What changed in this filing

/stocks — the workspaceLOADING

Item 1. Business

2024-03-19 compared with 2023-03-23 · 490 added, 424 removed, 496 unchanged (65% of the section changed)

10 unchanged sentences

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

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

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

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

(RELIANCE II and RELIGHT).

Relmada also intends, in 2024, to enter human

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

with psychedelic effects for metabolic indications.

Phase 2 Clinical Trial

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

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

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

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

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

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

Other demographic characteristics were balanced across all arms.

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

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

background antidepressant therapy.

Subjects in the REL-1017 treatment arms received one loading dose of either 75 mg (25 mg arm) or 100

mg (50 mg arm) of REL-1017.

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

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

to stable background antidepressant therapy.

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

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

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

They returned for follow-up visits

at Day 14 and Day 21.

They returned for follow-up

visits at Day 14 and Day 21.

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

11 unchanged sentences

and the Symptoms of Depression Questionnaire (SDQ).

Improvements on the MADRS endpoint appeared on Day

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

Improvements on the MADRS endpoint appeared on

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

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

1 unchanged sentence

from the CGI-S and CGI-I scales.

Analysis of Change from Baseline to Day

7 and to Day 14 ITT Population

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

3 unchanged sentences

The AEs observed in the Phase 2a clinical study

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

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

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

2 unchanged sentences

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.

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

On April 1, 2021, Relmada announced the initiation

3 unchanged sentences

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

In addition, on

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

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

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

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

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

the cardiac safety profile of REL-1017.

On August 9, 2022, Relmada

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

On October 13, 2022, Relmada

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

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.

10 unchanged sentences

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.

Additionally, in a prespecified

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

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

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

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

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

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

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

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

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

REL-1017 was well-tolerated

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

The most commonly

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

new safety signals were detected.

On August 23, 2023, Relmada announced the dosing

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

Human Abuse Potential (HAP) Studies

25 unchanged sentences

Consistent results are seen for the secondary endpoints.

Psilocybin Program (REL-P11):

On October 11, 2023, Relmada announced that it

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

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

The Company plans to commence a single-ascending dose Phase

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

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

Pre-clinical data in a rodent model of metabolic

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

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

Key Upcoming Anticipated Milestones

1 unchanged sentence

These include:

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.

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

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

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

Our Development Program

2 unchanged sentences

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

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

in a given year receive treatment.

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

received treatment in 2021.

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

3 unchanged sentences

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.

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 their 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

13 unchanged sentences

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

NMDA receptors are present in many parts of the CNS

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

such as executive function, learning and memory.

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

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

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.

While our current strategy is currently to focus

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

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

Psilocybin Program

Relmada acquired the development and commercial

rights to a novel psilocybin and derivative program from Arbormentis LLC in July of 2021.

The original focus of the program was limited

to neurodegenerative diseases.

Psilocybin has neuroplastogen™ effects that have the potential to ameliorate the consequences of

multiple neurodegenerative conditions.

The pleiotropic metabolic effects of low-dose psilocybin were discovered while studying its neuroplastogen™

potential in a rodent model deficient in neurogenesis – obese rodents maintained on a high fructose, high fat diet (HFHFD).

Specifically,

in a rodent model of metabolic dysfunction-associated steatotic liver disease (MASLD), beneficial effects of psilocybin were observed

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

Our Corporate History and Background

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.

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

of depression and other CNS diseases.

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

Currently, none of our product candidates have

been approved for sale in the United States or elsewhere.

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

11 unchanged sentences

We have assembled a management team along with

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

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

We plan to further develop esmethadone as our priority

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

a full clinical development program.

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

from competition.

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

available, market dynamics and potential for adding value.

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

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

We plan to further develop esmethadone as our

priority program.

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

involves a full clinical development program.

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

products from competition.

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

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

Market Opportunity

We believe that the market for addressing areas of

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

We believe that the market for addressing areas

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

a sizable revenue opportunity for us.

2 unchanged sentences

13% for cancer and 12% for cardiovascular disease.

The depression treatment market is segmented on the

basis of antidepressants drugs, devices, and therapies.

The depression treatment market is segmented on

the basis of antidepressants drugs, devices, and therapies.

Antidepressants are the largest and most popular market segment.

3 unchanged sentences

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

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

Auvelity ® (Axsome).

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

Auvelity TM (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, 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

We have over 50 issued patents and pending patent

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

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

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

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

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.

some of our 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) and may be eligible for an additional 6 months of pediatric exclusivity

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

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

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

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

(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, 2022, 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, 2023, the Company has not generated

any revenue related to this license agreement.

