What changed in this filing

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Item 1. Business

2023-03-23 compared with 2022-03-25 · 519 added, 523 removed, 401 unchanged (72% of the section changed)

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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, 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

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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 adequate antidepressant treatments with an antidepressant medication.

In the REL-1017-202 study, 62 subjects, average

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 adequate antidepressant treatments with an antidepressant

Phase 2 Clinical Trial

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

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

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and PPP analyses and results.

Key findings:

We observed that subjects in both the REL-1017 25

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in the placebo group, including:

the Montgomery-Asberg Depression Rating Scale (MADRS);

the Clinical Global Impression – Severity

(CGI-S) scale;

the Clinical Global Impression – Improvement (CGI-I) scale;

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<

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.

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from the CGI-S and CGI-I scales.

Analysis of Change from Baseline to

Day 7 and to Day 14 ITT Population

Means Difference

25mg vs Placebo

50mg vs Placebo

Analysis of Change from Baseline to Day

7 and to Day 14 ITT Population

REL-1017 25mg vs Placebo

REL-1017 50mg vs Placebo

LS = Least Squares;

d = Cohen’s effect size

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 in d-Methadone, and there was no

evidence of either treatment induced psychotomimetic and dissociative AEs or withdrawal signs and symptoms upon treatment

discontinuation.

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 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 major depressive disorder 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 conducted in 55 clinical sites in the United States with planned enrollment of 364 MDD patients

with inadequate response to standard antidepressants in their current depression episode.

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 would 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 the initiation of RELIANCE III study, 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 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

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 maximum tolerated dose, showed a highly statistically significant difference in abuse potential versus

oxycodone with p-values less than 0.001.

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.

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.

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.

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.

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 2.2 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).

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) 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,

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.

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.

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 to placebo.

Key Upcoming Anticipated Milestones

We expect multiple key milestones over the next 12-18

12-18 months.

These include:

Results of RELIANCE III monotherapy MDD trial 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 II, the second of two adjunctive MDD trials, in the first half of 2024.

Initiation of a new Phase III adjunctive MDD trial in mid-2023 with completion anticipated

in the second half of 2024.

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

Our Development Program

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

In addition to the high failure rate, only one of the marketed products

for depression, esketamine (marketed by Johnson and Johnson as Spravato), an in-clinic nasal spray treatment 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

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

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 its adverse side effects, esmethadone is being developed as a rapidly acting, oral

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

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

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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.

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 frontline 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.

While our current strategy is currently to focus on the further development

of esmethadone as an adjunctive treatment for MDD, we may in the future re-commence testing of esmethadone as a monotherapy for MDD.

addition, we are evaluating other indications that Relmada may explore in the future, including restless leg syndrome and other glutamatergic

system activation related diseases.

Our Corporate History and Background

We are a clinical-stage, publicly traded biotechnology 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.

Currently, none of our product candidates have

been approved for sale in the United States or elsewhere.

We are a clinical-stage, publicly traded biotechnology

company developing New Chemical Entities (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.

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.

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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 generating revenues

for the foreseeable future.

We had net loss of approximately $125,751,800 and $59,456,400 for the years ended December 31, 2021 and 2020,

respectively.

At December 31, 2021, we have an accumulated deficit of approximately $305,067,100.

We have not generated revenues and do not anticipate

generating revenues for the foreseeable future.

We had net loss of approximately $157,043,800 and $125,751,800 for the years ended December

31, 2022 and 2021, respectively.

At December 31, 2022, we had an accumulated deficit of approximately $462,110,900.

Business Strategy

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We have 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 esmethadone.

We plan to further develop esmethadone as our

priority program.

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

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

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.

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from competition.

We will continue to prioritize our product development activities after taking into account the resources we have available,

market dynamics and potential for adding value.

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

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.

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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.

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

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

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

Auvelity ® (Axsome).

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.

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 month of pediatric exclusivity and up to 10 years in the E.U.

We believe an extensive intellectual property estate

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

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 beyond 2033.

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,

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

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 month 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.

Esmethadone License Agreement

As a result of a prior acquisition, the Company assumed an obligation to pay third parties (Dr.

As a result of a prior acquisition, the Company assumed

an obligation to pay third parties (Dr.

Inturrisi and Dr.

