What changed in this filing

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Item 1. Business

2026-03-10 compared with 2025-03-05 · 1236 added, 1128 removed, 713 unchanged (77% of the section changed)

3 unchanged sentences

order to create new development opportunities.

We prioritize creativity, diverse perspectives, integrity and tenacity to expedite our

goal of bringing life-changing therapies to people with limited treatment options.

Our portfolio includes two development programs utilizing TARA-002,

an investigational cell therapy based on the broad immunopotentiator, OK-432, which was originally granted marketing approval by the Japanese

Ministry of Health and Welfare as an immunopotentiating cancer therapeutic agent.

TARA-002 is currently approved in Japan and Taiwan for

lymphatic malformations, or LMs, and multiple oncologic indications.

We have secured worldwide rights to the asset excluding Japan and

Taiwan and are exploring its use in oncology and rare disease indications.

TARA-002 was developed from the same master cell bank of genetically

distinct group A Streptococcus pyogenes as OK-432 (marketed as Picibanil® in Japan by Chugai Pharmaceutical Co., Ltd., or Chugai Pharmaceutical).

We are currently developing TARA-002 in non-muscle invasive bladder cancer, or NMIBC, and in LMs.

Our lead oncology program

is TARA-002 in NMIBC, which is cancer found in the tissue that lines the inner surface of the bladder that has not spread into the bladder

Bladder cancer is the sixth most common cancer in the United States, with NMIBC representing approximately 80% of bladder cancer

Approximately 65,000 patients are diagnosed with NMIBC in the United States each year.

Very few new therapeutics have been

approved for NMIBC since the 1990s and the current standard of care for NMIBC includes intravesical Bacillus Calmette-Guérin,

Following the completion of Phase 1a and 1b clinical trials to

evaluate safety, preliminary efficacy and the dosing of TARA-002, at the 40KE (Klinische Einheit, or KE, is a German term indicating a

specified weight of dried cells in vial) dose level, we initiated and are currently conducting our ADVANCED-2 clinical trial.

is a Phase 2 open-label trial evaluating intravesical TARA-002 in at least 102 patients with high-grade carcinoma in situ, or CIS in the

U.S., Canada, Argentina, and Ukraine.

Cohort A of the Phase 2 trial is expected to enroll 27 patients with CIS (± Ta/T1 with Ta

defined as non-invasive papillary carcinoma and T1 as defined as carcinoma invading the lamina propria), BCG-Naïve or BCG-Exposed,

who have not received intravesical BCG for at least 24 months prior to CIS diagnosis.

Cohort B of the Phase 2 trial is expected to enroll

75-100 patients with BCG-Unresponsive CIS (± Ta/T1) and is expected to be registrational based on the FDA’s August 2024 Draft

Guidance on BCG-Unresponsive Nonmuscle Invasive Bladder Cancer:

Developing Drugs and Biological Products for Treatment.

We expect to complete Cohort A (BCG-Naïve or BCG-Exposed)

of the clinical trial and share 12-month interim data by mid-2025 and complete a interim analysis in Cohort B (BCG-Unresponsive) of the

clinical trial by the end of 2025.

The interim analysis will include data from approximately 25 six-month evaluable patients.

In addition to the ADVANCED-2

trial, we plan to continue to explore the anti-tumor activity related to the administration of TARA-002 via systemic administration.

continue to believe that combination therapy may play a meaningful role in the NMIBC treatment paradigm and intend to evaluate TARA-002

We prioritize creativity, integrity and tenacity to expedite our goal of bringing life-changing

therapies to people with limited treatment options.

Our portfolio includes two

development programs utilizing TARA-002, an investigational cell therapy based on the broad immunopotentiator, OK-432, which was originally

granted marketing approval by the Japanese Ministry of Health and Welfare as an immunopotentiating cancer therapeutic agent.

therapy is currently approved in Japan and Taiwan for lymphatic malformations, or LMs, and multiple oncologic indications.

We have secured

worldwide rights to the asset excluding Japan and Taiwan and are exploring its use in oncology and rare disease indications.

was developed from the same master cell bank of genetically distinct group A Streptococcus pyogenes as OK-432 (marketed as Picibanil®

in Japan by Chugai Pharmaceutical Co., Ltd., or Chugai Pharmaceutical).

We are currently developing TARA-002 in non-muscle invasive bladder

cancer, or NMIBC, and LMs.

We are also pursuing IV Choline Chloride, an investigational phospholipid substrate replacement therapy, for

patients receiving parenteral support, or PS, which includes both nutrition and fluids.

Neither TARA-002 nor IV Choline

Chloride have been approved by the FDA or other comparable regulatory authorities for use for any indications.

We have devoted substantial

efforts to the development of both TARA-002 and IV Choline Chloride and, to date, have not generated any revenues from product sales.

We do not expect to generate revenues in the near-term, and it is possible we may never generate revenues in the future.

To finance our

current strategic plans, including the conduct of ongoing and future clinical trials and further research and development, we will need

to raise additional capital.

Management’s Discussion and Analysis of Financial Condition and Results of Operations—Liquidity

and Capital Resources” for additional information about our liquidity and capital resource needs.

TARA-002 in NMIBC

Our lead oncology program is

TARA-002 in NMIBC, which is cancer found in the tissue that lines the inner surface of the bladder that has not spread into the bladder

Bladder cancer is the sixth most common cancer in the U.S., with NMIBC representing approximately 80% of bladder cancer diagnoses.

Approximately 65,000 patients are diagnosed with NMIBC in the U.S.

Very few new therapeutics have been approved for NMIBC since

the 1990s and the current standard of care for NMIBC includes intravesical Bacillus Calmette-Guérin, or BCG.

Following the completion of our ADVANCED-1 and ADVANCED-1EXP trials

in October 2024 and September 2024, respectively, to evaluate safety, preliminary efficacy and the dosing of TARA-002, at the 40KE (Klinische

Einheit, or KE, is a German term indicating a specified weight of dried cells in vial) dose level, we initiated and are currently conducting

our ADVANCED-2 clinical trial.

ADVANCED-2 is a Phase 2 open-label clinical trial evaluating intravesical TARA-002 in patients with high-grade

carcinoma in situ, or CIS.

Cohort A of the Phase 2 trial has completed enrollment and enrolled 31 patients with CIS (± Ta/T1, with

Ta defined as non-invasive papillary carcinoma and T1 defined as carcinoma invading the lamina propria) who are either BCG-Naïve

or BCG-Exposed and who have not received intravesical BCG for at least 24 months prior to CIS diagnosis.

Cohort B of the Phase 2 trial

is expected to enroll 75 to 100 patients with BCG-Unresponsive CIS (± Ta/T1) and is designed to be registrational based on the

FDA’s August 2024 Draft Guidance for Industry on BCG-Unresponsive Nonmuscle Invasive Bladder Cancer:

Developing Drugs and Biological

Products for Treatment.

Trial subjects in ADVANCED-2 receive an induction course, with or without a reinduction, of six weekly intravesical

instillations of TARA-002, followed by a maintenance course of three weekly instillations every three months.

In February 2026, we presented

updated interim data from our ongoing Phase 2 open-label ADVANCED-2 trial reporting results that continue to support TARA-002’s

potential as a mainstay in the NMIBC treatment landscape and demonstrating meaningful and durable activity in BCG-Unresponsive and BCG-Naïve

NMIBC patients.

The dataset includes 43 BCG-Unresponsive

patients and 31 BCG-Naïve patients who received at least 1 dose of TARA-002;

35 BCG-Unresponsive patients and 29 BCG-Naïve patients

completed at least one response assessment and were evaluable for efficacy as of a January 28, 2026 data cutoff.

Complete response, or

CR, rates at the six months and 12 months landmark time points include all participants who were either evaluable at that time point or

had experienced disease progression or treatment failure prior to the scheduled visit.

For the BCG-Unresponsive cohort,

the CR rate at any time was 65.7% (23/35).

The CR rate was 68.2% (15/22) at six months and 33.3% (5/15) at 12 months.

Among responders,

the Kaplan-Meier, or KM, estimated probability of maintaining a CR for six months was 71.1% (95% confidence interval, or CI:

and 100% (5/5) maintained their CR from nine to 12 months.

Re-induction therapy successfully converted most initial non-responders to

responders with durable responses:

61.5% (8/13) of re-induced patients converted to a CR at six months.

For the BCG-Naïve cohort,

the CR rate at any time was 72.4% (21/29).

The CR rate was 66.7% (18/27) at six months and 57.9% (11/19) at 12 months.

Among responders,

the KM estimated probability of maintaining a CR for six months was 73.1% (95% CI:

52.9, 93.4), and 100% (11/11) maintained their CR from

nine to 12 months.

Re-induction therapy successfully converted most initial non-responders to responders with durable responses:

(4/6) of re-induced patients converted to a CR at six months.

The majority of treatment-related

adverse events, or TRAEs, were Grade 1 and transient with no Grade 3 or greater TRAEs and no related serious adverse events, or SAEs,

as assessed by study investigators.

No patients discontinued treatment due to TRAEs.

The most commonly occurring TRAEs were dysuria (14%),

bladder spasm (9%), fatigue (7%) and micturition urgency (5%).

We expect to complete enrollment

of the BCG-Unresponsive registrational cohort of the ADVANCED-2 trial in the second half of 2026.

Enrollment is complete in the BCG-Naïve

cohort of the ADVANCED-2 trial with 31 patients.

In December 2025, we announced the FDA had provided written feedback supporting a proposed

registrational design for a controlled trial in BCG-Naïve patients (who have never been exposed and those who have not received BCG

within the last 24 months and are ineligible to receive BCG or contraindicated, cannot tolerate BCG, do not have access to

BCG, or refuse BCG).

The FDA has agreed that BCG is not required as a comparator and that intravesical chemotherapy is an acceptable comparator

to TARA-002 in BCG-Naïve patients.

The FDA also is aligned with the primary endpoint of the trial as the CR rate at month 6 with

duration of response as a key secondary endpoint.

We intend to initiate the ADVANCED-3 trial in the second half of 2026.

We have engaged

the FDA to determine how to include BCG-Exposed patients in our clinical trials of TARA-002, for whom no FDA-approved treatments are available

and who have limited options to access investigational treatment through clinical trials.

In addition to our existing clinical

trials in NMIBC, we plan to continue to explore the anti-tumor activity related to the administration of TARA-002 via systemic administration.

We continue to believe that combination therapy may play a meaningful role in the NMIBC treatment paradigm and intend to evaluate TARA-002

in combination with other therapies.

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TARA-002, both within urothelial cancer and other types of cancer affecting different parts of the body.

We are also pursuing intravenous, or IV, Choline Chloride, an

investigational phospholipid substrate replacement therapy, for patients receiving parenteral support, or PS, which includes both nutrition

Choline is a known important substrate for phospholipids that are critical for healthy liver function and also plays an important

role in modulating gene expression, cell membrane signaling, brain development, neurotransmission, muscle function and bone health.

patients are unable to synthesize choline from enteral nutrition sources, and there are currently no available PS formulations containing

IV Choline Chloride for Patients

We are also pursuing IV Choline

Chloride, an investigational phospholipid substrate replacement therapy, for patients receiving PS which includes both nutrition and fluids.

Choline is a known important substrate for phospholipids that are critical for healthy liver function and also plays an important role

in modulating gene expression, cell membrane signaling, brain development, neurotransmission, muscle function and bone health.

are unable to synthesize choline from enteral nutrition sources, and there are currently no available PS formulations containing choline.

Every year in the U.S.

there are approximately 90,000 people who require PS at home and of those approximately 30,000 are on

long-term PS.

there are approximately 90,000 people who require PS at home and of those approximately 30,000 are on long-term

IV Choline Chloride has the potential to become the first FDA-approved IV choline formulation for PS patients.

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IV Choline Chloride

has been granted Orphan Drug Designation by the FDA for the prevention and/or treatment of choline deficiency in patients on long-term

has been granted Orphan Drug Designation, or ODD, by the FDA for the prevention and/or treatment of choline deficiency in patients on

long-term PN.

Patent and Trademark Office, or USPTO, has issued us a U.S.

patent claiming a choline composition and a U.S.

patent claiming

a method for treating choline deficiency with a choline composition, each with a term expiring in 2041.

claiming a method for treating choline deficiency with a choline composition, each with a term expiring in 2041.

In April 2024, we announced

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for IV Choline Chloride.

We plan to advance the development of IV Choline Chloride as a source of choline for adult and adolescent patients

on long-term PS and intend to initiate THRIVE-3, a registrational Phase 3 clinical trial in the first half of 2025.

THRIVE-3 is a seamless

Phase 2b/3 trial with a dose confirmation portion (n=24) followed by a double-blinded, randomized, placebo-controlled portion to assess

the efficacy and safety of IV Choline Chloride over 24 weeks in adolescents and adults on long-term PS when oral or enteral nutrition

is not possible, insufficient, or contraindicated (n=100).

The primary endpoint of the clinical trial is a pharmacokinetic, or PK, endpoint

measuring the change from baseline in plasma choline concentration.

We also plan to include a number of secondary endpoints related to

liver, bone, and memory.

The FDA has also granted IV Choline Chloride Fast Track Designation as a source of choline when oral or enteral

nutrition is not possible, insufficient, or contraindicated.

In September 2024, we presented the results of THRIVE-1, a prospective,

observational study evaluating the prevalence of choline deficiency and liver injury in patients dependent on PS in the U.S., U.K, and

Europe at the ESPEN Congress.

The study found that 78% of patients who are dependent on PS were choline deficient, and that 63% of choline

deficient participants had liver dysfunction, including steatosis, cholestasis and hepatobiliary injury, underscoring the need for IV

Choline supplementation in this patient population.

We are also pursuing TARA-002

in LMs, which are rare, non-malignant cysts of the lymphatic vascular system that primarily form in the head and neck region of children

before the age of two.

In July 2020, the FDA granted Rare Pediatric Disease Designation for TARA-002 for the treatment of LMs and in May

2022 the European Commission granted Orphan Drug Designation to TARA-002 for the treatment of LMs.

In addition to the clinical experience

in Japan, we have secured the rights to a dataset from one of the largest ever conducted Phase 2 trials in LMs, in which OK-432 was administered

via a compassionate use program led by the University of Iowa to over 500 pediatric and adult patients.

We have an open investigational

new drug application, or IND, for TARA-002 in LMs with the Vaccines and Related Products Division of the FDA, or Vaccines Division.

In October 2023, we initiated STARBORN-1, which is a Phase 2 single-arm,

open-label, prospective clinical trial to evaluate the safety and efficacy of intracystic injection of TARA-002 for the treatment of macrocystic

and mixed-cystic LMs (≥ 50% macrocystic disease) in participants six months to less than 18 years of age in the U.S.

Including an age

de-escalation safety lead-in, the clinical trial will enroll approximately 30 patients who will receive up to four injections of TARA-002

spaced approximately six weeks apart.

The primary endpoint of the clinical trial is the proportion of participants with macrocystic LMs

and mixed-cystic LMs who demonstrated clinical success, defined as having either a complete response (90% to 100% reduction from baseline

in total LM volume) or substantial response (60% to less than 90% reduction in total LM volume) as measured by axial imaging.

In September 2024, we announced interim data from the first safety

cohort in the STARBORN-1 trial.

Of three patients treated in the first cohort, which enrolled individuals six years to less than 18 years

of age, two patients treated with TARA-002 achieved a complete response after receiving one injection of TARA-002;

the responses were

seen in a patient with a macrocystic LM and a patient with a maxillofacial cyst called a ranula.

The tolerability observed in this cohort

was consistent with patients’ historical experience with OK-432 and included treatment emergent adverse events, or TEAEs, of pain,

swelling, fatigue and body temperature increases.

All TEAEs were mild to moderate and resolved.

We expect to provide an interim update from our STARBORN-1 trial by the end of the first half of 2025.

We believe TARA-002 may also have the potential to be used to treat

other maxillofacial cysts based on the historical literature from the TARA-002 predecessor, OK-432, as well as recent data from the STARBORN-1

trial in which the one pediatric patient with a ranula achieved a complete response after a single 1KE injection of TARA-002.

While completing

STARBORN-1 in LMs is our priority, we believe there may be an opportunity in the future to explore the potential of TARA-002 to treat

different types of maxillofacial cysts.

We have devoted substantial efforts to the development of these programs

and do not have any approved products and have not generated any revenue from product sales.

Neither TARA-002 nor IV Choline Chloride

have been approved for use for any indication by the FDA.

We do not expect to generate revenues in the near-term, and it is possible we

may never generate revenues in the future.

To finance our current strategic plans, including the conduct of ongoing and future clinical

trials and further research and development costs, we will need to raise additional capital.

Management’s Discussion

and Analysis of Financial Condition and Results of Operations—Liquidity and Capital Resources” for additional information

about our liquidity and capital resource needs.

In September 2024, we presented

the results of THRIVE-1, a prospective, observational study evaluating the prevalence of choline deficiency and liver injury in patients

dependent on PS in the U.S., U.K.

The study found that 78% of patients who are dependent on PS were choline deficient, and

that 63% of choline deficient participants had liver dysfunction, including steatosis, cholestasis and hepatobiliary injury, underscoring

the need for IV Choline supplementation in this patient population.

In January 2026, we advanced

the development of IV Choline Chloride as a source of choline for adult and adolescent patients on long-term PS and initiated THRIVE-3,

a registrational Phase 3 clinical trial.

THRIVE-3 is a seamless Phase 2b/3 trial with a dose confirmation portion (n=24) followed by a

double-blinded, randomized, placebo-controlled portion to assess the efficacy and safety of IV Choline Chloride over 24 weeks in adolescents

and adults on long-term PS when oral or enteral nutrition is not possible, insufficient, or contraindicated (n=100).

The primary endpoint

of the clinical trial is a pharmacokinetic, or PK, endpoint measuring the change from baseline in plasma choline concentration.

plan to include a number of secondary endpoints related to liver, bone and memory.

The FDA granted IV Choline Chloride Fast Track Designation,

or FTD, as a source of choline when oral or enteral nutrition is not possible, insufficient, or contraindicated.

TARA-002 in LMs

We are also pursuing

TARA-002 in macrocystic and mixed-cystic LMs, which are rare, non-malignant cysts of the lymphatic vascular system that primarily

form in the head and neck region of children before the age of two.

In July 2020, the FDA granted Rare Pediatric Disease

Designation, or RPDD, for TARA-002 for the treatment of LMs and in May 2022 the European Commission granted

Orphan Medicinal Product Designation to TARA-002 for the treatment of LMs.

In December 2025, the FDA granted both FDA Breakthrough

Therapy Designation, or BTD, and FTD for TARA-002 for the treatment of macrocystic and mixed cystic LMs in pediatric patients.

In addition to the clinical experience in Japan, we have secured the rights to a dataset from one of the largest ever conducted

Phase 2 trials in LMs, in which OK-432 was administered via a compassionate use program led by the University of Iowa to over 500

pediatric and adult patients.

We have an open investigational new drug application, or IND, for TARA-002 in LMs with the Vaccines

and Related Products Division of the FDA, or Vaccines Division.

In October 2023, we initiated

STARBORN-1, which is a Phase 2 single-arm, open-label, prospective clinical trial to evaluate the safety and efficacy of intracystic injection

of TARA-002 for the treatment of macrocystic and mixed-cystic LMs (≥ 50% macrocystic disease) in participants six months to less than

18 years of age in the U.S.

Including an age de-escalation safety lead-in, the clinical trial will enroll approximately 30 patients who

will receive up to four injections of TARA-002 spaced approximately six weeks apart.

The primary endpoint of the clinical trial is the

proportion of participants with macrocystic LMs and mixed-cystic LMs who demonstrated clinical success, defined as having either a CR

(90% to 100% reduction from baseline in total LM volume) or substantial response (60% to less than 90% reduction in total LM volume) as

measured by axial imaging.

In November 2025, we announced

interim results from our ongoing Phase 2 STARBORN-1 trial evaluating TARA-002 in pediatric patients with macrocystic and mixed cystic

As of the data cutoff date of November 12, 2025, 12 patients had received at least one dose of TARA-002.

Of the eight patients who

were evaluable at the eight-week post-treatment assessment, 100% achieved clinical success.

88% of patients achieved clinical success

with just one or two doses of TARA-002.

Among macrocystic patients, 83% (5/6) achieved a CR, and the only mixed cystic patient treated

also achieved a CR.

Two patients who reached the 32-week post-treatment assessment remain disease-free.

