What changed in this filing

/stocks — the workspaceLOADING

Item 2. Management’s Discussion and Analysis

2022-08-11 compared with 2022-05-05 · 330 added, 279 removed, 136 unchanged (82% of the section changed)

MANAGEMENT’S DISCUSSION AND

ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATION

MANAGEMENT’S DISCUSSION

AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATION

FORWARD-LOOKING STATEMENT NOTICE

This Quarterly Report on Form 10-Q (this Report) contains

forward looking statements that involve risks and uncertainties, principally in the sections entitled “Description of Business,”

“Risk Factors,” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations.”

All statements other than statements of historical fact contained in this Quarterly Report, including statements regarding future events,

our future financial performance, business strategy and plans and objectives of management for future operations, are forward-looking

We have attempted to identify forward-looking statements by terminology including “anticipates,” “believes,”

“can,” “continue,” “could,” “estimates,” “expects,” “intends,”

“may,” “plans,” “potential,” “predicts,” “should,” or “will” or

the negative of these terms or other comparable terminology.

Although we do not make forward-looking statements unless we believe we have

a reasonable basis for doing so, we cannot guarantee their accuracy.

These statements are only predictions and involve known and unknown

risks, uncertainties and other factors, including the risks outlined under “Risk Factors” or elsewhere in this Quarterly Report,

which may cause our or our industry’s actual results, levels of activity, performance or achievements expressed or implied by these

forward-looking statements.

This Quarterly Report on Form 10-Q (this Report)

contains forward looking statements that involve risks and uncertainties, principally in the sections entitled “Description of

Business,” “Risk Factors,” and “Management’s Discussion and Analysis of Financial Condition and Results

of Operations.” All statements other than statements of historical fact contained in this Quarterly Report, including statements

regarding future events, our future financial performance, business strategy and plans and objectives of management for future operations,

are forward-looking statements.

We have attempted to identify forward-looking statements by terminology including “anticipates,”

“believes,” “can,” “continue,” “could,” “estimates,” “expects,”

“intends,” “may,” “plans,” “potential,” “predicts,” “should,”

or “will” or the negative of these terms or other comparable terminology.

Although we do not make forward-looking statements

unless we believe we have a reasonable basis for doing so, we cannot guarantee their accuracy.

These statements are only predictions

and involve known and unknown risks, uncertainties and other factors, including the risks outlined under “Risk Factors” or

elsewhere in this Quarterly Report, which may cause our or our industry’s actual results, levels of activity, performance or achievements

expressed or implied by these forward-looking statements.

Moreover, we operate in a very competitive and rapidly changing environment.

New risks emerge from time to

time and it is not possible for us to predict all risk factors, nor can we address the impact of all factors on our business or the extent

to which any factor, or combination of factors, may cause our actual results to differ materially from those contained in any forward-looking

All forward-looking statements included in this document are based on information available to us on the date hereof, and

we assume no obligation to update any such forward-looking statements.

New risks emerge from time to time and it is not possible for us to predict all risk factors, nor can we address the impact of all factors

on our business or the extent to which any factor, or combination of factors, may cause our actual results to differ materially from

those contained in any forward-looking statements.

All forward-looking statements included in this document are based on information

available to us on the date hereof, and we assume no obligation to update any such forward-looking statements.

You should not place undue reliance on any forward-looking

statement, each of which applies only as of the date of this Quarterly Report on Form-10-Q.

Before you invest in our securities, you should

be aware that the occurrence of the events described in the section entitled “Risk Factors” and elsewhere in this Quarterly

Report could negatively affect our business, operating results, financial condition and stock price.

Except as required by law, we undertake

no obligation to update or revise publicly any of the forward-looking statements after the date of this Quarterly Report on Form-10-Q

to conform our statements to actual results or changed expectations.

Before you invest in our securities, you

should be aware that the occurrence of the events described in the section entitled “Risk Factors” and elsewhere in this

Quarterly Report could negatively affect our business, operating results, financial condition and stock price.

Except as required by

law, we undertake no obligation to update or revise publicly any of the forward-looking statements after the date of this Quarterly Report

on Form-10-Q to conform our statements to actual results or changed expectations.