Paolo Manfredi – see below):

(A) royalty payments up to 2% on net sales of licensed products that are not sold by sublicensee

and (B) on each and every sublicense earned royalty payment received by licensee from its sublicensee on sales of license product by sublicensee,

the higher of (i) 20% of the royalties received by licensee;

(A) royalty payments up to 2%

on net sales of licensed products that are not sold by sublicensee and (B) on each and every sublicense earned royalty payment received

by licensee from its sublicensee on sales of license product by sublicensee, the higher of (i) 20% of the royalties received by licensee;

or (ii) up to 2% of net sales of sublicensee.

The Company will also make

milestone payments of up to $4 or $2 million, for the first commercial sale of product in the field that has a single active pharmaceutical

ingredient, and for the first commercial sale of product in the field of product that has more than one active pharmaceutical ingredient,

respectively.

As of December 31, 2021, the Company has not generated any revenue related to this license agreement.

The Company will also make milestone payments of up to $4 or $2 million, for the first

commercial sale of product in the field that has a single active pharmaceutical ingredient, and for the first commercial sale of product

in the field of product that has more than one active pharmaceutical ingredient, respectively.

As of December 31, 2022, the Company has

not generated any revenue related to this license agreement.

Inturrisi / Manfredi

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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.

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, 2021, no events have occurred, and the Company

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

(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, 2022, no events have occurred,

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

The License Agreement includes standard termination

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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.

The License Agreement was not otherwise modified.

Wonpung License Agreement

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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.

of March 23, 2022, no discussions are active between the Company and Wonpung.

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 23, 2023, 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.

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 Arbomentis, 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 and psychiatric disorders, leveraging its 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,

Marco Pappagallo, our Acting Chief Medical Officer, are among the scientists affiliated with Arbormentis, LLC.

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

and psychiatric disorders, leveraging its 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

Paolo Manfredi, our Acting Chief Scientific Officer and co-inventor of REL-1017, and Dr.

Marco Pappagallo, our Acting Chief

Clinical Officer, are among the scientists affiliated with Arbormentis, LLC.

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 the second

of three Phase 3 trials for the adjunctive treatment of MDD.

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.

Scientific support of leading experts:

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approved and filed patent applications provide coverage beyond 2033.

The pharmaceutical and biotechnology industry is characterized by intense

competition, rapid product development and technological change.

Competition is intense among manufacturers of prescription pharmaceuticals

and other product areas where we may develop and market products in the future.

Most of our competitors are large, well-established pharmaceutical

or healthcare companies with considerably more financial, marketing, sales and technical resources than are available to us.

Additionally,

many of our competitors have research and development capabilities that may allow such competitors 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.

The pharmaceutical and biotechnology industry is

characterized by intense competition, rapid product development and technological change.

Competition is intense among manufacturers

of prescription pharmaceuticals and other product areas where we may develop and market products in the future.

Most of our competitors

are large, well-established pharmaceutical or healthcare companies with considerably more financial, marketing, sales and technical resources

than are available to us.

Additionally, many of our competitors have research and development capabilities that may allow such competitors

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.

Regarding our competitive position in the industry,

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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,

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,

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FDA Approval Process

In the United States, pharmaceutical products

are subject to extensive regulation by the FDA.

In the United States, pharmaceutical products are

subject to extensive regulation by the FDA.

The Federal Food, Drug, and Cosmetic Act (FD&C Act) and other federal and state statutes

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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.

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.

Preclinical tests include laboratory evaluation

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

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 of

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

of the product.

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Clinical trials must be conducted:

compliance with federal regulations;

in compliance with federal regulations;

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

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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.

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

Each protocol involving testing on U.S.

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

FDA 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.

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

FDA 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.

The study protocol and informed consent information

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An IRB may also require the

clinical trial at the site to be halted, either temporarily or permanently, for failure to comply with the IRB’s requirements, or

may impose other conditions.

Clinical trials to support NDAs for marketing

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

clinical trial at the site to be halted, either temporarily or permanently, for failure to comply with the IRB’s requirements,

or may impose other conditions.

Clinical trials to support NDAs for marketing 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.

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in rare instances, such as where the study is a large multicenter trial demonstrating internal consistency and a statistically very persuasive

finding of a clinically meaningful effect on mortality, irreversible morbidity or prevention of a disease with a potentially serious outcome

and confirmation of the result in a second trial would be practically or ethically impossible.

finding of a clinically meaningful effect on mortality, irreversible morbidity or prevention of a disease with a potentially serious

outcome and confirmation of the result in a second trial would be practically or ethically impossible.

After completion of the required clinical testing,

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Drug Designation are exempt from these user fees.

