What changed in this filing

/stocks — the workspaceLOADING

Item 1. Business

2025-03-27 compared with 2024-03-19 · 574 added, 609 removed, 377 unchanged (76% of the section changed)

1 unchanged sentence

Relmada Therapeutics, Inc.

(Relmada, the Company,

we or us) (a Nevada corporation), is a clinical-stage biotechnology company focused on the development of esmethadone (d-methadone, dextromethadone,

REL-1017), an N-methyl-D-aspartate (NMDA) receptor antagonist.

Esmethadone, an isomer of methadone, is a new chemical entity (NCE) that

potentially addresses areas of high unmet medical need in the treatment of central nervous system (CNS) diseases and other disorders.

Our lead product candidate, esmethadone, is being

developed as a rapidly acting, oral agent for the treatment of depression and other potential indications.

On October 15, 2019, we reported

top-line data from study REL-1017-202.

During late 2022, we announced RELIANCE I and III, both Phase 3 trials, did not achieve their primary

Relmada has completed its long term, open label study and plans to complete two additional ongoing adjunctive Phase 3 trials

(RELIANCE II and RELIGHT).

Relmada also intends, in 2024, to enter human

studies of its proprietary, modified-release formulation of psilocybin (REL-P11) in doses that we believe are lower than those associated

with psychedelic effects for metabolic indications.

Phase 2 Clinical Trial

In the REL-1017-202 study, 62 subjects, with an

average age of 49.2 years, with an average Hamilton Depression Rating Scale score of 25.3 and an average Montgomery-Asberg Depression

Rating Scale (MADRS) score of 34.0 (severe depression), were randomized.

Other demographic characteristics were balanced across all arms.

After an initial screening period, subjects were randomized to one of three arms:

placebo, REL-1017 25 mg or REL-1017 50 mg, in addition

to stable background antidepressant therapy.

Subjects in the REL-1017 treatment arms received one loading dose of either 75 mg (25 mg

arm) or 100 mg (50 mg arm) of REL-1017.

Subjects were treated inpatient for 7 days and discharged home at Day 9.

They returned for follow-up

visits at Day 14 and Day 21.

Efficacy was measured on Days 2, 4 and 7 in the dosing period and on Day 14, one week after treatment discontinuation.

61 subjects received all treatment doses and were included in the per-protocol population (PPP) treatment analysis;

57 subjects completed

All 62 randomized subjects were part of the intention-to-treat (ITT) analysis.

No differences were observed between the ITT

and PPP analyses and results.

We observed that subjects in both the REL-1017

25 mg and 50 mg treatment groups experienced statistically significant improvement on all efficacy measures tested as compared to subjects

in the placebo group, including:

the Clinical Global Impression – Severity (CGI-S) scale;

the Clinical Global Impression

– Improvement (CGI-I) scale;

and the Symptoms of Depression Questionnaire (SDQ).

Improvements on the MADRS endpoint appeared on

Day 4 in both REL-1017 dose groups and continued through Day 7 and Day 14, seven days after treatment discontinuation, with P values<

0.03 and large effect sizes (a measure of quantifying the difference between two groups), ranging from 0.7 to 1.0.

Similar findings emerged

from the CGI-S and CGI-I scales.

The study also confirmed the tolerability profile

of REL-1017, which was observed in the Phase 1 studies.

Subjects experienced only mild and moderate adverse events (AEs), and no serious

adverse events, without significant differences between placebo and treatment groups.

The AEs observed in the Phase 2a clinical study

were of the same nature as those observed in the Phase 1 clinical studies of d-Methadone, and there was no evidence of either treatment

induced psychotomimetic and dissociative AEs or withdrawal signs and symptoms upon treatment discontinuation.

Phase 3 Program

On December 20, 2020, Relmada announced that the

first patient had been enrolled in the first Phase 3 clinical trial (RELIANCE I) for the Company’s lead product candidate, REL-1017,

as an adjunctive treatment for Major Depressive Disorder (MDD).

On April 1, 2021, Relmada announced the initiation

of RELIANCE II, the second of two sister pivotal Phase 3 clinical trials (RELIANCE I and RELIANCE II) for the Company’s lead product

candidate, REL-1017, as an adjunctive treatment for MDD.

On October 4, 2021, Relmada announced the initiation

of RELIANCE III study, a monotherapy trial for the Company’s lead product candidate, REL-1017.

In addition, on

October 4, 2021, Relmada announced that in order to support potential regulatory submissions seeking approval for REL-1017 as adjunctive

and monotherapy treatment, the Food and Drug Administration (FDA) confirmed that, based on what was known at the time, Relmada would

not be required to conduct a two-year carcinogenicity study of REL-1017, as sufficient clinical data had been generated to date.

FDA also confirmed that Relmada would not need to conduct a TQT cardiac study in humans to support cardiac safety in potential regulatory

submissions for REL-1017, as the data already provided and the data to be generated by the Phase 3 program would be adequate to evaluate

the cardiac safety profile of REL-1017.

On August 9, 2022, Relmada

announced that the FDA granted Fast Track designation to REL-1017 as a monotherapy for the treatment of MDD.

On October 13, 2022,

Relmada announced that its RELIANCE III study, evaluating REL-1017 in the monotherapy setting for MDD, did not achieve its primary endpoint,

which was a statistically significant improvement in depression symptoms compared to placebo as measured by MADRS on Day 28.

In the study,

the REL-1017 treatment arm showed a MADRS reduction of 14.8 points at Day 28 versus 13.9 points for the placebo arm, a higher than expected

placebo response.

On December 7, 2022,

Relmada announced that its RELIANCE I study, evaluating REL-1017 as an adjunctive treatment for MDD, did not achieve its primary endpoint,

which was a statistically significant improvement in depression symptoms compared to placebo as measured by MADRS on Day 28.

In the study,

the REL-1017 treatment arm (n= 113) showed a MADRS reduction of 15.1 points at Day 28 versus 12.9 points for the placebo arm (n=114),

which is a clinically meaningful difference of 2.3 points on the MADRS.

The study also showed a nominally statistically significant difference

in the response rate, with a response rate of 39.8% in the REL-1017 arm vs 27.2% in the placebo arm (p<0.05).

Additionally, in a prespecified

per protocol population analysis, the REL-1017 treatment arm (n=101) showed a MADRS reduction of 15.6 points at Day 28 versus 12.5 points

for the placebo arm (n=97), a difference of 3.1 points, with nominal p=0.051.

who completed the RELIANCE trials were eligible to rollover into the long-term, open-label study, Study 310, which also included subjects

who had not previously participated in a REL-1017 clinical trial.

This rollover study completed subject visits on July 11, 2023.

20, 2023, Relmada announced efficacy results for the de novo (or new to treatment) patients (204 patients) and safety results for all

subjects (627 patients) from Study 310 of REL-1017 in patients with MDD.

Patients treated daily with REL-1017 for up to one year experienced

rapid, clinically meaningful, and sustained improvements in depressive symptoms and associated functional impairment.

REL-1017 was well-tolerated

with long-term dosing, showing low rates of adverse events and discontinuations due to adverse events.

The most commonly

reported adverse events deemed to be treatment-related all occurred included headache, nausea and dizziness.

new safety signals were detected.

On August 23, 2023, Relmada announced the dosing

of the first patient in RELIGHT, a Phase 3 clinical trial for REL-1017, as an adjunctive treatment for MDD.

Human Abuse Potential (HAP) Studies

Top-line Results - Oxycodone:

On July 27, 2021, Relmada announced top-line results

that showed that all three doses of REL-1017 (25 mg, 75 mg and 150 mg, the therapeutic, supratherapeutic and maximum tolerated doses (MTD),

respectively) tested in recreational opioid users, demonstrated a highly statistically significant difference vs.

the active control drug,

oxycodone 40 mg.

The study’s primary endpoint was a measure of “likability” with the subjects rating the maximum effect

(or Emax) for Drug Liking “at the moment”, using a 1-100 bipolar rating scale (known as a visual analog scale or VAS), with

100 as the highest likability, 50 as neutral (placebo-like), and 0 the highest dislike.

In summary, all tested doses of REL-1017, including

the 150 mg MTD, showed a highly statistically significant difference in abuse potential versus oxycodone with p-values less than 0.05.

Consistent results were seen for the secondary endpoints.

Additionally, all REL-1017 doses including 150 mg (6 times the therapeutic dose

and MTD) were statistically equivalent to placebo (p<0.05).

These results support the lack of opioid effects of REL-1017.

Top-line Results - Ketamine:

On February 23, 2022, Relmada announced top-line

results that showed that all three doses of REL-1017 (25 mg, 75 mg, and 150 mg, the therapeutic, supratherapeutic and MTD, respectively)

tested in recreational drug users, demonstrated a substantial (30+ points) and statistically significant difference vs.

the active control

drug, intravenous ketamine 0.5 mg/kg over 40 minutes, and, importantly, were statistically equivalent to placebo.

The study’s primary

endpoint was a measure of “likability” with the subjects rating the maximum effect (or Emax) for Drug Liking “at this

moment”, using a 1-100 bipolar rating scale (known as a visual analog scale or VAS), with 100 as the highest likability, 50 as neutral

(placebo-like), and 0 the highest dislike.

Consistent results are seen for the secondary endpoints.

Psilocybin Program (REL-P11):

On October 11, 2023, Relmada announced that it

intends to enter human studies of its proprietary, modified-release formulation of psilocybin (REL-P11) for metabolic indications in doses

that we believe are lower than those associated with psychedelic effects.

The Company plans to commence a single-ascending dose Phase

1 trial in obese patients in the first half of 2024 to define the pharmacokinetic, safety and tolerability profile of Relmada’s

modified-release psilocybin formulation (REL-P11) in this population, followed by a Phase 2a trial to establish clinical proof-of-concept.

Pre-clinical data in a rodent model of metabolic

dysfunction-associated steatotic liver disease (MASLD) demonstrated beneficial effects of psilocybin, on multiple metabolic parameters,

including reduced hepatic steatosis, reduced body weight gain, and fasting blood glucose levels.

(Relmada, the

Company, we or us) (a Nevada corporation), is a publicly traded, clinical-stage biotechnology company.

We substantially redesigned

our development programs following a comprehensive strategic review occasioned by disappointing interim analysis results in December

2024 indicating that our then lead development candidate, esmethadone (d-methadone, dextromethadone, or REL-1017) for the adjunctive

treatment of Major Depressive Disorder (MDD), was unlikely to succeed in its pivotal trial.

We concluded in our review that the most

promising path to create shareholder value was to lever our extensive drug development expertise and clinical operations

capabilities by acquiring new development candidates, while pausing further work on REL-1017.

