5 unchanged sentences
Company Summary
−Removed: We are a biopharmaceutical company focused on the development of our novel, potentially first-in-class product candidate, neffy ® (previously referred to as ARS-1) for the emergency treatment of Type I allergic reactions, including anaphylaxis.
−Removed: neffy is a proprietary composition of epinephrine with an innovative absorption enhancer called Intravail ® , which allows neffy to provide injection-like absorption of epinephrine at a low dose, in a small, easy-to-carry, easy-to-use, rapidly administered and reliable nasal spray.
−Removed: Type I severe allergic reactions are serious and potentially life-threatening events that can occur within minutes of exposure to an allergen and require immediate treatment with epinephrine injection, the only FDA-approved medication for these reactions.
−Removed: While epinephrine injection devices have been shown to be highly effective, there are well published limitations that result in many patients and caregivers delaying or not administering treatment in an emergency situation.
−Removed: These limitations include fear of the needle, lack of portability, needle-related safety concerns, lack of reliability, and complexity of the devices.
−Removed: 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.
+Added: We are a biopharmaceutical company focused on the commercialization and development of neffy (previously referred to as ARS-1 and currently identified in the EU by the trade name EURneffy ) for the needle-free intranasal delivery of epinephrine for the emergency treatment of Type I allergic reactions, including anaphylaxis.
+Added: neffy is the first and only FDA and European Commission (“EC”)-approved needle-free epinephrine product, and the first new delivery method for epinephrine in more than 35 years.
+Added: neffy is a proprietary composition of epinephrine with an innovative absorption enhancer called Intravail, which allows neffy to safely provide intranasal delivery of epinephrine at a low dose within the exposures of approved injectable products across a range of dosing conditions (including repeat dosing and allergen challenge).
+Added: We believe neffy ’s “no needle, no injection” approach addresses a significant unmet need in the use of epinephrine, which, except for neffy , is currently approved only in injectable formulations for the emergency treatment of Type I allergic reactions.
There are approximately 40 million people in the United States who experience Type I allergic reactions.
−Removed: 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.
−Removed: Even if patients or caregivers carry an autoinjector, more than half either delay or do not administer the device when needed in an emergency.
−Removed: In aggregate, we estimate that 90% of patients prescribed an epinephrine device are not achieving an optimal treatment outcome today.
−Removed: 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.
−Removed: 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.
−Removed: 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”).
−Removed: 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).
−Removed: 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).
−Removed: 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.
−Removed: This request came after the favorable benefit-risk assessment of the PADAC to approve neffy without need for additional studies.
−Removed: 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.
−Removed: 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.
−Removed: However, the timing for regulatory approvals is outside of our control and may be delayed and is uncertain.
+Added: Of this group, approximately 20 million people are reported in the last 3 years of claims data to have been diagnosed and experienced severe Type I allergic reactions that may lead to anaphylaxis, and approximately 6.5 million were prescribed an epinephrine autoinjector.
+Added: However (in 2023, for example), only 3.2 million filled their active epinephrine autoinjector prescription, and of those, only half consistently carry their prescribed autoinjector with them due to the many drawbacks of these devices.
+Added: We believe the market opportunity for neffy in the United States is significant.
+Added: At the current list price for neffy and our target total gross-to-net yield, the estimated 6.5 million patients prescribed an epinephrine autoinjector in the United States represents an initial addressable market opportunity of approximately $3 billion in annual net sales with an additional 13.5 million diagnosed patients that have not been prescribed an epinephrine autoinjector.
+Added: The drawbacks of approved epinephrine devices, with the exception of neffy and our intranasal epinephrine technology product candidates, include the use of needles, which can result in patient and caregiver injury as well as hesitation and delays in administration due principally to apprehension and pain of needles, allowing 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.
+Added: In particular, intra-muscular injections also subject to dosing errors and risk of accidental blood vessel injections, which can cause a significant spike in the intravascular delivery of epinephrine potentially leading to serious cardiovascular complications or events.
+Added: We believe neffy’s and our intranasal epinephrine technology product candidates’ design, particularly the compact size and “no needle, no injection” delivery, eliminates needle-related apprehension and pain, improves portability and ease of use, is highly reliable, and will increase prescriptions for epinephrine, making it more likely that patients and caregivers will 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.
+Added: Data from our studies of neffy and our intranasal epinephrine technology product candidates demonstrated nasally delivered epinephrine reached blood levels comparable to those of already approved epinephrine injectable products across single dosing, repeat dosing, self-administration or allergen challenge conditions, and produced clinically significant pharmacodynamic responses that were greater than or comparable to reference injection products.
+Added: Pharmacodynamic response is a surrogate for efficacy and was observed approximately one minute after dosing with neffy and our intranasal epinephrine technology product candidates Pharmacodynamic response as a surrogate for efficacy was considered the primary basis for approval in the European Union with the EMA approval of neffy 2 mg.
+Added: On August 9, 2024, the FDA approved neffy 2 mg for the emergency treatment of Type I allergic reactions, including anaphylaxis, in adults and children who weigh 30 kg or greater.
+Added: As a result, we initiated commercial launch of neffy 2 mg in the United States, with product becoming available for shipment on September 23, 2024.
+Added: This commercialization effort currently includes a direct sales force of 118 individuals targeting high-volume epinephrine prescribers that is supported by branded direct-to-consumer marketing, disease awareness campaigns with advocacy groups and non-personal promotion such as non-personal promotion including continuing medical education programs in collaboration with allergist societies, speaker bureaus, peer-to-peer programs and participation in regional and national medical conferences.
+Added: On March 5, 2025, the FDA approved the supplemental NDA for neffy 1 mg dose for the emergency treatment of Type I allergic reactions, including anaphylaxis, in patients who are four years of age and older and weigh 15 kg to less than 30 kg.
+Added: Commercial Launch Initiated on September 23, 2024
+Added: On August 22, 2024, the EC granted marketing authorization in the EU for EURneffy (the trade name for neffy 2 mg in the European Union and United Kingdom), for the emergency treatment of allergic reactions (anaphylaxis), in adults and children who weigh 30 kg or greater.
+Added: Through our collaboration with ALK (discussed below), we anticipate that EURneffy will be made available to patients in certain EU member states in 2025.
+Added: Regulatory review of neffy is ongoing in Canada, the United Kingdom, China, Japan, and Australia.
+Added: ARS has filed in Canada in January 2025 and the United Kingdom in December 2024 on behalf of ALK, while Pediatrix, Alfresa and CSL have filed in China, Japan and Australia during the fourth quarter of 2024, respectively.
+Added: Regulatory decisions are anticipated by mid-2025 in the U.K., the second-half of 2025 in Japan, year-end 2025 in Canada, and in the first-half of 2026 in China and Australia.
+Added: neffy has already been approved or is under regulatory review in countries representing approximately 98% of the current global epinephrine autoinjector sales.
+Added: 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 2b randomized, placebo controlled outpatient clinical trial in chronic spontaneous urticaria patients on a chronic antihistamine treatment regimen who still experience flares or exacerbations.
+Added: This Phase 2b study is anticipated to be initiated in the second quarter of 2025, with topline data anticipated in early 2026, followed by the potential initiation of a single pivotal efficacy study in 2026.
Epinephrine and Allergic Reactions Background
4 unchanged sentences
The only out-of-hospital delivery option today is an intra-muscular injectable product, typically offered as prefilled syringes or auto-injector devices, such as EpiPen, which is marketed by Viatris Inc., and generic versions of EpiPen, marketed by Teva Pharmaceuticals, Inc.
−Removed: These intra-muscular auto-injection devices have several limitations that result in under-utilization by patients and may lead to serious complications and hospitalizations.
−Removed: These limitations include:
+Added: These intra-muscular auto-injection devices have several limitations that include:
lack ease of portability with only 50% of patients filling prescriptions carrying the device;
8 unchanged sentences
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.
−Removed: These patients are additive to the 3.2 million patients that do fill a prescription per year.
−Removed: 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.
−Removed: neffy is an investigational drug currently in clinical trials for the emergency treatment of allergic reactions (type I) including anaphylaxis.
−Removed: neffy is not approved by the FDA, EMA or other health authorities.
−Removed: neffy is designed to address the shortcomings of intra-muscular injectable devices.
−Removed: 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.
−Removed: 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.
−Removed: Comparable PK and PD to injection products .
−Removed: In our clinical trials, we observed that neffy has comparable PK and PD compared to marketed epinephrine injectables.
+Added: These patients are additive to the 3.2 million patients that do fill a prescription per year, for an estimated total initial addressable market of 6.5 million, representing approximately $3 billion in annual net sales based on neffy ’s current list price and target total gross-to-net yield to ARS Pharma.
+Added: In addition, there are an estimated 13.5 million unique patients who are diagnosed, but never received an epinephrine prescription.
+Added: neffy 2 mg is approved by the FDA and EC for the emergency treatment of Type I allergic reactions, including anaphylaxis, for adults and children who weigh 30 kg or greater;
+Added: neffy 1 mg is approved by the FDA for the emergency treatment of Type I allergic reactions, including anaphylaxis, for patients who are four years of age and older and weigh 15 kg to less than 30 kg .
+Added: neffy and our intranasal epinephrine technology product candidates are designed to address the shortcomings of intra-muscular injectable devices.
+Added: neffy and our intranasal epinephrine technology product candidates are 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.
+Added: Based on the factors set forth below, we believe that neffy and our intranasal epinephrine technology product candidates 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.
Needle-free, easy-to-use, pocket-sized and highly reliable nasal spray.
−Removed: 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.
−Removed: 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.
−Removed: Dosing neffy also cannot be obstructed by common anaphylaxis co-morbidities such as vomiting or angioedema of the lips, face, mouth or tongue.
−Removed: No inhalation or breathing is needed during administration of neffy .
+Added: neffy and our intranasal epinephrine technology product candidates are 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.
+Added: 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 our intranasal epinephrine technology in our human factors validation study using the intended commercial instructions for use and quick reference guide.
+Added: Unlike autoinjector delivery that has patients and caregivers hold an injection in place for three seconds, neffy and our intranasal epinephrine technology product candidates delivery requires no holding time with epinephrine being delivered nearly instantaneously into the systemic circulation via the nose after device activation.
+Added: Dosing neffy and our intranasal epinephrine technology product candidates cannot be obstructed by common anaphylaxis co-morbidities such as vomiting or angioedema of the lips, face, mouth or tongue.
+Added: No inhalation or breathing is needed during administration of neffy or our intranasal epinephrine technology product candidates.
No risk of needle-related injuries .
−Removed: neffy has no risk of needle-related injuries including injection into a blood vessel, lacerations, or caregiver self-injection since the sprayer device does not have a needle.
+Added: neffy and our intranasal epinephrine technology product candidates have no risk of needle-related injuries including injection into a blood vessel, lacerations, or caregiver self-injection since the sprayer device does not have a needle.
+Added: Accidental injections to the hands or fingers of a caregiver or a child occur more than 3,500 times a year in the United States with epinephrine injection devices.
Less hesitation to dose epinephrine.
Early administration of epinephrine can reduce the severity, risk of hospitalization and mortality associated with severe Type I allergic reactions.
−Removed: In patient surveys we have conducted, patients indicated a relief from fear of injection and an expectation to utilize neffy without delay in a manner more consistent with recommended guidelines due to neffy being a nasal spray.
+Added: In patient surveys we have conducted, patients indicated a relief from fear of injection and an expectation to utilize neffy without delay in a manner more consistent with recommended guidelines due to neffy and our intranasal epinephrine technology product candidates being a nasal spray.
Low potent dose of epinephrine .
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.
−Removed: neffy has high bioavailability matching the approved doses of injection at a low dose of 2.0 or 1.0 mg intranasally.
−Removed: Even in the unlikely situation where epinephrine would be 100% bioavailable after administration of neffy , the resulting exposure is expected to be tolerable.
−Removed: Due to its low dose of epinephrine and high bioavailability, neffy has minimal to no GI symptoms.
+Added: neffy and our intranasal epinephrine technology product candidates have high bioavailability matching the approved doses of injection at a low dose of 2.0 or 1.0 mg intranasally.
+Added: Even in the unlikely situation where epinephrine would be 100% bioavailable after administration of neffy or our intranasal epinephrine technology product candidates, the resulting exposure is expected to be tolerable.
+Added: Due to its low dose of epinephrine and high bioavailability, neffy and our intranasal epinephrine technology product candidates have 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 .
−Removed: neffy is expected to have a shelf-life at least comparable to the 18 month shelf-life of auto-injector products, but with improved stability and shelf-life at high-temperature than existing products in the market (up to 3 months at 50 o C or 122 o F) that allows neffy to retain potency even if accidentally left in a high temperature environment.
+Added: neffy 2 mg has a shelf-life of 30 months at room temperature, as opposed to the reported shelf-life range of approved injection products from the date of product manufacture of 18 to 24 months, and volume-weighted average shelf-life of between 22 and 23 months.
+Added: Furthermore, neffy 2 mg has improved stability and shelf-life at high-temperature compared to existing products in the market (testing met specifications in conditions up to 3 months at 50 o C or 122 o F), which allows neffy to retain potency even if accidentally left in a high temperature environment.