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.

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.

Priority review can be applied

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

The review process

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

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

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 be approved.

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

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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

and the NDA contains data that provide substantial evidence that the drug is safe and effective in the indication studied.

After FDA evaluates the NDA and the manufacturing facilities, it issues

either an approval letter or a complete response letter.

A complete response letter generally outlines the deficiencies in the submission

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

If, or when, those deficiencies

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

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).

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

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.

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

After FDA evaluates the NDA and the manufacturing

facilities, it issues either an approval letter or a complete response letter.

A complete response letter generally outlines the deficiencies

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

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

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.

Fast Track Designation

FDA is required to facilitate the development,

and expedite the review, of drugs that are intended for the treatment of a serious or life-threatening disease or condition for which

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 filing 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.

FDA is required to facilitate the development, and expedite the review,

of drugs that are intended for the treatment of a serious or life-threatening disease or condition for which 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.

If a submission is granted Fast Track Designation,

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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

is no longer supported by data emerging in the clinical trial process.

Under the Orphan Drug Act, FDA may grant Orphan

Drug Designation to drugs intended to treat a rare disease or condition – generally a disease or condition that affects fewer than

Under the Orphan Drug Act, FDA may grant Orphan Drug

Designation to drugs intended to treat a rare disease or condition – generally a disease or condition that affects fewer than 200,000

individuals in the U.S.

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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

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disease or condition, or the same drug for a different disease or condition.

Among the other benefits of Orphan Drug Designation are tax

credits for certain research and an exemption from the NDA application user fee.

Among the other benefits of Orphan Drug Designation are

tax credits for certain research and an exemption from the NDA application user fee.

Disclosure of Clinical Trial Information

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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.

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.

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

Pediatric Information

Under the Pediatric Research Equity Act (PREA),

NDAs or supplements to NDAs must contain data to assess the safety and effectiveness of the drug for the claimed indications in all relevant

Under the Pediatric Research Equity Act (PREA), NDAs

or supplements to NDAs must contain data to assess the safety and effectiveness of the drug for the claimed indications in all relevant

pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which the drug is safe and effective.

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for an indication for which orphan designation has been granted.

The Best Pharmaceuticals for Children Act (BPCA) provides NDA holders

a six-month extension of any exclusivity – patent or nonpatent – for a drug if certain conditions are met.

Conditions for

exclusivity include FDA’s determination that information relating to the use of a new drug in the pediatric population may produce

health benefits in that population, FDA making a written request for pediatric studies, and the applicant agreeing to perform, and reporting

on, the requested studies within the statutory timeframe.

Applications under the BPCA are treated as priority applications, with all of

the benefits that designation confers.

The Best Pharmaceuticals for Children Act (BPCA)

provides NDA holders a six-month extension of any exclusivity – patent or nonpatent – for a drug if certain conditions are

Conditions for exclusivity include FDA’s determination that information relating to the use of a new drug in the pediatric

population may produce health benefits in that population, FDA making a written request for pediatric studies, and the applicant agreeing

to perform, and reporting on, the requested studies within the statutory timeframe.

Applications under the BPCA are treated as priority

applications, with all of the benefits that designation confers.

Post-Approval Requirements

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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.

Generic Competition

In seeking approval for a drug through an NDA,

applicants are required to list with the FDA each patent whose claims cover the applicant’s product.

Upon approval of a drug, each

of the patents listed in the application for the drug is then published in the FDA’s Approved Drug Products with Therapeutic Equivalence

In seeking approval for a drug through an NDA, applicants

are required to list with the FDA each patent whose claims cover the applicant’s product.

Upon approval of a drug, each of the

patents listed in the application for the drug is then published in the FDA’s Approved Drug Products with Therapeutic Equivalence

Evaluations, commonly known as the Orange Book.

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The ANDA applicant may also elect to submit a section viii

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

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.

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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.

Orange Book, there may not be a Paragraph IV certification, and, thus, no ANDA may be filed before the expiration of the exclusivity

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

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Controlled Substances

The active ingredients in esmethadone are listed in the Comprehensive

Drug Abuse Prevention and Control Act of 1970 (CSA) and regulations promulgated by the United States Drug Enforcement Administration (DEA)

as controlled substances.

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

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, and other entities handling controlled

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.

Facilities that manufacture, distribute, import or export any controlled

substance must register annually with the DEA.