Hence we accelerated ongoing efforts

to augment our development pipeline while diversifying its risk, which culminated in the recently announced licensing of NDV-01, a

novel delivery formulation of a widely used chemotheraphy regimen used to treat non muscle-invasive bladder cancer (NMIBC) that is

currently in Phase 2, and the acquisition of Sepranolone, a Phase 2b-ready neurosteroid with potential applications in Prader-Willi

syndrome (PWS), Tourette Syndrome (TS), essential tremor and other diseases related to excessive GABAergic activity.

We also had been developing REL-P11, a modified-release

formulation of psilocybin, as an investigational agent for the treatment of metabolic disease.

The REL-P11 program has successfully completed

a Phase 1 safety study.

However, in light of an ongoing strategic review of this business opportunity, the changing regulatory landscape

for psychedelics, its early stage of development and the acquisition of new, more advanced product candidates, this program has also

REL-1017 Program Updates

Since 2013, we had been developing esmethadone

as our lead product candidate as an oral agent for the treatment of depression and other potential indications.

In December 2024,

we reported that the pre-planned interim analysis, conducted by the Independent Data Monitoring Committee (DMC), of Reliance II, our Phase

3 study of esmethadone as a potential adjunctive treatment for MDD, indicated that the study was futile and unlikely to meet the primary

efficacy endpoint with statistical significance, and that we would pause the Reliance II and Relight Phase 3 studies of esmethadone.

Following this 2024 REL-1017 setback, which we

believe mostly likely resulted from an overwhelming placebo response—a trend that has become more common than exceptional in central

nervous system (CNS) clinical trials—the program has been paused pending a comprehensive data review, after which we will make a

decision regarding the future of this program.

Strategic Business Review and New Approach

Following a comprehensive evaluation of the Company’s

business strategy and growth opportunities, management and the Board of Directors have implemented a revised approach aimed at maximizing

shareholder value.

This refined strategy remains focused on:

– Advancing novel and differentiated therapeutic solutions

Unmet Medical Needs – Targeting areas with significant gaps in treatment

Market Opportunities – Prioritizing programs with substantial commercial potential

● Intellectual

Property Protection – Strengthen and extending patent coverage to safeguard long-term value

Key Strategic Priorities

Under this updated approach, we will continue

to emphasize:

Development Expertise – Focusing on high-value therapeutic areas while rigorously assessing development risks, market viability,

and success probabilities

Diversification – Expanding and balancing our portfolio to mitigate risk and enhance growth potential

● Prioritizing

Mid- to Late-Stage Programs – Concentrating resources on assets with clear path to commercialization

● Accelerating

Market Entry – Streamline development timelines to bring therapies to patients faster

Cost-Effective Development Paths – Optimizing resource allocation and strategic partnerships

Commercialization Strategy – Focusing on opportunities that require minimal sales and marketing infrastructure

This strategic framework positions the Company for long-term

growth while maintaining execution and financial prudence.

Progress in Strategic Execution

We commenced a strategic review in December 2024

of our then existing development pipeline and the opportunities open to us given our core strengths in every aspect of drug development,

with particular expertise in CNS.

That process recently resulted in a series of transactions that have considerably expanded and strengthened

Relmada’s potential to create shareholder value.

Over the past three months, we have successfully closed two important transactions,

NDV-01 in-licensing and Sepranolone acquisition, which align with our new strategy.

On February 6, 2025, Relmada announced the acquisition

from Asarina Pharma AB (Asarina) of Sepranolone, a Phase 2b ready neurosteroid being developed for the potential treatment of PWS, TS,

essential tremor and other diseases related to the excessive GABAergic activity.

On March 25, 2025, Relmada announced the in-license

agreement from Trigone Pharma Ltd.

(Trigone) of NDV-01, a novel delivery formulation of a widely used chemotherapeutic regimen used to

Key Upcoming Anticipated Milestones

1 unchanged sentence

These include:

Complete enrollment in the ongoing RELIANCE II study, which is planned to enroll approximately 300 patients, with top-line data in the second half of 2024.

Complete enrollment in the RELIGHT study (study 304), which is planned to enroll approximately 300 patients, by the end of 2024.

Initiate Phase 1 trial in obese patients with the modified-release formulation of psilocybin (REL-P11) in the first half of 2024.

Our Development Program

NDV-01 Phase 2a data presentation at the 2025 American Urological Association Meeting – 1 st Half 2025

NDV-01 United States Investigative New Drug clearance – 2 nd Half 2025

Sepranolone – Initiation of clinical trial in PWS – Year-end 2025

Our Development Programs

Sepranolone Program

The GABAergic system is the primary inhibitory

neurotransmitter pathway.

It consists of two types of receptors, GABA A and GABAB.

GABA A receptors are a major target

for neuropsychiatric drugs, including benzodiazepines, barbituates and anesthetic agents.

The GABAergic system regulates a host of physiological

and neurological functions and their related moods and behaviors.

The principal positive physiologic modulators of the GABAergic system

are the neurotransmitter GABA (γ-aminobutyric acid) and the positive allosteric modulator Allopregnaolone.

GABA generally inhibits

nervous system excitability and thereby produces a calming effect that reduces anxiety and compulsive behavior, among other manifestations.

While Allopregnanolone typically enhances GABA’s calming effects, in some individuals it paradoxically exacerbates anxiety and compulsive

Sepranolone is a synthetic version of Isoallopregnanolone,

a naturally occurring neurosteroid that counteracts the effects of Allopregnanolone.

Sepranolone is designed to normalize GABA A receptor

activity by targeting two specific receptor subtypes (alpha-2 and alpha-4) without directly interfering with GABA signaling, making it

a novel and selective treatment approach for diseases such as PWS and TS and other disorders that feature compulsive behavior.

Data from an open-label Phase 2a randomized study

demonstrated that Sepranolone has the potential to improve TS symptoms versus standard of care alone, as measured by changes in the YGTSS

scoring system (the world-standard Yale Global Tic Severity Scale) compared to baseline.

In the 12-week, dual-center, parallel-group

study, 26 subjects were treated with Sepranolone (10 mg), administered by subcutaneous injection twice weekly in addition to standard

of care (SOC) versus standard of care alone.

The Phase 2a results showed competitive tic reduction

and improved quality of life while displaying no CNS off-target effects.

Sepranolone not only reduced tic severity in its primary clinical

endpoint as measured by YGTSS by 28% (p=0.051) – but also achieved positive results in four key secondary endpoints compared with

standard of care:

greater increase of Quality of Life (using the Gilles de la Tourette Syndrome Quality of

Life) total score (GTS-QOL)

greater reduction in impairment (YGTSS)

greater reduction of the premonitory urge to tic (PUTS – the Premonitory Urge to Tic

Importantly, no off-target CNS effects or systemic

side effects were observed in this study.

Further, Sepranolone has been evaluated in multiple clinical neuro/hormonal studies involving

over 335 participants and has demonstrated a favorable safety profile.

Relmada is currently evaluating the nonclinical

and clinical strategy for the development of Sepranolone.

NDV-01 Program

The second program we recently in-licensed, NDV-01,

is a novel intravesicular delivery technology designed for the long-acting, controlled release of gemcitabine and docetaxel.

This combination

therapy has gained significant interest as an alternative to Bacillus Calmette-Guérin (BCG) for treating NMIBC, especially given

the global BCG shortage since 2019.

Clinical studies have shown that gemcitabine and docetaxel achieve response rates and Recurrence-Free

Survival comparable to or better than BCG.

However, conventional administration is cumbersome, requiring sequential drug delivery over

three hours, with limited tumor exposure time.

NDV-01 potentially addresses these limitations

by enabling a single administration in approximately 10 minutes, delivering sustained, localized chemotherapy for up to 10 days.

extended exposure enhances the therapeutic effect while improving patient convenience.

NDV-01 is currently in a Phase 2 clinical trial

evaluating its safety and efficacy in patients with aggressive NMIBC.

NDV-01 is formulated as a controlled-release intravesical

therapy containing gemcitabine and docetaxel.

By maintaining continuous drug exposure within the bladder, NDV-01 may optimize local efficacy

while minimizing systemic absorption and associated side effects.

Unlike conventional intravesical instillations, which result in fluctuating

drug levels, NDV-01 provides a continuous release of both agents over 10 days.

This sustained delivery may improve cancer cell eradication

and reduce recurrence risk while lowering the frequency of administration.

Esmethadone (d-Methadone, dextromethadone, REL-1017) as a treatment

In 2021, the National Institute of Mental Health

(NIMH) estimated that 21.0 million adults aged 18 or older in the United States had at least one major depressive episode in the past

According to data from nationally representative surveys supported by NIMH, about 61% of adult Americans diagnosed with major depression

received treatment in 2021.

Of those receiving treatment with as many as four different standard antidepressants, 33% of drug-treated

depression patients do not achieve adequate therapeutic benefits according to the Sequenced Treatment Alternatives to Relieve Depression

(STAR*D) trial published in the American Journal of Psychiatry.

addition to the high failure rate, only two of the marketed products for depression, esketamine (marketed by Johnson and Johnson as Spravato®),

an in-clinic nasal spray treatment, and dextromethorphan-bupropion (marketed by Axsome as Auvelity ä ),

can demonstrate rapid antidepressant effects, while the other currently approved products can take two to eight weeks to show activity.

The urgent need for improved, faster acting antidepressant treatments is underscored by the fact that severe depression can be life-threatening,

due to heightened risk of suicide.

Esmethadone Overview and Mechanism of Action

Esmethadone’s mechanism of action, as a

1 unchanged sentence

as well as all atypical antipsychotics used adjunctively with standard, FDA-approved antidepressants.

Working through the same brain mechanisms

as ketamine and esketamine but potentially lacking their adverse side effects, esmethadone is being developed as a rapidly acting, oral

agent for the treatment of depression and potentially other CNS conditions.

In chemistry an enantiomer, also known as an optical

isomer, is one of two stereoisomers that are mirror images of each other that are non-superimposable (not identical), much as one’s

left and right hands are the same except for being reversed along one axis.

A racemic compound, or racemate, is one that has equal amounts

of left- and right-handed enantiomers of a chiral molecule.

For racemic drugs, often only one of a drug’s enantiomers is responsible

for the desired physiologic effects, while the other enantiomer is less active or inactive.

As a single isomer of racemic methadone, esmethadone

has been shown to possess NMDA antagonist properties with virtually no traditional opioid or ketamine-like adverse events at the expected

therapeutic doses.

In contrast, racemic methadone is associated with common opioid side effects that include anxiety, nervousness, restlessness,

sleep problems (insomnia), nausea, vomiting, constipation, diarrhea, drowsiness, and others.

