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Item 1. Business

2024-03-21 compared with 2023-03-23 · 271 added, 271 removed, 680 unchanged (44% of the section changed)

As used in this Annual Report, unless the context indicates or otherwise requires, “ARS,”

the “company,”

“we,”

“us,”

“our,”

and other similar terms refer to ARS Pharmaceuticals, Inc., a Delaware corporation and its consolidated subsidiaries.

As used in this Annual Report, unless the context indicates or otherwise requires, “ARS,” “ARS Pharma,” the “company,” “we,” “us,” “our,” and other similar terms refer to ARS Pharmaceuticals, Inc., a Delaware corporation and its consolidated subsidiaries.

neffy is a trademark of ours that we use in this Annual Report.

This Annual Report also includes trademarks, trade names, and service marks that are the property of other organizations.

Solely for convenience, our trademarks and trade names referred to in this Annual Report appear without the ® or symbols, but those references are not intended to indicate, in any way, that we will not assert, to the fullest extent under applicable law, our rights, or the right of the applicable licensor, to our trademark and trade names.

The use or display of other companies’ trade names or trademarks do not suggest or imply a relationship or affiliation with, or endorsement or sponsorship of us by, any other companies.

Company Summary

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Delay in treatment can allow the allergic reaction to progress in severity leading to symptoms that seriously impact patient quality of life, to potential need for emergency services and/or hospitalizations, and to life-threatening symptoms or events.

There are approximately 25 to 40 million people in the United States who experience Type I allergic reactions.

There are approximately 40 million people in the United States who experience Type I allergic reactions.

Of this group, approximately 20 million people have been diagnosed and experienced severe Type I allergic reactions that may lead to anaphylaxis, but only 3.2 million currently have an active epinephrine autoinjector prescription, and of those, only half consistently carry their prescribed autoinjector.

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In aggregate, we estimate that 90% of patients prescribed an epinephrine device are not achieving an optimal treatment outcome today.

We believe neffy ’s “no needle, no injection”

delivery that eliminates needle-related apprehension and injury concerns, with its small pocket size, ease of use, and high reliability would, if approved, increase prescriptions for epinephrine and make it more likely for patients and caregivers to administer epinephrine sooner, achieve more rapid symptom relief and prevent the allergic reaction from progressing to a level of severity that could lead to hospitalization or even death.

We believe neffy ’s “no needle, no injection” delivery that eliminates needle-related apprehension and injury concerns, with its small pocket size, ease of use, and high reliability would, if approved, increase prescriptions for epinephrine and make it more likely for patients and caregivers to administer epinephrine sooner, achieve more rapid symptom relief and prevent the allergic reaction from progressing to a level of severity that could lead to hospitalization or even death.

Data from our studies of neffy in more than 700 subjects demonstrated nasally delivered epinephrine reached blood levels comparable to those of already approved epinephrine injectable products.

Our NDA was accepted for review by FDA in the fourth quarter of 2022 with an anticipated mid-2023 PDUFA target action date, and if our NDA is approved, we believe neffy will be the first “no needle, no injection”

marketed epinephrine product for the emergency treatment of Type I allergic reactions.

Following the acceptance of our NDA in October 2022 for review by the FDA, on May 11, 2023, the FDA held a virtual meeting of its Pulmonary-Allergy Drugs Advisory Committee (“PADAC”).

At that meeting, on the question of whether the data from our neffy PK/PD results support a favorable benefit-risk assessment in adults for the emergency treatment of Type I allergic reactions including anaphylaxis, the PADAC voted 16 (yes) and 6 (no).

On the question of whether the neffy PK/PD results support a favorable benefit-risk assessment in children ≥30 kg for the emergency treatment of Type I allergic reactions including anaphylaxis, the PADAC voted 17 (yes) and 5 (no).

On September 19, 2023, the FDA issued a CRL for our NDA requesting completion of a PK/PD study assessing repeat doses of neffy compared to repeat doses of an epinephrine injection product under allergen-induced allergic rhinitis.

This request came after the favorable benefit-risk assessment of the PADAC to approve neffy without need for additional studies.

We reported topline data in February 2024 from this additional repeat dose study requested by the FDA, and plan to submit our response to the FDA’s CRL early in the second quarter of 2024, with an anticipated PDUFA target action date in the middle of the second half of 2024.

If our NDA is approved, we believe neffy will be the first “no needle, no injection” marketed epinephrine product for the emergency treatment of Type I allergic reactions.

However, the timing for regulatory approvals is outside of our control and may be delayed and is uncertain.

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apprehension stemming from the use of a needle that leads to approximately 40% to 60% of patients delaying administration by up to 18 minutes even if they are carrying the device;

a high rate of dosing errors, with meta-analyses reporting up to 35% of patients still failing to dose correctly even after training;

a high rate of dosing errors, with meta-analyses reporting 23% of patients still failing to dose correctly even after training;

safety concerns including lacerations, caregiver self-injection and frequent potentially cardiotoxic blood vessel injections, which occurred in approximately 14% of EpiPen subjects in our patient self-administration studies.

As a result, many of the approximately 25 to 40 million patients at risk of severe Type I allergic reactions do not receive or fill prescriptions for intra-muscular injectables.

As a result, many of the approximately 40 million patients at risk of severe Type I allergic reactions do not receive or fill prescriptions for intra-muscular injectables.

Of 3.2 million patients that do fill their prescriptions, approximately half do not carry the intra-muscular injectable products with them on a regular basis, while many of the other half delay or hesitate treatment during a severe Type I allergic reaction.

This may contribute to treatment postponement, prolonging troublesome symptoms, reducing quality of life and increasing the risk of complications or even death.

In addition to the 3.3 million patients who currently fill their prescriptions for an epinephrine injectable device, we estimate that approximately 2.5 million patients received a prescription in the last 3 years, but either did not fill or renew it.

In addition to the 3.2 million patients who currently fill their prescriptions for an epinephrine injectable device, we estimate that approximately 3.3 million patients received a prescription, but either did not fill or renew it.

We believe the advantages of neffy will be attractive to this group and lead to an increase in the number of patients filling their prescription as further described below.

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Notwithstanding their widespread lack of use, we estimate that net sales of intra-muscular injectable products approved for outpatient use in the United States was approximately $1 billion in 2023 among the approximately 3.2 million patients who filled a prescription.

neffy TM is an investigational drug currently in clinical trials for the emergency treatment of allergic reactions (type I) including anaphylaxis.

neffy TM is not approved by the FDA, EMA or other health authorities.

neffy is an investigational drug currently in clinical trials for the emergency treatment of allergic reactions (type I) including anaphylaxis.

neffy is not approved by the FDA, EMA or other health authorities.

neffy is designed to address the shortcomings of intra-muscular injectable devices.

neffy is a convenient “no needle, no injection,”

solution designed to be easier to carry, more reliable and easier to administer, without the aversion, safety concerns and fear and pain of needles associated with intra-muscular injectables.

neffy is a convenient “no needle, no injection,” solution designed to be easier to carry, more reliable and easier to administer, without the aversion, safety concerns and fear and pain of needles associated with intra-muscular injectables.

Based on the factors set forth below, we believe that neffy can transform the paradigm of epinephrine delivery from cumbersome, unreliable, intra-muscular injectable devices to an intranasal delivery method that makes patients more likely to administer epinephrine sooner, thus achieving more rapid symptom relief and preventing symptoms from becoming serious or life-threatening.

Comparable PK and PD to injection products .

In our clinical trials, we observed that neffy has comparable pharmacokinetics (“PK”) and pharmacodynamics (“PD”) compared to marketed epinephrine injectables.

In our clinical trials, we observed that neffy has comparable PK and PD compared to marketed epinephrine injectables.

Needle-free, easy-to-use, pocket-sized and highly reliable nasal spray.

neffy is easier to carry than approved intra-muscular injectables because it is pocket-sized, increasing the likelihood that the device is available for use in an emergency.

Our registrational self-administration study (EPI-17) with 2.0 mg neffy demonstrated that adult patients had zero critical dosing errors, and 100% of trained adults and trained children were able to dose successfully in two human factors validation study with a total of 150 subjects.

Our registrational self-administration study (EPI-17) with 2.0 mg neffy demonstrated that adult patients had zero critical dosing errors, and 100% of untrained adults and untrained children were able to successfully self-administer neffy in our human factors validation study using the intended commercial instructions for use and quick reference guide.

Dosing neffy also cannot be obstructed by common anaphylaxis co-morbidities such as vomiting or angioedema of the lips, face, mouth or tongue.

No inhalation or breathing is needed during administration of neffy .

No risk of needle-related injuries .

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Low potent dose of epinephrine .

Delivery of higher exposures of epinephrine increases the risk of overexposure and potential adverse events.

Delivery of higher exposures of epinephrine increases the risk of overexposure and potential adverse events including gastrointestinal (GI) symptoms due to swallowing of the excess epinephrine that is not absorbed.

neffy has high bioavailability matching the approved doses of injection at a low dose of 2.0 or 1.0 mg intranasally.

Even in the unlikely situation where epinephrine would be 100% bioavailable after administration of neffy , the resulting exposure is expected to be tolerable.

Due to its low dose of epinephrine and high bioavailability, neffy has minimal to no GI symptoms.

GI symptoms such as vomiting occur in approximately 20% of anaphylaxis events and the presence of such GI events due to administration of higher dose epinephrine products could confound the evaluation of anaphylaxis treatment response and monitoring.

Increased stability over existing treatment options .

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Combination of previously validated product components .

neffy consists of a unique combination of three validated products, which we believe will significantly reduce neffy’s clinical and commercial development risks:

epinephrine, which has been approved by regulators and accepted by the physician community as the only effective option to treat Type I allergic reactions;

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Well positioned for regulatory submissions, and if approved, advance to commercialization.

Our NDA was accepted for review by FDA in the fourth quarter of 2022 with an anticipated mid-2023 PDUFA target action date and we believe that the completed trials are sufficient to serve as the basis for its approval in the United States.

In Europe, our Market Authorization Application (“MAA”) was filed and validated for review by EMA in the fourth quarter of 2022.

Our response to the FDA’s CRL is planned to be submitted early in the second quarter of 2024 following completion of the PK/PD study requested by the FDA in its September 19, 2023 CRL.

This study assessed repeat doses of neffy compared to repeat doses of epinephrine injection under allergen-induced allergic rhinitis conditions.

In Europe, our Market Authorization Application (“MAA”) is under review and we anticipate a regulatory decision (CHMP Opinion) by mid-2024.

Potential for high demand and attractive product uptake conditions.

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In addition, our market research indicates that insurance plans (payors) perceive neffy as a differentiated product candidate, which we believe supports the potential for favorable market access for neffy at net prices comparable to, or at a premium to, the approved intra-muscular injectables.

We currently own or exclusively license a robust global intellectual property portfolio including issued composition of matter and method patents relating to neffy that are not expected to expire until 2038 before consideration of any potential patent term extension.

Our Management Team, Financing History and Investors

We were created to innovate, develop and commercialize neffy , a novel, potentially first-in-class treatment that addresses Type I allergy patients’

desire and need for a no needle, no injection, easy-to-use, portable and reliable solution for delivering epinephrine.

We were created to innovate, develop and commercialize neffy , a novel, potentially first-in-class treatment that addresses Type I allergy patients’ desire and need for a no needle, no injection, easy-to-use, portable and reliable solution for delivering epinephrine.

To achieve this goal, we have assembled a management team with extensive experience in the development and commercialization of drugs, such as recently approved nasal sprays NARCAN (naloxone nasal spray) and VALTOCO (diazepam nasal spray).

Our company was founded by Richard Lowenthal, M.S., MSEL, Robert Bell, Ph.D.

and Sarina Tanimoto, M.D., M.B.A.

and Sarina Tanimoto, M.D., MBA.

Pratik Shah, Ph.D.

was our first external investor.

Lowenthal, our Co-Founder and Chief Executive Officer, has more than 25 years of biotechnology and pharmaceutical development experience including leading the regulatory approvals of VALTOCO (diazepam nasal spray) and NARCAN (naloxone nasal spray).

Lowenthal, our Co-Founder, President, Chief Executive Officer, and one of our directors, has more than 25 years of biotechnology and pharmaceutical development experience including leading the regulatory approvals of VALTOCO (diazepam nasal spray) and NARCAN (naloxone nasal spray).

Bell, our Co-Founder and Chief Scientific Officer, has more than 25 years of product development experience including leading R&D at Barr Laboratories, Somerset Pharmaceuticals and UDL Laboratories.

Tanimoto, our Co-Founder and Chief Medical Officer, has more than 20 years of pharmaceutical experience in clinical drug development including supporting the approval of multiple nasal spray products such as VALTOCO and NARCAN.