Combination of previously validated product components .
−Removed: neffy consists of a unique combination of three validated products, which we believe will significantly reduce neffy’s clinical and commercial development risks:
+Added: neffy consists of a unique combination of three validated products, which we believe will significantly reduce neffy’s 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;
1 unchanged sentence
and Intravail, an innovative absorption enhancer that has been previously included in the formulations of FDA approved products, such as VALTOCO and TOSYMRA nasal spray.
−Removed: We believe the cost of goods for neffy will allow us to achieve gross profit margins similar to branded oral small molecule drugs assuming prices comparable to the marketed injectable products.
−Removed: Well positioned for regulatory submissions, and if approved, advance to commercialization.
−Removed: 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.
−Removed: This study assessed repeat doses of neffy compared to repeat doses of epinephrine injection under allergen-induced allergic rhinitis conditions.
−Removed: In Europe, our Market Authorization Application (“MAA”) is under review and we anticipate a regulatory decision (CHMP Opinion) by mid-2024.
+Added: We believe the cost of goods for neffy will allow us to achieve gross profit margins similar to branded oral small molecule products at our current list price for neffy and our expected total gross-to-net yield.
Potential for high demand and attractive product uptake conditions.
−Removed: We have conducted extensive market research with physicians, patients, parents and other caregivers that shows neffy has a clinical product profile that is highly desirable and addresses key unmet needs.
+Added: We have conducted extensive market research with physicians, patients, parents and other caregivers that shows neffy clinical product profile that is highly desirable and addresses key unmet needs.
We believe we can successfully commercialize neffy by targeting high-prescribing allergists, pediatricians and primary care physicians who we believe will prescribe neffy as it would be a very attractive treatment option within the patient community.
−Removed: 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.
−Removed: 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 adjustment.
+Added: In addition, our market research indicates that insurance plans (payors) perceive neffy as a differentiated product candidate, which has been validated by successful contracting with payers at a total gross-to-net yield which is in line with other innovator branded products.
+Added: We anticipate approximately 52% of commercially insured patients will have unrestricted access to neffy as of April 1, 2025.
+Added: We currently own or exclusively license a robust global intellectual property portfolio including issued composition of matter and method patents relating to neffy and our intranasal epinephrine technology product candidates that are not expected to expire until 2039 before consideration of any potential patent term adjustment.
Our Management Team, Financing History and Investors
13 unchanged sentences
Brian Dorsey, Chief Operating Officer and Alex Fitzpatrick, Chief Legal Officer.
−Removed: Since our inception, we have raised over $360 million in proceeds, including equity financing from a syndicate of leading life sciences investors that include, among others, RA Capital, SR One and Deerfield, from our licensing and collaboration agreements and from our reverse merger with Silverback Therapeutics, Inc.
−Removed: 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.
−Removed: 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.
−Removed: 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 .
−Removed: Our Pipeline:
−Removed: Suite of neffy Programs
−Removed: We are focused on advancing neffy through regulatory approvals for the emergency treatment of Type I allergic reactions, including anaphylaxis, and commercialization.
−Removed: 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.
−Removed: 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.
−Removed: 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).
−Removed: 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).
−Removed: 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.
−Removed: This request came after the favorable benefit-risk assessment of the PADAC to approve neffy without need for additional studies.
−Removed: 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.
−Removed: 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.
−Removed: 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.
−Removed: Our partners expect to submit regulatory filings equivalent to an NDA in China and Japan by year end 2024.
−Removed: 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.
−Removed: The interim pediatric data including subjects greater than 30 kg in weight is included in our initial NDA.
−Removed: 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.
−Removed: 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.
−Removed: 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.
−Removed: 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.
+Added: Since our inception, we have raised $518.9 million in proceeds, including equity financing from a syndicate of leading life sciences investors that include, among others, RA Capital, SR One and Deerfield, from our licensing and collaboration agreements and from our reverse merger with Silverback Therapeutics, Inc.
+Added: We have entered into licensing and collaboration agreements for neffy with Alfresa Pharma for Japanese rights, Pediatrix Therapeutics (founded by F-Prime Capital, Eight Roads and Creacion Ventures) for Chinese rights and CSL Seqirus for Australia and New Zealand rights.
+Added: We have also entered into a licensing and collaboration agreement with ALK for territories outside the United States and the territories covered by the Alfresa, Pediatrix and CSL agreements;
+Added: these territories include Canada, the United Kingdom, European Union and other countries.
+Added: Our strategy is focused on commercializing and developing neffy as the first and only 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:
−Removed: Obtain FDA approval of neffy .
−Removed: 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.
−Removed: This request came after the favorable benefit-risk assessment of the PADAC on May 11, 2023 to approve neffy without need for additional studies.
−Removed: 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.
−Removed: 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.
−Removed: neffy has received Fast Track designation.
−Removed: However, the timing for regulatory approvals is outside ARS Pharma’s control, may be delayed and is uncertain.
−Removed: Commercialize neffy in the United States .
−Removed: 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 40 to 45% of the current epinephrine prescriptions.
−Removed: Our promotion will target high-prescribing allergists, pediatricians and primary care physicians through both traditional and non-traditional professional channels.
−Removed: 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.
−Removed: 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.
+Added: Continue to educate healthcare providers about neffy:
+Added: We began our commercialization efforts in the United States during the fourth quarter of 2024 by deploying a combination of direct promotion through a current sales force of 118 individuals comprising sales reps, virtual sales consultants and area sales managers, and non-personal promotion efforts, which are intended to reach, at a minimum, healthcare professionals that account for 40 to 45% of the current epinephrine prescriptions.
+Added: Our promotion targets high-prescribing allergists, pediatricians and primary care physicians through both traditional and non-traditional professional channels.
+Added: As of March 2025, approximately 2,500 healthcare professionals have enrolled in our neffy experience program that allows healthcare professionals to use neffy firsthand as rescue therapy for anaphylaxis during in-clinic allergen challenge, and obtain direct clinical experience using neffy .
+Added: We anticipate that our promotional reach will eventually exceed greater than 80% of the current epinephrine prescriptions in the United States through a combination of sales force expansion by early 2026 and non-personal promotion that includes continuing medical education programs in collaboration with allergist societies, speaker bureaus, peer-to-peer programs and participation in regional and national medical conferences.
+Added: Continue to obtain payer coverage and grow sales of neffy.
+Added: Quickly attaining broad market access for severe allergy patients is a key element to ensuring a seamless patient experience to acquiring neffy and rapidly growing neffy sales.
+Added: We have successfully contracted with key payers including Express Scripts, the second largest pharmacy benefit manager in the United States.
+Added: We believe payers recognize the value and innovation of neffy for Type I allergic patients, including potential cost-savings to the healthcare system due to greater carriage and early use of epinephrine devices.
+Added: We are on track to achieve access to commercial lives under contract of 60% or greater by the end of the first quarter of 2025, and 80% by the early part of the third quarter of 2025.
+Added: With our payer contracting strategy, a $25 or less co-pay savings card, a $199 cash price, and patient assistance programs, we anticipate that the out-of-pocket cost for acquiring neffy to patients may be less than or similar to that of generic epinephrine autoinjectors, thereby minimizing cost barriers to acquiring neffy .
+Added: Accelerate direct to consumer marketing efforts of neffy.
+Added: We believe that the epinephrine market has been a historically promotionally sensitive product category, and that the favorable product attributes of neffy are attractive to consumers.
+Added: Using 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, as well as the 3.3 million patients who have received a prescription, but either refused or discontinued treatment.
+Added: These 6.5 million patients are primarily treated by the same high-prescribing allergists and pediatricians that our sales force is targeting.
+Added: We believe that our direct-to-consumer marketing strategy will also activate the 13.5 million patients who are diagnosed and under the care of physicians (primarily non-allergists), but who have not been prescribed an epinephrine intramuscular injectable between 2020-2022.
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.
−Removed: In Europe, our MAA is under review, and we anticipate a decision (CHMP Opinion) by mid-2024.
−Removed: 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 .
−Removed: Conduct additional studies of neffy to address additional Type I allergic reactions .
+Added: The EC granted marketing authorization in the EU for EURneffy (the trade name for neffy 2 mg in the EU), for the emergency treatment of allergic reactions (anaphylaxis), in adults and children who weigh 30 kg or greater.
+Added: Through our collaboration with ALK, we anticipate that neffy will be made available to patients in certain EU member states, the United Kingdom and Canada.
+Added: ALK anticipates peak sales for neffy of approximately $425 million USD in Canada, the United Kingdom and European Union.
+Added: Regulatory review of neffy is ongoing in Canada, the United Kingdom, China, Japan, and Australia with filings for marketing approval submitted in the fourth quarter of 2024 or January 2025.
+Added: Regulatory decisions are anticipated by mid-2025 in the U.K., the second-half of 2025 in Japan, year-end 2025 in Canada, and in the first-half of 2026 in China and Australia.
+Added: Conduct additional studies of neffy and our intranasal epinephrine technology product candidates to address additional Type I allergic reactions .
There remains a significant unmet need for treatments for allergies that can produce Type I reactions.
−Removed: 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.
−Removed: 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.
+Added: We are conducting clinical studies to support the expansion of labeling for neffy and our intranasal epinephrine technology product candidates to outpatient epinephrine use in other Type I allergy conditions such as urticaria for which epinephrine intra-muscular injectables are not approved.
+Added: 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 2b randomized placebo-controlled outpatient clinical trial in chronic spontaneous urticaria patients who are on a chronic antihistamine regimen, but still experience flares, in the second quarter of 2025, with topline data anticipated in early 2026.
Overview of Type I Allergic Reactions and Current Challenges
23 unchanged sentences
Role of Epinephrine in Treating Type I Allergic Reactions
−Removed: Epinephrine intra-muscular injectables are the only current out-of-hospital treatment for severe Type I allergic reactions and are recommended to be prescribed to all patients who have experienced a severe Type I allergic reaction and have either experienced anaphylaxis or are at risk of anaphylaxis.
+Added: Epinephrine, either in the form of neffy or injection products for out-of-hospital use, is recommended to be prescribed to all patients who have experienced a severe Type I allergic reaction and have either experienced anaphylaxis or are at risk of anaphylaxis.
When properly used, these devices can allow for the early administration of epinephrine to stop or reduce the intensity of the systemic allergic reaction before refractory anaphylaxis develops.
25 unchanged sentences
A low dose of epinephrine is important for safety as overexposure to epinephrine can lead to adverse events.
−Removed: Limitations of Existing Epinephrine Products
+Added: Limitations of Existing Injectable Epinephrine Products
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.
1 unchanged sentence
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.
−Removed: 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.
+Added: 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, and 3.3 million received, but did not fill an epinephrine autoinjector prescription during 2020-2022.
+Added: The remaining 13.5 million patients that have been diagnosed with a Type I severe allergic reaction between 2020-2022 did not receive an epinephrine prescription from their physician, and are managed almost entirely by non-allergist physicians who we believe are not well-educated about the management of Type I severe allergic reactions.
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.
8 unchanged sentences
In our clinical studies, we observed instances of potential accidental blood vessel injection in approximately 14% of patients dosing themselves with EpiPen.
−Removed: 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.
−Removed: Clinical Development of neffy
−Removed: 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.
−Removed: 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.
−Removed: 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.
−Removed: 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.
−Removed: 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.
−Removed: 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.
−Removed: FDA also agreed that successfully demonstrating that neffy met these criteria in three primary studies described below would be sufficient to serve as a basis for our registration program for adults.
−Removed: Furthermore, FDA also agreed that a single study in pediatric subjects also described below would be sufficient to support our pediatric labeling.
−Removed: 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.
−Removed: 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.
−Removed: The adult registrational program using the 2.0 mg neffy was intended to generate bioavailability, PDs and safety data in three primary studies:
−Removed: (i) during single and repeat dosing in healthy subjects (EPI-15), (ii) during self-administration by subjects with severe Type I allergies (EPI-17), and (iii) during rhinitis induced by a nasal challenge with an allergen (EPI-16).
−Removed: EPI-15 was conducted in the United States on behalf of ARS Pharma by WCCT Global, Inc., a third-party contract research organization, and selected for 59 healthy male or female volunteers between the ages of 18 to 55 years.
−Removed: EPI-16 was conducted in the United States on behalf of ARS Pharma by Altasciences Clinical Los Angeles, Inc., a third-party contract research organization, and selected 36 male or female volunteers between the ages of 18 to 55 years with a positive history of seasonal allergic rhinitis related to tree or grass allergens as demonstrated by skin prick test and nasal allergen challenge at screening.
−Removed: 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.
−Removed: 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).
−Removed: 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.
−Removed: The interim results of this study from 57 subjects including 16 subjects dosed with 2.0 mg neffy were included in our initial NDA that was accepted for review by FDA in the fourth quarter of 2022.
−Removed: In addition, we have completed two proof of concept clinical studies that evaluated the bioavailability of our 2.0 mg neffy dose.
−Removed: These two earlier-stage studies were conducted in the United States on behalf of ARS Pharma by WCCT Global, Inc.
