What changed in this filing

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Item 1. Business

2026-07-29 compared with 2025-08-11 · 496 added, 523 removed, 1169 unchanged (47% of the section changed)

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The current generation of our product candidate is referred to as “CypCaps™.”

During the year ended April 30, 2024, we determined

that research and development in the treatment of diabetes would no longer be pursued.

On November 17, 2023, the Board formed the Strategic

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programs and our relationship with SG Austria Pte.

Ltd (“SG Austria”), including that all licensed patents have expired and

(“SG Austria”), including that all licensed patents have expired and

that know-how relating to our Cell-in-a-Box® technology solely resides with SG Austria.

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Our reevaluation for addressing the

FDA concerns has resulted in delays stemming from the review of the non-clinical package provided by SG Austria and changes to the FDA

FDA concerns has resulted in delays stemming from the review of the nonclinical package provided by SG Austria and changes to the FDA

review process.

The Cell-in-a-Box® encapsulation technology

is designed to present genetically engineered live human cells to targeted tissues.

The Cell-in-a-Box® encapsulation technology is

designed to present genetically engineered live human cells to targeted tissues.

The technology is intended to result in the formation

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to the FDA concerning the safety of the microcapsules.

We have been developing therapies for pancreatic

tumors by using genetically engineered live human cells that we believe may be capable of converting a cancer prodrug into its cancer-killing

We have been developing therapies for pancreatic tumors

by using genetically engineered live human cells that we believe may be capable of converting a cancer prodrug into its cancer-killing

We encapsulate those cells using the Cell-in-a-Box® technology and place those capsules in the body as close as possible to

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options to use highly toxic cancer-killing drugs in tightly controlled perivascular spaces.

Until the Strategic Scientific Committee completes

its evaluation of our programs and we enter into a new framework for its relationship with SG Austria, spending on our development programs

has been curtailed.

Until the Scientific Committee

completes its evaluation of our programs and we enter into a new framework for our relationship with SG Austria, spending on our

development programs has been curtailed.

Investigational New Drug Application and Clinical

On September 1, 2020, we submitted an IND to the

FDA for a planned clinical trial in LAPC.

On September 1, 2020, we submitted an IND to the FDA

for a planned clinical trial in LAPC.

On October 1, 2020, we received notice from the FDA that it had placed our IND on clinical hold.

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we must do to have the clinical hold lifted.

In order to address the clinical hold, the FDA

has requested that we:

In order to address the clinical hold, the FDA has

requested that we:

Provide additional sequencing data and genetic stability studies;

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Provide a discussion with data for trial of the potential for cellular and humoral immune reactivity against the heterologous rat CYP2B1 protein and potential for induction of autoimmune-mediated toxicities in our study population.

We assembled a scientific and regulatory team

to address the FDA requests.

We assembled a scientific and regulatory team to address

the FDA requests.

That team has been working diligently to complete the items requested by the FDA.

The following provides a detailed summary of our

activities to have the clinical hold lifted:

The following provides a detailed summary of our activities

to have the clinical hold lifted:

Stability Studies on Our Clinical Trial Product Candidate for Pancreatic Cancer .

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The clinical hold did not reflect any deficiencies of the clinical trial proposed.

We seek to resolve these non-clinical issues to enable FDA review of a new clinical protocol that reflects the standard of care for LAPC.

We assembled a scientific and regulatory team

of experts to address the FDA requests.

During the year ended April 30, 2025, our scientific consultants have been in active dialog with

the FDA seeking permission to forego the large animal study.

The technology upon which the LAPC treatment will be based, intra-arterial

chemotherapy, has been used in five clinical trials in humans.

The data available from these human clinical trials supersedes large animal

The treatment may not be a treatment of pancreatic cancer, but a method of improving and possibly enabling complete surgical

resection of the tumor.

We are waiting for the FDA’s responses and hope the FDA will accept that the LAPC treatment now meets manufacturing

standard requirements, which have significantly improved since the clinical hold was first placed.

The FDA may require additional preclinical

studies when the meeting takes place.

We are in ongoing dialogue with SG Austria to prepare for the next steps and add requested information

to the drug master file upon which the Company still relies on.

We seek to resolve these nonclinical issues to enable FDA review of a new clinical protocol that reflects the standard of care for LAPC.

We assembled a scientific and regulatory team of experts

to address the FDA requests.

During the year ended April 30, 2026, our scientific consultants have been in active dialog with the FDA.

The technology upon which the LAPC treatment will be based, intra-arterial chemotherapy The treatment may not be a treatment of pancreatic

cancer, but a method of improving and possibly enabling complete surgical resection of the tumor.

We are waiting for the FDA’s responses

and hope the FDA will accept that the LAPC treatment now meets manufacturing standard requirements, which have significantly improved

since the clinical hold was first placed.

The FDA may require additional preclinical studies when the meeting takes place.

We are in ongoing

dialogue with SG Austria to prepare for the next steps including encapsulation of the cells, testing the glide force and pressure testing

of pushing the cells through syringes and catheters.

History of the Business

In 2013, we restructured our operations to focus

on biotechnology.

On January 6, 2015, we changed our name from “Nuvilex, Inc.” to “PharmaCyte Biotech, Inc.” to

reflect the nature of our business.

In 2013, we restructured our operations to focus on

biotechnology.

On January 6, 2015, we changed our name from “Nuvilex, Inc.” to “PharmaCyte Biotech, Inc.” to reflect

the nature of our business.

We are a biotechnology company focused on developing

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into the following agreements.

Commencing in May 2011, we entered into a series

of agreements and amendments with SG Austria Pte.

(“SG Austria”) to acquire certain assets from SG Austria as well as

an exclusive, worldwide license to use, with a right to sublicense, the Cell-in-a-Box® technology and trademark for the development

Commencing in May 2011, we entered into a series of

agreements and amendments with SG Austria Pte.

(“SG Austria”) to acquire certain assets from SG Austria as well as an

exclusive, worldwide license to use, with a right to sublicense, the Cell-in-a-Box® technology and trademark for the development

of therapies for cancer (“SG Austria APA”).

In June 2013, we and SG Austria entered a Third

Addendum to the SG Austria APA (“Third Addendum”).

The Third Addendum materially changed the transaction contemplated by the

SG Austria APA.

Under the Third Addendum, we acquired 100% of the equity interests in Bio Blue Bird and received a 14.5% equity interest

in SG Austria.

In June 2013, we and SG Austria entered a Third Addendum

to the SG Austria APA (“Third Addendum”).

The Third Addendum materially changed the transaction contemplated by the SG Austria

Under the Third Addendum, we acquired 100% of the equity interests in Bio Blue Bird and received a 14.5% equity interest in SG Austria.

(i) $500,000 to retire all outstanding debt of Bio Blue Bird;

and (ii) $1.0 million to SG Austria.

SG Austria $1,572,193 in exchange for a 14.5% equity interest of SG Austria.

The transaction required SG Austria to return to us the 66,667

shares of our common stock held by SG Austria and for us to return to SG Austria the 67 shares of common stock of Austrianova we held.

We also paid SG Austria $1,572,193

in exchange for a 14.5% equity interest of SG Austria.

The transaction required SG Austria to return to us the 66,667 shares of our common

stock held by SG Austria and for us to return to SG Austria the 67 shares of common stock of Austrianova we held.

Effective as of the same date we entered the Third

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and trademark for the development of therapies for cancer.

With respect to Bio Blue Bird, Bavarian Nordic

A/S (“Bavarian Nordic”) and GSF-Forschungszentrum für Umwelt u.

With respect to Bio Blue Bird, Bavarian Nordic A/S

(“Bavarian Nordic”) and GSF-Forschungszentrum für Umwelt u.

Gesundheit GmbH (collectively, “Bavarian Nordic/GSF”)

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valid claim of the licensed patent rights.

Bavarian Nordic/GSF and Bio Blue Bird amended

the Bavarian Nordic License Agreement in December 2006 (“First Amendment to Bavarian Nordic/GSF License Agreement”) to reflect

Bavarian Nordic/GSF and Bio Blue Bird amended the

Bavarian Nordic/GSF License Agreement in December 2006 (“First Amendment to Bavarian Nordic/GSF License Agreement”) to reflect

(i) the license granted was exclusive;

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expenses for the existing patents;

and (iv) to make clear that the license will survive as a license granted by one of the licensors

if the other licensor rejects performance under the Bavarian Nordic License Agreement due to any actions or declarations of insolvency.

and (iv) to make clear that the license will survive as a license granted by one of the licensors if

the other licensor rejects performance under the Bavarian Nordic/GSF License Agreement due to any actions or declarations of insolvency.

In October 2016, Bavarian Nordic/GSF and Bio Blue

Bird further amended the Bavarian Nordic License Agreement (“Second Amendment to Bavarian Nordic/GSF License Agreement”) in

Bird further amended the Bavarian Nordic/GSF License Agreement (“Second Amendment to Bavarian Nordic/GSF License Agreement”)

(i) include the right to import in the scope of the license;

(ii) reflect ownership and notification of improvements;

clarify which provisions survive expiration or termination of the Bavarian Nordic License Agreement;

(iv) provide rights to Bio Blue Bird

to the clinical data after the expiration of the licensed patent rights;

and (v) change the notice address and recipients of Bio Blue

clarify which provisions survive expiration or termination of the Bavarian Nordic/GSF License Agreement;

(iv) provide rights to Bio Blue

Bird to the clinical data after the expiration of the licensed patent rights;

and (v) change the notice address and recipients of Bio

Market Opportunity and Competitive Landscape

We are developing for live cell encapsulation-based

therapies for cancer.