Shah, our Chairman, has more than 30 years of experience founding and leading biopharmaceutical companies and healthcare investment decisions including his role as Executive Chairman of Design Therapeutics, former Chairman of Synthorx (now part of Sanofi) and former Chief Executive Officer of Auspex Pharmaceuticals (now part of Teva Pharmaceuticals).

Shah, our Chairman, has more than 30 years of experience founding and leading biopharmaceutical companies and healthcare investment decisions including his role as Chairman and Chief Executive Officer of Design Therapeutics, former Chairman of Synthorx (now part of Sanofi) and former Chief Executive Officer of Auspex Pharmaceuticals (now part of Teva Pharmaceuticals).

Our commercial team is led by Eric Karas, Chief Commercial Officer, who has more than 25 years of sales, marketing, market access and strategic planning experience across multiple specialty products, including leading commercial initiatives for NARCAN nasal spray at Emergent BioSolutions and Adapt Pharmaceutical (now part of Emergent BioSolutions).

Harris Kaplan, Executive Vice President, Commercial Strategy has been involved in the development and launch of 125 new products totaling more than $300 billion in peak revenues, and Dan Relovsky, Senior Vice President of Marketing, has extensive and relevant launch experience across a number of therapeutic categories.

The other key members of the ARS team bring extensive finance, business development and commercial operations experience and include Kathleen Scott, Chief Financial Officer;

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We have entered into licensing and collaboration agreements for neffy with Alfresa Pharma for Japanese rights, and Pediatrix Therapeutics (founded by F-Prime Capital, Eight Roads and Creacion Ventures) for Chinese rights.

We previously entered into a licensing and collaboration agreement with Recordati for development and commercialization rights in the European Union (“EU”), Iceland, Liechtenstein, Norway, Switzerland, the United Kingdom, Russia/CIS, Turkey, the Middle East and French-speaking African countries.

In the first quarter of 2023, we entered into an agreement with Recordati to terminate our prior agreement with it and reacquire Recordati’s rights to develop and commercialize neffy .

Our Pipeline:

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neffy is an intranasal composition of epinephrine that is designed to address the limitations of epinephrine intra-muscular injectable products that are available on the market today.

We submitted our NDA for the 2.0 mg neffy dose for adults and children greater than 30 kg in weight to the FDA in the third quarter of 2022.

Our NDA was accepted for review by FDA in the fourth quarter of 2022 with an anticipated mid-2023 PDUFA target action date.

In the EU, our MAA for the 2.0 mg neffy dose for subjects greater than 30 kg in weight was filed and validated for review by EMA in the fourth quarter of 2022.

Following the acceptance of our NDA in October 2022 for review by the FDA, on May 11, 2023, the FDA held a virtual meeting of the PADAC.

This request came after the favorable benefit-risk assessment of the PADAC to approve neffy without need for additional studies.

We reported topline results in February 2024 from this additional repeat dose study requested by the FDA, and anticipate submitting our response to the FDA CRL early in the second quarter of 2024, with an anticipated PDUFA target action date in the middle of the second half of 2024.

In the EU, our MAA for the 2.0 mg neffy dose for subjects greater than 30 kg in weight was filed and validated for review by EMA in the fourth quarter of 2022, and we expect a decision (CHMP Opinion) by mid-2024.

We have also entered into partnerships for the development and commercialization of neffy in regions outside of the U.S., including our partnerships with Alfresa Pharma in Japan and Pediatrix Therapeutics in China to develop and commercialize neffy in those countries.

Furthermore, we also plan to pursue additional expansion in our pediatric labeling with neffy and are conducting a single-arm pharmacokinetic study in subjects 4 to 18 years of age.

Our partners expect to submit regulatory filings equivalent to an NDA in China and Japan by year end 2024.

Furthermore, we also plan to pursue additional expansion in our pediatric labeling with neffy and have completed a single-arm PK study in subjects 4 to 18 years of age.

The interim pediatric data including subjects greater than 30 kg in weight is included in our initial NDA.

We plan to submit a supplemental NDA (“sNDA”) for neffy for children weighing 15 to 30 kilograms to the FDA in 2023.

We plan to submit a supplemental NDA (“sNDA”) for the 1 mg neffy dose for children weighing 15 to 30 kilograms to the FDA following the potential FDA approval of the 2.0 mg neffy dose in the middle of the second half of 2024.

We also plan to submit a post-approval variation to EMA for 1.0 mg neffy following the potential approval of our MAA for the 2.0 mg neffy dose.

In addition, we believe neffy may be able to target other conditions in addition to Type I allergic reactions, and we have identified additional indications for further examination and potential future development.

Our strategy is focused on developing and commercializing neffy as a potentially first-in-class approved intranasal treatment for the approximately 16 million patients in the United States who have been diagnosed and experienced severe Type I allergic reactions and are at risk of anaphylaxis, in geographic regions outside of the United States and for other allergy indications.

Our strategy is focused on developing and commercializing neffy as a potentially first-in-class approved intranasal treatment for the approximately 20 million patients in the United States under the active care of physicians between 2020-2022 who have been diagnosed with severe Type I allergic reactions and are at risk of anaphylaxis, for patients in geographic regions outside of the United States and for patients in other allergy indications.

Key elements of our strategy include:

Obtain FDA approval of neffy .

Our NDA was accepted for review by FDA in the fourth quarter of 2022 with an anticipated mid-2023 PDUFA target action date.

This request came after the favorable benefit-risk assessment of the PADAC on May 11, 2023 to approve neffy without need for additional studies.

We reported topline data in February 2024 from this additional repeat dose study requested by the FDA, and anticipate submitting our response to the FDA’s CRL early in the second quarter of 2024, with an anticipated PDUFA target action date in the second half of 2024.

If approved within our expected timeframe, neffy would be the first FDA-approved emergency treatment for Type I allergic reactions that is not an injection and that has no needle, which we believe would be an attractive treatment option for these patients.

neffy has received Fast Track designation.

However, the timing for regulatory approvals is outside ARS Pharma’s control, may be delayed and is uncertain.

Commercialize neffy in the United States .

If neffy is approved by the FDA, we plan to initially commercialize it in the United States by deploying a combination of direct promotion, virtual sales consultants, and non-personal promotion intended to reach, at a minimum, the healthcare professionals that account for 45% of the current epinephrine prescriptions.

Our promotion will target high-prescribing allergists, pediatricians and primary care physicians through both traditional and non-traditional professional channels.

Through these efforts, combined with direct-to-consumer omnichannel strategies to drive awareness and patients asking for neffy , we believe we can quickly and efficiently reach a majority of the approximately 3.2 million patients in the United States who filled a prescription for an epinephrine intra-muscular injectable device in 2023.

In addition, we believe that the potential for neffy to address the limitations of auto-injectors will allow us to expand the market opportunity for neffy over time to include the broader population of approximately 2.5 million patients who have received a prescription, but either refused or discontinued treatment in the last three years, as well as the approximately 11 million patients who are diagnosed and under the care of physicians, but have not been prescribed an epinephrine intra-muscular injectable.

In addition, we believe that the potential for neffy to address the limitations of auto-injectors will allow us to expand the market opportunity for neffy over time to include the broader population of approximately 3.3 million patients who have received a prescription, but either refused or discontinued treatment, as well as the approximately 13.5 million patients who are diagnosed and under the care of physicians, but have not been prescribed an epinephrine intra-muscular injectable over the last three-years.

Commercialize neffy outside of the United States with our partners .

We believe that there is significant commercial potential for neffy in markets outside of the United States.

In Europe, our MAA was filed and validated for review by EMA in the fourth quarter of 2022.

We intend to submit regulatory filings equivalent to an NDA in Japan and China in collaboration with Alfresa Pharma and Pediatrix Therapeutics, respectively, to whom we have granted exclusive licenses in those regions for the development and commercialization of neffy .

In Europe, our MAA is under review, and we anticipate a decision (CHMP Opinion) by mid-2024.

We intend to submit regulatory filings by year end 2024 equivalent to an NDA in Japan and China in collaboration with Alfresa Pharma and Pediatrix Therapeutics, respectively, to whom we have granted exclusive licenses in those regions for the development and commercialization of neffy .

Conduct additional studies of neffy to address additional Type I allergic reactions .

There remains a significant unmet need for treatments for allergies that can produce Type I reactions.

We are conducting clinical studies to support the expansion of labeling for neffy to outpatient epinephrine use in other Type I allergy conditions for which epinephrine intra-muscular injectables are not approved.

We are conducting clinical studies to support the expansion of labeling for neffy to outpatient epinephrine use in other Type I allergy conditions such as urticaria for which epinephrine intra-muscular injectables are not approved.

We reported positive topline results demonstrating statistically significant and clinically meaningful improvements in treatment-refractory chronic urticaria patients at the American Academy of Allergy and Immunology medical conference in February 2024, and anticipate initiating a Phase 2 clinical trial in the outpatient urticaria setting during 2024.

Overview of Type I Allergic Reactions and Current Challenges

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Common Symptoms of Type I Allergic Reactions

Chest tightness, wheezing, difficulty breathing

Upper airway or laryngeal angioedema including swelling of throat

Chest tightness, wheezing, difficulty breathing ~50%+ frequency

Upper airway or laryngeal Angioedema including swelling of throat ~20+% frequency

Cardiovascular

Hypotension, presyncope (feeling faint), loss of consciousness

Hypotension, presyncope (feeling faint), loss of consciousness ~20% frequency

Dermatological

Urticaria (hives) and pruritus (itching)

Urticaria (hives) and pruritus (itching) ~50%+ frequency

Angioedema including swelling of lips, tongue and mouth ~ 50%+ frequency

Gastrointestinal

Abdominal pain and vomiting

Abdominal pain and vomiting ~20% frequency

* Reprinted with permission from Dr.

Pete Smith (Medical Media Kits) and Mary Johnson

Analysis of symptom frequency during anaphylaxis in the United States (n = 4,805 events)

Role of Epinephrine in Treating Type I Allergic Reactions

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In June 2017, the FDA approved Symjepi epinephrine injection, which is a pre-filled syringe for the same indication.

These injection devices were approved by the FDA without pharmacokinetic data based on an assumption that injections and devices were all effectively the same as the reference listed drug of intra-muscular injection with a needle and syringe.

These injection devices were approved by the FDA without PK data based on an assumption that injections and devices were all effectively the same as the reference listed drug of intra-muscular injection with a needle and syringe.

Intra-muscular injection with a needle and syringe is considered the gold standard, and is almost exclusively used in non-community use clinical settings.

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A single dose with either an intra-muscular injection with needle and syringe or an auto-injector device results in resolution of allergic reaction for approximately 90% of cases within 5 to 15 minutes.

Epinephrine works due to its agonistic effects on the body’s adrenergic receptors (alpha and beta receptors).

By activating alpha-1 receptors, epinephrine prevents and relieves airway edema, hypotension and shock.

By activating beta-1 receptors, epinephrine increases the rate and force of cardiac contractions.

Lastly, epinephrine’s effect on beta-2 receptors leads to bronchodilation and decreased allergy causing mediator release by mast cells.

Alpha-1 receptors responsible for systolic blood pressure increases are the least sensitive to epinephrine, followed by beta-1 receptors that are responsible for heart rate increases, while beta-2 receptors responsible for stopping mast cell degranulation and the allergic reactions are the most sensitive to epinephrine.

Treatment guidelines recommend that epinephrine be administered immediately at the first sign of a severe allergic reaction.

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0.1 mg, 0.15 mg and 0.3 mg are the approved doses for the epinephrine auto-injectors.

Approximately 80% of epinephrine auto-injectors prescribed in the United States for outpatient use are the 0.3 mg dose level for persons greater than 30 kg in weight, approximately 15% contain doses of 0.15 mg for persons between 15 to 30 kg and less than 5% contain 0.1 mg doses for persons less than 15 kg.

Approximately 77% of epinephrine auto-injectors prescribed in the United States in 2023 for outpatient use are the 0.3 mg dose level for persons greater than 30 kg in weight, approximately 22% contain doses of 0.15 mg for persons between 15 to 30 kg and 1% contain 0.1 mg doses for persons less than 15 kg.

A low dose of epinephrine is important for safety as overexposure to epinephrine can lead to adverse events.

Limitations of Existing Epinephrine Products

* Reprinted from RECAPEM (image described in the public-domain and freely available).

Epinephrine intra-muscular injectables have been proven to be highly effective if they are administered timely and effectively, and work as intended, but the limitations of these products include painful application, inconvenient size and a complicated mechanism of administration.

These limitations discourage patients and caregivers from carrying these devices and administering epinephrine in a timely manner.

Both uptake and use of intra-muscular injection devices has been limited among eligible patients with severe Type I allergic reactions at risk of anaphylaxis.

Of the approximately 16 million people in the United States who have been diagnosed and experienced Type I severe allergic reactions, only 3.3 million currently have an active and filled epinephrine autoinjector prescription.