It has been shown that the left (levo) isomer,

l-methadone, is largely responsible for methadone’s opioid activity, while the right (dextro) isomer, esmethadone, at the currently

therapeutic doses used in development is virtually inactive as an opioid while maintaining affinity for the NMDA receptor.

NMDA receptors are present in many parts of the

CNS and play important roles in regulating neuronal activity and promoting synaptic plasticity in brain areas important for cognitive

functions such as executive function, learning and memory.

Based on these premises, esmethadone could show benefits in several different

CNS indications.

Working through the same brain

mechanisms as ketamine and esketamine but potentially lacking their adverse side effects, esmethadone is being developed as a rapidly

acting, oral agent for the treatment of depression and potentially other CNS conditions.

Relmada has paused this program pending a comprehensive data review,

after which a decision regarding the future of this program will be made.

Esmethadone (d-methadone, dextromethadone, REL-1017) in other indications

While our current strategy is currently to focus

on the further development of esmethadone as an adjunctive treatment for MDD, we are evaluating other indications that Relmada may explore

in the future, including restless leg syndrome and other glutamatergic system activation related diseases.

While our strategy was to focus on the development of esmethadone as

an adjunctive treatment for MDD, we are also evaluating other indications that Relmada may explore in the future, including restless leg

syndrome and other glutamatergic system activation related diseases.

Psilocybin Program

10 unchanged sentences

on multiple metabolic parameters, including reduced hepatic steatosis, reduced body weight gain, and fasting blood glucose levels.

Relmada has paused this program in light of an

ongoing strategic review of this business opportunity, the changing regulatory landscape for psychedelics, its early stage of development

and the acquisition of new, more advanced product candidates.

Our Corporate History and Background

1 unchanged sentence

company developing NCEs and novel versions of drug products that potentially address areas of high unmet medical need in the treatment

of depression and other CNS diseases.

We are also developing a novel modified release formulation of psilocybin for the treatment of metabolic

Currently, none of our product candidates have

been approved for sale in the United States or elsewhere.

of cancer, neurological disorders, depression and other diseases.

Currently, none of our product candidates has been approved for sale

in the United States or elsewhere.

We have no commercial products, nor do we have a sales or marketing infrastructure.

In order to market and sell our products we must conduct clinical trials on patients and obtain regulatory approvals from appropriate

regulatory agencies, like the FDA in the United States, and similar organizations elsewhere in the world.

In order to market

and sell our products we must conduct clinical trials on patients and obtain regulatory approvals from appropriate regulatory agencies,

like the FDA in the United States, and similar organizations elsewhere in the world.

We have not generated revenues and do not anticipate

2 unchanged sentences

31, 2024 and 2023, respectively.

At December 31, 2023, we had an accumulated deficit of approximately $560,902,700.

As of December 31, 2024, we had an accumulated deficit of approximately $640,882,000.

Business Strategy

Our strategy is to leverage our considerable industry

experience, understanding of CNS markets and development expertise to identify, develop and commercialize product candidates with significant

market potential that can fulfill unmet medical needs in the treatment of CNS diseases.

We have assembled a management team along with

both scientific advisors, including recognized experts in the fields of depression, and business advisors with significant industry and

regulatory experience to lead and execute the development and commercialization of esmethadone.

We plan to further develop esmethadone as our

priority program.

As the drug esmethadone is an NCE, the regulatory pathway required to support a new drug application (NDA) submission

involves a full clinical development program.

We plan to continue to generate intellectual property (IP) that will further protect our

products from competition.

We will also continue to prioritize our product development activities after taking into account the resources

we have available, market dynamics and potential for adding value.

Market Opportunity

We believe that the market for addressing areas

of high unmet medical need in the treatment of CNS diseases will continue to be large for the foreseeable future and that it will represent

a sizable revenue opportunity for us.

For example, the World Health Organization (WHO) has estimated that CNS diseases affect nearly 2

billion people globally, making up approximately 40% of total disease burden (based on disability adjusted life years), compared with

13% for cancer and 12% for cardiovascular disease.

The depression treatment market is segmented on

the basis of antidepressants drugs, devices, and therapies.

Antidepressants are the largest and most popular market segment.

The antidepressants

segment consists of large pharmaceutical and generic companies, such as Eli Lilly, Pfizer, GlaxoSmithKline, Allergan, Sage Therapeutics

and Johnson & Johnson.

Some of the notable drugs produced by these companies are Cymbalta ® (Eli Lilly), Effexor ®

(Pfizer), Pristiq ® (Pfizer), ZURZUVANE TM (Sage), Spravato ® (Johnson & Johnson) and

Auvelity TM (Axsome).

Our strategy is to leverage our considerable

industry experience, understanding of pharmaceutical markets and development expertise to identify, develop and commercialize product

candidates with significant market potential that can fulfill unmet medical needs.

We have assembled a management team along with both

scientific advisors and business advisors with significant industry and regulatory experience to lead and execute the development and

commercialization of our product candidates.

Intellectual Property Portfolio and Market Exclusivity

We have over 50 issued patents and pending patent

applications related to REL-1017 for multiple uses, including psychological and neurological conditions, potentially provide coverage

We have also secured an Orphan Drug Designation from the FDA for d-methadone for “the treatment of postherpetic neuralgia”

(postherpetic neuralgia is lasting pain in areas of skin affected by previous outbreaks of shingles, caused by the varicella-zoster, or

herpes zoster, virus) which, upon potential NDA approval, carries 7-year FDA Orphan Drug marketing exclusivity.

We have more than 40 issued patents and pending

patent applications related to Sepranolone for multiple uses, including diseases and disorders exhibiting compulsive behaviors such as

PWS, TS, obsessive-compulsive disorder, and gambling disorder, potentially providing coverage beyond 2030.

We have more than 10 issued patents and pending

patent applications related to NDV-01 for multiple uses, including formulations and methods for controlled release of therapeutics for

treatment of diseases such as bladder cancer, potentially providing coverage beyond 2038.

We have more than 50 issued patents and pending

patent applications related to REL-1017 for multiple uses, including psychological and neurological conditions, potentially providing

coverage beyond 2033.

We have also secured an Orphan Drug Designation from the FDA for d-methadone for “the treatment of postherpetic

neuralgia” (postherpetic neuralgia is lasting pain in areas of skin affected by previous outbreaks of shingles, caused by the varicella-zoster,

or herpes zoster, virus) which, upon potential NDA approval, carries 7-year FDA Orphan Drug marketing exclusivity.

In the European Union,

5 unchanged sentences

and up to 10 years of exclusivity in the European Union.

We believe an extensive intellectual property estate of US and foreign patents

and applications, once approved, will protect our technology and products.

We believe an extensive intellectual property

estate of US and foreign patents and applications, once approved, will protect our technology and products.

Esmethadone License Agreement

12 unchanged sentences

any revenue related to this license agreement.

Sepranolone Acquisition

On February 3, 2025, we entered into an Asset

Purchase Agreement with Asarina, a Swedish corporation, pursuant to which we purchased, subject to the terms and conditions set forth

therein, from Asarina all right, title, and interest in Sepranolone.

The total purchase price was €3,000,000.

The Company paid Asarina

$2,756,000 on February 5, 2025, which includes a credit of $250,000 for a previous payment made by the Company to Asarina pursuant to

an exclusivity agreement in October 2024.

We will only assume liabilities arising after

the effective date of the Purchase Agreement.

All other liabilities, including those arising before the effective date of the Purchase

Agreement, taxes, employment-related liabilities, and those related to the negotiation and consummation of the Purchase Agreement, will

remain with Asarina.

NDV-01 In-License Agreement

On March 24, 2025, we entered into an Exclusive

License Agreement with Trigone, an Israeli company.

The license agreement is for Trigone’s NDV-01 product, which is a novel, sustained-release,

intravesical gemcitabine/docetaxel, ready-for-use product candidate for the treatment of NMIBC.

Under the terms of the agreement, the

Company made a $3,500,000 upfront payment on March 25, 2025, and issued 3,017,420 shares of common stock, which represent 10% of the Company’s

outstanding shares, for exclusive worldwide rights to NDV-01, excluding Israel, India and South Africa.

In addition, the Company will pay up to $200 million

in development, regulatory and sales milestones pending successful commercialization.

The Company will also pay a royalty of 3% on any

Following the completion of the ongoing Phase 2 study, the Company will assume responsibility for NDV-01’s development,

manufacturing and commercialization.

Inturrisi / Manfredi

In January 2018, we entered into an Intellectual

Property Assignment Agreement (the Assignment Agreement) and License Agreement (the License Agreement and together with the Assignment

Agreement, the Agreements) with Dr.

In January 2018, the Company entered into an

Intellectual Property Assignment Agreement (the Assignment Agreement) and License Agreement (the License Agreement and together with

the Assignment Agreement, the Agreements) with Dr.

Inturrisi and Dr.

Paolo Manfredi (collectively, the Licensor).

Pursuant to the Agreements,

Relmada assigned its existing rights, including patents and patent applications, to esmethadone in the context of psychiatric use (the

Existing Invention) to Licensor.

Licensor then granted Relmada under the License Agreement a perpetual, worldwide, and exclusive license

to commercialize the Existing Invention and certain further inventions regarding esmethadone.

In consideration of the rights granted to

Relmada under the License Agreement, Relmada paid the Licensor an upfront, non-refundable license fee of $180,000.

Additionally, Relmada

will pay Licensor $45,000 every three months until the earliest to occur of the following events:

(i) the first commercial sale of a licensed

product anywhere in the world, (ii) the expiration or invalidation of the last to expire or be invalidated of the patent rights anywhere

in the world, or (iii) the termination of the License Agreement.

Relmada will also pay Licensor tiered royalties with a maximum rate of

2%, decreasing to 1.75%, and 1.5% in certain circumstances, on net sales of licensed products covered under the License Agreement.

will also pay Licensor tiered payments up to a maximum of 20%, and decreasing to 17.5%, and 15% in certain circumstances, of all consideration

received by Relmada for sublicenses granted under the License Agreement.

As of December 31, 2023, no events have occurred, and the Company

continues to pay Licensor $45,000 every three months.

to the Agreements, Relmada assigned its existing rights, including patents and patent applications, to esmethadone in the context of

psychiatric use (the Existing Invention) to Licensor.

Licensor then granted Relmada under the License Agreement a perpetual, worldwide,

and exclusive license to commercialize the Existing Invention and certain further inventions regarding esmethadone, in the context of

other indications such as those contemplated above.