The Cell-in-a-Box ® capsules

are comprised of cotton’s natural component – cellulose.

We are developing live cell encapsulation-based therapies

The Cell-in-a-Box ® capsules are

comprised of cotton’s natural component – cellulose.

Other materials used by competitors include alginate, collagen, chitosan,

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When thawed, the cells are recovered with approximately 85% viability.

We are unaware of any

other cell encapsulation material that is capable of protecting their encapsulated cells to this degree.

The implications of this property

of the Cell-in-a-Box ® technology are obvious – long-term storage of encapsulated cells and shipment of encapsulated

cells over long distances.

The implications of

this property of the Cell-in-a-Box ® technology are obvious – long-term storage of encapsulated cells and shipment

of encapsulated cells over long distances.

We believe our live cell encapsulation technology

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and about 7% of all cancer deaths.

Our goal is to satisfy a clear unmet medical need

for patients with LAPC whose tumors no longer respond after 4-6 months of treatment with the chemotherapy combination of Abraxane ® plus

Our goal is to meet the medical need for patients

with LAPC whose tumors no longer respond after 4-6 months of treatment with the chemotherapy combination of Abraxane ® plus

gemcitabine or the four-drug combination known as FOLFIRINOX.

For these patients, there is currently no effective therapy.

there will be no therapy comparable to our Cell-in-a-Box ® plus low dose of ifosfamide combination therapy when it

is used in these patients.

For these patients, there are currently only limited therapy options.

believe there will be no therapy comparable to our Cell-in-a-Box ® plus low dose of ifosfamide combination therapy

when it is used in these patients.

We face intense competition in the field of treating

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Addendum to the Asset Purchase Agreement.

The Fourth Addendum required us to make the following payment the payment was timely made in

The Fourth Addendum required us to make the following payment.

The payment was timely made in

full under the payment deadlines set forth in the Fourth Addendum:

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Twenty percent royalty on gross revenues received by us or our affiliates from a sublicense or right to use the patents or the licenses granted by us or our affiliates;

Fifty percent of any other financial and non-financial consideration received

from sublicensees of the Cell-in-a-Box® technology;

Fifty percent of any other financial and non-financial consideration received from sublicensees of the Cell-in-a-Box® technology;

The removal of all milestone payments.

Sources and Availability of Raw Materials

The entire encapsulation process relating to the

encapsulation of the cells for the oncology is to be carried out by Austrianova.

The entire encapsulation process relating to the encapsulation

of the cells for the oncology is to be carried out by Austrianova.

Austrianova is the sole source of our product candidates.

Austrianova is responsible for acquiring all of the necessary raw materials used in this process, including the cellulose sulfate necessary

for encapsulating the live cells, a process proprietary to Austrianova.

Austrianova from time to time has experienced significant supply

chain delays, and we believe Austrianova may also be experiencing liquidity issues as well.

If Austrianova is unwilling or unable to perform

such manufacturing for us, we may not be able to locate a replacement manufacturer for our product candidates.

is responsible for acquiring all of the necessary raw materials used in this process, including the cellulose sulfate necessary for encapsulating

the live cells, a process proprietary to Austrianova.

Austrianova from time to time has experienced significant supply chain delays, and

we believe Austrianova may also be experiencing liquidity issues as well.

If Austrianova is unwilling or unable to perform such manufacturing

for us, we may not be able to locate a replacement manufacturer for our product candidates.

Intellectual Property and Trade Secrets

Intellectual property and patent protection are

of paramount importance to our business, as are the trade secrets and other strategies we have employed with Austrianova to protect the

proprietary Cell-in-a-Box® technology.

Although we believe we take reasonable measures to protect our intellectual property and trade

secrets and those of Austrianova, we cannot guarantee we will be able to protect and enforce our IP or obtain patent protection for our

product candidates as needed.

Intellectual property and patent protection are of

paramount importance to our business, as are the trade secrets and other strategies we have employed with Austrianova to protect the proprietary

Cell-in-a-Box® technology.

Although we believe we take reasonable measures to protect our intellectual property and trade secrets

and those of Austrianova, we cannot guarantee we will be able to protect and enforce our IP or obtain patent protection for our product

candidates as needed.

We license technology and trademarks relating to two areas:

(i) live cell encapsulation with cells that

express cytochrome P450 where the capsule is permeable to prodrug molecules and the cells are retained within the capsules and (ii) treatment

(i) live cell encapsulation with cells that express

cytochrome P450 where the capsule is permeable to prodrug molecules and the cells are retained within the capsules and (ii) treatment

of solid cancerous tumors.

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reflect the nature of our current business.

Our corporate headquarters are located at 3960

Howard Hughes Parkway, Suite 500, Las Vegas, Nevada 89169.

Our corporate headquarters are located at 3960 Howard

Hughes Parkway, Suite 500, Las Vegas, Nevada 89169.

Our telephone number is (917) 595-2850.

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pharmaceuticals and biologics in the U.S.

Its regulatory authority is based in the FDCA and the Public Health Service Act.

Pharmaceutical

products and biologics are also subject to other federal, state and local statutes and regulations.

A failure to comply with any applicable

requirements during the product development, approval, or post-approval periods, may lead to administrative or judicial sanctions.

sanctions could include, among other things, the imposition by the FDA or by an Institutional Review Board (“IRB”) of a hold

on clinical trials, FDA refusal to approve pending marketing applications or supplements, withdrawal of previously granted approval, warning

letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, civil penalties

or criminal prosecution.

The steps required before a new drug or biologic

may be marketed in the U.S.

Its regulatory authority is based in the FDCA and the Public Health Service Act (the “PHSA”).

Pharmaceutical products and biologics are also subject to other federal, state and local statutes and regulations.

A failure to comply

with any applicable requirements during the product development, approval, or post-approval periods, may lead to administrative or judicial

These sanctions could include, among other things, the imposition by the FDA or by an Institutional Review Board (“IRB”)

of a hold on clinical trials, FDA refusal to approve pending marketing applications or supplements, withdrawal of previously granted approval,

warning letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, civil

penalties or criminal prosecution.

The steps required before a new drug or biologic may

be marketed in the U.S.

generally include:

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Clinical Development

Before a drug or biological product candidate

may be tested in human subjects, it must undergo preclinical testing.

Preclinical tests generally include laboratory evaluations of a

product candidate’s chemical and biological activities, formulation and stability, as well as studies to evaluate toxicity in animals

and potential for other adverse events, which support subsequent clinical testing and rationale for subsequent therapeutic use.

The Consolidated Appropriations Act for 2023,

signed into law on December 29, 2022, (P.L.

117-328) amended both the FDCA and PHSA to specify that nonclinical testing for drugs and

biologics, respectively, may, but is not required to, include in vivo animal testing.

According to the amended language, a sponsor

may fulfill nonclinical testing requirements by completing various in vitro assays (e.g., cell-based assays, organ chips, or microphysiological

Before a drug or biological product candidate may

be tested in human subjects, it must undergo preclinical testing.

Preclinical tests generally include laboratory evaluations of a product

candidate’s chemical and biological activities, formulation and stability, as well as studies to evaluate toxicity in animals and

potential for other adverse events, which support subsequent clinical testing and rationale for subsequent therapeutic use.

The Consolidated Appropriations Act for 2023, signed

into law on December 29, 2022, (P.L.

117-328) amended both the FDCA and PHSA to specify that nonclinical testing for drugs and biologics,

respectively, may, but is not required to, include in vivo animal testing.

According to the amended language, a sponsor may fulfill

nonclinical testing requirements by completing various in vitro assays (e.g., cell-based assays, organ chips, or microphysiological

systems), in silico studies (i.e., computer modeling), other human or non-human biology-based tests (e.g., bioprinting), or in

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to the FDA and human clinical trials have been initiated.

An IND is a request for authorization from the

FDA to administer an investigational product candidate to humans.

An IND is a request for authorization from the FDA

to administer an investigational product candidate to humans.

This authorization is required before interstate shipping and administration

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also be imposed by the FDA at any time before or during studies due to safety concerns or non-compliance.

A clinical trial involves the administration of

the investigational product candidate to patients under the supervision of qualified investigators following GCP standards, which include

A clinical trial involves the administration of the

investigational product candidate to patients under the supervision of qualified investigators following GCP standards, which include

the requirement that all research subjects provide their informed consent in writing for their participation in any clinical trial (unless

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in 2017, and the government has begun enforcing those requirements against non-compliant clinical trial sponsors.

Human clinical trials are typically conducted

in three sequential phases that may overlap or be combined:

Human clinical trials are typically conducted in three

sequential phases that may overlap or be combined:

Phase 1 Clinical Trial :

The product candidate

is initially introduced into health human subjects and tested for safety, and such trials typically include a preliminary determination

is initially introduced into healthy human subjects and tested for safety, and such trials typically include a preliminary determination

of a product candidate’s safe dosage range.

