Safety and Efficacy of Albuterol Administered by the Halix™ Dry Powder Inhaler in Subjects With Asthma

Study Design: This is a phase 2A, open label, cumulative dose, randomized 2-way crossover
study designed to assess the safety, efficacy, pharmacodynamics, pharmacokinetics (PK), and
extrapulmonary pharmacodynamics of cumulative doses of Halix™ albuterol 90mcg compared with
cumulative doses of Ventolin HFA MDI. After completing all screening assessments and meeting
all eligibility criteria [including SABA-free screening forced expiratory volume in 1 second
(FEV1) ≥50% to <85% of that predicted for age, gender, height, and ethnicity], enrolled
subjects will withdraw from use of Ventolin MDI with substitution of Atrovent HFA as the only
inhaled bronchodilator for at least 72 hours before each of 2 Treatment Days. On each
Treatment Day study treatments will consist of single doses of study drug (albuterol)
administered at 30-minute intervals as follows:

Halix™ albuterol UDDI - 1 + 1 + 2 + 4 inhalations [90 mcg per inhalation] Ventolin albuterol
MDI -- 2 + 2 + 4 + 8 inhalations [90 mcg (1 puff) per inhalation]

The order in which each treatment will be administered to a subject will be based on
randomization to one of 2 possible sequences. Equal numbers of subjects will be assigned to
each sequence. The beginning of each Treatment Day will be separated by a washout period of
at least 72 hours after the preceding Treatment Day; the washout period not to exceed 240
hours. After Treatment Day 2, subjects will be assessed at an End-of-Study (EOS) Visit which
will occur 1 to 5 days after the last administration of study drug.

Prior to each Treatment Day, the subject must not have used >8 actuations of (non-study drug)
rescue Ventolin MDI on each of 3 or more days during the previous 7 days and must not have
used any non-study drug rescue Ventolin MDI during the 72 hours prior to the start of the
Treatment Day. The Treatment Day will not proceed if either of these instances has occurred.

Within the 75 minutes prior to the first study drug dose on each of the 2 Treatment Days, the
following procedures will be performed: vital signs (BP and HR), ECG, collection of urine for
pregnancy test if subject is a WOCBP, collection of blood for baseline glucose, potassium,
and PK, and spirometry at 60 minutes and at 30 minutes prior to the anticipated time of first
study drug dose. The average of the FEV1 at 60 minutes and 30 minutes prior to the first
study drug dose on Treatment Day 1 must be ≥ 50% and < 85% of percent predicted in order for
the Treatment Day to proceed. On Treatment Day 2, the average of the FEV1 at 60 minutes and
30 minutes obtained predose must be ≥ 50% and <85% of predicted in order for Treatment Day 2
to proceed.

After the first study drug dose on Treatment Day 1 and on Treatment Day 2, and after each of
the following two cumulative doses on each Treatment Day, subjects will undergo spirometry at
5 (+ 2) minutes and at 25 (+/- 2) minutes post-dose. Blood for glucose, potassium and PK
sample will be collected at 15 (+/- 5) minutes after the first study drug dose and after each
of the following two cumulative doses and vital signs and ECG will be performed at 15 (+/- 5)
minutes after the first study drug dose and after each of the following two cumulative doses.
Following the last cumulative study drug dose on each Treatment Day, blood for PK sample will
be collected at 10, 20, 45, 120, 180, 240, 300, 360, 480, 600 and 720 minutes after the last
dose. After the last cumulative dose, spirometry will be performed at 5 (+ 2) minutes and at
25 (+/- 2) minutes. ECG and vital signs will be performed at 15 (+/-5) minutes after the last
cumulative dose. After the last cumulative dose, blood will be collected for glucose and
potassium at 45 and 120 minutes. Vital signs (BP and HR) will be measured hourly after the
last cumulative dose up to 360 minutes and at 480, 600, and 720 minutes after the last dose.
The time of each study drug dose will be recorded as the time of the last inhalation of study
drug for each individual cumulative dose administered when multiple inhalations are required
to administer the dose.