Inturrisi / Manfredi

9 unchanged sentences

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.

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.

(i) the first commercial sale of a licensed

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

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

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

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

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

received by Relmada for sublicenses granted under the License Agreement.

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

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

The License Agreement includes standard termination

18 unchanged sentences

Wonpung License Agreement

In 2007, the Company entered into a License Development

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

Wonpung has exclusive territorial rights in countries

it selects in Asia to market up to two drugs the Company is currently developing and a right of first refusal (“ROFR”) for

up to an additional five drugs that the Company may develop in the future as defined in more detail in the license agreement.

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.

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

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

Wonpung has exclusive territorial rights in countries it selects in Asia

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

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

If the parties cannot agree to terms of a license

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

As of March 19, 2024, no discussions

are active between the Company and Wonpung.

The Company received an upfront license fee of

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

The licensing terms for

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

The terms of each licensing agreement will expire on the

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

licensed product in the licensed territory.

The licensing

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

The terms of each licensing agreement will expire

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

such licensed product in the licensed territory.

Psilocybin License Agreement

In July 2021, we executed a License Agreement with Arbormentis, LLC

which gives us the development and commercial rights to a novel psilocybin and derivate program.

Under the terms of the agreement, we

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

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

commercialization milestones.

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

therapy resulting from this agreement.

The license agreement is terminable by us but is perpetual and not terminable by the licensor absent

material breach of its terms by us.

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

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.

In July 2021, we executed a License Agreement

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

Under the terms

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

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

and commercialization milestones.

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

commercialized therapy resulting from this agreement.

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

the licensor absent material breach of its terms by us.

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

targeting neurological, psychiatric and metabolic disorders.

We will leverage Arbormentis’ understanding of neuroplasticity, and

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

Importantly, neuroplasticity also plays

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

Paolo Manfredi, our Acting Chief Scientific Officer and

co-inventor of REL-1017, and Dr.

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

Key Strengths

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

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).

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

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

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

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

Scientific support of leading experts:

Our scientific advisors include clinicians and scientists who are affiliated with a number of highly regarded medical institutions such as Harvard, Cornell, Yale, and University of Pennsylvania.

Substantial IP portfolio and market protection:

Substantial esmethadone IP portfolio and market protection:

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.

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

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

support of leading experts:

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

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

The pharmaceutical and biotechnology industry

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

Competition is intense among manufacturers

5 unchanged sentences

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

Our products could be rendered obsolete or made uneconomical

by the development of new products.

Our products could be rendered obsolete or made uneconomical by

the development of new products.

Regarding our competitive position in the industry,

1 unchanged sentence

Government Regulation

Government authorities in the United States, at the

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

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,

4 unchanged sentences

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

2 unchanged sentences

Failure to comply with applicable U.S.

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

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

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

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

5 unchanged sentences

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

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.

18 unchanged sentences

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

for patients in clinical trials must also be submitted to an institutional review board (IRB) for approval.

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

FDA may not permit a clinical trial to begin,

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

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

trial patients.

The study protocol and informed consent information for patients in clinical trials must also be submitted to an institutional

review board (IRB) for approval.

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

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

7 unchanged sentences

In most cases, FDA requires two adequate and well-controlled

Phase 3 clinical trials to demonstrate the efficacy of the drug.

A single Phase 3 trial with other confirmatory evidence may be sufficient

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.

Phase 3 clinical trials, each convincing on its own, to demonstrate the efficacy of the drug.

A single Phase 3 trial with other confirmatory

evidence may be sufficient in rare instances, such as (i) 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

or (ii) when in conjunction with other confirmatory evidence.

After completion of the required clinical testing,

10 unchanged sentences

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.

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 be approved.

FDA has agreed to certain

performance goals in the review of NDAs to encourage timeliness.

Applications for most standard review drug products are reviewed within

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

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

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

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

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

1 unchanged sentence

one or more clinical sites to assure compliance with GCP.

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

drug is manufactured.

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

is manufactured.

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

4 unchanged sentences

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

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

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.

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

An approval letter

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

As a condition of NDA approval,

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

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

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

special monitoring and the use of patient registries.

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

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

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

identified following initial marketing.

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.

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 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.

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,

2 unchanged sentences

and the applicant pays applicable user fees.

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

the last section of the NDA is submitted.

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

last section of the NDA is submitted.

