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Item 1. Business

2024-03-13 compared with 2023-03-08 · 1164 added, 1380 removed, 232 unchanged (92% of the section changed)

We are a New York

City based clinical-stage biopharmaceutical company committed to advancing transformative therapies for the treatment of cancer and rare

We were founded on the principle of applying modern scientific, regulatory or manufacturing advancements to established mechanisms

in 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.

therapy is currently approved in Japan and Taiwan for 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 and Taiwan

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

are a New York City based clinical-stage biopharmaceutical company committed to advancing transformative therapies for the treatment

of cancer and rare diseases.

We were founded on the principle of applying modern scientific, regulatory or manufacturing advancements

to established mechanisms in 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.

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.

This cell therapy is currently approved in Japan and Taiwan for 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 and Taiwan 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.

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 muscle.

Bladder cancer is the sixth most common cancer in the United States, with NMIBC representing approximately

80% of bladder cancer diagnoses.

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,

The mechanism of action of TARA-002 is similar to that of BCG.

TARA-002 and BCG are both intravesically administered, elicit

a Th1 type immune response and produce a similar array of locally activated cytokines and immune cells.

We are conducting a Phase 1 dose-finding, open-label clinical trial

to evaluate TARA-002 in treatment-naïve and treatment-experienced NMIBC patients with carcinoma in situ, or CIS, and high-grade papillary

tumors (Ta), known as the ADVANCED-1 trial.

In the initial dose escalation phase, or Phase 1a portion, of the trial, patients receive

six weekly intravesical doses of TARA-002.

The primary objective of the trial is to evaluate the safety, tolerability and preliminary

signs of anti-tumor activity of TARA-002, with the goal of establishing a recommended dose for a future Phase 2 clinical trial.

is ongoing and we expect data from the Phase 1a portion of the trial in the second quarter of 2023.

therapeutics have been approved for NMIBC since the 1990s and the current standard of care for NMIBC includes intravesical Bacillus Calmette–Guérin,

The mechanism of action of TARA-002 is similar in some ways to that of BCG.

TARA-002 and BCG are both intravesically administered,

elicit a Th1 type immune response and produce a locally-activated generally similar array of cytokines and immune cells.

are conducting a Phase 1 open-label clinical trial to evaluate TARA-002 in treatment-naïve and treatment-experienced NMIBC patients

with carcinoma in situ, or CIS, and high-grade papillary tumors, or Ta, known as the ADVANCED-1 trial.

In the initial dose escalation

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

Einheit, or KE, is a German term indicating a specified weight of dried cells in vial).

The primary objective of the trial is to evaluate

the safety, tolerability and preliminary signs of anti-tumor activity of TARA-002, with the goal of establishing a recommended Phase

In April 2023, we announced positive preliminary data from the Phase 1a dose escalation component of the ongoing ADVANCED-1 trial

through the 40KE dose, in which TARA-002 indicated favorable tolerability and anti-tumor activity in NMIBC patients.

A maximum tolerated

dose was not determined, and dose escalation remains ongoing in exploratory cohorts.

Preliminary 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 trial, and no dose limiting toxicities were observed.

The Company has 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 treatment-related adverse events, as assessed

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

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

bladder spasm.

Most bladder 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 at the 20KE dose, and tumor regression

was observed in the other two patients.

Results from 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 trial.

The ongoing open-label expansion trial, or ADVANCED-1EXP, is evaluating

intravesical TARA-002 at the 40KE dose in up to 12 CIS patients, including BCG-naïve, BCG-unresponsive, and BCG-inadequately treated

Dosing is progressing in the trial, and we anticipate having preliminary data from this trial in the first half of 2024.

Based on the preliminary

results of ADVANCED-1, we are proceeding with the clinical development of TARA-002 for the treatment of NMIBC.

In September 2023, we

initiated ADVANCED-2, a Phase 2 open-label trial evaluating intravesical TARA-002 in at least 102 patients with high-grade CIS.