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Phase 3 Clinical Trial :

Such trials are

undertaken with an expanded patient population to further evaluate dosage, clinical efficacy and safety in an expanded patient population,

often at geographically dispersed clinical study sites.

These studies are intended to establish the overall risk-benefit ratio of the

product candidate and provide, if appropriate, an adequate basis for product labeling.

These trials may include comparisons with placebo

and/or other comparator treatments.

Such trials are undertaken

with an expanded patient population to further evaluate dosage, clinical efficacy and safety in an expanded patient population, often

at geographically dispersed clinical study sites.

These studies are intended to establish the overall risk-benefit ratio of the product

candidate and provide, if appropriate, an adequate basis for product labeling.

These trials may include comparisons with placebo and/or

other comparator treatments.

The duration of treatment is often extended to mimic the actual use of a product during marketing.

Post-approval trials, sometimes referred to as

Phase 4 clinical trials, may be conducted after initial marketing approval.

These trials are used to gain additional experience from the

treatment of patients in the intended therapeutic indication.

In certain instances, the FDA may mandate the performance of Phase 4 clinical

trials as a condition of approval of an NDA or BLA.

Congress also amended the FDCA, as part of the

Consolidated Appropriations Act for 2023, in order to require sponsors of a Phase 3 clinical trial, or other “pivotal study”

of a new drug or biologic to support marketing authorization, to design and submit a diversity action plan for such clinical trial.

action plan must include the sponsor’s diversity goals for enrollment, as well as a rationale for the goals and a description of

how the sponsor will meet them.

Sponsors must submit a diversity action plan to the FDA by the time the sponsor submits the relevant clinical

trial protocol to the agency for review.

Post-approval trials, sometimes referred to as Phase

4 clinical trials, may be conducted after initial marketing approval.

These trials are used to gain additional experience from the treatment

of patients in the intended therapeutic indication.

In certain instances, the FDA may mandate the performance of Phase 4 clinical trials

as a condition of approval of an NDA or BLA.

Congress also amended the FDCA, as part of the Consolidated

Appropriations Act for 2023, in order to require sponsors of a Phase 3 clinical trial, or other “pivotal study” of a new drug

or biologic to support marketing authorization, to design and submit a diversity action plan for such clinical trial.

The action plan

must include the sponsor’s diversity goals for enrollment, as well as a rationale for the goals and a description of how the sponsor

will meet them.

Sponsors must submit a diversity action plan to the FDA by the time the sponsor submits the relevant clinical trial protocol

to the agency for review.

The FDA may grant a waiver for some or all of the requirements for a diversity action plan.

is unknown at this time how the diversity action plan may affect Phase 3 trial planning and timing or what specific information FDA will

expect in such plans, but if the FDA objects to a sponsor’s diversity action plan, it may delay trial initiation.

Progress reports detailing the results of the

clinical trials must be submitted at least annually to the FDA and more frequently if serious adverse events occur.

The decision to terminate

development of an investigational product candidate may be made by either a health authority body, such as the FDA, by IRB/ethics committees,

or by the sponsor for various reasons.

The FDA may order the temporary or permanent discontinuation of a clinical trial at any time, or

impose other sanctions, if it believes that the clinical trial either is not being conducted in accordance with FDA requirements or presents

It is unknown at

this time how the diversity action plan may affect Phase 3 trial planning and timing or what specific information FDA will expect in such

plans, but if the FDA objects to a sponsor’s diversity action plan, it may delay trial initiation.

Progress reports detailing the results of the clinical

trials must be submitted at least annually to the FDA and more frequently if serious adverse events occur.

The decision to terminate development

of an investigational product candidate may be made by either a health authority body, such as the FDA, by IRB/ethics committees, or by

the sponsor for various reasons.

The FDA may order the temporary or permanent discontinuation of a clinical trial at any time, or impose

other sanctions, if it believes that the clinical trial either is not being conducted in accordance with FDA requirements or presents

an unacceptable risk to the patients enrolled in the trial.

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its institution if the clinical trial is not being conducted in accordance with the clinical protocol, GCP, or other IRB requirements

or if the product candidate has been associated with unexpected serious harm to patients.In some cases, a clinical trial is overseen by

an independent group of qualified experts organized by the trial sponsor, known as a data safety monitoring board (or DSMB).

or if the product candidate has been associated with unexpected serious harm to patients.

In some cases, a clinical trial is overseen

by an independent group of qualified experts organized by the trial sponsor, known as a data safety monitoring board (or DSMB).

provides authorization for whether a trial may move forward at designated checkpoints based on access that only the group maintains to

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approval for the product in the specified indication.

New Drug Applications and Biologic Licensing

To obtain approval to market a drug or biologic

in the U.S., a marketing application must be submitted to the FDA that provides data establishing the safety and effectiveness of the

product candidate for the proposed indication.

The application includes all relevant data available from pertinent preclinical studies

and clinical trials, including negative or ambiguous results as well as positive findings, together with detailed information relating

to the product’s chemistry, manufacturing and controls, as well as proposed labeling, among other things.

Data can come from company-sponsored

clinical trials intended to test the safety and effectiveness of a product, or from several alternative sources, including studies initiated

by investigators.

To support marketing approval, the data submitted must be sufficient in quality and quantity to establish the safety

and effectiveness of the investigational product candidate to the satisfaction of the FDA.

In most cases, the NDA, in the case of a drug,

or BLA, in the case of a biologic, must be accompanied by a substantial user fee.

New Drug Applications and Biologic Licensing Applications

To obtain approval to market a drug or biologic in

the U.S., a marketing application must be submitted to the FDA that provides data establishing the safety and effectiveness of the product

candidate for the proposed indication.

The application includes all relevant data available from pertinent preclinical studies and clinical

trials, including negative or ambiguous results as well as positive findings, together with detailed information relating to the product’s

chemistry, manufacturing and controls, as well as proposed labeling, among other things.

Data can come from company-sponsored clinical

trials intended to test the safety and effectiveness of a product, or from several alternative sources, including studies initiated by

investigators.

To support marketing approval, the data submitted must be sufficient in quality and quantity to establish the safety and

effectiveness of the investigational product candidate to the satisfaction of the FDA.

In most cases, the NDA, in the case of a drug, or

BLA, in the case of a biologic, must be accompanied by a substantial user fee.

These fees are typically adjusted annually, but exemptions

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The resubmitted application is also subject to review before the FDA accepts it for filing.

After the NDA or BLA submission is accepted for

filing, the FDA begins an in-depth review.

After the NDA or BLA submission is accepted for filing,

the FDA begins an in-depth review.

The FDA has agreed to certain performance goals in the review of NDAs and BLAs.

Under the goals

and policies agreed to by the FDA under the Prescription Drug User Fee Act (“PDUFA”), for original NDAs and BLAs, the FDA

has ten months from the filing date in which to complete its initial review of a standard application and respond to the applicant, and

six months from the filing date for an application with "priority review." For all BLAs and new molecular entity (“NME”)

Under the goals and

policies agreed to by the FDA under the Prescription Drug User Fee Act (“PDUFA”), for original NDAs and BLAs, the FDA has

ten months from the filing date in which to complete its initial review of a standard application and respond to the applicant, and six

months from the filing date for an application with “priority review.” For all BLAs and new molecular entity (“NME”)

NDAs, the ten and six-month time periods run from the filing date;

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FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions.

Before approving an NDA or a BLA, the FDA will

typically inspect the facilities at which the product is manufactured.

The FDA will not approve the product candidate unless it determines

that the manufacturing processes and facilities substantially comply with cGMP requirements and are adequate to assure consistent production

Before approving an NDA or a BLA, the FDA will typically

inspect the facilities at which the product is manufactured.

The FDA will not approve the product candidate unless it determines that

the manufacturing processes and facilities substantially comply with cGMP requirements and are adequate to assure consistent production

of the product within required specifications.

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the sponsor and one or more clinical trial sites to assure compliance with GCP requirements and the integrity of the clinical data submitted

FDA also may require the development of a risk

evaluation and mitigation strategy (“REMS”) if it determines that a REMS is necessary to ensure that the benefits of the drug

outweigh its risks and to assure the safe use of the drug or biological product.

FDA also may require the development of a risk evaluation

and mitigation strategy (“REMS”) if it determines that a REMS is necessary to ensure that the benefits of the drug outweigh

its risks and to assure the safe use of the drug or biological product.

The REMS could include medication guides, physician communication

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development programs.

After the FDA evaluates the NDA or BLA and the

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

After the FDA evaluates the NDA or BLA and the product

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

An approval letter authorizes commercial

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of any requested additional information, the FDA ultimately may decide that the application does not satisfy the regulatory criteria for

If a product receives regulatory approval from

the FDA, the approval is limited to the conditions of use (e.g., patient population, indication) described in the application.

depending on the specific risks to be addressed, the FDA may require that contraindications, warnings or precautions be included in the

product labeling, require that post-approval trials, including Phase 4 clinical trials, be conducted to further assess a product’s

safety after approval, require testing and surveillance programs to monitor the product after commercialization, or impose other conditions,

If a product receives regulatory approval from the

FDA, the approval is limited to the conditions of use (e.g., patient population, indication) described in the application.