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

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 200,000

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.

2 unchanged sentences

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

Orphan Drug Designation does not convey

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

Orphan Drug Designation does not convey any

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

The first NDA applicant to receive FDA approval

1 unchanged sentence

marketing period in the U.S.

for that product, for that indication.

During the seven-year exclusivity period, FDA may not approve any

other applications to market the same drug for the same disease, except in limited circumstances, such as a showing of clinical superiority

to the product with orphan drug exclusivity.

Orphan drug exclusivity does not prevent FDA from approving a different drug for the same

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.

for the active ingredient in that product, for that indication.

During the seven-year exclusivity period,

FDA may not approve any other applications to market the same drug for the same disease, except in limited circumstances, such as a showing

of clinical superiority to the product with orphan drug exclusivity.

Orphan drug exclusivity does not prevent FDA from approving a different

drug for the same 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.

Disclosure of Clinical Trial Information

5 unchanged sentences

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.

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.

Competitors 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.

22 unchanged sentences

or use of the product.

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

cGMPs after approval.

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

certain state agencies.

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

manufacturing facilities to assess compliance with cGMPs.

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

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

Regulatory authorities may withdraw product approvals

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

or if previously unrecognized problems are subsequently discovered.

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

after approval.

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

state agencies.

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

facilities to assess compliance with cGMPs.

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

production and quality-control to maintain compliance with cGMPs.

Regulatory authorities may withdraw product approvals or request product

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

unrecognized problems are subsequently discovered.

FDA strictly regulates marketing, labeling, advertising

and promotion of drugs that are placed on the market.

Advertising and promotion of drugs must be in compliance with the Federal Food,

Drug, and Cosmetic Act (FDCA) and its implementing regulations and only for the approved indications and in a manner consistent with

the approved labeling.

FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses,

and a company that is found to have improperly promoted off-label uses may be subject to significant liability, including investigation

by federal and state authorities.

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.

29 unchanged sentences

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

Upon NDA approval of a new chemical entity (NCE)

such as esmethadone, which is a drug that contains no active moiety that has been approved by FDA in any other NDA, that drug receives

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

may be submitted one year before NCE exclusivity expires if a Paragraph IV certification is filed.

If there is no listed patent in the

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

Certain changes to a drug, such as the addition of a new indication to the package insert, can be the subject of a three-year

period of exclusivity if the application contains reports of new clinical investigations (other than bioavailability studies) conducted

or sponsored by the sponsor that were essential to approval of the application.

FDA cannot approve an ANDA for a generic drug that includes

the change during the period of exclusivity.

In the case of a non-racemic drug containing as an active ingredient

a single enantiomer that is contained in a racemic drug approved in another NDA, the NDA for the non-racemic drug may elect to have the

single enantiomer not be considered the same active ingredient as that contained in the approved racemic drug and therefore eligible for

NCE exclusivity, if certain conditions are met.

Upon NDA approval of a NCE such as esmethadone,

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

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

An ANDA may be submitted one

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

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

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

Certain changes

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

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

that were essential to approval of the application.

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

period of exclusivity.

In the case of a non-racemic drug containing as

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

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

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

These conditions include:

(1) the single enantiomer has not been previously approved except

in the approved racemic drug, (2) the NDA for the non-racemic drug includes full reports of new clinical investigations necessary for

the approval of the product conducted or sponsored by the applicant and not submitted for approval of the racemic drug, and (3) the NDA

for the non-racemic drug is not submitted for approval of a condition of use in a therapeutic category in which the approved racemic drug

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

In addition, FDA will not approve the non-racemic

drug for any condition of use in the therapeutic category in which the racemic drug has been approved for a period of 10 years after approval

of the non-racemic drug, and the labeling of the non-racemic drug will include a statement in the indication that the non-racemic drug

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

The applicant for the

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

(1) the single enantiomer

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

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

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

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

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

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

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

racemic drug.

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

Patent Term Extension

17 unchanged sentences

Controlled Substances

The active ingredients in esmethadone are regulated

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

by the United States Drug Enforcement Administration (DEA).

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

for entities handling controlled substances.

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

inventory, recordkeeping, reporting and storage requirements on entities that manufacture, distribute, import and export, prescribe, dispense

or otherwise physically handle controlled substances.

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

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

channels of commerce.

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 active ingredients in esmethadone are regulated as controlled substances

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

Enforcement Administration (DEA).

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

controlled substances.

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

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

handle controlled substances.