A of the Phase 2 trial is expected to enroll 27 patients with CIS (± Ta/T1), BCG-Naïve or BCG-experienced, 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).

The Company expects to share preliminary results from a pre-planned risk-benefit analysis of the

ongoing Phase 2 open-label ADVANCED-2 trial in the second half of 2024.

The analysis is expected to include approximately 10 patients

who are six-month evaluable.

addition, we continue to conduct pre-clinical studies on TARA-002 to better characterize the mechanism of action to help us understand

how TARA-002 may perform in potential combinations with other agents used to treat NMIBC.

We use pre-clinical data to help us define

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

We are also pursuing TARA-002 in LMs, which are rare, non-malignant

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

We have an open IND for LMs with the Vaccines and

Related Products Division of the FDA, or Vaccines Division.

We received feedback from the Vaccines Division on the protocol for our proposed

Phase 2 clinical trial evaluating TARA-002 in LMs.

In the second half of 2023 we expect to initiate this Phase 2 single arm, open-label

clinical trial to evaluate the safety and efficacy of TARA-002 in pediatric patients with macrocystic and mixed-cystic LMs.

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

We are conducting trial preparation activities and have identified

multiple trial sites.

We have an investigational new drug application for

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

2023, we initiated STARBORN-1 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.

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

TARA-002 spaced approximately six weeks apart.

primary endpoint of the 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.

The third development program in our portfolio is intravenous, or IV,

Choline Chloride, an investigational phospholipid substrate replacement therapy initially in development for patients receiving parenteral

nutrition, or PN, who have intestinal failure associated liver disease, or IFALD.

IV Choline Chloride has been granted Orphan Drug Designation

by the FDA for this indication and has also been granted Fast Track Designation for the treatment of IFALD.

Following a positive end of

Phase 2 meeting with the FDA, we received feedback on the design of the studies necessary to complete a registration package for IV Choline

Chloride for the treatment of IFALD, including a Phase 1 pharmacokinetic, or PK, trial and a Phase 3 clinical trial.

Prior to initiating

these clinical trials, we are conducting a prevalence study to enhance understanding of the PN patient population and we plan to use this

information to determine the next steps for the development program.

In September 2021, we reported results of the retrospective part

of the prevalence study, which supported the significant unmet medical need in patients dependent on PN who have IFALD.

We are currently

conducting the prospective part of the prevalence study, which is a multi-center, cross-sectional observational study to assess the prevalence

of choline deficiency, as well as cholestasis and steatosis, in patients dependent on PN.

We expect to have results of the study in the

third quarter of 2023.

In April 2022, the U.S.

Patent and Trademark office, or USPTO, issued to us Patent No.

US 11,311,503 claiming a

sterile aqueous choline salt composition with a term expiring in 2041.

We have devoted substantial

efforts to the development of these programs but do not have any approved products and have not generated any revenue from product sales.

TARA-002 has not yet been approved for use for treatment of NMIBC, LMs or any other indications.

We do not expect to generate revenues

in the near-term, if ever.

Choline Chloride, an investigational phospholipid substrate replacement therapy, for patients receiving parenteral nutrition, or PN.

FDA has granted IV Choline Chloride Orphan Drug Designation for the prevention of choline deficiency in PN patients.

We have conducted

a two-part prevalence study to enhance our understanding of the PN patient population.

The first, or retrospective, part of the prevalence

study was completed in September 2021, when we reported results that supported that there was a significant unmet medical need in patients

dependent on PN.

We have concluded the second, or prospective part, of the prevalence study, which is a multi-center, cross-sectional

observational study that assessed the prevalence of choline deficiency in patients dependent on PN.

We shared these results with the FDA

to inform our discussion on next steps for the IV Choline Chloride program.

There are currently no IV formulations of choline available

or in development for PN patients.

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 indications.

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

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and capital resource needs.