In consideration of the rights granted to Relmada under the License Agreement, Relmada

paid the Licensor an upfront, non-refundable license fee of $180,000.

Additionally, Relmada will pay Licensor $45,000 every three months

until the earliest to occur of the following events:

(i) the first commercial sale of a licensed product anywhere in the world, (ii)

the expiration or invalidation of the last to expire or be invalidated of the patent rights anywhere in the world, or (iii) the termination

of the License Agreement.

Relmada will also pay Licensor tiered royalties with a maximum rate of 2%, decreasing to 1.75%, and 1.5% in

certain circumstances, on net sales of licensed products covered under the License Agreement.

Relmada will also pay Licensor tiered payments

up to a maximum of 20%, and decreasing to 17.5%, and 15% in certain circumstances, of all consideration received by Relmada for sublicenses

granted under the License Agreement.

As of December 31, 2024, no events have occurred, and the Company continues to pay Licensor $45,000

every three months.

The License Agreement includes standard termination

rights for Licensor in the event of our insolvency, challenge of the licensed patents and uncured material breach of our obligations under

the License Agreement.

In addition, the License Agreement contains certain “Key Man” provisions such that Licensor may terminate

the License Agreement if we terminate the employment of our Chief Executive Officer, Dr Sergio Traversa, for any reason other than for

specified causes determined by a majority of our Board of Directors (including fraud, gross negligence, unauthorized use of our confidential

information, conduct including harassment or discrimination, breach of fiduciary duty or uncured material breach), or if we (a) substantially

Traversa’s job responsibilities or decision-making rights in connection with the development and commercialization of

esmethadone, (b) remove him from the role of Chief Executive Officer other than in connection with a permitted change-of-control transaction,

(c) materially reduce his compensation, or (d) assign or transfer our rights under the License Agreement or the esmethadone intellectual

property without Dr.

Traversa’s consent, in each case (termination or the events in (a) through (d)) during the period commencing

on the effective date and ending on the later of five years from the original effective date of the License Agreement or December 31,

The December 2019 amendment to the License Agreement made certain clarifications to the nature of a termination for Cause, including

to clarify that termination due to Dr.

Traversa’s death or disability does not give Licensor the right to terminate the License

On December 27, 2022, the Licensor and the Company entered into a new amendment extending the “Key Man” provision

period until December 31, 2027.

rights for Licensor in the event of our insolvency, challenge of the licensed patents and uncured material breach of our obligations

under the License Agreement.

In addition, the License Agreement contains certain “Key Man” provisions such that Licensor

may terminate the License Agreement if we terminate the employment of our Chief Executive Officer, Dr Sergio Traversa, for any reason

other than for specified causes determined by a majority of our Board of Directors (including fraud, gross negligence, unauthorized use

of our confidential information, conduct including harassment or discrimination, breach of fiduciary duty or uncured material breach),

or if we (a) substantially modify Dr.

Traversa’s job responsibilities or decision-making rights in connection with the development

and commercialization of esmethadone, (b) remove him from the role of Chief Executive Officer other than in connection with a permitted

change-of-control transaction, (c) materially reduce his compensation, or (d) assign or transfer our rights under the License Agreement

or the esmethadone intellectual property without Dr.

Traversa’s consent, in each case (termination or the events in (a) through

(d)) during the period commencing on the effective date and ending on the later of five years from the original effective date of the

License Agreement or December 31, 2022.

The December 2019 amendment to the License Agreement made certain clarifications to the nature

of a termination for Cause, including to clarify that termination due to Dr.

Traversa’s death or disability does not give Licensor

the right to terminate the License Agreement.

On December 27, 2022, the Licensor and the Company entered into a new amendment extending

the “Key Man” provision period until December 31, 2027.

The License Agreement was not otherwise modified.

Wonpung License Agreement

In 2007, the Company entered into a License Development and Commercialization

Agreement with Wonpung Mulsan Co, a shareholder of the Company.

Wonpung has exclusive territorial rights in countries it selects in Asia

to market up to two drugs the Company is currently developing and a right of first refusal (ROFR) for up to an additional five drugs that

the Company may develop in the future as defined in more detail in the license agreement.

If the parties cannot agree to terms of a license

agreement then the Company shall be able to engage in discussions with other potential licensors.

As of March 19, 2024, no discussions

are active between the Company and Wonpung.

The Company received an upfront license fee of

$1,500,000 and will earn royalties of up to 12% of net sales for up to two licensed products it is currently developing.

The licensing

terms for the ROFR products are subject to future negotiations and binding arbitration.

The terms of each licensing agreement will expire

on the earlier of any time from 15 years to 20 years after licensing or on the date of commercial availability of a generic product to

such licensed product in the licensed territory.

Psilocybin License Agreement

In July 2021, we executed a License Agreement

with Arbormentis, LLC which gives us the development and commercial rights to a novel psilocybin and derivate program.

Under the terms

of the agreement, we paid Arbormentis, LLC an up-front fee of $12.7 million consisting of a mix of cash and warrants to purchase the Company’s

common stock, in addition to potential milestone payments totaling up to approximately $160 million related to pre-specified development

and commercialization milestones.

Arbormentis, LLC is also eligible to receive a low single digit percentage royalty on net sales of any

commercialized therapy resulting from this agreement.

The license agreement is terminable by us but is perpetual and not terminable by

the licensor absent material breach of its terms by us.

We will collaborate with Arbormentis, LLC on the development of new therapies

targeting neurological, psychiatric and metabolic disorders.

We will leverage Arbormentis’ understanding of neuroplasticity, and

focusing on this emerging new class of drugs targeting the neuroplastogen mechanism of action.

Importantly, neuroplasticity also plays

a key role in the activity of REL-1017, Relmada’s lead program.

Paolo Manfredi, our Acting Chief Scientific Officer and

co-inventor of REL-1017, and Dr.

Marco Pappagallo, Safety/Adjudication Officer, are among the scientists affiliated with Arbormentis,

On July 16, 2021, the Company entered into a

License Agreement with Arbormentis, LLC, a privately held Delaware limited liability company, by which the Company acquired development

and commercial rights to a novel psilocybin and derivate program from Arbormentis, LLC, worldwide excluding the countries of Asia.

Company will collaborate with Arbormentis, LLC on the development of new therapies targeting neurological and psychiatric disorders,

leveraging Arbormentis’ understanding of neuroplasticity, and focusing on this emerging new class of drugs targeting the neuroplastogen

mechanism of action.

Under the terms of the License Agreement, the Company paid Arbormentis, LLC an up-front fee of $12.7 million, consisting

of a mix of cash and warrants to purchase the Company’s common stock, in addition to potential milestone payments totaling up to

approximately $160 million related to pre-specified development and commercialization milestones.

Arbormentis, LLC is also eligible to

receive a low single digit percentage royalty on net sales of any commercialized therapy resulting from this agreement.

The license agreement

is terminable by the Company but is perpetual and not terminable by the licensor absent material breach of its terms by us.

Key Strengths

We believe that the key elements for our market success include:

Compelling lead product opportunity, REL-1017 currently in two Phase 3 trials for the adjunctive treatment of MDD (RELIANCE II and RELIGHT) that build on the knowledge gleaned from RELIANCE I, which did not meet its primary endpoint.

Robust and highly statistically significant, efficacy seen with esmethadone in a randomized Phase 2 trial with the primary endpoint at 7 days, with onset of action seen at 4 days, and the effect carrying through to 14 days (7 days post treatment).

Successful Phase 1 safety studies of esmethadone and strong clinical activity signal in depression established in three independent animal models in preclinical studies.

Potential in additional multiple indications in underserved markets with large patient population in other affective disorders, and cognitive disorders.

Substantial esmethadone IP portfolio and market protection:

approved and filed patent applications provide coverage beyond 2033.

Portfolio diversification with the development of a novel psilocybin (REL-P11) for the treatment of metabolic indications.

This program is expected to enter human studies, to define its pharmacokinetic, safety and tolerability profile, in first half of 2024.

support of leading experts:

Our scientific advisors include clinicians and scientists who are affiliated with a number of highly regarded

medical institutions such as Harvard, Cornell, Yale, and University of Pennsylvania.

Compelling lead product opportunities in NDV-01 and Sepranolone

Experienced management team with considerable drug development expertise

Multiple potential bladder cancer related indications for NDV-01

Extensive safety database for Sepranolone as well as promising signal of efficacy in Tourette Syndrome

Substantial and growing IP portfolio for both Sepranolone and NDV-01

Scientific support of leading experts:

Our scientific advisors include clinicians and scientists who are affiliated with a number of highly regarded medical institutions.

The pharmaceutical and biotechnology industry

7 unchanged sentences

to develop new or improved products that may compete with our products.

Our products could be rendered obsolete or made uneconomical by

the development of new products.

Our products could be rendered obsolete or made uneconomical

by the development of new products.

Regarding our competitive position in the industry,

1 unchanged sentence

Government Regulation

Government authorities in the United States, at

the federal, state and local level, and in other countries and jurisdictions extensively regulate, among other things, the research, development,

testing, manufacture, quality control, approval, packaging, storage, recordkeeping, labeling, advertising, promotion, distribution, marketing,

post-approval monitoring and reporting, and import and export of pharmaceutical products.

The processes for obtaining regulatory approvals

in the United States and in foreign countries and jurisdictions, along with subsequent compliance with applicable statutes and regulations

and other regulatory authorities, require the expenditure of substantial time and financial resources.

Government authorities in the United States,

at the federal, state and local level, and in other countries and jurisdictions extensively regulate, among other things, the research,

development, testing, manufacture, quality control, approval, packaging, storage, recordkeeping, labeling, advertising, promotion, distribution,

marketing, post-approval monitoring and reporting, and import and export of pharmaceutical products.

The processes for obtaining regulatory

approvals in the United States and in foreign countries and jurisdictions, along with subsequent compliance with applicable statutes

and regulations and other regulatory authorities, require the expenditure of substantial time and financial resources.

FDA Approval Process

5 unchanged sentences

Failure to comply with applicable U.S.

requirements may subject a company to a variety of administrative or judicial sanctions, such as

FDA refusal to approve pending NDAs, warning or untitled letters, product recalls, product seizures, total or partial suspension of production

or distribution, injunctions, fines, civil penalties and criminal prosecution.

Pharmaceutical product development for a new product

or certain changes to an approved product in the U.S.

typically involves preclinical laboratory and animal tests, the submission to FDA

of an investigational new drug application (IND) which must become effective before clinical testing may commence, and adequate and well-controlled

clinical trials to establish the safety and effectiveness of the drug for each indication for which FDA approval is sought.

of FDA pre-market approval requirements typically takes many years and the actual time required may vary substantially based upon the

type, complexity and novelty of the product or disease.