The DEA registration is specific to a particular location, activity, and controlled substance

For example, separate registrations are required for importation and manufacturing activities, and the authority granted under

each registration determines which schedules of controlled substances the registrant may handle.

However, certain DEA registrations permit

coincident activities without obtaining a separate DEA registration, such as authorizing a manufacturer to also distribute controlled

substances produced by that registrant.

The CSA classifies controlled substances into one of five schedules

– Schedule I, II, III, IV, or V – depending on the potential for abuse and physical or psychological dependence.

substances by definition have a high potential for abuse, have no currently accepted medical use in treatment in the U.S.

and lack accepted

safety for use under medical supervision.

They may not be marketed or sold for dispensing to patients in the U.S.

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 presenting the highest

potential for abuse and physical or psychological dependence, and Schedule V substances presenting 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.

In particular, distribution and dispensing of Schedule II drugs are strictly controlled.

all 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 recordkeeping, reporting and security requirements, but these

requirements are less restrictive than Schedule II drugs.

The DEA inspects manufacturers, distributors, importers, and exporters

to review compliance with the 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.

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.

Facilities that manufacture, distribute, import

or export any controlled substance must register annually with the DEA.

The DEA registration is specific to a particular location, activity,

and controlled substance schedule.

For example, separate registrations are required for importation and manufacturing activities, and

the authority granted under each registration determines which schedules of controlled substances the registrant may handle.

certain DEA registrations permit coincident activities without obtaining a separate DEA registration, such as authorizing a manufacturer

to also distribute controlled substances produced by that registrant.

The CSA classifies controlled substances into

one of five schedules – Schedule I, II, III, IV, or V – depending on the potential for abuse and physical or psychological

Schedule I substances by definition have a high potential for abuse, have no currently accepted medical use in treatment

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.

The DEA conducts cyclic inspections of manufacturers, distributors,

importers, and exporters to review compliance with the 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 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.

DEA conducts cyclic inspections to determine

whether registrants are complying with these requirements.

Practitioners such as pharmacies and physicians, as well as other types

of entities that handle controlled substances, such as researchers and analytical laboratories, are also subject to DEA registration,

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

The CSA also imposes quota requirements on certain controlled substances.

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 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 maintain compliance 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,

refuse to renew necessary registrations, or initiate administrative proceedings to revoke those registrations.

In certain circumstances,

violations of the CSA and DEA regulations could lead to criminal prosecution.

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.

Practitioners such as pharmacies and physicians,

as well as other types of entities that handle controlled substances, such as researchers and analytical laboratories, are also subject

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

The CSA also imposes quota requirements on certain

controlled substances.

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 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 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.

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 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.

Other Healthcare Laws

In the United States, biotechnology company activities are subject

to regulation by various federal, state and local authorities in addition to the FDA, including but not limited to, the Centers for Medicare

& Medicaid Services (CMS), other divisions of the U.S.

Department of Health and Human Services (e.g., the Office of Inspector General

and the Office for Civil Rights), the U.S.

In the United States, biotechnology company activities

are subject to regulation by various federal, state and local authorities in addition to the FDA, including but not limited to, the Centers

for Medicare& Medicaid Services (CMS), other divisions of the U.S.

Department of Health and Human Services (e.g., the Office of Inspector

General and the Office for Civil Rights), the U.S.

Department of Justice (DOJ) and individual U.S.

Attorney offices within the DOJ, and state

and local governments.

Attorney offices within the DOJ, and

state and local governments.

The federal Anti-Kickback Statute prohibits, among

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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.

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.

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.

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,

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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.

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, and the additional federal criminal statutes created by the Health

Insurance Portability and Accountability Act of 1996 (HIPAA), which prohibits, among other things, knowingly and willfully executing or

attempting to execute a scheme to defraud any healthcare benefit program or obtain by means of false or fraudulent pretenses, representations

or promises of any money or property owned by or under the control of any healthcare benefit program in connection with the delivery of

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, and the additional federal criminal statutes created by the Health Insurance

Portability and Accountability Act of 1996 (HIPAA), which prohibits, among other things, knowingly and willfully executing or attempting

to execute a scheme to defraud any healthcare benefit program or obtain by means of false or fraudulent pretenses, representations or

promises of any money or property owned by or under the control of any healthcare benefit program in connection with the delivery of

or payment for healthcare benefits, items or services.

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to have actual knowledge of the statute or specific intent to violate it in order to commit a violation.