−Removed: and Altasciences Clinical Los Angeles, Inc, respectively, and selected a total of 26 healthy male or female volunteers between the ages of 18 to 55 years, and 42 male or female volunteers between the ages of 18 to 55 years who had an ongoing history of type I allergies.
−Removed: 2.0 mg neffy is intended to be the dose that is comparable to approved 0.3 mg epinephrine intra-muscular injection products for persons greater than 30 kg in weight, which represents approximately 80% of the prescriptions in the United States.
−Removed: 1.0 mg neffy is intended to be the dose for persons 15 to 30 kg in weight.
−Removed: 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.
+Added: In comparison, neffy is perceived by patients and parents as a potentially “game changing” device that can improve the management of severe Type I allergic reactions by addressing the current limitations of epinephrine intra-muscular injectable devices.
+Added: Clinical Development of neffy and our Intranasal Epinephrine Technology
+Added: Our intranasal technology, including 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.
+Added: On August 9, 2024, the FDA approved neffy 2 mg for the emergency treatment of Type I allergic reactions, including anaphylaxis, in adults and children who weigh 30 kg or greater.
+Added: As a result, we initiated the commercial launch of neffy 2 mg in the United States, with product becoming available for shipment on September 23, 2024.
+Added: On March 5, 2025, the FDA approved neffy 1 mg for the emergency treatment of Type I allergic reactions, including anaphylaxis, in patients who are four years of age and older and weigh 15 kg to less than 30 kg.
+Added: Based on our clinical studies completed to date and FDA labeling, 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.
+Added: 2.0 mg neffy is intended to be the dose that is comparable to approved 0.3 mg epinephrine intra-muscular injection products for persons 30 kg or greater in weight, which represents approximately 80% of the prescriptions in the United States.
+Added: 1.0 mg neffy is intended to be the dose for persons 15 kg to less than 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 PK parameters (C max , t max , early partial AUCs, AUC 0-t ).
19 unchanged sentences
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
−Removed: (people 15 – 30 kg weight).
+Added: (people 15 kg – 30 kg weight).
Exposures with repeat doses of neffy were greater than IM to ensure efficacy, and comparable to EpiPen to ensure safety.
20 unchanged sentences
Shelf-life at least comparable to injection products, but also with high temperature stability
−Removed: 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.
−Removed: 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.
+Added: Drug stability studies show that neffy has a shelf-life at room temperature greater than the volume-weighted average shelf-life of 22 to 23 months for epinephrine injectable products based on stability data from the 2.0 mg dose of neffy for 30 months and from the 1.0 mg dose of neffy for 24 months.
+Added: In addition, at high temperatures, 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
−Removed: 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.
+Added: Following the acceptance of our new drug application (“NDA”) in October 2022 for review by the FDA, on May 11, 2023, the FDA held a virtual meeting of the 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).
−Removed: 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).
−Removed: 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.
+Added: On the question of whether the neffy PK/PD results support a favorable benefit-risk assessment in children weighing 30 kg or greater for the emergency treatment of Type I allergic reactions including anaphylaxis, the PADAC voted 17 (yes) and 5 (no).
+Added: On September 19, 2023, the FDA issued a complete response letter (“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.
1 unchanged sentence
We reported topline results in February 2024 from this additional repeat dose study requested by the FDA.
−Removed: 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.
+Added: 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 intra-muscular 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.
−Removed: We have completed this updated testing, and no measurable levels of nitrosamine impurities were detectable.
−Removed: 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.
−Removed: 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.
+Added: We completed this updated testing, and no measurable levels of nitrosamine impurities were detectable.
+Added: We submitted our response to the FDA CRL in April 2024.
+Added: On August 9, 2024, the FDA approved neffy 2 mg for the emergency treatment of Type I allergic reactions, including anaphylaxis, in adults and children who weigh 30 kg or greater.
+Added: As a result, we initiated commercial launch of neffy 2 mg in the United States, with product becoming available for shipment on September 23, 2024.
+Added: On March 5, 2025, the FDA approved neffy 1 mg for the emergency treatment of Type I allergic reactions, including anaphylaxis, in patients who are four years of age and older and weigh 15 kg to less than 30 kg.
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.
−Removed: 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.
−Removed: 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.
+Added: The needle-free, portable, easy-to-use and potentially safer clinical profile of our intranasal epinephrine technology product candidates supported by PK and PD data could enable the broader adoption of epinephrine in the outpatient setting for these other indications.
+Added: We reported positive topline results demonstrating statistically significant and clinically meaningful improvements in treatment-refractory chronic urticaria patients, and anticipate initiating a Phase 2b randomized placebo-controlled clinical trial in the outpatient urticaria setting in the second quarter of 2025, with topline data anticipated in early 2026, followed potentially by a single pivotal registration study in 2026.
Development outside the United States
−Removed: 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.
−Removed: We are also pursuing pediatric approval of neffy in Europe based on the same US pediatric study.
−Removed: 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.
−Removed: 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 .
+Added: On August 22, 2024, the EC granted marketing authorization in the EU for EURneffy (the trade name for neffy 2 mg in the EU), for the emergency treatment of allergic reactions (anaphylaxis), in adults and children who weigh 30 kg or greater.
+Added: Through our collaboration with ALK, we anticipate that EURneffy will be made available to patients in certain EU member states in 2025.
+Added: In the first quarter of 2025 we submitted a post-approval variation to EMA for the 1.0 mg neffy for patients who weigh 15 kg to less than 30 kg in the first quarter of 2025.
+Added: Using the same clinical studies that supported neffy approval by FDA and EC, we have also filed for regulatory approval of neffy in Canada and the United Kingdom on behalf of our partner ALK.
+Added: Our partners in Japan, China and Australia filed for regulatory approval of neffy in their respective regions in the fourth quarter of 2024.
+Added: Regulatory decisions are expected in UK by mid-2025, Canada and Japan by year-end 2025, and China and Australia in the first half of 2026.
Commercialization Opportunity and Commercialization Plan
Type I Allergy Market Overview
−Removed: neffy is a needle-free, low-dose intranasal epinephrine nasal spray in clinical development for use as a rescue medication for people with Type I severe allergic reactions including anaphylaxis.
+Added: neffy is a needle-free, low-dose intranasal epinephrine nasal spray approved for use as a rescue medication for people with Type I severe allergic reactions including anaphylaxis.
neffy was designed to provide injection-like absorption of epinephrine, in a small, easy-to-carry, easy-to-use, rapidly administered, and reliable nasal spray device.
7 unchanged sentences
Intended for use at the first signs of an allergic response, neffy is designed to provide patients and their families with a new option to rapidly resolve symptoms and prevent progression to severe anaphylaxis.
−Removed: If approved for use, we believe our first-in-class nasal spray may transform the way we think about and use life-saving epinephrine.
−Removed: Existing US Market Opportunity
+Added: We believe our first-in-class nasal spray may transform the way we think about and use life-saving epinephrine.
+Added: Existing U.S.
+Added: Market Opportunity
We estimate approximately 40 million people in the United States have experienced Type I allergic reactions.
2 unchanged sentences
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.
−Removed: 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.
−Removed: Based on market access research and data from IQVIA, we estimate that 2023 U.S.
−Removed: net sales for intra-muscular injectable devices were approximately $1 billion.
−Removed: Approximately 80% of the epinephrine intra-muscular injectables sold in the United States in 2023 were for the 0.3 mg dose for adults and children greater than 30 kg in weight.
+Added: We believe neffy could address the needs of the approximately 3.2 million patients in the United States who currently fill intra-muscular injectable prescriptions, the approximately 3.3 million former injectable patients in the United States that either refused to fill, or did not renew an intra-muscular injectable device prescription, and the more than 13.5 million eligible Type I allergy patients in the United States who are at risk of severe allergic reactions that are not prescribed an epinephrine product.
+Added: Based on the current list price of neffy and our target total gross-to-net yield, we estimate that the initial addressable market opportunity of 6.5 million patients who have been prescribed epinephrine during 2020-2022 is approximately $3 billion in annual net sales for neffy .
+Added: We estimate the addressable market opportunity for the 13.5 million patients who have been diagnosed during 2020-2022, but were not prescribing epinephrine, is approximately $7 billion in annual net sales for neffy .
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.
2 unchanged sentences
In our market research, parents and people with current or prior epinephrine auto-injector prescriptions were asked if and when they would adopt a new nasal spray device product such as neffy .
−Removed: A majority indicated they would adopt neffy within three months of it coming to market,
+Added: 75% of patients indicated they would adopt neffy within one year of approval
81% of patients indicated they would use neffy sooner than their current auto-injector device,
1 unchanged sentence
88% reported they would be more willing to use neffy in public.
−Removed: These data suggest that neffy has the potential to be rapidly adopted by most of the approximately 3.2 million patients in the United States today who fill their epinephrine auto-injector prescription, if approved.
−Removed: These patients serve as our base estimate for the current epinephrine market for neffy .
Key potential growth levers for neffy within the existing epinephrine market for the emergency treatment of Type I allergic reactions, which currently consists of only intra-muscular injectable products include:
7 unchanged sentences
The exodus of patients who have received prescriptions from the market has been attributed to a number of factors, including reduced promotional activities in recent years, limited adherence program effectiveness (lapsed prescriptions) and patient adversity to currently marketed products (i.e., fear of needles and concerns regarding poor reliability).
−Removed: In our market research of 88 former patients who refused to fill or renew a prescription, approximately 89% indicated a willingness to return to the market and request neffy if approved.
+Added: In our market research of 88 former patients who refused to fill or renew a prescription, approximately 89% indicated a willingness to return to the market and request neffy .
We hope to engage with these patients through programs to encourage appropriate epinephrine use with neffy and increase consistency of epinephrine acquisition to help manage their condition.
4 unchanged sentences
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.
−Removed: 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.
−Removed: 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.
−Removed: 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.
+Added: Outside of the 6.5 million patients who were recently prescribed an epinephrine injectable device, there are approximately 13.5 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.
+Added: 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 between 2020-2022.
+Added: In our market research, physicians indicated they would prescribe neffy to 75 to 85% of the patients who were eligible, but do not currently receive an intra-muscular injectable prescription.
Development in new allergy indications.
−Removed: There are approximately 10 million patients with allergy conditions (e.g., urticaria flares and asthma exacerbations) where epinephrine has never been formally developed as a prescription product, despite being used in-hospital to resolve such acute symptoms.
−Removed: Such patients in other conditions experience multiple episodes each year, and we believe they would likely use multiple neffy each year to resolve their symptoms.
−Removed: Therefore, the market opportunity for treating such conditions may be as large as the type I allergy including anaphylaxis indication.
−Removed: 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.
+Added: There are approximately 1 million patients in the United States diagnosed with chronic spontaneous urticaria and treated with antihistamines or biologic treatments, such as Xolair, that still experience frequent flares, which is an indication for which epinephrine has never been formally developed as a prescription product, despite being used in-hospital to resolve such acute symptoms.
+Added: Such patients experience multiple episodes each year, and we believe they would likely use multiple doses of our intranasal epinephrine technology product candidate each year to resolve their symptoms.
+Added: Therefore, the market opportunity for treating flares in chronic spontaneous urticaria patients may be as meaningful as the Type I allergy including anaphylaxis indication.
+Added: Assuming that one sprayer device is used monthly to treat such flares in chronic spontaneous urticaria, we estimate that the market opportunity in the United States alone is greater than $2 billion in net sales in this indication, if approved.
+Added: Although both patients treated with either antihistamines or biologic treatments, such as Xolair, can experience frequent flares that may be suitable for treatment with our intranasal epinephrine technology product candidates , our development strategy has focused first on patients treated with only antihistamines.
+Added: Our intranasal epinephrine technology product candidates may offer significant pharmacoeconomic value to payers by reducing the likelihood of step-up therapy to a much more expensive biologic treatment.
+Added: 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 2b randomized placebo-controlled outpatient clinical trial in chronic spontaneous urticaria patients on a chronic antihistamine regimen, but who still experience flares, in the second quarter of 2025, with topline data anticipated in early 2026.
Ex-US Market Opportunity
Outside of the United States, we estimate that there are an additional 15 million patients in Europe, and over 30 million patients in Asia including China and Japan, that experience Type I allergic reactions that are clinically appropriate for being prescribed neffy .
−Removed: In 2022, epinephrine intra-muscular injectable sales outside the United States were approximately $300 million based on IQVIA data.
−Removed: In Europe and Japan, sales of epinephrine injectable devices are approximately $220 million.
We believe education around Type I allergic reactions and marketing of intra-muscular injectables has been limited in these regions, and that promotion and the availability of neffy would significantly expand the market.
−Removed: Market research conducted in Europe with 120 patients who have an epinephrine auto-injector prescription indicated that 98% would prefer neffy , and that they would acquire approximately twice as many neffy devices compared to their current injectable device, if approved.
−Removed: To target these opportunities outside of the United States, we have entered into licensing and collaboration agreements with Alfresa Pharma for Japanese rights to neffy and Pediatrix Therapeutics (founded by F-Prime Capital, Eight Roads and Creacion Ventures) for Chinese rights to neffy .