Business Overview

3 unchanged sentences

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

Esmethadone 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.

Esmethadone 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

3 unchanged sentences

This was a double-blind, placebo-controlled Phase 2 clinical trial evaluating the safety, tolerability

and efficacy of two oral doses of REL-1017, 25 mg once a day and 50 mg once a day, as an adjunctive treatment in patients with major depressive

disorder (MDD), who experienced an inadequate response to 1 to 3 treatments with an antidepressant medication.

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.

and efficacy of two oral doses of REL-1017, 25 mg once a day and 50 mg once a day, as an adjunctive treatment in patients with major

depressive disorder (MDD), who experienced an inadequate response to 1 to 3 treatments with an antidepressant medication.

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

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

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 visits.

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.

No differences were observed between the ITT and PPP analyses and results.

Key findings:

6 unchanged sentences

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

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.

1 unchanged sentence

from the CGI-S and CGI-I scales.

Analysis of Change from Baseline to Day

7 and to Day 14 ITT Population

Analysis of Change from Baseline to

Day 7 and to Day 14 ITT Population

REL-1017 25mg vs Placebo

1 unchanged sentence

LS = Least Squares;

d = Cohen’s effect size

d = Cohen’s effect

The study also confirmed the tolerability profile

3 unchanged sentences

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

were of the same nature as those observed in the Phase 1 clinical studies in 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 MDD.

Following discussions with the Food and Drug Administration

(FDA), Relmada’s adjunctive MDD Phase 3 program includes the following key attributes:

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 MDD.

Following discussions with the Food and Drug

Administration (FDA), Relmada’s adjunctive MDD Phase 3 program includes the following key attributes:

The Phase 3 program consists of two sister, two-arm, placebo-controlled clinical trials.

Each trial is being conducted in 55 clinical sites in the United States and will include planned enrollment of 364 MDD patients with inadequate response to standard antidepressants in their current depression episode.

Each trial is being conducted in 55 clinical sites in the United States.

Patients will add either a 25 mg oral dose of REL-1017 once per day or placebo to their ongoing antidepressant treatment.

The primary endpoint to be evaluated will be the change from baseline on the MADRS score at day-28 for REL-1017 compared to placebo.

Success on this endpoint with the collection of sufficient safety data could support the use of REL-1017 for chronic treatment, if approved.

The change from baseline and the 7-day MADRS score will serve as a key secondary endpoint and will provide information on the time to treatment effect.

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.

Patients who complete RELIANCE I and RELIANCE II are eligible to rollover into the long-term, open-label

study, which also includes subjects who had not previously participated in a REL-1017 clinical trial.

On October 4, 2021, Relmada announced RELIANCE III,

the ongoing monotherapy trial for the Company’s lead product candidate, REL-1017, which aims to randomize 364 patients and it is

expected to be completed in mid-2022.

In addition, in order to support potential regulatory

submissions seeking approval for REL-1017 as monotherapy and adjunctive treatment, the FDA confirmed that, based on what is known at this

time, Relmada will not be required to conduct a two-year carcinogenicity study of REL-1017, as sufficient clinical data have been generated

The FDA also confirmed that Relmada does not need to conduct a thorough QT analysis (TQT) cardiac study in humans to support

cardiac safety in potential regulatory submissions for REL-1017, as the data provided so far and the data generated by the Phase 3 program

will be adequate to evaluate the cardiac safety profile of REL-1017.

The primary endpoint to be evaluated will be the change from baseline

on the MADRS score at day-28 for REL-1017 compared to placebo.

Success on this endpoint with the collection of sufficient safety

data could support the use of REL-1017 for chronic treatment, if approved.

The change from baseline and the 7-day MADRS score will serve as a

key secondary endpoint and will provide information on the time to treatment effect.

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

On August 9, 2022, Relmada announced that the FDA granted Fast Track

designation to REL-1017 as a monotherapy for the treatment MDD.

Patients who complete the RELIANCE trials are

eligible to rollover into the long-term, open-label study, which also is expected to include subjects who had not previously participated

in a REL-1017 clinical trial.