Both patient adoption and use of intra-muscular injection devices has been limited among eligible patients with severe Type I allergic reactions at risk of anaphylaxis.

Of the approximately 20 million people in the United States under the active care of physicians between 2020-2022 who have been diagnosed with Type I severe allergic reactions, only 3.2 million had an active and filled epinephrine autoinjector prescription in 2022.

In studies published in peer-reviewed journals, only 23% to 48% of patients self-administered with an auto-injector during a severe Type I allergic reaction, likely due to less than half of patients actually carrying their prescribed injection device, and only half administering even if the device was available.

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The FDA has reported that EpiPen device failures lead to multiple deaths and dozens of hospitalizations annually.

The injection needle can be painful and dangerous not just due to the risk of skin lacerations and the possibility of the needle hitting a patient’s bone during administration, but also the risk of serious, sudden cardiovascular events resulting from accidental blood vessel injection.

In our clinical studies, we observed instances of potential accidental blood vessel injection in approximately 14% of patients dosing themselves with EpiPen.

In comparison, neffy is perceived by patients and parents as a potentially “game changing”

device that, if approved, could improve the management of severe Type I allergic reactions by addressing the current limitations of epinephrine intra-muscular injectable devices.

In comparison, neffy is perceived by patients and parents as a potentially “game changing” device that, if approved, could improve the management of severe Type I allergic reactions by addressing the current limitations of epinephrine intra-muscular injectable devices.

Clinical Development of neffy

neffy is designed to provide injection-like absorption of epinephrine at a 1.0 or 2.0 mg dose comparable to 0.3 mg injection, in a small, easy-to-carry, easy-to-use, rapidly administered and reliable nasal spray.

Based on our development work to date, we believe neffy ’s “no needle, no injection”

clinical profile supports differentiation over intra-muscular injections for the emergency treatment of Type I allergic reactions, including anaphylaxis.

We submitted our NDA to the FDA in the third quarter of 2022 based on a rigorous clinical development program agreed upon during pre-NDA meeting discussion with the FDA in mid-2021.

Our NDA was accepted for review by FDA in the fourth quarter of 2022 with an anticipated mid-2023 PDUFA target action date.

The FDA reference listed drug is intra-muscular needle-in-syringe injection products but there are several approved epinephrine intra-muscular injection products, including intra-muscular auto-injectors such as EpiPen, that establish a range of exposures that have indistinguishable efficacy, time to observed clinical effect and safety.

During our pre-NDA meeting in mid-2021, FDA agreed that bracketing based on the primary parameters of C max , t max and early partial AUCs from the range of PKs observed in listed epinephrine injection products was the best approach to ensure efficacy and safety, while bracketing by AUC 0-t was considered an important parameter to ensure safety.

neffy is designed to provide injection-like absorption of epinephrine at a 2.0 or 1.0 mg dose comparable to 0.3 mg or 0.15 mg injection, in a small, easy-to-carry, easy-to-use, rapidly administered and reliable nasal spray.

Based on our development work to date, we believe neffy ’s “no needle, no injection” clinical profile supports differentiation over intra-muscular injections for the emergency treatment of Type I allergic reactions, including anaphylaxis.

We submitted our NDA to the FDA in the third quarter of 2022 based on a rigorous clinical development program agreed upon with the FDA.

The FDA reference listed drug is intra-muscular needle-in-syringe injection products but there are several approved epinephrine injection products, including auto-injectors such as EpiPen, that establish a range of exposures that have indistinguishable efficacy, time to observed clinical effect and safety.

The FDA agreed that bracketing based on the primary parameters of C max , t max and early partial AUCs from the range of PKs observed in listed epinephrine injection products was the best approach to ensure efficacy and safety, while bracketing by AUC 0-t was considered an important parameter to ensure safety.

PD measures of epinephrine activity such as systolic blood pressure and pulse rate were agreed to be supportive, and to be not meaningfully lower than injection.

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Furthermore, FDA also agreed that a single study in pediatric subjects also described below would be sufficient to support our pediatric labeling.

For our registrational program, EpiPen was agreed to be used as the upper bracket for exposures to ensure safety, while IM was agreed to be used as the lower bracket for exposures to ensure efficacy.

We have completed three registrational clinical trials in adults using our 2.0 neffy dose for which we submitted our NDA to the FDA in the third quarter of 2022.

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EPI-17 was conducted in the United States on behalf of ARS Pharma by Novum Pharmaceutical Research Services, a third party contract research organization, and selected 45 male or female volunteers between the ages of 18 to 55 years who had an ongoing history of Type I allergies.

To support our proposed pediatric labeling, we are also conducting a single-arm pharmacokinetic study in subjects 4 to 18 years of age with either 1.0 mg or 2.0 mg of neffy depending on the subject’s weight (EPI-10).

To support our proposed pediatric labeling, we have completed a single-arm PK study in subjects 4 to 18 years of age with either 1.0 mg or 2.0 mg of neffy depending on the subject’s weight (EPI-10).

EPI-10 is being conducted in the United States by ARS Pharma and selected 42 male or female subjects between the ages of 4 and 18 years who have Type I allergies that required that the subject or caregiver been prescribed an epinephrine product.

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1.0 mg neffy is intended to be the dose for persons 15 to 30 kg in weight.

Our NDA for the 2.0 mg dose of neffy for adults and children 30 kg and greater in weight was accepted for review by FDA in the fourth quarter of 2022 with an anticipated mid-2023 PDUFA target action date.

We plan to submit a supplemental NDA for the 1.0 mg dose of neffy in 2023 for subjects 15 to 30 kg in weight.

In our clinical studies in both adults and children, 2.0 mg neffy gave comparable epinephrine exposures that were within the range of approved intra-muscular injection products (needle-in-syringe products and EpiPen) on key pharmacokinetic parameters (C max , t max , early partial AUCs, AUC 0-t ).

The integrated data analysis summarizing the key outcomes for registration are shown below.

The hemodynamic response, measured by systolic blood pressure and heart rate, after administration of neffy was comparable to some injection products including EpiPen, and was greater than 0.3 mg intra-muscular needle-with-syringe.

Our NDA for the 2.0 mg dose of neffy for adults and children 30 kg and greater in weight was accepted for review by FDA in the fourth quarter of 2022.

In our clinical studies in both adults and children, 2.0 mg neffy gave comparable epinephrine exposures that were within the range of approved intra-muscular injection products (needle-in-syringe products and EpiPen) on key PK parameters (C max , t max , early partial AUCs, AUC 0-t ).

An integrated data analysis graph summarizing the key outcomes for registration for both single and repeat doses of neffy is shown below.

Single doses of 2.0 mg neffy compared to single doses of approved 0.3 mg injection products

Repeat doses of 2.0 mg neffy compared to repeat doses of approved 0.3 mg injection products

The hemodynamic response, measured by systolic blood pressure and heart rate, was observed even 1 minute after administration of neffy , and was comparable to some injection products including EpiPen, and was greater than 0.3 mg intra-muscular needle-with-syringe.

These hemodynamic responses were within normal physiologic ranges that are typically experienced during exercise or climbing stairs.

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There were no serious treatment-related adverse events, and adverse events reported have generally not resulted in side effects more severe than grade 1, and were comparable to injection products.

Since neffy is given without needle, there was also no needle-related injuries or accidental blood vessel injections.

In contrast, for patients self-administering devices, which involved 132 subjects dosed for each of EpiPen and Symjepi, approximately 14% of subjects dosed with EpiPen (auto-injector) and 2% of subjects dosed with Symjepi (pre-filled needle-in-syringe) experienced a potential blood vessel injection leading to a rapid bolus dose of epinephrine, which could lead to serious side effects including cardiovascular events and cerebral hemorrhage according to the FDA EpiPen label.

Since neffy is given without a needle, there was also no needle-related injuries or accidental blood vessel injections.

In contrast, for patients self-administering devices, which involved 132 subjects dosed with EpiPen, approximately 14% of subjects dosed with EpiPen (auto-injector) experienced a potential blood vessel injection leading to a rapid bolus dose of epinephrine, which could lead to serious side effects including cardiovascular events and cerebral hemorrhage according to the FDA EpiPen label.

No subjects dosed with neffy experienced a blood vessel injection since it is not possible via the nasal route of administration.

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Supporting Clinical Data

Comparable PKs at a low dose of epinephrine

C max , t max and AUCs were within the range of approved intra-muscular injection products with a low intranasal dose of 2.0 mg n effy (people >30 kg in weight) and 1.0 mg n effy

(people 15 –

30 kg weight).

Comparable PKs to epinephrine

C max , t max and AUCs were within the range of approved intra-muscular injection products with a low intranasal dose of 2.0 mg neffy (people >30 kg in weight) and 1.0 mg neffy

(people 15 – 30 kg weight).

Exposures with repeat doses of neffy were greater than IM to ensure efficacy, and comparable to EpiPen to ensure safety.

Low dose of epinephrine avoids side-effects that can be confused with anaphylaxis symptoms

Minimal to no gastrointestinal side effects with 1.0 or 2.0 mg neffy such as vomiting, diarrhea or abdominal pain that can occur if excess non-absorbed epinephrine is swallowed, confounding clinical monitoring since those same gastrointestinal side effects are symptoms of anaphylaxis during approximately 20% of events.

Robust PDs within a range comparable to injection products with no risk of accidental blood vessel injections

PD responses including systolic blood pressure and heart rate were within normal physiologic changes and comparable to auto-injector products, with maximum changes less that of the EpiPen.

PD responses including systolic blood pressure and heart rate were within normal physiologic changes and comparable to auto-injector products, with maximum changes less than EpiPen.

neffy has no potential for the accidental blood vessel injections observed with injection products such as EpiPen, which can lead to rapid and high epinephrine exposures that cause rapid increases in systolic blood pressure and can lead to cerebral hemorrhage or other cardiovascular side effects.

No meaningful pain or irritation after administration

Visual analogue scale scores were an average of 5 to 8 on a 100 mm scale, and show no meaningful pain (or burning or stinging sensation) after administration, attributable to n effy being an aqueous formulation.

There is also no irritation observed based on formal scoring.

Needle containing intra-muscular injection products are known to be painful and cause reluctance to dose.

No critical dosing errors during self-administration with 2.0 mg n effy by type I allergy adult subjects (EPI-17).

Zero percent error rate in two human factors studies with 150 persons, when used by trained adults or trained children and when used by untrained passers-byers.

No critical dosing errors during self-administration with 2.0 mg neffy by type I allergy adult subjects (EPI-17).

Zero percent error rate in human factor validation studies with intended commercial instructions for use and quick reference guide, when used by untrained adults or untrained children.

Ability to dose neffy is not affected by any of the frequently observed anaphylaxis-related symptoms such as angioedema or swelling of the face, lips, tongue or larynx (~50% frequency), gastrointestinal symptoms such as vomiting or dysphagia (~20% frequency), or upper airway or breathing difficulty (~50% frequency).

Easy to carry

neffy is comparable in size to a wireless earbud case, and multiple neffy devices can fit in a patient or parent’s pocket to satisfy guideline recommendations.

High reliability

neffy ’s sprayer device is designed to deliver the effective dose more than 99.999% of the time, with no recalls or warnings among the millions of the same nasal sprayer devices sold to date.

No breathing or inhalation required

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Shelf-life at least comparable to injection products, but also with high temperature stability

Drug stability studies show that n effy has a shelf-life at least comparable to the 18 month shelf-life of EpiPen, but with high temperature stability, based on stability data from the 2.0 mg dose of neffy for 12 months and the 1.0 mg dose of neffy for 24 months.

Drug stability studies show that neffy has a shelf-life at least comparable to the 18 month shelf-life of EpiPen, but with high temperature stability, based on stability data from the 2.0 mg dose of neffy for 12 months and the 1.0 mg dose of neffy for 24 months.

neffy remains within specifications even when exposed to temperatures of 50 o C (122 o F) for at least three months, or temperatures of 40 o C (104 o F) for at least six months.

Regulatory Review of neffy by the FDA

Following the acceptance of our NDA in October 2022 for review by the FDA, on May 11, 2023, the FDA held a virtual meeting of the PADAC.

This request came after the favorable benefit-risk assessment of the PADAC to approve neffy without need for additional studies.

In addition, the FDA and ARS Pharma had previously aligned in August 2023 on final physician’s labeling and a post-marketing requirement to conduct this study as informative for labeling.

We reported topline results in February 2024 from this additional repeat dose study requested by the FDA.

In this study, repeat doses of neffy under allergen-induced allergic rhinitis conditions demonstrated a PK and PD profile comparable to or better than repeat doses of intramuscular injection.

The results are shown below:

As part of the CRL, the FDA also requested additional information on nitrosamine impurities to be tested for based on new draft guidance issued in August 2023 after the neffy NDA submission.

