What changed in this filing

/stocks — the workspaceLOADING

Item 1. Business

2026-03-19 compared with 2025-03-27 · 455 added, 630 removed, 321 unchanged (77% of the section changed)

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Relmada Therapeutics, Inc.

(Relmada, the

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

We substantially redesigned

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

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

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

We concluded in our review that the most

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

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

Hence we accelerated ongoing efforts

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

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

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

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

(Relmada, the Company, we or us) (a Nevada

corporation), is a publicly traded, clinical-stage biotechnology company.

We substantially redesigned our development programs following

a comprehensive strategic review in late 2024 and early 2025.

We concluded in our review that the most promising path to create shareholder

value was to lever our extensive drug development expertise and clinical operations capabilities by acquiring new development candidates,

while terminating further work on esmethadone (d-methadone, dextromethadone or REL-1017).

Hence we accelerated ongoing efforts to augment

our development pipeline while diversifying its risk, which culminated in the licensing of NDV-01, a novel delivery formulation of a chemotherapy

regimen widely used to treat non muscle-invasive bladder cancer (NMIBC) that is currently in Phase 2, and the acquisition of sepranolone,

a Phase 2b-ready neurosteroid with potential applications in Prader-Willi syndrome (PWS), Tourette Syndrome (TS), essential tremor and

other diseases related to excessive GABAergic activity.

Following the 2024 REL-1017 setback and subsequent

post hoc analyses, the program was terminated effective July 7, 2025.

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

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

The REL-P11 program has successfully completed

a Phase 1 safety study.

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

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

REL-1017 Program Updates

Since 2013, we had been developing esmethadone

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

In December 2024,

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

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

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

Following this 2024 REL-1017 setback, which we

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

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

decision regarding the future of this program.

Strategic Business Review and New Approach

Following a comprehensive evaluation of the Company’s

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

shareholder value.

This refined strategy remains focused on:

– Advancing novel and differentiated therapeutic solutions

Unmet Medical Needs – Targeting areas with significant gaps in treatment

Market Opportunities – Prioritizing programs with substantial commercial potential

● Intellectual

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

Key Strategic Priorities

Under this updated approach, we will continue

to emphasize:

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

and success probabilities

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

● Prioritizing

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

● Accelerating

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

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

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

This strategic framework positions the Company for long-term

growth while maintaining execution and financial prudence.

Effective May 12, 2025, this program was

Currently, our lead product, NDV-01 is a novel, controlled-release

intravesical formulation of gemcitabine and docetaxel.

NDV-01 is currently in a Phase 2 clinical trial in Isreal to assess its safety

and efficacy in patients with aggressive forms of NMIBC.

We intend to develop NDV-01 for two separate indications:

(1) the treatment of

high-risk, 2nd line Bacillus Calmette-Guérin (BCG)-unresponsive NMIBC and (2) the treatment of intermediate risk patients in the

adjuvant setting.

We expect to initiate Phase 3 programs for each indication mid-2026.

Our second product, sepranolone is a novel neurosteroid epimer of allopregnanolone.

Sepranolone is being developed for the potential treatment of PWS, TS, essential tremor and other diseases related to excessive GABAergic

We expect to initiate a Phase 2b study in PWS mid-2026.

Progress in Strategic Execution

We commenced a strategic review in December 2024

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

with particular expertise in CNS.

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

Relmada’s potential to create shareholder value.

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

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

On February 6, 2025, Relmada announced the acquisition

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

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

On February 6, 2025, Relmada announced the acquisition from Asarina

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

and other diseases related to the excessive GABAergic activity.

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

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These include:

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

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

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

NDV-01 United States Investigational New Drug (IND) clearance by the

Food and Drug Administration (FDA) to initiate a clinical trial in NMIBC – Mid-2026

NDV-01 High-risk, 2nd line BCG-unresponsive NMIBC Phase 3 Trial Initiation

NDV-01 Intermediate Risk in the Adjuvant Setting Phase 3 Trial Initiation

sepranolone - Initiation of a Phase 2 clinical trial in PWS –

NDV-01 Initial 3-Month Data from Phase 3 High-risk, 2nd line BCG-unresponsive NMIBC Trial – Year-end 2026

Our Development Programs

Sepranolone Program

The GABAergic system is the primary inhibitory

neurotransmitter pathway.