The safety profile of TARA-002

in this trial has been favorable, with the majority of adverse events, or AEs, being mild to moderate in severity.

No SAEs were reported.

The most common AEs were swelling and fatigue, and only one patient discontinued treatment due to a Grade 2 AE of fatigue.

These results underscore

the potential of TARA-002 to address an unmet need for pediatric patients with LMs, for whom there are currently no approved therapies.

Many patients currently rely on invasive surgical procedures or off-label use of chemotherapies and chemicals, which can be associated

with high complication rates and challenging side effects, particularly in pediatric populations.

Other Potential Opportunities

We believe TARA-002 may also

have the potential to be used to treat other maxillofacial cysts based on the historical literature from the TARA-002 predecessor, OK-432,

as well as recent data from the STARBORN-1 trial in which the one pediatric patient with a ranula achieved a CR after a single 1KE injection

While completing STARBORN-1 in LMs is our priority, we believe there may be an opportunity in the future to explore the potential

of TARA-002 to treat different types of maxillofacial cysts.

Our Product Candidate Pipeline

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the current status of our product candidate pipeline:

Orphan Drug Designations by the FDA for the prevention and/or treatment of choline deficiency in patients on long-term PN and Fast Track

Designation as a source of choline when oral or enteral nutrition is not possible, insufficient, or contraindicated.

granted Rare Pediatric Disease designation by the FDA and Orphan Drug Designation by the European Commission for the treatment of LMs.

* Currently in pre-clinical studies to define dosing.

** IV Choline granted ODD by the FDA

for the prevention and/or treatment of choline deficiency in patients on long-term PN and FTD as a source of choline

when oral or enteral nutrition is not possible, insufficient, or contraindicated.

*** TARA-002 granted RPDD, as well

as BTD and FTD by the FDA and Orphan Medicinal Product Designation by the European Commission for the treatment

† Trial also includes BCG-Exposed patients

1 Subject to regulatory clearance

2 Potential expansion opportunity for NMIBC program

Our Corporate Strategy:

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Progress the registrational clinical

trial of TARA-002 for the treatment of BCG-Unresponsive NMIBC and intend to discuss with the FDA a protocol for a registrational trial

evaluating TARA-002 in BCG-Naïve NMIBC

Progress the Phase 2 ADVANCED-2 registrational trial to assess

the safety and anti-tumor activity of TARA-002 in BCG-Unresponsive NMIBC patients with CIS and complete the proof-of-concept cohort of

the clinical trial evaluating TARA-002 in BCG-Naïve NMIBC patients with CIS.

Discuss with the FDA the design of, and initiate, a

registrational trial evaluating TARA-002 in patients with BCG-Naïve NMIBC.

Expand the NMIBC program for TARA-002

into systemic priming dosing and combination therapy

Complete non-clinical studies

to determine the best approach to administering a systemic priming dose of TARA-002 prior to intravesical installation of TARA-002 in

NMIBC patients.

Define the appropriate combination approach for TARA-002 and initiate a proof-of-concept study to evaluate TARA-002 in

combination with a checkpoint inhibitor for the treatment of BCG-Unresponsive NMIBC.

Initiate the registrational seamless

trial of TARA-002 for the treatment of BCG-Unresponsive NMIBC

Complete enrollment of ADVANCED-2

Cohort B in BCG-Unresponsive NMIBC patients with CIS.

Initiate ADVANCED-3 registrational clinical

trial of TARA-002 for the treatment of BCG-Naïve NMIBC

Complete the BCG-Naïve cohort of ADVANCED-2 for patients with

CIS and initiate the registrational ADVANCED-3 trial evaluating TARA-002 in patients with BCG-Naïve NMIBC.

Progress the registrational seamless

Phase 2b/3 trial evaluating IV Choline Chloride in patients receiving PS

We intend to initiate the

Phase 2b/3 THRIVE-3 registrational trial evaluating IV Choline Chloride in patients receiving PS in the first half of 2025.

Progress THRIVE-3, a seamless

Phase 2b/3 trial assessing the efficacy and safety of low and high dose IV Choline Chloride in adolescent and adult patients receiving

long-term PS when oral or enteral nutrition is not possible, insufficient, or contraindicated.

Progress the Phase 2 clinical trial of

TARA-002 in patients with macrocystic and mixed-cystic LMs;

continue exploration of TARA-002 in other maxillofacial cysts

Based on the robust dataset for the originator product OK-432

in LMs and the full Clinical Study Report, or CSR, of the randomized Phase 2 clinical trial of OK-432 in LMs led by the University of

Iowa, we are encouraged by the potential for TARA-002 to treat patients with LMs.

We initiated the STARBORN-1 Phase 2 trial evaluating

TARA-002 in pediatric patients with macrocystic and mixed-cystic LMs and expect to progress the initial safety lead-in and expansion cohorts

of the clinical trial in 2025.

Given the extensive body of literature of the use of OK-432 in the treatment of various maxillofacial cysts,

we plan to develop a clinical program to explore the potential of TARA-002 in maxillofacial cysts.

confirm with FDA the registrational pathway for TARA-002 in LMs

We initiated the STARBORN-1

Phase 2 trial evaluating TARA-002 in pediatric patients with macrocystic and mixed-cystic LMs and expect to complete enrollment of the

trial in the second half of 2026.

In addition, we expect to meet with the FDA to determine the registrational path forward for TARA-002

in LMs in the first half of 2026.

Build our operational capabilities to

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Across the rare disease populations

(LMs and patients on PS) as well as bladder cancer, where the patient population is large, a high volume of patients are concentrated

in a small number of centers of excellence.

We believe this concentration of treatment centers will potentially enable us to efficiently

cover our addressable market with a relatively small commercial footprint.

Across our rare disease programs, there is significant unmet

need and no available FDA-approved therapies to meet the needs of these patients currently.

In NMIBC, there is also a significant unmet

need, and we believe TARA-002’s important attributes, such as fast, simple administration by a nurse with no cumbersome additional

steps or required safety protocols and a favorable tolerability profile, will position the potential therapy favorably with patients and

physicians versus other treatment options.

TARA-002, our lead program,

is an investigational cell therapy developed from the master cell line of the same genetically distinct Streptococcus pyogenes (group

A, type 3) Su strain as OK-432, a broad immunopotentiator marketed as Picibanil® in Japan by Chugai Pharmaceutical.

(LMs and patients on PS) as well as bladder cancer, a high volume of patients are concentrated in a small number of centers of excellence.

We believe this concentration of treatment centers will potentially enable us to efficiently cover our addressable market with a relatively

small commercial footprint.

Across our rare disease programs, there is significant unmet need and no available FDA-approved therapies

to meet the needs of these patients currently.

In NMIBC, there is also a significant unmet need, and we believe TARA-002’s important

attributes, such as fast, simple administration by a nurse with no cumbersome additional steps or required safety protocols and a favorable

tolerability profile, will position the potential therapy favorably with patients and physicians versus other treatment options.

TARA-002, our lead program, is

an investigational cell therapy developed from the master cell line of the same genetically distinct Streptococcus pyogenes (group A,

type 3) Su strain as OK-432, a broad immunopotentiator marketed as Picibanil® in Japan by Chugai Pharmaceutical.

We are using the

1 unchanged sentence

to manufacture OK-432.

We have designated this product candidate as TARA-002 in order to differentiate the regulatory path in the United

States and other geographies from that of OK-432 in Japan.

We have designated this product candidate as TARA-002 in order to differentiate the regulatory path in the U.S.

and other geographies from that of OK-432 in Japan.

We entered into an agreement

6 unchanged sentences

proprietary manufacturing process and technical support provided by Chugai Pharmaceutical to support a contract development and manufacturing

organization, or CDMO, in the production of TARA-002 at a current Good Manufacturing Practices, or cGMP, compliant facility in the United

Under the agreement with Chugai Pharmaceutical, we have sole responsibility for the development and commercialization of TARA-002

worldwide, excluding Japan and Taiwan.

This agreement is exclusive through June 17, 2030, or following any termination of the agreement

by either party.

organization, or CDMO, in the production of TARA-002 at a current Good Manufacturing Practices, or cGMP, compliant facility in the U.S.

Under the agreement with Chugai Pharmaceutical, we have sole responsibility for the development and commercialization of TARA-002 worldwide,

excluding Japan and Taiwan.

This agreement is exclusive through June 17, 2030, or following any termination of the agreement by either

In Japan, OK-432 is indicated

the treatment of lymphangiomas (lymphatic malformations);

the prolongation of survival time in patients with gastric cancer (postoperative

cases) or primary lung cancer in combination with chemotherapy;

and the reduction of cancerous pleural effusion or ascites in patients

with lung cancer or gastrointestinal cancer respectively, head and neck cancer (maxillary cancer, laryngeal cancer, pharyngeal cancer,

and tongue cancer) and thyroid cancer that are resistant to other drugs.

We are developing TARA-002

for the treatment of NMIBC and LMs initially in the United States, and plan to also seek approval in other regions in the future and may

also explore additional indications where its utility as an immunopotentiator has been hypothesized to be of therapeutic benefit.

the treatment of lymphangiomas (LMs);

the prolongation of survival time in patients with gastric cancer (postoperative cases) or

primary lung cancer in combination with chemotherapy;

and the reduction of cancerous pleural effusion or ascites in patients with lung

cancer or gastrointestinal cancer respectively, head and neck cancer (maxillary cancer, laryngeal cancer, pharyngeal cancer, and tongue

cancer) and thyroid cancer that are resistant to other drugs.

We are developing TARA-002 for

the treatment of NMIBC and LMs initially in the U.S., and plan to also seek approval in other regions in the future and may also explore

additional indications where its utility as an immunopotentiator has been hypothesized to be of therapeutic benefit.

TARA-002 in NMIBC

Disease Overview

Bladder cancer is the sixth

most common cancer in the United States, with NMIBC representing approximately 80% of bladder cancer diagnoses.

NMIBC is cancer found

in the tissue that lines the inner surface of the bladder that has not spread into the bladder muscle.

Bladder cancer is the sixth most

common cancer in the U.S., with NMIBC representing approximately 80% of bladder cancer diagnoses.

NMIBC is cancer found in the tissue

that lines the inner surface of the bladder that has not spread into the bladder muscle.

There are three subtypes of NMIBC:

non-invasive papillary carcinoma, or Ta, CIS, and carcinoma invading the lamina propria, or T1.

Among the types of NMIBC, Ta accounts

for most NMIBC cases (70%), whereas T1 and CIS account for 20% and 10%, respectively.

There are approximately 65,000 incident cases of NMIBC in the United

States every year, and based upon currently available data we believe that approximately 45% (approximately 30,000) are made up of high-grade

tumor types that are considered higher risk, and therefore candidates for immunotherapies, such as TARA-002.

In addition, NMIBC has one

of the highest rates of recurrence with the five-year rate estimated at up to 70%.

Among the types of NMIBC, Ta accounts for most NMIBC cases (70%), whereas T1 and CIS account for 20% and 10%, respectively.

There are approximately 65,000

incidents of NMIBC in the U.S.

every year, and based upon currently available data we believe that approximately 45% (approximately 30,000)

are made up of high-grade tumor types that are considered higher risk, and therefore candidates for immunotherapies, such as TARA-002.

In addition, NMIBC has one of the highest rates of recurrence with the five-year rate estimated at up to 70%.

Treatment for NMIBC is typically

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BCG has been the subject

of multiple supply shortages in the US in the past decade due to the inability to meet demand to treat the large population of patients

of multiple supply shortages in the U.S.

in the past decade due to the inability to meet demand to treat the large population of patients

There has been a significant increase in bladder cancer recurrence and progression with an escalated number of patients who

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Clinical Development

We conducted a Phase 1 open-label clinical trial to evaluate TARA-002

in treatment-naïve and treatment-experienced NMIBC patients with CIS and Ta, known as the ADVANCED-1 trial.

In the initial dose escalation

phase of the clinical trial, patients received six weekly intravesical doses of TARA-002, evaluating the 10KE, 20KE and 40KE doses.

primary objective of the clinical trial was to evaluate the safety, tolerability and preliminary signs of anti-tumor activity of TARA-002,

with the goal of establishing a recommended Phase 2 dose.

Data from the ADVANCED-1 trial suggested that intravesical TARA-002

was generally well tolerated at the three dose levels evaluated in the initial phase of the clinical trial (10KE, 20KE, and 40KE), and

no dose limiting toxicities were observed.

A maximum tolerated dose was not determined, and we selected the 40KE dose for use in subsequent

clinical trials.

The majority of reported adverse events were Grades 1 and 2 across all dose levels, and TEAEs, as assessed by study investigators,

were in line with typical responses to bacterial immunopotentiation and included fatigue, headache, fever and chills.

The most common

urinary symptoms were urinary urgency, urinary frequency, urinary tract pain/burning, incomplete emptying and bladder spasm.

irritations resolved soon after administration, or in a few hours to a few days.

A total of nine patients were enrolled in the dose escalation

portion of the study through the 40KE dose.

Of those, three patients with CIS, one of whom was a heavily pre-treated BCG-Unresponsive

patient, achieved a complete response, or CR, at the 20KE dose, and tumor regression was observed in the other two patients.

six patients with high-grade, non-invasive papillary, or HGTa, tumors showed five of six patients with high-grade recurrence free survival,

or HGRFS, at week 12.

The patient who did not achieve HGRFS was dosed at 10KE, the lowest dose of TARA-002 offered in the clinical trial.

An exploratory cohort of dose escalation at the 80KE was also completed demonstrating similar tolerability to the 40KE dose.

Additionally, we completed

an open-label expansion clinical trial, or ADVANCED-1EXP, evaluating intravesical TARA-002 at the 40KE dose in CIS patients, including

BCG-Naïve, BCG-Unresponsive, and BCG-Experienced patients and are conducting an open-label Phase 2 clinical trial, or ADVANCED-2,

assessing intravesical TARA-002 in NMIBC patients with CIS (± Ta/T1) who are BCG-Naïve (n=27) and BCG-Unresponsive (n≈100).

In April 2024, we announced

positive data from three-month evaluable NMIBC patients with CIS pooled across our clinical studies, including ADVANCED-1 Phase 1a, ADVANCED-1

EXP Phase 1b and ADVANCED-2 Phase 2 trials of TARA-002 in patients with high-risk NMIBC, including BCG-Unresponsive, BCG-Experienced and

BCG-Naïve patients.

The overall three-month CR rate prior to reinduction for the 16 evaluable patients was 38%, with a CR rate of

63% in CIS-only patients and 13% in patients with CIS +Ta/T1 (T1 is defined as carcinoma invading the lamina propria).

A 43% CR rate was

observed in BCG-Unresponsive/Experienced patients.

TARA-002 demonstrated a favorable safety and tolerability profile.

The majority of

reported adverse events were Grades 1 and 2 across all dose levels, and there were no Grade 3 or higher TEAEs.

TEAEs as assessed by study

investigators, were in line with typical responses to bacterial immunopotentiation, and included fatigue, headache, fever and chills.

The most common urinary symptoms were urinary urgency, urinary frequency, urinary tract pain/burning, incomplete emptying and bladder

Most bladder irritations resolved in a few hours to a few days.

Additional details regarding the data, which support the potential

for TARA-002 in treating high risk patients can be found in the following table:

Three Month Evaluable Patients

BCG-Unresponsive/Experienced

By Stage of Disease at Baseline

Phase 2 Naïve

Data cutoff date:

March 19, 2024

Following the completion

of our ADVANCED-1 and ADVANCED-1EXP trials in October 2024 and September 2024, respectively, to evaluate safety, preliminary efficacy

and the dosing of TARA-002, at the 40KE dose level, we initiated and are currently conducting our ADVANCED-2 clinical trial.

is a Phase 2 open-label clinical trial evaluating intravesical TARA-002 in patients with high-grade CIS.

Cohort A of the Phase 2 trial

has completed enrollment and enrolled 31 patients with CIS (± Ta/T1) who are either BCG-Naïve or BCG-Exposed and who have

not received intravesical BCG for at least 24 months prior to CIS diagnosis.

Cohort B of the Phase 2 trial is expected to enroll 75 to

100 patients with BCG-Unresponsive CIS (± Ta/T1) and is designed to be registrational based on the FDA’s August 2024 Draft

Guidance for Industry on BCG-Unresponsive Nonmuscle Invasive Bladder Cancer:

Developing Drugs and Biological Products for Treatment.

subjects in ADVANCED-2 receive an induction course, with or without a reinduction, of six weekly intravesical instillations of TARA-002,

followed by a maintenance course of three weekly instillations every three months.

In April 2025, we presented interim

data from our ADVANCED-2 trial with an April 16, 2025 data cutoff.

The BCG-Unresponsive dataset included a total of five patients, all

of whom were six- and nine-month evaluable, and three of whom were evaluable at 12 months.

The CR rate at any time in BCG-Unresponsive

patients was 100% (5/5).

The CR rate in BCG-Unresponsive patients was 100% (5/5) at six months, 80% (4/5) at nine months, and 67% (2/3)

at 12 months.

The BCG-Naïve dataset

included a total of 21 patients, including 16 evaluable at six months, eight at nine months, and seven at 12 months.

The CR rate at any

time in BCG-Naïve patients was 76% (16/21).

The CR rate in BCG-Naïve patients was 63% (10/16) at six months, 63% (5/8) at nine

months, and 43% (3/7) at 12 months.

The majority of AEs were Grade

1 and transient with no Grade 3 or greater TRAEs, as assessed by study investigators.

No patients discontinued treatment due to TRAEs.

The most common AEs were in line with typical responses to bacterial immunopotentiation, such as flu-like symptoms.

The most common urinary

symptoms reflect urinary tract instrumentation effects, such as bladder spasm, burning sensation and urinary tract infection.

irritations resolved shortly after administration or within a few hours to a few days.

In December 2025, we presented

interim results from our ongoing Phase 2 ADVANCED-2 clinical trial of TARA-002 in patients with NMIBC.

The dataset included 20 patients

who were evaluable at three months, 18 patients who were evaluable at six months and three patients who were evaluable at nine months

with a data cutoff of November 19, 2024.

The CR rate across BCG exposures was 72% (13/18) at six months and 70% (14/20) at any time, with

100% (9/9) of patients maintaining a CR from three months to six months.

In addition, two of three patients maintained a CR at nine months.

In the pivotal cohort of the ADVANCED-2 trial in BCG-Unresponsive patients, the CR rate was 100% (4/4) at six-months and 80% (4/5) at

In the proof-of concept cohort of BCG-Naïve patients, the CR rate was 64% (9/14) at six months and 67% (10/15) at any time.

BCG-Unresponsive

High-grade CR at any time

High-grade CR at timepoint

High-grade CR at Month 6 by Baseline Diagnosis

Data cutoff date:

November 19, 2024

The BCG-Unresponsive cohort has been designed to be registrational

and aligned with the FDA’s August 2024 Draft Guidance BCG-Unresponsive Nonmuscle Invasive Bladder Cancer:

Developing Drugs and Biological

Products for Treatment.

Clinical trial subjects receive an induction course of six weekly intravesical instillations, and following mandatory

biopsy at three months, receive either a reinduction course of six weekly intravesical instillations of TARA-002, or the first maintenance

course of three weekly installations every three months, for an additional 12 months.

We anticipate sharing interim 12-month data from

the ADVANCED-2 trial by mid-2025 and results from a interim analysis of approximately 25 six-month evaluable BCG-Unresponsive patients

by the end of 2025.

We intend to discuss with the FDA a protocol for a registrational trial evaluating TARA-002 in BCG-Naïve patients,

and expect to provide an update on the design of this clinical trial following regulatory alignment.

updated interim data from our ADVANCED-2 trial of TARA-002 in BCG-Naïve patients.

The dataset included 31 BCG-Naïve patients

who received at least one dose of TARA-002;

29 patients completed at least one response assessment and were evaluable for efficacy as

of a November 7, 2025 data cutoff.

CR rates at the six months and 12 months landmark time points include all participants who were either

evaluable at that time point or had experienced disease progression or treatment failure prior to the scheduled visit.

The CR rate at

any time was 72% (21/29).

The CR rate was 69% (18/26) at six months and 50% (7/14) at 12 months.

Among initial responders, 88% (14/16)

maintained their response through six months and 100% (3/3) through 12 months.

Re-induction therapy successfully salvaged most initial

nonresponders, resulting in high conversion rates and durable responses:

80% (4/5) of re-induced patients converted to a CR at 6 months,

and 100% (4/4) of those responders maintained their CR at 12 months.

The majority of TRAEs were

Grade 1 and transient with no Grade 3 or greater TRAEs as assessed by study investigators.