Further, depending

on the specific risks to be addressed, the FDA may require that contraindications, warnings or precautions be included in the product

labeling, require that post-approval trials, including Phase 4 clinical trials, be conducted to further assess a product’s safety

after approval, require testing and surveillance programs to monitor the product after commercialization, or impose other conditions,

including distribution and use restrictions or other risk management mechanisms under a REMS, which can materially affect the potential

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FDA Review and Approval Process for Combination

A combination product is a product composed of

a combination of two or more FDA-regulated product constituent parts or products, e.g., drug-device or biologic-device.

Such products

often raise regulatory, policy and review management challenges because they integrate constituent parts that are regulated under different

types of regulatory requirements and by different FDA Centers, namely, the Center for Drug Evaluation and Research, or CDER, the Center

for Devices and Radiological Health, or CDRH, or the Center for Biologics Evaluation and Research, or CBER.

Differences in regulatory

pathways for each constituent part can impact the regulatory processes for all aspects of product development and management, including

preclinical testing, clinical investigation, marketing applications, manufacturing and quality control, adverse event reporting, promotion

and advertising, and post-approval modifications.

A combination product is a product composed of a combination

of two or more FDA-regulated product constituent parts or products, e.g., drug-device or biologic-device.

Such products often raise regulatory,

policy and review management challenges because they integrate constituent parts that are regulated under different types of regulatory

requirements and by different FDA Centers, namely, the Center for Drug Evaluation and Research, or CDER, the Center for Devices and Radiological

Health, or CDRH, or the Center for Biologics Evaluation and Research, or CBER.

Differences in regulatory pathways for each constituent

part can impact the regulatory processes for all aspects of product development and management, including preclinical testing, clinical

investigation, marketing applications, manufacturing and quality control, adverse event reporting, promotion and advertising, and post-approval

modifications.

Specifically, under regulations issued by the FDA, a combination product may be:

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any investigational drug, biologic, or device packaged separately that according to its proposed labeling is for use only with another individually specified investigational drug, biologic, or device where both are required to achieve the intended use, indication, or effect.

The FDA’s Office of Combination Products,

or OCP, was established to provide prompt determination of the FDA Center with primary jurisdiction over the review and regulation of

a combination product;

ensure timely and effective premarket review by overseeing the timeliness of and coordinating reviews involving

more than one center;

The FDA’s Office of Combination Products, or

OCP, was established to provide prompt determination of the FDA Center with primary jurisdiction over the review and regulation of a combination

ensure timely and effective premarket review by overseeing the timeliness of and coordinating reviews involving more than one

ensure consistent and appropriate post-market regulation;

resolve disputes regarding review timeliness;

and review/revise

agreements, guidance and practices specific to the assignment of combination products.

OCP determines which Center will have primary

jurisdiction for the combination product, referred to as the Lead Center, based on the combination product’s “primary mode

of action,” or PMOA.

and review/revise agreements,

guidance and practices specific to the assignment of combination products.

OCP determines which Center will have primary jurisdiction

for the combination product, referred to as the Lead Center, based on the combination product’s “primary mode of action,”

A mode of action is the means by which a product achieves an intended therapeutic effect or action.

is the mode of action that provides the most important therapeutic action of the combination product, or the mode of action expected to

make the greatest contribution to the overall intended therapeutic effects of the combination product.

The Lead Center has primary responsibility

for the review and regulation of a combination product;

however a second Center is often involved in the review process, especially to

provide input regarding the “secondary” component(s).

The PMOA is the mode of action

that provides the most important therapeutic action of the combination product, or the mode of action expected to make the greatest contribution

to the overall intended therapeutic effects of the combination product.

The Lead Center has primary responsibility for the review and

regulation of a combination product;

however a second Center is often involved in the review process, especially to provide input regarding

the “secondary” component(s).

In most instances, the Lead Center applies its usual regulatory pathway.

For example, a drug-biologic combination product assigned to CDER will typically be reviewed under an NDA, while a drug-biologic combination

product assigned to CBER is typically reviewed under through a BLA.

Often it is difficult for OCP to determine with

reasonable certainty the most important therapeutic action of the combination product.

In those difficult cases, OCP will consider consistency

with other combination products raising similar types of safety and effectiveness questions, or which Center has the most expertise to

evaluate the most significant safety and effectiveness questions raised by the combination product.

A sponsor may use a voluntary formal

process, known as a Request for Designation, when the product classification is unclear or in dispute, to obtain a binding decision as

to which Center will regulate the combination product.

If the sponsor objects to that decision, the sponsor may request that OCP reconsider

its decision.

For example, a drug-biologic

combination product assigned to CDER will typically be reviewed under an NDA, while a drug-biologic combination product assigned to CBER

is typically reviewed under through a BLA.

Often it is difficult for OCP to determine with reasonable

certainty the most important therapeutic action of the combination product.

In those difficult cases, OCP will consider consistency with

other combination products raising similar types of safety and effectiveness questions, or which Center has the most expertise to evaluate

the most significant safety and effectiveness questions raised by the combination product.

A sponsor may use a voluntary formal process,

known as a Request for Designation, when the product classification is unclear or in dispute, to obtain a binding decision as to which

Center will regulate the combination product.

If the sponsor objects to that decision, the sponsor may request that OCP reconsider its

Combination products are subject to FDA user fees

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for which an NDA is submitted is subject to the NDA fee under PDUFA.

Since a combination product incorporates two or

more constituent parts that have different regulatory requirements, a combination product manufacturer must comply with all cGMP requirements

Since a combination product incorporates two or more

constituent parts that have different regulatory requirements, a combination product manufacturer must comply with all cGMP requirements

that apply to each constituent part.

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Post Approval Regulations

After regulatory approval of a drug or

biologic is obtained, a company is required to comply with pervasive and continuing FDA requirements.

For example, as a condition of

approval of an NDA or BLA, the FDA may require post-marketing testing, including a Phase 4 clinical trial and surveillance to

further assess and monitor the product’s safety and effectiveness after commercialization has begun.

In addition, NDA and BLA

holders are subject to regulations governing, among other things, monitoring and recordkeeping activities, reporting of adverse

experiences with the product, product sampling and distribution restrictions, complying with promotion and advertising requirements,

which include restrictions on promoting drugs for unapproved uses or patient populations (i.e., “off-label use”) and

limitations on industry-sponsored scientific and educational activities.

If there are any modifications to the product, including

changes in indications, labeling or manufacturing processes or facilities, the applicant may be required to submit and obtain FDA

approval of a new NDA/BLA or an NDA/BLA supplement, which may require the applicant to develop additional data or conduct additional

nonclinical studies and clinical trials.

The FDA may also place other conditions on approvals including the requirement for a REMS

to assure the safe use of the product.

A REMS could include medication guides, physician communication plans or elements to assure

safe use, such as restricted distribution methods, patient registries and other risk minimization tools.

Any of these limitations on

approval or marketing could restrict the commercial promotion, distribution, prescription or dispensing of products.

approvals may be withdrawn for non-compliance with regulatory standards or if problems occur following initial marketing.

FDA regulations also require drug and biologic

manufacturers to implement and maintain quality control and manufacturing procedures that conform to cGMP standards to assure and preserve

the long-term stability of the approved product.

The FDA periodically inspects The cGMP regulations include requirements relating to organization

of personnel, buildings and facilities, equipment, control of components and drug product containers and closures, production and process

After regulatory approval of a drug or biologic is

obtained, a company is required to comply with pervasive and continuing FDA requirements.

For example, as a condition of approval of an

NDA or BLA, the FDA may require post-marketing testing, including a Phase 4 clinical trial and surveillance to further assess and monitor

the product’s safety and effectiveness after commercialization has begun.

In addition, NDA and BLA holders are subject to regulations

governing, among other things, monitoring and recordkeeping activities, reporting of adverse experiences with the product, product sampling

and distribution restrictions, complying with promotion and advertising requirements, which include restrictions on promoting drugs for

unapproved uses or patient populations (i.e., “off-label use”) and limitations on industry-sponsored scientific and educational

If there are any modifications to the product, including changes in indications, labeling or manufacturing processes or facilities,

the applicant may be required to submit and obtain FDA approval of a new NDA/BLA or an NDA/BLA supplement, which may require the applicant

to develop additional data or conduct additional nonclinical studies and clinical trials.

The FDA may also place other conditions on approvals

including the requirement for a REMS to assure the safe use of the product.

A REMS could include medication guides, physician communication

plans or elements to assure safe use, such as restricted distribution methods, patient registries and other risk minimization tools.

of these limitations on approval or marketing could restrict the commercial promotion, distribution, prescription or dispensing of products.

Product approvals may be withdrawn for non-compliance with regulatory standards or if problems occur following initial marketing.

FDA regulations also require drug and biologic manufacturers

to implement and maintain quality control and manufacturing procedures that conform to cGMP standards to assure and preserve the long-term

stability of the approved product.

The cGMP regulations include requirements relating to organization of

personnel, buildings and facilities, equipment, control of components and drug product containers and closures, production and process

controls, packaging and labeling controls, holding and distribution, laboratory controls, records and reports and returned or salvaged

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mandated modification of promotional materials and labeling and the issuance of corrective information.