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

GABA A receptors are a major target

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

The GABAergic system regulates a host of physiological

and neurological functions and their related moods and behaviors.

The principal positive physiologic modulators of the GABAergic system

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

GABA generally inhibits

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

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

Sepranolone is a synthetic version of Isoallopregnanolone,

a naturally occurring neurosteroid that counteracts the effects of Allopregnanolone.

Sepranolone is designed to normalize GABA A receptor

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

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

Data from an open-label Phase 2a randomized study

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

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

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

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

of care (SOC) versus standard of care alone.

The Phase 2a results showed competitive tic reduction

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

Sepranolone not only reduced tic severity in its primary clinical

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

standard of care:

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

Life) total score (GTS-QOL)

greater reduction in impairment (YGTSS)

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

Importantly, no off-target CNS effects or systemic

side effects were observed in this study.

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

over 335 participants and has demonstrated a favorable safety profile.

Relmada is currently evaluating the nonclinical

and clinical strategy for the development of Sepranolone.

NDV-01 Program

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

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

This combination

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

NDV-01, our lead program, was in-licensed on

March 24, 2025, NDV-01, is a novel intravesicular delivery technology designed for the long-acting, controlled release of gemcitabine

and docetaxel.

This combination therapy has gained significant interest as an alternative to BCG for treating NMIBC, especially given

the global BCG shortage since 2019.

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

three hours, with limited tumor exposure time.

NDV-01 potentially addresses these limitations

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

extended exposure enhances the therapeutic effect while improving patient convenience.

NDV-01 is currently in a Phase 2 clinical trial

evaluating its safety and efficacy in patients with aggressive NMIBC.

three to four hours, with limited tumor exposure time.

NDV-01 potentially addresses these limitations by enabling a single

administration in less than 5 minutes, delivering sustained, localized chemotherapy for up to 10 days.

This extended exposure enhances

the therapeutic effect while improving patient convenience.

NDV-01 is formulated as a controlled-release intravesical

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and reduce recurrence risk while lowering the frequency of administration.

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

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.

Relmada has paused this program pending a comprehensive data review,

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

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

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

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

syndrome and other glutamatergic system activation related diseases.

Psilocybin Program

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.

Relmada has paused this program in light of an

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

and the acquisition of new, more advanced product candidates.

NDV-01 is currently in a Phase 2 clinical trial evaluating its safety

and efficacy in patients with aggressive NMIBC.

The Phase 2 study is a single-arm, single-center study evaluating the safety and efficacy

of NDV-01 in patients with High Grade-NMIBC.

Patients are treated with NDV-01 in a biweekly induction phase, follow by monthly maintenance

for up to one year, with regular assessments via cystoscopy, cytology, and biopsy, as indicated.

The primary efficacy endpoints are safety

and complete response rate (Complete Response Rate at 12 months), and secondary efficacy endpoints are duration of response (DOR) and

event free survival (EFS).

Twelve-Month Safety and Efficacy Data

We obtained twelve-month safety and efficacy data for our Phase 2 study

of NDV-01 in high-risk NMIBC.

Among 48 enrolled patients who received at least one dose, no new safety signals were observed with respect

to the type, frequency or severity of adverse events.

No patients experienced Grade ≥3 treatment-related adverse events, and no patients

discontinued treatment due to adverse events.

Of the 48 patients, 30 (63%) experienced a treatment-related adverse event.

Among treatment-related

adverse events, 54% were transient uncomfortable urination (dysuria), 8% were asymptomatic positive urine culture and 8% were hematuria.