After Treatment Day 2, subjects will be assessed at an End-of-Study (EOS) that will occur 1
to 5 days after the day of the last administration of study drug.

Inclusion Criteria:

1. Has provided written informed consent

2. Speaks and understands the English language

3. Males or females 18 to 55 years of age (inclusive) at the Consent Visit

4. Nonsmoker or ex-smoker who has abstained from smoking for at least 1 year prior to the
Consent Visit and who has a < 10 pack/year history of lifetime cigarette use

5. Has no history of use of nicotine gum, nicotine patch, e-cigarettes/vaping
preparations in the 3 months before the Consent Visit

6. Has a body mass index (BMI) of 18.5 to 40.0 (calculated as kg/m2)

7. Has stable (for at least 6 months) physician-diagnosed asthma with historical
documentation of the diagnosis

8. Must be receiving one (1) of the following required inhaled asthma therapies listed
below for at least 30 days prior to the Screening Visit: (1) only SABA, which is used
for rescue, or (2) low to medium doses of ICS (alone or in combination with SABA
and/or LABA), used regularly as maintenance asthma therapy

9. Demonstrates acceptable spirometry performance (i.e., meets American Thoracic Society
[ATS]/European Respiratory Society [ERS] acceptability/repeatability criteria

10. Has a pre-bronchodilator FEV1 of ≥50 to <85% of predicted normal value after
withholding SABA ≥ 8 hours and (if applicable) LABA for 48 hours

11. Has confirmed FEV1 reversibility to inhaled Ventolin HFA aerosol 180 mcg, defined as a
post-Ventolin increase in FEV1 of ≥15 % at or before 30 minutes postdose - NOTE: only
2 reversibility attempts are allowed and, if applicable, a second attempt must occur
at least 24 hours after the first attempt and within the 21-day Screening Period

12. Ability to maintain a peak inspiratory flow rate of at least 60 L/min measured by the
In-check DIAL device at the medium low resistance setting at the Screening Visit.

13. At the Screening Visit, demonstrates adequate understanding of and ability to
successfully inhale from an MDI as determined by the investigator and through
demonstrated successful use of the Vitalograph® (Lenexa, KS) aerosol inhalation
monitor (AIM™) (training/validation device for MDI) using a placebo MDI canister.

[Note: potential subjects who cannot demonstrate successful MDI technique using with
the AIM device (with placebo canister) after in-clinic training at the Screening Visit
will not be eligible for continued participation in the study.]

14. At the Screening Visit, demonstrates adequate understanding of and ability to
successfully inhale when using the Halix™ UDDI [Note: a placebo UDDI not containing
any drug powder will be supplied for each potential subject to become familiar with
the inhaler and practice inhalation technique] [Note: potential subjects who cannot
demonstrate successful inhalation technique using the Halix™ UDDI after in-clinic
training at the Screening Visit will not be eligible for continued participation in
the study].

15. Willing and able to comply with all aspects of the study protocol including avoiding
use of certain concomitant medications and attending the required clinic visits (i.e.,
has no conflicting plans that would prohibit attendance at scheduled study visits
including each of the 2 Treatment Day Visits)

Exclusion Criteria:

1. Female subjects of childbearing potential (CBP) who are not using reliable
contraception (e.g., abstinence, double barrier method, oral/implantable/transdermal
contraception, Depo-Provera, intrauterine device, having one male sexual partner who
has undergone vasectomy); a woman is of CBP unless she is premenarchal, is at least 2
years postmenopausal, is without a uterus and/or both ovaries, has had a bilateral
tubal ligation, or has undergone the Essure procedure with confirmation of tubal
blockage.

[Note: If a female is identified as less than 2 years postmenopausal, a serum
follicle-stimulating hormone (FSH) determination will be performed as a part of
screening laboratory assessments. If an FSH result of < 40 mIU/mL is obtained, the
female will be determined to be of CBP and her unwillingness to use reliable
contraception as defined above will be exclusionary for the study.]