No patients discontinued treatment due to TRAEs.

The most commonly occurring TRAEs were dysuria (13%), fatigue (13%) and hematuria (6%).

In February 2026, we presented updated interim data from our ADVANCED-2

trial, reporting results that continue to support TARA-002.

The dataset includes 43 BCG-Unresponsive

patients and 31 BCG-Naïve patients who received at least one dose of TARA-002;

35 BCG-Unresponsive patients and 29 BCG-Naïve

patients completed at least one response assessment and were evaluable for efficacy as of a January 28, 2026 data cutoff.

the six months and 12 months landmark time points include all participants who were either evaluable at that time point or had experienced

disease progression or treatment failure prior to the scheduled visit.

For the BCG-Unresponsive cohort,

the CR rate at any time was 65.7% (23/35).

The CR rate was 68.2% (15/22) at six months and 33.3% (5/15) at 12 months.

Among responders,

the KM estimated probability of maintaining a CR for six months was 71.1% (95% CI:

46.7, 95.5), and 100% (5/5) maintained their CR from

nine to 12 months.

Re-induction therapy successfully converted most initial non-responders to responders with durable responses:

(8/13) of re-induced patients converted to a CR at six months.

For the BCG-Naïve cohort,

the CR rate at any time was 72.4% (21/29).

The CR rate was 66.7% (18/27) at six months and 57.9% (11/19) at 12 months.

Among responders,

the KM estimated probability of maintaining a CR for six months was 73.1% (95% CI:

52.9, 93.4), and 100% (11/11) maintained their CR from

nine to 12 months.

Re-induction therapy successfully converted most initial non-responders to responders with durable responses:

(4/6) of re-induced patients converted to a CR at six months.

The majority of TRAEs were Grade

1 and transient with no Grade 3 or greater TRAEs and no related SAEs as assessed by study investigators.

No patients discontinued treatment

due to TRAEs.

The most commonly occurring TRAEs were dysuria (14%), bladder spasm (9%), fatigue (7%) and micturition urgency (5%).

In December 2025, we announced

that the FDA has provided written feedback supporting a proposed registrational design for a controlled trial in BCG-Naïve patients

(who have never been exposed and those who have not received BCG within the last 24 months and are ineligible to receive BCG or contraindicated,

cannot tolerate BCG, do not have access to BCG, or refuse BCG).

The FDA has agreed that BCG is not required as a comparator and that intravesical

chemotherapy is an acceptable comparator to TARA-002 in BCG-Naïve patients.

The FDA also is aligned with the primary endpoint of

the trial as the CR rate at month six with duration of response as a key secondary endpoint.

We intend to initiate this registrational

clinical trial in the second half of 2026.

We have engaged the FDA to determine how to include BCG-Exposed patients in our clinical trials

of TARA-002, for whom no FDA-approved treatments are available and who have limited options to access investigational treatment through

clinical trials.

Non-clinical Development

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of administration for OK-432 in Japan.

In addition, we have completed subcutaneous systemic toxicology studies of TARA-002 and we intend

to initiate a proof-of-concept study exploring systemic administration of TARA-002 in 2025.

In addition, we have completed subcutaneous systemic toxicology studies of TARA-002 and we are

considering a proof-of-concept study exploring systemic administration of TARA-002.

Regulatory Interactions

In October 2021, we announced that the Office of Tissues and Advanced

Therapies Division, now referred to as the Office of Therapeutic Products, of the FDA’s Center for Biologics Evaluation and Research,

or CBER, cleared our IND application for TARA-002 in NMIBC.

We have had ongoing dialogue with the FDA to align on the potential clinical

trial design of a registrational trial of TARA-002 for the treatment of BCG-Naïve NMIBC, as well as a combination trial with TARA-002

and a checkpoint inhibitor for the treatment of NMIBC and the design of a clinical trial evaluating the systemic priming dose of TARA-002

in BCG-Naïve and BCG-Exposed NMIBC.

In addition, we have had interactions with regulatory authorities

in six countries outside the U.S.

in order to open clinical trial sites for the ADVANCED-2 trial in these international locations.

In October 2021, we announced

that the Office of Tissues and Advanced Therapies Division, now referred to as the Office of Therapeutic Products, of the FDA’s

Center for Biologics Evaluation and Research, or CBER, cleared our IND for TARA-002 in NMIBC.

Manufacturing

manufactured using an equivalent, but modernized, proprietary manufacturing process as is used to produce OK-432 by Chugai

Pharmaceutical.

We propagated a master cell bank using the same master cell line of the genetically distinct strain of Streptococcus

pyogenes (A group, type 3) Su strain as OK-432.

The bacteria is rendered inactive during the manufacturing process, consistent with

the process used for OK-432.

We have contracted a cGMP compliant CDMO to manufacture TARA-002.

The manufacturing facility

of our CDMO for TARA-002 currently has a twenty million vial annual capacity with the ability to expand capacity by five hundred percent.

With TARA-002’s efficient two-hour doubling time, we have an approximate two-week batch completion rate and manufactured 47 successful

consecutive batches by the end of 2024.

The facility which manufactures TARA-002 has been inspected by the FDA and at the most recent

inspection no Form 483s were issued.

TARA-002 is manufactured using

an equivalent, but modernized, proprietary manufacturing process as is used to produce OK-432 by Chugai Pharmaceutical.

We propagated

a master cell bank using the same master cell line of the genetically distinct strain of Streptococcus pyogenes (A group, type 3) Su strain

The bacteria is rendered inactive during the manufacturing process, consistent with the process used for OK-432.

We have contracted

a cGMP compliant CDMO to manufacture TARA-002 in the U.S.

IV Choline Chloride for PS Patients

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IV Choline Chloride has

been granted Orphan Drug Designation, or ODD, by the FDA for the prevention and/or treatment of choline deficiency in patients on long-term

been granted ODD by the FDA for the prevention and/or treatment of choline deficiency in patients on long-term PN.

The FDA granted IV

Choline Chloride FTD as a source of choline when oral or enteral nutrition is not possible, insufficient, or contraindicated.

We have entered into a license

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Disease Overview

PN typically consists of carbohydrate (typically derived from

dextrose), fat (lipid emulsion with essential fatty acids), protein (in the form of a balanced free amino acid solution), electrolytes,

trace elements, and most vitamins and essential nutrients known to be required by the human body, with the notable exception of choline.

PS is a medical treatment, representing PN plus fluids and is used to manage and treat malnourishment and is indicated when there is impaired

gastrointestinal function and contraindications to enteral nutrition.

The American Society for Parenteral and Enteral Nutrition and the

Academy of Nutrition and Dietetics’ Dietitians in Nutrition Support both recommend that choline be required in PN products (Vanek

et al., 2012);

PN typically consists of

carbohydrate (typically derived from dextrose), fat (lipid emulsion with essential fatty acids), protein (in the form of a balanced free

amino acid solution), electrolytes, trace elements, and most vitamins and essential nutrients known to be required by the human body,

with the notable exception of choline.

PS is a medical treatment, representing PN plus fluids and is used to manage and treat malnourishment

and is indicated when there is impaired gastrointestinal function and contraindications to enteral nutrition.

ASPEN and the Academy of

Nutrition and Dietetics’ Dietitians in Nutrition Support both recommend that choline be required in PN products (Vanek et al., 2012);

however, there are currently no FDA-approved intravenous choline chloride products.

Humans can produce choline endogenously

in the liver, but the amount that the body naturally synthesizes is not sufficient to meet human needs, making it an essential nutrient.

As a result, humans must obtain choline from their diets.

The development of IV Choline Chloride is intended to provide a source of choline

when oral or enteral nutrition is not possible, insufficient, or contraindicated.

Humans can produce choline endogenously in the liver,

but the amount that the body naturally synthesizes is not sufficient to meet human needs, making it an essential nutrient.

humans must obtain choline from their diets.

The development of IV Choline Chloride is intended to provide a source of choline when oral

or enteral nutrition is not possible, insufficient, or contraindicated.

Clinical Development

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and quickly returned to baseline levels when treatment was discontinued.

In April 2024, we announced

alignment with the FDA on a registrational path forward for IV Choline Chloride.

Previously, we had been pursuing an indication in intestinal

failure-associated liver disease, or IFALD, and following feedback from the FDA, are pursuing a broader indication as a source of choline

when oral or enteral nutrition is not possible, insufficient, or contraindicated.

Feedback from the FDA on our IV Choline Chloride program

indicated that a single study with an endpoint of restoring choline levels in PS patients could serve as the basis for a regulatory submission

for IV Choline Chloride.

We plan to advance the development of IV Choline Chloride as a source of choline for adult and adolescent patients

on long-term PS and intend to initiate THRIVE-3, a registrational Phase 3 clinical trial in the first half of 2025.

THRIVE-3 is a seamless

Phase 2b/3 trial with a dose confirmation portion (n=24) followed by a double-blinded, randomized, placebo-controlled portion to assess

the efficacy and safety of IV Choline Chloride over 24 weeks in adolescents and adults on long-term PS when oral or enteral nutrition

is not possible, insufficient, or contraindicated (n=100).

The primary endpoint of the clinical trial is a pharmacokinetic, or PK, endpoint

In September 2024, we presented

the results of THRIVE-1, a prospective, observational study evaluating the prevalence of choline deficiency and liver injury in patients

dependent on PS in the U.S., U.K.

The study found that 78% of patients who are dependent on PS were choline deficient, and

that 63% of choline deficient participants had liver dysfunction, including steatosis, cholestasis and hepatobiliary injury, underscoring

the need for IV Choline supplementation in this patient population.

In January 2026, we advanced

the development of IV Choline Chloride as a source of choline for adult and adolescent patients on long-term PS and initiated THRIVE-3.

THRIVE-3 is a seamless Phase 2b/3 trial with a dose confirmation portion (n=24) followed by a double-blinded, randomized, placebo-controlled

portion to assess the efficacy and safety of IV Choline Chloride over 24 weeks in adolescents and adults on long-term PS when oral or

enteral nutrition is not possible, insufficient, or contraindicated (n=100).

The primary endpoint of the clinical trial is a PK endpoint

measuring the change from baseline in plasma choline concentration.

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liver, bone and memory.

The FDA has also granted IV Choline Chloride Fast Track Designation as a source of choline when oral or enteral

nutrition is not possible, insufficient, or contraindicated.

In September 2024, we presented

the results of THRIVE-1, a prospective, observational study evaluating the prevalence of choline deficiency and liver injury in patients

dependent on PS in the U.S., U.K, and Europe at the ESPEN Congress.

The study found that 78% of patients who are dependent on PS were

choline deficient, and that 63% of choline deficient participants had liver dysfunction, including steatosis, cholestasis and hepatobiliary

injury, underscoring the need for IV Choline supplementation in this patient population.

Preclinical Development

Preclinical Studies

Conducted by us for IV Choline Chloride

Brief Description

In vitro protein binding

Evaluation of Protein Binding by Choline Chloride in Plasma Using Rapid Equilibrium Dialysis

In vitro cardiac ion channel study

In Vitro Assessment of the Effect of Choline on Currents Mediated by hERG, Cav1.2, and Peak and Late Nav1.5 Channels Expressed in Human Embryonic Kidney, or HEK, Cells

In vitro drug-drug interaction

Evaluation of Transporter Inhibition by Choline Chloride in Transporter-Transfected HEK293 Cells

Evaluation of OCT2, MATE1 and MATE2-K Inhibition by Choline Chloride in Transporter-Transfected HEK293 Cells

Evaluation of Transporter Inhibition by Choline Chloride in Caco-2 Cells

Evaluation of Time Dependent Cytochrome P450 Inhibition (IC50 Shift) by Choline Chloride in Human Liver Microsomes

Evaluation of Direct Cytochrome P450 Inhibition by Choline Chloride in Human Liver Microsomes

Evaluation of Cytochrome P450 Induction by Choline Chloride in Human Hepatocytes

Evaluation of Transporter Inhibition by Choline Chloride in Caco-2 Cells

Evaluating of Cytochrome P450 2C8, 2C9, and 2C19 mRNA Induction by Choline Chloride in Human Hepatocytes

In vitro BSEP inhibition

Assessment of Choline as an Inhibitor of Human BSEP Mediated Transport

Assessment of Choline as a Substrate of Human BSEP Mediated Transport

Non-clinical pharmacology studies

Non-GLP Pilot Single Dose, Escalating Dose Tolerance Study of Choline by Intravenous Infusion in Male Beagle Dogs

GLP Single-dose IV Cardiovascular Study in Surgically Instrumented Male Dogs Monitored by Telemetry

GLP Combined Single-dose IV Neurobehavioral and Respiratory Study

In addition to the studies performed by Dr.

we have completed a number of preclinical in vitro and non-clinical pharmacology studies for IV Choline Chloride.

Regulatory Interactions

IV Choline Chloride has been

granted Orphan Drug Designation, or ODD, by the FDA for the prevention and/or treatment of choline deficiency in patients on long-term

granted ODD by the FDA for the prevention and/or treatment of choline deficiency in patients on long-term PN.

In April 2024, we announced

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In October 2024, the FDA

granted Fast Track Designation to IV Choline Chloride as a source of choline when oral or enteral nutrition is not possible, insufficient,

or contraindicated.

granted FTD to IV Choline Chloride as a source of choline when oral or enteral nutrition is not possible, insufficient, or contraindicated.

Manufacturing

Our end-to-end manufacturing

of IV Choline Chloride is conducted in the United States by a cGMP compliant CDMO.

The facility which manufactures IV Choline Chloride

has been inspected by the FDA and at the most recent inspection no Form 483s were issued.

of IV Choline Chloride is conducted in the U.S.

by a cGMP compliant CDMO.

TARA-002 in LMs

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macrocystic and microcystic LMs.

While the exact prevalence

of LMs is not known, in the United States, the condition is thought to be present in approximately one in every 4,000 live births and

we believe there are approximately 1,400-1,800 LM cases per year.

While the exact prevalence of

LMs is not known, in the U.S., the condition is thought to be present in approximately one in every 4,000 live births and we believe there

are approximately 1,400-1,800 LM cases per year.

We are not aware of any approved

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immune activities induce a strong local inflammatory reaction in the cyst wall, resulting in fluid drainage, shrinkage and fibrotic adhesion

A randomized, Phase 2 clinical trial led by the University of Iowa

studied the use of OK-432 in patients with LM from 1998 to 2005.

Most eligible subjects were between 6 months and 18 years of age with

macrocystic or mixed-cystic LMs (with ≥ 50% macrocytic disease) of the head and/or neck.

There were three treatment groups:

treatment, or ITG, delayed treatment, or DTG, and open label treatment group.

The ITG received treatment with OK-432 upon diagnosis.

DTG received OK-432 treatment following a six-month observation period;

the cross-over design was intended to investigate spontaneous

The open-label treatment group included infants younger than six months of age, adults older than 18 years of age, patients

with LMs involving sites other than the head and neck (such as the axilla, thorax, and extremities), and patients treated on an emergent

A randomized, Phase 2 clinical

trial led by the University of Iowa studied the use of OK-432 in patients with LMs from 1998 to 2005.

Most eligible subjects were between

six months and 18 years of age with macrocystic or mixed-cystic LMs (with ≥ 50% macrocystic disease) of the head and/or neck.

were three treatment groups:

immediate treatment, or ITG, delayed treatment, or DTG, and open label treatment group.

The ITG received

treatment with OK-432 upon diagnosis.

The DTG received OK-432 treatment following a six-month observation period;

the cross-over design

was intended to investigate spontaneous resolution.

The open-label treatment group included infants younger than six months of age, adults

older than 18 years of age, patients with LMs involving sites other than the head and neck (such as the axilla, thorax and extremities),

and patients treated on an emergent basis.

The open label treatment group were treated immediately with OK-432.

Response to therapy was measured by quantitating change in

Clinical success was defined as a complete (90% to 100%) or substantial (60% to 89%) response to treatment based on radiographically

confirmed shrinkage in lesions.

The study results were based on a retrospective analysis of source

verified data that included the full dataset of subjects enrolled in the Phase 2 randomized clinical trial between January 1998 and August

2005, including data in the published study (Smith et al.

2009) that included subjects enrolled between January 1998 and November 2004.

Overall, 310 subjects were

enrolled with intent to treat:

Response to therapy was

measured by quantitating change in lesion size.

Clinical success was defined as a complete (90% to 100%) or substantial (60% to 89%) response

to treatment based on radiographically confirmed shrinkage in lesions.

The study results were based

on a retrospective analysis of source verified data that included the full dataset of subjects enrolled in the Phase 2 randomized clinical

trial between January 1998 and August 2005, including data in the published study (Smith et al.

2009) that included subjects enrolled

between January 1998 and November 2004.

Overall, 310 subjects were enrolled

with intent to treat:

246 subjects were randomized to the immediate (ITG, N=171) and delayed (DTG, N=75) treatment groups;

subjects were nonrandomized and assigned to the open-label group.

Analysis of the primary efficacy endpoint (N=150) demonstrated clinical

success (complete and/or substantial response) in 69% of patients in the ITG 6 months after enrollment, while 7.5% of patients in the

DTG experienced spontaneous regression of a LM during this time interval (p < 0.0001)).

When the results were analyzed by lesion type

across all treatment groups, a successful outcome was observed in 84% and 60% of patients with macrocystic and mixed-cystic LM, respectively.

None of the patients with microcystic LM demonstrated clinical success with OK-432 therapy.

The results of the retrospective analysis

were consistent with the results observed in the original analysis (Smith et al.

were nonrandomized and assigned to the open-label group.

Analysis of the primary efficacy endpoint (N=150) demonstrated clinical success

(complete and/or substantial response) in 69% of patients in the ITG 6 months after enrollment, while 7.5% of patients in the DTG experienced

spontaneous regression of a LM during this time interval (p < 0.0001).

When the results were analyzed by lesion type across all treatment

groups, a successful outcome was observed in 84% and 60% of patients with macrocystic and mixed-cystic LMs, respectively.

patients with microcystic LMs demonstrated clinical success with OK-432 therapy.

The results of the retrospective analysis were consistent

with the results observed in the original analysis (Smith et al.

69% of patients

in the immediate treatment group had a complete or substantial response to OK-432, meeting the primary endpoint, while 7.5% of patients

in the delayed treatment group had a complete or substantial response after six months of observation and before treatment.

Success was defined as complete or substantial response.

in the ITG had a complete or substantial response to OK-432, meeting the primary endpoint, while 7.5% of patients in the DTG had a complete

or substantial response after six months of observation and before treatment.

Clinical Success was defined as complete or substantial response.

Results were analyzed by lesion type across all treatment groups

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was also present.

Success was defined as complete or substantial response.

data prior to dosing with OK-432.

Clinical Success was defined as complete or substantial response.

Reflects data prior to dosing with OK-432.

After dosing, the clinical success rate was 66%, which was not statistically different from the ITG.

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TARA-002 Clinical Development

We have an open investigational IND for LMs with the Vaccines

In October 2023, we initiated the STARBORN-1 trial, a Phase 2 single arm, open-label clinical trial to evaluate the safety and

efficacy of TARA-002 in approximately 30 pediatric patients ages 6 months to less than 18 years old with macrocystic and mixed-cystic

We have an open IND for LMs with

the FDA’s Vaccines Division.

In October 2023, we initiated the STARBORN-1 trial, a Phase 2 single arm, open-label clinical trial

to evaluate the safety and efficacy of TARA-002 in approximately 30 pediatric patients ages six months to less than 18 years old with

macrocystic and mixed-cystic LMs.

The clinical trial design includes a safety lead-in phase followed by an expansion phase.

The primary endpoint of the clinical trial

is the proportion of participants with macrocystic and mixed cystic LMs who demonstrate clinical success, defined as having either a complete

response (90% to 100% reduction from baseline in total LM volume) or substantial response (60% to less than 90% reduction in total LM

volume) as measured by axial imaging.

Of three patients treated in the first cohort, which enrolled individuals six years to less than

18 years of age, two patients treated with TARA-002 achieved a complete response after receiving one dose of TARA-002;

the responses were

seen in a patient with a macrocystic lymphatic malformation and a patient with a maxillofacial cyst called a ranula.

endpoint of the clinical trial is the proportion of participants with macrocystic and mixed cystic LMs who demonstrate clinical success,

defined as having either a CR (90% to 100% reduction from baseline in total LM volume) or substantial response (60% to less than 90% reduction

in total LM volume) as measured by axial imaging.

In November 2025, we announced

interim results from our ongoing Phase 2 open-label STARBORN-1 trial.