Efficacy and Tolerability

Efficacy Evaluable Patients (Complete Response (CR))

12 month KM analysis

N= 48 patients in overall population;

Kaplan-Meier analysis;

10 patients awaiting 3 month response assessment

BCG-UR Subpopulation* CR

12 month KM analysis

N= 20 patients dosed in BCG-UR subpopulation;

* BCG-UR defined by FDA definition;

Bacillus Calmette-Guérin (BCG)- Unresponsive;

Kaplan-Meier analysis;

awaiting 3 month assessment

No patient had progression to muscle-invasive disease

No patient underwent radical cystectomy

The Company also previously announced the successful completion and

receipt of written feedback from a Type B pre-IND submissions with the U.S.

Food and Drug Administration (FDA) regarding the planned Phase

3 program for NDV-01 in NMIBC patients.

Relmada secured FDA alignment on certain key elements of the planned Phase 3 pivotal program for

NDV-01, expected to begin in mid-2026, and incorporating two studies for two separate indications:

A single-arm, open-label clinical trial in this high-grade, BCG-unresponsive with Carcinoma in situ (CIS) population

A single registrational study in intermediate risk NMIBC in the adjuvant setting, which will follow an open-label, randomized-to-observation design

Also, importantly, the FDA agreed with our proposal to rely on FDA’s

prior findings of safety for Gemzar and Taxotere and published literature for the non-clinical safety assessment of NDV-01 because this

is a proposed 505(b)(2) approval.

About the Planned High-Grade Registrational

The planned pivotal Phase 3 study in 2nd-line, refractory, high-grade

BCG-unresponsive NMIBC with CIS will be an open-label, single-arm trial evaluating:

Primary endpoint:

CR rate at any time

Key secondary endpoint:

Cystoscopy, cytology, and biopsy per protocol

The design reflects FDA’s

written guidance on the study population, endpoint selection, and evaluation methodology and is consistent with prior FDA precedents for

single-arm registrational trials in NMIBC.

About the Planned

Intermediate-Risk Registrational Study

The planned pivotal Phase 3 study in intermediate-risk NMIBC in the

adjuvant setting will be an open label randomized-to-observation study:

Primary endpoint:

Disease Free Survival (DFS)

Key secondary endpoint:

Cystoscopy, cytology, and biopsy per protocol

The design reflects FDA’s written guidance on the study population,

endpoint selection, and evaluation methodology.

Sepranolone Program

The GABAergic system is the primary inhibitory

neurotransmitter pathway.

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

GABA A receptors are

a major target for neuropsychiatric drugs, including benzodiazepines, barbiturates and anesthetic agents.

The GABAergic system regulates

a host of physiological and neurological functions and their related moods and behaviors.

The principal positive physiologic modulators

of the GABAergic system are the neurotransmitter GABA (γ-aminobutyric acid) and the positive allosteric modulator Allopregnanolone.

GABA generally inhibits nervous system excitability and thereby produces a calming effect that reduces anxiety and compulsive behavior,

among other manifestations.

While Allopregnanolone typically enhances GABA’s calming effects, in some individuals it paradoxically

exacerbates anxiety and compulsive behavior.

Sepranolone is a synthetic version of isoallopregnanolone,

a naturally occurring neurosteroid that counteracts the effects of allopregnanolone.

Sepranolone is designed to normalize GABA A receptor

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

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

Data from an open-label Phase 2a randomized study

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

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

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

26 subjects were treated with sepranolone (10 mg, administered by subcutaneous injection twice weekly in addition to standard of care

(SOC) versus standard of care alone.

The Phase 2a results showed competitive tic reduction and improved

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

Sepranolone not only reduced tic severity in its primary clinical endpoint

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

69% greater increase of Quality of Life (using the Gilles de la Tourette Syndrome Quality of Life) total score (GTS-QOL)

50% greater reduction in impairment (YGTSS)

44% greater reduction of the premonitory urge to tic (PUTS – the Premonitory Urge to Tic scale)

35% greater clinical improvement and ~75% fewer patients worsening on the Tourette Syndrome-Clinical Global Impression (TS-CGI) scale

Importantly, no off-target CNS effects or systemic side effects were

observed in this study.

