What changed in this filing

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Item 1. Business

2025-03-10 compared with 2024-03-15 · 132 added, 206 removed, 1118 unchanged (23% of the section changed)

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(“ Signature ”).

On December 28, 2015, Signature, Signature Acquisition

Corp., a wholly-owned subsidiary of Signature (“ SAQ ”), and Ensysce Biosciences, Inc.

(“ EB ”) entered

into an Agreement and Plan of Merger (“ EB-ST Agreement ”).

Pursuant to the EB-ST Agreement, SAQ merged with and into

EB with EB surviving the merger as a wholly-owned subsidiary of Signature.

As part of the transaction, Signature changed its name to

“Ensysce Biosciences, Inc.” (“ Former Ensysce ”) and changed EB’s name to EBI Operating Inc.

31, 2021, LACQ, Former Ensysce, and Merger Sub entered into the Merger Agreement.

On June 30, 2021, pursuant to the Merger Agreement,

Merger Sub merged with and into Former Ensysce, with Former Ensysce surviving the transaction as a wholly-owned subsidiary of LACQ.

part of the transaction, LACQ changed its name to “Ensysce Biosciences, Inc.” and Former Ensysce changed its name to EBI

In December 2015, Signature merged with and into

Ensysce Biosciences, Inc.

(“ Former Ensysce ”).

In June 2021, Former Ensysce merged with and into Leisure Acquisition

Corporation (“ LACQ ”).

As part of the transaction, LACQ changed its name to “Ensysce Biosciences, Inc.”

mailing address of our principal executive office is 7946 Ivanhoe Avenue, Suite 201, La Jolla, California 92037.

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or the MPAR® platform.

The TAAP platform is designed to seek to improve the care of patients with chronic pain while reducing the

The TAAP platform is designed to seek to improve the care of patients with severe pain while reducing the

human and economic costs associated with prescription opioid drug abuse.

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to be able to be combined with our MPAR® technology for overdose protection.

Additionally, nafamostat di-mesylate (“ nafamostat ”),

which is an ingredient in our overdose protection combination products, is also being developed for the intended purpose of treating

infection and pulmonary lung diseases.

technology under the TAAP platform when applied to opioid drugs is designed to release clinically effective opioid drugs only when exposed

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A second oral HAP study was completed in March

Most recently, a study to evaluate efficacy was completed in December 2023.

A study to evaluate efficacy was completed in December 2023.

MPAR ® technology is designed to limit the bioavailability of active opioid following co-ingestion of multiple doses, whether

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by the FDA in January 2024.

A second study, PF614-MPAR-102, designed to evaluate the overdose protection across a range of dosages, initiated

enrollment of subjects in December 2024 and is continuing enrollment.

pipeline has been developed over the course of 15 years of research and investment and includes three clinical-stage product candidates.

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be useful in addressing other treatments.

For example, we discovered the ability of nafamostat in inhibiting the action of enzymes associated

with the COVID-19 infection, and, as such, have devoted efforts to develop an oral and inhalation drug product of nafamostat, for use

against coronaviral infections and other pulmonary diseases such as cystic fibrosis.

is our lead TAAP prodrug candidate under development for the treatment of acute or chronic pain.

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at higher than prescribed dose levels in an overdose scenario.

is an enzyme inhibitor (protease inhibitor) used in our combination overdose protection technology, MPAR®.

Due to its ability to

inhibit the action of enzymes associated with the COVID-19 infection, we are also developing an oral drug product of nafamostat, for

use against coronaviral infections and other pulmonary diseases such as cystic fibrosis.

An IND was submitted (149877) for the evaluation

of oral nafamostat in coronaviral infections.

A Phase 1 trial to evaluate safety and PK was completed in 2021.

Abuse and Drug Overdose

pain medications are essential for improving the care and outcomes of a majority of Americans who live with chronic pain.

An NIH study,

updated September 2018, reported that 25.3 million adults suffered from pain every day for the preceding three months and almost 40 million

adults experience severe levels of pain, which is linked to worse health status.