2. A woman who is pregnant (has a positive serum pregnancy test at Screening Visit), is
lactating, or is likely/planning to become pregnant during the study

3. Vital signs at the Screening Visit (after at least 2 minutes seated at rest) showing
SBP either < 80 mmHg or >150 mmHg; DBP > 90 mmHg; or HR either < 40 bpm or > 100 bpm
(vital signs outside these criteria may be repeated once after an additional seated
rest period of at least 2 minutes- if vital signs exclusion criteria are not met after
the repeat measurements of SBP, DBP, or HR, screening may continue)

4. Chronic obstructive pulmonary disease or other significant lung disease (e.g. chronic
bronchitis, emphysema, bronchiectasis with a need for treatment, cystic fibrosis, or
bronchopulmonary dysplasia)

5. Oral corticosteroid use at any dose within the 6 weeks prior to the Screening Visit

6. Receipt of any marketed (e.g. omalizumab, mepolizumab, reslizumab) or investigational
biologic within 3 months of the date of the Screening Visit or within 5 half-lives of
the drug, whichever is longer

7. Currently a smoker, or a former smoker with > 10 pack-year history, or a former smoker
who stopped smoking <1 year before the Screening Visit

8. A history of life-threatening asthma defined as any history of significant asthma
episodes(s) requiring intubation associated with hypercapnia, respiratory arrest,
hypoxic seizures, or asthma-related syncopal episode(s)

9. Emergency room visit or hospitalization for any acute respiratory condition in the 3
months prior to the Screening Visit

10. Current history of uncontrolled hypertension or uncontrolled diabetes, in the opinion
of the Investigator (NOTE: controlled hypertension and/or controlled diabetes are not
exclusionary)

11. Presence of cancer not in remission for at least 5 years prior to the Screening Visit
(excludes non-melanomatous skin cancer)

12. Hospitalized for psychiatric disorder in the previous 12 months or has a history of
attempted suicide within 5 years prior to the Screening Visit

13. Unable to abstain from protocol-defined prohibited medications during the study

14. Clinical laboratory tests (after ≥4 hours fasting) at the Screening Visit that show
results outside the normal ranges for the following clinical laboratory tests that, in
the Investigator's opinion, are judged to be clinically significant:

- hemoglobin

- hematocrit

- total white blood cell count (WBC)

- platelet count

- serum glucose

- serum potassium

- ALT

- AST

- alkaline phosphatase

- serum creatinine

15. Clinical laboratory tests at the Screening Visit that show any of the following:

- positive serum hCG (female subjects only)

- positive urine drug screen (exception is evidence of authorized prescribed
medications)

- positive urine cotinine test

16. Presence of any uncontrolled (in the Investigator's medical opinion) systemic disease,
including, but not limited to renal, hepatic, hematologic, gastrointestinal,
endocrine, pulmonary, cardiac, neurologic, or psychiatric disease

17. Electrocardiogram obtained at Screening Visit that shows (in the Investigator's
medical opinion) medically significant abnormalities (e.g., left bundle branch block,
frequent premature ventricular contractions, chronic atrial fibrillation, or QTcB
interval prolongation > 450 msec for males and > 470 msec for females)

18. Presence of current drug or alcohol abuse, in the Investigator's opinion, making it
unlikely that the requirements of the subject's participation in the protocol will be
met

19. History of allergic reaction (known hypersensitivity) to albuterol sulfate and/or
lactose, in any formulation

20. History of intolerance to aerosolized β2-adrenergic agonists

21. Receipt of a drug or biologic in an investigational research study within the 30 days
prior to the Screening Visit

22. An elective surgical or medical procedure currently is planned or scheduled to be
performed during the study (this excludes routine immunotherapy/desensitization
procedures that are being performed on a regular schedule and have been unchanged for
at least 3 months prior to the Screening Visit)

23. Presence of a clinically diagnosed upper respiratory tract infection within the 7 days
prior to the Screening Visit