In addition, in order

to support potential regulatory submissions seeking approval for REL-1017 as monotherapy and adjunctive treatment, the FDA confirmed

that, based on what is known at this time, Relmada will not be required to conduct a two-year carcinogenicity study of REL-1017, as sufficient

clinical data have been generated to date.

The FDA also confirmed that Relmada does not need to conduct a thorough QT analysis (TQT)

cardiac study in humans to support cardiac safety in potential regulatory submissions for REL-1017, as the data provided so far and the

data generated by the Phase 3 program will be adequate to evaluate the cardiac safety profile of REL-1017.

Human Abuse Potential (HAP) Study top-line results - Oxycodone:

On July 27, 2021, we 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, respectively)

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

the active control drug, oxycodone

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 maximum

On July 27, 2021, we 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 maximum

tolerated dose, showed a highly statistically significant difference in abuse potential versus oxycodone with p-values less than 0.05.

Results are detailed in the table below:

Mean Emax for Drug Liking

P-value for Difference vs.

oxycodone 40 mg

P-value for REL-1017 vs.

These statistically significant data clearly demonstrate

a very meaningful difference between REL-1017 and oxycodone at all three tested doses.

These results, along with previously published

literature, support the lack of opioid effects of REL-1017.

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 on REL-1017.

Human Abuse Potential (HAP) Study top-line

results - Ketamine:

On February 23, 2022, we 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,

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 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.

Results of the primary endpoint are summarized in

the table below:

Mean Emax for Drug Liking

P-value for Difference vs.

ketamine 0.5mg/Kg over 40 minutes

P-value for REL-1017 vs.

These statistically significant data clearly demonstrate

a very meaningful difference between REL-1017 and ketamine at all three tested doses.

The REL-1017 results were also statistically equivalent

On February 23, 2022,

we 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, 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

Key Upcoming Anticipated Milestones

We expect multiple key milestones over the next

12-18 months.

These include:

Results of RELIANCE III monotherapy MDD rial in mid-2022.

Results of RELIANCE I and RELIANCE II adjunctive MDD trials in the second half of 2022.

Results of RELIANCE – OLS (Long-term, Open-label) study in MDD in the second half of 2022.

Results of RELIANCE III monotherapy MDD trials in the second half of 2022 with last patient enrolled by the end of August, 2022.

Results of RELIANCE I and RELIANCE II adjunctive MDD trials in the

second half of 2022.

Results of RELIANCE – OLS (Long-term, Open-label) study in MDD in the first half of 2023.

Our Development Program

Esmethadone (d-Methadone, dextromethadone, REL-1017)

as a treatment for MDD

In 2014, the National Institute of Mental Health (NIMH)

estimated that 15.7 million adults aged 18 or older in the United States had at least one major depressive episode in the past year.

to data from nationally representative surveys supported by NIMH, only about half of Americans diagnosed with major depression in a given

year receive treatment.

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.

Esmethadone (d-Methadone, dextromethadone,

REL-1017) as a treatment for MDD

In 2014, the National Institute of Mental Health

(NIMH) estimated that 15.7 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, only about half of Americans diagnosed with major depression

in a given year receive treatment.

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.

In addition to the high failure rate, only one

4 unchanged sentences

Esmethadone Overview and Mechanism of Action

Esmethadone’s mechanism of action, as a low

affinity, non-competitive NMDA channel blocker or antagonist, is fundamentally differentiated from most currently FDA-approved antidepressants,

Esmethadone’s mechanism of action, as a

low affinity, non-competitive NMDA channel blocker or antagonist, is fundamentally differentiated from most currently FDA-approved antidepressants,

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.

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

6 unchanged sentences

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.

Esmethadone (d-methadone, dextromethadone, REL-1017)

in other indications

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.

Esmethadone (d-methadone, dextromethadone,

REL-1017) in other indications

In addition to developing esmethadone as an adjunctive

treatment of MDD, we are evaluating the utility of esmethadone as a front line monotherapy treatment for MDD.

Additionally, other indications that Relmada may explore

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

Additionally, other indications that Relmada

may explore in the future, include, restless leg syndrome and other glutamatergic system activation related diseases.