Preclinical tests include laboratory evaluation

requirements may subject a company to a variety of administrative or judicial sanctions, such

as FDA refusal to approve pending NDAs, warning or untitled letters, product recalls, product seizures, total or partial suspension of

production or distribution, injunctions, fines, civil penalties and criminal prosecution.

Pharmaceutical product development for a new

product or certain changes to an approved product in the U.S.

typically involves nonclinical laboratory and animal tests, the submission

to FDA of an investigational new drug application (IND) which must become effective before clinical testing may commence, and adequate

and well-controlled clinical trials to establish the safety and effectiveness of the drug for each indication for which FDA approval

Satisfaction of FDA pre-market approval requirements typically takes many years and the actual time required may vary substantially

based upon the type, complexity and novelty of the product or disease.

Nonclinical tests include laboratory evaluation

of product chemistry, formulation and toxicity, as well as animal trials to assess the characteristics and potential safety and efficacy

of the product.

The conduct of the preclinical tests must comply with federal regulations and requirements, including good laboratory

The results of preclinical testing are submitted to FDA as part of an IND along with other information, including information

The conduct of the nonclinical tests must comply with federal regulations and requirements, including good laboratory

The results of nonclinical testing are submitted to FDA as part of an IND along with other information, including information

about product chemistry, manufacturing and controls, and a proposed clinical trial protocol.

Long-term preclinical tests, such as animal

Long-term nonclinical tests, such as animal

tests of reproductive toxicity and carcinogenicity, may continue after the IND is submitted.

1 unchanged sentence

of each IND is required prior to the commencement of clinical testing in humans.

If FDA has neither commented on nor questioned the IND

within this 30-day period, the clinical trial proposed in the IND may begin.

Clinical trials involve the administration of the investigational

new drug to healthy volunteers or patients under the supervision of a qualified investigator.

During this period, if FDA concludes that a deficiency

exists in a clinical investigation that may be grounds for the imposition of clinical hold, FDA will usually attempt to discuss and satisfactorily

resolve the matter with the IND applicant.

If such resolution is not possible, FDA may issue a clinical hold order by telephone or other

means of rapid communication or in writing.

No more than 30 days after imposition of the clinical hold, a written explanation of the

basis for the hold will be issued by FDA and sent to the applicant.

The applicant must respond in writing to each deficiency before the

clinical hold can be lifted.

If FDA has neither commented on nor questioned the IND within this 30-day period, the clinical trial proposed

in the IND may begin.

Clinical trials involve the administration of the investigational new drug to healthy volunteers or patients under

the supervision of a qualified investigator.

Clinical trials must be conducted:

in compliance with federal regulations;

(ii) in compliance with good clinical practice, or GCP, an international standard meant to protect

the rights and health of patients and to define the roles of clinical trial sponsors, administrators and monitors;

as well as (iii) under

protocols detailing the objectives of the trial, the parameters to be used in monitoring safety and the effectiveness criteria to be

(i) in compliance with federal regulations;

(ii) in compliance

with good clinical practice, or GCP, an international standard meant to protect the rights and health of patients and to define the roles

of clinical trial sponsors, administrators and monitors;

as well as (iii) under protocols detailing the objectives of the trial, the

parameters to be used in monitoring safety and the effectiveness criteria to be evaluated.

Each protocol involving testing on U.S.

patients and subsequent protocol amendments must be submitted to FDA as part of the

and subsequent protocol amendments must be submitted to FDA as part of the IND.

FDA may not permit a clinical trial to begin,

or may order the temporary, or permanent, discontinuation of a clinical trial at any time, or impose other sanctions, if it believes that

the clinical trial either is not being conducted in accordance with FDA requirements or presents an unacceptable risk to the clinical

or may order the temporary, or permanent, discontinuation of a clinical trial at any time, or impose other sanctions, if it believes

that the clinical trial either is not being conducted in accordance with FDA requirements or presents an unacceptable risk to the clinical

trial patients.

5 unchanged sentences

approval are typically conducted in three sequential phases, but the phases may overlap.

In Phase 1, the initial introduction of the drug

into healthy human subjects or patients, the drug is tested to assess metabolism, pharmacokinetics, pharmacological actions, side effects

associated with increasing doses, and, if possible, early evidence of effectiveness.

Phase 2 usually involves trials in a limited patient

population to determine the effectiveness of the drug for a particular indication, dosage tolerance and optimum dosage, and to identify

common adverse effects and safety risks.

If a drug demonstrates evidence of effectiveness and an acceptable safety profile in Phase 2

evaluations, Phase 3 trials are undertaken to obtain the additional information about clinical efficacy and safety in a larger number

of patients, typically at geographically dispersed clinical trial sites, to permit FDA to evaluate the overall benefit-risk relationship

In Phase 1, the initial introduction of the

drug into healthy human subjects or patients, the drug is tested to assess metabolism, pharmacokinetics, pharmacological actions, side

effects associated with increasing doses, and, if possible, early evidence of effectiveness.

Phase 2 usually involves trials in a limited

patient population to determine the effectiveness of the drug for a particular indication, dosage tolerance and optimum dosage, and to

identify common adverse effects and safety risks.

If a drug demonstrates evidence of effectiveness and an acceptable safety profile in

Phase 2 evaluations, Phase 3 trials are undertaken to obtain the additional information about clinical efficacy and safety in a larger

number of patients, typically at geographically dispersed clinical trial sites, to permit FDA to evaluate the overall benefit-risk relationship

of the drug and to provide adequate information for the labeling of the drug.

9 unchanged sentences

FDA approval of the NDA is required before marketing of the product may begin in the U.S.

NDA must include the results of all preclinical, clinical and other testing and a compilation of data relating to the product’s

NDA must include the results of all nonclinical, clinical and other testing and a compilation of data relating to the product’s

pharmacology, chemistry, manufacture and controls.

7 unchanged sentences

FDA has 60 days from its receipt of an NDA to

determine whether the application will be accepted for filing based on the agency’s threshold determination that it is sufficiently

complete to permit substantive review.

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

FDA has agreed to certain

performance goals in the review of NDAs to encourage timeliness.

Applications for most standard review drug products are reviewed within

twelve months from submission of NDAs for new molecular entities (NMEs) and ten months from submission of NDAs for non-NMEs.

review can be applied to drugs that FDA determines offer major advances in treatment or provide a treatment where no adequate therapy

The review process for both standard and priority review may be extended by FDA for three additional months to consider certain

late-submitted information or information intended to clarify information already provided in the submission.

determine whether the application will be filed based on the agency’s threshold determination that it is sufficiently complete

to permit substantive review.

Once the submission is filed, FDA begins an in-depth review.

FDA has agreed to certain performance goals

in the review of NDAs to encourage timeliness.

Applications for most standard review drug products are reviewed within twelve months

from submission of NDAs for new molecular entities (NMEs) and ten months from submission of NDAs for non-NMEs.

Priority review can be

applied to drugs that FDA determines offer major advances in treatment or provide a treatment where no adequate therapy exists.

process for both standard and priority review may be extended by FDA for three additional months to consider certain late-submitted information

or information intended to clarify information already provided in the submission.

FDA may also refer applications for novel drug

products, or drug products that present difficult questions of safety or efficacy, to an outside advisory committee – typically

a panel that includes clinicians and other experts – for review, evaluation and a recommendation as to whether the application should

a panel that includes clinicians and other experts – for review, evaluation and a recommendation as to whether the application

should be approved.

FDA is not bound by the recommendation of an advisory committee, but it generally follows such recommendations.

1 unchanged sentence

one or more clinical sites to assure compliance with GCP.

Additionally, FDA will inspect the facility or the facilities at which the drug

is manufactured.

Additionally, FDA will inspect the facility or the facilities at which the

drug is manufactured.

FDA will not approve the product unless compliance with current good manufacturing practices (cGMPs) is satisfactory

4 unchanged sentences

in the submission and may require substantial additional testing, or information, in order for FDA to reconsider the application.

or when, those deficiencies have been addressed to FDA’s satisfaction in a resubmission of the NDA, FDA will issue an approval letter.

or when, those deficiencies have been addressed to FDA’s satisfaction in a resubmission of the NDA, FDA will issue an approval

FDA has committed to reviewing such resubmissions in two or six months depending on the type of information included.

An approval letter

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

As a condition of NDA approval,

FDA may require a risk evaluation and mitigation strategy (REMS) to help ensure that the benefits of the drug outweigh the potential risks.

REMS can include medication guides, communication plans for healthcare professionals, and elements to assure safe use (ETASU).

include, but are not limited to, special training or certification for prescribing or dispensing, dispensing only under certain circumstances,

special monitoring and the use of patient registries.

The requirement for a REMS can materially affect the potential market and profitability

Moreover, product approval may require substantial post-approval testing and surveillance to monitor the drug’s safety

Once granted, product approvals may be withdrawn if compliance with regulatory standards is not maintained or problems are

identified following initial marketing.

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

As a condition of

NDA approval, FDA may require a risk evaluation and mitigation strategy (REMS) to help ensure that the benefits of the drug outweigh

the potential risks.

REMS can include medication guides, communication plans for healthcare professionals, and elements to assure safe

ETASU can include, but are not limited to, special training or certification for prescribing or dispensing, dispensing only

under certain circumstances, special monitoring and the use of patient registries.

The requirement for a REMS can materially affect the

potential market and profitability of the drug.

Moreover, product approval may require substantial post-approval testing and surveillance

to monitor the drug’s safety or efficacy.

Once granted, product approvals may be withdrawn if compliance with regulatory standards

is not maintained or problems are identified following initial marketing.

Changes to some of the conditions established

in an approved application, including changes in indications, labeling, or manufacturing processes or facilities, require submission and

FDA approval of a new NDA or NDA supplement before the change can be implemented.

An NDA supplement for a new indication typically requires

clinical data similar to that in the original application, and FDA uses the same procedures and actions in reviewing NDA supplements as

it does in reviewing NDAs.

in an approved application, including changes in indications, labeling, or manufacturing processes or facilities, require submission

and FDA approval of a new NDA or NDA supplement before the change can be implemented.

An NDA supplement for a new indication typically

requires clinical data similar to that in the original application, and FDA uses the same procedures and actions in reviewing NDA supplements

as it does in reviewing NDAs.

Fast Track Designation

2 unchanged sentences

there is no effective treatment and which demonstrate the potential to address unmet medical needs for the condition.

Under the Fast Track

program, the sponsor of a new drug candidate may request that FDA designate the drug candidate for a specific indication as a Fast Track

drug concurrent with, or after, the submission of the IND for the drug candidate.