High impact chronic pain affects over 10 million Americans

and is characterized by extended periods of suffering which impair life quality to a severe degree.

Prescription opioids drugs, such

as morphine, hydromorphone, hydrocodone, and oxycodone, have a long history of use for the management of severe and chronic pain.

Prescriptions

for opioid medications in 2021 totaled 153 million, with $4.2 billion in market size in the United States.

In 2023, 34.9%

of adults had chronic pain, with 8.5% of those having high impact chronic pain.

Millions of adults suffered from pain every day for the

preceding three months and almost 40 million adults experience severe levels of pain, which is linked to worse health status.

chronic pain is characterized by extended periods of suffering which impair life quality to a severe degree.

Prescription opioids drugs,

such as morphine, hydromorphone, hydrocodone, and oxycodone, have a long history of use for the management of severe and chronic pain.

Prescriptions for opioid medications in 2023 totaled almost 140 million, with $3.8 billion in market size in the United States.

CDC recently provided recommendations for clinicians who provide pain care, defining acute pain (duration less than 1 month), subacute

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died each day from opioid-related overdoses.

In 2021 the total number of opioid-related deaths rose to 109,600, with 45 people dying

each day from a prescription opioid overdose.

In 2021, the total number of opioid-related deaths rose to 109,600, whereas in 2022 that

number had declined to 81,806.

large increase in overall overdose deaths is now driven by use of synthetic opioids, in particular fentanyl, as prescription opioids

have become harder to obtain.

From 2017 to 2018 the prescription opioid-involved death rates decreased by 13.5% showing that attention

to the problem had beneficial effect.

However, 2.1 million people reported having opioid use disorder (“ Opioid Use Disorder ”)

Based on information from the CDC, the most common drugs involved in prescription opioid overdose deaths include Methadone,

Oxycodone (such as OxyContin®), and Hydrocodone (such as Vicodin®).

The CDC indicates that improving opioid prescribing, treatment

of opioid use disorder, and prevention of opioid use disorder would help to improve the opioid crisis.

Misuse or abuse of opioids is

often done in one of the following manners:

Prescription opioid-involved death rates from 2019 to 2022 were relatively flat at 14,319 to 14,716, respectively,

showing that attention to the problem had yielded a beneficial effect.

However, 6.1 million Americans over the age of 12 were reported

to be suffering from opioid use disorder (“ OUD ”) in 2024.

Based on information from the CDC, the most common drugs

involved in prescription opioid overdose deaths include Methadone, Oxycodone (such as OxyContin®), and Hydrocodone (such as Vicodin®).

The CDC indicates that improving opioid prescribing, treatment of opioid use disorder, and prevention of opioid use disorder would help

to improve the opioid crisis.

Misuse or abuse of opioids is often done in one of the following manners:

Excessive Tablet Abuse .

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like Adderall are manufactured in pill form and are intended for oral ingestion.

As of Q4 2022, seventy-five percent of Adderall prescriptions

As of late 2022, seventy-five percent of Adderall prescriptions

are prescribed to the 10.5 million adults, age 22 or older, that are diagnosed with attention deficit hyperactivity disorder, or ADHD.

ADHD is the most common neurodevelopment disorder in children.

Five million adults misuse stimulant medication annually, by using alternative

consumption methods to achieve a more intense high faster;

The number of prescriptions have fallen in 2023 and 2024 due to shortages of the medication.

ADHD is the most common neurodevelopment

disorder in children.

Five million adults misuse stimulant medication annually, by using alternative consumption methods to achieve a

more intense high faster;

snorting or injecting are most-common methods of abuse.

Both of these methods

involve crushing pills.

Both of these methods involve crushing pills.

believe that having prescription drug products available that have a reduced potential for abuse by crushing and injecting, snorting,

and chewing could provide an even greater reduction of prescription opioid related deaths in the abuse of opioids or amphetamines.

market opportunity is multifaceted.

The oral form could be used alone or in combination with other antiviral drugs that target separate

processes needed for virus product, such as RNA replication or viral protein processing.