Our Corporate History and Background

2 unchanged sentences

of depression and other CNS diseases.

Currently, none of our product candidates have been

approved for sale in the United States or elsewhere.

Currently, none of our product candidates have

been approved for sale in the United States or elsewhere.

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

3 unchanged sentences

generating revenues for the foreseeable future.

We had net loss of $39,745,783 for the three months ended March 31, 2022.

We had net loss of $79,680,751 for the six months ended June 30, 2022.

At June 30, 2022,

we have an accumulated deficit of $384,747,863.

1 unchanged sentence

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.

assembled a management team along with both scientific, 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

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

7 unchanged sentences

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

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.

2 unchanged sentences

13% for cancer and 12% for cardiovascular disease.

The depression treatment market is segmented on the

basis of antidepressants drugs, devices, and therapies.

The depression treatment market is segmented

on the basis of antidepressants drugs, devices, and therapies.

Antidepressants are the largest and most popular market segment.

4 unchanged sentences

Pristiq® (Pfizer), Zulresso® (Sage) and Spravato® (Johnson & Johnson).

Intellectual Property Portfolio and Market Exclusivity

Intellectual Property Portfolio and Market

We have over 50 issued patents and pending patent

applications related to REL-1017 for multiple uses, including psychological and neurological conditions.

We have also secured an Orphan

Drug Designation from the FDA for d-methadone for “the treatment of postherpetic neuralgia”, which, upon NDA approval, carries

7-year FDA Orphan Drug marketing exclusivity.

In the European Union, some of our actual and prospective products may be eligible up to

10 years of market exclusivity, which includes 8 years data exclusivity and 2 years market exclusivity.

In addition to any granted patents,

REL-1017 will be eligible for market exclusivity to run concurrently with the term of the patent for 5 years in the U.S.

(Hatch Waxman

Act) plus additional 6 months of pediatric exclusivity 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.

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”,

which, upon NDA approval, carries 7-year FDA Orphan Drug marketing exclusivity.

In the European Union, some of our actual and prospective

products may be eligible up to 10 years of market exclusivity, which includes 8 years data exclusivity and 2 years market exclusivity.

In addition to any granted patents, REL-1017 will be eligible for market exclusivity to run concurrently with the term of the patent for

5 years in the U.S.

(Hatch Waxman Act) plus additional 6 months of pediatric exclusivity and up to 10 years of exclusivity in the European

We believe an extensive intellectual property estate of US and foreign patents and applications, once approved, will protect our

technology and products.

Key Strengths

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

Compelling lead product opportunity, REL-1017 currently in Phase 3 trials for the adjunctive and monotherapy treatment of MDD.

Robust and highly statistically significant, efficacy seen with esmethadone in a randomized Phase 2 trial, 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).

Completed 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.

Compelling lead product opportunity, REL-1017 currently in Phase 3 trials for the adjunctive and monotheraphy treatment of MDD.

Robust, and highly statistically significant, efficacy seen with esmethadone

in a randomized Phase 2 trial, 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

Scientific 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.

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.

Substantial IP portfolio and market protection:

approved and filed patent applications provide coverage beyond 2033.

approved and filed

patent applications potentially provide coverage beyond 2033.

A vailable 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, D.C.

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,

Results of Operations

For the Three Months Ended March 31, 2022 versus March 31, 2021

For the Three Months Ended June 30, 2022 versus June 30, 2021

Operating Expenses

2 unchanged sentences

Research and Development Expense

Research and development expense for the three months

ended March 31, 2022 was approximately $25,012,900 compared to $14,022,200 for the three months ended March 31, 2021, an increase of approximately

The change was primarily driven by:

Increase in study costs of $7,783,500 associated with the execution of our four Phase 3 trials;

Decrease in manufacturing and drug storage costs of $612,500;

Decrease in compensation expense of $453,600 due to lower employee-related costs;

Increase in stock-based compensation expense of $712,700;

Increase in other research expenses of $3,560,600 primarily associated with the addition of consultants contracted to assist in the execution of our Phase 3 trials.