We have completed this updated testing, and no measurable levels of nitrosamine impurities were detectable.

We anticipate submitting our response to the FDA’s CRL early in the second quarter of 2024, with an anticipated PDUFA target action date for 2.0 mg neffy in the middle of the second half of 2024.

We anticipate filing 1.0 mg neffy as a supplemental NDA immediately following the potential approval of the 2.0 mg dose of neffy in the middle of the second half of 2024.

Planned Clinical Trials in Additional Indications

Epinephrine has been used empirically by physicians and included in treatment guidelines for multiple allergy conditions that do not fall under the emergency treatment of Type I allergic reactions indication that epinephrine auto-injectors are labelled for.

The needle-free, portable, easy-to-use and potentially safer clinical profile of neffy supported by pharmacokinetic and pharmacodynamic data could enable the broader adoption of epinephrine in the outpatient setting for these other indications.

We are conducting proof of concept studies evaluating neffy in additional allergy indications where neffy could potentially be used multiple times a year to treat acute episodes.

The needle-free, portable, easy-to-use and potentially safer clinical profile of neffy supported by PK and PD data could enable the broader adoption of epinephrine in the outpatient setting for these other indications.

We reported positive topline results demonstrating statistically significant and clinically meaningful improvements in treatment-refractory chronic urticaria patients in February 2024, and anticipate initiating a Phase 2 clinical trial in the outpatient urticaria setting.

Development outside the United States

In Europe, our MAA was filed and validated for review by EMA in the fourth quarter of 2022.In the Day 120 comments, we received during EMA’s review of our prior 1.0 mg dose neffy MAA submission, EMA required a preclinical dog anaphylaxis study, which we completed with data showing no meaningful differences in epinephrine absorption of neffy in dogs in a normal state or an anaphylactic state.

In April 2022, we voluntarily withdrew our 1.0 mg neffy MAA submission to re-submit a 2.0 mg neffy MAA submission and allow EMA to review both our 2.0 mg neffy and preclinical dog anaphylaxis study results.

In Europe, our MAA was filed and validated for review by EMA in the fourth quarter of 2022, and we anticipate a decision (CHMP Opinion) by mid-2024.

We are also pursuing pediatric approval of neffy in Europe based on the same US pediatric study.

We plan to submit a post-approval variation to EMA for the 1.0 mg neffy following the potential approval of the 2.0 mg neffy dose.

Our partners in Japan and China expect that they will file for regulatory approval in their respective regions at end of 2023 or early 2024 following our anticipated FDA approval of neffy .

Our partners in Japan and China expect that they will file for regulatory approval in their respective regions in 2024 following the potential FDA approval of neffy .

Commercialization Opportunity and Commercialization Plan

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Existing US Market Opportunity

We estimate approximately 25 to 40 million people in the United States have experienced Type I allergic reactions.

Of this group, approximately 16 million people have been diagnosed and experienced severe Type I allergic reactions that may lead to anaphylaxis, but only about 3.3 million of them filled a prescription in 2021 for an epinephrine intra-muscular injectable device, including auto-injectors, equating to approximately 10 million devices.

Of those 3.3 million people, roughly half don’t carry these devices due to many drawbacks that can result in patient and caregiver injury, hesitation, and delays in administration principally because of apprehension and pain of needles.

We estimate approximately 40 million people in the United States have experienced Type I allergic reactions.

Of this group, approximately 20 million people have been diagnosed and experienced severe Type I allergic reactions that may lead to anaphylaxis, but only about 3.2 million of them filled a prescription in 2022 for an epinephrine intra-muscular injectable device, including auto-injectors, equating to approximately 5 million two-pack units.

Of those 3.2 million people, roughly half don’t carry these devices due to many drawbacks that can result in patient and caregiver injury, hesitation, and delays in administration principally because of apprehension and pain of needles.

In turn, the failure or delay of epinephrine delivery can allow the allergic reaction to progress in severity causing life-threatening symptoms or events that potentially require emergency services and/or hospitalization.

We believe neffy could address the needs of not only the approximately 3.3 million patients in the United States who currently fill intra-muscular injectable prescriptions, but also the more than 22 million eligible Type I allergy patients in the United States who are at risk of severe allergic reactions that are not prescribed or do not fill their epinephrine prescriptions, including approximately 2.5 million former injectable patients in the United States in the last three years that either refused to fill, or did not renew an intramuscular injectable device prescription.

We believe neffy could address the needs of not only the approximately 3.2 million patients in the United States who currently fill intra-muscular injectable prescriptions, but also the more than 17 million eligible Type I allergy patients in the United States who are at risk of severe allergic reactions that are not prescribed or do not fill their epinephrine prescriptions, including approximately 3.3 million former injectable patients in the United States that either refused to fill, or did not renew an intramuscular injectable device prescription.

Based on market access research and data from IQVIA, we estimate that 2023 U.S.

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We have conducted multiple market research studies with caregivers, generally parents, and patients with severe Type I allergic reactions in the United States to evaluate potential market perceptions of neffy and currently available epinephrine delivery devices.

Based on two independent quantitative market research studies including a total of 350 patients and 75 allergists, pediatricians and primary care physicians, approximately 80% of patients with a current epinephrine auto-injector prescription stated that they would prefer neffy .

Based on quantitative market research studies including a total of 480 patients and 185 allergists, pediatricians and primary care physicians, approximately 88% of patients with a current epinephrine auto-injector prescription stated that they would prefer neffy .

Furthermore, 99% of the physicians surveyed stated they would prescribe if their patient asked for neffy , indicating that neffy prescriptions would likely be highly driven by patient preference and awareness of neffy .

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81% of patients indicated they would use neffy sooner than their current auto-injector device,

65 to 72% of patients indicated that they would use neffy first instead of an over-the-counter antihistamine

72% of patients indicated that they would use neffy first instead of an over-the-counter antihistamine

88% reported they would be more willing to use neffy in public.

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Potential promotional lift due to new marketing and education efforts by a branded product such as neffy .

The existing market for epinephrine intra-muscular injectable products is characterized by being highly promotionally sensitive, particularly from a consumer perspective, and our market research has indicated that neffy ’s user-friendly product profile has the potential to resonate significantly with consumers.

We estimate that branded marketing of EpiPen prior to generic entry contributed a promotional lift of 31% over base epinephrine intra-muscular injectable market trends.

We plan to reach and support patients directly through efficient direct-to-consumer advertising after educating professional physician practices and securing appropriate payer coverage for neffy .

We plan to reach and support patients directly through efficient direct-to-consumer advertising after educating professional physician practices and securing appropriate payor coverage for neffy .

Targeting the approximately 3.3 million former patients that either do not fill their epinephrine intra-muscular injectables prescriptions or whose prescriptions have recently lapsed .

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In our market research of 350 patients with an active intra-muscular injectable prescription, approximately 70% to 80% of patients reported an intention to acquire additional devices compared to their current injectable device if neffy is approved by the FDA.

Currently, we estimate only between 20% to 30% of patients currently obtain more than one pack (containing two devices) per year today.

Currently, we estimate only between 20% to 30% of patients obtain more than one pack (containing two devices) per year today.

US Market Expansion Opportunity

While we believe the existing epinephrine intra-muscular injectables market is a large commercial opportunity for neffy with multiple independent opportunities for further growth, IQVIA claims data indicates that many diagnosed, identifiable eligible patients do not receive prescriptions for intra-muscular injectables.

Outside of the five million patients who were recently prescribed an epinephrine injectable device, there are approximately 11 million patients who are under the care of physicians per IQVIA claims data, but have not been prescribed an epinephrine intra-muscular injectable device, as well as another approximately 9 million patients not currently under the care of physicians.

Over time, targeting the approximately 11 million identified and diagnosed in-office patients in IQVIA claims data with Type I allergic reactions that are eligible but have not been prescribed epinephrine device.

Outside of the six million patients who were recently prescribed an epinephrine injectable device, there are approximately 14 million patients who are under the care of physicians per IQVIA claims data, but have not been prescribed an epinephrine intra-muscular injectable device, as well as another approximately 20 million patients not currently under the care of physicians.

Over time, targeting the approximately 13.5 million identified and diagnosed in-office patients in IQVIA claims data with Type I allergic reactions that are eligible but have not been prescribed epinephrine device over the last three years.

In our market research, physicians indicated they would prescribe neffy to more than half of the patients who were eligible, but do not currently receive an intra-muscular injectable prescription.

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Therefore, the market opportunity for treating such conditions may be as large as the type I allergy including anaphylaxis indication.

We are conducting a randomized, placebo-controlled proof of concept study evaluating the safety and efficacy of neffy in approximately 24 subjects with frequent urticaria flares.

We expect to complete enrollment and report topline data from this study in the second half of 2023.

We reported positive topline results demonstrating statistically significant and clinically meaningful improvements in treatment-refractory chronic urticaria patients in February 2024, and anticipate initiating a Phase 2 clinical trial in the outpatient urticaria setting.

Ex-US Market Opportunity

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We previously entered into a licensing and collaboration agreement with Recordati for development and commercialization rights in the EU, Iceland, Liechtenstein, Norway, Switzerland, the United Kingdom, Russia/CIS, Turkey, the Middle East and French-speaking African countries.

In the first quarter of 2023, we entered into an agreement with Recordati to terminate our prior agreement with it and reacquire Recordati’s rights to develop and commercialize neffy .

Commercial Strategy

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We expect to expand medical affairs capabilities prior to commercial launch to establish additional relationships with key opinion leaders and gain insight into current practice patterns and burdens.

The medical affairs team will also collaborate with the commercial team to help payers fully understand neffy’s value proposition and the limitations associated with needle injectors.

The medical affairs team will also collaborate with the commercial team to help payors fully understand neffy’s value proposition and the limitations associated with needle injectors.

We also plan to begin to raise awareness and support meaningful education through partnership with patient advocacy groups and medical societies as well as a disease education campaign including through social media and digital.

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We believe a broad understanding of this evidence will help to establish and increase the urgency to treat patients with neffy and support our rapid launch uptake following FDA approval, if achieved.

We plan to initially commercialize neffy in the United States with a combination of direct promotion, virtual sales consultants, and non-personal promotion intended to reach, at a minimum, the healthcare professionals that account for 45% of the current epinephrine prescriptions.

Our promotion will focus the launch on the highest potential practicing allergists, pediatricians, and primary care physicians.

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We intend to establish neffy as the dominant and most recognized brand in the category.

We believe neffy ’s potential brand recognition and user-friendly profile can be an important driver of growth and source of competitive differentiation, especially as the first “no needle, no injection”

solution for severe Type I allergic reactions.

We have designed neffy to offer healthcare professionals, patients and caregivers a simple, injection-free, portable, highly reliable and user-friendly alternative that facilitates early administration of epinephrine to provide rapid symptom relief and to stop the allergic reaction from progressing to more serious events.

We believe the attractiveness and meaningful differentiation of neffy across both physicians and payers will stimulate a high patient and parent desire to switch to or return to managing their condition with neffy .

We believe the attractiveness and meaningful differentiation of neffy across both physicians and payors will stimulate a high patient and parent desire to switch to or return to managing their condition with neffy .

We intend to secure affordable market access for all consumers by optimizing contracting, co-pay support and distribution of neffy .

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Health insurers surveyed have indicated that neffy is perceived as differentiated brand from epinephrine auto-injector products, with its needle-free route of administration and increased likelihood of being carried as the most important product attributes.

Based on these analyses and our planned contracting strategy, we believe payers can support favorable and broad market access for neffy .

Based on these analyses and our planned contracting strategy, we believe payors can support favorable and broad market access for neffy .

Further, we will offer comprehensive patient support programs in the form of co-pay buydowns to help ensure access and affordability for all patients.

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Both products use the same device that we have chosen for neffy .

We believe that NARCAN’s widespread use clearly demonstrates market uptake in response to the advantages of an intranasal product via proven device over injection, considering in particular that NARCAN is used in life threatening rescue situations where reliable administration is required for confident administration, similar to severe Type I allergic reactions.

Beyond just reliability, we believe that an intranasal product has unique advantages for treating a severe Type I allergic reaction due to patient and parent fear and avoidance of injection and because time is of the essence.

This perspective is distinct from other diseases with chronic use of injection products, administration by a trained professional is required, or where the injection is more manageable and tolerated.

In our market research, respondents have described neffy as “game-changing”

and we believe neffy , if approved, can make a significant difference in patient lives and outcomes.

In our market research, respondents have described neffy as “game-changing” and we believe neffy , if approved, can make a significant difference in patient lives and outcomes.

If approved, we plan to establish a distribution channel in the United States for the commercialization of neffy .

We expect to sell neffy to wholesalers, who, in turn, will sell our neffy to retailors and other customers.

We expect to sell neffy to wholesalers, who, in turn, will sell our neffy to retailers and other customers.