Our Product Candidate Pipeline

The following chart summarizes

the current status of our product candidate pipeline:

Product Candidate Pipeline

following chart summarizes the current status of our product candidate pipeline:

Granted Rare Pediatric Disease Designation for the treatment of LMs

Orphan Drug and Fast Track Designations by the U.S.

1 PK study to be conducted in addition to Phase 3 study

Our Corporate Strategy:

We are an oncology and rare disease company focused on applying modern

scientific advancements to established mechanisms to deliver efficient de-risked clinical programs.

Leveraging the drug development and

commercialization experience of our management team, our goal is to build a leading biopharmaceutical company focused on bringing life-saving

therapies to patients with significant unmet needs.

Our current key initiatives are listed below:

Progress clinical program supporting

TARA-002 for the treatment of NMIBC.

Orphan Drug Designations by the U.S.

Corporate Strategy:

are an oncology and rare disease company focused on applying modern scientific advancements to established mechanisms to deliver efficient

de-risked clinical programs.

Leveraging the drug development and commercialization experience of our management team, our goal is to

build a leading biopharmaceutical company focused on bringing life-saving therapies to patients with significant unmet needs.

key initiatives are listed below:

Progress clinical program supporting TARA-002 for the treatment of NMIBC

Complete the ongoing Phase

1 clinical trial to assess the safety and tolerability of TARA-002 in patients with high-grade NMIBC, involving a dose escalation phase

in which we are evaluating the safety, tolerability and preliminary signs of anti-tumor activity of TARA-002 to determine dosage for

a future Phase 2 clinical trial.

We then intend to further assess safety and preliminary signs of anti-tumor activity of TARA-002 in

both BCG-naïve and BCG-exposed NMIBC patients with CIS in an expanded cohort of our Phase 1 and Phase 2 clinical trials.

Progress clinical program for TARA-002

in LMs by initiating a Phase 2 clinical trial in patients with macrocystic and mixed-cystic LMs.

1 expansion ADVANCED-1EXP clinical trial to further assess the safety and tolerability of TARA-002 in patients with high-grade NMIBC, and progress

the Phase 2 ADVANCED-2 clinical trial to assess the safety and anti-tumor activity of TARA-002 in both BCG-unresponsive and BCG-naïve

NMIBC patients with CIS.

Progress the Phase 2 clinical trial of TARA-002 in patients with macrocystic and mixed-cystic LMs

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

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

Following feedback from the Vaccines Division, we expect to initiate

a Phase 2 clinical trial evaluating TARA-002 in pediatric patients with macrocystic and mixed-cystic LMs.

Complete prospective prevalence study

of patients receiving PN and who have IFALD to refine a development pathway for IV Choline Chloride.

We are currently conducting

a prospective prevalence study to enhance understanding of the PN patient population and plan to use this information to inform the next

steps for the development program.

We received FDA feedback on a potential design of the studies necessary to complete a registration

package for IV Choline Chloride for the treatment of IFALD, including a Phase 1 pharmacokinetic study and a Phase 3 trial.

to use the results of our multinational prevalence study of the PN patient population to inform our strategy for IV Choline Chloride.

Explore opportunities to expand our

pipeline of uses for TARA-002 alone and in combination with other therapies.

We are exploring the use

of TARA-002 in combination with other therapies and are working to identify additional opportunities to develop TARA-002 in indications

beyond NMIBC and LMs.

We are conducting non-clinical experiments and modeling to better characterize the potential benefits of combination

therapy with TARA-002, particularly in NMIBC.

In addition, our leadership team has a strong track record of licensing, acquiring and

optimizing product candidates and we intend to leverage this skill set to identify opportunities for potential combination opportunities

for TARA-002, in NMIBC and other oncology indications.

The immunological activity of TARA-002’s originator product, OK-432, has

been effectively interrogated in patients in numerous indications.

We plan to continue to carefully evaluate the case reports and the

literature and perform non-clinical characterization studies to better understand the mechanism of action of TARA-002 and its potential

activity in indications beyond NMIBC and LM in which there is unmet need.