Further, sepranolone has been evaluated in multiple clinical neuro/hormonal studies involving over 335 participants.

Sepranolone was well tolerated with no serious treatment emergent adverse

events reported.

The most common adverse events were of mild or moderate intensity related to injection sites, with pain, erythema and

pruritus being the most common.

Relmada expects to initiate a Phase 2 pilot study

of sepranolone in PWS in mid-2026.

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 cancer, neurological disorders, depression and other diseases.

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

in the United States or elsewhere.

company developing new chemical entities (NCE) and novel versions of drug products that potentially address areas of high unmet medical

need in the treatment of cancer, neurological disorders, and other diseases.

Currently, none of our product candidates has

been approved for sale in the United States or elsewhere.

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

In order to market

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

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

We have not generated revenues and do not anticipate

generating revenues for the foreseeable future.

We had net loss of approximately $79,979,400 and $98,791,700 for the years ended December

31, 2024 and 2023, respectively.

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

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

We have not generated revenues and do not anticipate generating revenues

for the foreseeable future.

We had net loss of approximately $57,385,200 and $79,979,400 for the years ended December 31, 2025 and 2024,

respectively.

As of December 31, 2025, we had an accumulated deficit of approximately $698,267,200.

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

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

TS, obsessive-compulsive disorder, and gambling disorder, potentially providing coverage beyond 2038.

We have more than 10 issued patents and pending

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

We have more than 50 issued patents and pending

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

coverage beyond 2033.

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

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

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

In the European Union,

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.

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;

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, 2024, the Company has not generated

any revenue related to this license agreement.

Following the 2024 REL-1017 setback and subsequent post hoc analyses,

this license agreement was terminated effective July 7, 2025.

Sepranolone Acquisition

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an exclusivity agreement in October 2024.

We will only assume liabilities arising after

the effective date of the Purchase Agreement.

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

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

remain with Asarina.

We only assumed liabilities arising after the effective date of the

Purchase Agreement.

All other liabilities, including those arising before the effective date of the Purchase Agreement, taxes, employment-related

liabilities, and those related to the negotiation and consummation of the Purchase Agreement, remained with Asarina.

NDV-01 In-License Agreement

On March 24, 2025, we entered into an Exclusive

License Agreement with Trigone, an Israeli company.

On March 24, 2025, the Company entered into an Exclusive License Agreement

with Trigone, a privately held Israeli company.

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

1 unchanged sentence

Under the terms of the agreement, the

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

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

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

in development, regulatory and sales milestones pending successful commercialization.

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

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

manufacturing and commercialization.

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

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

In addition, the Company will pay up to $200

million in development, regulatory and commercial milestones pending successful commercialization.

The Company will also pay a royalty

of 3% on any net sales.

As of December 31, 2025, a milestone had been achieved with a $2 million

The milestone payment was accrued for as of December 31, 2025 and paid to Trigone in January 2026.

Inturrisi / Manfredi

In January 2018, the Company entered into an

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

the Assignment Agreement, the Agreements) with Dr.

Inturrisi and Dr.

Paolo Manfredi (collectively, the Licensor).

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

psychiatric use (the Existing Invention) to Licensor.

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

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

other indications such as those contemplated above.

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

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

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

until the earliest to occur of the following events:

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

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

of the License Agreement.

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

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

Relmada will also pay Licensor tiered payments

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

granted under the License Agreement.

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

every three months.

The License Agreement includes standard termination

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

under the License Agreement.

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

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

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

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

or if we (a) substantially modify Dr.

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

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

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

or the esmethadone intellectual property without Dr.

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

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

License Agreement or December 31, 2022.

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

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

Traversa’s death or disability does not give Licensor

the right to terminate the License Agreement.

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

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

The License Agreement was not otherwise modified.

On July 7, 2025, the Company delivered to Dr.