Research and development expense for the three months ended June 30,

2022 was approximately $30,912,700 compared to $17,331,500 for the three months ended June 30, 2021, an increase of approximately $13,581,200.

The increase was primarily due to:

Increase in study costs of

$6,651,300 associated with the execution of our Phase 3 studies.

Increase in manufacturing and drug storage costs of $132,500;

Increase in compensation expense of $58,100 due to a increase in research and development employees and their related bonuses;

A decrease in stock-based compensation expense of $724,400;

Increase in other research expenses of $7,463,700 primarily associated with the addition of consultants, clinical research associates, and medical science liaisons contracted to assist in the execution of our Phase 3 trials.

General and Administrative Expense

General and administrative expense for the three months

ended March 31, 2022 was approximately $13,284,600 compared to $8,383,000 for the three months ended March 31, 2021, an increase of approximately

The change was primarily due to:

Decrease in compensation expense of $115,600 due to lower employee-related costs;

Increase in stock-based compensation expense of $5,366,800 primarily related to options granted to employees;

Decrease in other general and administrative expenses of $349,600 primarily due to a decrease in consulting services.

General and administrative expense for the three

months ended June 30, 2022 was approximately $14,599,400 compared to $9,130,400 for the three months ended June 30, 2021, an increase

of approximately $5,469,000.

The increase was primarily due to:

in compensation expense of $151,600 related a decrease of general and administrative employees;

Increase in stock-based compensation expense of $4,751,000 primarily related to options granted to employees, as well as key consultants;

Increase in other general and administrative expenses of $869,600 primarily due to an increase in consulting services.

Other Income (Expense)

Interest / investment (expense) income was approximately

$(1,448,400) and $190,000 for the three months ended March 31, 2022 and 2021, respectively.

Realized loss on short-term investments was

approximately $15,000 and $52,800 for the three months ended March 31, 2022 and 2021, respectively.

Unrealized loss on short-term investments

was approximately $1,763,300 and $177,200 for the three months ended March 31, 2022 and 2021, respectively.

The Company did not provide for income taxes for

the three months ended March 31, 2022 and 2021, since there was a loss and a full valuation allowance against all deferred tax assets.

Interest / investment income was approximately

$387,300 and $322,800 for the three months ended June 30, 2022 and 2021, respectively.

Realized gain on short-term investments was approximately

$24,500 for the three months ended June 30, 2022 compared to a realized loss of approximately $123,600 for the three months ended June

Unrealized loss on short-term investments was approximately $1,186,300 for the three months ended June 30, 2022 compared to

an unrealized loss of approximately $289,300 for the three months ended June 30, 2021.

Gain of settlement of fees was $6,351,600 for the

three months ended June 30,2022.

The net loss for the Company for the three months

ended March 31, 2022 and 2021 was approximately $39,745,800 and $22,215,200, respectively.

ended June 30, 2022 and 2021 was approximately $39,935,000 and $26,551,900, respectively.

The Company had loss per share basic and diluted

of $1.40 and $1.34 for the three months ended March 31, 2022 and 2021, respectively.

of $1.33 and $1.56 for the three months ended June 30, 2022 and 2021, respectively.

The Company did not provide for income taxes

for the six months ended June 30, 2022 and 2021, since there was a loss and a full valuation allowance against all deferred tax assets.

Results of Operations

For the Six Months Ended June 30, 2022 versus June 30, 2021

Operating Expenses

Research and development

General and administrative

Research and Development Expense

Research and development expense for the six months ended June 30,

2022 was approximately $55,925,500 compared to $31,353,700 for the six months ended June 30, 2021, an increase of approximately $24,571,800.

The increase was primarily due to:

Increase in study costs of $14,434,700 associated with the execution

of our Phase 3 studies.

Decrease in manufacturing and drug storage costs of $479,900;

Increase in pre-clinical and toxicology expenses of $336,200;

Decrease in compensation expense of $395,500 due to a decrease in research and development employees and their related bonuses;

A decrease in stock-based compensation expense of $11,900;

Increase in other research expenses of $10,688,200 primarily associated

with the addition of consultants, clinical research associates, and medical science liaisons contracted to assist in the execution of

our Phase 3 trials.