−Removed: We intend to pursue strategic partnerships for the commercialization of neffy in additional regions outside of the United States, subject to FDA approval of neffy .
−Removed: 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.
−Removed: 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 .
+Added: Market research conducted in Europe with 120 patients who have an epinephrine auto-injector prescription indicated that 98% would prefer neffy , and that they would acquire approximately twice as many neffy devices compared to their current injectable device.
+Added: To target these opportunities outside of the United States, we have entered into licensing, collaboration and partnership agreements, including with Alfresa Pharma for Japanese rights to neffy and Pediatrix Therapeutics (founded by F-Prime Capital, Eight Roads and Creacion Ventures) for Chinese rights to neffy , CSL for Australian and New Zealand rights to neffy , and ALK for, among other things, rights to neffy in all other territories outside of the United States.
+Added: ALK anticipates peak sales in excess of $425 million for its licensed regions alone, principally comprising Canada, the United Kingdom and the European Union.
Commercial Strategy
2 unchanged sentences
As a result, we believe that driving consumer awareness, so that patients and parents ask their healthcare provider for neffy , while minimizing both access and educational barriers to acceptance is essential.
−Removed: Our plan to execute on our go-to-market strategy for neffy includes the following:
−Removed: We plan to create healthcare professional and consumer awareness and anticipation prior to launch .
−Removed: We are refining our go-to-market strategy and creating awareness about our company and our technology.
−Removed: 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.
−Removed: 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.
−Removed: 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.
−Removed: Based on the unmet needs that we identified, our pre-launch activities may be focused on delivering disease awareness and education surrounding the appropriate epinephrine use to prevent anaphylaxis to allergists and pediatricians as well as parents and patients in partnership with allergy and professional advocacy groups.
−Removed: These disease education efforts will more specifically reinforce the importance of early administration of epinephrine at the first sign of a severe Type I allergic reaction, help stakeholders understand the factors that are associated with hesitation to fill and use epinephrine earlier in a reaction, and the importance of alternative epinephrine delivery options to support those affected by severe allergic reactions.
−Removed: In our market research, 42% of patients who had used an epinephrine injectable device during a recent episode reported that they delayed use by an average of approximately 9 minutes.
−Removed: If neffy were available, these patients reported that they would reduce their average wait time to use by 45%.
−Removed: Additionally, 47% of patients reported they were more likely to fill prescriptions and 86% of patients reported they would carry neffy with them.
−Removed: 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.
−Removed: 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 40 to 45% of the current epinephrine prescriptions.
−Removed: Our promotion will focus the launch on the highest potential practicing allergists, pediatricians, and primary care physicians.
+Added: Our go-to-market strategy for neffy includes the following key elements:
+Added: We have initiated the commercialization of 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 40 to 45% of the current epinephrine prescriptions.
+Added: Our launch has focused on the highest potential practicing allergists, pediatricians, and primary care physicians.
In our market research, approximately 80% of patients see their treating physicians at least every six months, and 98% at least once a year.
−Removed: We plan to optimize our field representatives based on planned research on current market dynamics, geo-targeting and assessment of current professional-industry interaction preferences initially to reach these professionals.
−Removed: We expect significant reach to be achieved based on expanded use of non-personal promotional tactics and virtual sales representatives to reach healthcare professionals and focus on the sequential activation of patient demand through direct-to-consumer tactics that will help also drive physician awareness due to overlapping exposure.
−Removed: We intend to partner with patient advocacy organizations as well as influencers and leverage an omnichannel strategy including direct-to-patient and parent tactics, social and traditional media, digital presence, and additional public relations to drive awareness, for patients to ask for neffy , and communicate our value proposition .
+Added: We have optimized our field representatives based on research on current market dynamics, geo-targeting and assessment of current professional-industry interaction preferences initially to reach these professionals.
+Added: As of January 2025, about three months after launch, approximately 50% of the prioritized 4,000 top decile healthcare providers (deciles 8 to 10) have already prescribed neffy .
+Added: Our current sales force of 118 individuals includes sales reps, virtual sales consultants and area sales managers, and we anticipate potentially expanding our sales force to over 200 individuals by early 2026.
+Added: We expect significant reach of approximately 80% of epinephrine prescriptions to be achieved based on expanded use of non-personal promotional tactics to reach healthcare professionals and focus on the sequential activation of patient demand through direct-to-consumer tactics that will help also drive physician awareness due to overlapping exposure.
+Added: As of March 2025, approximately 2,500 healthcare professionals have enrolled in our neffy experience program that allows healthcare professionals to use neffy firsthand as rescue therapy for anaphylaxis during in-clinic allergen challenge.
+Added: We intend to secure affordable market access for all consumers by optimizing contracting, co-pay support and distribution of neffy .
+Added: To ensure access and affordability for neffy , we have engaged and successfully contracted with insurers and payers to convey the clinical rationale and value proposition of neffy .
+Added: We are on track to achieve commercial coverage of 60% or greater by the end of the first quarter of 2025, and commercial coverage of 80% or greater by the early part of the third quarter of 2025.
+Added: The second largest pharmacy benefit manager in the United States, ExpressScripts, added neffy to its national commercial formularies at Tier 2 preferred, which is the lowest possible tier for a branded innovator product, only 9 weeks after product availability on September 23, 2024.
+Added: With our contracting strategy, a $25 or less co-pay savings card, a $199 cash price, and patient assistance programs, we anticipate that the out-of-pocket cost to patients for acquiring neffy may be less than or similar to that of generic epinephrine autoinjectors.
+Added: Prior to our anticipated inclusion on formularies by a vast majority of payers later in 2025, our neffyconnect program provides patients, caregivers, and healthcare professionals (HCPs) with information about patient support programs, such as medication fulfillment services and financial support to guide their treatment journey, including navigating insurance requirements and potential barriers to access.
+Added: In particular, the program has been facilitating prior authorization formwork required by payers today that do not currently include neffy in their formulary, with a majority of prior authorizations submitted by healthcare providers currently being approved on the first pass.
+Added: We believe our comprehensive market access strategy can ensure access and affordability for all patients that may be interested in neffy .
+Added: We intend to leverage an omnichannel strategy including direct-to-patient and parent tactics, social and traditional media, digital presence, and additional public relations including partnerships with patient advocacy organizations as well as influencers to drive awareness, for patients to ask for neffy , and communicate our value proposition .
The pent-up patient demand that we believe is ready to be activated by neffy is reflected in our market research where 87% of patients indicated a high likelihood to proactively visit their physician in-person and ask about getting a new prescription for neffy (43% of patients indicating a 10 out of 10 likelihood, and 44% of patients indicating a 7-9 out of 10 likelihood).
1 unchanged sentence
In addition, the severe Type I allergy market has historically been highly promotionally sensitive, and in recent years, there has been limited investment in education or promotion, which we believe provides an opportunity for significant promotional lift from our planned marketing efforts.
+Added: To activate this pent-up patient demand for neffy , we intend to launch an extensive branded direct-to-consumer marketing campaign to raise awareness of neffy , and motivate action, including television, radio, print, digital and social media in the second quarter of 2025 following attainment of our commercial payer coverage goals in mid-2025 and availability of the 1 mg neffy dose, for patients who are four years of age and older and weigh 15 kg to less than 30 kg, in the second quarter of 2025.
+Added: This neffy direct-to-consumer marketing campaign will also coincide with the “back to school” increased seasonal volume of epinephrine prescriptions during the summer that is driven by the pediatric population, which is approximately half of the epinephrine injection market today.
We intend to establish neffy as the dominant and most recognized brand in the category.
2 unchanged sentences
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 .
−Removed: We intend to secure affordable market access for all consumers by optimizing contracting, co-pay support and distribution of neffy .
−Removed: To ensure access and affordability for neffy , we plan to engage with payors to convey the clinical rationale and value proposition of neffy .
−Removed: To date, we have conducted extensive market research with approximately 50 decision-makers at payors to help forecast the potential commercial opportunity for neffy in the United States.
−Removed: 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.
−Removed: Based on these analyses and our planned contracting strategy, we believe payors can support favorable and broad market access for neffy .
−Removed: Further, we will offer comprehensive patient support programs in the form of co-pay buydowns to help ensure access and affordability for all patients.
We intend to expand the market beyond the 3.2 million patients currently filling epinephrine injection device prescriptions.
We believe that the severe Type I allergy market is currently significantly underpenetrated due to the lack of, and limitations in, current treatment options.
−Removed: We believe the availability of neffy could drive increased device uptake among the existing 3.2 million patients currently filling epinephrine injection device prescriptions, adoption by the approximately 3.3 million patient that receive, but do not fill their prescription, and the 13.5 million patients diagnosed and managed by physicians who do not currently have an epinephrine auto-injector, especially those incorrectly using antihistamines as a substitute.
+Added: We believe the availability of neffy could drive increased device uptake among the existing 3.2 million patients currently filling epinephrine injection device prescriptions, adoption by the approximately 3.3 million patients that receive, but do not fill their prescription, and the 13.5 million patients diagnosed and managed by physicians who do not currently have an epinephrine auto-injector, especially those incorrectly using antihistamines as a substitute.
Other launches of intranasal products for emergency use into previously injection-only markets such as NARCAN (marketed by Emergent BioSolutions), VALTOCO (marketed by Neurelis), NAYZILAM (marketed by UCB) and BAQSIMI (marketed by Eli Lilly) have rapidly captured a significant percentage of the existing market, and also expanded their respective markets.
3 unchanged sentences
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.
−Removed: 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.
−Removed: If approved, we plan to establish a distribution channel in the United States for the commercialization of neffy .
−Removed: We expect to sell neffy to wholesalers, who, in turn, will sell our neffy to retailers and other customers.
−Removed: 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.
−Removed: We also plan to explore other non-traditional distribution channels including telemedicine.
+Added: In our market research, respondents have described neffy as “game-changing” and we believe neffy can make a significant difference in patient lives and outcomes.
+Added: We have established a distribution channel in the United States for the commercialization of neffy .
+Added: We are selling neffy to wholesalers, who, in turn, sell neffy to retailers and other customers.
+Added: We are using 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.
+Added: neffy is also available through telemedicine.
To target markets outside of the United States, we have entered into strategic partnerships with several pharmaceutical companies to obtain regulatory approval and market neffy .
−Removed: These include Alfresa Pharma for Japan and Pediatrix Therapeutics for China.
−Removed: We intend to pursue strategic partnerships for the commercialization of neffy in additional regions outside of the United States, subject to FDA approval of neffy .
−Removed: We anticipate that in certain markets additional clinical trials of neffy may be required to obtain regulatory approval and/or ensure market access.
+Added: These include Alfresa Pharma for Japan, Pediatrix Therapeutics for China, CSL for Australia and New Zealand, and ALK for all other regions outside of the United States including Canada, the United Kingdom and the European Union.
+Added: The EC has granted marketing authorization for EURneffy (the trade name for neffy 2 mg in the European Union), and regulatory filings are actively under review in Canada, the United Kingdom, Japan, China and Australia and New Zealand, with additional filings anticipated in other countries.
+Added: Regulatory decisions are expected in UK by mid-2025, Canada and Japan by year-end 2025, and China and Australia in the first half of 2026.
Our industry is highly competitive and subject to rapid technological changes.
1 unchanged sentence
Many of our potential competitors have substantially greater financial, technical, commercial and human resources than we do and significantly more experience in the discovery, development and regulatory approval of product candidates and the commercialization of those products.
−Removed: We believe that the key competitive factors that will affect the development and commercial success of neffy and the other product candidates that we may develop are their efficacy, safety and tolerability profile, convenience in dosing, product labeling, value and price, in addition to whether there are alternative therapies approved for other indications and prescribed for off-label use and the availability of reimbursement from the government and other third parties.
+Added: We believe that the key competitive factors that will affect the development and commercial success of neffy , our intranasal epinephrine technology product candidates and the other product candidates that we may develop are their efficacy, safety and tolerability profile, convenience in dosing, product labeling, value and price, in addition to whether there are alternative therapies approved for other indications and prescribed for off-label use and the availability of reimbursement from the government and other third parties.
Our commercial opportunity could be reduced if our competitors have products which are better in one or more of these categories.
−Removed: We expect that, if approved, neffy would compete with a number of existing products and other product candidates that target Type I allergic reactions, including certain products that are or may become generic products.
+Added: neffy competes with a number of existing products and other product candidates that target Type I allergic reactions, including certain products that are or may become generic products.
Additionally, the development of new treatment methods for the diseases we are targeting could render our current or future product candidates non-competitive or obsolete.
−Removed: We anticipate that, if approved, neffy will compete primarily against epinephrine intra-muscular injectable products, for the emergency treatment of Type I allergic reactions including EpiPen and its generics, which are marketed by Viatris, Inc.
+Added: neffy competes primarily against epinephrine intra-muscular injectable products, for the emergency treatment of Type I allergic reactions including EpiPen and its generics, which are marketed by Viatris, Inc.
and Teva Pharmaceuticals, Inc., respectively;
2 unchanged sentences
and Symjepi, which is marketed by Sandoz, Inc., a Novartis division.
−Removed: 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.
−Removed: We are also not aware of any “no needle, no injection” epinephrine product candidate for the pediatric population that is in clinical development.