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

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

The CSA classifies controlled substances into

16 unchanged sentences

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

Esmethadone is the single isomer of methadone,

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

Any Schedule I substance,

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

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

Rescheduling is dependent on FDA approval and the FDA must make

a recommendation to the DEA on the appropriate schedule.

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

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

any such action.

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

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

state based on federal rescheduling.

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 and DEA regulations impose certain security,

recordkeeping and reporting requirements on DEA registrants.

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

and exporters to review compliance with these requirements.

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

to issuing a controlled substance registration.

21 unchanged sentences

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 also established annual aggregate quotas

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

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

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

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

scientific, research and industrial needs.

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

bulk manufacturers through an application process.

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

bulk active pharmaceutical ingredients to make finished drugs.

Manufacturers may not exceed the manufacturing or procurement quota granted

in a given quarter or year.

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

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

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

Failure to maintain compliance with applicable

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

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

1 unchanged sentence

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.

The United States and the majority of countries

are signatories to the United Nations (UN) international drug control treaties which dictate certain scheduling, licensing, restrictions

and other requirements involving controlled substances.

Because psilocybin is classified as a Schedule I controlled substance under the

UN Convention on Psychotropic Substances, 1971 most countries maintain laws and regulations comparable to those in the United Stated

related to methadone, psilocybin and other controlled substances.

Other Healthcare Laws

2 unchanged sentences

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 Health and Human Services (HHS) (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

2 unchanged sentences

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

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.

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.

Recently, several pharmaceutical

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

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

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

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

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

In addition, certain marketing practices,

3 unchanged sentences

federal civil False Claims Act.

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

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

regardless of the payor.

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.

Similar to the federal Anti-Kickback Statute, a person or entity does not need

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 (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.

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.

Further, pursuant to the federal Physician Payment

Sunshine Act, 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.

to submit required information may result in civil monetary penalties.

In addition, several states now require prescription

5 unchanged sentences

Some states require the reporting of certain drug pricing information, including information pertaining to and justifying price increases

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.

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

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

approvals from the FDA, exclusion from participation in government contracting, healthcare reimbursement or other federal or state government

healthcare programs, including Medicare and Medicaid, integrity oversight and reporting obligations, imprisonment, and reputational harm.

Although effective compliance programs can mitigate the risk of investigation and prosecution for violations of these laws, these risks

cannot be entirely eliminated.

Any action for an alleged or suspected violation can cause a drug company to incur significant legal expenses

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

and new high-cost drug introductions.

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 may face civil penalties.

Data privacy and security regulations by both

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

Health Insurance Portability and Accountability

Act of 1996 (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 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.

to the federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to

violate it in order to commit a violation.

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, may not have the same effect, and often are not preempted by HIPAA, thus complicating

compliance efforts.

For example, the California Consumer Privacy Act (CCPA), which went into effect on January 1, 2020, creates

new data privacy obligations for covered companies and provides new privacy rights to California residents.

On January 1, 2023, the California

Privacy Rights Act (CPRA), which substantially amends the CCPA, went into effect.

The CCPA and CPRA provide for unlimited civil penalties

for violations, as well as a private right of action for data breaches that is expected to increase data breach litigation.

Consumer Data Protection Act, which took effect on January 1, 2023, requires businesses subject to the legislation to conduct data protection

assessments in certain circumstances and requires opt-in consent from consumers to acquire and process their sensitive personal information,

which includes information revealing a consumer’s physical and mental health diagnosis and genetic and biometric information that

can identify a consumer.

Colorado enacted the Colorado Privacy Act, and Connecticut enacted the Connecticut Data Privacy Act, each of

which took effect on July 1, 2023, and Utah enacted the Consumer Privacy Act, which became effective on December 31, 2023, and each of

these laws may increase the complexity, variation in requirements, restrictions, and potential legal risks.

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.

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.

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

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

reimburses under Medicare Part B and Part D.

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

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

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

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

In August 2023, HHS announced the ten Medicare Part

D drugs and biologics that it selected for negotiations.

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

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

A drug or biological product that

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

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

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

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

The IRA also imposes rebates on Medicare Part D and Part

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

In addition, the IRA extends enhanced subsidies for

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

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

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

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

It is unclear

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

Insurance Coverage and Reimbursement

23 unchanged sentences

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

A vailable Information

Available Information

Reports we file with the Securities and Exchange

3 unchanged sentences

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

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

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

We understand

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

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

Inclusion & Diversity

26 unchanged sentences

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.

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