Nafamostat delivered orally was evaluated in

a Phase 1 study for safety and tolerability with the anticipation of further evaluating an oral nafamostat drug product against COVID-19

in Phase 2 trials, however at this time the oral nafamostat program is not the company’s primary focus.

Technology Platform Solution

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Serial PK sampling was performed after each study drug administration up to

120 hours postdose.

120 hours post dose.

Safety including regular assessments of AEs, vital signs (pulse rate, blood pressure, respiratory rate, and SpO 2

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of pain relief from both doses of PF614 was identified, and PF614 did decrease the intensity of pain.

End of Phase 2 regulatory meeting request for PF614 IND 116794 was submitted on October 13, 2023, with a meeting was held on January

The meeting clarified the non-clinical and clinical Phase 3 study plans for the further development of PF614 which are expected

to initiate in mid-2024.

End of Phase 2 regulatory meeting was held on January 30, 2024.

The meeting clarified the non-clinical and clinical Phase 3 study plans

for the further development of PF614 which are expected to initiate in mid-2025.

initiated a Phase 1 study that is evaluating PF614-MPAR in study entitled “A Single Dose, 2 Part Study to Evaluate the Pharmacokinetics

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for PF614-MPAR was submitted in 2023 and responses to questions were received in February 2024.

PF614-MPAR-102

Phase 1b Clinical Trial

primary objectives of the Phase 1b study are to assess the pharmacokinetics of oxycodone when PF614 is administered alone and with formulated

nafamostat, evaluate a food effect, and explore PF614-MPAR delivered in a multi-ascending dose study.

The study initiated in December

2024 and will continue through 2025.

life sciences industry is characterized by rapidly advancing technologies, intense competition, and a strong emphasis on proprietary

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Vertex has recently announced

a non-opioid pain product that inhibits NaV1.8 and has entered Phase 3 development.

the approval of a non-opioid pain product, suzetrigine, that inhibits NaV1.8.

The clinical data provided to date has indicated that suzetrigine

did not provide superior pain relief compared to the opioid control arm of the Phase 3 study.

do not believe there are other companies developing products that have an overdose mechanism similar to our MPAR ® technology.

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and MPAR® Patents and Applications for Opioids

our merger with Signature, we became the owner of patent families that include several granted U.S.

patents, as well as granted patents

and pending patent applications in numerous foreign jurisdictions, including Australia, Brazil, Canada, China, Europe, India, Japan,

and Russia, relating to chemically modified opioids, such as oxycodone, methadone, and hydromorphone, covalently linked using specific

linkers to a gastrointestinal enzyme-cleavable moiety and pharmaceutical compositions containing these modified opioids, pharmaceutical

compositions containing these modified opioids and a gastrointestinal enzyme inhibitor, and methods of using the same to treat pain.

Three of these patent families are directed to ketone containing opioids and cover PF614 and PF614-MPAR and certain methadone TAAP product

candidates that are still in the discovery phase.

These three families contain issued patents in the United States and certain foreign

jurisdictions, including Australia, Brazil, Canada, China, Europe, India, Japan, and Russia and expire between 2030 and 2032, subject

to any applicable patent term extension that might be available in a jurisdiction.

We also own pending United States, Patent Cooperation

Treaty (PCT), and Taiwan applications directed to oral formulations of PF614-MPAR, which if pursued and issued would expire in 2042,

subject to any potential patent term adjustment or extension that may be available in a jurisdiction.

We also own one patent family that

includes granted patents in the United States, as well as granted patents and pending patent applications in numerous foreign jurisdictions,

including Australia, Brazil, Canada, China, Europe, India, Japan, and Russia, relating to chemically modified ketone-containing agents,

such as oxycodone, methadone, and hydromorphone, covalently linked using specific linkers to a gastrointestinal enzyme-cleavable moiety,

pharmaceutical compositions containing these modified ketone-containing agents, pharmaceutical compositions containing these modified

ketone-containing agents and a gastrointestinal enzyme inhibitor, and methods of using the same to treat pain, would cover certain methadone

TAAP product candidates that are still in discovery phase and expire in 2032.