Paolo Manfredi formal notice of termination of the License Agreement entered into in January 2018, under which we had licensed

certain rights, including patents and patent applications, to esmethadone, in the context of other indications, thus ending the Company’s

esmethadone development program.

As a result of the notice of termination, all material obligations under the license agreement with the

Licensor ceased as of October 5, 2025, which was 90 days after the date of the notice.

There were no fees or costs associated with the

termination of the License Agreement.

Psilocybin License Agreement

On July 16, 2021, the Company entered into a

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

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

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

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

mechanism of action.

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

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

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

Arbormentis, LLC is also eligible to

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

The license agreement

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

On May 12, 2025, the Company delivered to Arbormentis LLC a formal

notice of termination of the License Agreement entered into in July 2021, under which the Company had licensed development and commercial

rights to a noval psilocybin and derivative, thus ending the Company’s psilocybin development program.

As a result of the cancellation,

all obligations under the license agreement with Arbormentis ceased as of August 10, 2025, which was 90 days after the date of notice.

There were no fees or costs associated with the termination of the License Agreement.

Key Strengths

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

Compelling lead product opportunities in NDV-01 and Sepranolone

Compelling lead product

opportunities in NDV-01 and sepranolone

Multiple potential bladder

cancer related indications for NDV-01

Extensive safety database for sepranolone as well as promising signal

of efficacy in TS

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

Experienced management team with considerable drug development expertise

Multiple potential bladder cancer related indications for NDV-01

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

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

Scientific support of leading experts:

Scientific support of leading

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

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are subject to extensive regulation by the FDA.

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

and regulations govern, among other things, the research, development, testing, manufacture, storage, recordkeeping, approval, labeling,

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

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 nonclinical laboratory and animal tests, the submission

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

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

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

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

Nonclinical tests include laboratory evaluation

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

of the product.

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

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

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

Long-term nonclinical tests, such as animal

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

A 30-day waiting period after the submission

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

During this period, if FDA concludes that a deficiency

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

resolve the matter with the IND applicant.

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

means of rapid communication or in writing.

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

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

The applicant must respond in writing to each deficiency before the

clinical hold can be lifted.

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

in the IND may begin.

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

the supervision of a qualified investigator.

The Federal Food, Drug, and Cosmetic Act (FDCA) and other federal and state statutes and

regulations govern, among other things, the research, development, testing, manufacture, storage, recordkeeping, approval, labeling, promotion

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

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 new drug applications (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 non-clinical 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.

Non-clinical 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.

conduct of the non-clinical tests must comply with federal regulations and requirements, including good laboratory practices.

of non-clinical testing are submitted to FDA as part of an IND along with other information, including information about product chemistry,

manufacturing and controls, and a proposed clinical trial protocol.

Long-term non-clinical tests, such as animal tests of reproductive

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

A 30-day waiting period after the submission of each IND is required

prior to the commencement of clinical testing in humans.

During this period, if FDA concludes that a deficiency exists in a clinical investigation

that may be grounds for the imposition of clinical hold, FDA will usually attempt to discuss and satisfactorily resolve the matter with

the IND applicant.

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

or in writing.

No more than 30 days after imposition of the clinical hold, a written explanation of the basis for the hold will be issued

by FDA and sent to the applicant.

The applicant must respond in writing to each deficiency before the clinical hold can be lifted.

FDA has neither commented on nor questioned the IND within this 30-day period, the clinical trial proposed in the IND may begin.

trials involve the administration of the investigational new drug to healthy volunteers or patients under the supervision of a qualified

investigator.

Clinical trials must be conducted:

(i) in compliance with federal regulations;

(ii) in compliance

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

of clinical trial sponsors, administrators and monitors;

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

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

(ii) in compliance with good clinical practice,

or GCP, an international standard meant to protect the rights and health of patients and to define the roles of clinical trial sponsors,

administrators and monitors;

as well as (iii) under protocols detailing the objectives of the trial, the parameters to be used in monitoring

safety and the effectiveness criteria to be evaluated.

Each protocol involving testing on U.S.