In addition, the distribution of prescription

pharmaceutical and biological products is subject to the Prescription Drug Marketing Act (“PDMA”) which regulates the distribution

of drugs and drug samples at the federal level, and sets minimum standards for the registration and regulation of drug distributors by

Both the PDMA and state laws limit the distribution of prescription product samples and impose requirements to ensure accountability

in distribution.

The Drug Supply Chain Security Act (“DSCSA”) was enacted with the aim of building an electronic system to

identify and trace certain prescription drugs distributed in the U.S., including most biological products.

The DSCSA mandates phased-in

and resource-intensive obligations for pharmaceutical manufacturers, wholesale distributors and dispensers over a 10-year period, which

culminated in November 2023.

Most recently, the FDA announced a one-year stabilization period to November 2024, giving entities subject

to the DSCSA additional time to finalize interoperable tracking systems and to ensure supply chain continuity.

From time to time, new

legislation and regulations may be implemented that could significantly change the statutory provisions governing the approval, manufacturing

and marketing of products regulated by the FDA.

For example, FDA released proposed regulations in February 2022 to amend the national

standards for licensing of wholesale drug distributors by the states;

establish new minimum standards for state licensing third-party

logistics providers;

and create a federal system for licensure for use in the absence of a state program, each of which is mandated by

In addition, the distribution of prescription pharmaceutical

and biological products is subject to the Prescription Drug Marketing Act (“PDMA”) which regulates the distribution of drugs

and drug samples at the federal level, and sets minimum standards for the registration and regulation of drug distributors by the states.

Both the PDMA and state laws limit the distribution of prescription product samples and impose requirements to ensure accountability in

distribution.

The Drug Supply Chain Security Act (“DSCSA”) was enacted with the aim of building an electronic system to identify

and trace certain prescription drugs distributed in the U.S., including most biological products.

The DSCSA mandates phased-in and resource-intensive

obligations for pharmaceutical manufacturers, wholesale distributors and dispensers over a 10-year period, which culminated in November 2023.

Most recently, the FDA announced a one-year stabilization period to November 2024, giving entities subject to the DSCSA additional time

to finalize interoperable tracking systems and to ensure supply chain continuity.

From time to time, new legislation and regulations may

be implemented that could significantly change the statutory provisions governing the approval, manufacturing and marketing of products

regulated by the FDA.

For example, FDA released proposed regulations in February 2022 to amend the national standards for licensing of

wholesale drug distributors by the states;

establish new minimum standards for state licensing third-party logistics providers;

a federal system for licensure for use in the absence of a state program, each of which is mandated by the DSCSA.

It is impossible to predict whether further legislative or regulatory changes will be enacted, or FDA regulations, guidance or interpretations

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Advertising and Promotion

The FDA and other federal regulatory agencies

tightly regulate the marketing and promotion of drugs and biologics through, among other things, standards and regulations for direct-to-consumer

The FDA and other federal regulatory agencies tightly

regulate the marketing and promotion of drugs and biologics through, among other things, standards and regulations for direct-to-consumer

advertising, communications regarding unapproved uses, industry-sponsored scientific and educational activities and promotional activities

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and approves the application for any patent term extension.

Similar provisions are available in Europe and

other foreign jurisdictions to extend the term of a patent that covers an approved drug, biologic or medical device.

In the future, if

any of our product candidates receive FDA approval, we expect to apply for patent term extension on patents covering those products that

may be eligible for such patent term restoration.

Similar provisions are available in Europe and other

foreign jurisdictions to extend the term of a patent that covers an approved drug, biologic or medical device.

In the future, if any of

our product candidates receive FDA approval, we expect to apply for patent term extension on patents covering those products that may

be eligible for such patent term restoration.

Pediatric Exclusivity

Pediatric exclusivity is a type of non-patent

marketing exclusivity available in the U.S.

Pediatric exclusivity is a type of non-patent marketing

exclusivity available in the U.S.

and, if granted, it provides for the attachment of an additional six months of marketing protection

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The issuance of a Written Request by the FDA does not require the sponsor to undertake the described studies.

Reference Product Exclusivity for Biological

March 2010, the Patient Protection and Affordable

Care Act was enacted in the U.S.

Reference Product Exclusivity for Biological Products

In March 2010, the Patient Protection and

Affordable Care Act was enacted in the U.S.

and included the Biologics Price Competition and Innovation Act of 2009, or the BPCIA.

The BPCIA amended

the PHSA to create an abbreviated approval pathway for biological products that are biosimilar to or interchangeable with an FDA-licensed

reference biological product.

Since that time, the FDA has approved numerous biosimilar products, issued several guidance documents outlining

its approach to reviewing and approving biosimilars and interchangeable biosimilar, and created a public database that contains information

on all FDA-licensed biological products, including biosimilars, called the Purple Book.

The BPCIA amended the PHSA to create an abbreviated approval pathway for biological products that are biosimilars to or

interchangeable with an FDA-licensed reference biological product.

Since that time, the FDA has approved numerous biosimilar

products, issued several guidance documents outlining its approach to reviewing and approving biosimilars and interchangeable

biosimilar, and created a public database that contains information on all FDA-licensed biological products, including biosimilars,

called the Purple Book.

In 2024, the FDA approved a record number of biosimilars,

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competition may increase in therapeutic areas relevant to our pipeline.

A biosimilar product is defined as one that is

highly similar to a reference product notwithstanding minor differences in clinically inactive components and for which there are no clinically

A biosimilar product is defined as one that is highly

similar to a reference product notwithstanding minor differences in clinically inactive components and for which there are no clinically

meaningful differences between the biological product and the reference product in terms of the safety, purity and potency of the product.

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biosimilar may be substituted for the reference product without the intervention of the healthcare provider who prescribed the reference

The biosimilar applicant must demonstrate that

the product is biosimilar based on data from (1) analytical studies showing that the biosimilar product is highly similar to the

reference product;

The biosimilar applicant must demonstrate that the

product is biosimilar based on data from (1) analytical studies showing that the biosimilar product is highly similar to the reference

(2) animal studies (including toxicity);

and (3) one or more clinical studies to demonstrate safety, purity

and potency in one or more appropriate conditions of use for which the reference product is approved.

In addition, the applicant must

show that the biosimilar and reference products have the same mechanism of action for the conditions of use on the label, route of administration,

dosage and strength, and the production facility must meet standards designed to assure product safety, purity and potency.

and (3) one or more clinical studies to demonstrate safety, purity and potency

in one or more appropriate conditions of use for which the reference product is approved.

In addition, the applicant must show that the

biosimilar and reference products have the same mechanism of action for the conditions of use on the label, route of administration, dosage

and strength, and the production facility must meet standards designed to assure product safety, purity and potency.

A reference biological product is granted 12 years

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In Europe, and throughout the world, other countries have enacted anti-bribery laws and/or regulations similar

On February 10, 2025, President Trump issued Executive

Order 14209, which mandates a 180-day pause on new FCPA investigations and enforcement actions by the Department of Justice (DOJ), with

limited exceptions.

The order also directs a comprehensive review of FCPA enforcement guidelines, potentially signaling a shift in enforcement

While the Securities and Exchange Commission (SEC) retains independent enforcement authority under the FCPA, it may also

scale back enforcement during this review period.

We continue to monitor developments and assess potential impacts on our compliance

obligations and risk exposure.

Orphan Drug Status

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Orphan drug designation does not convey any advantage in or shorten the duration of the regulatory review and approval

Upon the approval of the first NDA or BLA for

a drug or biologic designated as an Orphan Drug for a specified indication, the sponsor of that NDA or BLA is entitled to seven years

of exclusive marketing rights in the U.S.

for the drug or biologic for the particular indication, during which time the FDA may not approve

any other applications to market the same drug for the same indication, except in very limited circumstances.

However, Orphan Drug exclusivity

for an approved indication does not prevent the approval of a different drug for the same rare disease or condition, nor does it block

the approval of the same drug for different conditions.

Upon the approval of the first NDA or BLA for a drug

or biologic designated as an Orphan Drug for a specified indication, the sponsor of that NDA or BLA is entitled to seven years of exclusive

marketing rights in the U.S.

for the drug or biologic for the particular indication, during which time the FDA may not approve any other

applications to market the same drug for the same indication, except in very limited circumstances.

However, Orphan Drug exclusivity for

an approved indication does not prevent the approval of a different drug for the same rare disease or condition, nor does it block the

approval of the same drug for different conditions.

Additionally, if a drug designated as an orphan product receives marketing approval

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of the same indication.

Recent court cases have challenged FDA’s

approach to determining the scope of orphan drug exclusivity;

Recent court cases have challenged FDA’s approach

to determining the scope of orphan drug exclusivity;

however, at this time the agency continues to apply its long-standing interpretation

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and European Union.

Fast Track, Breakthrough Therapy and Priority

Review Designations

Fast Track, Breakthrough Therapy and Priority Review

The FDA is authorized to grant designations, including

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important new drugs or biologics to patients earlier than under standard FDA review procedures.

To be eligible for a fast-track designation, the

FDA must determine, based on the request of a sponsor, that a product is intended to treat a serious or life-threatening disease or condition

To be eligible for a fast-track designation, the FDA

must determine, based on the request of a sponsor, that a product is intended to treat a serious or life-threatening disease or condition

and demonstrates the potential to address an unmet medical need.