While we own these patent families, we have not updated

records in the various patent offices to reflect our ownership of these patent families.

Failure to update such ownership may result

in an innocent purchaser potentially acquiring rights in such patents that are adverse to our interests.

Furthermore, as noted above,

we have not obtained assignments for certain patent applications relating to abuse-resistant amphetamines.

are the owner of patent families that include several granted U.S.

patents, as well as granted patents and pending patent applications

in numerous foreign jurisdictions, including Australia, Brazil, Canada, China, Europe, India, Japan, and Russia, relating to chemically

modified opioids, such as oxycodone, methadone, and hydromorphone, covalently linked using specific linkers to a gastrointestinal enzyme-cleavable

moiety and pharmaceutical compositions containing these modified opioids, pharmaceutical compositions containing these modified opioids

and a gastrointestinal enzyme inhibitor, and methods of using the same to treat pain.

Three of these patent families are directed to

ketone containing opioids and cover PF614 and PF614-MPAR and certain methadone TAAP product candidates that are still in the discovery

These three families contain issued patents in the United States and certain foreign jurisdictions, including Australia, Brazil,

Canada, China, Europe, India, Japan, and Russia and expire between 2030 and 2032, subject to any applicable patent term extension that

might be available in a jurisdiction.

We also own pending United States, Patent Cooperation Treaty (PCT), and Taiwan applications directed

to oral formulations of PF614-MPAR, which if pursued and issued would expire in 2042, subject to any potential patent term adjustment

or extension that may be available in a jurisdiction.

We also own one patent family that includes granted patents in the United States,

as well as granted patents and pending patent applications in numerous foreign jurisdictions, including Australia, Brazil, Canada, China,

Europe, India, Japan, and Russia, relating to chemically modified ketone-containing agents, such as oxycodone, methadone, and hydromorphone,

covalently linked using specific linkers to a gastrointestinal enzyme-cleavable moiety, pharmaceutical compositions containing these

modified ketone-containing agents, pharmaceutical compositions containing these modified ketone-containing agents and a gastrointestinal

enzyme inhibitor, and methods of using the same to treat pain, would cover certain methadone TAAP product candidates that are still in

discovery phase and expire in 2032.

While we own these patent families, we have not updated records in the various patent offices to

reflect our ownership of these patent families.

Failure to update such ownership may result in an innocent purchaser potentially acquiring

rights in such patents that are adverse to our interests.

Furthermore, as noted above, we have not obtained assignments for certain patent

applications relating to abuse-resistant amphetamines.

believe that one patent covering PF614 will be eligible for up to five years of patent term extension in the United States and intend

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Patents Applications

own pending applications in the U.S., Canada and Europe directed to the use of orally administered nafamostat for the treatment of infections

caused by coronaviruses, including COVID-19, and pending United States, PCT, and Taiwan patent applications directed to oral formulations

own pending applications in the U.S., Canada and Europe directed to the use of orally administered nafamostat and extended-release formulations

of nafamostat.

We intend to pursue these applications in the United States and other significant commercial markets and any patents that

may be issued would expire in 2041 and 2042, respectively, subject to any applicable patent term adjustment or extension in a particular

jurisdiction.

Additionally, we acquired one European patent from Mucokinetica Ltd.

that is directed to the use of certain compounds,

including nafamostat, for the manufacture of a medicament for the treatment of respiratory diseases with mucostasis or poor mucus clearance.

This patent was validated in Germany, France, Italy, and the United Kingdom and expires in 2028, subject to any applicable patent term

extension that might be available in Europe Union or United Kingdom.

Currently, we do not have any issued patent or pending application

directed to methods of treating infections caused by coronaviruses, including COVID-19, with inhaled nafamostat, but intend to file pending

applications upon development of a suitable inhalation formulation of nafamostat.

We believe that one patent covering nafamostat will

be eligible for up to five years of patent term extension in the United States and Europe and intend to pursue such extension.

to patent exclusivity, under the provisions of the Hatch-Waxman Act, upon any approval in the United States, we believe that nafamostat

will be eligible for five-year NCE regulatory exclusivity, during which time no 505(b)(2) NDA or ANDA can be approved that contains the

same active moiety as the chemical entity in the nafamostat NDA.