Further, pursuant to the Patient Protection and

Affordable Care Act (ACA), the Centers for Medicare & Medicaid Services, or CMS, has issued a final rule that requires manufacturers

of prescription drugs to collect and report information on certain payments or transfers of value to physicians (defined to include doctors,

dentists, optometrists, podiatrists and chiropractors), physician assistants, certain types of advance practice nurses and teaching hospitals,

as well as ownership and investment interests held by physicians and their immediate family members.

The reported data is made available

in searchable form on a public website on an annual basis.

Further, pursuant to the Patient Protection and Affordable Care Act

(ACA), the Centers for Medicare & Medicaid Services (CMS), has issued a final rule that requires manufacturers of prescription drugs

to collect and report information on certain payments or transfers of value to physicians (defined to include doctors, dentists, optometrists,

podiatrists and chiropractors), physician assistants, certain types of advance practice nurses and teaching hospitals, as well as ownership

and investment interests held by physicians and their immediate family members.

The reported data is made available in searchable form

on a public website on an annual basis.

Failure to submit required information may result in civil monetary penalties.

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In addition, certain states require pharmaceutical companies to implement compliance programs and/or marketing codes.

Certain states and

local jurisdictions also require the registration of pharmaceutical sales and medical representatives.

Compliance with these laws is difficult

and time consuming, and companies that do not comply with these state laws face civil penalties.

Certain states

and local jurisdictions also require the registration of pharmaceutical sales and medical representatives.

Compliance with these laws

is difficult and time consuming, and companies that do not comply with these state laws face civil penalties.

Efforts to ensure that business arrangements with

third parties comply with applicable healthcare laws and regulations involve substantial costs.

If a drug company’s operations are

found to be in violation of any such requirements, it may be subject to significant penalties, including civil, criminal and administrative

If a drug company’s operations

are found to be in violation of any such requirements, it may be subject to significant penalties, including civil, criminal and administrative

penalties, damages, fines, disgorgement, imprisonment, the curtailment or restructuring of its operations, loss of eligibility to obtain

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and divert management’s attention from the operation of the business, even if such action is successfully defended.

Data privacy and security regulations by both the federal government

and the states in which business is conducted may also be applicable.

HIPAA, as amended by the Health Information Technology for Economic

and Clinical Health Act (HITECH), and its implementing regulations, imposes requirements relating to the privacy, security and transmission

of individually identifiable health information.

HIPAA requires covered entities to limit the use and disclosure of protected health information

to specifically authorized situations and requires covered entities to implement security measures to protect health information that

they maintain in electronic form.

Among other things, HITECH made HIPAA’s security standards directly applicable to business associates,

independent contractors or agents of covered entities that receive or obtain protected health information in connection with providing

a service on behalf of a covered entity.

HITECH also created four new tiers of civil monetary penalties, amended HIPAA to make civil and

criminal penalties directly applicable to business associates, and gave state attorneys general new authority to file civil actions for

damages or injunctions in federal courts to enforce the federal HIPAA laws and seek attorneys’ fees and costs associated with pursuing

federal civil actions.

In addition, state laws govern the privacy and security of health information in specified circumstances, many

of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts.

Data privacy and security regulations by both the

federal government and the states in which business is conducted may also be applicable.

HIPAA, as amended by the Health Information

Technology for Economic and Clinical Health Act (HITECH), and its implementing regulations, imposes requirements relating to the privacy,

security and transmission of individually identifiable health information.

HIPAA requires covered entities to limit the use and disclosure

of protected health information to specifically authorized situations and requires covered entities to implement security measures to

protect health information that they maintain in electronic form.

Among other things, HITECH made HIPAA’s security standards directly

applicable to business associates, independent contractors or agents of covered entities that receive or obtain protected health information

in connection with providing a service on behalf of a covered entity.

HITECH also created four new tiers of civil monetary penalties,

amended HIPAA to make civil and criminal penalties directly applicable to business associates, and gave state attorneys general new authority

to file civil actions for damages or injunctions in federal courts to enforce the federal HIPAA laws and seek attorneys’ fees and

costs associated with pursuing federal civil actions.

In addition, state laws govern the privacy and security of health information in

specified circumstances, many of which differ from each other in significant ways and may not have the same effect, thus complicating

compliance efforts.

Healthcare Reform

Healthcare reforms that have been adopted, and

that may be adopted in the future, could result in further reductions in coverage and levels of reimbursement for pharmaceutical products,

increases in rebates payable under U.S.

