Efficacy & Clinical Data | neffy® (epinephrine nasal spray) for HCPs

PD data

neffy has a rapid effect on heart rate¹*^†

Effects on heart rate by
epinephrine treatment (After 1 dose)¹

A chart depicting the heart rate response (beats per minute) for neffy® (epinephrine nasal spray), needle-syringe epinephrine, and auto-injector epinephrine

neffy 2.0 mg
(n=42)
0.3 mg epinephrine
(needle-syringe) (n=42)
0.3 mg epinephrine
(auto-injector) (n=42)

neffy had an effect on heart rate within 1 minute

neffy 2.0 mg
(n=42)
0.3 mg epinephrine
(needle-syringe) (n=42)
0.3 mg epinephrine
(auto-injector) (n=42)

*The clinical meaning of PD responses observed in healthy subjects is unclear in the context of treating anaphylaxis.¹

^†PD analysis of a single dose of neffy 2.0 mg compared to 0.3 mg IM injection and 0.3 mg epinephrine (auto-injector) administered by caregivers in healthy volunteers.¹

BPM, beats per minute; HR, heart rate; IM, intramuscular; PD, pharmacodynamic.

neffy has a rapid effect on systolic blood
pressure¹*^†

Effects on systolic blood pressure
by epinephrine treatment (After 1 dose)¹

A chart depicting systolic blood pressure response (systolic blood pressure) for neffy® (epinephrine nasal spray), needle-syringe epinephrine, and auto-injector epinephrine

neffy 2.0 mg
(n=42)
0.3 mg epinephrine
(needle-syringe) (n=42)
0.3 mg epinephrine
(auto-injector) (n=42)

neffy had an effect on systolic blood pressure within 1 minute

neffy 2.0 mg
(n=42)
0.3 mg epinephrine
(needle-syringe) (n=42)
0.3 mg epinephrine
(auto-injector) (n=42)

*The clinical meaning of PD responses observed in healthy subjects is unclear in the context of treating anaphylaxis.¹

^†PD analysis of a single dose of neffy 2.0 mg compared to 0.3 mg IM injection and 0.3 mg epinephrine (auto-injector) administered by caregivers in healthy volunteers.¹

mm Hg, millimeters of mercury; SBP, systolic blood pressure.

ORAL FOOD CHALLENGE (OFC)

100% of patients achieved symptom resolution with 1 dose²

Patients had symptom relief as early as 1 minute²
Most patients experienced symptom relief within 5 minutes²
Symptoms resolved in a median time of 15 minutes^2‡
neffy was demonstrated to be safe and tolerable with no serious adverse events observed during the study^2,3

^‡One patient developed a biphasic reaction 2 hours and 45 minutes following administration of neffy and was treated with epinephrine at the time of that reaction.^2,3

PHASE 3 STUDY DESIGN

Simulating real-world type I allergic
reactions with OFC

Overview:

This Phase 3, open-label study evaluated the efficacy and safety of a single dose of neffy (1.0 mg or 2.0 mg epinephrine) in Japanese pediatric patients with anaphylactic reactions (≥Grade 2)²

Clinical symptoms (skin/mucosa, digestive, respiratory, circulatory, nerves) were induced via OFC and graded per the Anaphylaxis Guideline²
neffy was administered based on weight: 15 to <30 kg: 1.0 mg; ≥30 kg: 2.0 mg²

Patients:

15 Japanese pediatric patients (ages 6–17) with confirmed food allergy reactions (Grade 2+ in gastrointestinal, respiratory, or circulatory symptoms)²

Endpoints:

Primary endpoint²:

Improvement rate from baseline at 15 minutes or before alternative treatment*
(Main symptom prioritization: cardiovascular > respiratory > gastrointestinal)

Selected secondary endpoints²:

Patients not requiring alternative treatment
Symptom grade over time
Time to resolution by organ system