In addition, if an ANDA or 505(b)(2) applicant were to file its application

referencing the NDA for nafamostat before expiration of our use patent and the applicant asserted that the patent is invalid or would

not be infringed, it may be subject to additional waiting periods prior to the FDA’s approval (including a statutory thirty-month

stay, starting at the end of the five-year NCE regulatory exclusivity period, if we sue for infringement, or a shorter period if the

patent expires of there are certain settlements or judicial decisions in the patent litigation) and may ultimately be required to wait

until the natural expiration of our compositions patents if the patents are found to be valid and infringed by the challenging applicant.

For more information please see “— Patent and Patent Applications .”

Some of the claims are directed to the use of oral nafamostat for the treatment of infections caused by coronaviruses,

including COVID-19, and pending United States, PCT, and Taiwan patent applications directed to oral formulations of nafamostat.

to pursue these applications in the United States and other significant commercial markets and any patents that may be issued would expire

in 2041 and 2042, respectively, subject to any applicable patent term adjustment or extension in a particular jurisdiction.

Additionally,

we acquired one European patent from Mucokinetica Ltd.

that is directed to the use of certain compounds, including nafamostat, for the

manufacture of a medicament for the treatment of respiratory diseases with mucostasis or poor mucus clearance.

This patent was validated

in Germany, France, Italy, and the United Kingdom and expires in 2028, subject to any applicable patent term extension that might be

available in Europe Union or United Kingdom.

Currently, we do not have any issued patent or pending application directed to methods of

treating infections caused by coronaviruses, including COVID-19, with inhaled nafamostat, but intend to file pending applications upon

development of a suitable inhalation formulation of nafamostat.

We believe that one patent covering nafamostat will be eligible for up

to five years of patent term extension in the United States and Europe and intend to pursue such extension.

In addition to patent exclusivity,

under the provisions of the Hatch-Waxman Act, upon any approval in the United States, we believe that nafamostat will be eligible for

five-year NCE regulatory exclusivity, during which time no 505(b)(2) NDA or ANDA can be approved that contains the same active moiety

as the chemical entity in the nafamostat NDA.

In addition, if an ANDA or 505(b)(2) applicant were to file its application referencing

the NDA for nafamostat before expiration of our use patent and the applicant asserted that the patent is invalid or would not be infringed,

it may be subject to additional waiting periods prior to the FDA’s approval (including a statutory thirty-month stay, starting

at the end of the five-year NCE regulatory exclusivity period, if we sue for infringement, or a shorter period if the patent expires

of there are certain settlements or judicial decisions in the patent litigation) and may ultimately be required to wait until the natural

expiration of our compositions patents if the patents are found to be valid and infringed by the challenging applicant.

For more information

please see “— Patent and Patent Applications .”

and MPAR® Patents and Applications for Amphetamines

the merger with Signature, we became the owner of one patent family that includes pending applications in the United States and numerous

European foreign jurisdictions relating to chemically modified amphetamines covalently linked to a gastrointestinal enzyme-cleavable

moiety, pharmaceutical compositions containing the modified amphetamines, pharmaceutical compositions containing the modified amphetamines

and a gastrointestinal enzyme inhibitor and methods of using the same to treat a subject.

While we own this patent family, we have not

updated the records in the various patent offices to reflect our ownership of this patent family.

Failure to update such ownership may

result in an innocent purchaser potentially acquiring rights in such patents that are adverse to our interests.

In addition, we own pending

United States and European patent applications directed to pharmaceutical compositions containing chemically modified amphetamines covalently

linked to a gastrointestinal enzyme-cleavable moiety and a trypsin inhibitor and methods of using the same to treat a subject.

not obtained assignments from all of the inventors of these applications to date, which could negatively impact our ability to pursue

or enforce this application.