Healthcare reforms that have been adopted, and that may be adopted

in the future, could result in further reductions in coverage and levels of reimbursement for pharmaceutical products, increases in rebates

payable under U.S.

government rebate programs and additional downward pressure on pharmaceutical product prices.

On September 9, 2021, the Biden administration published a wide-ranging list of policy proposals, most of which would need to be carried

out by Congress, to reduce drug prices and drug payment.

The Department of Health and Human Services (HHS) plan includes, among other

reform measures, proposals to lower prescription drug prices, including by allowing Medicare to negotiate prices and disincentivizing

price increases, and to support market changes that strengthen supply chains, promote biosimilars and generic drugs, and increase price

transparency.

Many similar proposals, including the plans to give Medicare Part D authority to negotiate drug prices, require drug manufacturers

to pay rebates on drugs whose prices increase greater than the rate of inflation, and cap out-of-pocket costs, have already been included

in policy statements and legislation currently being considered by Congress.

It is unclear to what extent these and other statutory, regulatory,

and administrative initiatives will be enacted and implemented.

Healthcare reform proposals

recently culminated in the enactment of the Inflation Reduction Act (IRA), which will, among other things, allow the Department of Health

and Human Services (HHS) to negotiate the selling price of certain drugs and biologics that CMS reimburses under Medicare Part B and Part

D (excluding drugs and biologics that are designated and approved for only one rare disease or condition), although 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.

The negotiated prices, which will first become effective in 2026,

will be capped at a statutory ceiling price.

Beginning in October 2022 for Medicare Part D and January 2023 for Medicare Part B, the IRA

will also penalize drug manufacturers that increase prices of Medicare Part D and Part B drugs at a rate greater than the rate of inflation.

In addition, the IRA will eliminate, beginning in 2025, the coverage gap under Medicare Part D by significantly lowering the enrollee

maximum out-of-pocket cost and requiring manufacturers to subsidize, through a newly established manufacturer discount program, 10% of

Part D enrollees’ prescription costs for brand drugs below the out-of-pocket maximum, and 20% once the out-of-pocket maximum has

been reached.

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.

Insurance Coverage and Reimbursement

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Human Capital

As of December 31, 2021, we had a total of 10

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

human capital.

As of December 31, 2022, we had a total of 14 employees.

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.

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As of December 31, 2022, our employee population was approximately 60% female.

Total Rewards and

Employee Engagement

We maintain a competitive

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

Our performance-based compensation strategy is designed to recognize and reward employees for their contribution to our success, and we

strive to provide strong, equitable incentives for performance.

Total Rewards and Employee Engagement

We maintain a competitive compensation and benefits

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

Our performance-based

compensation strategy is designed to recognize and reward employees for their contribution to our success, and we strive to provide strong,

equitable incentives for performance.

Compensation is comprised of two elements:

base compensation, which is

determined based upon a number of factors, including size, scope and impact of the employee’s role, the market value associated

with the employee’s role, leadership skills, length of service and individual performance;

and an annual bonus, which is a cash

award determined based on a combination of individual and company performance during the period to which the bonus relates.

determine compensation on the basis of merit and without regard to demographic characteristics.

During 2021, we employed a third-party

consultant to assist us in evaluating our pay practices.

In conducting this exercise, we found no meaningful difference in compensation

based upon gender, race or any other defining characteristic examined.

base compensation, which is determined based upon a

number of factors, including size, scope and impact of the employee’s role, the market value associated with the employee’s

role, leadership skills, length of service and individual performance;

and an annual bonus, which is a cash award determined based on

a combination of individual and company performance during the period to which the bonus relates.

We seek to determine compensation on

the basis of merit and without regard to demographic characteristics.

During 2022, we employed a third-party consultant to assist us

in evaluating our pay practices.

In conducting this exercise, we found no meaningful difference in compensation based upon gender, race

or any other defining characteristic examined.

COVID-19 Response

We moved swiftly in our

response to the COVID-19 pandemic to promote the safety of our associates and best serve our members and communities.

In March of 2020,

we transitioned our workforce to remote work environments, while maintaining service operations.

We continued to pay employees who missed

work for COVID-19 related reasons and avoided role reductions as a direct result of COVID-19.

We moved swiftly in our response to the COVID-19

pandemic to promote the safety of our associates and best serve our members and communities.

In March of 2020, we transitioned our workforce

to remote work environments, while maintaining service operations.

We continued to pay employees who missed work for COVID-19 related

reasons and avoided role reductions as a direct result of COVID-19.

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