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

patients and subsequent protocol amendments

must be submitted to FDA as part of the IND.

FDA may not permit a clinical trial to begin,

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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.

Phase 2 usually involves trials in a limited

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

identify common adverse effects and safety risks.

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

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

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

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

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

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,

an NDA is prepared and submitted to FDA.

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.

Phase 2 usually involves trials in a limited patient population to

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

effects and safety risks.

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

3 trials are undertaken to obtain the additional information about clinical efficacy and safety in a larger number of patients, typically

at geographically dispersed clinical trial sites, to permit FDA to evaluate the overall benefit-risk relationship of the drug and to provide

adequate information for the labeling of the drug.

In many cases, particularly for prevalent diseases, the FDA requires two adequate and

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

In many other conditions,

particularly for rare disease therapies, a single adequate and well-controlled Phase 3 trial may be sufficient when in conjunction with

confirmatory evidence.

A single adequate and well-controlled Phase 3 trial may also be sufficient, through it is less common, 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.

After completion of the required clinical testing, an NDA is prepared

and submitted to FDA.

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

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

pharmacology, chemistry, manufacture and controls.

The NDA must include the

results of all non-clinical, clinical and other testing and a compilation of data relating to the product’s pharmacology, chemistry,

manufacture and controls.

The cost of preparing and submitting an NDA is substantial.

The submission of most

NDAs is additionally subject to a substantial application user fee, and the applicant under an approved NDA is also subject to an annual

program fee for each prescription product.

The submission of most NDAs is additionally subject

to a substantial application user fee, and the applicant under an approved NDA is also subject to an annual program fee for each prescription

These fees are typically increased annually.

Sponsors of applications for drugs granted Orphan

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 filed based on the agency’s threshold determination that it is sufficiently complete

to permit substantive review.

Sponsors of applications for drugs granted Orphan 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 filed based on the agency’s threshold determination that it is sufficiently complete to permit substantive review.

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

FDA has agreed to certain performance goals

in the review of NDAs to encourage timeliness.

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

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

Priority review can be

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

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

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

FDA has agreed to certain performance goals in the review of NDAs to encourage

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 information that the FDA considers to be a major amendment to the

FDA may also refer applications for novel drug

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Among the other benefits of Orphan Drug

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

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

Disclosure of Clinical Trial Information

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provisions of the approved labeling.

Adverse event reporting and submission of periodic

reports are required following FDA approval of an NDA.

FDA also may require post-marketing testing, known as Phase 4 testing, REMS and

surveillance to monitor the effects of an approved product, or FDA may place conditions on an approval that could restrict the distribution

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.

Adverse event reporting and submission of periodic reports are required

following FDA approval of an NDA.

FDA also may require post-marketing testing, known as Phase 4 testing, REMS and surveillance to monitor

the effects of an approved product, or FDA may place conditions on an approval that could restrict the distribution or use of the product.

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

manufacturers and certain of their subcontractors are required to register their establishments with FDA and certain state agencies.

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.

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

Evaluations, commonly known as the Orange Book.

Drugs listed in the Orange Book can, in turn, be cited by potential generic competitors

in support of approval of an abbreviated new drug application (ANDA).

An ANDA provides for marketing of a drug product that has the same

active ingredients in the same strengths and dosage form as the listed drug and has been shown through bioequivalence testing to be therapeutically

equivalent to the listed drug.

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

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

Drugs approved in this way

are commonly referred to as “generic equivalents” to the listed drug and can often be substituted by pharmacists under prescriptions

written for the original listed drug.

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.

Drugs listed in the Orange Book can, in turn, be cited by potential generic competitors in support

of approval of an abbreviated new drug application (ANDA).

An ANDA provides for marketing of a drug product that has the same active ingredients

in the same strengths and dosage form as the listed drug and has been shown through bioequivalence testing to be therapeutically equivalent

to the listed drug.

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

of, non-clinical or clinical tests to prove the safety or effectiveness of their drug product.