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The FDA may give a priority review designation

to a drug or biologic that that treats a serious condition and, if approved, would provide a significant improvement in safety or effectiveness.

to a drug or biologic that treats a serious condition and, if approved, would provide a significant improvement in safety or effectiveness.

The FDA determines at the time that the marketing application is submitted, on a case-by-case basis, whether the proposed drug or biologic

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Drugs or biologics designated as breakthrough

therapies may also eligible for accelerated approval.

The FDA must take certain actions with respect to breakthrough therapies, such as

holding timely meetings and providing advice, which are intended to expedite the development and review of an application for approval

therapies may also be eligible for accelerated approval.

The FDA must take certain actions with respect to breakthrough therapies, such

as holding timely meetings and providing advice, which are intended to expedite the development and review of an application for approval

of a breakthrough therapy.

Even if a product qualifies for one or more of

these programs, the FDA may later decide that the product no longer meets the conditions for qualification or decide that the time period

for FDA review or approval will not be shortened.

Even if a product qualifies for one or more of these

programs, the FDA may later decide that the product no longer meets the conditions for qualification or decide that the time period for

FDA review or approval will not be shortened.

Furthermore, fast track designation, breakthrough therapy designation and priority review

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that the therapeutic effect is reasonably likely to predict the ultimate long-term clinical benefit of a drug or biologic.

The accelerated approval pathway is most often

used in settings in which the course of a disease is long, and an extended period of time is required to measure the intended clinical

benefit of a drug or biologic, even if the effect on the surrogate or intermediate clinical endpoint occurs rapidly.

Thus, accelerated

approval has been used extensively in the development and approval of drugs or biologics for treatment of a variety of cancers in which

the goal of therapy is generally to improve survival or decrease morbidity and the duration of the typical disease course requires lengthy

and sometimes large trials to demonstrate a clinical or survival benefit.

The accelerated approval pathway is most often used

in settings in which the course of a disease is long, and an extended period of time is required to measure the intended clinical benefit

of a drug or biologic, even if the effect on the surrogate or intermediate clinical endpoint occurs rapidly.

Thus, accelerated approval

has been used extensively in the development and approval of drugs or biologics for treatment of a variety of cancers in which the goal

of therapy is generally to improve survival or decrease morbidity and the duration of the typical disease course requires lengthy and

sometimes large trials to demonstrate a clinical or survival benefit.

The accelerated approval pathway is usually contingent

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to verify the claimed clinical benefits of the product.

All promotional materials for drug candidates

approved under accelerated regulations are subject to prior review by the FDA.

All promotional materials for drug candidates approved

under accelerated regulations are subject to prior review by the FDA.

Regulation Outside of the U.S.

In addition to regulations in the U.S., we will

be subject to a variety of foreign regulations governing clinical trials and commercial sales and distribution of our products outside

In addition to regulations in the U.S., we will be

subject to a variety of foreign regulations governing clinical trials and commercial sales and distribution of our products outside of

Whether or not we obtain FDA approval for a product candidate, we must obtain approval from the comparable regulatory authorities

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approval in one country or jurisdiction may negatively impact the regulatory process in others.

European Union drug development, review

In the European Union, our product candidates

also may be subject to extensive regulatory requirements.

European Union drug development, review and

In the European Union, our product candidates also

may be subject to extensive regulatory requirements.

As in the U.S., medicinal products can be marketed only if marketing authorization

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in the European Union are subject to significant regulatory controls.

The Clinical Trials Directive 2001/20/EC, the

Directive 2005/28/EC on GCP, and the related national implementing provisions of the individual EU Member States previously governed the

system for the approval of clinical trials in the European Union.

Under this system, an applicant had to obtain prior approval from the

competent national authority of the EU Member States in which the clinical trial is to be conducted.

Furthermore, the applicant could

only start a clinical trial at a specific study site after the competent ethics committee has issued a favorable opinion.

The Clinical Trials Directive 2001/20/EC, the Directive

2005/28/EC on GCP, and the related national implementing provisions of the individual EU Member States previously governed the system

for the approval of clinical trials in the European Union.

Under this system, an applicant had to obtain prior approval from the competent

national authority of the EU Member States in which the clinical trial is to be conducted.

Furthermore, the applicant could only start

a clinical trial at a specific study site after the competent ethics committee has issued a favorable opinion.

In 2014, the new Clinical Trials Regulation, (EU)

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Trials Regulation became applicable, the Clinical Trials Regulation will at that time begin to apply to the clinical trial.

The Clinical Trials Regulation aims to simplify

and streamline the approval of clinical trials in the European Union.

The Clinical Trials Regulation aims to simplify and

streamline the approval of clinical trials in the European Union.

The main characteristics of the regulation include:

a streamlined

application procedure via a single entry point, the “EU portal” or Clinical Trial Information System, or CTIS;

of documents to be prepared and submitted for the application as well as simplified reporting procedures for clinical trial sponsors;

and a harmonized procedure for the assessment of applications for clinical trials, which is divided in two parts.

Part I is assessed by

the competent authorities of all EU Member States in which an application for authorization of a clinical trial has been submitted (Member

States concerned).

Part II is assessed separately by each Member State concerned.

Strict deadlines have been established for the assessment

of clinical trial applications.

The role of the relevant ethics committees in the assessment procedure will continue to be governed by

the national law of the concerned EU Member State.

a streamlined application

procedure via a single entry point, the “EU portal” or Clinical Trial Information System, or CTIS;

a single set of documents

to be prepared and submitted for the application as well as simplified reporting procedures for clinical trial sponsors;

and a harmonized

procedure for the assessment of applications for clinical trials, which is divided in two parts.

Part I is assessed by the competent authorities

of all EU Member States in which an application for authorization of a clinical trial has been submitted (Member States concerned).

II is assessed separately by each Member State concerned.

Strict deadlines have been established for the assessment of clinical trial

applications.

The role of the relevant ethics committees in the assessment procedure will continue to be governed by the national law

of the concerned EU Member State.

However, overall related timelines will be defined by the Clinical Trials Regulation.

Use of the CTIS became mandatory for new clinical trial application submissions as of February 1, 2023.

To obtain a marketing authorization of a drug

in the European Union, we may submit marketing authorization applications, or MAA, either under the so-called centralized or national

authorization procedures.

Use of the CTIS

became mandatory for new clinical trial application submissions as of February 1, 2023.

To obtain a marketing authorization of a drug in the

European Union, we may submit marketing authorization applications, or MAA, either under the so-called centralized or national authorization

Centralized procedure

The centralized procedure provides for the grant

of a single marketing authorization following a favorable opinion by the European Medicines Agency, or EMA, that is valid in all EU member

The centralized procedure provides for the grant of

a single marketing authorization following a favorable opinion by the European Medicines Agency, or EMA, that is valid in all EU member

states, as well as Iceland, Liechtenstein and Norway.

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Pediatric studies

Prior to obtaining a marketing authorization in

the European Union, applicants have to demonstrate compliance with all measures included in an EMA-approved Pediatric Investigation Plan,

Prior to obtaining a marketing authorization in the

European Union, applicants have to demonstrate compliance with all measures included in an EMA-approved Pediatric Investigation Plan,

or PIP, covering all subsets of the pediatric population, unless the EMA has granted a product-specific waiver, a class waiver, or a deferral

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a medicine in children is not needed or is not appropriate, such as for diseases that only affect the elderly population.

Before a marketing authorization application can

be filed, or an existing marketing authorization can be amended, the EMA determines that companies actually comply with the agreed studies

Before a marketing authorization application can be

filed, or an existing marketing authorization can be amended, the EMA determines that companies actually comply with the agreed studies

and measures listed in each relevant PIP.

European Union regulatory exclusivity

In the European Union, new products authorized

for marketing (i.e., reference products) qualify for eight years of data exclusivity and an additional two years of market exclusivity

upon marketing authorization.

The data exclusivity period prevents generic or biosimilar applicants from relying on the pre-clinical and

clinical trial data contained in the dossier of the reference product when applying for a generic or biosimilar marketing authorization

in the European Union during a period of eight years from the date on which the reference product was first authorized in the European

The market exclusivity period prevents a successful generic or biosimilar applicant from commercializing its product in the EU

until ten years have elapsed from the initial authorization of the reference product in the EU.

The ten-year market exclusivity period

can be extended to a maximum of eleven years if, during the first eight years of those ten years, the marketing authorization holder obtains

an authorization for one or more new therapeutic indications which, during the scientific evaluation prior to their authorization, are

held to bring a significant clinical benefit in comparison with existing therapies.

In the European Union, new products authorized for

marketing (i.e., reference products) qualify for eight years of data exclusivity and an additional two years of market exclusivity upon

marketing authorization.

The data exclusivity period prevents generic or biosimilar applicants from relying on the pre-clinical and clinical

trial data contained in the dossier of the reference product when applying for a generic or biosimilar marketing authorization in the

European Union during a period of eight years from the date on which the reference product was first authorized in the European Union.

The market exclusivity period prevents a successful generic or biosimilar applicant from commercializing its product in the EU until ten

years have elapsed from the initial authorization of the reference product in the EU.