−Removed: We are aware of several companies developing higher dose intranasal candidates including Bryn Pharma, Hikma Pharmaceuticals, Inc.
−Removed: (previously INSYS Therapeutics, Inc.), Nasus Pharma, Orexo AB and Belhaven BioPharma.
−Removed: Amphastar Pharmaceuticals, Inc.
−Removed: is reported to be developing an intranasal candidate, but has not disclosed its dose.
+Added: 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 a PK/PD profile bracketed by the approved injection products for all PK and PD parameters requested by the FDA across all relevant dosing conditions including single dosing, repeat dosing, self-administration and during allergen challenge.
+Added: We are aware of several companies developing higher dose spray candidates including Bryn Pharma, Hikma Pharmaceuticals, Inc.
+Added: (previously INSYS Therapeutics, Inc.), Nasus Pharma, Orexo AB, Insignis Therapeutics and Belhaven BioPharma.
Aquestive Therapeutics is developing a sublingual candidate based on a prodrug of epinephrine.
Manufacturing and Supply
−Removed: 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.
+Added: We do not own or operate manufacturing facilities for the production of neffy or our intranasal epinephrine technology product candidates 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.
1 unchanged sentence
We currently employ internal resources and third-party consultants as needed to manage our CMOs.
−Removed: 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.
+Added: These CMOs offer a comprehensive range of contract manufacturing and packaging services and have successfully handled the scale up of neffy in connection with its 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.
7 unchanged sentences
Reddy Laboratories and Inalco, which are based in India and Italy, respectively.
−Removed: The unit dose sprayer device used to delivery drug product in neffy is produced by Aptar Pharma (“Aptar”).
−Removed: Aptar produces devices in France and we believe Aptar has sufficient capacity to satisfy our long-term requirements.
−Removed: The patent for the Aptar unit dose nasal spray device expired in early 2020, and we believe there will be generic supplies available soon after launch.
−Removed: Manufacturing drug product for neffy is conducted by Renaissance Pharmaceuticals, Inc.
−Removed: (“Renaissance Pharma”), which has been actively involved in supporting the manufacture of neffy devices in our clinical development.
+Added: The unit dose sprayer device used to delivery drug product in neffy is produced by Aptar Pharma (“Aptar”) and Silgan Dispensing Systems (“Silgan”).
+Added: Aptar produces devices in France and the United States, while Silgan produces devices in Germany, and both have sufficient capacity to satisfy our long-term requirements.
+Added: The patent for the Aptar unit dose nasal spray device expired in early 2020.
+Added: Manufacturing drug product for neffy and our intranasal epinephrine technology product candidates is conducted by Renaissance Pharmaceuticals, Inc.
+Added: (“Renaissance Pharma”), which has been actively involved in supporting the manufacture of neffy and our intranasal epinephrine technology product candidates.
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.
−Removed: 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.
−Removed: If approved, we anticipate that our label will indicate that neffy is stable at room temperature for 24 months at 25 o C.
−Removed: 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.
+Added: Our registration stability studies demonstrate that neffy is stable at room temperature for up to 30 months, based on stability data meeting specifications with the 2.0 mg dose of neffy for 30 months and the 1.0 mg dose of neffy for 24 months.
+Added: Epinephrine injectable products have a reported shelf-life range from the date of product manufacture of 18 to 24 months, with a volume-weighted average shelf-life of approximately 22 to 23 months.
+Added: Our FDA and EC label indicates that neffy 2.0 mg is stable at room temperature for 30 months at 25 o C.
+Added: 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, without labeling permitting excursions up to such temperature, or neffy not requiring any special storage conditions.
Intellectual Property
4 unchanged sentences
As of December 31, 2024, 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.
−Removed: In total, as of that date, our patent portfolio consisted of six issued U.S.
−Removed: patents, granted patents in each of Australia, Canada, China, Hong Kong, Japan, Mexico, Singapore, South Korea, Europe, the United Kingdom, three pending U.S.
−Removed: non-provisional patent applications, and over fifteen pending foreign patent applications directed to intranasal epinephrine formulations and methods of their use, among other things.
+Added: In total, as of that date, our patent portfolio consisted of seven issued U.S.
+Added: patents, granted patents in each of Australia, Canada, China, Hong Kong, Israel, Japan, Mexico, Singapore, South Korea, Europe, the United Kingdom, two pending U.S.
+Added: non-provisional patent applications, a pending U.S.
+Added: provisional patent application, 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.
22 unchanged sentences
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.
−Removed: 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.
−Removed: 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.
+Added: We made a $0.5 million milestone payment to Aegis upon the achievement of a regulatory milestone during 2019, a $1.0 million payment to Aegis upon the FDA’s acceptance of our U.S.
+Added: NDA filing, which occurred in the third quarter of 2022, a $2.5 million milestone payment to Aegis for achieving FDA approval of neffy 2.0 mg in September 2024, and a $5.0 million milestone payment to Aegis for the first commercial sale of neffy 2.0 mg in October 2024.
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”).
7 unchanged sentences
During the term of the agreement, (1) we and Alfresa are obligated to use commercially reasonable efforts to develop a Alfresa Licensed Product throughout the Alfresa Territory, and (2) Alfresa is obligated to use commercially reasonable efforts to (A) seek pricing and reimbursement approval, (B) seek and maintain regulatory approval for the Alfresa Licensed Products through the Alfresa Territory, and (C) market, promote and otherwise commercialize Alfresa Licensed Products in the field throughout the Alfresa Territory.
−Removed: Under the agreement, we received a one-time upfront payment of $2.0 million and earned $5 million upon the achievement of a clinical milestone during 2021.
−Removed: We are eligible to receive regulatory milestones of up to $8.0 million in the aggregate.
+Added: Under the agreement, we received a one-time upfront payment of $2.0 million, earned $5.0 million upon the achievement of a clinical milestone during 2021, and earned $6.0 million upon the completion of a regulatory milestone in Japan.
+Added: We are eligible to receive a final regulatory milestone of $2.0 million.
Further, we are eligible to receive a negotiable transfer price expected to be in the low-double-digit percentage on net sales subject to the regulatory approval to commercialize neffy in Japan.
20 unchanged sentences
Manufacturing Agreement with Renaissance
−Removed: In September 2020, we entered into a manufacturing agreement with Renaissance Lakewood, LLC (“Renaissance”), which was subsequently amended in July 2023.
+Added: In September 2020, we entered into a manufacturing agreement with Renaissance Lakewood, LLC (“Renaissance”), which was subsequently amended in July 2023 and September 2024 (the “Renaissance Agreement”).
Pursuant to the agreement, Renaissance agreed to manufacture for, and provide to us, neffy nasal unit dose sprays (“Renaissance Products”).
2 unchanged sentences
We may also request Renaissance to perform certain services related to the Renaissance Product, for which we will pay reasonable compensation to Renaissance.
−Removed: 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.
−Removed: until the earlier of the fifth anniversary of the (i) target U.S.
−Removed: launch date and (ii) the initial U.S.
+Added: The initial term of the Renaissance Agreement commenced on September 17, 2024 and will terminate (a) for Renaissance Product designated for commercial sale in the U.S., on December 31 immediately following the fifth anniversary of the initial U.S.
launch date (“U.S.
−Removed: 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.
+Added: Initial Term”), and (b) for Renaissance Product designated for commercial sale in the EU, on December 31 immediately following the fifth anniversary of 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”).
1 unchanged sentence
Renewal Term and/or the EU Renewal Term by providing the requisite prior notice to the other party.
−Removed: Either party may terminate the agreement (1) for uncured material breach of the other party, (2) upon notice for insolvency-related events of the other party that are not discharged within a defined time period, (3) on a product-by-product basis if the manufacture, distribution or sale would materially contravene any applicable law, (4) by providing the requisite notice if (a) we have not submitted a regulatory filing for any Renaissance Product in the U.S.
−Removed: on or before June 30, 2022, (b) the authorization and approval to distribute or sell Renaissance Product in the U.S.
−Removed: is not granted on or before the target U.S.
−Removed: launch date, (c) the authorization and approval representing more than a targeted number of units of Renaissance Product sold in the U.S.
−Removed: during the last calendar year is withdrawn by the FDA, or (d) we decided in our sole discretion to cease commercializing the Renaissance Product in the U.S., (5) in the case of a force majeure event that continues for six months or more, or (6) a violation by the other party of trade control or anti-corruption laws.
+Added: Either party may terminate the agreement (1) for uncured material breach of the other party, (2) upon notice for insolvency-related events of the other party that are not discharged within a defined time period, (3) on a product-by-product basis if the manufacture, distribution or sale would materially contravene any applicable law, (4) by providing the requisite notice if (a) the authorization and approval to distribute or sell Renaissance Product in the U.S.
+Added: is not granted on or before a specified date, (b) the authorization and approval representing more than a certain number of units of Renaissance Product sold in the U.S.
+Added: during the last calendar year is withdrawn by the FDA, or (c) we decided in our sole discretion to cease commercializing the Renaissance Product in the U.S., (5) in the case of a force majeure event that continues for six months or more, or (6) a violation by the other party of trade control or anti-corruption laws.
+Added: Supply Agreement with Ompi
+Added: In October 2024, we entered into a supply agreement (the “Ompi Agreement”) with Nuova Ompi S.r.l.
+Added: (the “Ompi”), pursuant to which Ompi has agreed to supply glass microvials to support our manufacture and commercialization of neffy .
+Added: Under the Ompi Agreement, we have committed to purchase, and Ompi has committed to supply, specified annual minimum quantities of glass microvials, which may be increased with prior notice by us or through the rolling forecast process, subject to a specified annual cap.
+Added: Ompi is obligated to establish the relevant manufacturing force, assets and capabilities needed to comply with its supply obligations.
+Added: In December 2024, as partial consideration for the supply arrangement, we made an upfront payment of €3.0 million (approximately $3.2 million in U.S.
+Added: dollars) to Ompi.
+Added: The supply price for the glass microvials is specified in the Ompi Agreement, subject to an annual adjustment that is capped at a specified percentage except in the case of material and extraordinary increase in Ompi’s cost of manufacturing the glass microvials.
+Added: The Ompi Agreement will expire on December 31, 2035, and may be terminated (i) upon the parties’ mutual written consent, (ii) by the Company for any reasonable business reasons (in which case the termination will become effective at the end of the following calendar year), or (iii) by the non-breaching party if the other party is in material breach of the Ompi Agreement and fails to cure such breach within 90 days after receipt of notice thereof from the non-breaching party.
+Added: Collaboration, License and Distribution Agreement with ALK
+Added: ALK Agreement
+Added: In November 2024, we entered into a collaboration, license and distribution agreement (the “ALK Agreement”) with ALK-Abelló A/S (“ALK”).
+Added: Pursuant to the ALK Agreement, we granted to ALK a worldwide (other than the United States, Japan, mainland China, Hong Kong, Taiwan, Macau, Australia and New Zealand) (“ALK Territory”), exclusive license under certain of our patents and know-how to develop, manufacture and commercialize products containing epinephrine administered intranasally, including EURneffy (the tradename for neffy 2 mg in the European Union) (epinephrine nasal spray) (“Products”), for all human uses, including the immediate or emergency treatment of allergic reactions (including Type I) and anaphylaxis and urticaria, and other future indications as agreed by the parties.
+Added: If we develop any new intranasally administered product that contains epinephrine and files a new drug application in the United States for such product (“New Product”), upon ALK’s request such New Product will be included as a Product under the ALK Agreement, subject to ALK bearing the costs of development of such New Product for its licensed territory.
+Added: Under the ALK Agreement, we are obligated to transfer to ALK the existing marketing authorizations for the Products in ALK’s territory.
+Added: We are also required to conduct certain development and regulatory activities for Products in support of obtaining further regulatory approval of Products in ALK’s territory, and will transfer such regulatory approvals to ALK.
+Added: ALK is obligated to use commercially reasonable efforts to obtain and maintain regulatory approval for Products through the European Commission and within specified countries within ALK’s territory.
+Added: Following such approval for a Product in each indication within specified countries within ALK’s territory, ALK is obligated to use commercially reasonable efforts to commercialize such Product in such indication in such countries and to achieve first commercial sale of a Product in certain countries in accordance with a timeline specified in the ALK Agreement.
+Added: Under the ALK Agreement, ALK made an upfront payment to us of $145.0 million in November 2024.
+Added: We are eligible to receive regulatory and development milestones of up to $20.0 million and commercial sales-based milestones of up to $300.0 million, provided that $55.0 million of such sales-based milestones are contingent upon us obtaining regulatory approval for the Product in Canada by a specified time.
+Added: We are entitled to receive tiered royalty payments on net sales in the mid- to high-teens, subject to certain standard reductions and offsets.
+Added: Royalties will be payable, on a Product-by-Product and country-by-country basis, until the latest of the expiration of the licensed patents covering such Product in such country, 15 years from first commercial sale of such Product in such country, or expiration of regulatory exclusivity for such Product in such country.
+Added: The contract will expire upon the expiration of the last to expire royalty term for all Products in the ALK Territory, unless terminated earlier.