FDA must determine if the drug candidate qualifies for

Fast Track Designation within 60 days of receipt of the sponsor’s request.

Under the Fast

Track program, the sponsor of a new drug candidate may request that FDA designate the drug candidate for a specific indication as a Fast

Track drug concurrent with, or after, the submission of the IND for the drug candidate.

FDA must determine if the drug candidate qualifies

for Fast Track Designation within 60 days of receipt of the sponsor’s request.

If a submission is granted Fast Track Designation,

2 unchanged sentences

and the applicant pays applicable user fees.

However, FDA’s time period goal for reviewing an application does not begin until the

last section of the NDA is submitted.

However, FDA’s time period goal for reviewing an application does not begin until

the last section of the NDA is submitted.

Additionally, Fast Track Designation may be withdrawn by FDA if FDA believes that the designation

6 unchanged sentences

the generic identity of the drug and its potential orphan use are disclosed publicly by FDA.

Orphan Drug Designation does not convey any

advantage in, or shorten the duration of, the regulatory review and approval process.

Orphan Drug Designation does not convey

any advantage in, or shorten the duration of, the regulatory review and approval process.

The first NDA applicant to receive FDA approval

10 unchanged sentences

Disclosure of Clinical Trial Information

Sponsors of clinical trials of FDA regulated products,

including drugs, are required to register and disclose certain clinical trial information.

Information related to the product, patient

population, phase of investigation, study sites and investigators, and other aspects of the clinical trial is then made public as part

of the registration.

Sponsors of clinical trials of FDA regulated

products, including drugs, are required to register and disclose certain clinical trial information.

Information related to the product,

patient population, phase of investigation, study sites and investigators, and other aspects of the clinical trial is then made public

as part of the registration.

Sponsors are also obligated to discuss the results of their clinical trials after completion.

Disclosure of the results

of these trials can be delayed in certain circumstances for up to two years after the date of completion of the trial.

Competitors may

use this publicly available information to gain knowledge regarding the progress of development programs.

of the results of these trials can be delayed in certain circumstances for up to two years after the date of completion of the trial.

Competitors may use this publicly available information to gain knowledge regarding the progress of development programs.

Pediatric Information

25 unchanged sentences

or use of the product.

In addition, quality control, drug manufacture, packaging and labeling procedures must continue to conform to cGMPs

after approval.

Drug manufacturers and certain of their subcontractors are required to register their establishments with FDA and certain

state agencies.

Registration with FDA subjects entities to periodic unannounced inspections by FDA, during which the Agency inspects manufacturing

facilities to assess compliance with cGMPs.

Accordingly, manufacturers must continue to expend time, money and effort in the areas of

production and quality-control to maintain compliance with cGMPs.

Regulatory authorities may withdraw product approvals or request product

recalls if a company fails to comply with regulatory standards, if it encounters problems following initial marketing, or if previously

unrecognized problems are subsequently discovered.

In addition, quality control, drug manufacture, packaging and labeling procedures must continue to conform to

cGMPs after approval.

Drug manufacturers and certain of their subcontractors are required to register their establishments with FDA and

certain state agencies.

Registration with FDA subjects entities to periodic unannounced inspections by FDA, during which the Agency inspects

manufacturing facilities to assess compliance with cGMPs.

Accordingly, manufacturers must continue to expend time, money and effort in

the areas of production and quality-control to maintain compliance with cGMPs.

Regulatory authorities may withdraw product approvals

or request product recalls if a company fails to comply with regulatory standards, if it encounters problems following initial marketing,

or if previously unrecognized problems are subsequently discovered.

FDA strictly regulates marketing, labeling, advertising

18 unchanged sentences

Other than the requirement for bioequivalence testing, ANDA applicants are not required to conduct, or

submit results of, preclinical or clinical tests to prove the safety or effectiveness of their drug product.

submit results of, nonclinical or clinical tests to prove the safety or effectiveness of their drug product.

Drugs approved in this way

1 unchanged sentence

written for the original listed drug.

The ANDA applicant is required to certify to the

FDA concerning any patents listed for the approved product in the FDA’s Orange Book.

Specifically, the applicant must certify that

(i) the required patent information has not been filed;

The ANDA applicant is required to certify to

the FDA concerning any patents listed for the approved product in the FDA’s Orange Book.

Specifically, the applicant must certify

that (i) the required patent information has not been filed;

(ii) the listed patent has expired;

(iii) the listed patent has

not expired but will expire on a particular date and approval is sought after patent expiration;

or (iv) the listed patent is invalid

or will not be infringed by the new product (a Paragraph IV certification).

The ANDA applicant may also elect to submit a section viii

statement certifying that its proposed ANDA label does not contain (or carve out) any language regarding the patented method-of-use rather

than certify to a listed method-of-use patent.

If the applicant does not challenge the listed patents or certifies that the listed patents

will not be infringed by the new product, the ANDA application will not be approved until all the listed patents claiming the referenced

product have expired.

If the ANDA applicant has provided a Paragraph IV certification, the NDA and patent holders may then initiate a

patent infringement lawsuit in response.

The filing of a patent infringement lawsuit within 45 days of the receipt of a such certification

automatically prevents the FDA from approving the ANDA until the earlier of 30 months, expiration of the patent, settlement of the lawsuit,

or a decision in the infringement case that is favorable to the ANDA applicant.

Upon NDA approval of a NCE such as esmethadone,

which is a drug that contains no active moiety that has been approved by FDA in any other NDA, that drug receives five years of marketing

exclusivity during which FDA cannot receive any ANDA seeking approval of a generic version of that drug.

An ANDA may be submitted one

year before NCE exclusivity expires if a Paragraph IV certification is filed.

If there is no listed patent in the Orange Book, there may

not be a Paragraph IV certification, and, thus, no ANDA may be filed before the expiration of the exclusivity period.

Certain changes

to a drug, such as the addition of a new indication to the package insert, can be the subject of a three-year period of exclusivity if

the application contains reports of new clinical investigations (other than bioavailability studies) conducted or sponsored by the sponsor

that were essential to approval of the application.

FDA cannot approve an ANDA for a generic drug that includes the change during the

period of exclusivity.

In the case of a non-racemic drug containing as

an active ingredient a single enantiomer that is contained in a racemic drug approved in another NDA, the applicant for the non-racemic

drug may elect, in the NDA, to have the single enantiomer not be considered the same active ingredient as that contained in the approved

racemic drug and therefore eligible for NCE exclusivity, if certain conditions are met.

(iii) the listed patent

has not expired but will expire on a particular date and approval is sought after patent expiration;

or (iv) the listed patent is

invalid or will not be infringed by the new product (a Paragraph IV certification).

The ANDA applicant may also elect to submit a section

viii statement certifying that its proposed ANDA label does not contain (or carve out) any language regarding the patented method-of-use

rather than certify to a listed method-of-use patent.

If the applicant does not challenge the listed patents or certifies that the listed

patents will not be infringed by the new product, the ANDA application will not be approved until all the listed patents claiming the

referenced product have expired.

If the ANDA applicant has provided a Paragraph IV certification, the NDA and patent holders may then

initiate a patent infringement lawsuit in response.

The filing of a patent infringement lawsuit within 45 days of the receipt of a such

certification automatically prevents the FDA from approving the ANDA until the earlier of 30 months, expiration of the patent, settlement

of the lawsuit, or a decision in the infringement case that is favorable to the ANDA applicant.

Upon NDA approval of an NCE, which is a drug

that contains no active moiety that has been approved by FDA in any other NDA, that drug receives five years of marketing exclusivity

during which FDA cannot receive any ANDA seeking approval of a generic version of that drug.

An ANDA may be submitted one year before

NCE exclusivity expires if a Paragraph IV certification is filed.

If there is no listed patent in the Orange Book, there may not be a

Paragraph IV certification, and, thus, no ANDA may be filed before the expiration of the exclusivity period.

Certain changes to a drug,

such as the addition of a new indication to the package insert, can be the subject of a three-year period of exclusivity if the application

contains reports of new clinical investigations (other than bioavailability studies) conducted or sponsored by the sponsor that were

essential to approval of the application.

FDA cannot approve an ANDA for a generic drug that includes the change during the period of

In the case of a non-racemic drug containing

as an active ingredient a single enantiomer that is contained in a racemic drug approved in another NDA, such as esmethadone, the applicant

for the non-racemic drug may elect, in the NDA, to have the single enantiomer not be considered the same active ingredient as that contained

in the approved racemic drug and therefore eligible for NCE exclusivity, if certain conditions are met.

These conditions include:

(1) the single enantiomer

has not been previously approved except in the approved racemic drug, (2) the NDA for the non-racemic drug includes full reports of new

clinical investigations necessary for the approval of the product conducted or sponsored by the applicant and not submitted for approval

of the racemic drug, and (3) the NDA for the non-racemic drug is not submitted for approval of a condition of use in a therapeutic category

in which the approved racemic drug has been approved or for which any other enantiomer of the racemic drug has been approved.

FDA will not approve the non-racemic drug for any condition of use in the therapeutic category in which the racemic drug has been approved

for a period of 10 years after approval of the racemic drug, and the labeling of the non-racemic drug will include a statement in the

indication that the non-racemic drug is not approved, and has not been shown to be safe and effective, for any condition of use of the

racemic drug.

The applicant for the non-racemic drug may make this election only in an application submitted before October 1, 2027.

the single enantiomer has not been previously approved except in the approved racemic drug, (2) the NDA for the non-racemic drug includes

full reports of new clinical investigations necessary for the approval of the product conducted or sponsored by the applicant and not

submitted for approval of the racemic drug, and (3) the NDA for the non-racemic drug is not submitted for approval of a condition of

use in a therapeutic category in which the approved racemic drug has been approved or for which any other enantiomer of the racemic drug

has been approved.

In addition, FDA will not approve the non-racemic drug for any condition of use in the therapeutic category in which

the racemic drug has been approved for a period of 10 years after approval of the racemic drug, and the labeling of the non-racemic drug

will include a statement in the indication that the non-racemic drug is not approved, and has not been shown to be safe and effective,

for any condition of use of the racemic drug.

The applicant for the non-racemic drug may make this election only in an application submitted

before October 1, 2027.

Patent Term Extension

17 unchanged sentences

Controlled Substances

The active ingredients in esmethadone are regulated as controlled substances

pursuant to the Comprehensive Drug Abuse Prevention and Control Act of 1970 (CSA) and regulations promulgated by the United States Drug

Enforcement Administration (DEA).

The CSA and its implementing regulations establish a closed chain of distribution for entities handling

controlled substances.