The ten-year market exclusivity period can be extended

to a maximum of eleven years if, during the first eight years of those ten years, the marketing authorization holder obtains an authorization

for one or more new therapeutic indications which, during the scientific evaluation prior to their authorization, are held to bring a

significant clinical benefit in comparison with existing therapies.

European Union orphan designation and exclusivity

The criteria for designating an orphan medicinal

product in the European Union, are similar in principle to those in the U.S.

Under Article 3 of Regulation (EC) 141/2000, a medicinal

product may be designated as orphan if (1) it is intended for the diagnosis, prevention or treatment of a life-threatening or chronically

debilitating condition;

(2) either (a) such condition affects no more than five in 10,000 persons in the European Union when the application

is made, or (b) the product, without the benefits derived from orphan status, would not generate sufficient return in the European Union

to justify investment;

and (3) there exists no satisfactory method of diagnosis, prevention or treatment of such condition authorized

for marketing in the European Union, or if such a method exists, the product will be of significant benefit to those affected by the condition,

as defined in Regulation (EC) 847/2000.

Orphan medicinal products are eligible for financial incentives such as reduction of fees or fee

waivers and are, upon grant of a marketing authorization, entitled to ten years of market exclusivity for the approved therapeutic indication.

The criteria for designating an orphan medicinal product

in the European Union, are similar in principle to those in the U.S.

Under Article 3 of Regulation (EC) 141/2000, a medicinal product

may be designated as orphan if (1) it is intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating

(2) either (a) such condition affects no more than five in 10,000 persons in the European Union when the application is made,

or (b) the product, without the benefits derived from orphan status, would not generate sufficient return in the European Union to justify

and (3) there exists no satisfactory method of diagnosis, prevention or treatment of such condition authorized for marketing

in the European Union, or if such a method exists, the product will be of significant benefit to those affected by the condition, as defined

in Regulation (EC) 847/2000.

Orphan medicinal products are eligible for financial incentives such as reduction of fees or fee waivers

and are, upon grant of a marketing authorization, entitled to ten years of market exclusivity for the approved therapeutic indication.

The application for orphan designation must be submitted before the application for marketing authorization.

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duration of, the regulatory review and approval process.

The ten-year market exclusivity in the European

Union may be reduced to six years if, at the end of the fifth year, it is established that the product no longer meets the criteria for

orphan designation, for example, if the product is sufficiently profitable not to justify maintenance of market exclusivity.

Additionally,

marketing authorization may be granted to a similar product for the same indication at any time if:

The ten-year market exclusivity in the European Union

may be reduced to six years if, at the end of the fifth year, it is established that the product no longer meets the criteria for orphan

designation, for example, if the product is sufficiently profitable not to justify maintenance of market exclusivity.

Additionally, marketing

authorization may be granted to a similar product for the same indication at any time if:

the second applicant can establish that its product, although similar, is safer, more effective or otherwise clinically superior;

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PRIME designation

The EMA grants access to the Priority Medicines,

or PRIME, program to investigational medicines for which it determines there to be preliminary data available showing the potential to

address an unmet medical need and bring a major therapeutic advantage to patients.

As part of the program, the EMA provides early and

enhanced dialogue and support to optimize the development of eligible medicines and speed up their evaluation, aiming to bring promising

treatments to patients sooner.

The EMA grants access to the Priority Medicines, or

PRIME, program to investigational medicines for which it determines there to be preliminary data available showing the potential to address

an unmet medical need and bring a major therapeutic advantage to patients.

As part of the program, the EMA provides early and enhanced

dialogue and support to optimize the development of eligible medicines and speed up their evaluation, aiming to bring promising treatments

to patients sooner.

Periods of authorization and renewals

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General Data Protection Regulation

The collection, use, disclosure, transfer, or

other processing of personal data regarding individuals in the European Union, including personal health data, is subject to the European

Union’s General Data Protection Regulation (“GDPR”), which became effective on May 25, 2018.

The GDPR is wide-ranging

in scope and imposes numerous requirements on companies that process personal data, including requirements relating to processing health

and other sensitive data, obtaining consent of the individuals to whom the personal data relates, providing information to individuals

regarding data processing activities, implementing safeguards to protect the security and confidentiality of personal data, providing

notification of data breaches, and taking certain measures when engaging third-party processors.

The GDPR also imposes strict rules on

the transfer of personal data to countries outside the European Union, including the U.S., and permits data protection authorities to

impose large penalties for violations of the GDPR, including potential fines of up to €20 million or 4% of annual global revenues,

whichever is greater.

The GDPR also confers a private right of action on data subjects and consumer associations to lodge complaints with

supervisory authorities, seek judicial remedies, and obtain compensation for damages resulting from violations of the GDPR.

with the GDPR will be a rigorous and time-intensive process that may increase the cost of doing business or require companies to change

their business practices to ensure full compliance.

In July 2023, the European Commission adopted

an adequacy decision for a new mechanism for transferring data from the European Union to the U.S.

The collection, use, disclosure, transfer, or other

processing of personal data regarding individuals in the European Union, including personal health data, is subject to the European Union’s

General Data Protection Regulation (“GDPR”), which became effective on May 25, 2018.

The GDPR is wide-ranging in scope and

imposes numerous requirements on companies that process personal data, including requirements relating to processing health and other

sensitive data, obtaining consent of the individuals to whom the personal data relates, providing information to individuals regarding

data processing activities, implementing safeguards to protect the security and confidentiality of personal data, providing notification

of data breaches, and taking certain measures when engaging third-party processors.

The GDPR also imposes strict rules on the transfer

of personal data to countries outside the European Union, including the U.S., and permits data protection authorities to impose large

penalties for violations of the GDPR, including potential fines of up to €20 million or 4% of annual global revenues, whichever is

The GDPR also confers a private right of action on data subjects and consumer associations to lodge complaints with supervisory

authorities, seek judicial remedies, and obtain compensation for damages resulting from violations of the GDPR.

Compliance with the GDPR

will be a rigorous and time-intensive process that may increase the cost of doing business or require companies to change their business

practices to ensure full compliance.

In July 2023, the European Commission adopted an adequacy

decision for a new mechanism for transferring data from the European Union to the U.S.

– the EU-U.S.

Data Privacy Framework,

which provides individuals in the European Union with several new rights, including the right to obtain access to their data, or obtain

correction or deletion of incorrect or unlawfully handled data.

The adequacy decision followed the signing of an executive order introducing

new binding safeguards to address the points raised by the Court of Justice of the European Union in its decision on a case known as Schrems

Data Privacy Framework, which

provides individuals in the European Union with several new rights, including the right to obtain access to their data, or obtain correction

or deletion of incorrect or unlawfully handled data.

The adequacy decision followed the signing of an executive order introducing new

binding safeguards to address the points raised by the Court of Justice of the European Union in its decision on a case known as Schrems

II , which invalidated the previous EU-U.S.

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the loss of current or prospective customers or other business relationships.

Following the United Kingdom’s withdrawal

from the European Union, the GDPR has been implemented in the United Kingdom (as the U.K.

GDPR sits alongside the amended

United Kingdom Data Protection Act 2018 which implements certain derogations in the EU GDPR into United Kingdom law.

Following the United Kingdom’s withdrawal from

the European Union, the GDPR has been implemented in the United Kingdom (as the U.K.

GDPR sits alongside the amended United

Kingdom Data Protection Act 2018 which implements certain derogations in the EU GDPR into United Kingdom law.

Under the U.K.

companies not established in the United Kingdom but who process personal data in relation to the offering of goods or services to individuals

in the United Kingdom, or to monitor their behavior will be subject to the U.K.

GDPR, companies

not established in the United Kingdom but who process personal data in relation to the offering of goods or services to individuals in

the United Kingdom, or to monitor their behavior will be subject to the U.K.

GDPR – the requirements of which are (at this time)

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of operations.

As previously mentioned, the primary trend in

As previously mentioned, the primary trend in the

healthcare industry and elsewhere is cost containment.

Government authorities and other third-party payors have attempted to

control costs by limiting coverage and the amount of reimbursement for particular medical products and services, implementing reductions

in Medicare and other healthcare funding and applying new payment methodologies.

For example, in March 2010, the Patient Protection and

Affordable Care Act (“ACA”) was enacted, which, among other things, increased the minimum Medicaid rebates owed by most manufacturers

Government authorities and other third-party payors have attempted to control

costs by limiting coverage and the amount of reimbursement for particular medical products and services, implementing reductions in Medicare

and other healthcare funding and applying new payment methodologies.

For example, in March 2010, the Patient Protection and Affordable

Care Act (“ACA”) was enacted, which, among other things, increased the minimum Medicaid rebates owed by most manufacturers

under the Medicaid Drug Rebate Program;

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models to lower Medicare and Medicaid spending.

Legislative and regulatory changes under the ACA

are possible, but it is unknown what form any such changes or any law would take and how or whether it may affect the biopharmaceutical

industry as a whole or our business in the future.

We expect that changes or additions to the ACA, the Medicare and Medicaid programs,

and changes stemming from other healthcare reform measures, especially with regard to healthcare access, financing or other legislation

in individual states, could have a material adverse effect on the healthcare industry in the U.S.