+Added: Either we or ALK may terminate the ALK Agreement in the case of the other party’s insolvency or in the event of an uncured material breach of the other party, except that we may not terminate the ALK Agreement for ALK’s material breach of its commercial diligence obligations.
+Added: ALK may terminate the ALK Agreement for convenience upon prior written notice or for a safety or regulatory concern.
+Added: We may terminate the ALK Agreement in the event ALK makes certain challenges to certain of our patents.
+Added: Prior to a change of control and outside of a set period of time after which we commence change of control negotiations, we may terminate the ALK Agreement with respect to all countries in the European Economic Area (“EEA”) upon prior written notice to ALK and payment of a termination fee that is the higher of an agreed mid-nine digit amount and the fair market value of the Products business in the EEA at the time of such termination.
+Added: We may also terminate the ALK Agreement if ALK commercializes a non-injectable epinephrine product or manufactures such a product in the United States.
+Added: ALK Supply Agreement
+Added: On November 9, 2024, in connection with the ALK Collaboration Agreement, ARS and ALK also entered into a commercial supply agreement (the “Supply Agreement”), under which ARS will supply ALK’s requirements (and ALK will purchase from ARS its requirements) of Products for five years for a specified supply price, after which ALK may elect to transition to itself or its contract manufacturer the manufacture and supply of Products.
+Added: Either we or ALK may terminate the Supply Agreement in the event of an uncured material breach of the other party.
Government Regulation and Product Approval
5 unchanged sentences
Regulation of Combination Products in the United States
−Removed: neffy is comprised of drug and delivery device components that would normally be subject to different regulatory frameworks by the FDA and frequently regulated by different centers at the FDA.
+Added: Our intranasal epinephrine technology, including neffy , is comprised of drug and delivery device components that would normally be subject to different regulatory frameworks by the FDA and frequently regulated by different centers at the FDA.
These products are known as combination products.
2 unchanged sentences
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.
−Removed: 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.
+Added: A combination product with a primary mode of action attributable to the drug component, such as neffy and our intranasal epinephrine technology product candidates, 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.
−Removed: 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.
+Added: In addition, under FDA regulations, combination products such as neffy and our intranasal epinephrine technology product candidates are subject to cGMP requirements applicable to both drugs and devices, including the Quality System Regulations applicable to medical devices.
Drug Development Process
228 unchanged sentences
There may be significant delays in obtaining reimbursement for newly-approved drugs, and coverage may be more limited than the purposes for which the drug or therapeutic biologic is approved by the FDA or similar foreign regulatory authorities.
−Removed: Additionally, we may need to conduct expensive pharmaco-economic studies to demonstrate the medical necessity and cost-effectiveness of our product candidates.
There can be no assurance that our product candidates will be considered medically necessary or cost-effective.
21 unchanged sentences
and established a Center for Medicare Innovation at CMS to test innovative payment and service delivery models to lower Medicare and Medicaid spending, potentially including prescription drug spending.
−Removed: Since its enactment, there have been judicial, administrative, executive, and Congressional legislative challenges to certain aspects of the ACA.
−Removed: For example, on June 17, 2021, the U.S.
−Removed: 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.
−Removed: Further, prior to the U.S.
−Removed: Supreme Court ruling, on January 28, 2021, President Biden issued an executive order to initiate a special enrollment period for purposes of obtaining health insurance coverage through the ACA marketplace.
−Removed: 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.
−Removed: 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.
+Added: Since its enactment, there have been amendments and judicial, administrative, executive, and Congressional legislative challenges to certain aspects of the ACA.
+Added: For example, on August 16, 2022, the Inflation Reduction Act of 2022 (“IRA”) was signed 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.
−Removed: It is unclear how such challenges and the healthcare reform measures of the Biden administration will impact the ACA.
+Added: It is unclear how such challenges and the healthcare reform measures of the second Trump 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.
−Removed: 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.
−Removed: Congress is considering additional health reform measures.
+Added: Further, there may be additional health reform measures.
Moreover, there has been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products, which has resulted in several U.S.
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.
−Removed: 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.
−Removed: In response to Biden’s executive order, on September 9, 2021, the U.S.
−Removed: 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.
−Removed: 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.
+Added: For example, the IRA, among other things, (i) directs the U.S.
+Added: Department of Health and Human Services (“HHS”) to negotiate the price of certain high-expenditure, single-source drugs that have been on the market for at least 7 years covered under Medicare (the “Medicare Drug Price Negotiation Program”), 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 under the law, and (ii) imposes rebates with respect to certain drugs 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.
−Removed: These provisions take effect progressively starting in fiscal year 2023.
−Removed: 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.
−Removed: It is currently unclear how the IRA will be implemented but is likely to have a significant impact on the pharmaceutical industry.
−Removed: 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.
−Removed: It is unclear whether the models will be utilized in any health reform measures in the future.
−Removed: 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.
+Added: These provisions began to take effect progressively starting in fiscal year 2023.
+Added: On August 15, 2024, HHS announced the agreed-upon price of the first ten drugs that were subject to price negotiations, although the Medicare Drug Price Negotiation Program is currently subject to legal challenges.
+Added: On January 17, 2025, HHS selected fifteen additional products covered under Part D for price negotiation in 2025.
+Added: Each year thereafter more Part B and Part D products will become subject to the Medicare Drug Price Negotiation Program.
+Added: Further, on December 7, 2023, an initiative to control the price of prescription drugs through the use of march-in rights under the Bayh-Dole Act was announced.
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.
50 unchanged sentences
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.
−Removed: 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.
+Added: Clinical Trials in the EU
+Added: Similarly to the United States, the various phases of non-clinical and clinical research in the EU are subject to significant regulatory controls.
+Added: Non-clinical studies are performed to demonstrate the health or environmental safety of new chemical or biological substances.
+Added: Non-clinical studies must be conducted in compliance with the principles of good laboratory practice, as set forth in EU Directive 2004/10/EC.
+Added: In particular, non-clinical studies, both in vitro and in vivo , must be planned, performed, monitored, recorded, reported and archived in accordance with the GLP principles, which define a set of rules and criteria for a quality system for the organizational process and the conditions for non-clinical studies.
+Added: These GLP standards reflect the Organization for Economic Co-operation and Development requirements.
+Added: Clinical trials of medicinal products in the EU must be conducted in accordance with EU and national regulations and the International Conference on Harmonization (“ICH”), guidelines on GCPs, as well as the applicable regulatory requirements and the ethical principles that have their origin in the Declaration of Helsinki.
+Added: At the EU level, clinical trials are governed by the Clinical Trials Regulation (EU) No 536/2014 (“CTR”), which entered into application on January 31, 2022 repealing and replacing the former Clinical Trials Directive 2001/20 (“CTD”).
+Added: The CTR is intended to harmonize and streamline clinical trial authorizations, simplify adverse-event reporting procedures, improve the supervision of clinical trials and increase transparency.
+Added: Specifically, the Regulation, which is directly applicable in all EU Member States, introduces a streamlined application procedure through a single-entry point, the "EU portal", the Clinical Trials Information System (“CTIS”);
+Added: a single set of documents to be prepared and submitted for the application;
+Added: as well as simplified reporting procedures for clinical trial sponsors.
+Added: A harmonized procedure for the assessment of applications for clinical trials has been introduced and is divided into two parts.
+Added: Part I assessment is led by the competent authorities of a reference Member State selected by the trial sponsor and relates to clinical trial aspects that are considered to be scientifically harmonized across EU Member States.
+Added: This assessment is then submitted to the competent authorities of all concerned Member States in which the trial is to be conducted for their review.
+Added: Part II is assessed separately by the competent authorities and Ethics Committees in each concerned EU Member State.
+Added: Individual EU Member States retain the power to authorize the conduct of clinical trials on their territory.
+Added: The CTR foresaw a three-year transition period that ended on January 31, 2025.
+Added: Since this date, all new or ongoing trials are subject to the provisions of the CTR.
In all cases, the clinical trials must be conducted in accordance with GCP and the applicable regulatory requirements and the ethical principles that have their origin in the Declaration of Helsinki.
−Removed: To obtain regulatory approval of an investigational drug or biological product under EU regulatory systems, we must submit a marketing authorization application either under the so-called centralized or national authorization procedures.
−Removed: The application used to file an NDA in the United States is similar to that required in the EU, but the exact requirements for authorization may vary.
−Removed: Centralized Procedure.
−Removed: The centralized procedure provides for the grant of a single marketing authorization by the European Commission following a favorable opinion by the EMA that is valid in all EU member states, as well as Iceland, Liechtenstein and Norway.
−Removed: The centralized procedure is compulsory for medicines produced by specified biotechnological processes, products designated as orphan medicinal products, and products with a new active substance indicated for the treatment of specified diseases, such as HIV/AIDS, cancer, diabetes, neurodegenerative disorders or autoimmune diseases, other immune dysfunctions and viral diseases.
−Removed: The centralized procedure is optional for other products that represent a significant therapeutic, scientific or technical innovation, or whose authorization would be in the interest of public health or which contain a new active substance for indications other than those specified to be compulsory.
−Removed: National Authorization Procedures .
−Removed: There are also two other possible routes to authorize medicinal products in several EU countries, which are available for investigational medicinal products that fall outside the scope of the centralized procedure:
−Removed: Decentralized procedure.
−Removed: Using the decentralized procedure, an applicant may apply for simultaneous authorizations in more than one EU Member State of medicinal products that have not yet been authorized in any EU Member State and that do not fall within the mandatory scope of the centralized procedure.
−Removed: Mutual recognition procedure.
−Removed: In the mutual recognition procedure, a medicine is first authorized in one EU Member State, in accordance with the national procedures of that country.
−Removed: Following this, further marketing authorizations can be sought from other EU countries in a procedure whereby the countries concerned agree to recognize the validity of the original, national marketing authorization.
+Added: EU Review and approval process
+Added: In the EU, medicinal products can only be commercialized after a related marketing authorization (“MA”), has been granted.
+Added: To obtain an MA for a product in the EU, an applicant must submit a Marketing Authorization Application (“MAA”), either under a centralized procedure administered by the European Medicines Agency (“EMA”) or one of the procedures administered by the competent authorities of EU Member States (decentralized procedure, national procedure or mutual recognition procedure).
+Added: An MA may be granted only to an applicant established in the EU.
+Added: The centralized procedure provides for the grant of a single MA by the European Commission that is valid throughout the EEA (which is comprised of the 27 EU Member States plus Iceland, Liechtenstein and Norway).
+Added: Pursuant to Regulation (EC) No 726/2004, the centralized procedure is compulsory for specific products, including for (i) medicinal products derived from biotechnological processes, (ii) products designated as orphan medicinal products, (iii) advanced therapy medicinal products, and (iv) products with a new active substance indicated for the treatment of HIV/AIDS, cancer, neurodegenerative diseases, diabetes, auto-immune and other immune dysfunctions and viral diseases.
+Added: For products with a new active substance indicated for the treatment of other diseases and products that are highly innovative or for which a centralized process is in the interest of patients, authorization through the centralized procedure is optional on related approval.
+Added: Under the centralized procedure, the EMA’s Committee for Medicinal Products for Human Use(“CHMP”), conducts the initial assessment of a product.
+Added: The CHMP is also responsible for several post-authorization and maintenance activities, such as the assessment of modifications or extensions to an existing MA.
+Added: The maximum timeframe for the evaluation of an MAA under the centralized procedure is 210 days, excluding clock stops when additional information or written or oral explanation is to be provided by the applicant in response to questions of the CHMP.
+Added: Accelerated assessment may be granted by the CHMP in exceptional cases, when a medicinal product targeting an unmet medical need is expected to be of major interest from the point of view of public health and, in particular, from the viewpoint of therapeutic innovation.
+Added: If the CHMP accepts a request for accelerated assessment, the time limit of 210 days will be reduced to 150 days (excluding clock stops).
+Added: The CHMP can, however, revert to the standard time limit for the centralized procedure if it considers that it is no longer appropriate to conduct an accelerated assessment.
+Added: Unlike the centralized authorization procedure, the decentralized MA procedure requires a separate application to, and leads to separate approval by, the competent authorities of each EU Member State in which the product is to be marketed.
+Added: This application is identical to the application that would be submitted to the EMA for authorization through the centralized procedure.
+Added: The reference EU Member State prepares a draft assessment and drafts of the related materials within 120 days after receipt of a valid application.
+Added: The resulting assessment report is submitted to the concerned EU Member States who, within 90 days of receipt, must decide whether to approve the assessment report and related materials.
+Added: If a concerned EU Member State cannot approve the assessment report and related materials due to concerns relating to a potential serious risk to public health, disputed elements may be referred to the Heads of Medicines Agencies’ Coordination Group for Mutual Recognition and Decentralised Procedures – Human (“CMDh”), for review.
+Added: The subsequent decision of the European Commission is binding on all EU Member States.
+Added: The mutual recognition procedure allows companies that have a medicinal product already authorized in one EU Member State to apply for this authorization to be recognized by the competent authorities in other EU Member States.
+Added: Like the decentralized procedure, the mutual recognition procedure is based on the acceptance by the competent authorities of the EU Member States of the MA of a medicinal product by the competent authorities of other EU Member States.