The interim analysis included a total of 12 patients who enrolled

in the trial and received ≥ one dose of TARA-002 as of the November 12, 2025 data cutoff.

Of those, eight patients were evaluable at

an eight-week post-treatment assessment, two withdrew prior to the eight-week assessment and two remain in dosing.

Patients receive up

to four injections of TARA-002 spaced approximately six weeks apart.

Of the eight patients who were evaluable, the majority (7/8) achieved

clinical success with one or two doses.

Only one patient, who presented with a 1,739 mL macrocystic LM, required all four doses, and achieved

Overall, 80% (8/10) of patients

that completed treatment achieved clinical success and 100% (8/8) of patients who completed the eight-week response assessment achieved

clinical success.

83% (5/6) of macrocystic patients achieved a CR (90% to 100% reduction in total LM volume) and one patient achieved

a substantial response (60% to less than 90% reduction in total LM volume).

The only mixed cystic patient treated achieved a CR.

Two LMs patients in the interim

analysis reached the 32-week post-treatment assessment and remain disease-free.

One patient deemed a CR was subsequently diagnosed with

a ranula (a different type of maxillofacial cyst from LMs).

Two patients withdrew before the eight-week post-treatment assessment, including

one patient who was misdiagnosed and had a rare form of cancer and did not respond to treatment and one patient who dropped out after

achieving a notable resolution of their macrocystic LM.

The patient received two doses of TARA-002 with 160 mL aspiration at the first

dose, which was reduced to a 10 mL aspiration at the second dose.

The majority of AEs were

mild to moderate, with no serious AEs reported.

The most common AEs were swelling and fatigue.

One patient discontinued treatment due

to a Grade 2 AE of fatigue.

Historical Safety Profile on OK-432, predecessor

therapy to TARA-002

The most common adverse events with treatment with OK-432 were local

injection site reactions, fever, fatigue, and decreased appetite, with resolution within two weeks.

Treatment emergent serious adverse

events, or SAEs, (treatment emergent SAEs are defined as any SAE occurring or worsening on or after the first dose of study drug and within

The most common AEs with

treatment with OK-432 were local injection site reactions, fever, fatigue and decreased appetite, with resolution within two weeks.

emergent SAEs (treatment emergent SAEs are defined as any SAE occurring or worsening on or after the first dose of study drug and within

35 days after the last dose of study drug) associated with OK-432 treatment were reported in 4.1% of patients, with the most severe events

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OK-432, predecessor therapy to TARA-002

A comprehensive preclinical development program for OK-432, including

in vitro and in vivo pharmacology and toxicology studies, was conducted by Chugai Pharmaceutical to support the filing and

approval of an NDA with the Japan Pharmaceuticals and Medical Devices Agency.

We believe these studies may help inform the design of a

development plan for TARA-002 in LMs.

In addition, there is a significant body of literature exploring the use of OK-432 in other

maxillofacial cysts demonstrating strong potential for TARA-002 to be explored in the treatment of these cysts as well.

A comprehensive preclinical

development program for OK-432, including in vitro and in vivo pharmacology and toxicology studies, was conducted by Chugai Pharmaceutical

to support the filing and approval of an NDA with the Japan Pharmaceuticals and Medical Devices Agency.

We believe these studies may

help inform the design of a development plan for TARA-002 in LMs.

In addition, there is a significant body of literature exploring

the use of OK-432 in other maxillofacial cysts demonstrating strong potential for TARA-002 to be explored in the treatment of these cysts

Regulatory Interactions

In July 2020, the FDA granted Rare Pediatric Disease Designation for

TARA-002 for the treatment of LMs.

The FDA grants Rare Pediatric Disease Designation for serious diseases that primarily affect children

ages 18 years or younger and fewer than 200,000 persons in the United States.

Under the FDA’s Rare Pediatric Disease Priority Review

Voucher program, a sponsor who receives an approval of an NDA or BLA for a product for the prevention or treatment of a rare pediatric

disease may be eligible for a voucher, which can be redeemed to obtain priority review for any subsequent marketing application or may

be sold or transferred prior to such redemption.

Currently in order to obtain a voucher, the NDA or BLA for a product candidate that was

granted Rare Disease Designation before December 20, 2024 must be approved by September 30, 2026, unless the program is extended by Congress.

In May 2022 the European Commission granted Orphan Drug Designation

to TARA-002 for the treatment of LMs.

In July 2020, the FDA granted

RPDD for TARA-002 for the treatment of LMs.

The FDA grants RPDD for serious diseases that primarily affect children ages 18 years or younger

and fewer than 200,000 persons in the U.S.

Under the FDA’s Rare Pediatric Disease Priority Review Voucher Program, a sponsor who

receives an approval of an NDA or BLA for a product for the prevention or treatment of a rare pediatric disease may be eligible for a

voucher, which can be redeemed to obtain priority review for any subsequent marketing application or may be sold or transferred prior

to such redemption.

Under the current provisions in the law, the Rare Pediatric Disease Priority Review Voucher Program will sunset on

September 30, 2029, which means that the FDA may only award a Priority Review Voucher, or PRV, for an approved Rare Pediatric Disease

product application if the sponsor has received RPDD for the product and the product is subsequently approved by September 30, 2029.

May 2022, the European Commission granted Orphan Medicinal Product Designation to TARA-002 for the treatment of LMs.

In December 2025, the FDA

granted both BTD and FTD for TARA-002 for the treatment of macrocystic and mixed cystic LMs in pediatric patients.

Manufacturing

manufactured using an equivalent, but modernized, proprietary manufacturing process as is used to produce OK-432 by Chugai

Pharmaceutical.

We propagated a master cell bank using the same master cell line of the genetically distinct strain of Streptococcus

pyogenes (A group, type 3) Su strain as OK-432.

The bacteria is rendered inactive during the manufacturing process, consistent with

the process used for OK-432.

The facility which manufactures TARA-002 has been inspected by the FDA and at the most recent

inspection no Form 483s were issued.

TARA-002 is manufactured using

an equivalent, but modernized, proprietary manufacturing process as is used to produce OK-432 by Chugai Pharmaceutical.

We propagated

a master cell bank using the same master cell line of the genetically distinct strain of Streptococcus pyogenes (A group, type 3) Su

strain as OK-432.

The bacteria is rendered inactive during the manufacturing process, consistent with the process used for OK-432.

have contracted a cGMP compliant CDMO to manufacture TARA-002 in the U.S.

Collaborations and License Agreements

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commercialization of the New Product in the Protara Territory.

On July 14, 2020, we and Chugai Pharmaceutical entered into an amendment

of the Chugai Agreement, or the Chugai Pharmaceutical Amendment, with an effective date as of June 30, 2020.

The Chugai Amendment extended

the date through which Chugai will exclusively provide the Existing Product and materials to us from June 30, 2020 to June 30, 2021, extended

the date through which Chugai will not provide materials or technical support to any third-party for the purpose of development and commercialization

in a given area from the fifth anniversary to the eleventh anniversary of the original effective date (extended to June 17, 2030), and

provides for further such extensions on the occurrence of certain events and milestones.

The Chugai Amendment also provides that, in addition

to the designated fee payable upon the initial indication approval in the Chugai Agreement described below, we will pay Chugai Pharmaceutical

a designated fee in the low, single digit millions for each additional indication approval.

On July 14, 2020, we and

Chugai Pharmaceutical entered into an amendment of the Chugai Agreement, or the Chugai Pharmaceutical Amendment, with an effective date

as of June 30, 2020.

The Chugai Amendment extended the date through which Chugai will exclusively provide the Existing Product and materials

to us from June 30, 2020 to June 30, 2021, extended the date through which Chugai will not provide materials or technical support to any

third-party for the purpose of development and commercialization in a given area from the fifth anniversary to the eleventh anniversary

of the original effective date (extended to June 17, 2030), and provides for further such extensions on the occurrence of certain events

and milestones.

The Chugai Amendment also provides that, in addition to the designated fee payable upon the initial indication approval

in the Chugai Agreement described below, we will pay Chugai Pharmaceutical a designated fee in the low, single digit millions for each

additional indication approval.

As consideration for Chugai

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manufacturing and supplying, or causing our CDMO to manufacture and supply, the New Product to Chugai Pharmaceutical.

The Chugai Agreement will

remain in full force and effect until the first anniversary of the date of FDA approval of the New Product, unless terminated sooner,

or the Chugai Term.

Following the Chugai Service Period and during the Chugai Term, Chugai Pharmaceutical may terminate the Chugai Agreement,

in whole or in part, without cause, by providing us 90 days prior written notice.

Following such termination, we would maintain exclusive

access to Chugai Materials, subject to the termination clauses outlined below.

We may terminate the Chugai Agreement, in whole only, by

providing Chugai Pharmaceutical 90 days’ prior written notice if (i) we decide to discontinue the New Product development;

we decide that the FDA’s requirements for the New Product are not likely to be met;

or (iii) the FDA identifies a safety issue regarding

the New Product.

Chugai Agreement will remain in full force and effect until the first anniversary of the date of FDA approval of the New Product, unless

terminated sooner, or the Chugai Term.

Following the Chugai Service Period and during the Chugai Term, Chugai Pharmaceutical may terminate

the Chugai Agreement, in whole or in part, without cause, by providing us 90 days prior written notice.

Following such termination, we

would maintain exclusive access to Chugai Materials, subject to the termination clauses outlined below.

We may terminate the Chugai Agreement,

in whole only, by providing Chugai Pharmaceutical 90 days’ prior written notice if:

(i) we decide to discontinue the New Product

(ii) we decide that the FDA’s requirements for the New Product are not likely to be met;

or (iii) the FDA identifies

a safety issue regarding the New Product.

In addition, either party

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with the payments ranging from $62,500 to $125,000.

We may terminate the Research Agreement upon 30 days’ prior

written notice to the University.

Either party may terminate the project under the Research Agreement and all commitments and obligations

with respect thereto upon 30 days’ prior written notice to the other party.

In the event of any termination of the project under

the Research Agreement by the University, (a) the University agrees to complete certain phases of the project and (b) we will continue

to provide annual funding until the completion of the second phase of the project.

Upon termination of the project by us, the Agreement

will terminate and we will reassign to the University the IND for LMs.

We may terminate the Research

Agreement upon 30 days’ prior written notice to the University.

Either party may terminate the project under the Research Agreement

and all commitments and obligations with respect thereto upon 30 days’ prior written notice to the other party.

In the event of

any termination of the project under the Research Agreement by the University, (a) the University agrees to complete certain phases of

the project and (b) we will continue to provide annual funding until the completion of the second phase of the project.

Upon termination

of the project by us, the Agreement will terminate and we will reassign to the University the IND for LMs.

Choline License Agreement

On September 27, 2017, we entered into a choline license agreement,

or the Choline Agreement, with Alan L.

On September 27, 2017, we

entered into a choline license agreement, or the Choline Agreement, with Alan L.

Buchman, M.D., pursuant to which Dr.

Buchman granted us an exclusive, worldwide, non-transferable

license in and to certain licensed orphan designations, a certain licensed IND, certain existing study data and certain licensed know-how

to develop, make, use, sell, offer for sale and import the licensed product during the term of the Choline Agreement.

We are solely responsible

for all fees and expenses under the Choline Agreement, including all due diligence obligations, regulatory authority fees, attorney fees

and consulting fees.

Buchman granted

us an exclusive, worldwide, non-transferable license in and to certain licensed orphan designations, a certain licensed IND, certain existing

study data and certain licensed know-how to develop, make, use, sell, offer for sale and import the licensed product during the term of

the Choline Agreement.

We are solely responsible for all fees and expenses under the Choline Agreement, including all due diligence obligations,

regulatory authority fees, attorney fees and consulting fees.

During the term of the Choline Agreement, Dr.

Buchman may not work with any third parties on any product competing

with the licensed product.

In consideration for the rights and licenses granted under the Choline Agreement, we made an initial upfront

payment of $50,000 to Dr.

Buchman may not work with

any third parties on any product competing with the licensed product.

In consideration for the rights and licenses granted under the Choline

Agreement, we made an initial upfront payment of $50,000 to Dr.

Certain milestone and royalty

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Buchman a minimum annual royalty that ranges from $25,000 to $75,000.

We have an obligation to pay Dr.

Buchman sales royalties based on aggregate

net sales of IV Choline Chloride in each calendar quarter, with the tiered royalty rates ranging from 5.0% to 10.5% of net sales.

event of development or commercialization activity by any sublicensees, we also agreed to pay Dr.

Buchman a royalty in the mid-single

digit percentage of (i) net cash receipts, after payment of taxes, received by us from sublicensees for their sales of licensed products

and (ii) any other consideration received by us from such sublicensees;

in each case, including a fair monetary value for any transaction

that is not a bona fide arms-length transaction or that is for consideration other than monetary.

Further, in the event of a sale or transfer

of a priority review voucher regarding the license product, regardless of whether any development or commercialization activity is undertaken

by us or our sublicensees, we agreed to pay Dr.

Buchman a milestone payment representing the mid-single digit percentage of (i) net cash

receipts, after payment of taxes and (ii) any other consideration;

in each case, received by us, our affiliates, or our sublicensees,

We have an obligation to pay

Buchman sales royalties based on aggregate net sales of IV Choline Chloride in each calendar quarter, with the tiered royalty rates

ranging from 5.0% to 10.5% of net sales.

In the event of development or commercialization activity by any sublicensees, we also agreed

Buchman a royalty in the mid-single digit percentage of (i) net cash receipts, after payment of taxes, received by us from

sublicensees for their sales of licensed products and (ii) any other consideration received by us from such sublicensees;

in each case,

including a fair monetary value for any transaction that is not a bona fide arms-length transaction or that is for consideration other

than monetary.

Further, in the event of a sale or transfer of a PRV, regarding the license product, regardless of whether any development

or commercialization activity is undertaken by us or our sublicensees, we agreed to pay Dr.

Buchman a milestone payment representing the

mid-single digit percentage of (i) net cash receipts, after payment of taxes and (ii) any other consideration;

in each case, received

by us, our affiliates, or our sublicensees, including a fair monetary value for any transaction that is not a bona fide arms-length transaction

or that is for consideration other than monetary.

We will also pay Dr.

up to $775,000 in additional payments upon the achievement of various regulatory approval milestones.

The Choline Agreement will

remain in full force and effect until the last sale of the licensed product under the Choline Agreement.

After we received the FDA’s

written minutes from the initial FDA meeting concerning the development of the first licensed product for one or more of the licensed

indications, we paid an additional payment of $100,000 to Dr.

The Choline Agreement will remain

in full force and effect until the last sale of the licensed product under the Choline Agreement.

After we received the FDA’s written

minutes from the initial FDA meeting concerning the development of the first licensed product for one or more of the licensed indications,

we paid an additional payment of $100,000 to Dr.

Buchman and elected to not terminate the Choline Agreement at that time.

The Choline Agreement may be terminated by Dr.

Buchman if, following regulatory approval of a licensed product, we have not made our first

sale of a licensed product within such country within a specified time period.

We may terminate the Choline Agreement for convenience

upon 90 days’ prior written notice to Dr.

Buchman may terminate the Choline Agreement for non-payment of any payment

due that has not been cured.

Either party may terminate the Choline Agreement if the other party is in material breach and has not cured

such breach within 60 days’ notice.

Agreement may be terminated by Dr.

Buchman if, following regulatory approval of a licensed product, we have not made our first sale of

a licensed product within such country within a specified time period.

We may terminate the Choline Agreement for convenience upon 90

days’ prior written notice to Dr.

Buchman may terminate the Choline Agreement for non-payment of any payment due that

has not been cured.

Either party may terminate the Choline Agreement if the other party is in material breach and has not cured such breach

within 60 days’ notice.

In addition, Dr.

Buchman may terminate the Choline Agreement upon 60 days’ prior written

notice if (a) we cease or threaten to cease to carry on our business;

(b) a petition or resolution for the making of an administration

order or for the bankruptcy, winding-up or dissolution of us is presented or passed;

(d) a receiver or administrator takes possession of our assets or (e) any similar procedure is commenced against us in the

United States.

Buchman may terminate the Choline Agreement upon 60 days’ prior written notice if:

(a) we cease or threaten to cease to carry on our business;

(b) a petition or resolution for the making of an administration order or

for the bankruptcy, winding-up or dissolution of us is presented or passed;

(d) a receiver or administrator takes possession of our assets;

or (e) any similar procedure is commenced against us in the U.S.

License Agreement

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right to grant sublicenses to non-affiliate third parties, to develop, make, have made, use, sell, offer for sale and import certain products

for use in the field of fatty liver disease in humans receiving total parenteral nutrition, by administering, as monotherapy, a pharmaceutical

composition comprising intravenous choline, wherein the fatty liver disease is selected from intestinal failure-associated liver disease,

or IFALD, non-alcoholic fatty liver, non-alcoholic steatohepatitis, or NASH, NASH-associated liver fibrosis, or non-alcoholic cirrhosis.

Notwithstanding the exclusive rights granted to us, the Institute will retain the right to make, use and practice such patents in its

own laboratories solely for non-commercial scientific purposes and for continued non-commercial research.

for use in the field of fatty liver disease in humans receiving total PN, by administering, as monotherapy, a pharmaceutical composition

comprising intravenous choline, wherein the fatty liver disease is selected from IFALD, non-alcoholic fatty liver, non-alcoholic steatohepatitis,

or NASH, NASH-associated liver fibrosis, or non-alcoholic cirrhosis.

Notwithstanding the exclusive rights granted to us, the Institute

will retain the right to make, use and practice such patents in its own laboratories solely for non-commercial scientific purposes and

for continued non-commercial research.

As consideration for the

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one-time milestone payments in the aggregate amount of $375,000 upon the achievement of certain regulatory approval milestones, of which

$100,000 was paid on January 28, 2020 upon us having consummated certain private placements.

$100,000 was paid on January 28, 2020 upon us having consummated certain private placements of securities.

Unless terminated earlier,

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Intellectual Property

Our intellectual property

is critical to our business and we strive to protect it, including by obtaining and maintaining patent protection in the U.S.

Our intellectual property is

critical to our business and we strive to protect it, including by obtaining and maintaining patent protection in the U.S.

and internationally

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that we hold may be challenged, circumvented or invalidated by third parties.

Our commercial success will also depend in part on not infringing the

proprietary rights of third parties.

In addition, we have licensed rights under proprietary technologies of third parties to develop,

manufacture and commercialize specific aspects of our products and services.

It is uncertain whether the issuance of any third-party patent

would require us to alter our development or commercial strategies, alter our processes, obtain licenses or cease certain activities.

The expiration of patents or patent applications licensed from third parties or our breach of any license agreements or failure to obtain

a license to proprietary rights that it may require to develop or commercialize our future technology may have a material adverse impact

If third parties prepare and file patent applications in the United States that also claim technology to which we have rights,

we may have to participate in interference proceedings in the U.S.

Patent and Trademark Office, or USPTO, to determine priority of invention.

For a more comprehensive discussion of the risks related to our intellectual property, please see “ Risk Factors—Risks Related

Our commercial success will also

depend in part on not infringing the proprietary rights of third parties.

In addition, we have licensed rights under proprietary technologies

of third parties to develop, manufacture and commercialize specific aspects of our products and services.

It is uncertain whether the

issuance of any third-party patent would require us to alter our development or commercial strategies, alter our processes, obtain licenses

or cease certain activities.

The expiration of patents or patent applications licensed from third parties or our breach of any license

agreements or failure to obtain a license to proprietary rights that it may require to develop or commercialize our future technology

may have a material adverse impact on it.

If third parties prepare and file patent applications in the U.S.

that also claim technology

to which we have rights, we may have to participate in interference proceedings in the USPTO to determine priority of invention.

more comprehensive discussion of the risks related to our intellectual property, please see “ Risk Factors—Risks Related

to Our Intellectual Property.

TARA-002 is a genetically distinct Su strain of Streptococcus

pyogenes (group A, type 3).

TARA-002 is produced through a proprietary manufacturing process, during which the bacteria is inactivated.

We believe a significant barrier to entry exists, as we believe only Chugai Pharmaceutical and we have the specific strain and possess

the know-how to manufacture the product.

We anticipate that, if approved by the FDA, TARA-002 will be protected by 12 years of biologic

is a genetically distinct Su strain of Streptococcus pyogenes (group A, type 3).

TARA-002 is produced through a proprietary manufacturing

process, during which the bacteria is inactivated.

We believe a significant barrier to entry exists, as we believe only Chugai Pharmaceutical

and we have the specific strain and possess the know-how to manufacture the product.