The DEA is responsible for enforcing the law and regulations that impose registration, security, inventory, recordkeeping,

reporting and storage requirements on entities that manufacture, distribute, import and export, prescribe, dispense or otherwise physically

handle controlled substances.

The law and regulations require those individuals or entities that handle controlled substances to comply

with these requirements in order to ensure legitimate use and prevent the diversion of controlled substances to illicit channels of commerce.

The active ingredients in esmethadone and psilocybin

are regulated as controlled substances pursuant to the Comprehensive Drug Abuse Prevention and Control Act of 1970 (CSA) and regulations

promulgated by the United States Drug Enforcement Administration (DEA).

The CSA and its implementing regulations establish a closed chain

of distribution for entities handling controlled substances.

The DEA is responsible for enforcing the law and regulations that impose

registration, security, inventory, recordkeeping, reporting and storage requirements on entities that manufacture, distribute, import

and export, prescribe, dispense or otherwise physically handle controlled substances.

The law and regulations require those individuals

or entities that handle controlled substances to comply with these requirements in order to ensure legitimate use and prevent the diversion

of controlled substances to illicit channels of commerce.

The CSA classifies controlled substances into

2 unchanged sentences

and lack accepted safety for use under medical supervision.

They may not be marketed or sold for dispensing to patients in

Pharmaceutical products having a currently accepted medical use and that are otherwise approved for marketing may be listed as

Schedule II, III, IV, or V substances depending on the comparative abuse potential of the drug or substance, with Schedule II

substances classified as having the highest potential for abuse and physical or psychological dependence, and Schedule V substances

classified as having the lowest relative potential for abuse and dependence.

Schedule II substances are subject to the strictest regulatory

requirements involving registration, storage, recordkeeping, reporting and security.

Schedule II drugs are subject to manufacturing quotas

and the distribution and dispensing of Schedule II drugs are more limited and tightly controlled.

For example, Schedule II drug prescriptions

cannot be refilled and must contain a written or electronic signature of a practitioner when presented to a pharmacy.

Schedules III, IV

and V controlled substances are subject to registration, recordkeeping, reporting and security requirements, but these requirements are

less restrictive than Schedule II drugs.

Drugs classified as schedule I drugs may not be marketed, sold

or prescribed for dispensing to patients in the U.S.

Controlled substances that have a currently accepted medical use and that are otherwise

approved for marketing may be listed as Schedule II, III, IV, or V substances depending on the comparative abuse potential of the

drug or substance, Schedule II substances by definition are classified as having the highest potential for abuse and physical or

psychological dependence, whereas Schedule V substances are classified as having the lowest relative potential for abuse and dependence.

Schedule II substances are subject to the strictest regulatory requirements involving registration, storage, recordkeeping, reporting

and security.

Schedule II drugs are subject to manufacturing quotas and the distribution and dispensing of Schedule II drugs are more

limited and tightly controlled.

For example, Schedule II drug prescriptions cannot be refilled and must contain a written or electronic

signature of a practitioner when presented to a pharmacy.

Schedules III, IV and V controlled substances are subject to registration,

recordkeeping, reporting and security requirements, but these requirements are less restrictive than Schedule II drugs.

Esmethadone is the single isomer of methadone,

is currently classified as a Schedule II substance, and psilocybin is currently classified as a Schedule I substance.

Any Schedule I substance,

such as psilocybin, that is FDA-approved for marketing in the United States will need to be rescheduled from Schedule I to Schedule II-V

by the DEA before it can be commercially marketed, distributed, and sold.

Rescheduling is dependent on FDA approval and the FDA must make

a recommendation to the DEA on the appropriate schedule.

The DEA must conduct notice and comment rulemaking to reschedule any controlled

Such action is subject to public comment and potential requests for an administrative hearing objecting to, or supporting,

any such action.

In addition, because each state has its own statutory and regulatory requirements related to controlled substances, each

state or jurisdiction must also take appropriate administrative or legislative action to reschedule a controlled substance within that

state based on federal rescheduling.

Any Schedule I

substance, such as psilocybin, that obtains FDA-approval for marketing in the United States will need to be rescheduled from Schedule

I to Schedule II-V by the DEA before it can be commercially marketed, distributed, sold, prescribed or dispensed.

Rescheduling requires

the FDA to provide the DEA with a scientific and medical evaluation related to the FDA approval and the FDA also must make a recommendation

to the DEA on the appropriate schedule.

The DEA must conduct notice and comment rulemaking to reschedule any controlled substance.

action is subject to public comment and potential requests for an administrative hearing objecting to, or supporting, any such action.

In addition, because each state has its own statutory and regulatory requirements related to controlled substances (which often mirror

the federal scheduling), each state or jurisdiction must also take appropriate administrative or legislative action to reschedule a controlled

substance within that state based on federal rescheduling.

Facilities that manufacture, distribute, import

8 unchanged sentences

recordkeeping and reporting requirements on DEA registrants.

The DEA conducts cyclic inspections of manufacturers, distributors, importers,

and exporters to review compliance with these requirements.

CSA and DEA regulations including security, record keeping and reporting prior

to issuing a controlled substance registration.

The specific security requirements vary by the type of business activity and the schedule

and quantity of controlled substances handled by the registrant.

The most stringent requirements apply to manufacturers of Schedule I

and Schedule II substances.

For example, manufacturers and distributors must store Schedule I and II drugs in secure vault with specific

structural requirements.

Other physical security requirements that apply to all controlled substances include safes and cages, and the

use of alarm systems and surveillance cameras.

Regulations also require that registrants restrict employee access to controlled substances.

Once registered, manufacturing, distribution, exporting or importing facilities must maintain records documenting the manufacture, receipt,

distribution, import, or export of all controlled substances.

Manufacturers and distributors must also submit regular reports to the DEA

of the distribution of Schedule I and II controlled substances, Schedule III narcotic substances, and certain other designated

All DEA registrants must report any controlled substance thefts or significant losses and must obtain authorization to destroy

or dispose of controlled substances.

In addition to maintaining an importer and/or exporter registration, importers and exporters of controlled

substances must obtain a permit for every import or export of a Schedule I or II substance and a narcotic substance in Schedule III, IV

For all other drugs in Schedule III, IV and V, importers and exporters must submit an import or export declaration.

cyclic inspections to determine whether registrants are complying with these requirements.

The DEA will conduct a preregistration inspection to evaluate compliance

with these requirements before issuing a new registration.

The DEA also conducts cyclic inspections of current manufacturers, distributors,

importers, and exporters to review compliance with these requirements.

The specific security requirements vary by the type of business

activity and the schedule and quantity of controlled substances handled by the registrant.

The most stringent requirements apply to manufacturers

of Schedule I and Schedule II substances.

For example, manufacturers and distributors must store Schedule I and II drugs in

a secure vault with specific structural requirements.

Other physical security requirements that apply to all controlled substances include

safes and cages, and the use of alarm systems and surveillance cameras.

DEA regulations also require that registrants restrict employee

access to controlled substances.

Once registered, manufacturing, distribution, exporting or importing facilities must maintain records

documenting the receipt, manufacture, storage, distribution, import, or export of all controlled substances.

Manufacturers and distributors

must also submit regular reports to the DEA of the acquisition and distribution of Schedule I and II controlled substances, Schedule III

narcotic substances, and certain other designated substances.

All DEA registrants must report any controlled substance thefts or significant

losses and must obtain authorization to destroy or dispose of controlled substances.

In addition to maintaining an importer and/or exporter

registration, importers and exporters of controlled substances must obtain a permit for every import or export of a Schedule I or II

substance and a narcotic substance in Schedule III, IV and V.

For all other drugs in Schedule III, IV and V, importers and exporters

must submit an import or export declaration to be authorized to import or export these substances.

The DEA conducts cyclic inspections

to determine whether registrants are complying with these requirements.

Practitioners such as pharmacies and physicians,

1 unchanged sentence

to DEA registration, recordkeeping, reporting, and security requirements on the receipt, storage, and dispensing of controlled substances.

The DEA also established annual aggregate quotas

for manufacturing of certain controlled substances and companies are subject to quarterly individual manufacturing and procurement quotas.

The DEA establishes annually an aggregate production quota for the amount of substances within Schedules I and II and certain Schedule

III substances, that may be produced in the U.S.

based on the DEA’s estimate of the quantity needed to meet legitimate medical,

scientific, research and industrial needs.

The aggregate quota for each controlled substance is allocated among the various individual

bulk manufacturers through an application process.

Manufacturers of dosage forms are also subject to procurement quotas to obtain the

bulk active pharmaceutical ingredients to make finished drugs.

Manufacturers may not exceed the manufacturing or procurement quota granted

in a given quarter or year.

The quotas apply equally to the manufacturing of the active pharmaceutical ingredient and production of dosage

The DEA may adjust aggregate production quotas and individual manufacturing or procurement quotas from time to time during the

year, although the DEA has substantial discretion concerning whether or not to make such adjustments.

Failure to maintain compliance with applicable

DEA requirements, particularly as manifested in the loss or diversion of controlled substances, can result in an enforcement action.

DEA may seek civil penalties, refuse to renew necessary registrations, or initiate administrative proceedings to revoke those registrations.

The CSA also requires that the DEA establish

annual aggregate quotas for manufacturing of each Schedule II and some Schedule III drugs for the entire industry.

In addition, DEA registered

manufacturers must obtain annual individual manufacturing and procurement quotas.

The DEA establishes annually an aggregate production

quota for the amount of substances within Schedules I and II and certain Schedule III substances, that may be produced in the U.S.

on the DEA’s estimate of the quantity needed to meet legitimate medical, scientific, research and industrial needs.

The aggregate

quota for each controlled substance is allocated among the various individual bulk manufacturers through an application process.

Manufacturers

of dosage forms are also subject to procurement quotas to obtain the bulk active pharmaceutical ingredients to make finished drugs.

Manufacturers

may not exceed the manufacturing or procurement quota granted in a given year.

The quotas apply equally to the manufacturing of the active

pharmaceutical ingredient and production of dosage forms.

The DEA may adjust aggregate production quotas and individual manufacturing

or procurement quotas from time to time during the year, although the DEA has substantial discretion concerning whether or not to make

such adjustments.

Failure to comply with applicable DEA requirements,

particularly as manifested in the loss or diversion of controlled substances, can result in an enforcement action.

The DEA may seek civil

penalties for recordkeeping and reporting violations, refuse to renew necessary registrations, or initiate administrative proceedings

to revoke the DEA registrations.

In certain circumstances, violations of the CSA and DEA regulations could lead to criminal prosecution.