We expect to use a third-party logistics provider for key services related to logistics, warehousing and inventory management, distribution, contract administration, order management and chargeback processing and accounts receivable management.

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and Symjepi, which is marketed by Sandoz, Inc., a Novartis division.

We are not aware of any other company that has a “no needle, no injection”

epinephrine product candidate in clinical development in the United States that has demonstrated PKs bracketed by the approved injection products for all pharmacokinetic parameters requested by the FDA.

We are also not aware of any “no needle, no injection”

epinephrine product candidate for the pediatric population that is in clinical development.

We are not aware of any other company that has a “no needle, no injection” epinephrine product candidate in clinical development in the United States that has demonstrated PKs bracketed by the approved injection products for all PK parameters requested by the FDA.

We are also not aware of any “no needle, no injection” epinephrine product candidate for the pediatric population that is in clinical development.

We are aware of several companies developing higher dose intranasal candidates including Bryn Pharma, Hikma Pharmaceuticals, Inc.

(previously INSYS Therapeutics, Inc.), Nasus Pharma and Orexo AB.

(previously INSYS Therapeutics, Inc.), Nasus Pharma, Orexo AB and Belhaven BioPharma.

Amphastar Pharmaceuticals, Inc.

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We do not own or operate manufacturing facilities for the production of neffy , nor do we have plans to develop our own manufacturing operations for clinical materials or commercial products in the foreseeable future.

We currently depend on third-party contract manufacturing organizations (“CMOs”) for all of our required raw materials, drug substance and drug product for our preclinical research and clinical trials.

We currently rely on suppliers for raw materials including drug substance and multiple manufacturers for our product candidates and expect to rely on third-party suppliers and manufacturers for the commercial supply of any approved products.

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These CMOs offer a comprehensive range of contract manufacturing and packaging services and have successfully handled the scale up of neffy in preparation for commercialization.

neffy is presented as a nasal spray in aqueous solution with epinephrine as the active pharmaceutical ingredient (“API”) filled into glass vials and closed with a rubber stopper and assembled into the unit dose sprayer device.

Over time, epinephrine is oxidized and loses potency resulting in a finite shelf-life, and the neffy solution inside the unit dose sprayer changes to an amber to brown color.

Epinephrine is the API used in neffy .

We intend to use Cambrex Profarmco (“Cambrex”) as one of our commercial sources for epinephrine API.

Cambrex holds a U.S.

drug master file for epinephrine produced at its facility in Italy, and its manufacturing process is fully validated.

We have entered into a commercial supply agreement with Cambrex, and while we believe that Cambrex has sufficient capacity to satisfy our long-term requirements, there are several sources of API available, and we intend to launch with a second source of API and are in the process of qualifying this second API source.

Dodecyl maltoside or Intravail is purchased through our license agreement with Aegis Therapeutics, Inc.

from two manufacturers, Dr.

Dodecyl maltoside or Intravail is purchased through our license agreement with Aegis Therapeutics, LLC from two manufacturers, Dr.

Reddy Laboratories and Inalco, which are based in India and Italy, respectively.

The unit dose sprayer device used to delivery drug product in neffy is produced by Aptar Pharma (“Aptar”).

Aptar produces devices in France and we believe Aptar has sufficient capacity to satisfy our long-term requirements.

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Manufacturing drug product for neffy is conducted by Renaissance Pharmaceuticals, Inc.

(“Renaissance Pharma”), which has been actively involved in supporting the manufacture of neffy devices in our clinical development.

We intend to use its facility in Lakewood, New Jersey as our primary source for drug product manufacturing and final packaging.

We have entered into a commercial supply agreement with Renaissance Pharma, and believe they have sufficient capacity to satisfy our long-term requirements, although we are evaluating alternating sourcing options.

Ongoing stability studies demonstrate that neffy is stable at room temperature for at least 18 months, based on stability data from the 2.0 mg dose of neffy for 12 months and the 1.0 mg dose of neffy for 24 months, and we plan to continue to conduct ongoing registration stability studies that we anticipate will enable us to indicate on our label, if approved, that neffy is stable at room temperature for 18 months at 25 o C.

Ongoing registration stability studies demonstrate that neffy is stable at room temperature for at least 24 months, based on stability data from the 2.0 mg dose of neffy for 24 months and the 1.0 mg dose of neffy for 24 months.

If approved, we anticipate that our label will indicate that neffy is stable at room temperature for 24 months at 25 o C.

We have also conducted studies indicating that neffy is also stable at temperature excursions including 40 o C for up to six months, and at 50 o C for up to three months.

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As of December 31, 2023, our patent portfolio consisted of issued patents and pending patent applications that we co-own or exclusively license from Aegis Therapeutics LLC in the United States and other countries throughout the world.

In total, as of that date, our patent portfolio consisted of four issued U.S.

patents, one granted Australian patent, one granted Japanese patent, one granted Chinese patent, one granted patent in South Korea, one granted European patent, three granted United Kingdom patents, three pending U.S.

non-provisional patent applications, and over fifteen pending foreign patent applications directed to intranasal epinephrine formulations and methods of their use.

These issued patents and pending patent applications are expected to expire as early as 2038, absent any patent term adjustments or patent term extensions for regulatory delay.

In addition to patent protection, we also rely on trademark registration, trade secrets, know how, and other proprietary information to develop and maintain our competitive position.

In total, as of that date, our patent portfolio consisted of six issued U.S.

patents, granted patents in each of Australia, Canada, China, Hong Kong, Japan, Mexico, Singapore, South Korea, Europe, the United Kingdom, three pending U.S.

non-provisional patent applications, and over fifteen pending foreign patent applications directed to intranasal epinephrine formulations and methods of their use, among other things.

These issued patents and pending patent applications provide patent protection for neffy and are expected to expire as early as 2038, absent any patent term adjustments.

In addition to patent protection, we also rely on trademarks, trade secrets, know how, and other proprietary information to develop and maintain our competitive position.

We seek trademark protection in the United States and in certain other jurisdictions where available and when we deem appropriate.

We currently have registrations for our “

neffy ”

mark in the United States as well as in foreign jurisdictions, including the United Kingdom, European Union, and Japan.

We currently have registrations and pending applications for our “ neffy ” mark in the United States as well as in certain foreign jurisdictions.

Our commercial success will depend in part on obtaining and maintaining patent protection and trade secret protection of our current and future product candidates and the methods used to develop and manufacture them, as well as successfully defending these patents against third-party challenges.

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We cannot be sure that patents will be granted with respect to any of our pending patent applications or with respect to any patent applications filed by us in the future, nor can we be sure that any of our existing patents or any patents that may be granted to us in the future will be commercially useful in protecting our product candidates and processes.

For this and more comprehensive risks related to our intellectual property, please see “

Risk Factors—Risks Related to Our Intellectual Property.

The term of individual patents depends upon the legal term of the patents in the countries in which they are obtained.

In most countries in which we file, the patent term is 20 years from the earliest date of filing a non-provisional patent application.

In the United States, the patent term of a patent that covers an FDA-approved drug may also be eligible for patent term extension, which permits patent term restoration as compensation for the patent term lost during the FDA regulatory review process.

The Drug Price Competition and Patent Term Restoration Act of 1984 (the “Hatch-Waxman Act”) permits a patent term extension of up to five years beyond the expiration of the patent.

The length of the patent term extension is related to the length of time the drug is under regulatory review.

Patent term extension cannot extend the remaining term of a patent beyond a total of 14 years from the date of product approval, only one patent applicable to an approved drug may be extended and only those claims covering the approved drug, a method for using it, or a method for manufacturing it may be extended.

Similar provisions are available in Europe and other foreign jurisdictions to extend the term of a patent that covers an approved drug.

In the future, if and when our products receive FDA approval, we expect to apply for patent term extensions on patents covering those products.

We plan to seek patent term extensions to any of our issued patents in any jurisdiction where these are available, however there is no guarantee that the applicable authorities, including the FDA in the United States, will agree with our assessment of whether such extensions should be granted, and if granted, the length of such extensions.

For more information regarding the risks related to our intellectual property, see “

Risk Factors—Risks Related to Our Intellectual Property.

For this and more comprehensive risks related to our intellectual property, please see “ Risk Factors—Risks Related to Our Intellectual Property.

We also seek to protect our intellectual property in part by entering into confidentiality agreements with companies with whom we share proprietary and confidential information in the course of business discussions, and by having confidentiality terms in our agreements with our employees, consultants, scientific advisors, clinical investigators, and other collaborators and contractors and also by requiring our employees, commercial contractors, and certain consultants and investigators, to enter into invention assignment agreements that grant us ownership of any discoveries or inventions made by them while in our employ.

However, such confidentiality agreements and invention assignment agreements can be breached, and we may not have adequate remedies for any such breach.

For more information regarding the risks related to our intellectual property, see “

Risk Factors—Risks Related to Our Intellectual Property.

For more information regarding the risks related to our intellectual property, see “ Risk Factors—Risks Related to Our Intellectual Property.

The patent positions of specialty pharmaceutical companies like ours are generally uncertain and involve complex legal, scientific and factual questions.

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If third parties prepare and file patent applications in the United States that also claim technology to which we have rights, we may have to participate in interference or derivation proceedings in the U.S.

Patent and Trademark Office (the “USPTO”) to determine priority of invention.

For more information, see “

Risk Factors—Risks Related to Our Intellectual Property.

Patent and Trademark Office (the “USPTO”) to determine priority of invention.

For more information, see “ Risk Factors—Risks Related to Our Intellectual Property.

Our Collaboration and Licensing Agreements

License Agreement with Aegis

In June 2018, we entered into a license agreement with Aegis Therapeutics, LLC (“Aegis”), which was amended in July 2020 and January 2021.

Pursuant to the agreement, Aegis granted us an exclusive, worldwide, sublicensable license under patents and know-how relating to the INTRAVAIL drug delivery technology to research, develop, make (subject to Aegis supplying the INTRAVAIL drug delivery technology to us under a supply agreement), use, sell, offer for sale, import, and otherwise commercialize products incorporating epinephrine compounds (“Aegis Licensed Compounds”), including the neffy nasal spray.

During the term of the agreement, we are required to use commercially reasonable efforts to obtain regulatory approval for products containing one or more Aegis Licensed Compounds and using the excipient (including INTRAVAIL) (“Aegis Licensed Products”) and to thereafter maximize sales of the Aegis Licensed Products, and Aegis may not directly or indirectly exploit an Aegis Licensed Product or Aegis Licensed Compound or derivatives thereof without our consent.

In June 2018, we entered into a license agreement with Aegis Therapeutics, LLC (“Aegis”), which was amended in July 2020 and January 2021.

Under the agreement, Aegis received an upfront license fee of $50,000 and is entitled to receive development milestone payments of up to $3.95 million in aggregate and commercialization milestone payments up to $16.0 million in the aggregate for each Aegis Licensed Product.

We made a $0.5 million milestone payment to Aegis upon the achievement of a regulatory milestone during 2019, and a $1.0 million payment to Aegis upon the FDA’s acceptance of our US NDA filing, which occurred in the third quarter of 2022.

We will be required to pay Aegis a milestone payment of $2.5 million contingent upon the FDA approval of the first Aegis Licensed Product and a milestone payment of $5.0 million contingent upon first commercial sale of the first Aegis Licensed Product.

Additionally, Aegis is entitled to receive a low- to mid-single-digit percentage royalty, subject to reductions under certain conditions including due to generic competition or below threshold levels of profitability in specific countries around the world, on net sales of all Aegis Licensed Products during the applicable royalty term, which commences on the first commercial sale of a Aegis Licensed Product in a country and ends upon the later of the expiration of all licensed patents covering such Aegis Licensed Product in such country or 15 years after the date of the first commercial sale of the Aegis Licensed Product in such country (“Aegis Royalty Term”).

The agreement will continue until the expiration of the last-to-expire Aegis Royalty Term, unless sooner terminated.

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Collaboration and License Agreement with Alfresa

In April 2020, we entered into a collaboration and license agreement with Alfresa Pharma Corporation (“Alfresa”).

Pursuant to the agreement, we granted Alfresa (i) an exclusive, sublicensable license under our patents relating to neffy to develop, use and import epinephrine compositions (“Alfresa Licensed Compositions”) and related products (“Alfresa Licensed Products”) in Japan (the “Alfresa Territory”) and to promote, distribute, offer for sale and sell Alfresa Licensed Products in the Alfresa Territory, and (ii) a non-exclusive, sublicensable license to manufacture and commercialize Alfresa Licensed Products under the license described in clause (i), under our technology to make and have made Alfresa Licensed Compositions and Alfresa Licensed Products in and outside the Alfresa Territory solely for the purpose of exercising the license described in clause (i) in the Alfresa Territory.

In April 2020, we entered into a collaboration and license agreement with Alfresa Pharma Corporation (“Alfresa”).