If issued, these patent applications would expire between 2031 and 2040, subject to any applicable patent

term adjustment or extension that might be available in a jurisdiction.

are the owner of one patent family that includes pending applications in the United States and numerous European foreign jurisdictions

relating to chemically modified amphetamines covalently linked to a gastrointestinal enzyme-cleavable moiety, pharmaceutical compositions

containing the modified amphetamines, pharmaceutical compositions containing the modified amphetamines and a gastrointestinal enzyme

inhibitor and methods of using the same to treat a subject.

While we own this patent family, we have not updated the records in the various

patent offices to reflect our ownership of this patent family.

Failure to update such ownership may result in an innocent purchaser potentially

acquiring rights in such patents that are adverse to our interests.

In addition, we own pending United States and European patent applications

directed to pharmaceutical compositions containing chemically modified amphetamines covalently linked to a gastrointestinal enzyme-cleavable

moiety and a trypsin inhibitor and methods of using the same to treat a subject.

We have not obtained assignments from all of the inventors

of these applications to date, which could negatively impact our ability to pursue or enforce this application.

If issued, these patent

applications would expire between 2031 and 2040, subject to any applicable patent term adjustment or extension that might be available

in a jurisdiction.

and Trade Secrets

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do not currently own or operate manufacturing facilities for the production of clinical or commercial quantities of our product candidates.

Our drug substance and drug products are manufactured for us by contract manufacturing organizations, or CMOs, to our specifications.

Any manufacturing problem or the loss of a CMO could be disruptive to our operations.

Our drug substance and drug products are manufactured for us by CMOs, to our specifications.

Any manufacturing problem or the loss of

a CMO could be disruptive to our operations.

lead product candidate, PF614, is a small molecule opioid prodrug.

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and reduced control over production costs, delivery schedules, reliability, and quality.

LLC manufactures PF614 and other clinical trial materials under cGMP conditions and provides stability studies with respect to our PF614

clinical trials.

We do not currently have a binding written agreement with Purisys.

In the event that Purisys is unable to perform the

services promised under future agreements, we may be subject to unforeseen costs and delays with respect to our clinical trials and may

be unable to replace the Purisys arrangements on terms as favorable to us.

See “ Risk Factors—We expect to be completely

dependent on third parties to manufacture our product candidates, and our commercialization of our product candidates could be halted,

delayed or made less profitable if those third parties fail to maintain a compliance status acceptable to the FDA or comparable foreign

regulatory authorities, fail to provide to us with sufficient quantities of our product candidates or fail to do so at acceptable quality

levels or prices ” for more information.

CDMO manufactures PF614 and other clinical trial drug products under cGMP conditions and provides stability studies with respect to our

PF614 clinical trials.

Societal has completed the manufacture of PF614 50 and 100 mg capsules that have been used in clinical studies

PF614-102, PF614-103, PF614-104 and PF614-201.

We expect to enter into additional related agreements with Societal CDMO as we manufacture

future batches of PF614.

In the event that Societal is unable to perform the services anticipated under future agreements, we may be

subject to unforeseen costs and delays with respect to our clinical trials.

See “ Risk Factors—We expect to be completely

dependent on third parties to manufacture our product candidates, and our commercialization of our product candidates could be halted,

delayed or made less profitable if those third parties fail to maintain a compliance status acceptable to the FDA or comparable foreign

regulatory authorities, fail to provide to us with sufficient quantities of our product candidates or fail to do so at acceptable quality

levels or prices ” for more information.

have received funding under federal grant award programs through governmental agencies, such as the NIH and NIDA.

For the year ended

December 31, 2023, we received federal grant funding totaling $2.2 million, $1.3 million from NIH related to the Phase 1 clinical trial

for PF614-MPAR and $0.9 million from NIDA for preclinical development of our opioid use disorder-MPAR ® technology.

remaining funding under approved grants totaled $2.2 million as of December 31, 2023, covering the period through August 2024.

apply for additional grant funding from these or similar governmental agencies in the future.

to the GEM Agreement, we are entitled to draw down up to $60 million of gross proceeds (“ Aggregate Limit ”) from GEM

Global in exchange for shares of our common stock, subject to meeting the terms and conditions of the GEM Agreement.