^*Improvement was defined as a decrease in the grade of each organ symptom by 1 or more compared to the pre-dose grade.² Foods that were determined or suspected to be as causative allergen were divided into single doses or multiple doses and were recorded (ie, chicken egg, wheat, milk, peanut, cashew nut, walnut, soba, etc).²

SYMPTOM SEVERITY GUIDE²

Mild (Grade 1)

Localized redness, itching, or swelling (lip/eyelid)
Mild stomach pain, nausea, or single vomiting
Intermittent cough, nasal congestion, sneezing

Moderate (Grade 2)

Generalized redness, severe itching, face swelling
Severe stomach pain, repeated vomiting/diarrhea
Repetitive cough, wheezing, mild dizziness
Fast heart rate (tachycardia), mild low blood pressure

Severe (Grade 3) – EMERGENCY

Widespread swelling, trouble breathing, hoarseness
Continuous vomiting, loss of bowel control
Severe wheezing, difficulty swallowing, throat tightness, cyanosis
Severe low blood pressure, irregular heartbeat, cardiac arrest
Anxiety, fainting, loss of consciousness

PK data

neffy pharmacokinetic data

PATIENTS WITH RHINITIS

neffy remained effective even
in patients with rhinitis^1*†

Epinephrine plasma concentration-time profiles following 1 or 2 dose(s) in healthy adults with and without NAC-induced rhinitis¹

Mean Epinephrine Concentration: Single Dose¹

A chart depicting the mean epinephrine concentration over an hour after a single dose of neffy® (epinephrine nasal spray) in those without nasal allergen challenge, neffy® (epinephrine nasal spray) in those with nasal allergen challenge, and needle-syringe epinephrine

neffy 2.0 mg
(with NAC)
0.3 mg epinephrine
(needle-syringe)

Mean Epinephrine Concentration: Twice Dose¹

A chart depicting the mean epinephrine concentration over an hour after two doses of neffy® (epinephrine nasal spray) in those without nasal allergen challenge, neffy® (epinephrine nasal spray) in those with nasal allergen challenge, and needle-syringe epinephrine

neffy 2.0 mg
(with NAC)
0.3 mg epinephrine
(needle-syringe)

*PK data are not indicative of efficacy and the clinical significance is not known.¹

^†Study analyzed PK and PD of neffy 2.0 mg in seasonal allergy patients under normal conditions and nasal allergen challenge induced rhinitis compared with 0.3 mg IM injection.¹

IM, intramuscular; NAC, nasal allergen challenge; PD, pharmacodynamic; pg/mL, picograms per milliliter; PK, pharmacokinetic.

Safety data

neffy 2 mg

neffy was well tolerated in a robust clinical study program¹

Common adverse reactions in primary studies¹
Adverse reaction^*	*neffy* 2.0 mg (1 dose) (n=134)^†	*neffy* 2.0 mg (2 doses)^‡ (n=85)^†
Throat irritation	2%	19%
Headache	6%	18%
Nasal discomfort	10%	13%
Feeling jittery	1%	11%
Tremor	0%	8%
Rhinorrhea	3%	7%

No serious TEAEs in all clinical trials^2,4-6
Most TEAEs were considered mild or moderate and resolved quickly^2,4-6
No risk of needle-related injuries such as lacerations, finger sticks, or blood vessel injections^1,7,8

A hand holding neffy® (epinephrine nasal spray) in a green-teal gradient circle, including a callout of it not being the actual product size

^*Data include subjects with nasal allergen challenge induced rhinitis.¹

^†The trials used a crossover design and, therefore, the total number of subjects do not match the number of unique subjects (n=175).¹

^‡Two nasal doses of neffy 2.0 mg were administered 10 minutes apart.¹

TEAE, treatment-emergent adverse event.