We anticipate that, if approved by the FDA, TARA-002

will be protected by 12 years of biologic exclusivity.

In addition, the USPTO has issued to us U.S.

12,551,514 claiming a

method of treating NMIBC with a combination of non-viable cells of streptococcus pyogenes and an immune checkpoint inhibitor,

with a term expiring in 2044.

IV Choline Chloride:

With respect to IV Choline Chloride, we have acquired an exclusive,

worldwide license to U.S.

Patent 8,865,641 B2 from the Feinstein Institute for Medical Research providing protection in the United States

With respect to IV Choline Chloride,

we have acquired an exclusive, worldwide license to U.S.

Patent 8,865,641 B2 from the Feinstein Institute for Medical Research providing

protection in the U.S.

The patent applies to a method of treating a fatty liver disease in a subject.

In particular, the method comprises administering

to the subject an effective amount of a cholinergic pathway stimulating agent, wherein the fatty liver disease is selected from non-alcoholic

fatty liver, alcoholic fatty liver, or NASH, alcoholic steatohepatitis, or ASH, NASH-associated liver fibrosis, ASH-associated liver fibrosis,

non-alcoholic cirrhosis and alcoholic cirrhosis.

In particular, the method

comprises administering to the subject an effective amount of a cholinergic pathway stimulating agent, wherein the fatty liver disease

is selected from non-alcoholic fatty liver, alcoholic fatty liver, or NASH, alcoholic steatohepatitis, or ASH, NASH-associated liver fibrosis,

ASH-associated liver fibrosis, non-alcoholic cirrhosis and alcoholic cirrhosis.

In addition, in 2022, the USPTO issued to us Patent No.

US 11,311,503 claiming a sterile

aqueous choline salt composition with a term expiring in 2041.

We expect to list such patent in the FDA’s Orange Book List of Approved

Drug Products with Therapeutic Equivalence Evaluations if IV Choline Chloride is approved by the FDA.

Further, in 2024, the USPTO issued

to us Patent No.

US 12,083,081 claiming a method of treating choline deficiency with a choline composition, also with a term expiring

US 11,311,503 claiming a sterile aqueous choline salt composition with a term expiring in 2041.

We expect to list such patent in the FDA’s

Orange Book List of Approved Drug Products with Therapeutic Equivalence Evaluations if IV Choline Chloride is approved by the FDA.

in 2024, the USPTO issued to us Patent No.

US 12,083,081 claiming a method of treating choline deficiency with a choline composition,

also with a term expiring in 2041.

The term of individual patents

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non-provisional patent application related to the U.S.

In addition, in the United States, the term of a U.S.

patent that covers

an FDA-approved drug may also be eligible for patent term extension, which permits patent term restoration as compensation for the patent

term lost during the FDA regulatory review process.

The Hatch-Waxman Act permits a patent term extension of up to five years beyond the

expiration of the patent.

In addition, in the U.S., the term of a U.S.

patent that covers an FDA-approved

drug may also be eligible for patent term extension, which permits patent term restoration as compensation for the patent term lost during

the FDA regulatory review process.

The Hatch-Waxman Act permits a patent term extension of up to five years beyond the expiration of the

The length of the patent term extension is related to the length of time the drug is under regulatory review.

Patent term extension cannot extend the remaining term of a patent beyond a total of 14 years from the date of product approval and only

one patent applicable to an approved drug may be extended.

Similar provisions are available in Europe and other foreign jurisdictions

to extend the term of a patent that covers an approved drug.

In the future, if and when our products receive FDA approval, we expect to

apply for patent term extensions on patents covering certain of those products, when applicable.

Patent term extension

cannot extend the remaining term of a patent beyond a total of 14 years from the date of product approval and only one patent applicable

to an approved drug may be extended.

Similar provisions are available in Europe and other foreign jurisdictions to extend the term of

a patent that covers an approved drug.

In the future, if and when our products receive FDA approval, we expect to apply for patent term

extensions on patents covering certain of those products, when applicable.

We also rely on trade secrets

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our drug candidates in accordance with cGMP as well as regulations for use in clinical trials and for commercial product.

The manufacture

The manufacturing

of pharmaceuticals is subject to extensive cGMP regulations, which impose various procedural and documentation requirements and govern

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both TARA-002 and IV Choline Chloride.

TARA-002 is manufactured using an equivalent, but modernized,

proprietary manufacturing process as is used to produce OK-432 by Chugai Pharmaceutical, starting with a master cell line propagated by

us but utilizing the same genetically distinct strain of Streptococcus pyogenes (A group, type 3) Su strain, which is inactivated during

the manufacturing process, as OK-432.

TARA-002 is manufactured

using an equivalent, but modernized, proprietary manufacturing process as is used to produce OK-432 by Chugai Pharmaceutical, starting

with a master cell line propagated by us but utilizing the same genetically distinct strain of Streptococcus pyogenes (A group, type 3)

Su strain, which is inactivated during the manufacturing process, as OK-432.

Both TARA-002 and IV Choline

Chloride are or will be manufactured in the United States.

The starting materials for TARA-002 were provided to us pursuant to an agreement

with Chugai Pharmaceutical.

Chloride are or will be manufactured in the U.S.

The starting materials for TARA-002 were provided to us pursuant to an agreement with

Chugai Pharmaceutical.

The regulatory starting materials for IV Choline Chloride are available commercially.

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We plan to become a fully-integrated

commercial biopharmaceutical company in the United States pursuing our mission of supporting and improving the lives of patients suffering

from cancer and rare diseases.

If approved by the FDA, we

plan to commercialize all of our current product candidates in the United States first and then in other geographies, if approved by the

regulatory authorities in those other locations.

As we advance TARA-002 and IV Choline Chloride through our respective clinical development

programs, we plan to grow our commercial organization in support of anticipated product launches.

commercial biopharmaceutical company in the U.S.

pursuing our mission of supporting and improving the lives of patients suffering from

cancer and rare diseases.

If approved by the FDA, we plan

to commercialize all of our current product candidates in the U.S.

first and then either alone or with partners in other geographies,

if approved by the regulatory authorities in those other locations.

As we advance TARA-002 and IV Choline Chloride through our respective

clinical development programs, we plan to grow our commercial organization in support of anticipated product launches.

The process for commercialization

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the development, patenting, manufacturing and marketing of healthcare products competitive with those that we are developing.

With respect to our lead product candidate, TARA-002, for the

treatment of NMIBC and LMs, the active ingredient in TARA-002 is a genetically distinct strain of Streptococcus pyogenes (group A, type

3) Su strain, which is inactivated during the manufacturing process.

With respect to our lead product candidate, TARA-002, for the treatment

of NMIBC and LMs, the active ingredient in TARA-002 is a genetically distinct strain of Streptococcus pyogenes (group A, type 3) Su strain,

which is inactivated during the manufacturing process.

TARA-002 is produced through a proprietary manufacturing process.

We anticipate that, if approved by the FDA, TARA-002 will be protected by 12 years of biologic exclusivity.

In addition, based on the

prevalence of the disease, TARA-002 is likely to have seven years of concurrent Orphan Drug Designation exclusivity for the treatment

We anticipate

that, if approved by the FDA, TARA-002 will be protected by 12 years of biologic exclusivity.

In addition, based on the prevalence of

the disease, TARA-002 is likely to have seven years of concurrent ODD exclusivity for the treatment of LMs.

Further, the USPTO issued

to us Patent No.

12,551,514 claiming a method of treating NMIBC with a combination of non-viable cells of streptococcus pyogenes

and an immune checkpoint inhibitor, with a term expiring in 2044.

There are no approved pharmacotherapies

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For example, the current standard of care for NMIBC includes intravesical BCG TICE (manufactured by Merck & Co., Inc.).

products approved for the treatment of NMIBC include Merck & Co., Inc.’s Keytruda, Endo International plc’s Valstar, and

Ferring B.V.’s Adstiladrin and ImmunityBio, Inc.’s VesAnktiva in combination with BCG.

Additional product candidates in development

include but may not be limited to Japanese BCG Laboratory’s BCG Tokyo, Pfizer Inc.’s Sasanlimab in combination with BCG, CG

Oncology Inc.’s CG0070, enGene Inc.’s, EG-70, Pfizer Inc.’s PADCEV, Janssen’s TAR200 combined with gemcitabine

plus or minus Cetrelimab, Urogen Pharma Ltd.’s Jelmyto, Theralase Technologies Inc.’s Ruvidar, and Auro BioSciences, Inc.’s

Additional pharmaceutical and biotechnology companies with product candidates in development for the treatment of NMIBC include

but may not be limited to Verity, AstraZeneca PLC, Bristol-Myers Squibb Company, Roche Group, Asieris Pharmaceuticals, BeiGene, Ltd, NanOlogy,

products approved for the treatment of NMIBC include Merck & Co., Inc.’s Keytruda, Endo International plc’s Valstar, Ferring

B.V.’s Adstiladrin, ImmunityBio, Inc.’s VesAnktiva in combination with BCG and Janssen’s Inlexzo.

Additional product

candidates in development include but may not be limited to Japanese BCG Laboratory’s BCG Tokyo, Pfizer Inc.’s Sasanlimab

in combination with BCG, CG Oncology Inc.’s CG0070, enGene Inc.’s, EG-70, Pfizer Inc.’s PADCEV, Janssen’s TAR-200

plus Cetrelimab, Urogen Pharma Ltd.’s Jelmyto, Theralase Technologies Inc.’s Ruvidar, and Auro BioSciences, Inc.’s Aura-0011.

Additional pharmaceutical and biotechnology companies with product candidates in development for the treatment of NMIBC include but may

not be limited to Verity, AstraZeneca PLC, Bristol-Myers Squibb Company, Roche Group, Asieris Pharmaceuticals, BeiGene, Ltd, NanOlogy,

LLC, Linton Pharm Co., Ltd., Lindis Biotech GmbH, Taizhou Hanzhong biomedical co.

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authorities at federal, state, and local levels, as well as in foreign countries, extensively regulate, among other things, the research,

development, testing, manufacture, quality control, import, export, safety, effectiveness, labeling, packaging, storage, distribution,

development, testing, manufacturing, quality control, import, export, safety, effectiveness, labeling, packaging, storage, distribution,

record keeping, approval, advertising, promotion, marketing, post-approval monitoring and post-approval reporting of drugs and biologics

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approval or licensure of our product candidates.

In the United States, the

FDA regulates drugs under the Federal Food, Drug and Cosmetic Act, or FDCA and biologics additionally under the Public Health Services

Act, or PHSA, as well as their respective implementing regulations.

The application process and requirements for approval of BLAs are

very similar to those for NDAs.

In the U.S., the FDA regulates

drugs under the Federal Food, Drug, and Cosmetic Act, and biologics additionally under the Public Health Service Act, or PHSA, as well

as their respective implementing regulations.

Drugs are approved via NDAs while biologics are approved via BLAs.

The application process

and requirements for approval of BLAs are very similar to those for NDAs.

Failure to comply with applicable U.S.

requirements may subject a company to a variety of administrative

or judicial sanctions, such as clinical hold, FDA refusal to file NDA/BLAs and/or to approve pending NDAs or BLAs, warning or untitled

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

and criminal prosecution.

The process required by the FDA before biopharmaceutical product candidates

may be marketed in the United States generally involves the following:

requirements may subject

a company to a variety of administrative or judicial sanctions, such as clinical hold, FDA refusal to file NDAs or BLAs and/or to approve

pending NDAs or BLAs, warning or untitled letters, product recalls, product seizures, total or partial suspension of production or distribution,

injunctions, fines, civil penalties and criminal prosecution.

process required by the FDA before biopharmaceutical product candidates may be marketed in the U.S.

generally involves the following:

completion of preclinical laboratory tests and animal studies performed in accordance with the FDA’s current Good Laboratory Practices, or cGLP, regulations;

submission to the FDA of an IND, which must become effective before clinical trials may begin and must be updated annually or when significant changes are made;

by an independent Institutional Review Board, or IRB, or ethics committee at each clinical site before the clinical trial is commenced;

performance of adequate and well-controlled human clinical trials to

establish the safety and efficacy of a drug product candidate and the safety, purity and potency of a biologic product candidate for its

intended purpose;

preparation of and submission to the FDA of an NDA or BLA, including

a substantial application user fee unless a waiver applies, after completion of all pivotal clinical trials that includes substantial

evidence of safety, purity and potency or efficacy from results of non-clinical testing and clinical trials;

a determination by the FDA within 60 days of its receipt of an NDA or BLA to accept the application for review;

satisfactory completion of an FDA Advisory Committee review, if applicable;

approval by an independent Institutional Review Board, or IRB, or ethics committee at each clinical site before the clinical trial is commenced;

performance of adequate and well-controlled human clinical trials to establish the safety and efficacy of a drug product candidate and the safety, purity and potency of a biologic product candidate for its intended purpose;

preparation of and submission to the FDA of an NDA or BLA, including a substantial application user fee unless a waiver applies, after completion of all pivotal clinical trials that includes substantial evidence of safety, purity and potency or efficacy from results of non-clinical testing and clinical trials;

a determination by the FDA within 60 days of its receipt of an NDA or BLA to file the application for review;

satisfactory completion of an FDA pre-approval inspection of the manufacturing facility or facilities at which the proposed product is produced to assess compliance with cGMP, and of selected clinical investigation sites to assess compliance with current Good Clinical Practices, or cGCP;

FDA review and approval, or licensure, of the NDA or BLA to permit commercial marketing of the product for particular indications for use in the United States.

FDA review and approval, or licensure, of the NDA or BLA to permit commercial

marketing of the product for particular indications for use in the U.S.;

Compliance with any post-approval requirements, including the potential

requirement to implement a Risk Evaluation and Mitigation Strategy, or REMS, to conduct post-approval studies.

Preclinical and Clinical Development

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The conduct of the preclinical tests must comply with federal regulations and requirements, including

Good Laboratory Practices, an international standard meant to ensure the presence of a standard quality system under which laboratory

work and non-clinical studies are conducted, recorded and archived.

The IND includes results

of animal and in vitro studies assessing the toxicology, pharmacokinetics, pharmacology, and pharmacodynamic characteristics of

the product candidate;

chemistry, manufacturing, and controls information;

cGLP regulations, an international standard meant to ensure the presence of a standard quality system under which laboratory work and

non-clinical studies are conducted, recorded and archived.

The IND includes results of animal

and in vitro studies assessing the toxicology, PKs, pharmacology and pharmacodynamic characteristics of the product candidate;

manufacturing, and controls information;

the general investigational plan;

the proposed protocol(s)

for clinical trials;

and any available human data or literature to support the use of the investigational product.

Long-term preclinical

tests, such as tests of reproductive toxicity and carcinogenicity in animals, may continue after the IND is submitted.

An IND must become

effective before human clinical trials may begin.

The IND automatically becomes effective 30 days after receipt by the FDA, unless the

FDA, within the 30-day time period, raises safety concerns or questions about the proposed clinical trial.

In such a case, the IND may

be placed on clinical hold and the IND sponsor and the FDA must resolve any outstanding concerns or questions before the clinical trial

Submission of an IND therefore may or may not result in FDA authorization to begin a clinical trial.

Clinical trials involve the administration of the investigational

product to human subjects under the supervision of qualified investigators in accordance with GCPs, an international standards designed

to protect the rights and health of patients which includes the requirement that all research subjects provide their informed consent

for their participation in any clinical trial, and to define the roles, qualifications and responsibilities of clinical trial sponsors,

administrators and monitors.

Clinical trials are conducted under protocols detailing, among other things, the objectives of the clinical

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

A separate submission to the existing

IND must be made for each successive clinical trial conducted during product development and for any subsequent protocol amendments.

an independent IRB for each site proposing to conduct the clinical trial must review and approve the plan for any clinical trial and its

informed consent form before the clinical trial begins at that site, and must monitor the clinical trial until completed.

Regulatory authorities,

the IRB or the sponsor may suspend a clinical trial at any time on various grounds, including a finding that the subjects are being exposed

to an unacceptable health risk or that the clinical trial is unlikely to meet its stated objectives.

Some studies also include oversight

by an independent group of qualified experts organized by the clinical trial sponsor, known as a data safety monitoring board, which provides

authorization for whether or not a clinical trial may move forward at designated check points based on access to certain data from the

clinical trial and may recommend that the clinical trial be stopped if it determines that there is an unacceptable safety risk for subjects

or other grounds, such as no demonstration of efficacy.

There are also requirements governing the reporting of ongoing clinical trials

and clinical trial results to public registries.

the proposed protocol(s) for clinical trials;

and any available

human data or literature to support the use of the investigational product.

Long-term preclinical tests, such as tests of reproductive

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

An IND must become effective before human clinical trials

The IND automatically becomes effective 30 days after receipt by the FDA, unless the FDA, within the 30-day time period, raises

safety concerns or questions about the proposed clinical trial.

In such a case, the IND may be placed on clinical hold and the IND sponsor

and the FDA must resolve any outstanding concerns or questions before the clinical trial can begin.

Submission of an IND therefore may

or may not result in FDA authorization to begin a clinical trial.

Clinical trials involve the administration

of the investigational product to human subjects under the supervision of qualified investigators in accordance with cGCPs, an international

standard designed to protect the rights and health of human subjects participating in research, which includes the requirement that all

research participants provide their informed consent for their participation in any clinical trial, and to define the roles, qualifications

and responsibilities of clinical trial sponsors, administrators and monitors.

Clinical trials are conducted under protocols detailing,

among other things, the objectives of the clinical trial, the parameters to be used in monitoring safety and the effectiveness criteria

to be evaluated.

A separate submission to the existing IND must be made for each successive clinical trial conducted during product development

and for any subsequent protocol amendments.

Furthermore, an independent IRB for each site proposing to conduct the clinical trial must

review and approve the plan for any clinical trial and its informed consent form before the clinical trial begins at that site, and must

monitor the clinical trial until completed.

Regulatory authorities, the IRB or the sponsor may suspend a clinical trial at any time on

various grounds, including a finding that the subjects are being exposed to an unacceptable health risk or that the clinical trial is

unlikely to meet its stated objectives.

Some studies also include oversight by an independent group of qualified experts organized by

the clinical trial sponsor, known as a data safety monitoring board, which provides authorization for whether or not a clinical trial

may move forward at designated check points based on access to certain data from the clinical trial and may recommend that the clinical

trial be stopped if it determines that there is an unacceptable safety risk for subjects or other grounds, such as no demonstration of

There are also requirements governing the reporting of ongoing clinical trials and clinical trial results to public registries.

Human clinical trials are

typically conducted in three sequential phases that may overlap.

1—The investigational product is initially introduced into healthy human subjects or patients with the target disease or condition.

These clinical trials are designed to test the safety, dosage tolerance, absorption, metabolism, distribution and elimination of the

investigational product in humans, the side effects associated with increasing doses, and, if possible, to gain early evidence on effectiveness.

Phase 1—The investigational product is initially introduced into healthy human subjects or patients with the target disease or condition.

These clinical trials are designed to test the safety, dosage tolerance, absorption, metabolism, distribution and elimination of the investigational product in humans, the side effects associated with increasing doses, and, if possible, to gain early evidence on effectiveness.

Phase 2—The investigational product is administered to a limited patient population with a specified disease or condition to evaluate the preliminary efficacy, optimal dosages and dosing schedule and to identify possible adverse side effects and safety risks.

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These clinical trials are intended to establish the overall risk/benefit ratio of the investigational product and to provide an adequate basis for product approval.

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

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

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

in rare instances, including (1) where the study is a large multicenter clinical trial demonstrating internal consistency and a statistically

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

serious outcome and confirmation of the result in a second clinical trial would be practically or ethically impossible or (2) when in

conjunction with confirmatory evidence.

In some cases, the FDA may require, or companies may voluntarily pursue, additional clinical trials

after a product is approved to gain more information about the product.

These post-approval trials may be made a condition to approval

of the NDA or BLA.

Concurrent with clinical trials, companies may complete additional animal studies and develop additional information

about the biological characteristics of the product candidate, and must finalize a process for manufacturing the product in commercial

quantities in accordance with cGMP requirements.

The manufacturing process must be capable of consistently producing quality batches of

the product candidate and, among other things, must develop methods for testing the identity, strength, quality and purity of the final

product, or for biologics, the safety, purity and potency.

Additionally, appropriate packaging must be selected and tested and stability

studies must be conducted to demonstrate that the product candidate does not undergo unacceptable deterioration over its shelf life.