+Added: The holder of a national MA may submit an application to the competent authority of an EU Member State requesting that this authority recognize the MA delivered by the competent authority of another EU Member State.
+Added: An MA has, in principle, an initial validity of five years.
+Added: The MA may be renewed after five years on the basis of a re-evaluation of the risk-benefit balance by the EMA or by the competent authority of the EU Member State in which the original MA was granted.
+Added: To support the application, the MA holder must provide the EMA or the competent authority with a consolidated version of the Common Technical Document providing up-to-date data concerning the quality, safety and efficacy of the product, including all variations introduced since the MA was granted, at least nine months before the MA ceases to be valid.
+Added: The European Commission or the competent authorities of the EU Member States may decide on justified grounds relating to pharmacovigilance, to proceed with one further five year renewal period for the MA.
+Added: Once subsequently definitively renewed, the MA shall be valid for an unlimited period.
+Added: Any authorization which is not followed by the actual placing of the medicinal product on the EU market (for a centralized MA) or on the market of the authorizing EU Member State within three years after authorization ceases to be valid (the so-called sunset clause).
+Added: Innovative products that target an unmet medical need and are expected to be of major public health interest may be eligible for a number of expedited development and review programs, such as the Priority Medicines, or PRIME, scheme, which provides incentives similar to the breakthrough therapy designation in the U.S.
+Added: PRIME is a voluntary scheme aimed at enhancing the EMA’s support for the development of medicinal products that target unmet medical needs.
+Added: Eligible products must target conditions for which there is an unmet medical need (there is no satisfactory method of diagnosis, prevention or treatment in the EU or, if there is, the new medicinal product will bring a major therapeutic advantage) and they must demonstrate the potential to address the unmet medical need by introducing new methods of therapy or improving existing ones.
+Added: Benefits accrue to sponsors of product candidates with PRIME designation, including but not limited to, early and proactive regulatory dialogue with the EMA, frequent discussions on clinical trial designs and other development program elements, and potentially accelerated MAA assessment once a dossier has been submitted.
+Added: In the EU, a “conditional” MA may be granted in cases where all the required safety and efficacy data are not yet available.
+Added: The European Commission may grant a conditional MA for a medicinal product if it is demonstrated that all of the following criteria are met:
+Added: (i) the benefit-risk balance of the medicinal product is positive;
+Added: (ii) it is likely that the applicant will be able to provide comprehensive data post-authorization;
+Added: (iii) the medicinal product fulfils an unmet medical need;
+Added: and (iv) the benefit of the immediate availability to patients of the medicinal product is greater than the risk inherent in the fact that additional data are still required.
+Added: The conditional MA is subject to conditions to be fulfilled for generating the missing data or ensuring increased safety measures.
+Added: It is valid for one year and must be renewed annually until all related conditions have been fulfilled.
+Added: Once any pending studies are provided, the conditional MA can be converted into a traditional MA.
+Added: However, if the conditions are not fulfilled within the timeframe set by the EMA and approved by the European Commission, the MA will cease to be renewed.
+Added: An MA may also be granted “under exceptional circumstances” where the applicant can show that it is unable to provide comprehensive data on efficacy and safety under normal conditions of use even after the product has been authorized and subject to specific procedures being introduced.
+Added: These circumstances may arise in particular when the intended indications are very rare and, in the state of scientific knowledge at that time, it is not possible to provide comprehensive information, or when generating data may be contrary to generally accepted ethical principles.
+Added: Like a conditional MA, an MA granted in exceptional circumstances is reserved to medicinal products intended to be authorized for treatment of rare diseases or unmet medical needs for which the applicant does not hold a complete data set that is required for the grant of a standard MA.
+Added: However, unlike the conditional MA, an applicant for authorization in exceptional circumstances is not subsequently required to provide the missing data.
+Added: Although the MA “under exceptional circumstances” is granted definitively, the risk-benefit balance of the medicinal product is reviewed annually, and the MA will be withdrawn if the risk-benefit ratio is no longer favorable.
+Added: Pediatric Development in the EU
+Added: In the EU, Regulation (EC) No 1901/2006 provides that all MAAs for new medicinal products have to include the results of trials conducted in the pediatric population, in compliance with a pediatric investigation plan (“PIP”), agreed with the EMA’s Pediatric Committee (“PDCO”).
+Added: The PIP sets out the timing and measures proposed to generate data to support a pediatric indication of the medicinal product for which MA is being sought.
+Added: The PDCO can grant a deferral of the obligation to implement some or all of the measures provided in the PIP until there are sufficient data to demonstrate the efficacy and safety of the product in adults.
+Added: Further, the obligation to provide pediatric clinical trial data can be waived by the PDCO when these data are not needed or appropriate because the product is likely to be ineffective or unsafe in children, the disease or condition for which the product is intended occurs only in adult populations, or when the product does not represent a significant therapeutic benefit over existing treatments for pediatric patients.
+Added: Once the MA is obtained in all EU Member States and study results are included in the product information, even when negative, the product is eligible for a six-month extension to the Supplementary Protection Certificate, or SPC, if any is in effect at the time of authorization or, in the case of orphan medicinal products, a two-year extension of orphan market exclusivity.
+Added: Manufacturing Regulation in the EU
+Added: In addition to an MA, various other requirements apply to the manufacturing and placing on the EU market of medicinal products.
+Added: The manufacturing of medicinal products in the EU requires a manufacturing authorization and import of medicinal products into the EU requires a manufacturing authorization allowing for import.
+Added: The manufacturing authorization holder must comply with various requirements set out in the applicable EU laws, regulations and guidance, including EU cGMP standards.
+Added: Similarly, the distribution of medicinal products within the EU is subject to compliance with the applicable EU laws, regulations and guidelines, including the requirement to hold appropriate authorizations for distribution granted by the competent authorities of EU Member States.
+Added: Marketing authorization holders and/or manufacturing and import authorization, or MA holders and/or distribution authorization holders may be subject to civil, criminal or administrative sanctions, including suspension of manufacturing authorization, in case of non-compliance with the EU or EU Member States’ requirements applicable to the manufacturing of medicinal products.
+Added: Data and Market Exclusivity
The EU also provides opportunities for market exclusivity.
−Removed: For example, upon receiving marketing authorization, new chemical entities generally receive eight years of data exclusivity and an additional two years of market exclusivity.
−Removed: If granted, data exclusivity prevents regulatory authorities in the EU from referencing the innovator’s data to assess a generic or biosimilar application.
+Added: For example, upon receiving an MA , new chemical entities generally receive eight years of data exclusivity and an additional two years of market exclusivity.
+Added: If granted, data exclusivity prevents regulatory authorities in the EU from referencing the innovator’s data to assess a generic or biosimilar application for eight years from the date of authorization of the innovative product, after which a generic or biosimilar MAA can be submitted, and the innovator’s data may be referenced .
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.
+Added: The overall ten-year period may, occasionally, be extended for a further year to a maximum of 11 years if, during the first eight years of those ten years, the MA holder obtains an authorization for one or more new therapeutic indications which, during the scientific evaluation prior to their authorization, are held to bring a significant clinical benefit in comparison with existing therapies.
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.
−Removed: 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.
−Removed: In addition, orphan drug designation can be granted if the drug is intended for a life threatening or chronically debilitating condition in the EU and without incentives it is unlikely that sales of the drug in the EU would be sufficient to justify the investment required to develop the drug.
−Removed: Orphan drug designation is only available if there is no other satisfactory method approved in the EU of diagnosing, preventing or treating the condition, or if such a method exists, the proposed orphan drug will be of significant benefit to patients.
−Removed: Orphan drug designation provides opportunities for free or reduced-fee protocol assistance, fee reductions for marketing authorization applications and other post-authorization activities and ten years of market exclusivity following drug approval, which can be extended to 12 years if trials are conducted in accordance with an agreed-upon pediatric investigational plan.
−Removed: The exclusivity period may be reduced to six years if the designation criteria are no longer met, including where it is shown that the product is sufficiently profitable not to justify maintenance of market exclusivity.
−Removed: Orphan drug designation does not convey any advantage in, or shorten the duration of, the regulatory review and approval process.
−Removed: In the EU, early access mechanisms for innovative medicines (such as compassionate use programs and named patient supplies), pricing and reimbursement, and promotion and advertising, amongst other things, are subject to national regulations and oversight by national competent authorities and therefore significantly vary from country to country.
−Removed: Sanctions for non-compliance with the aforementioned requirements, which may include administrative and criminal penalties, are generally determined and enforced at national level.
−Removed: However, under the EU financial penalties regime, the EMA can investigate and report on alleged breaches of the EU pharmaceutical rules by holders of a marketing authorization for centrally authorized medicinal products and the European Commission could adopt decisions imposing significant financial penalties on infringing marketing authorization holders.
−Removed: The United Kingdom left the EU on January 31, 2020.
−Removed: Following the transition period which ended on December 31, 2020, Brexit could materially impact the regulatory regime with respect to the development, manufacture, importation, approval and commercialization of our product candidates in the United Kingdom in the coming years.
+Added: Orphan Designation in the EU
+Added: In the EU, Regulation (EC) No.
+Added: 141/2000, as implemented by Regulation (EC) No.
+Added: 847/2000 provides that a medicinal product can be designated as an orphan medicinal product by the European Commission if its sponsor can establish that:
+Added: (i) the product is intended for the diagnosis, prevention or treatment of life-threatening or chronically debilitating conditions;
+Added: (ii) either (a) such conditions affect not more than 5 in 10,000 persons in the EU when the application is made, or (b) the product without the benefits derived from orphan status, would not generate sufficient return in the EU to justify the necessary investment in developing the medicinal product;
+Added: and (iii) there exists no satisfactory authorized method of diagnosis, prevention, or treatment of the condition that has been authorized in the EU, or even if such method exists, the product will be of significant benefit to those affected by that condition.
+Added: Regulation (EC) No 847/2000 sets out further provisions for implementation of the criteria for designation of a medicinal product as an orphan medicinal product.
+Added: An application for the designation of a medicinal product as an orphan medicinal product must be submitted at any stage of development of the medicinal product but before filing of an MAA.
+Added: An MA for an orphan medicinal product may only include indications designated as orphan.
+Added: For non-orphan indications treated with the same active pharmaceutical ingredient, a separate marketing authorization has to be sought.
+Added: Orphan medicinal product designation entitles an applicant to incentives such fee reductions or fee waivers, protocol assistance, and access to the centralized marketing authorization procedure.
+Added: Upon grant of a marketing authorization, orphan medicinal products are entitled to a ten-year period of market exclusivity for the approved therapeutic indication, which means that the EMA cannot accept another marketing authorization application or accept an application to extend for a similar product and the European Commission cannot grant a marketing authorization for the same indication for a period of ten years.
+Added: The period of market exclusivity is extended by two years for orphan medicinal products that have also complied with an agreed PIP.
+Added: No extension to any supplementary protection certificate can be granted on the basis of pediatric studies for orphan indications.
+Added: Orphan medicinal product designation does not convey any advantage in, or shorten the duration of, the regulatory review and approval process.
+Added: The period of market exclusivity may, however, be reduced to six years if, at the end of the fifth year, it is established that the product no longer meets the criteria on the basis of which it received orphan medicinal product designation, including where it can be demonstrated on the basis of available evidence that the original orphan medicinal product is sufficiently profitable not to justify maintenance of market exclusivity or where the prevalence of the condition has increased above the threshold.
+Added: Additionally, an MA may be granted to a similar medicinal product with the same orphan indication during the 10 year period if:
+Added: (i) if the applicant consents to a second original orphan medicinal product application, (ii) if the manufacturer of the original orphan medicinal product is unable to supply sufficient quantities;
+Added: or (iii) if the second applicant can establish that its product, although similar, is safer, more effective or otherwise clinically superior to the original orphan medicinal product.
+Added: A company may voluntarily remove a product from the register of orphan products.
+Added: Post-authorization Requirements in the EU
+Added: Where an MA is granted in relation to a medicinal product in the EU, the holder of the MA is required to comply with a range of regulatory requirements applicable to the manufacturing, marketing, promotion and sale of medicinal products.
+Added: Similar to the United States, both MA holders and manufacturers of medicinal products are subject to comprehensive regulatory oversight by the EMA, the European Commission and/or the competent regulatory authorities of the individual EU Member States.
+Added: The holder of an MA must establish and maintain a pharmacovigilance system and appoint an individual qualified person for pharmacovigilance who is responsible for oversight of that system.
+Added: Key obligations include expedited reporting of suspected serious adverse reactions and submission of periodic safety update reports, or PSURs.
+Added: All new MAAs must include a risk management plan, or RMP, describing the risk management system that the company will put in place and documenting measures to prevent or minimize the risks associated with the product.
+Added: The regulatory authorities may also impose specific obligations as a condition of the MA.
+Added: Such risk- minimization measures or post-authorization obligations may include additional safety monitoring, more frequent submission of PSURs, or the conduct of additional clinical trials or post-authorization safety studies.