General and Administrative Expense

General and administrative expense for the six

months ended June 30, 2022 was approximately $27,884,000 compared to $17,513,300 for the six months ended June 30, 2021, an increase

of approximately $10,370,700.

The increase was primarily due to:

Decrease in compensation expense of $267,200 primarily related a decrease

of general and administrative employees;

Increase in stock-based compensation expense of $10,117,900 related

to option grants to employees and key consultants;

Increase in other general and administrative expenses of $520,000

primarily due to an increase in consulting services.

Other Income (Expense)

Interest / investment income was approximately

$717,300 and $742,800 for the six months ended June 30, 2022 and 2021, respectively.

Realized gain on short-term investments was approximately

$9,500 for the six months ended June 30, 2022 compared to a realized loss of approximately $176,400 for the six months ended June 30,2021.

Unrealized loss on short-term investments was approximately $2,949,600 and $466,400 for the six months ended June 30, 2022 and 2021, respectively.

Gain on settlement fees of $6,351,600 for the six months ended June 30, 2022.

The net loss for the Company for the six months

ended June 30, 2022 and 2021 was approximately $79,680,800 and $48,767,100, respectively.

The Company had loss per share basic and diluted

of $2.73 and $2.90 for the six months ended June 30, 2022 and 2021, respectively.

The Company did not provide for income taxes

for the six months ended June 30, 2022 and 2021, since there was a loss and a full valuation allowance against all deferred tax assets.

As shown in the accompanying financial statements,

the Company incurred negative operating cash flows of $19,429,743 for the three months ended March 31, 2022 and has an accumulated deficit

of $344,812,895 from inception through March 31, 2022.

the Company incurred negative operating cash flows of $41,055,884 for the six months ended June 30, 2022 and has an accumulated deficit

of $384,747,863 from inception through June 30, 2022.

At June 30, 2022, the Company had cash and short term investments of $211,955,077.

Relmada has funded its past operations through

equity raises and in the three months ended March 31, 2022, the Company raised net proceeds of $29,583,542 from the sale of common stock

through our ATM equity offering, $64,800 through the exercise of options and $300,006 through the exercise of warrants.

Subsequent to quarter end, in April 2022, we entered

into a new Open Market Sale Agreement with Jefferies, as sales agent, pursuant to which we may offer and sell, from time to time,

through Jefferies, shares of our common stock, having an aggregate offering price of up to $100,000,000.

We are not obligated to sell

any shares under the agreement.

On April 8, 2022, we raised net proceeds of $13,284,548 from the sale of common stock through this ATM

Management believes that the Company’s existing

cash and cash equivalents will enable it to fund operating expenses and capital expenditure requirements for at least 12 months from the

issuance of these unaudited condensed consolidated financial statements.

Beyond that point management will evaluate the size and scope

of any subsequent trials that will affect the timing of additional financings through public or private sales of equity or debt securities

or from bank or other loans or through strategic collaboration and/or licensing agreements.

Any such expenditures related to any subsequent

clinical trials will not be incurred until such additional financing is raised.

Further, additional financing related to subsequent clinical

trials does not affect the Company’s conclusion that based on the cash on hand and the budgeted cash flow requirements, the Company

has sufficient funds to maintain operations for at least 12 months from the issuance of these unaudited condensed consolidated financial

The following table sets forth selected cash flow information for the

periods indicated below:

Three Months Ended

equity raises and in the six months ended June 30, 2022, the Company raised net proceeds of $42,728,599 from the sale of common stock

through our ATM equity offering, and $417,544 through the exercise of options and $895,356 through the exercise of warrants.

On April 8, 2022, we raised net proceeds of $13,145,057

from the sale of common stock through our ATM equity offering.

On April 6, 2022, we entered into a new Open Market Sale Agreement with

Jefferies, as sales agent, pursuant to which we may offer and sell, from time to time, through Jefferies, shares of our common stock,

having an aggregate offering price of up to $100,000,000.

We are not obligated to sell any shares under the agreement.