In addition, the sponsor of an investigational drug in a Phase 2 or

Phase 3 clinical trial for a serious or life-threatening disease is required to make available, such as by posting on its website, its

policy on evaluating and responding to requests for expanded access to such investigational drug.

In most cases the FDA requires

two adequate and well-controlled Phase 3 clinical trials to demonstrate the efficacy of a drug.

A single Phase 3 trial with other confirmatory

evidence may be sufficient in rare instances, including (1) where the study is a large multicenter clinical trial demonstrating internal

consistency and a statistically very persuasive finding of a clinically meaningful effect on mortality, irreversible morbidity or prevention

of a disease with a potentially serious outcome and confirmation of the result in a second clinical trial would be practically or ethically

impossible or (2) when in conjunction with confirmatory evidence.

In some cases, the FDA may require, or companies may voluntarily pursue,

additional clinical trials after a product is approved to gain more information about the product.

These post-approval trials may be made

a condition to approval of the NDA or BLA.

Concurrent with clinical trials, companies may complete additional animal studies and develop

additional information about the biological characteristics of the product candidate, and must finalize a process for manufacturing the

product in commercial quantities in accordance with cGMP requirements.

The manufacturing process must be capable of consistently producing

quality batches of the product candidate and, among other things, must develop methods for testing the identity, strength, quality and

purity of the final product, or for biologics, the safety, purity and potency.

Additionally, appropriate packaging must be selected and

tested and stability studies must be conducted to demonstrate that the product candidate does not undergo unacceptable deterioration over

its shelf life.

In addition, the sponsor

of an investigational drug in a Phase 2 or Phase 3 clinical trial for a serious or life-threatening disease is required to make available,

such as by posting on its website, its policy on evaluating and responding to requests for expanded access to such investigational drug.

Application Submission, Review and Approval

Assuming successful completion of all required testing in accordance

with all applicable regulatory requirements, the results of product development, non-clinical studies and clinical trials are submitted

to the FDA as part of an NDA or BLA requesting approval to market the product for one or more indications in the U.S.

The NDA or BLA must

include all relevant data available from all preclinical and clinical trials, including negative or ambiguous results as well as positive

findings, together with detailed information relating to the product’s chemistry, manufacturing, controls, and proposed labeling,

among other things.

The submission of an NDA or BLA requires payment of a substantial application user fee to the FDA, unless a waiver

or exemption applies.

Assuming successful completion

of all required testing in accordance with all applicable regulatory requirements, the results of product development, non-clinical studies

and clinical trials are submitted to the FDA as part of an NDA or BLA requesting approval to market the product for one or more indications

The NDA or BLA must include all relevant data available from all preclinical and clinical trials, including negative or ambiguous

results as well as positive findings, together with detailed information relating to the product’s chemistry, manufacturing, controls,

and proposed labeling, among other things.

The submission of an NDA or BLA requires payment of a substantial application user fee to the

FDA, unless a waiver or exemption applies.

These fees are typically increased annually.

The FDA has 60 days from its receipt of an NDA or BLA to determine

whether the application will be filed based on the FDA’s determination that it is adequately organized and sufficiently complete

to permit substantive review.

The FDA has 60 days from its

receipt of an NDA or BLA to determine whether the application will be filed based on the FDA’s determination that it is adequately

organized and sufficiently complete to permit substantive review.

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

For new molecular entities, the FDA’s

goal is to review standard applications within ten months after it files the application, or, if the application qualifies for priority

review, six months after the FDA files the application.

In both standard and priority reviews, the review process may be extended by FDA

requests for additional information or clarification.

The FDA reviews the application to determine, among other things, whether a product

is safe, pure and potent and the facility in which it is manufactured, processed, packed, or held meets standards designed to assure the

product’s continued safety, purity and potency.

The FDA may convene an advisory committee – typically a panel that includes

clinicians, statisticians and other experts – to provide insight on application review questions.

The FDA is not bound by the recommendation

of the advisory committee, but generally follows such recommendation.

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

facility or facilities where the product is manufactured.

The FDA will not approve an application unless it determines that the manufacturing

processes and facilities are in compliance with cGMP requirements and adequate to assure consistent production of the product within required

specifications.

Additionally, before approving an NDA or BLA, the FDA will typically inspect one or more clinical sites to assure compliance

If the FDA determines that the application, manufacturing process or manufacturing facilities are not acceptable, it will outline

the deficiencies in the submission and often will request additional testing or information.

Notwithstanding the submission of any requested

additional information, the FDA ultimately may decide that the application does not satisfy the regulatory criteria for approval.

The FDA will issue an approval letter or a Complete Response letter.

An approval letter authorizes commercial marketing of the product with specific prescribing information for specific indications.

Response letter will describe all of the deficiencies that the FDA has identified in the NDA or BLA.

In issuing the Complete Response

letter, the FDA may recommend actions that the applicant might take to place the application in condition for approval, including requests

for additional information or clarification.

The FDA may delay or refuse approval of an application if applicable regulatory criteria

are not satisfied, require additional testing or information and/or require post-marketing testing and surveillance to monitor safety

or efficacy of a product.

If, or when, deficiencies outlined in a Complete Response letter have been addressed to the FDA’s satisfaction

in a resubmission of the NDA or BLA, the FDA will issue an approval letter.

The FDA has committed to reviewing such resubmissions in two

or six months depending on the type of information included.

As a condition of NDA or

BLA approval, the FDA may impose limitations on the indicated uses for which such product may be marketed.

new molecular entities, the FDA’s goal is to review standard applications within ten months after it files the application, or,

if the application qualifies for priority review, six months after the FDA files the application.

In both standard and priority reviews,

the review process may be extended by FDA requests for additional information or clarification.

The FDA reviews the application to determine,

among other things, whether a product is safe, pure and potent and the facility in which it is manufactured, processed, packed, or held

meets standards designed to assure the product’s continued safety, purity and potency.

The FDA may convene an advisory committee

– typically a panel that includes clinicians, statisticians and other experts – to provide insight on application review questions.

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

Before approving an NDA

or BLA, the FDA will typically inspect the facility or facilities where the product is manufactured.

The FDA will not approve an application

unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to assure consistent

production of the product within required specifications.

Additionally, before approving an NDA or BLA, the FDA will typically inspect

one or more clinical sites to assure compliance with cGCP.

If the FDA determines that the application, manufacturing process or manufacturing

facilities are not acceptable, it will outline the deficiencies in the submission and often will request additional testing or information.

Notwithstanding the submission of any requested additional information, the FDA ultimately may decide that the application does not satisfy

the regulatory criteria for approval.

The FDA will issue an approval

letter or a Complete Response letter, or CRL, upon completion of review of an NDA or BLA.

An approval letter authorizes commercial marketing

of the product with specific prescribing information for specific indications.

A CRL will describe all of the deficiencies that the FDA

has identified in the NDA or BLA.

In issuing the CRL, the FDA may recommend actions that the applicant might take to place the application

in condition for approval, including requests for additional information or clarification.

The FDA may delay or refuse approval of an

application if applicable regulatory criteria are not satisfied, require additional testing or information and/or require post-marketing

testing and surveillance to monitor safety or efficacy of a product.

If, or when, deficiencies outlined in a CRL have been addressed to

the FDA’s satisfaction in a resubmission of the NDA or BLA, the FDA will issue an approval letter.

The FDA has committed to reviewing

such resubmissions in two or six months depending on the type of information included.

As a condition of NDA or BLA

approval, the FDA may impose limitations on the indicated uses for which such product may be marketed.

For example, the FDA may impose

a Risk Evaluation and Mitigation Strategy, or REMS, to ensure the benefits of the product outweigh its risks.

A REMS is a safety strategy

to manage a known or potential serious risk associated with a product and to enable patients to have continued access to such medicines

by managing their safe use, and 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.

The FDA also may condition approval on, among other

things, changes to proposed labeling or the development of adequate controls and specifications.

Once approved, the FDA may withdraw the

product approval if compliance with pre- and post-marketing requirements is not maintained or if problems occur after the product reaches

the marketplace.

The FDA may require one or more post-approval trials and surveillance to further assess and monitor the product’s

safety and effectiveness after commercialization, and may limit further marketing of the product based on the results of these post-marketing

Disclosure of Clinical

Trial Information

Sponsors of clinical trials of FDA regulated products, including

drugs, are required to register and disclose certain clinical trial information.

Information related to the product, patient population,

phase of investigation, study sites and investigators, and other aspects of the clinical trial is then made public as part of the registration.

a REMS, to ensure the benefits of the product outweigh its risks.

A REMS is a safety strategy to manage a known or potential serious risk

associated with a product and to enable patients to have continued access to such medicines by managing their safe use, and 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.

The FDA also may condition approval on, among other things, changes to proposed labeling or the development

of adequate controls and specifications.

Once approved, the FDA may withdraw the product approval if compliance with pre- and post-marketing

requirements is not maintained or if problems occur after the product reaches the marketplace.

The FDA may require one or more post-approval

trials and surveillance to further assess and monitor the product’s safety and effectiveness after commercialization, and may limit

further marketing of the product based on the results of these post-marketing trials.

Disclosure of Clinical Trial Information

Sponsors of clinical trials

of FDA regulated products, including drugs, are required to register and disclose certain clinical trial information.

Information related

to the product, patient population, phase of investigation, study sites and investigators, and other aspects of the clinical trial is

then made public as part of the registration.

Sponsors are also obligated to discuss the results of their clinical trials after completion.

Disclosure of the results of these clinical

trials can be delayed in certain circumstances for up to two years after the date of completion of the clinical trial.

Competitors may

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

The government recently released

a regulation and policy to expand and enhance the requirements related to registering and reporting the results of clinical trials, which

may result in greater enforcement of these requirements in the future.

Disclosure of the results of these clinical trials can be delayed in certain circumstances for up to two years after the date of completion

of the clinical trial.

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

The government published a regulation and policy to expand and enhance the requirements related to registering and reporting

the results of clinical trials, which may result in greater enforcement of these requirements in the future.

Orphan Drug Designation

Under the Orphan Drug Act, the FDA may grant Orphan Drug Designation

to a drug or biologic intended to treat a rare disease or condition, which is a disease or condition that affects fewer than 200,000 individuals

in the United States, or more than 200,000 individuals in the United States for which there is no reasonable expectation that the cost

of developing and making available in the United States a drug or biologic for this type of disease or condition will be recovered from

sales in the United States for that drug or biologic.

Orphan Drug Designation must be requested before submitting an NDA or BLA.

the FDA grants Orphan Drug Designation, the generic identity of the therapeutic agent and its potential orphan use are disclosed publicly

Orphan Drug Designation does not convey any advantage in, or shorten the duration of, the regulatory review or approval

If a product that has Orphan Drug Designation subsequently receives

the first FDA approval for the disease for which it has such designation, the product is entitled to orphan exclusivity, which means that

the FDA may not approve any other applications, including a full NDA or BLA, to market the same product for the same indication for seven

years, except in limited circumstances, such as a showing of clinical superiority to the product with orphan drug exclusivity.

exclusivity does not prevent FDA from approving a different drug or biologic for the same disease or condition, or the same drug or biologic

for a different disease or condition.

Among the other benefits of Orphan Drug Designation are tax credits for certain research and a waiver

of the BLA application fee.

A designated orphan product

may not receive orphan exclusivity if it is approved for a use that is broader than the indication for which it received Orphan Drug Designation.

In addition, exclusive marketing rights in the United States may be lost if the FDA later determines that the request for designation

was materially defective or if the manufacturer is unable to assure sufficient quantities of the product to meet the needs of patients

with the rare disease or condition.

Under the Orphan Drug Act, the

FDA may grant ODD to a drug or biologic intended to treat a rare disease or condition, which is a disease or condition that affects fewer

than 200,000 individuals in the U.S., or more than 200,000 individuals in the U.S.

for which there is no reasonable expectation that the

cost of developing and making available in the U.S.

a drug or biologic for this type of disease or condition will be recovered from sales

for that drug or biologic.

ODD must be requested before submitting an NDA or BLA.

After the FDA grants ODD, the generic identity

of the therapeutic agent and its potential orphan use are disclosed publicly by the FDA.

ODD does not convey any advantage in, or shorten

the duration of, the regulatory review or approval process.

If a product that has ODD subsequently

receives the first FDA approval for the disease for which it has such designation, the product is entitled to orphan exclusivity, which

means that the FDA may not approve any other applications, including a full NDA or BLA, to market the same product for the same indication

for seven years, except in limited circumstances, such as a showing of clinical superiority to the product with orphan drug exclusivity.

Orphan exclusivity does not prevent the FDA from approving a different drug or biologic for the same disease or condition, or the same

drug or biologic for a different disease or condition.

Among the other benefits of ODD are tax credits for certain research and a waiver

of the FDA application fee.

A designated orphan product may

not receive orphan exclusivity if it is approved for a use that is broader than the indication for which it received ODD.

exclusive marketing rights in the U.S.

may be lost if the FDA later determines that the request for designation was materially defective

or if the manufacturer is unable to assure sufficient quantities of the product to meet the needs of patients with the rare disease or

Rare Pediatric Disease Priority Review Voucher

The FDA incentivizes the

development of drugs and biologics that meet the definition of a “rare pediatric disease” defined to mean a serious or life-threatening

disease in which the serious of life-threatening manifestations primarily affect individuals aged from birth to 18 years and the disease

affects fewer than 200,000 individuals in the United States or affects 200,000 or more in the United States and for which there is no

reasonable expectation that the cost of developing and making in the United States a drug for such disease or condition will be received

from sales in the United States of such drug.

The sponsor of a product candidate granted Rare Pediatric Disease Designation may be eligible

for a voucher that can be used to obtain a priority review for a subsequent NDA or BLA after the date of approval of the designated Rare

Pediatric Disease drug product, referred to as a priority review voucher, or PRV.

To receive a Rare Pediatric Disease PRV, a sponsor must

notify the FDA, upon submission of the NDA or BLA, of its intent to request a voucher.

If the FDA determines that the NDA or BLA is a

Rare Pediatric Disease product application, and if the NDA or BLA is approved, the FDA will award the sponsor of the application a PRV

upon approval of the NDA or BLA.

The FDA may revoke a Rare Pediatric Disease PRV if the product for which it was awarded is not marketed

within 365 days of the product’s approval.

The sponsor submitting the PRV must notify the FDA of is intent to submit

the voucher with the NDA or BLA at least 90 days prior to submission of the NDA or BLA and must pay a priority review user fee in addition

to any other required user fee.

The FDA must take action on an NDA or BLA under priority review within six months of the FDA’s filing

of the NDA or BLA.

A Rare Pediatric Disease Designation does not guarantee that a sponsor will receive a PRV upon approval of its NDA

If a PRV is received, it may be sold or transferred an unlimited number of times prior to its redemption.

The Rare Pediatric Disease PRV Program has always had a scheduled

sunset date established in the law.

Under the current provisions in the law, as amended by the Continuing Appropriations and Extensions

Act, 2025, the Rare Pediatric Disease PRV Program will begin to sunset after December 20, 2024, which means that although Congress has

extended the law in the past, and has proposed extending it again, it has not yet done so.

Thus, after December 20, 2024, the FDA may

only award a PRV for an approved Rare Pediatric Disease product application if the sponsor has received Rare Pediatric Disease Designation

for the product by December 20, 2024, and the product is approved by September 30, 2026.

Accordingly, without further statutory amendments,

a drug for which the FDA has granted Rare Pediatric Disease Designation after December 20, 2024 may not be awarded a Rare Pediatric Disease

PRV even if approved by September 30, 2026, and the FDA may not award any Rare Pediatric Disease PRVs after September 30, 2026.

The FDA incentivizes the development

of drugs and biologics for diseases that meet the definition of a “rare pediatric disease” defined to mean a serious or life-threatening

disease in which the serious or life-threatening manifestations primarily affect individuals aged from birth to 18 years and the disease

affects fewer than 200,000 individuals in the U.S.

or affects 200,000 or more in the U.S.

and for which there is no reasonable expectation

that the cost of developing and making in the U.S.

a drug for such disease or condition will be received from sales in the U.S.

The sponsor of a product candidate granted RPDD may be eligible for a voucher that can be used to obtain a priority review for a

subsequent NDA or BLA after the date of approval of the designated Rare Pediatric Disease drug product, referred to as a PRV.

a Rare Pediatric Disease PRV, a sponsor must notify the FDA, upon submission of the NDA or BLA, of its intent to request a voucher.

the FDA determines that the NDA or BLA is a Rare Pediatric Disease product application, and if the NDA or BLA is granted priority review

by the FDA and subsequently approved, the FDA will award the sponsor of the application a PRV upon approval of the NDA or BLA.

may revoke a Rare Pediatric Disease PRV if the product for which it was awarded is not marketed in the U.S.

within 365 days of the product’s

The sponsor submitting the PRV must notify the FDA of is intent to submit the voucher with the NDA or BLA at least 90 days prior

to submission of the NDA or BLA and must pay a priority review user fee in addition to any other required user fee.

The FDA must take

action on an NDA or BLA under priority review within six months of the FDA’s filing of the NDA or BLA.

A RPDD does not guarantee

that an applicant will receive a priority review or a PRV upon approval of its NDA or BLA.

If a PRV is received, under the Rare Pediatric

Disease PRV Program, it may be sold or transferred an unlimited number of times prior to its redemption.

The Rare Pediatric Disease

PRV Program has always had a scheduled sunset date established in the law.

Under the current provisions in the law, the Rare Pediatric

Disease PRV Program will sunset on September 30, 2029, which means that the FDA may only award a PRV for an approved Rare Pediatric Disease

product application if the sponsor has received RPDD for the product by and the product is subsequently approved by September 30, 2029.

Fast Track Designation

Under the FDA’s Fast Track program, the sponsor of a new

drug candidate may request that the FDA designate the drug candidate for a specific indication as a Fast Track drug concurrent with, or

after, the submission of the IND for the drug candidate.

The FDA must determine if the drug candidate qualifies for Fast Track Designation

within 60 days of receipt of the sponsor’s request.

Fast Track Designation is intended to facilitate development and expedite review

of drugs to treat serious and life-threatening conditions so that an approved product can reach the market expeditiously.

If a submission

is granted Fast Track Designation, the sponsor may engage in more frequent interactions with the FDA, and the FDA may review sections

of the NDA or BLA before the full application is complete.

This rolling review is available if, in agreement with the FDA, the applicant

provides a schedule for the submission of the remaining information.

However, the FDA does not start the review clock for the application

until the last section of the NDA or BLA is submitted.

Fast Track Designation may be withdrawn by the FDA at any time if they believe

that the designation is no longer supported by data emerging data in the development process.

Under the FDA’s Fast Track

program, the sponsor of a new drug candidate may request that the FDA designate the drug candidate for a specific indication as a Fast

Track drug concurrent with, or after, the submission of the IND for the drug candidate.

The FDA must determine if the drug candidate qualifies

for FTD within 60 days of receipt of the sponsor’s request.

FTD is intended to facilitate development and expedite review of drugs

to treat serious and life-threatening conditions so that an approved product can reach the market expeditiously.

If a product receives

FTD, the sponsor may engage in more frequent interactions with the FDA, and the FDA may conduct a rolling review, meaning the FDA will

review sections of the NDA or BLA before the full application is complete.

This rolling review is available if, in agreement with the

FDA, the applicant provides a schedule for the submission of the remaining information.

However, the FDA does not start the review clock

for the application until the last section of the NDA or BLA is submitted.

FTD may be withdrawn by the FDA at any time if the FDA believes

that the designation is no longer supported by emerging data in the development process.

Breakthrough Therapy Designation

Additionally, a drug candidate may be eligible for designation

as a breakthrough therapy if the drug is intended, alone or in combination with one or more other drugs or biologics, to treat a serious

or life-threatening condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over currently

approved therapies on one or more clinically significant endpoints.

The FDA expects that such evidence generally would be derived from

early phase clinical trials such as Phase 1 or Phase 2 clinical trials.

For purposes of Breakthrough Therapy Designation, preliminary

Additionally, a drug candidate

may be eligible for designation as a breakthrough therapy if the drug is intended, alone or in combination with one or more other drugs

or biologics, to treat a serious or life-threatening condition and preliminary clinical evidence indicates that the drug may demonstrate

substantial improvement over currently approved therapies on one or more clinically significant endpoints.

The FDA expects that such evidence

generally would be derived from early phase clinical trials such as Phase 1 or Phase 2 clinical trials.

For purposes of BTD, preliminary

clinical evidence refers to evidence that is sufficient to indicate that the drug may demonstrate substantial improvement in effectiveness

or safety over available therapies.