+Added: In the EU, the advertising and promotion of medicinal products are subject to both EU and EU Member States’ laws governing promotion of medicinal products, interactions with physicians and other healthcare professionals, misleading and comparative advertising and unfair commercial practices.
+Added: General requirements for advertising and promotion of medicinal products, such as direct-to-consumer advertising of prescription medicinal products are established in EU law.
+Added: However, the details are governed by regulations in individual EU Member States and can differ from one country to another.
+Added: For example, applicable laws require that promotional materials and advertising in relation to medicinal products comply with the product’s Summary of Product Characteristics, or SmPC, which may require approval by the competent national authorities in connection with an MA.
+Added: The SmPC is the document that provides information to physicians and other healthcare professionals concerning the safe and effective use of the product.
+Added: Promotional activity that does not comply with the SmPC is considered off-label and is prohibited in the EU.
+Added: Combination Products in the EU
+Added: The EU regulates medical devices and medicinal products separately, and through different legislative instruments.
+Added: Products that are a combination of a medicinal product and a medical device may be regulated as either a medicinal product, a medical device or, subject to certain requirements, on the basis of both sets of rules.
+Added: The applicable requirements governing placing a drug-device combination on the EU market will vary depending on the type of drug-device combination product and on which of the components of the combination has the primary mode of action.
+Added: Drug-device combination products that form a single integral product that is not reusable and for which the action of the medicinal product is principal to that of the medical device are governed by the regulatory framework applicable to medicinal products.
+Added: However, the General Safety and Performance Requirements (“GSPRs”), of Annex I to Regulation (EU) 2017/745 on Medical Devices (“MDR”), will be applicable to the safety and performance of the medical device part of the product in the context of its use with the medicinal product.
+Added: In these circumstances, an MAA must be submitted to the competent authorities responsible for evaluating the safety and effectiveness of medicinal products.
+Added: As part of the MAA, the applicant must also submit, where available, the results of the assessment of the conformity of the medical device part of the product with the MDR contained in the manufacturer's EU Declaration of Conformity of the device or the relevant Certificate of Conformity issued by a Notified Body.
+Added: If the MAA does not include the results of the conformity assessment, and where the conformity assessment of the device, if used separately, requires the involvement of a Notified Body, the competent authorities must require the applicant to provide a Notified Body Opinion on the conformity of the device with the relevant GSPRs.
+Added: Based on this approach, the competent authorities responsible for medicinal products will review the specific aspects of the medical devices part of the product which are relevant to the safety and efficacy of the medicinal product and the Notified Body – where applicable – will evaluate the relevant GSPRs of the device.
+Added: Drug-device combination products that form a single integral product that is not reusable and for which the action of the medicinal products is ancillary to that of the medical device are governed by the regulatory framework applicable to medical devices in accordance with the MDR.
+Added: However, the quality, safety and usefulness of the medicinal product must also be verified as part of the device and a scientific opinion from a national competent authority of an EU Member State or from the EMA, depending on its nature and therapeutic intention, must be sought regarding the quality and safety of the medicinal product, including the benefit or risk of its incorporation into the medical device.
+Added: Where a medical device incorporates a medicinal product as an integral part as a single use drug delivery system, which is intended exclusively for use in the given combination and which is not reusable, it is regulated as a medicinal product.
+Added: In this case, the relevant General Safety and Performance Requirements, or GSPRs of the MDR will apply to the safety and performance of the device element.
+Added: By contrast, drug-device combination products which do not form a single integral product will be regulated separately.
+Added: This may include, for example a drug-device combination product where a medical device and a medicinal product are co-packaged and the medical device is intended solely to be used for the administration of the co-packaged medicinal product.
+Added: In these circumstances, the medicinal product will be governed by the regulatory framework applicable to medicinal products and the medical device will be governed by the MDR.
+Added: However, the characteristics of a medical device used for the administration of a medicinal product may impact the quality, safety and efficacy profile of the medicinal product.
+Added: As a result, as part of the MAA submitted to the competent authorities for the medicinal product, the applicant may need to provide additional information regarding the characteristics of the co-packaged medical device that may impact on the quality, safety and/or efficacy of the medicinal product.
+Added: Similar requirements may apply where the products are not co-packaged but the medicinal product information makes an explicit reference to a specific medical device.
+Added: Medicinal Products in the United Kingdom
+Added: The United Kingdom’s (“UK”), withdrawal from the EU on January 31, 2020, commonly referred to as Brexit, has changed the regulatory relationship between the UK and the EU.
+Added: The Medicines and Healthcare products Regulatory Agency (“MHRA”) is now the UK’s standalone regulator for medicinal products and medical devices.
+Added: The UK is no longer subject to EU regulations (Northern Ireland continues to follow certain limited EU regulatory rules, including in relation to medical devices, but not in relation to medicinal products).
+Added: The UK regulatory framework in relation to clinical trials is governed by the Medicines for Human Use (Clinical Trials) Regulations 2004, as amended, which is derived from the EU CTD, as implemented into UK national law through secondary legislation.
+Added: On January 17, 2022, the UK MHRA, launched an eight-week consultation on reframing the UK legislation for clinical trials.
+Added: The UK Government published its response to the consultation on March 21, 2023, confirming that it would bring forward changes to the legislation and such changes were laid in parliament on December 12, 2024.
+Added: These resulting legislative amendments will, if implemented in their current form, bring the UK into closer alignment with the EU CTR.
+Added: In October 2023, the MHRA announced a new Notification Scheme for clinical trials which enables a more streamlined and risk-proportionate approach to initial clinical trial applications for Phase 4 and low-risk Phase 3 clinical trial applications.
+Added: Marketing authorizations in the UK are governed by the Human Medicines Regulations (SI 2012/1916), as amended.
+Added: Since January 1, 2021, an applicant for the EU centralized procedure marketing authorization can no longer be established in the UK.
+Added: As a result, since this date, companies established in the UK cannot use the EU centralized procedure and instead must follow one of the UK national authorization procedures or one of the remaining post-Brexit international cooperation procedures to obtain a marketing authorization to market products in the UK.
+Added: All existing EU marketing authorizations for centrally authorized products were automatically converted or grandfathered into UK marketing authorization, effective in Great Britain only, free of charge on January 1, 2021, unless the marketing authorization holder opted-out of this possibility.
+Added: Northern Ireland remained within the scope of EU authorizations in relation to centrally authorized medicinal products until January 1, 2025.
+Added: However, on January 1, 2025, a new arrangement as part of the so-called “Windsor Framework” came into effect and reintegrated Northern Ireland under the regulatory authority of the MHRA with respect to medicinal products.
+Added: The Windsor Framework removes EU licensing processes and EU labelling and serialization requirements in relation to Northern Ireland and introduces a UK-wide licensing process for medicines.
+Added: The MHRA has also introduced changes to national marketing authorization procedures.
+Added: This includes introduction of procedures to prioritize access to new medicines that will benefit patients, including a 150-day assessment route, a rolling review procedure and the International Recognition Procedures which entered into application on January 1, 2024.
+Added: Since January 1, 2024, the MHRA may rely on the International Recognition Procedure (“IRP”), when reviewing certain types of marketing authorization applications.
+Added: This procedure is available for applicants for marketing authorization who have already received an authorization for the same product from a reference regulator.
+Added: These include the FDA, the EMA, and national competent authorities of individual EEA countries.
+Added: A positive opinion from the CHMP, or a positive end of procedure outcome from the mutual recognition or decentralized procedures are considered to be authorizations for the purposes of the IRP.
+Added: There is no pre-marketing authorization orphan designation for medicinal products in the UK.
+Added: Instead, the MHRA reviews applications for orphan designation in parallel to the corresponding marketing authorization application.
+Added: The criteria are essentially the same as those in the EU but have been tailored for the market.
+Added: This includes the criterion that prevalence of the condition in the UK, rather than the EU, must not be more than five in 10,000.
+Added: Upon the grant of a marketing authorization with orphan status, the medicinal product will benefit from up to 10 years of market exclusivity from similar products in the approved orphan indication.
+Added: The start of this market exclusivity period will be set from the date of first approval of the product in the UK.
+Added: Drug-device combination products in the UK
+Added: Similarly to the EU, the UK regulates medical devices and medicinal products separately and through different legislative instruments.
+Added: Medical devices are governed by the Medical Device Regulations (UK MDR) 2002, as amended which are based on the (now superseded) EU Medical Devices Directive, as opposed to the EU MDR which does not apply in the UK .
+Added: Products that are a combination of a medicinal product and a medical device may be regulated as either a medicinal product, a medical device or, subject to certain requirements, on the basis of both sets of rules depending on the type of drug-device combination.
+Added: Devices that are used to administer medicinal products that are included separately in a pack with the medicine or that can be refilled with medication contained in the same pack as the device are regulated as medical devices.
+Added: Devices that are used for administering medicinal products where the device and medicinal product form a single integral product designed to be used exclusively in the given combination and which are not re-usable or refillable are regulated as medicinal products but certain requirements of the UK MDR apply with respect to safety and performance related features of a device.
+Added: Devices that incorporate, as an integral part, a substance which if used separately, may be considered to be a medicinal product and where the substance is liable to act upon the body with action ancillary to that of the device are regulated are subject to the UK MDR but the body carrying out relevant conformity assessment procedures must consult with the MHRA on the medicinal aspects of the device.
+Added: The MHRA can provide guidance to a company that is unsure which set of regulatory rules to follow.
+Added: Pricing, Coverage and Reimbursement
+Added: Reimbursement authorities in Europe may be more restrictive than payors in the United States.
+Added: In Europe, pricing and reimbursement schemes vary widely from country to country.
+Added: For example, some countries provide that products may be marketed only after an agreement on reimbursement price has been reached.
+Added: Such pricing negotiations with governmental authorities can take considerable time after receipt of marketing approval for a product.
+Added: Political, economic and regulatory developments may further complicate pricing negotiations, and pricing negotiations may continue after reimbursement has been obtained.
+Added: In addition, the European Union provides options for its Member States to restrict the range of products for which their national health insurance systems provide reimbursement and to control the prices of medicinal products for human use.
+Added: EU Member States may approve a specific price for a product, may adopt a system of direct or indirect controls on the profitability of the company placing the product on the market.
+Added: Other EU Member States allow companies to fix their own prices for products but monitor and control prescription volumes and issue guidance to physicians to limit prescriptions.
+Added: In addition, some EU Member States may require the completion of additional studies that compare the cost-effectiveness of a particular medicinal product candidate to currently available therapies.
+Added: This Health Technology Assessment (“HTA”), process is the procedure according to which the assessment of the public health impact, therapeutic impact and the economic and societal impact of use of a given medicinal product in the national healthcare systems of the individual country is conducted.
+Added: The outcome of HTA regarding specific medicinal products will often influence the pricing and reimbursement status granted to these medicinal products by the competent authorities of individual EU Member States.
+Added: In December 2021, Regulation No 2021/2282 on Health Technology Assessment (“HTA Regulation”), was adopted.
+Added: The HTA Regulation is intended to boost cooperation among EU Member States in assessing health technologies, including new medicinal products, and providing the basis for cooperation at EU level for joint clinical assessments in these areas.
+Added: The HTA Regulation began to apply on January 12, 2025 through a phased implementation and is intended to harmonize the clinical benefit assessment of HTA across the EU.
+Added: In light of the fact that the UK has left the EU, Regulation No 2021/2282 on HTA will not apply in the UK.
+Added: However, the UK Medicines and Healthcare products Regulation Agency (“MHRA”) is working with UK HTA bodies and other national organizations, such as the Scottish Medicines Consortium (“SMC”), the National Institute for Health and Care Excellence (“NICE”), and the All-Wales Medicines Strategy Group, to introduce new pathways supporting innovative approaches to the safe, timely and efficient development of medicinal products, including, effective as of 31 March 2025, relaunching the Innovative Licensing and Access Pathway with more predicable timelines and closer involvement of the National Health Service.
For other countries outside of the EU, such as countries in Eastern Europe, Latin America or Asia, the requirements governing the conduct of clinical trials, product licensing, pricing and reimbursement vary from country to country.
In all cases, again, the clinical trials are conducted in accordance with GCP and the applicable regulatory requirements and the ethical principles that have their origin in the Declaration of Helsinki.
−Removed: If we or our potential collaborators fail to comply with applicable foreign regulatory requirements, we may be subject to, among other things, fines, suspension or withdrawal of regulatory approvals, product recalls, seizure of products, operating restrictions and criminal prosecution.
+Added: If we or our potential collaborators fail to comply with applicable foreign regulatory requirements, we may be subject to, among other things, fines, suspension, variation or withdrawal of regulatory approvals, product recalls, seizure of products, operating restrictions and criminal prosecution.
Corporate Information
−Removed: 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.
−Removed: (“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.
−Removed: Pursuant to the Merger Agreement, Silverback changed its name to ARS Pharmaceuticals, Inc.
−Removed: 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.
5 unchanged sentences
As of December 31, 2024, we had 155 full-time employees and 5 part-time employees.
−Removed: Of these employees, two held Ph.D.
+Added: Of these employees, three held Ph.D.
None of our employees are represented by labor unions or covered by collective bargaining agreements.
1 unchanged sentence
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.