Moreover, there has been heightened governmental

scrutiny over the manner in which manufacturers set prices for their marketed products, which has resulted in several Congressional inquiries

and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to product pricing, review

Legislative and regulatory changes under the ACA are

possible, but it is unknown what form any such changes or any law would take and how or whether it may affect the biopharmaceutical industry

as a whole or our business in the future.

We expect that changes or additions to the ACA, the Medicare and Medicaid programs, and changes

stemming from other healthcare reform measures, especially with regard to healthcare access, financing or other legislation in individual

states, could have a material adverse effect on the healthcare industry in the U.S.

Moreover, there has been heightened governmental scrutiny

over the manner in which manufacturers set prices for their marketed products, which has resulted in several Congressional inquiries and

proposed and enacted federal and state legislation designed to, among other things, bring more transparency to product pricing, review

the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for drug

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was signed into law, or the IRA.

Among other things, the IRA has multiple provisions that may impact the prices of drug products

that are both sold into the Medicare program and throughout the U.S.

Starting in 2023, a manufacturer of a drug or biological product

covered by Medicare Parts B or D must pay a rebate to the federal government if the drug product’s price increases faster than the

rate of inflation.

Among other things, the IRA has multiple provisions that may impact the prices of drug products that

are both sold into the Medicare program and throughout the U.S.

Starting in 2023, a manufacturer of a drug or biological product covered

by Medicare Parts B or D must pay a rebate to the federal government if the drug product’s price increases faster than the rate

of inflation.

This calculation is made on a drug product by drug product basis and the amount of the rebate owed to the federal government

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Those lawsuits are currently ongoing.

In addition to the IRA’s drug price negotiation

provisions, President Biden’s Executive Order 14087, issued in October 2022, called for the CMS Innovation Center to prepare and

submit a report to the White House on potential payment and delivery modes that would complement to IRA, lower drug costs, and promote

access to innovative drugs.

In February 2023, CMS published its report which described three potential models focusing on affordability,

accessibility and feasibility of implementation for further testing by the CMS Innovation Center.

As of February 2024, the CMS Innovation

Center continues to test the proposed models and has started to roll out plans for access model testing of certain product types (e.g.,

cell and gene therapies) by states and manufacturers.

In addition to the IRA’s drug price

negotiation provisions, President Biden’s Executive Order 14087, issued in October 2022, called for the CMS Innovation Center

to prepare and submit a report to the White House on potential payment and delivery modes that would complement the IRA, lower

drug costs, and promote access to innovative drugs.

In February 2023, CMS published its report which described three potential

models focusing on affordability, accessibility and feasibility of implementation for further testing by the CMS Innovation Center.

As of February 2024, the CMS Innovation Center continues to test the proposed models and has started to roll out plans for access

model testing of certain product types (e.g., cell and gene therapies) by states and manufacturers.

At the state level, individual states are increasingly

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demand for our products, once approved, or put pressure on our product pricing.

In the European Union, many member states have

increased the amount of discounts required on pharmaceuticals and these efforts could continue as countries attempt to manage healthcare

expenditures, especially in light of the severe fiscal and debt crises experienced by many countries in the European Union.

pressure on healthcare costs in general, particularly prescription products, has become intense.

As a result, increasingly high barriers

are being erected to the entry of new medicinal products.

Political, economic and regulatory developments may further complicate pricing

negotiations, and pricing negotiations may continue after reimbursement has been obtained.

Reference pricing used by various EU member

states, and parallel trade, i.e., arbitrage between low-priced and high-priced member states, can further reduce prices.

no assurance that any country that has price controls or reimbursement limitations for medicinal products will allow favorable reimbursement

and pricing arrangements for any products, if approved in those countries.

In the European Union, many member states have increased

the amount of discounts required on pharmaceuticals and these efforts could continue as countries attempt to manage healthcare expenditures,

especially in light of the severe fiscal and debt crises experienced by many countries in the European Union.

The downward pressure on

healthcare costs in general, particularly prescription products, has become intense.

As a result, increasingly high barriers are being

erected to the entry of new medicinal products.

Political, economic and regulatory developments may further complicate pricing negotiations,

and pricing negotiations may continue after reimbursement has been obtained.

Reference pricing used by various EU member states, and parallel

trade, i.e., arbitrage between low-priced and high-priced member states, can further reduce prices.

There can be no assurance that any

country that has price controls or reimbursement limitations for medicinal products will allow favorable reimbursement and pricing arrangements

for any products, if approved in those countries.

We cannot predict the likelihood, nature or extent

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become more intense.

The marketability of any product for which we

receive regulatory approval for commercial sale may suffer if the government and third-party payors fail to provide adequate coverage

and reimbursement.

The marketability of any product for which we receive

regulatory approval for commercial sale may suffer if the government and third-party payors fail to provide adequate coverage and reimbursement.

Also, an increasing emphasis on managed care in the U.S.

has increased and will continue to increase the pressure on

pharmaceutical pricing.

has increased and will continue to increase the pressure on pharmaceutical pricing.

Coverage policies and third-party reimbursement rates may change at any time.

Even if favorable coverage and reimbursement

status is attained for one or more products for which we receive regulatory approval, less favorable coverage policies and reimbursement

rates may be implemented in the future.

Even if favorable coverage and reimbursement status is attained

for one or more products for which we receive regulatory approval, less favorable coverage policies and reimbursement rates may be implemented

in the future.

Healthcare Laws and Compliance Requirements

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committed a violation.

In addition, the ACA codified case law that a

claim including items or services resulting from a violation of the federal Anti-Kickback Statute is grounds for the government or a whistleblower

In addition, the ACA codified case law that a claim

including items or services resulting from a violation of the federal Anti-Kickback Statute is grounds for the government or a whistleblower

to assert that a claim for payment of items or services resulting from such violation constitutes a false or fraudulent claim for purposes

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of the statute, or the specific intent to violate it, to have committed a violation.

In addition, we may be subject to data privacy

and security regulation by both the federal government and the states in which we conduct our business.

HIPAA, as amended by the Health

Information Technology for Economic and Clinical Health Act (“HITECH”) and its implementing regulations, imposes requirements

on covered entities relating to the privacy, security, and transmission of individually identifiable health information, known as protected

health information.

Among other things, HITECH makes HIPAA’s security standards and certain privacy standards directly applicable

to “business associates,” defined as a person or organization, other than a member of a covered entity’s workforce,

that creates, receives, maintains, or transmits protected health information on behalf of a covered entity for a function or activity

regulated by HIPAA.

HITECH also increased the civil and criminal penalties that may be imposed against covered entities, business associates

and individuals.

It also 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 attorney’s fees and costs associated with pursuing these actions.

We are not a covered

entity or a business associate under HIPAA, however, we are indirectly affected by HIPAA because the protected health information held

by investigators conducting our clinical trials are subject to HIPAA and can only be used for our research consistent with HIPAA requirements

imposed on those investigators.

In addition, other federal and state laws, such as the California Consumer Privacy Act (CCPA), govern

the privacy and security of the personal information of California residents and may, in certain circumstances, apply to health information.

Other states have implemented laws protecting identifiable health and personal information, many of which laws differ from each other

in significant ways and may not be preempted by HIPAA, thus complicating compliance efforts.

In addition, we may be subject to data privacy and

security regulation by both the federal government and the states in which we conduct our business.

HIPAA, as amended by the Health Information

Technology for Economic and Clinical Health Act (“HITECH”) and its implementing regulations, imposes requirements on covered

entities relating to the privacy, security, and transmission of individually identifiable health information, known as protected health

Among other things, HITECH makes HIPAA’s security standards and certain privacy standards directly applicable to “business

associates,” defined as a person or organization, other than a member of a covered entity’s workforce, that creates, receives,

maintains, or transmits protected health information on behalf of a covered entity for a function or activity regulated by HIPAA.

also increased the civil and criminal penalties that may be imposed against covered entities, business associates and individuals.

also 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 attorney’s fees and costs associated with pursuing these actions.

We are not a covered entity or a business

associate under HIPAA, however, we are indirectly affected by HIPAA because the protected health information held by investigators conducting

our clinical trials are subject to HIPAA and can only be used for our research consistent with HIPAA requirements imposed on those investigators.

In addition, other federal and state laws, such as the California Consumer Privacy Act (CCPA), govern the privacy and security of the

personal information of California residents and may, in certain circumstances, apply to health information.

Other states have implemented

laws protecting identifiable health and personal information, many of which laws differ from each other in significant ways and may not

be preempted by HIPAA, thus complicating compliance efforts.

The federal Physician Payments Sunshine Act under

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CMS makes the reported information publicly available.

Many states have also adopted laws similar to

each of the above federal laws, which may be broader in scope and apply to items or services reimbursed by any third-party payor, including

Many states have also adopted laws similar to each

of the above federal laws, which may be broader in scope and apply to items or services reimbursed by any third-party payor, including

commercial insurers.

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Report on Form 10-K.

Financial Information Concerning Geographic

Financial Information Concerning Geographic Areas

We had no revenues in the fiscal years ended April

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general social, economic and political conditions in these foreign markets.

We are dependent on business relationships with

parties in multiple countries, as disclosed in Item 1A.

We are dependent on business relationships with parties

in multiple countries, as disclosed in Item 1A.

“Risk Factors—Risks Related to Our Dependence on Third Parties.”

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