Management believes that the Company’s

existing cash and cash equivalents will enable it to fund operating expenses and capital expenditure requirements for at least 12 months

from the issuance of these unaudited condensed consolidated financial statements.

Beyond that point management will evaluate the size

and scope of any subsequent trials that will affect the timing of additional financings through public or private sales of equity or

debt securities or from bank or other loans or through strategic collaboration and/or licensing agreements.

Any such expenditures related

to any subsequent clinical trials will not be incurred until such additional financing is raised.

Further, additional financing related

to subsequent clinical trials does not affect the Company’s conclusion that based on the cash on hand and the budgeted cash flow

requirements, the Company has sufficient funds to maintain operations for at least 12 months from the issuance of these unaudited condensed

consolidated financial statements.

The following table sets forth selected cash flow information for

the periods indicated below:

Cash used in operating activities

1 unchanged sentence

$ (33,296,890 )

Cash provided by (used in) investing activities

Cash (used in) provided by investing activities

(10,168,188 )

Cash provided by financing activities

Net increase (decrease) in cash and cash equivalents

For the three months ended March 31, 2022, cash

used in operating activities was $19,429,743 primarily due to the net loss of $39,745,783, a decrease in accounts payable of $522,353,

and an increase in accrued expenses of $870,905, offset by non-cash stock compensation charges of $11,930,681, unrealized losses of $1,763,287,

realized losses of $15,022, a decrease in prepaid expenses of $6,237,575, and a decrease in short-term lease payment receivable of $20,923.

For the three months ended March 31, 2021, cash

used in operating activities was $16,085,475 primarily due to the net loss of $22,215,181, prepaid expense of $87,505, and accounts payable

of $263,679, offset by non-cash stock compensation charges of $5,851,284, unrealized loss of $177,163, realized loss of $52,789 and accrued

expenses of $379,601.

For the three months ended March 31, 2022, cash

used by investing activities was $10,027,668 related to the purchase of $25,915,957 and the sale of $15,888,289 short-term investments.

For the three months ended March 31, 2021, cash

used in investing activities was $15,465,841 related to the purchase of $20,663,535 and the sale of $36,129,376 short-term investments.

Net cash provided by financing activities for the three months ended

March 31, 2022 was $29,948,348 due to sales of common stock of $29,583,542, proceeds from warrants exercised for common stock of $300,006,

and proceeds from options exercised for common stock of $64,800.

Net (decrease) increase in cash and cash equivalents

$ (7,182,573 )

For the six months ended June 30, 2022, cash used

in operating activities was $41,055,884 primarily due to the net loss of $79,680,751, decrease in accounts payable of 3,652,816, increase

in other current assets of $256,192, realized gain of 9,480, offset by non-cash stock compensation charges of $24,225,697, decrease in

prepaid expenses and other assets of $7,810,846, increase in accrued expenses of $7,513,045 and unrealized loss of $2,949,624.

For the six months ended June 30, 2021, cash used

in operating activities was $33,296,890 primarily due to the net loss of $48,767,125, increase in prepaid expense and other assets of

$645,690, decrease in accrued expenses of $796,162, offset by non-cash stock compensation charges of $14,119,660, increase in accounts

payable of $2,109,447, unrealized loss of $466,444, and realized loss of $176,379.

For the six months ended June 30, 2022, cash used in investing activities

was $10,168,188 related to the net purchase and sale of short-term investments.

For the six months ended June 30, 2021, cash

provided by investing activities was $9,553,562 related to the net purchase and sale of short-term investments.

Net cash provided by financing activities for

the three months ended March 31, 2021 was $1,928,279 due proceeds from options exercised for common stock of $467,773 and proceeds from

options exercised for common stock of $1,460,506.

the six months ended June 30, 2022 was $44,041,499 due to proceeds from options exercised for common stock of $417,544, proceeds from

warrants exercised for common stock of $895,356, and sales of common stock of $42,728,599.

Net cash provided by financing activities for

the six months ended June 30, 2021 was $25,917,276 due to proceeds from options exercised for common stock of $517,271, proceeds from

warrants exercised for common stock of $1,941,955, and sales of common stock of $23,458,050.