neffy 1 mg

neffy was well tolerated in a robust clinical study program¹

Common adverse reactions in a primary study in pediatric patients^*
Adverse reaction	*neffy* 1.0 mg (1 doses) (n=21)
Nasal congestion	4 (19%)
Upper respiratory tract congestion	3 (14%)
Dry throat	2 (10%)
Nasal dryness	2 (10%)
Paresthesia	2 (10%)

No serious TEAEs in all clinical trials^2,4-6
Most TEAEs were considered mild or moderate and resolved quickly^2,4-6
No risk of needle-related injuries such as lacerations, finger sticks, or blood vessel injections^1,7,8

^*Data include subjects with nasal allergen challenge induced rhinitis.¹

TEAE, treatment-emergent adverse event.

neffy demonstrated a favorable safety profile in pediatric patients,
as well as adults, with no serious adverse events reported in the trials^2,3,8

SUMMARY OF PRIMARY CLINICAL TRIALS

neffy 2 mg primary adult and pediatric studies^1,7

Study	Objectives	Study design	Product, dose, & administration	Patients (n)
EPI 15	PK and PD of *neffy* compared to IM and auto-injector injection dosed once and twice	6-arm, randomized, crossover study	Part 1: *neffy* 2 mg; 0.3 mg IM; auto-injector 0.3 mg IM Part 2: *neffy* 2 mg twice (L/R); *neffy* 2 mg twice (R/R); auto-injector 0.3 mg twice	Healthy patients (42)
EPI 16	PK and PD of *neffy* under normal and NAC-induced rhinitis compared to IM injection	4-arm, randomized, partial crossover study	*neffy* 2 mg; *neffy* 2 mg w/ NAC-induced rhinitis; 0.3 mg IM; 0.5 mg IM	Seasonal allergy patients (36)
EPI 17	PK and PD of *neffy* with patient self-administration	2-arm, randomized, crossover study	*neffy* 2 mg (self-administration); 0.3 mg IM (medical staff administration)	Type I allergy patients (42)
EPI 10	PK and PD in pediatric type I allergy patients	Single-arm; single-dose	*neffy* 2 mg	Pediatric allergy patients (21)
EPI 18	PK and PD of *neffy* compared to IM in type I allergy patients with seasonal rhinitis	5-arm, randomized, crossover study	NAC: *neffy* 2 mg twice (L/R); 0.3 mg IM twice Rhinitis: 0.3 mg IM twice (L/R); *neﬀy* 2 mg twice (L/R); *neﬀy* 2 mg twice (R/R)	Type I allergy patients with seasonal rhinitis (41)

IM, intramuscular; L, left; NAC, nasal allergen challenge; PD, pharmacodynamic; PK, pharmacokinetic; R, right.

References: 1. neffy [prescribing information]. San Diego, CA: ARS Pharmaceuticals Operations, Inc. 2. Data on file. JP03 CSR. ARS Pharmaceuticals Operations, Inc. 2024.
3. Ebisawa M, Fleischer DM, Li HH, et al. neffy, epinephrine nasal spray, development, from pharmacokinetics and pharmacodynamics to real-world data in pediatric food allergy patients. Presented at the Annual Meeting of the American College of Allergy, Asthma and Immunology; October 24-28, 2024; Boston, MA. 4. Data on file. EPI-15 CSR. ARS Pharmaceuticals Operations, Inc. 2024. 5. Data on file. EPI-16 CSR. ARS Pharmaceuticals Operations, Inc. 2022. 6. Data on file. EPI-18 CSR. ARS Pharmaceuticals Operations, Inc. 2024. 7. Ellis AK, Casale TB, Kaliner M, et al. Development of neffy, an epinephrine nasal spray, for severe allergic reactions. Pharmaceutics. 2024;16(6):811. 8. Posner LS, Camargo Jr CA. Update on the usage and safety of epinephrine auto-injectors, 2017. Drug Healthc Patient Saf. 2017;9:9-18.

PD data

neffy has a rapid effect on heart rate¹*^†

neffy has a rapid effect on systolic blood
pressure¹*^†