This equity line

facility is available for a period of 36 months from the closing date of the Merger.

A draw down is subject to limitations on the amount

that is drawn under the facility and must comply with certain conditions precedent including the listing of our shares on a principal

market (which includes Nasdaq), having the necessary number of shares that are issuable pursuant to the draw down registered under an

effective registration statement, and other notice and timing requirements.

Upon our valid exercise of a draw down, pursuant to delivery

of a notice and in accordance with other conditions, GEM Global is required to pay, in cash, a per-share amount equal to 90% of the average

closing bid price of the shares of our common stock recorded by Nasdaq during the 30 consecutive trading days commencing on the first

trading day that is designated on the draw down notice.

In no event may our draw down requests exceed 400% (“ Draw Down Limit ”)

of the average daily trading volume for the 30 trading days immediately preceding the date we deliver the draw down notice.

upon the closing of the Merger, GEM Global became entitled to a commitment fee in the form of cash or freely tradeable shares of our

common stock in an amount equal to 2% of the Aggregate Limit or $1.2 million to be paid in two tranches.

The commitment fees have been

paid in full.

Additionally,

we issued a warrant with a 36-month term at the closing of the Merger granting GYBL the right to purchase 4,608 shares of our common

stock at a strike price per share equal to $1.5675, after several downward adjustments to the strike price.

Any failure by us to timely

transfer the shares under the warrant pursuant to GYBL’s exercise will entitle GYBL to compensation in addition to other remedies.

The number of shares underlying the warrant as well as the strike price is subject to adjustments for recapitalizations, reorganizations,

change of control, stock split, stock dividend and reverse stock splits.

The strike price is subject to adjustment for issuances of additional

common shares at a price per share less than the strike price.

GEM Agreement contains certain negative covenants restricting us from securing an equity line similar to the financing provided under

the GEM Agreement and requiring prompt notice of events constituting an alternate transaction.

An “ alternate transaction ”

includes an issuance of common stock at a price less than the then current market price, an “ at-the-market ” offering

of securities, and an issuance of options, warrants, or similar rights of subscription or the issuance of convertible equity or debt

See “ Risks Related to Our Business, Financial Condition and Capital Requirements ” for additional information.

pursuant to the terms of the GEM Agreement, we are required to indemnify GEM Global for any losses it incurs as a result of a breach

by us or of our representations and warranties and covenants under the GEM Agreement or for any misstatement or omission of a material

fact in a registration statement registering those shares pursuant to the GEM Agreement.

Also, GEM Global is entitled to be reimbursed

for legal or other costs or expenses reasonably incurred in investigating, preparing, or defending against any such loss.

have not raised any capital pursuant to the GEM facility and we may not raise any capital pursuant to it prior to its expiration.

pursuant to the terms of our recent financings may also affect our ability to use the GEM Facility.

December 31, 2024, we received federal grant funding totaling $5.2 million consisting of $3.1 million from NIH related to the Phase 1

clinical trial for PF614-MPAR and $2.1 million from NIDA for preclinical development of our opioid use disorder-MPAR ®

Current remaining funding under the PF614-MPAR grant totaled $1.6 million as of December 31, 2024, covering the period through

The PF614-MPAR grant includes a remaining $9.0 million of approved funding through May 2027.

We may apply for additional grant

funding from these or similar governmental agencies in the future.

the United States, pharmaceutical products are subject to extensive regulation by the FDA, and those pharmaceutical products that are

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and conducting follow-up, and 4) assessing risk and addressing potential harms of opioid use.

The guideline addresses the following

1) determining whether or not to initiate opioids for pain, 2) selecting opioids and determining opioid dosages, 3) deciding

duration of initial opioid prescription and conducting follow-up, and 4) assessing risk and addressing potential harms of opioid

Drug Safety Communication:

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independent contractors to support our organization.

None of our employees is represented by a labor union or covered by collective bargaining

agreements, and we believe our relationship with our employees is good.

None of our employees are represented by a labor union or covered by collective

bargaining agreements, and we believe our relationship with our employees is good.

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

What changed 10-K

Item 1. Business