0)12 (40.0)

Race, n (%) White

Black or African American7 (23.3)5 (16.7)

4 (13.3)8 (26.7)

3 (10.0)3 (10.0)

14 (46.7)16 (53.3)

Ethnicity, n (%)Hispanic or LatinoNot Hispanic or Latino

1 (3.3)11 (36.7)

0 (0)12 (40.0)

0 (0)6 (20.0)

1 (3.3)29 (96.7)

Age, Mean (Range), years 33.9 (20, 49) 32.2 (25, 45) 35.3 (20, 49) 33.5 (20, 49)

A PHASE 1 SAFETY STUDY OF REPEATED DOSES OF INTRANASAL OP0201 METERED DOSE INHALER COMPARED TO PLACEBO IN HEALTHY ADULTS: A POTENTIAL TREATMENT FOR OTITIS MEDIAJ Patel, MD1,2; MD Sirimanne, MBA2; CC Turkel, PhD, PharmD, MBA3

1University of Texas Medical Branch – Galveston, Division of Pediatric Infectious Diseases, Galveston, TX, USA; 2Novus Therapeutics, Inc., Clinical Development, Irvine, CA, USA; 3Novus Therapeutics, Inc., Irvine, CA, USA

Presented at the International Society for Otitis Media’s 20th International Symposium on Recent Advances in Otitis Media; June 9–13, 2019; Los Angeles, CA

BACKGROUND◦ Otitis Media (OM) is a highly prevalent disorder and is the most common disease seen in pediatric

practice in the United States1,2

◦ The global impact of OM is signi�cant; there are an estimated 700 million cases diagnosed each year, withapproximately half of these occurring in children less than 5 years of age1

◦ The Eustachian tube (ET), a compliant, liquid-lined tube connecting the middle ear (ME) and nasopharynx,functions to ventilate, protect, and clear �uid from the ME.3,4 ET dysfunction is an important underlyingcause of OM3

◦ OM may be characterized as Acute (AOM), which is a short-term in�ammation of the ME, or OM withEffusion (OME), which refers to �uid in the ME without prominent signs or symptoms of acute ear infection5

◦ Children younger than 7 years are at increased risk of OM because of their immature immune systems andunderdeveloped ET functioning6

◦ OP0201 nasal aerosol is a novel, drug-device surfactant product being developed by Novus Therapeutics,Inc., for the treatment and prevention of OM

◦ OP0201 is a 20:1 �xed combination of dipalmitoylphosphatidylcholine (DPPC, a phospholipid surfactant) andcholesteryl palmitate (CP, a neutral phospholipid spreading agent) suspended in propellant

— Both surfactant active ingredients are endogenous to human respiratory and nasal systems

— None of the ingredients contain animal or human derivatives

◦ OP0201 is delivered intranasally to each nostril using a metered dose inhaler that has been designed todeliver the drug to the mid-turbinate region of the nasal cavity

— This allows the usual nasal mucociliary clearance pathway to facilitate delivery of the drug to the ET

◦ OP0201 absorbs to the mucosal air-liquid interface, reducing ET interfacial surface tension and thusrestoring ET physiologic activity

STUDY OBJECTIVES◦ Primary: To evaluate the safety and tolerability of 14 days of daily intranasal OP0201 (30 mg/day or

60 mg/day) compared to placebo in healthy adults

◦ Secondary: To evaluate whether any systemic exposure of DPPC or CP can be detected at levels higher thanthose of endogenous DPPC and CP in serum of healthy adults

— Note: This objective is currently being evaluated and is not reported in this poster

METHODSStudy Design◦ This was a Phase 1, randomized, double-blind, placebo-controlled, parallel-group, dose-escalation study in

healthy adults at a single center in the United States (Figure 1)

Figure 1. Study Design

◦ The estimated duration of participation in the study for each subject is up to 54 days: Screening(Days -28 to -1), Treatment (Day 1), 16-day Residency (Days -1 to 15, with safety assessments onDays 4, 8, 14, and 15), and Study Exit (Day 21 [+5 days])

◦ Two dose cohorts were enrolled, with subjects randomized 4:1 to receive OP0201 (Cohort A: 30 mg/day;Cohort B: 60 mg/day) or placebo in each cohort (Table 1)

— A Safety Review Committee assessed blinded safety data from Cohort A after all subjects completed theDay 14 visit to determine if escalation to Cohort B would be appropriate

Subjects◦ Inclusion criteria:

— Healthy male or female adults, ages 18–50

— Able and willing to follow study protocol and provide informed consent

— Body Mass Index 18–30 kg/m2

— Minimum body weight of 50 kg at Screening

— Agree to use contraception

— Agree to refrain from immersing their head fully under water

— Have a physiologic tympanogram classi�ed as Type A (normal)

◦ Exclusion criteria:

— History of signi�cant medical condition

— Clinically signi�cant abnormal olfactory test �nding at Screening, de�ned as a total University ofPennsylvania Smell Identi�cation Test (UPSIT) score <35 (for females) or <34 (for males)

Safety ◦ Escalation to Cohort B was approved following review of blinded safety data by a Safety Review Committee

after completion of the Day 14 visit for all subjects in Cohort A

◦ There were no serious AEs reported

◦ Overall, 18 subjects (60%) reported TEAEs (Table 3)

— All TEAEs were mild or moderate in severity

— The only TEAEs that occurred in more than 1 subject and at a rate greater than placebo were nasaldiscomfort and headache (Table 4)