Drugs approved in this way are commonly

referred to as “generic equivalents” to the listed drug and can often be substituted by pharmacists under prescriptions written

for the original listed drug.

The ANDA applicant is required to certify to

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

In the case of a non-racemic drug containing

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

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

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

These conditions include:

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

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

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

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

has been approved.

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

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

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

for any condition of use of the racemic drug.

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

before October 1, 2027.

Patent Term Extension

16 unchanged sentences

NDA has not been submitted.

Controlled Substances

The active ingredients in esmethadone and psilocybin

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

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

The CSA and its implementing regulations establish a closed chain

of distribution for entities handling controlled substances.

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

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

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

The law and regulations require those individuals

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

of controlled substances to illicit channels of commerce.

The CSA classifies controlled substances into

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.

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

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

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

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

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

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

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

and security.

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

limited and tightly controlled.

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

signature of a practitioner when presented to a pharmacy.

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

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

Esmethadone is the single isomer of methadone,

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

Any Schedule I

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

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

Rescheduling requires

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

to the DEA on the appropriate schedule.

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

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

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

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

substance within that state based on federal rescheduling.

Facilities that manufacture, distribute, import

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 will conduct a preregistration inspection to evaluate compliance

with these requirements before issuing a new registration.

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

importers, and exporters to review compliance with these requirements.

The specific security requirements vary by the type of business

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

The most stringent requirements apply to manufacturers

of Schedule I and Schedule II substances.

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

a secure vault with specific structural requirements.

Other physical security requirements that apply to all controlled substances include

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

DEA regulations also require that registrants restrict employee

access to controlled substances.

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

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

Manufacturers and distributors

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

narcotic substances, and certain other designated substances.

All DEA registrants must report any controlled substance thefts or significant

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

In addition to maintaining an importer and/or exporter

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

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

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

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

The DEA conducts cyclic inspections

to determine whether registrants are complying with these requirements.

Practitioners such as pharmacies and physicians,

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 requires that the DEA establish

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

In addition, DEA registered

manufacturers must obtain annual individual manufacturing and procurement quotas.

The DEA establishes annually an aggregate production

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

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

The aggregate

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

Manufacturers

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

Manufacturers

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

The quotas apply equally to the manufacturing of the active

pharmaceutical ingredient and production of dosage forms.

The DEA may adjust aggregate production quotas and individual manufacturing

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

such adjustments.

Failure to comply with applicable DEA requirements,

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

The DEA may seek civil

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

to revoke the DEA registrations.

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

The various states, commonwealths, and the District

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

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

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

The United States and the majority of countries

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

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the DOJ, and state and local governments.

The federal Anti-Kickback Statute prohibits,

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

The federal Anti-Kickback Statute prohibits, among

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

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

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

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

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.

In addition, certain marketing practices,

including off-label promotion, may also violate false claims laws.

Additionally, the government may assert that a claim including items

or services resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the

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.

Protection and Affordable Care Act as amended by the Health Care and Education Reconciliation Act (collectively, the ACA) amended the

intent element of the federal statute so that a person or entity no longer needs to have actual knowledge of the statute or specific intent

to violate it in order to commit a violation.

This statute has been interpreted to apply to arrangements between pharmaceutical manufacturers

on the one hand and prescribers, purchasers and formulary managers, among others, on the other.

Although there are a number of statutory

exceptions and regulatory safe harbors protecting certain common activities from prosecution or other regulatory sanctions, the exceptions

and safe harbors are drawn narrowly, and practices that involve remuneration intended to induce prescribing, purchases or recommendations

may be subject to scrutiny if they do not qualify for an exception or safe harbor.

In addition, a person or entity does not need to have

actual knowledge of the Anti-Kickback Statute or specific intent to violate it in order to commit a violation.

Federal civil and criminal false claims laws, including the federal

civil False Claims Act, prohibit any person or entity from knowingly presenting, or causing to be presented, a false claim for payment

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

This includes claims

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

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

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.

In addition, certain marketing practices, including off-label promotion, may also

violate false claims laws.