We expressly reserved all rights to practice and grant licenses under our technology outside the scope of the licenses granted to Alfresa, including the right to manufacture Alfresa Licensed Compositions and Alfresa Licensed Products in the Alfresa Territory.

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Collaboration and Distribution Agreement with Pediatrix

In March 2021, we entered into a collaboration and distribution agreement with Pediatrix Therapeutics (“Pediatrix”).

Pursuant to the agreement, we granted Pediatrix (i) an exclusive, royalty-bearing, sublicensable license under our patents relating to neffy to develop, use, register and import epinephrine compositions (“Pediatrix Licensed Compositions”) and related products (“Pediatrix Licensed Products”) in China, Macau, Hong Kong and Taiwan (the “Pediatrix Territory”) and to promote, offer for sale and sell Pediatrix Licensed Products in the Pediatrix Territory;

In March 2021, we entered into a collaboration and distribution agreement with Pediatrix Therapeutics (“Pediatrix”).

and (ii) an exclusive, royalty-bearing, sublicensable license to manufacture Pediatrix Licensed Compositions and Pediatrix Licensed Products solely for the purpose of exercising the license described in clause (i) in the Pediatrix Territory.

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Additionally, we are eligible to receive a tiered royalty on the net sales of all Pediatrix Licensed Products during the applicable royalty term, which is less than one percent below a minimum annual sales threshold, and increasing to low-to-mid double-digit percentages above the minimum annual sales threshold, subject to reductions under certain conditions including due to generic competition.

Pediatrix’s obligation to pay us royalties continues on a Pediatrix Licensed Product-by- Pediatrix Licensed Product and region-by-region basis in the Pediatrix Territory, until the latest of (i) expiration of the last-to-expire valid claim of our patents covering such Licensed Product in such region;

(ii) the expiration of all regulatory exclusivities that cover such Licensed Product in such region;

or (iii) ten years after the first commercial sale of such Pediatrix Licensed Product in such region (the “Pediatrix Royalty Term”).

The agreement will continue until the expiration of the last-to-expire Pediatrix Royalty Term.

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Manufacturing Agreement with Renaissance

In September 2020, we entered into a manufacturing agreement with Renaissance Lakewood, LLC (“Renaissance”).

Pursuant to the agreement, Renaissance agreed to manufacture for, and provide to us, neffy nasal unit dose sprays (“Renaissance Products”).

In September 2020, we entered into a manufacturing agreement with Renaissance Lakewood, LLC (“Renaissance”), which was subsequently amended in July 2023.

Pursuant to the agreement, Renaissance agreed to manufacture for, and provide to us, neffy nasal unit dose sprays (“Renaissance Products”).

We are obligated to provide Renaissance with certain supplies to manufacture the Renaissance Products and to purchase from Renaissance a mid double-digit percentage of our annual aggregate Renaissance Product requirements in the EU, and a high double-digit percentage of our annual aggregate Renaissance Product requirements in the U.S.

The agreement contains conventional commercial pharmaceutical manufacturing provisions including certain minimum purchase amounts to be determined in the future based on forecast needs and minimum batch size projections.

We may also request Renaissance perform certain services related to the Renaissance Product, for which we will pay reasonable compensation to Renaissance.

We may also request Renaissance to perform certain services related to the Renaissance Product, for which we will pay reasonable compensation to Renaissance.

The initial term of the agreement commenced on the date it was entered into and continues (a) for Renaissance Product designated for commercial sale in the U.S.

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launch date and (ii) the initial U.S.

launch date (“U.S.

Initial Term”), and (b) for Renaissance Product designated for commercial sale in the EU and other countries, the earlier of the fifth anniversary of (i) the target EU launch date and (ii) the initial EU launch date (“EU Initial Term”), in each case unless earlier terminated by one of the parties.

Initial Term and EU Initial Term automatically renew for successive two-year terms (“Renewal Term”).

launch date (“U.S.

Initial Term and EU Initial Term automatically renew for successive two-year terms (“Renewal Term”).

Either party may elect not to renew the U.S.

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These products are known as combination products.

Under the Federal Food, Drug and Cosmetic Act (“FDCA”), the FDA is charged with assigning a center with primary jurisdiction, or a lead center, for review of a combination product.

The determination of which center will be the lead center is based on the “primary mode of action”

of the combination product.

Under the Federal Food, Drug and Cosmetic Act (“FDCA”), the FDA is charged with assigning a center with primary jurisdiction, or a lead center, for review of a combination product.

The determination of which center will be the lead center is based on the “primary mode of action” of the combination product.

Thus, if the primary mode of action of a drug-device combination product is attributable to the drug product, the FDA center responsible for premarket review of the drug product would have primary jurisdiction for the combination product.

A combination product with a primary mode of action attributable to the drug component, such as neffy , generally would be reviewed and approved pursuant to the drug approval processes set forth in the FDCA.

In reviewing the NDA for such a product, however, FDA reviewers would consult with their counterparts in the device center to ensure that the device component of the combination product –

the sprayer - met applicable requirements regarding safety, effectiveness, durability and performance.

In reviewing the NDA for such a product, however, FDA reviewers would consult with their counterparts in the device center to ensure that the device component of the combination product – the sprayer - met applicable requirements regarding safety, effectiveness, durability and performance.

In addition, under FDA regulations, combination products such as neffy are subject to cGMP requirements applicable to both drugs and devices, including the Quality System Regulations applicable to medical devices.

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The process required by the FDA before a drug may be marketed in the United States generally involves the following:

completion of extensive preclinical laboratory tests, preclinical animal studies and formulation studies in accordance with applicable regulations, including the FDA’s Good Laboratory Practice (“GLP”) regulations and other applicable regulations;

submission to the FDA of an investigational new drug (“IND”), which must become effective before human clinical trials may begin;

approval by an independent institutional review board (“IRB”) at each clinical site before each trial may be initiated;

performance of adequate and well-controlled human clinical trials in accordance with applicable regulations, including the FDA’s good clinical practice (“GCP”) regulations to establish the safety and efficacy of the proposed drug for its proposed indication;

submission to the FDA of an investigational new drug (“IND”), which must become effective before human clinical trials may begin;

approval by an independent institutional review board (“IRB”) at each clinical site before each trial may be initiated;

submission to the FDA of an NDA after completion of all pivotal trials;

a determination by the FDA within 60 days of its receipt of an NDA to file the NDA for review;

satisfactory completion of an FDA pre-approval inspection of the manufacturing facility or facilities where the drug is produced to assess compliance with cGMP requirements to assure that the facilities, methods and controls are adequate to preserve the drug’s identity, strength, quality and purity;

potential FDA audit of the preclinical and/or clinical trial sites that generated the data in support of the NDA to assess compliance with GCP regulations;

satisfactory completion of an FDA advisory committee review, if applicable;

satisfactory completion of an FDA PADAC review, if applicable;

FDA review and approval of the NDA prior to any commercial marketing or sale of the drug in the United States.

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The FDA may also impose clinical holds on a product candidate at any time before or during clinical trials due to safety concerns or non-compliance.

Clinical trials involve the administration of the product candidate to healthy volunteers or patients under the supervision of qualified investigators, generally physicians not employed by or under the trial sponsor’s control, in accordance with GCPs, which include the requirement that all research subjects provide their informed consent for their participation in any clinical trial.

Clinical trials are conducted under protocols detailing, among other things, the objectives of the clinical trial, dosing procedures, subject selection and exclusion criteria and the parameters to be used to monitor subject safety and assess efficacy.

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The FDA, the IRB, or the sponsor may suspend or terminate a clinical trial at any time on various grounds, including a finding that the research subjects or patients are being exposed to an unacceptable health risk.

Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution if the clinical trial is not being conducted in accordance with the IRB’s requirements or if the drug has been associated with unexpected serious harm to patients.

Additionally, some clinical trials are overseen by an independent group of qualified experts organized by the clinical trial sponsor, known as a data safety monitoring board or committee.

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a waiver of such fees may be obtained under certain limited circumstances.

In addition, the Pediatric Research Equity Act (“PREA”) requires a sponsor to conduct pediatric clinical trials for most drugs, for a new active ingredient, new indication, new dosage form, new dosing regimen or new route of administration.

Under PREA, original NDAs and supplements must contain a pediatric assessment unless the sponsor has received a deferral or waiver.

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Once the submission is accepted for filing, the FDA begins an in-depth review of the NDA.

Under the PDUFA guidelines that are currently in effect, the FDA has a goal of ten months from the date of “filing”

of a standard NDA for a new molecular entity to review and act on the submission.

This review typically takes twelve months from the date the NDA is submitted to FDA because the FDA has approximately two months to make a “filing”

decision after it the application is submitted The FDA does not always meet its PDUFA goal dates for standard and priority NDAs, and the review process is often significantly extended by FDA requests for additional information or clarification.

After the NDA submission is accepted for filing, the FDA reviews the NDA to determine, among other things, whether the proposed product is safe and effective for its intended use and whether the product is being manufactured in accordance with cGMP to assure and preserve the product’s identity, strength, quality and purity.

Under the PDUFA guidelines that are currently in effect, the FDA has a goal of ten months from the date of “filing” of a standard NDA for a new molecular entity to review and act on the submission.

This review typically takes twelve months from the date the NDA is submitted to FDA because the FDA has approximately two months to make a “filing” decision after it the application is submitted The FDA does not always meet its PDUFA goal dates for standard and priority NDAs, and the review process is often significantly extended by FDA requests for additional information or clarification.

The FDA may refer applications for novel drug products or drug products which present difficult questions of safety or efficacy to an advisory committee, typically a panel that includes clinicians and other experts, for review, evaluation and a recommendation as to whether the application should be approved and under what conditions.

The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions and typically follows the advisory committee’s recommendations.

The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions and typically follows such committee’s recommendations.

Before approving an NDA, the FDA will inspect the facilities at which the product is manufactured.

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Additionally, before approving an NDA, the FDA may inspect one or more clinical sites to assure compliance with GCP requirements.

After the FDA evaluates the application, manufacturing process and manufacturing facilities, it may issue an approval letter or a Complete Response Letter.

After the FDA evaluates the application, manufacturing process and manufacturing facilities, it may issue an approval letter or a CRL.

An approval letter authorizes commercial marketing of the drug with specific prescribing information for specific indications.

A Complete Response Letter indicates that the review cycle of the application is complete and the application will not be approved in its present form.

A Complete Response Letter usually describes all of the specific deficiencies in the NDA identified by the FDA.

The Complete Response Letter may require additional clinical data and/or (an) additional pivotal Phase 3 clinical trial(s), and/or other significant and time-consuming requirements related to clinical trials, preclinical studies or manufacturing.

If a Complete Response Letter is issued, the applicant may either resubmit the NDA, addressing all of the deficiencies identified in the letter, or withdraw the application.

A CRL indicates that the review cycle of the application is complete and the application will not be approved in its present form.

A CRL usually describes all of the specific deficiencies in the NDA identified by the FDA.

The CRL may require additional clinical data and/or (an) additional pivotal Phase 3 clinical trial(s), and/or other significant and time-consuming requirements related to clinical trials, preclinical studies or manufacturing.

If a CRL is issued, the applicant may either resubmit the NDA, addressing all of the deficiencies identified in the letter, or withdraw the application.

Even if such data and information are submitted, the FDA may ultimately decide that the NDA does not satisfy the criteria for approval.

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For example, the FDA may require Phase 4 testing, which involves clinical trials designed to further assess a drug safety and effectiveness, and may require testing and surveillance programs to monitor the safety of approved products that have been commercialized.

The FDA may also determine that a risk evaluation and mitigation strategy (“REMS”) is necessary to assure the safe use of the drug.

If the FDA concludes a REMS is needed, the sponsor of the NDA must submit a proposed REMS;

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Discovery of previously unknown problems with a product or the failure to comply with applicable FDA requirements can have negative consequences, including adverse publicity, judicial or administrative enforcement, warning letters from the FDA, mandated corrective advertising or communications with doctors, and civil or criminal penalties, among others.

Newly discovered or developed safety or effectiveness data may require changes to a product’s approved labeling, including the addition of new warnings and contraindications, and also may require the implementation of other risk management measures.

The FDA closely regulates the marketing, labeling, advertising and promotion of drug products.

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Failure to comply with these requirements can result in, among other things, adverse publicity, warning letters, corrective advertising and potential civil and criminal penalties.

Physicians may prescribe, in their independent professional medical judgment, legally available products for uses that are not described in the product’s labeling and that differ from those tested and approved by the FDA.

Physicians may believe that such off-label uses are the best treatment for many patients in varied circumstances.

The FDA does not regulate the behavior of physicians in their choice of treatments.

The FDA does, however, restrict manufacturer’s communications on the subject of off-label use of their products.