The various states, commonwealths, and the District

of Columbia, also regulate controlled substances and impose similar licensing, recordkeeping, and reporting requirements on entities that

handle controlled substances.

Entities must independently comply with the various state requirements in addition to the federal controlled

substance requirements.

of Columbia, also have established laws to regulate controlled substances and impose similar licensing, recordkeeping, and reporting

requirements on entities that manufacture, distribute, sell, dispense or prescribe controlled substances in their jurisdiction.

must independently comply with the various state requirements in addition to the federal controlled substance requirements.

The United States and the majority of countries

13 unchanged sentences

the DOJ, and state and local governments.

The federal Anti-Kickback Statute prohibits, among

other things, persons and entities from knowingly and willfully offering, soliciting or receiving or providing remuneration, directly

The federal Anti-Kickback Statute prohibits,

among other things, persons and entities from knowingly and willfully offering, soliciting or receiving or providing remuneration, directly

or indirectly, in cash or in kind, to induce, or in return for, purchasing, leasing, ordering or arranging for the purchase, lease or

order of any healthcare item or service reimbursable under Medicare, Medicaid, or other federally financed healthcare programs.

has been interpreted to apply to arrangements between pharmaceutical manufacturers on the one hand and prescribers, purchasers and formulary

managers, among others, on the other.

Although there are a number of statutory exceptions and regulatory safe harbors protecting certain

common activities from prosecution or other regulatory sanctions, the exceptions and safe harbors are drawn narrowly, and practices that

involve remuneration intended to induce prescribing, purchases or recommendations may be subject to scrutiny if they do not qualify for

an exception or safe harbor.

In addition, a person or entity does not need to have actual knowledge of the Anti-Kickback Statute or specific

intent to violate it in order to commit a violation.

statute has been interpreted to apply to arrangements between pharmaceutical manufacturers on the one hand and prescribers, purchasers

and formulary managers, among others, on the other.

Although there are a number of statutory exceptions and regulatory safe harbors protecting

certain common activities from prosecution or other regulatory sanctions, the exceptions and safe harbors are drawn narrowly, and practices

that involve remuneration intended to induce prescribing, purchases or recommendations may be subject to scrutiny if they do not qualify

for an exception or safe harbor.

In addition, a person or entity does not need to have actual knowledge of the Anti-Kickback Statute

or specific intent to violate it in order to commit a violation.

Federal civil and criminal false claims laws,

including the federal civil False Claims Act, prohibit any person or entity from knowingly presenting, or causing to be presented, a false

claim for payment to the federal government, or knowingly making, or causing to be made, a false statement to have a false claim paid.

This includes claims made to programs where the federal government reimburses, such as Medicare and Medicaid, as well as programs where

the federal government is a direct purchaser, such as when it purchases off the Federal Supply Schedule.

including the federal civil False Claims Act, prohibit any person or entity from knowingly presenting, or causing to be presented, a

false claim for payment to the federal government, or knowingly making, or causing to be made, a false statement to have a false claim

This includes claims made to programs where the federal government reimburses, such as Medicare and Medicaid, as well as programs

where the federal government is a direct purchaser, such as when it purchases off the Federal Supply Schedule.

Recently, several pharmaceutical

and other healthcare companies have been prosecuted under these laws for allegedly inflating drug prices they report to pricing services,

which in turn were used by the government to set Medicare and Medicaid reimbursement rates, and for allegedly providing free product to

customers with the expectation that the customers would bill federal programs for the product.

which in turn were used by the government to set Medicare and Medicaid reimbursement rates, and for allegedly providing free product

to customers with the expectation that the customers would bill federal programs for the product.

In addition, certain marketing practices,

3 unchanged sentences

federal civil False Claims Act.

Most states also have statutes or regulations similar to the federal Anti-Kickback Statute and civil False

Claims Act, which apply to items and services reimbursed under Medicaid and other state programs, or, in several states, apply regardless

of the payor.

Most states also have statutes or regulations similar to the federal Anti-Kickback Statute and civil

False Claims Act, which apply to items and services reimbursed under Medicaid and other state programs, or, in several states, apply

regardless of the payor.

Other federal statutes pertaining to healthcare

fraud and abuse include the civil monetary penalties statute, which prohibits, among other things, the offer or payment of remuneration

to a Medicaid or Medicare beneficiary that the offeror or payor knows or should know is likely to influence the beneficiary to order a

receive a reimbursable item or service from a particular supplier.

to a Medicaid or Medicare beneficiary that the offeror or payor knows or should know is likely to influence the beneficiary to order

a receive a reimbursable item or service from a particular supplier.

Further, pursuant to the federal Physician Payment

59 unchanged sentences

Healthcare reform proposals recently culminated in the enactment of the Inflation Reduction Act (IRA) in August 2022, which, among other

things, allows the HHS to directly negotiate the selling price of statutorily specified number of drugs and biologics each year that CMS

reimburses under Medicare Part B and Part D.

Only high-expenditure single-source drugs that have been approved for at least 7 years (11

years for biologics) can be selected by CMS for negotiation, with the negotiated price taking effect two years after the selection year.

Negotiations for Medicare Part D products take place in 2024 with the negotiated price taking effect in 2026, and negotiations for Medicare

Part B products will begin in 2026 with the negotiated price taking effect in 2028.

In August 2023, HHS announced the ten Medicare Part

D drugs and biologics that it selected for negotiations.

HHS will announce the negotiated maximum fair prices by September 1, 2024, and

this price cap, which cannot exceed a statutory ceiling price, will go into effect on January 1, 2026.

A drug or biological product that

has an orphan drug designation for only one rare disease or condition will be excluded from the IRA’s price negotiation requirements,

but will lose that exclusion if it receives designations for more than one rare disease or condition, or if it is approved for an indication

that is not within that single designated rare disease or condition, unless such additional designation or such disqualifying approvals

are withdrawn by the time CMS evaluates the drug for selection for negotiation.

The IRA also imposes rebates on Medicare Part D and Part

B drugs whose prices have increased at a rate greater than the rate of inflation.

In addition, the IRA extends enhanced subsidies for

individuals purchasing health insurance coverage in Patient Protection and Affordable Care Act (ACA) marketplaces through plan year 2025.

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

things, allows the HHS to directly negotiate the selling price of statutorily specified number of drugs and biologics each year that

CMS reimburses under Medicare Part B and Part D.

The negotiated price may not exceed a statutory ceiling price.

Only high-expenditure

single-source drugs that have been approved for at least 7 years (11 years for biologics) can be selected by CMS for negotiation, with

the negotiated price taking effect two years after the selection year.

For 2026, the first year in which negotiated prices become effective,

CMS selected 10 high-cost Medicare Part D products in 2023, negotiations began in 2024, and the negotiated maximum fair price for each

product has been announced.

CMS has selected 15 additional Medicare Part D drugs for negotiated maximum fair pricing in 2027.

an additional 15 drugs, which may be covered under either Medicare Part B or Part D, will be selected, and for 2029 and subsequent years,

20 Part B or Part D drugs will be selected.

A drug or biological product that has an orphan drug designation for only one rare disease

or condition will be excluded from the IRA’s price negotiation requirements, but will lose that exclusion if it receives designations

for more than one rare disease or condition, or if it is approved for an indication that is not within that single designated rare disease

or condition, unless such additional designation or such disqualifying approvals are withdrawn by the time CMS evaluates the drug for

selection for negotiation.

The IRA also imposes rebates on Medicare Part D and Part B drugs whose prices have increased at a rate greater

than the rate of inflation, and in November 2024, CMS finalized regulations for these inflation rebates.

In addition, the IRA extends

enhanced subsidies for individuals purchasing health insurance coverage in Patient Protection and Affordable Care Act (ACA) marketplaces

through plan year 2025.

The IRA permits the Secretary of HHS to implement many of these provisions through guidance, as opposed to regulation,

for the initial years.

Manufacturers that fail to comply with the IRA may be subject to various penalties, including civil monetary penalties.

It is unclear

to what extent other statutory, regulatory, and administrative initiatives will be enacted and implemented.

It is unclear to what extent other statutory, regulatory, and administrative initiatives will be enacted and implemented.

Insurance Coverage and Reimbursement

18 unchanged sentences

consistently or obtained in the first instance.

Corporate Information

Our principal executive offices are located at

2222 Ponce de Leon Blvd., Floor 3, Coral Gables, Florida 33134 and our telephone number is (786) 629-1376.

Our website address is www.relmada.com.

information contained in, or that can be accessed through, our website is not part of, and is not incorporated in, this Report.

Available Information

Reports we file with the Securities and Exchange

Commission (SEC) pursuant to the Exchange Act of 1934, as amended (the Exchange Act), including annual and quarterly reports, and other

reports we file, can be inspected and copied at the public reference facilities maintained by the SEC at 100 F Street NE, Washington,

Human Capital

As of December 31, 2023, we had a total of 20 employees.

We understand

people are our greatest asset and that our innovation and operational excellence are ultimately noted in our human capital.

depends in large part on our ability to recruit, develop and retain a qualified, productive, and engaged workforce.

Inclusion & Diversity

Inclusion and diversity is a focus of our corporate

human capital strategy.

By embracing inclusion and diversity, we enhance our work environment and drive business success.

to create a culture of inclusion in which our employees feel empowered to bring their full, authentic selves to work and pursue their

professional goals in a setting of equality.

Fostering such a culture welcomes different perspectives and generates innovation and growth.

We honor the diversity of our employees—in gender, race/ethnicity, age, gender identity, sexual orientation, socio-economic status,

language, nationality, abilities and life experiences.

As of December 31, 2023, our employee population was approximately 60% female.

As of December 31, 2024, we had a total of 17

We understand people are our greatest asset and that our innovation and operational excellence are ultimately noted in our

human capital.

Our success depends in large part on our ability to recruit, develop and retain a qualified, productive, and engaged workforce.

Total Rewards and Employee Engagement

We maintain a competitive compensation and benefits

We maintain competitive compensation and benefits

package including incentive compensation tied to both company and individual performance, and retirement benefits.

14 unchanged sentences

or any other defining characteristic examined.

Corporate Information

Our principal executive offices are located at

2222 Ponce de Leon Blvd., Floor 3, Coral Gables, Florida 33134 and our telephone number is (786) 629-1376.

Our website address is www.relmada.com.

information contained in, or that can be accessed through, our website is not part of, and is not incorporated in, this Annual Report.

Available Information

Reports we file with the Securities and Exchange

Commission (SEC) pursuant to the Exchange Act of 1934, as amended (the Exchange Act), including annual and quarterly reports, and other

reports we file, can be inspected and copied at the public reference facilities maintained by the SEC at 100 F Street NE, Washington,

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