The FDA must determine if the product candidate qualifies for Breakthrough Therapy Designation within

60 days of receipt of the sponsor’s request.

The FDA may take certain actions with respect to breakthrough therapies, including

holding meetings with the sponsor throughout the development process, providing timely advice to the product sponsor regarding development

and approval, involving more senior staff in the review process, assigning a cross-disciplinary project lead for the review team and taking

other steps to design the clinical studies in an efficient manner.

Breakthrough Therapy Designation may be withdrawn by the FDA at any

time if they believe that the designation is no longer supported by emerging data in the development process.

The FDA must determine if the product candidate qualifies for BTD within 60 days of receipt of the

sponsor’s request.

The FDA may take certain actions with respect to breakthrough therapies, including holding meetings with the

sponsor throughout the development process, providing timely advice to the product sponsor regarding development and approval, involving

more senior staff in the review process, assigning a cross-disciplinary project lead for the review team and taking other steps to design

the clinical studies in an efficient manner.

BTD may be withdrawn by the FDA at any time if they believe that the designation is no longer

supported by emerging data in the development process.

Post-Approval Requirements

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if compliance with regulatory requirements and standards is not maintained or if problems occur after the product reaches the market.

Later discovery of previously unknown problems with a product, including adverse events of unanticipated severity or frequency, or with

manufacturing processes, or failure to comply with regulatory requirements, may result in revisions to the approved labeling to add new

safety information;

Later discovery of previously unknown problems with a product, including AEs of unanticipated severity or frequency, or with manufacturing

processes, or failure to comply with regulatory requirements, may result in revisions to the approved labeling to add new safety information;

imposition of post-market studies or clinical trials to assess new safety risks;

or imposition of distribution restrictions

or other restrictions under a REMS program.

or imposition of distribution restrictions or other restrictions

under a REMS program.

Other potential consequences include, among other things:

restrictions on the marketing or manufacturing of a product, mandated

modification of promotional materials or issuance of corrective information, issuance by the FDA or other regulatory authorities of safety

alerts, Dear Healthcare Provider letters, press releases or other communications containing warnings or other safety information about

the product, or complete withdrawal of the product from the market or product recalls;

restrictions on the marketing or manufacturing of a product, mandated modification of promotional materials or issuance of corrective information, issuance by the FDA or other regulatory authorities of safety alerts, Dear Healthcare Provider letters, press releases or other communications containing warnings or other safety information about the product, or complete withdrawal of the product from the market or product recalls;

fines, warning or untitled letters or holds on post-approval clinical trials;

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there exists a danger to public health, to prepare or procure products in the event of shortages and critical public health needs, and

to authorize the creation and enforcement of regulations to prevent the introduction or spread of communicable diseases within the United

After a BLA is approved,

the product may also be subject to official lot release as a condition of approval.

to authorize the creation and enforcement of regulations to prevent the introduction or spread of communicable diseases within the U.S.

After a BLA is approved, the

product may also be subject to official lot release as a condition of approval.

As part of the manufacturing process, the manufacturer

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by pharmacists under prescriptions written for the original listed drug.

The ANDA applicant is required to certify certain statements to the

FDA with respect to any patents listed for the approved product in the FDA’s Orange Book.

Specifically, the applicant must certify

that (i) the required patent information has not been filed;

The ANDA applicant is required

to certify certain statements to the FDA with respect to any patents listed for the approved product in the FDA’s Orange Book.

Specifically,

the applicant must certify that:

(i) the required patent information has not been filed;

(ii) the listed patent has expired;

(iii) the listed patent has not expired

but will expire on a particular date and approval is sought after patent expiration;

or (iv) the listed patent is invalid or will not

be infringed by the new product.

The ANDA applicant may also elect to submit a section viii statement certifying that its proposed ANDA

label does not contain (or carve out) any language regarding the patented method-of-use rather than certify to a listed method-of-use

If the applicant does not challenge the listed patents, the ANDA application will not be approved until all the listed patents

claiming the referenced product have expired.

A certification that the new product will not infringe the already approved product’s

listed patents, or that such patents are invalid, is called a Paragraph IV certification.

If the ANDA applicant has provided a Paragraph

IV certification to the FDA, the applicant must also send notice of the Paragraph IV certification to the NDA and patent holders once

the ANDA has been accepted for filing by the FDA.

The NDA and patent holders may then initiate a patent infringement lawsuit in response

to the notice of the Paragraph IV certification.

The filing of a patent infringement lawsuit within 45 days of the receipt of a Paragraph

IV certification automatically prevents the FDA from approving the ANDA until the earliest of 30 months, expiration of the patent, settlement

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

The ANDA application also

will not be approved until any applicable non-patent exclusivity listed in the Orange Book for the referenced product has expired.

Upon NDA approval of a

new chemical entity, or NCE, which is a drug that contains no active moiety that has been approved by FDA in any other NDA, that

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

of that drug.

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

no listed patent in the Orange Book, there may not be a Paragraph IV certification, and, thus, no ANDA may be filed before the

expiration of the exclusivity period.

Certain changes to a drug, such as the addition of a new indication to the package insert, can

be the subject of a three-year exclusivity period if the application contains reports of new clinical investigations (other than

bioavailability studies) conducted or sponsored by the sponsor that were essential to the approval of the application.

cannot approve an ANDA for a generic drug that includes the change during the exclusivity period.

listed patent has not expired but will expire on a particular date and approval is sought after patent expiration;

or (iv) the listed

patent is invalid or will not be infringed by the new product.

The ANDA applicant may also elect to submit a section viii statement certifying

that its proposed ANDA label does not contain (or carve out) any language regarding the patented method-of-use rather than certify to

a listed method-of-use patent.

If the applicant does not challenge the listed patents, the ANDA application will not be approved until

all the listed patents claiming the referenced product have expired.

A certification that the new product will not infringe the already

approved product’s listed patents, or that such patents are invalid, is called a Paragraph IV certification.

If the ANDA applicant

has provided a Paragraph IV certification to the FDA, the applicant must also send notice of the Paragraph IV certification to the NDA

and patent holders once the ANDA has been accepted for filing by the FDA.

The NDA and patent holders may then initiate a patent infringement

lawsuit in response to the notice of the Paragraph IV certification.

The filing of a patent infringement lawsuit within 45 days of the

receipt of a Paragraph IV certification automatically prevents the FDA from approving the ANDA until the earliest of 30 months, expiration

of the patent, settlement of the lawsuit, or a decision in the infringement case that is favorable to the ANDA applicant.

The ANDA application will not be approved until any applicable non-patent exclusivity listed in the Orange Book for the referenced product has expired.

Upon NDA approval of a new chemical

entity, or NCE, which is a drug that contains no active moiety that has been approved by the FDA in any other NDA, that drug receives

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

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

If there is no listed patent in

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

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

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

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

The FDA cannot approve an ANDA for a generic drug that

includes the change during the exclusivity period.

Patent term extension

After NDA approval, owners of relevant drug patents may apply for up

to a five-year patent extension.

The allowable patent term extension is calculated as half of the drug’s testing phase (the time

between IND application and NDA submission) and all of the review phase (the time between NDA submission and approval up to a maximum

of five years).

The time can be shortened if the FDA determines that the applicant did not pursue approval with due diligence.

patent term after the extension may not exceed 14 years from the date of product approval.

Only one patent applicable to an approved drug

is eligible for extension and only those claims covering the approved drug, a method for using it, or a method for manufacturing it may

be extended, and the application for the extension must be submitted prior to the expiration of the patent.

For patents that might expire

during the application phase, the patent owner may request an interim patent extension.

An interim patent extension increases the patent

term by one year and may be renewed up to four times.

For each interim patent extension granted, the post-approval patent extension is

reduced by one year.

The director of the USPTO must determine that approval of the drug covered by the patent for which a patent extension

is being sought is likely.

Interim patent extensions are not available for a drug for which an NDA has not been submitted.

After NDA approval, owners

of relevant drug patents may apply for up to a five-year patent extension.

The allowable patent term extension is calculated as half of

the drug’s testing phase (the time between IND application and NDA submission) and all of the review phase (the time between NDA

submission and approval up to a maximum of five years).

The time can be shortened if the FDA determines that the applicant did not pursue

approval with due diligence.

The total patent term after the extension may not exceed 14 years from the date of product approval.

one patent applicable to an approved drug is eligible for extension and only those claims covering the approved drug, a method for using

it, or a method for manufacturing it may be extended, and the application for the extension must be submitted prior to the expiration

of the patent.

For patents that might expire during the application phase, the patent owner may request an interim patent extension.

interim patent extension increases the patent term by one year and may be renewed up to four times.

For each interim patent extension

granted, the post-approval patent extension is reduced by one year.

The director of the USPTO must determine that approval of the drug

covered by the patent for which a patent extension is being sought is likely.

Interim patent extensions are not available for a drug for

which an NDA has not been submitted.

Biosimilars and Reference Product Exclusivity

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between the biological product and the reference product in terms of safety, purity, and potency, must be shown through analytical studies,

animal studies, and a clinical trial or trials unless the Secretary of Health and Human Services waives a required element.

product may be deemed interchangeable with a previously approved product if it is biosimilar to the reference product and the product

demonstrates that it can be expected to produce the same clinical results as the reference product in any given patient and, for products

that are administered multiple times to an individual, the biologic and the reference biologic may be alternated or switched after one

has been previously administered without increasing safety risks or risks of diminished efficacy relative to exclusive use of the reference

Complexities associated with the larger, and often more complex, structures of biological products, as well as the processes

by which such products are manufactured, pose significant hurdles to implementation of the abbreviated approval pathway that are still

being worked out by the FDA.

animal studies, and a clinical trial or trials unless the Secretary of the U.S.

Department of Health and Human Services, or HHS, waives

a required element.

A biosimilar product may be deemed interchangeable with a previously approved product if it is biosimilar to the reference

product and the product demonstrates that it can be expected to produce the same clinical results as the reference product in any given

patient and, for products that are administered multiple times to an individual, the biologic and the reference biologic may be alternated

or switched after one has been previously administered without increasing safety risks or risks of diminished efficacy relative to exclusive

use of the reference biologic.

Complexities associated with the larger, and often more complex, structures of biological products, as

well as the processes by which such products are manufactured, pose significant hurdles to implementation of the abbreviated approval

pathway that are still being worked out by the FDA.

Under the BPCIA, an application

for a biosimilar product may not be submitted to the FDA until four years following the date that the reference product was first licensed

for a biosimilar product may not be submitted to the FDA until four years following the date that its reference product was first licensed

In addition, the approval of a biosimilar product may not be made effective by the FDA until 12 years from the date on which

the reference product was first licensed.

its reference product was first licensed.

During this 12-year period of exclusivity, another company may still market a competing version

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for which the drug is safe and effective.

Alternatively, for an original NDA for a new active ingredient, the application could instead

be required to include reports on a molecularly targeted pediatric cancer investigation, if the drug is intended for the treatment of

an adult cancer and directed at a molecular target that the FDA determines to be substantially relevant to the growth or progression of

a pediatric cancer.

The FDA may grant full or partial waivers, or deferrals, for submission of data.

exceptions, the PREA does not apply to any drug for an indication for which Orphan Drug Designation has been granted.

The Best Pharmaceuticals

for Children Act, or BPCA, provides NDA holders a six-month extension of any exclusivity—patent or nonpatent—for a drug and

BLA holders a six-month extension of market exclusivity for biologics if certain conditions are met.

Conditions for exclusivity include

With certain exceptions, the PREA

does not apply to any drug for an indication for which ODD has been granted.

This exemption does not apply to an original NDA for a new

active ingredient for an indication for which ODD has been granted if the NDA is subject to the molecularly targeted pediatric cancer

investigation requirement.

The Best Pharmaceuticals for

Children Act, or BPCA, provides NDA holders a six-month extension of any exclusivity—patent or nonpatent—for a drug and BLA

holders a six-month extension of market exclusivity for biologics if certain conditions are met.

Conditions for exclusivity include the

FDA’s determination that information relating to the use of a new drug or biologic in the pediatric population may produce health

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

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

on, the requested studies within the statutory timeframe.

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

the benefits that designation confers.

Applications under the BPCA are treated as priority applications.

Healthcare Laws and Compliance

In the United States, our

current and future operations are subject to regulation by various federal, state and local authorities in addition to the FDA, including

but not limited to, the Centers for Medicare & Medicaid Services, or CMS, other divisions of the U.S.

Department of Health and Human

Services, or HHS, (such as the Office of Inspector General, Office for Civil Rights and the Health Resources and Service Administration),

Department of Justice, or DOJ and individual U.S.

In the U.S., a pharmaceutical

company’s operations are subject to regulation by various federal, state and local authorities in addition to the FDA, including

but not limited to, the Centers for Medicare & Medicaid Services, or CMS, other divisions of the HHS (such as the Office of Inspector

General, Office for Civil Rights and the Health Resources and Service Administration), the U.S.

Department of Justice, or DOJ, and individual

Attorney offices within the DOJ, and state and local governments.

our clinical research, sales, marketing and scientific/educational grant programs will need to comply with the anti-fraud and abuse provisions

of the Social Security Act, the false claims laws, the privacy and security provisions of the Health Insurance Portability and Accountability

Act, or HIPAA, and similar state laws, each as amended, as applicable.

For example, clinical research, sales, marketing and scientific/educational

grant programs will need to comply with the anti-fraud and abuse provisions of the Social Security Act, the false claims laws, the privacy

and security provisions of the Health Insurance Portability and Accountability Act, or HIPAA, and similar state laws, each as amended,

as applicable.

The federal Anti-Kickback

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cumulative review of all of its facts and circumstances.

Our practices may not in all cases meet all of the criteria for protection under

a statutory exception or regulatory safe harbor.

Additionally, the intent

standard under the Anti-Kickback Statute was amended by the ACA to a stricter standard such that a person or entity no longer needs to

have actual knowledge of the statute or specific intent to violate it in order to have 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 constitutes a false

or fraudulent claim for purposes of the federal False Claims Act, or the FCA (discussed below).

A pharmaceutical company’s practices may not in all cases meet all of the

criteria for protection under a statutory exception or regulatory safe harbor.

Additionally, the intent standard

under the Anti-Kickback Statute was amended by the ACA to a stricter standard such that a person or entity no longer needs to have actual

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

Violations of the Anti-Kickback Statute

are subject to civil and criminal fines and penalties for each violation, plus up to three times the remuneration involved, imprisonment

and exclusion from government healthcare programs.

In addition, the ACA codified case law that a claim including items or services resulting

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

Act, or the FCA.

The federal false claims,

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items or services.

Like the Anti-Kickback Statute, the ACA amended the intent standard for certain healthcare fraud statutes under HIPAA

such that a person or entity no longer needs to have actual knowledge of the statute or specific intent to violate it in order to have

committed a violation.

Accordingly, HIPAA imposes criminal and civil liability for, among other things, executing a scheme or making materially

false statements in connection with the delivery of or payment for health care benefits, items or services.

Like the Anti-Kickback Statute,

the ACA amended the intent standard for certain healthcare fraud statutes under HIPAA such that a person or entity no longer needs to

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

Also, many states have similar,

and typically more prohibitive, fraud and abuse statutes or regulations that apply to items and services reimbursed under Medicaid and

other state programs, or, in several states, apply regardless of the payor.

We may be subject to data

privacy and security regulations by both the federal government and the states in which it conducts business.

HIPAA, as amended by the

Health Information Technology for Economic and Clinical Health Act, or HITECH, and its implementing regulations, imposes requirements

on “covered entities,” including certain healthcare providers, health plans, and healthcare clearinghouses, as well as their

respective “business associates” that create, receive, maintain or transmit individually identifiable health information for

or on behalf of a covered entity as well as their covered subcontractors relating to the privacy, security and transmission of individually

identifiable health information.

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

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

with providing a service on behalf of a covered entity.

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

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

civil actions for damages or injunctions in federal courts to enforce HIPAA and seek attorneys’ fees and costs associated with pursuing

federal civil actions.

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

many of which differ from each other in significant ways, are often not pre-empted by HIPAA, and may have a more prohibitive effect than

HIPAA, thus complicating compliance efforts.

We may develop products that,

once approved, may be administered by a physician.

Under currently applicable U.S.

law, certain products not usually self-administered

(including injectable drugs) may be eligible for coverage under Medicare through Medicare Part B.

Medicare Part B is part of original

Medicare, the federal health care program that provides health care benefits to the aged and disabled, and covers outpatient services

and supplies, including certain biopharmaceutical products, that are medically necessary to treat a beneficiary’s health condition.

As a condition of receiving Medicare Part B reimbursement for a manufacturer’s eligible drugs, the manufacturer is required to participate

in other government healthcare programs, including the Medicaid Drug Rebate Program and the 340B Drug Pricing Program.

The Medicaid Drug

Rebate Program requires pharmaceutical manufacturers to enter into and have in effect a national rebate agreement with the Secretary of

HHS as a condition for states to receive federal matching funds for the manufacturer’s outpatient drugs furnished to Medicaid patients.

Under the 340B Drug Pricing Program, the manufacturer must extend discounts to entities that participate in the program.

other state healthcare programs, or, in several states, apply regardless of the payor.

Pharmaceutical companies may

be subject to data privacy and security regulations by both the federal government and the states in which they conduct business.

as amended by the Health Information Technology for Economic and Clinical Health Act, or HITECH, and its implementing regulations, imposes

requirements on “covered entities,” including certain healthcare providers, health plans, and healthcare clearinghouses, as

well as their respective “business associates” that create, receive, maintain or transmit individually identifiable health

information for or on behalf of a covered entity as well as their covered subcontractors relating to the privacy, security and transmission

of individually identifiable health information.

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

applicable to business associates, independent contractors, including subcontractors, or agents of covered entities that receive or obtain

protected health information, or PHI, in connection with providing a service on behalf of a covered entity.

HITECH also created four new

tiers of civil monetary penalties, amended HIPAA to make civil and criminal penalties directly applicable to business associates and gave

state attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce HIPAA and seek attorneys’

fees and costs associated with pursuing federal civil actions.

In addition, many state laws, for example, Washington’s My Health

My Data Act and the California Consumer Privacy Act of 2018, or CCPA, as amended by the California Privacy Rights Act, or CPRA, govern

the privacy and security of health information in specified circumstances, many of which differ from each other in significant ways, are

often not pre-empted by HIPAA, and may have a more prohibitive effect than HIPAA, thus complicating compliance efforts.

The National Security Division

of the DOJ issued a new rule referred to as the Data Security Program, or DSP, to implement Executive Order 14117 aimed at preventing

access to “bulk U.S.

sensitive personal data” and “government-related data” by “countries of concern”

(including China, Russia, Iran, North Korea, Cuba, and Venezuela) and “covered persons” (as all such terms are defined in

Effective as of April 8, 2025, the DSP imposes stringent obligations on companies within its scope and prohibits or restricts

“covered data transactions” that grant countries of concern or covered persons access to bulk U.S.

sensitive personal data

or any amount of government-related data.

Under currently applicable

law, certain products not usually self-administered (including injectable drugs) may be eligible for coverage under Medicare through

Medicare Part B.

Medicare Part B is part of original Medicare, the federal health care program that provides health care benefits to the

aged and disabled, and covers outpatient services and supplies, including certain biopharmaceutical products, that are medically necessary

to treat a beneficiary’s health condition.

As a condition of receiving Medicare Part B reimbursement for a manufacturer’s

eligible drugs, the manufacturer is required to participate in other government healthcare programs, including the Medicaid Drug Rebate

Program and the 340B Drug Pricing Program.

The Medicaid Drug Rebate Program requires pharmaceutical manufacturers to enter into and have

in effect a national rebate agreement with the Secretary of HHS as a condition for states to receive federal matching funds for the manufacturer’s

outpatient drugs furnished to Medicaid patients.

Under the 340B Drug Pricing Program, the manufacturer must extend discounts to entities

that participate in the program.

In addition, many pharmaceutical

manufacturers must calculate and report certain price reporting metrics to the government, such as average sales price, or ASP, and best

manufacturers must calculate and report certain price reporting metrics to the government, such as average sales price, average

manufacturer price and best price.

Penalties may apply in some cases when such metrics are not submitted accurately and timely.

Further, these prices for drugs may

be reduced by mandatory discounts or rebates required by government healthcare programs or private payors and by any future relaxation

of laws that presently restrict imports of drugs from countries where they may be sold at lower prices than in the United States.

difficult to predict how Medicare coverage and reimbursement policies will be applied to our products in the future and coverage and reimbursement

under different federal healthcare programs are not always consistent.