The federal government has levied large civil and criminal fines against companies for alleged improper promotion of off-label use and has enjoined companies from engaging in off-label promotion.

The FDA and other regulatory agencies have also required that companies enter into consent decrees or permanent injunctions under which specified promotional conduct is changed or curtailed.

However, companies may share truthful and not misleading information that is otherwise consistent with a product’s FDA-approved labelling.

Hatch-Waxman Act

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A 505(b)(2) NDA is an application that contains full reports of investigations of safety and efficacy but where at least some of the information required for approval comes from investigations that were not conducted by or for the applicant and for which the applicant has not obtained a right of reference or use from the person by or for whom the investigations were conducted.

This regulatory pathway enables the applicant to rely, in part, on the FDA’s prior findings of safety and efficacy for an existing product, or published literature, in support of its application.

Section 505(j) establishes an abbreviated approval process for a generic version of approved drug products through the submission of an Abbreviated New Drug Application (“ANDA”).

This regulatory pathway enables the applicant to rely, in part, on the FDA’s prior findings of safety and efficacy for an existing product, or published literature, in support of its application.

Section 505(j) establishes an abbreviated approval process for a generic version of approved drug products through the submission of an Abbreviated New Drug Application (“ANDA”).

An ANDA provides for marketing of a generic drug product that has the same active ingredients, dosage form, strength, route of administration, labeling, performance characteristics and intended use, among other things, to a previously approved product.

ANDAs are termed “abbreviated”

because they are generally not required to include preclinical (animal) and clinical (human) data to establish safety and efficacy.

ANDAs are termed “abbreviated” because they are generally not required to include preclinical (animal) and clinical (human) data to establish safety and efficacy.

Instead, generic applicants must scientifically demonstrate that their product is bioequivalent to, or performs in the same manner as, the innovator drug through in vitro, in vivo, or other testing.

The generic version must deliver the same amount of active ingredients into a subject’s bloodstream in the same amount of time as the innovator drug and can often be substituted by pharmacists under prescriptions written for the reference listed drug.

In seeking approval for a drug through an NDA, applicants are required to list with the FDA each patent with claims that cover the applicant’s drug or a method of using the drug.

Upon approval of a drug, each of the patents listed in the application for the drug is then published in the FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations, commonly known as the Orange Book.

In seeking approval for a drug through an NDA, applicants are required to list with the FDA each patent with claims that cover the applicant’s drug or a method of using the drug.

Drugs listed in the Orange Book can, in turn, be cited by potential competitors in support of approval of an ANDA or 505(b)(2) NDA.

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The NDA and patent holders may then initiate a patent infringement lawsuit in response to the notice of the paragraph IV certification.

If the paragraph IV certification is challenged by an NDA holder or the patent owner(s) asserts a patent challenge to the paragraph IV certification, the FDA may not approve that application until the earlier of 30 months from the receipt of the notice of the paragraph IV certification, the expiration of the patent, when the infringement case concerning each such patent was favorably decided in the applicant’s favor or settled, or such shorter or longer period as may be ordered by a court.

This prohibition is generally referred to as the 30-month stay.

In instances where an ANDA or 505(b)(2) NDA applicant files a paragraph IV certification, the NDA holder or patent owner(s) regularly take action to trigger the 30-month stay, recognizing that the related patent litigation may take many months or years to resolve.

Thus, approval of an ANDA or 505(b)(2) NDA could be delayed for a significant period of time depending on the patent certification the applicant makes and the reference drug sponsor’s decision to initiate patent litigation.

The Hatch-Waxman Act establishes periods of regulatory exclusivity for certain approved drug products, during which the FDA cannot approve (or in some cases accept) an ANDA or 505(b)(2) application that relies on the branded reference drug.

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The Hatch-Waxman Act also provides three years of marketing exclusivity to the holder of an NDA (including a 505(b)(2) NDA) for a particular condition of approval, or change to a marketed product, such as a new formulation for a previously approved product, if one or more new clinical studies (other than bioavailability or bioequivalence studies) was essential to the approval of the application and was conducted/sponsored by the applicant.

This three-year exclusivity period protects against FDA approval of ANDAs and 505(b)(2) NDAs for the condition of the new drug’s approval.

As a general matter, the three year exclusivity does not prohibit the FDA from approving ANDAs or 505(b)(2) NDAs for generic versions of the original, unmodified drug product.

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Pediatric exclusivity, if granted, adds six months to existing exclusivity periods and patent terms.

This six-month exclusivity, which runs from the end of other exclusivity protection or patent term, may be granted based on the voluntary completion of a pediatric trial in accordance with an FDA-issued “Written Request”

for such a trial.

Other Healthcare Laws

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federal Anti-Kickback Statute prohibits, among other things, any person or entity from knowingly and willfully offering, paying, soliciting, receiving or providing any remuneration, directly or indirectly, overtly or covertly, to induce or in return for purchasing, leasing, ordering, or arranging for or recommending the purchase, lease, or order of any good, facility, item or service reimbursable, in whole or in part, under Medicare, Medicaid or other federal healthcare programs.

The term “remuneration”

has been broadly interpreted to include anything of value.

The term “remuneration” has been broadly interpreted to include anything of value.

This statute has been interpreted to apply to arrangements between pharmaceutical manufacturers on the one hand and prescribers, purchasers and formulary managers on the other hand.

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Instead, the legality of the arrangement will be evaluated on a case-by-case basis based on a cumulative review of all its facts and circumstances.

Several courts have interpreted the statute’s intent requirement to mean that if any one purpose of an arrangement involving remuneration is to induce referrals of federal healthcare covered business, the federal healthcare program anti-kickback statute has been violated.

Additionally, the intent standard under the federal anti-kickback statute was amended by the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act (collectively, the “ACA”) to a stricter standard such that a person or entity no longer needs to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation.

In addition, the ACA codified case law that a claim including items or services resulting from a violation of the federal healthcare program anti-kickback statute constitutes a false or fraudulent claim for purposes of the federal civil False Claims Act.

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federal government.

A claim includes “any request or demand”

for money or property presented to the U.S.

A claim includes “any request or demand” for money or property presented to the U.S.

Actions under the civil False Claims Act may be brought by the Attorney General or as a qui tam action by a private individual in the name of the government.

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federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the federal civil False Claims Act.

In addition, the federal civil monetary penalties law, subject to certain exceptions, prohibits, among other things, the offer or transfer of remuneration, including waivers of copayments and deductible amounts (or any part thereof), to a Medicare or state healthcare program beneficiary if the person knows or should know it is likely to influence the beneficiary’s selection of a particular provider, practitioner or supplier of services reimbursable by Medicare or a state healthcare program.

Health Insurance Portability and Accountability Act of 1996 (“HIPAA”) created additional federal criminal statutes that prohibit, among other actions, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program, including private third party payors, knowingly and willfully embezzling or stealing from a healthcare benefit program, willfully obstructing a criminal investigation of a healthcare offense, and knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false, fictitious or fraudulent statement in connection with the delivery of or payment for healthcare benefits, items or services.

Similar to the U.S.

federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation.

In addition, HIPAA, as amended by Health Information Technology for Economic and Clinical Health Act of 2009 (“HITECH”), imposes certain requirements on covered entities, which include certain healthcare providers, health plans and healthcare clearinghouses, and their business associates and covered subcontractors that receive or obtain protected health information in connection with providing a service on behalf of a covered entity relating to the privacy, security and transmission of individually identifiable health information.

The federal Physician Payments Sunshine Act requires certain manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, with specific exceptions, to report annually to CMS information related to payments or other transfers of value made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), other health care professionals (such as physicians assistants and nurse practitioners), and teaching hospitals, as well as information regarding ownership and investment interests held by physicians and their immediate family members.

The federal Physician Payments Sunshine Act requires certain manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, with specific exceptions, to report annually to the Centers for Medicare & Medicaid Services (“CMS”) information related to payments or other transfers of value made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), other health care professionals (such as physicians assistants and nurse practitioners), and teaching hospitals, as well as information regarding ownership and investment interests held by physicians and their immediate family members.

Similar state and local laws and regulations may also restrict business practices in the pharmaceutical industry, such as state anti-kickback and false claims laws, which may apply to business practices, including but not limited to, research, distribution, sales and marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third-party payors, including private insurers, or by patients themselves;

state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government, or otherwise restrict payments that may be made to healthcare providers and other potential referral sources;

state laws and regulations that require drug manufacturers to file reports relating to pricing information and marketing expenditures or which require tracking gifts and other remuneration and items of value provided to physicians, other healthcare providers and entities;

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Some third-party payors require pre-approval of coverage for new drugs before they will reimburse healthcare providers who use such therapies.

Generally, third-party payors limit coverage and reimbursement for new medication prior to a formal review by the payors’

pharmacy and therapeutics committees.

Generally, third-party payors limit coverage and reimbursement for new medication prior to a formal review by the payors’ pharmacy and therapeutics committees.

As such, several third-party payors have indicated that our products may be subject to denial or limited coverage prior to formal review.

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Third-party payors may limit coverage to specific products on an approved list, also known as a formulary, which might not include all of the FDA-approved products for a particular indication, or place products at certain formulary levels that result in lower reimbursement levels and higher cost-sharing obligation imposed on patients.

One third-party payor’s decision to cover a particular medical product or service does not ensure that other payors will also provide coverage for the medical product or service and the level of coverage and reimbursement can differ significantly from payor to payor.

As a result, the coverage determination process will often require us to provide scientific and clinical support for the use of our products to each payor separately and can be a time-consuming process, with no assurance that coverage and adequate reimbursement will be applied consistently or obtained in the first instance.

Additionally, a third-party payor’s decision to provide coverage for a product does not imply that an adequate reimbursement rate will be approved.

Further, coverage policies and third-party reimbursement rates may change at any time.

Even if favorable coverage and reimbursement status is attained, less favorable coverage policies and reimbursement rates may be implemented in the future.

Moreover, as a condition of participating in, and having products covered under, certain federal healthcare programs, such as Medicare and Medicaid, we are subject to federal laws and regulations that require pharmaceutical manufacturers to calculate and report certain price reporting metrics to the government, such as Medicaid Average Manufacturer Price (“AMP”), and Best Price, Medicare Average Sales Price, the 340B Ceiling Price, and Non-Federal AMP reported to the Department of Veteran Affairs, and with respect to Medicaid, pay statutory rebates on utilization of manufacturers’

products by Medicaid beneficiaries.

In international markets, reimbursement and healthcare payment systems vary significantly by country, and many countries have instituted price ceilings on specific products and therapies.

For example, the European Union provides options for its member states to restrict the range of medicinal products for which their national health insurance systems provide reimbursement and to control the prices of medicinal products for human use.

For example, the EU provides options for its member states to restrict the range of medicinal products for which their national health insurance systems provide reimbursement and to control the prices of medicinal products for human use.

A member state may approve a specific price for the medicinal product or it may instead adopt a system of direct or indirect controls on the profitability of the company placing the medicinal product on the market.

Pharmaceutical products may face competition from lower-priced products in foreign countries that have placed price controls on pharmaceutical products.

Furthermore, there can be no assurance that a product will be considered medically reasonable and necessary for a specific indication, that a product will be considered cost-effective by third-party payors, that an adequate level of reimbursement will be established even if coverage is available or that the third-party payors’

reimbursement policies will not adversely affect the ability to sell a product profitably.

Healthcare Reform

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required collection of rebates for drugs paid by Medicaid managed care organizations;

required manufacturers to participate in a coverage gap discount program, under which they must agree to offer point-of-sale discounts (increased to 70 percent, effective as of January 1, 2019) off negotiated prices of applicable brand drugs to eligible beneficiaries during their coverage gap period, as a condition for the manufacturer’s outpatient drugs to be covered under Medicare Part D;

imposed a non-deductible annual fee on pharmaceutical manufacturers or importers who sell certain “branded prescription drugs”

to specified federal government programs, implemented a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated for drugs that are inhaled, infused, instilled, implanted, or injected expanded the types of entities eligible for the 340B drug discount program;

imposed a non-deductible annual fee on pharmaceutical manufacturers or importers who sell certain “branded prescription drugs” to specified federal government programs, implemented a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated for drugs that are inhaled, infused, instilled, implanted, or injected expanded the types of entities eligible for the 340B drug discount program;

expanded eligibility criteria for Medicaid programs;

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For example, on June 17, 2021, the U.S.

Supreme Court dismissed a challenge on procedural grounds that argued the ACA is unconstitutional in its entirety because the “individual mandate”

was repealed by Congress.

Supreme Court dismissed a challenge on procedural grounds that argued the ACA is unconstitutional in its entirety because the “individual mandate” was repealed by Congress.

Further, prior to the U.S.

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The executive order also instructed certain governmental agencies to review and reconsider their existing policies and rules that limit access to healthcare, including among others, reexamining Medicaid demonstration projects and waiver programs that include work requirements, and policies that create unnecessary barriers to obtaining access to health insurance coverage through Medicaid or the ACA.