Additionally, the government may assert that a claim including items or services resulting from a violation

of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the federal civil False Claims Act.

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

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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.

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 reports must be submitted on an annual basis.

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.

In addition, several states now require prescription

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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.

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.

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

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

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.

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 imposes additional obligations on companies covered by the legislation and substantially modifies the CCPA, went into effect.

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.

The CPRA also creates a new state agency that is vested with authority to implement and enforce the

CCPA and CPRA.

Virginia’s 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

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) 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.

Healthcare reform proposals

recently culminated in the enactment of the Inflation Reduction Act (IRA) in August 2022, which, among other things, requires HHS to directly

negotiate the selling price of statutorily specified number of drugs and biologics each year that CMS reimburses under Medicare Part B

The negotiated price may not exceed a statutory ceiling price.

Only high-expenditure

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

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

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

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

product has been announced.

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

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

20 Part B or Part D drugs will be selected.

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

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

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

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

selection for negotiation.

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

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

In addition, the IRA extends

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

through plan year 2025.

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

for the initial years.

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

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

Only high-expenditure single-source drugs that have been approved

for at least 7 years (11 years for single-source biologics) are eligible to be selected by CMS for negotiation, with the negotiated price

taking effect two years after the selection year.

For 2026, the first year in which negotiated prices become effective, CMS selected 10

high-cost Medicare Part D products in 2023, negotiations began in 2024, and the negotiated maximum fair price for each product has been

In addition, CMS has selected and announced the negotiated maximum fair price for 15 additional Medicare Part D drugs, which

will be effective in 2027.

For 2028, CMS has selected an additional 15 drugs, comprised of drugs covered under Medicare Part D and, for

the first time, drugs payable under Medicare Part B.

For 2029 and subsequent years, 20 Part B or Part D drugs will be selected.

a drug or biological product that has an orphan drug designation for only one rare disease or condition will be excluded from the IRA’s

price negotiation requirements, but will lose that exclusion if it receives designations for more than one rare disease or condition,

or if it is approved for an indication that is not within that single designated rare disease or condition, unless such additional designation

or such disqualifying approvals are withdrawn by the time CMS evaluates the drug for selection for negotiation.

However, as a result

of a statutory amendment enacted in July 2025, beginning with the 2028 negotiated price applicability year, a drug may be designated for

more than one rare disease or condition and still be excluded from price negotiation, as long as the only approved indications are for

such rare diseases or conditions.

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

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

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.

The federal administration is pursuing executive

and regulatory actions directing HHS to pursue most favored nation (MFN) pricing targets for prescription drugs and to evaluate other

potential reforms including, for example, an executive order tasking the Center for Medicare and Medicaid Innovation (CMMI) to consider

new payment and healthcare models to limit drug spending, and promote MFN drug pricing, among other directives.

For example, on December

23, 2025, CMS issued proposed regulations to establish, under CMMI, two mandatory MFN demonstration models under Medicare Parts B and

D, respectively.

If these rules or other MFN pricing rules are finalized, they are likely to reduce prices of at least some drugs in the

United States, if they are also sold in comparator countries.

Even if a company does not market drugs in such countries, the company could

be indirectly affected if its drugs compete with drugs whose prices were reduced as a result of MFN pricing initiatives.

Further, at the U.S.

state level, legislatures

are increasingly enacting laws and implementing regulations designed to control pharmaceutical and biological product pricing, including

price or reimbursement constraints, discount requirements, marketing cost disclosure and price increase transparency reporting, and programs

designed to encourage importation from other countries and bulk purchasing.

Additional state and federal healthcare reform measures may

be adopted in the future, any of which could limit the amounts that federal and state governments will pay for healthcare products and

services or increase manufacturers’ operational costs and compliance risks.

Insurance Coverage and Reimbursement

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Total Rewards and Employee Engagement

We maintain 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.

We maintain 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.

We seek to determine compensation on

the basis of merit and without regard to demographic characteristics.

During 2023, 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 2025, 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

Corporate Information

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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