Medicare reimbursement rates may also reflect budgetary constraints

placed on the Medicare program.

these prices for drugs may be reduced by mandatory discounts or rebates required by government healthcare programs or private payors and

by any future relaxation of laws that presently restrict imports of drugs from countries where they may be sold at lower prices than in

It is difficult to predict how Medicare coverage and reimbursement policies will be applied to a pharmaceutical company’s

products in the future and coverage and reimbursement under different federal healthcare programs are not always consistent.

reimbursement rates may also reflect budgetary constraints placed on the Medicare program.

Additionally, the federal

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Insurance Program (with certain exceptions) report annually to CMS information related to certain payments or other transfers of value

made or distributed to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), other healthcare

made or distributed to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), certain other healthcare

professionals (such as physicians assistants and nurse practitioners), and teaching hospitals, or to entities or individuals at the request

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In order to distribute products

commercially, we must comply with state laws that require the registration of manufacturers and wholesale distributors of drug and biological

products in a state, including, in certain states, manufacturers and distributors who ship products into the state even if such manufacturers

or distributors have no place of business within the state.

Some states also impose requirements on manufacturers and distributors to

establish the pedigree of product in the chain of distribution, including some states that require manufacturers and others to adopt new

technology capable of tracking and tracing product as it moves through the distribution chain.

Several states and/or localities have enacted

legislation requiring pharmaceutical and biotechnology companies to establish marketing compliance programs, file periodic reports with

the state, make periodic public disclosures on sales, marketing, pricing, clinical trials and other activities, and/or register their

sales representatives, as well as to prohibit pharmacies and other healthcare entities from providing certain physician prescribing data

to pharmaceutical and biotechnology companies for use in sales and marketing, and to prohibit certain other sales and marketing practices.

All of our activities are potentially subject to federal and state consumer protection and unfair competition laws.

commercially, pharmaceutical companies must comply with state laws that require the registration of manufacturers and wholesale distributors

of drug and biological products in a state, including, in certain states, manufacturers and distributors who ship products into the state

even if such manufacturers or distributors have no place of business within the state.

Some states also impose requirements on manufacturers

and distributors to establish the pedigree of product in the chain of distribution, including some states that require manufacturers and

others to adopt new technology capable of tracking and tracing product as it moves through the distribution chain.

Several states and/or

localities have enacted legislation requiring pharmaceutical and biotechnology companies to establish marketing compliance programs, file

periodic reports with the state, make periodic public disclosures on sales, marketing, pricing, clinical trials and other activities,

and/or register their sales representatives, as well as to prohibit pharmacies and other healthcare entities from providing certain physician

prescribing data to pharmaceutical and biotechnology companies for use in sales and marketing, and to prohibit certain other sales and

marketing practices.

All of a pharmaceutical company’s activities are potentially subject to federal and state consumer protection

and unfair competition laws.

Ensuring business arrangements

with third parties comply with applicable healthcare laws and regulations is a costly endeavor.

If our operations are found to be in violation

of any of the federal and state healthcare laws described above or any other current or future governmental regulations that apply to

it, it may be subject to penalties, including without limitation, significant civil, criminal and/or administrative penalties, damages,

fines, disgorgement, imprisonment, exclusion from participation in government programs, such as Medicare and Medicaid, injunctions, private

“qui tam” actions brought by individual whistleblowers in the name of the government, or refusal to allow it to enter into

government contracts, contractual damages, reputational harm, administrative burdens, diminished profits and future earnings, additional

reporting obligations and oversight if we become subject to a corporate integrity agreement or other agreement to resolve allegations

of non-compliance with these laws, and the curtailment or restructuring of its operations, any of which could adversely affect our ability

to operate our business and our results of operations.

If a pharmaceutical company’s operations

are found to be in violation of any of the federal and state healthcare laws described above or any other current or future governmental

regulations that apply to it, it may be subject to penalties, including without limitation, significant civil, criminal and/or administrative

penalties, damages, fines, disgorgement, imprisonment, exclusion from participation in government programs, such as Medicare and Medicaid,

injunctions, private qui tam actions brought by individual whistleblowers in the name of the government, or refusal to allow it to enter

into government contracts, contractual damages, reputational harm, administrative burdens, diminished profits and future earnings, additional

reporting obligations and oversight if it becomes subject to a corporate integrity agreement or other agreement to resolve allegations

of non-compliance with these laws, and the curtailment or restructuring of its operations, any of which could adversely affect its ability

to operate its business and the results of its operations.

Coverage, Pricing and Reimbursement

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as to the coverage and reimbursement status of any product candidates for which we may obtain regulatory approval.

In the United States

and in foreign markets, sales of any products for which we receive regulatory approval for commercial sale will depend, in part, on the

extent to which third-party payors provide coverage and establish adequate reimbursement levels for such products.

In the United States,

third-party payors include federal and state healthcare programs, private managed care providers, health insurers and other organizations.

Adequate coverage and reimbursement from governmental healthcare programs, such as Medicare and Medicaid in the United States, and commercial

payors are critical to new product acceptance.

Our ability to commercialize

any products successfully also will depend in part on the extent to which coverage and reimbursement for these products and related treatments

will be available from government health administration authorities, private health insurers and other organizations.

Government authorities

and other third-party payors, such as private health insurers and health maintenance organizations, decide which therapeutics they will

pay for and establish reimbursement levels.

Coverage and reimbursement by a third-party payor may depend upon a number of factors, including

the third-party payor’s determination that use of a therapeutic is:

foreign markets, sales of any products for which a pharmaceutical company receives regulatory approval for commercial sale will depend,

in part, on the extent to which third-party payors provide coverage and establish adequate reimbursement levels for such products.

the U.S., third-party payors include federal and state healthcare programs, private managed care providers, health insurers and other

organizations.

Adequate coverage and reimbursement from governmental healthcare programs, such as Medicare and Medicaid in the U.S., and

commercial payors are critical to new product acceptance.

A pharmaceutical company’s

ability to commercialize any products successfully also will depend in part on the extent to which coverage and reimbursement for these

products and related treatments will be available from government health administration authorities, private health insurers and other

organizations.

Government authorities and other third-party payors, such as private health insurers and health maintenance organizations,

decide which therapeutics they will pay for and establish reimbursement levels.

Coverage and reimbursement by a third-party payor may

depend upon a number of factors, including the third-party payor’s determination that use of a therapeutic is:

a covered benefit under its health plan;

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neither experimental nor investigational.

We cannot be sure that reimbursement

will be available for any product that it commercializes and, if coverage and reimbursement are available, what the level of reimbursement

Coverage may also be more limited than the purposes for which the product is approved by the FDA or comparable foreign regulatory

Reimbursement may impact the demand for, or the price of, any product for which we obtain regulatory approval.

Coverage may also be more

limited than the purposes for which the product is approved by the FDA or comparable foreign regulatory authorities.

Reimbursement may

impact the demand for, or the price of, any product for which regulatory approval is obtained.

Third-party payors are increasingly

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in addition to questioning their safety and efficacy.

Obtaining reimbursement for our products may be particularly difficult because of

the higher prices often associated with branded drugs and drugs administered under the supervision of a physician.

We may need to conduct

expensive pharmacoeconomic studies in order to demonstrate the medical necessity and cost-effectiveness of our products, in addition to

the costs required to obtain FDA approvals.

Our product candidates may not be considered medically necessary or cost-effective.

coverage and reimbursement approval of a product from a government or other third-party payor is a time-consuming and costly process that

could require us to provide to each payor supporting scientific, clinical and cost-effectiveness data for the use of our product on a

payor-by-payor basis, with no assurance that coverage and adequate reimbursement will be obtained.

A payor’s decision to provide

coverage for a product does not imply that an adequate reimbursement rate will be approved.

Further, one payor’s determination to

provide coverage for a product does not assure that other payors will also provide coverage for the product.

Adequate third-party reimbursement

may not be available to enable us to maintain price levels sufficient to realize an appropriate return on our investment in product development.

If reimbursement is not available or is available only at limited levels, we may not be able to successfully commercialize any product

candidate that it successfully develops.

Obtaining coverage and reimbursement approval of a product from a government or

other third-party payor is a time-consuming and costly process that could require pharmaceutical companies to provide to each payor supporting

scientific, clinical and cost-effectiveness data for the use of a product on a payor-by-payor basis, with no assurance that coverage and

adequate reimbursement will be obtained.

A payor’s decision to provide coverage for a product does not imply that an adequate reimbursement

rate will be approved.

Further, one payor’s determination to provide coverage for a product does not assure that other payors will

also provide coverage for the product.

Different pricing and reimbursement

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from low-priced markets exert a commercial pressure on pricing within a country.

The marketability of any

product candidates 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.

In addition, emphasis on managed care, the increasing influence of health maintenance

organizations, and additional legislative changes in the United States has increased, and we expect will continue to increase, the pressure

on healthcare pricing.

The downward pressure on the rise in healthcare costs in general, particularly prescription medicines, medical

devices and surgical procedures and other treatments, has become very intense.

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.

Healthcare Reform

In the United States and

some foreign jurisdictions, there have been, and continue to be, several legislative and regulatory changes and proposed changes regarding

the healthcare system that could prevent or delay marketing approval of product candidates, restrict or regulate post-approval activities,

and affect the ability to profitably sell product candidates for which marketing approval is obtained.

Among policy makers and payors

in the United States and elsewhere, there is significant interest in promoting changes in healthcare systems with the stated goals of

containing healthcare costs, improving quality and/or expanding access.

In the United States, the pharmaceutical industry has been a particular

focus of these efforts and has been significantly affected by major legislative initiatives.

For example, in March 2010, the ACA was enacted, which intended to

broaden access to health insurance, reduce or constrain the growth of healthcare spending, enhance remedies against fraud and abuse, add

new transparency requirements for the healthcare and health insurance industries, impose new taxes and fees on the health industry and

impose additional health policy reforms.

The ACA has substantially changed the way healthcare is financed by both governmental and private insurers,

and significantly impacts the U.S.

pharmaceutical industry.

Other legislative changes

have been proposed and adopted since the ACA was enacted.

Current and Future Healthcare Reform

and some foreign

jurisdictions, there have been, and continue to be, several legislative and regulatory changes and proposed changes regarding the healthcare

system that could prevent or delay marketing approval of product candidates, restrict or regulate post-approval activities and affect

the ability to profitably sell product candidates for which marketing approval is obtained.

Among policy makers and payors in the U.S.

and elsewhere, there is significant interest in promoting changes in healthcare systems with the stated goals of containing healthcare

costs, improving quality and/or expanding access.

In the U.S., the pharmaceutical industry has been a particular focus of these efforts

and has been significantly affected by major legislative initiatives that directly and indirectly affect manufacturers’ ability

to successfully commercialize approved products and seek government coverage and reimbursement.

Legislative changes have

been proposed and adopted since the ACA was enacted.

For example, under the American Rescue Plan Act of 2021, effective January 1, 2024,

the statutory cap on Medicaid Drug Rebate Program rebates that manufacturers pay to state Medicaid programs has been eliminated.

Elimination of this cap has, in some cases, required pharmaceutical manufacturers to pay more in rebates than they have received on the

sale of products.

In addition, in 2024, CMS issued a final rule that decreased Medicare reimbursement for physician services by 2.8%,

effective January 1, 2025.

If federal spending is further reduced, anticipated budgetary shortfalls may also impact the ability of relevant

agencies, such as the FDA, to continue to function at current levels.

of this cap has, in some cases, required pharmaceutical manufacturers to pay more in rebates than they have received on the sale of products.

In addition, in 2024, CMS issued a final rule that decreased Medicare reimbursement for physician services by 2.8%, effective January

If federal spending is further reduced, anticipated budgetary shortfalls may also impact the ability of relevant agencies, such

as the FDA, to continue to function at current levels.

Several healthcare reform

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for brand drugs below the out-of-pocket limit, and 20% once the out-of-pocket limit has been reached.

The IRA also allows HHS to directly

The IRA also requires HHS to directly

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

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product has been announced.

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

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

20 Part B or Part D drugs will be selected.

A drug or biological product that has an Orphan Drug Designation for only one rare disease

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

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

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

selection for negotiation.

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

than the rate of inflation, and in November 2024, CMS finalized regulations for the Medicare Part B and Part D inflation rebates.

IRA also extends enhanced subsidies for individuals purchasing health insurance coverage in ACA marketplaces through plan year 2025.

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

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

These provisions

may be subject to legal challenges.

For example, the provisions related to the negotiation of selling prices of high-expenditure single-source

drugs and biologics have been challenged in multiple lawsuits brought by pharmaceutical manufacturers.

The outcome of these lawsuits is

uncertain, and some IRA drug discount provisions have not been challenged in litigation.

Thus, while it is unclear how the IRA will be

implemented, it will likely have a significant impact on the pharmaceutical industry and the pricing of pharmaceutical products.

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

D drugs, which will become effective in 2027.

For 2028, CMS has selected an additional 15 drugs, comprised of drugs covered under Medicare

Part D and, for the first time, drugs under Medicare Part B.

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

A drug or biological product that has an ODD for only one rare disease or condition will be excluded from the IRA’s price negotiation

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

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

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

The IRA also imposes rebates on Medicare Part

B and Part D drugs whose prices have increased at a rate greater than the rate of inflation, and in November 2024, CMS finalized regulations

for the Medicare Part B and Part D inflation rebates.

The IRA also extended enhanced subsidies for individuals purchasing health insurance

coverage in ACA marketplaces through plan year 2025, but those subsidies expired at the end of 2025.

The IRA permits the Secretary of

HHS to implement many of these provisions through guidance, as opposed to regulation, for the initial years.

Manufacturers that fail to

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

These provisions may be subject to legal

For example, the provisions related to the negotiation of selling prices of high-expenditure single-source drugs and biologics

have been challenged in multiple lawsuits brought by pharmaceutical manufacturers.

The outcome of these lawsuits is uncertain, and some

IRA drug discount provisions have not been challenged in litigation.

Thus, while it is unclear how the IRA will be implemented, it will

likely have a significant impact on the pharmaceutical industry and the pricing of pharmaceutical products.

The current federal administration is pursuing policies to reduce regulations

and expenditures across government agencies including at HHS, which include the FDA and CMS, and related agencies.

These actions include,

for example, directives to reduce agency workforce, which include the FDA and CMS, and related agencies.

In addition, on May 12, 2025,

President Trump issued an Executive Order that, among other things, required HHS, within 30 days, to establish and communicate to drug

manufacturers most favored nation, or MFN, price targets designed to bring drug prices for American patients in line with those in comparably

developed nations.

If significant progress towards MFN pricing is not achieved, the Executive Order requires HHS to propose a rulemaking

to implement MFN pricing.

Recently, on December 23, 2025, CMS issued proposed regulations to establish, under the Center for Medicare

and Medicaid Innovation, or CMMI, two mandatory MFN demonstration models under Medicare Parts B and D, respectively.

If these rules or

other MFN pricing rules are finalized, they are likely to reduce prices of at least some drugs in the U.S., if they are also sold in comparably

developed countries.

Even if we do not market drugs in such countries, we will be indirectly affected if our drugs competed with drugs

whose prices were reduced as a result of MFN pricing initiatives.

Further, as part of the Make America Healthy Again, or MAHA, Commission’s

recent Strategy Report, the federal administration is working across government agencies to increase enforcement on direct-to-consumer

pharmaceutical advertising.

These federal administrative actions and policies may significantly reduce U.S.

drug prices, potentially

impacting manufacturers’ global pricing strategies and profitability, while increasing their operational costs and compliance risks.

At the state level, legislatures

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and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.

the FDA released a final rule in 2020 providing guidance for states to build and submit importation proposals for drugs from Canada, and

the FDA authorized the first such plan in Florida in 2024.

the FDA released a final rule in 2020 providing guidance for states to build and submit importation proposals for drugs from Canada.

FDA authorized the first such plan in Florida in 2024, but the implementation of Florida’s plan has been extended.

The Foreign Corrupt Practices Act

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The FCPA also obligates companies whose

securities are listed in the United States to comply with accounting provisions requiring us to maintain books and records that accurately

and fairly reflect all transactions of the corporation, including international subsidiaries, and to devise and maintain an adequate system

of internal accounting controls for international operations.

securities are listed in the U.S.

to comply with accounting provisions including maintaining books and records that accurately and fairly

reflect all transactions of the corporation, including international subsidiaries, and to devise and maintain an adequate system of internal

accounting controls for international operations.

Data Privacy and Security Regulations

Numerous state, federal and

foreign laws, regulations and standards govern the collection, transfer, sharing, use, access to, confidentiality and security of health-related

and other personal information, and could apply now or in the future to our operations or the operations of our partners.

numerous federal and state laws and regulations, including data breach notification laws, health information privacy and security laws

and consumer protection laws and regulations govern the collection, use, disclosure, and protection of health-related and other personal

In addition, certain foreign laws govern the privacy and security of personal data, including health-related data.

and security laws, regulations, and other obligations are constantly evolving, may conflict with each other to complicate compliance efforts,

and can result in investigations, proceedings, or actions that lead to significant civil and/or criminal penalties and restrictions on

data processing.

See “ Risk Factors—General

Risk Factors—Pharmaceutical companies are subject to stringent and changing obligations related to data privacy and security.

actual or perceived failure to comply with such obligations could lead to regulatory investigations or actions;

a disruption of our business operations, including our clinical trials;

harm to our reputation;

and other adverse effects on

our business or prospects” for additional information about these privacy and security laws, regulations, and other obligations.

Additional Regulation

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state and federal laws regarding environmental protection and hazardous substances, including the Occupational Safety and Health Act,

the Resource Conservancy and Recovery Act and the Toxic Substances Control Act, affect our business.

These and other laws govern our use,

handling and disposal of various biological, chemical and radioactive substances used in, and wastes generated by, our operations.

our operations result in contamination of the environment or expose individuals to hazardous substances, we could be liable for damages

and governmental fines.

We believe that we are in material compliance with applicable environmental laws and that continued compliance

therewith will not have a material adverse effect on our business.

We cannot predict, however, how changes in these laws may affect our

future operations.

the Resource Conservancy and Recovery Act and the Toxic Substances Control Act, affect a pharmaceutical company’s business.

and other laws govern the use, handling and disposal of various biological, chemical and radioactive substances used in, and wastes generated

by operations.

If our operations result

in contamination of the environment or expose individuals to hazardous substances, we could be liable for damages and governmental fines.

We believe that we are in material compliance with applicable environmental laws and that continued compliance therewith will not have

a material adverse effect on our business.

We cannot predict, however, how changes in these laws may affect our future operations.

Other Regulations

We are also subject to numerous

federal, state and local laws relating to such matters as safe working conditions, manufacturing practices, environmental protection,

fire hazard control, and disposal of hazardous or potentially hazardous substances.

We may incur significant costs to comply with such

laws and regulations now or in the future.

Pharmaceutical companies

are also subject to numerous federal, state and local laws relating to such matters as safe working conditions, manufacturing practices,

environmental protection, fire hazard control and disposal of hazardous or potentially hazardous substances.

Pharmaceutical companies

may incur significant costs to comply with such laws and regulations now or in the future.

As of December 31, 2025,

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As of December 31, 2025, 29 of our

employees were engaged in research and development activities and 13 of our employees were engaged in business development, legal, finance,

market development, information systems, facilities, human resources or administrative support.

employees were engaged in research and development activities and 22 of our employees were engaged in administrative support, business

development, finance, human resources, information systems, legal, or market development.

As of December 31, 2025, all of our employees

were located in the United States.

None of our United States employees are represented by any collective bargaining agreements.

that we maintain good relations with our employees.

were located in the U.S.

None of our U.S.

employees are represented by any collective bargaining agreements.

We believe that we maintain

good relations with our employees.

Corporate Information

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the “Company” and “our” refer to Protara Therapeutics, Inc.

(formerly ArTara Therapeutics, Inc., formerly Proteon

Therapeutics, Inc.) and our subsidiaries.

and our subsidiaries.

Available Information

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Quarterly Reports on Form 10-Q, Current Reports on Form 8-K, and amendments to reports filed pursuant to Sections 13(a) and 15(d) of the

Securities Exchange Act of 1934, as amended, or the Exchange Act, will be made available free of charge on our website as soon as reasonably

practicable after we electronically file such material with, or furnish it to, the SEC.

Exchange Act, will be made available free of charge on our website as soon as reasonably practicable after we electronically file such

material with, or furnish it to, the SEC.

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