In addition, on August 16, 2022, President Biden signed the Inflation Reduction Act of 2022 (“IRA”) into law, which among other things, extends enhanced subsidies for individuals purchasing health insurance coverage in ACA marketplaces through plan year 2025.

The IRA also eliminates the “donut hole”

under the Medicare Part D program beginning in 2025 by significantly lowering the beneficiary maximum out-of-pocket cost and creating a new manufacturer discount program.

The IRA also eliminates the “donut hole” under the Medicare Part D program beginning in 2025 by significantly lowering the beneficiary maximum out-of-pocket cost and creating a new manufacturer discount program.

It is unclear how such challenges and the healthcare reform measures of the Biden administration will impact the ACA.

Other legislative changes have been proposed and adopted since the ACA was enacted, including aggregate reductions of Medicare payments to providers of 2% per fiscal year pursuant to the Budget Control Act of 2011 which went into effect on April 1, 2013, and due to subsequent legislative amendments, will remain in effect until 2032, unless additional Congressional action is taken.

Under current legislation, the actual reduction in Medicare payments will vary from 1% in 2022 to up to 4% in the final fiscal year of this sequester.

In addition, on January 2, 2013, the American Taxpayer Relief Act of 2012 was signed into law which, among other things, further reduced Medicare payments to several types of providers, including hospitals, imaging centers and cancer treatment centers, and increased the statute of limitations period for the government to recover overpayments to providers from three to five years.

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Presidential executive orders, congressional inquiries, and proposed and enacted legislation designed, among other things, to bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs and reform government program reimbursement methodologies for pharmaceutical products.

For example, at the federal level, in July 2021, the Biden administration released an executive order, “Promoting Competition in the American Economy,”

with multiple provisions aimed at prescription drugs.

In response to Biden’s executive order, on September 9, 2021, the U.S.

Department of Health and Human Services (“HHS”) released a Comprehensive Plan for Addressing High Drug Prices that outlines principles for drug pricing reform and sets out a variety of potential legislative policies that Congress could pursue as well as potential administrative actions HHS can take to advance these principles.

for such drugs and biologics under the law, and (ii) imposes rebates with respect to certain drugs and biologics covered under Medicare Part B or Medicare Part D to penalize price increases that outpace inflation.

For example, at the federal level, in July 2021, the Biden administration released an executive order, “Promoting Competition in the American Economy,” with multiple provisions aimed at prescription drugs.

In response to Biden’s executive order, on September 9, 2021, the U.S.

In addition, the IRA, among other things, (i) directs HHS to negotiate the price of certain high-expenditure, single-source drugs and biologics covered under Medicare, and subject drug manufacturers to civil monetary penalties and a potential excise tax by offering a price that is not equal to or less than the negotiated “maximum fair price” for such drugs and biologics under the law, and (ii) imposes rebates with respect to certain drugs and biologics covered under Medicare Part B or Medicare Part D to penalize price increases that outpace inflation.

The IRA permits HHS to implement many of these provisions through guidance, as opposed to regulation, for the initial years.

These provisions will take effect progressively starting in fiscal year 2023, although they may be subject to legal challenges.

These provisions take effect progressively starting in fiscal year 2023.

On August 29, 2023, HHS announced the list of the first ten drugs that will be subject to price negotiations, although the Medicare drug price negotiation program is currently subject to legal challenges.

It is currently unclear how the IRA will be implemented but is likely to have a significant impact on the pharmaceutical industry.

Further, the Biden administration released an additional executive order on October 14, 2022, directing HHS to submit a report on how the Center for Medicare and Medicaid Innovation can be further leveraged to test new models for lowering drug costs for Medicare and Medicaid beneficiaries.

It is unclear whether this executive order or similar policy initiatives will be implemented in the future.

In addition, the American Taxpayer Relief Act of 2021, effective January 1, 2024, would eliminate the statutory cap on rebate amounts owed by drug manufacturers under the Medicaid Drug Rebate Program (“MDRP”), which is currently capped at 100% of the AMP for a covered outpatient drug.

In response to the Biden administration’s October 2022 executive order, on February 14, 2023, HHS released a report outlining three new models for testing by the CMS Innovation Center which will be evaluated on their ability to lower the cost of drugs, promote accessibility, and improve quality of care.

It is unclear whether the models will be utilized in any health reform measures in the future.

Further, on December 7, 2023, the Biden administration announced an initiative to control the price of prescription drugs through the use of march-in rights under the Bayh-Dole Act.

On December 8, 2023, the National Institute of Standards and Technology published for comment a Draft Interagency Guidance Framework for Considering the Exercise of March-In Rights which for the first time includes the price of a product as one factor an agency can use when deciding to exercise march-in rights.

While march-in rights have not previously been exercised, it is uncertain if that will continue under the new framework.

Individual states in the United States have also become increasingly active in implementing regulations designed to control pharmaceutical product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures and, in some cases, mechanisms to encourage importation from other countries and bulk purchasing.

For example, on January 5, 2024, the FDA approved Florida’s Section 804 Importation Program (SIP) proposal to import certain drugs from Canada for specific state healthcare programs.

It is unclear how this program will be implemented, including which drugs will be chosen, and whether it will be subject to legal challenges in the United States or Canada.

Other states have also submitted SIP proposals that are pending review by the FDA.

Any such approved importation plans, when implemented, may result in lower drug prices for products covered by those programs.

In addition, regional healthcare authorities and individual hospitals are increasingly using bidding procedures to determine which drugs and suppliers will be included in their healthcare programs.

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Numerous state, local, federal and foreign laws, including consumer protection laws and regulations related to data privacy, security, and protection, govern the collection, dissemination, use, access to, confidentiality, and security of personal information, including health-related information.

Such obligations may include, without limitation, HIPAA, the Federal Trade Commission Act, the California Consumer Privacy Act of 2018 (“CCPA”), the Canadian Personal Information Protection and Electronic Documents Act, Canada’s Anti-Spam Legislation, the European Union’s General Data Protection Regulation 2016/679 (“EU GDPR”), and the EU GDPR as it forms part of United Kingdom (“UK”) law by virtue of section 3 of the European Union (Withdrawal) Act 2018 (“UK GDPR”).HIPAA, as amended by HITECH, imposes obligations, including mandatory contractual terms, on certain covered healthcare providers, health plans, and healthcare clearinghouses and their respective business associates and covered subcontractors that perform services for them that involve the use, or disclosure of, individually identifiable health information with respect to safeguarding the privacy, security and transmission of individually identifiable health information.

HIPAA, as amended by HITECH, imposes obligations, including mandatory contractual terms, on certain covered healthcare providers, health plans, and healthcare clearinghouses and their respective business associates and covered subcontractors that perform services for them that involve the use, or disclosure of, individually identifiable health information with respect to safeguarding the privacy, security and transmission of individually identifiable health information.

In addition, certain state and non-U.S.

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Privacy and security laws, regulations, and other obligations are constantly evolving, may conflict with each other to make compliance efforts more challenging, and can result in investigations, proceedings, or actions that lead to significant penalties and restrictions on data processing.

In addition, Congress and various other states have enacted or are considering new laws and regulations regarding the privacy and security of heath and other personal information to which we may become subject.

In addition, Congress and various other states have enacted or are considering new laws and regulations regarding the privacy and security of health and other personal information to which we may become subject.

Further, all 50 states have passed laws regulating the actions that a business must take if it experiences a data breach, such as prompt disclosure to affected customers.

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The CCPA provides for civil penalties for violations, as well as a private right of action for certain data breaches that result in the loss of personal information that may increase the likelihood of, and risks associated with, data breach litigation.

Moreover, the California Privacy Rights Act, or the CPRA, –

a consumer privacy ballot initiative that amends and expands the CCPA became effective on January 1, 2023, and expands the CCPA.

Moreover, the California Privacy Rights Act, or the CPRA, – a consumer privacy ballot initiative that amends and expands the CCPA became effective on January 1, 2023, and expands the CCPA.

The CPRA affords California residents significantly more control over their personal information, imposes heightened compliance obligations on covered companies, and establishes a new enforcement agency dedicated to consumer privacy.

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Foreign Corrupt Practices Act

Foreign Corrupt Practices Act of 1977 (“FCPA”) prohibits any U.S.

individual or business from paying, offering, or authorizing payment or offering of anything of value, directly or indirectly, to any foreign official, political party or candidate for the purpose of influencing any act or decision of the foreign entity in order to assist the individual or business in obtaining or retaining business.

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Whether or not we or our potential collaborators obtain FDA approval for a product, we must obtain the requisite approvals from regulatory authorities in foreign countries prior to the commencement of clinical trials or marketing of the product in those countries.

Certain countries outside of the United States have a similar process that requires the submission of an application for a clinical trial authorization (“CTA”) much like the IND prior to the commencement of human clinical trials.

In the EU, for example, a CTA must be submitted to each country’s national health authority and an application made to an independent ethics committee, much like the FDA and IRB, respectively.

Once the CTA is approved in accordance with a country’s requirements and a favorable ethics committee opinion has been issued, clinical trial development may proceed.

In the EU, for example, a CTA must be submitted to each country’s national health authority and an application made to an independent ethics committee, much like the FDA and IRB, respectively.

Once the CTA is approved in accordance with a country’s requirements and a favorable ethics committee opinion has been issued, clinical trial development may proceed.

The requirements and process governing the conduct of clinical trials are to a significant extent harmonized at the EU level, but could vary from country to country.

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For example, upon receiving marketing authorization, new chemical entities generally receive eight years of data exclusivity and an additional two years of market exclusivity.

If granted, data exclusivity prevents regulatory authorities in the EU from referencing the innovator’s data to assess a generic or biosimilar application.

During the additional two-year period of market exclusivity, a generic or biosimilar marketing authorization can be submitted, and the innovator’s data may be referenced, but no generic or biosimilar product can be marketed until the expiration of the market exclusivity.

However, there is no guarantee that a product will be considered by the EU’s regulatory authorities to be a new chemical entity, and products may not qualify for data exclusivity.

If granted, data exclusivity prevents regulatory authorities in the EU from referencing the innovator’s data to assess a generic or biosimilar application.

However, there is no guarantee that a product will be considered by the EU’s regulatory authorities to be a new chemical entity, and products may not qualify for data exclusivity.

The EMA grants orphan drug designation to promote the development of products for the treatment, prevention or diagnosis of life-threatening or chronically debilitating conditions affecting not more than five in 10,000 people in the EU.

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Corporate Information

On November 8, 2022 (the “Closing Date”), Silverback Therapeutics, Inc., a Delaware corporation (“Silverback”), now known as ARS Pharmaceuticals, Inc., completed its reverse merger (the “Merger”) with privately-held ARS Pharmaceuticals, Inc., in accordance with the terms of the agreement and plan of merger and reorganization, dated July 21, 2022, as amended on August 11, 2022 and October 25, 2022 (the “Merger Agreement”), whereby Sabre Merger Sub, Inc.

(“Merger Sub”), a Delaware corporation and wholly-owned subsidiary of Silverback, merged into ARS Pharma, with ARS Pharma surviving as Silverback’s wholly-owned subsidiary.

Pursuant to the Merger Agreement, Silverback changed its name to ARS Pharmaceuticals, Inc.

See Item 7- Management’s Discussion and Analysis of Financial Condition and Results of Operations of this Annual Report and Note 3 - Merger and Related Transactions of our financial statements for the year ended December 31, 2023 included in Item 8 of this Annual Report for more information regarding the Merger.

We incorporated in Delaware in January 2016.

Our corporate headquarters are located at 11682 El Camino Real, Suite 120, San Diego, California 92130, and our telephone number is (858) 771-9307.

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We have included our website in this Annual Report on Form 10-K solely as an inactive textual reference.

(“ARS Pharma”), in accordance with the terms of the agreement and plan of merger and reorganization, dated July 21, 2022, as amended on August 11, 2022 and October 25, 2022 (the “Merger Agreement”), whereby Sabre Merger Sub, Inc.

(“Merger Sub”), a Delaware corporation and wholly-owned subsidiary of Silverback, merged into ARS Pharma, with ARS Pharma surviving as Silverback’s wholly-owned subsidiary.

Pursuant to the Merger Agreement, Silverback changed its name to ARS Pharmaceuticals, Inc.

See Item 7- Management’s Discussion and Analysis of Financial Condition and Results of Operations of this Annual Report and Note 3- Merger and Related Transactions of our financial statements for the year ended December 31, 2022 included in Item 8 of this Annual Report for more information regarding the Merger.

As of December 31, 2022, we had seventeen full-time employees and three part-time employees.

As of December 31, 2023, we had 24 full-time employees and 2 part-time employees.

Of these employees, two held Ph.D.

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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business