Table 3. Overview of Incidence of Treatment-Emergent Adverse Events ([TEAEs]; Safety Analysis Set) OP0201 30 mgn (%) (N=12)

OP0201 60 mgn (%) (N=12)

All OP0201 Treatedn (%) (N=24)

All Placebon (%) (N=6)

Totaln (%) (N=30)

Any TEAE 5 (41.7) 9 (75.0) 14 (58.3) 4 (66.7) 18 (60.0)

Treatment-Related TEAE(s) 4 (33.3) 8 (66.7) 12 (50.0) 4 (66.7) 16 (53.3)

Serious TEAE(s) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)

Severe TEAE(s) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)

TEAE(s) Resulting in Study Drug Discontinuation

0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)

TEAE(s) Resulting in Death 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)

Table 4. Incidence of Study Drug-Related TEAEs by System Organ Class (SOC) and Preferred Term (Safety Analysis Set)

System Organ Class/ Preferred Term

OP0201 30 mg n (%) (N=12)

OP0201 60 mg n (%) (N=12)

All OP0201 Treated

n (%) (N=24)All Placebon (%) (N=6)

Totaln (%) (N=30)

Ear and labyrinth disorders 0 (0) 0 (0) 0 (0) 1 (16.7) 1 (3.3)

Tinnitus 0 (0) 0 (0) 0 (0) 1 (16.7) 1 (3.3)

General disorders and administration site conditions 0 (0) 1 (8.3) 1 (4.2) 0 (0) 1 (3.3)

Feeling cold 0 (0) 1 (8.3) 1 (4.2) 0 (0) 1 (3.3)

Infections and infestations 1 (8.3) 0 (0) 1 (4.2) 0 (0) 1 (3.3)

Nasopharyngitis 1 (8.3) 0 (0) 1 (4.2) 0 (0) 1 (3.3)

Investigations 0 (0) 4 (33.3) 4 (16.7) 2 (33.3) 6 (20.0)

Olfactory test abnormal 0 (0) 4 (33.3) 4 (16.7) 2 (33.3) 6 (20.0)

Nervous system disorders 3 (25.0) 1 (8.3) 4 (16.7) 1 (16.7) 5 (16.7)

Headache 3 (25.0) 0 (0) 3 (12.5) 1 (16.7) 4 (13.3)

Paresthesia 0 (0) 1 (8.3) 1 (4.2) 0 (0) 1 (3.3)

Respiratory, thoracic and mediastinal disorders 2 (16.7) 2 (16.7) 4 (16.7) 2 (33.3) 6 (20)

Nasal discomfort 1 (8.3) 2 (16.7) 3 (12.5) 0 (0) 3 (10.0)

Epistaxis 0 (0) 1 (8.3) 1 (4.2) 0 (0) 1 (3.3)

Nasal dryness 1 (8.3) 0 (0) 1 (4.2) 0 (0) 1 (3.3)

Burning sensation 0 (0) 0 (0) 0 (0) 1 (16.7) 1 (3.3)

Sneezing 0 (0) 1 (8.3) 1 (4.2) 0 (0) 1 (3.3)

Throat irritation 0 (0) 0 (0) 0 (0) 1 (16.7) 1 (3.3)

The number of subjects in each column cannot be added because a subject may have had more than one adverse event. A subject experiencing multiple occurrences of an adverse event was counted, at most, once per System Organ Class and Preferred Term.

CONCLUSIONS◦ In this Phase 1 study, intranasal OP0201 30 mg/day and 60 mg/day was safe and well tolerated in healthy

adult volunteers

◦ Future development studies are planned to evaluate OP0201 for the treatment of acute and chronic OM ininfants and children

DISCLOSURES◦ JP serves as a member of the OP0201-C-002 Study Safety Monitoring Committee, provides medical/safety

oversight, and consults on the design and data interpretation for the company’s clinical trials of OP0201nasal aerosol for otitis media

◦ MDS and CCT are employees of Novus Therapeutics, Inc.

ACKNOWLEDGMENTS◦ Editorial support was provided by IMPRINT Science, New York, NY, USA, with funding from Novus

Therapeutics, Inc.

REFERENCES1. Monasta L, Ronfani L, Marchetti F, et al. Burden of disease caused by otitis media: Systematic review and global

estimates. PLoS One. 2012;7(4):e36226.2. Marom T, Tan A, Wilkinson GS, et al. Trends in otitis media-related health care utilization in the United States,

2001-2011. JAMA Pediatr. 2014;168(1):68-75.3. Chandrasekhar SS, Mautone AJ. Otitis media: Treatment with intranasal aerosolized surfactant. Laryngoscope.

2004;114(3):472-485.4. Seibert JW, Danner CJ. Eustachian tube function and the middle ear. Otolaryngol Clin North Am. 2006;39(6):

1221-1235.5. Schilder AGM, Chonmaitree T, Cripps AW, et al. Otitis media. Nat Rev Dis Primers. 2016;2:1-18.6. Qureishi A, Lee Y, Bel�eld K, et al. Update on otitis media – prevention and treatment. Infect Drug Resist.

2014;7:15-24.

Screening Baseline Follow-up

Double-Blind Phase

Treatment

OP0201 60 mg/day (n=12)

OP0201 30 mg/day (n=12)

Randomization4:1

Cohort B(N=15)

Cohort A(N=15)

Placebo (n=3)

Study Start Study Exit

StudyDay -28 -1 1 15 21 (+5)

Placebo (n=3)