Effects of Inflation

Our assets are primarily monetary, consisting

of cash and cash equivalents.

Our assets are primarily monetary, consisting of cash and cash equivalents

and short term investments.

Because of their liquidity, these assets are not directly affected by inflation.

Because we intend to retain

and continue to use our equipment, we believe that the incremental inflation related to replacement costs of such items will not materially

affect our operations.

However, the rate of inflation affects our expenses, such as those for employee compensation and contract services,

which could increase our level of expenses and the rate at which we use our resources.

However, the rate of inflation

affects our expenses, such as those for employee compensation and contract services, which could increase our level of expenses and the

rate at which we use our resources.

Commitments and Contingencies

9 unchanged sentences

subjective or complex judgments, often as a result of the need to make estimates about the effect of matters that are inherently uncertain.

Our unaudited condensed consolidated financial

statements are presented in accordance with U.S.

Our unaudited condensed

consolidated financial statements are presented in accordance with U.S.

GAAP, and all applicable U.S.

GAAP accounting standards effective as of March 31, 2022

have been taken into consideration in preparing the unaudited consolidated financial statements.

The preparation of unaudited condensed

consolidated financial statements requires management to make estimates and assumptions that affect the reported amounts of assets, liabilities,

and disclosure of contingent assets and liabilities at the date of the financial statements and the reported amounts of revenues and expenses

for the reporting period.

Management bases its estimates on historical experience and on various assumptions that are believed to be reasonable

under the circumstances, the results of which form the basis for making judgments about the carrying value of assets and liabilities that

are not readily apparent from other sources.

On a continual basis, management reviews its estimates utilizing currently available information,

changes in facts and circumstances, historical experience, and reasonable assumptions.

After such reviews, and if deemed appropriate,

managements estimates are adjusted accordingly.

Actual results could differ from those estimates and assumptions under different and/or

future circumstances.

GAAP accounting standards effective

as of June 30, 2022 have been taken into consideration in preparing the unaudited consolidated financial statements.

The preparation

of unaudited condensed consolidated financial statements requires management to make estimates and assumptions that affect the reported

amounts of assets, liabilities, and disclosure of contingent assets and liabilities at the date of the financial statements and the reported

amounts of revenues and expenses for the reporting period.

Management bases its estimates on historical experience and on various assumptions

that are believed to be reasonable under the circumstances, the results of which form the basis for making judgments about the carrying

value of assets and liabilities that are not readily apparent from other sources.

On a continual basis, management reviews its estimates

utilizing currently available information, changes in facts and circumstances, historical experience, and reasonable assumptions.

such reviews, and if deemed appropriate, managements estimates are adjusted accordingly.

Actual results could differ from those estimates

and assumptions under different and/or future circumstances.

Management considers an accounting estimate to be critical if:

it requires assumptions to be made that were uncertain at the time the estimate was made;

changes in the estimate, or the use of different estimating methods that could have been selected, could have a material impact on results of operations or financial condition.

We evaluate our estimates and assumptions on an

ongoing basis and none of the Company’s estimates and assumptions used within the unaudited condensed consolidated financial statements

involve a high level of estimation uncertainty.

For additional discussion regarding the application of the significant accounting policies,

see Note 2 to the Company’s unaudited condensed consolidated financial statements included in this report.

QUANTITATIVE AND QUALITATIVE DISCLOSURES

ABOUT MARKET RISK.

it requires assumptions to be made that were uncertain at the time

the estimate was made;

changes in the estimate, or the use of different estimating methods

that could have been selected, could have a material impact on the results of operations or financial condition.

We evaluate our estimates and assumptions on

an ongoing basis and none of the Company’s estimates and assumptions used within the unaudited condensed consolidated financial

statements involve a high level of estimation uncertainty.

For additional discussion regarding the application of the significant accounting

policies, see Note 2 to the Company’s unaudited condensed consolidated financial statements included in this report.

QUANTITATIVE AND QUALITATIVE

DISCLOSURES ABOUT MARKET RISK.

There have been no material changes to our exposures

2 unchanged sentences

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-Q

Item 2. Management’s Discussion and Analysis