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 and Taiwan by Chugai Pharmaceutical.

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 cohorts of the trial this

Align with the FDA on the path forward for IV Choline Chloride for patients receiving PN

We continue to engage with

the FDA to define a path forward for IV Choline Chloride, including understanding the requirements for registrational clinical data needed

for a potential NDA filing for approval.

Explore opportunities to expand our pipeline of uses for TARA-002 alone and in combination with other therapies

are exploring the use of TARA-002 in combination with other therapies and are working to identify additional opportunities to develop

TARA-002 in indications beyond NMIBC and LMs.

We are conducting non-clinical experiments and modeling to better characterize the potential

benefits of combination therapy with TARA-002, particularly in NMIBC.

In addition, our leadership team has a strong track record of licensing,

acquiring and optimizing product candidates and we intend to leverage this skill set to identify potential combination

opportunities for TARA-002, in NMIBC and other oncology indications.

The immunological activity of TARA-002’s originator product,

OK-432, has been effectively interrogated in patients in numerous indications.

We plan to continue to carefully evaluate the case reports

and the literature and perform non-clinical characterization studies to better understand the mechanism of action of TARA-002 and its

potential activity in indications beyond NMIBC and LMs in which there is unmet need.

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 and Taiwan by Chugai Pharmaceutical.

We are using the same regulatory starting materials as OK-432 and manufacture TARA-002 using an updated version of the same proprietary

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

We entered into an agreement

with Chugai Pharmaceutical in June 2019, as amended in July 2020, to support our development of TARA-002.

The agreement provides us with

exclusive access to certain materials and documents relating to OK-432 including the master cell bank of Streptococcus pyogenes

used in the manufacturing of OK-432.

Additionally, the agreement provides technical support during a certain period.

We have utilized

the materials, proprietary manufacturing process and technical support provided by Chugai Pharmaceutical to produce TARA-002 at a cGMP-compliant

facility in the United States.

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.

In Japan, OK-432 is indicated

entered into an agreement with Chugai Pharmaceutical in June 2019, as amended in July 2020, to support our development of TARA-002.

The agreement provides us with exclusive access to certain materials and documents relating to OK-432 including the master cell bank

of Streptococcus pyogenes used in the manufacturing of OK-432.

Additionally, the agreement provides technical support during a

certain period.

We have utilized the materials, proprietary manufacturing process and technical support provided by Chugai

Pharmaceutical to produce TARA-002 at a current Good Manufacturing Practices-, or cGMP-, compliant facility in the United States.

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.

Japan, OK-432 is indicated for:

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 plan to pursue development

of TARA-002 for the treatment of NMIBC and LMs initially in the United States, and plan to also seek approval in Europe and other regions

in the future and may also explore additional indications where its utility as an immunostimulant has been hypothesized to be of therapeutic

TARA-002 in NMIBC

Disease Overview

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.

are developing TARA-002 for the treatment of NMIBC and LMs initially in the United States, and plan to also seek approval in Europe and

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.

Bladder cancer is the sixth

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There are three subtypes of NMIBC:

Ta (non-invasive papillary carcinoma), Tis (carcinoma in situ or CIS), and T1 (carcinoma invading the lamina propria).

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 three-year rate estimated at up to 80%.

Ta (non-invasive papillary carcinoma), Tis (CIS), and T1 (carcinoma invading the lamina propria).

Among the types of NMIBC, Ta accounts

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

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 three-year rate estimated at

Treatment for NMIBC is typically targeted to reduce unresectable persistence,

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The initial treatment for NMIBC includes

cystoscopy and complete transurethral resection of the bladder tumor (TURBT) for papillary Ta or T1, or biopsy for CIS.

cystoscopy and complete transurethral resection of the bladder tumor, or TURBT, for papillary Ta or T1, or biopsy for CIS.

A single postoperative

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options for patients with NMIBC.

Clinical Development

We are currently conducting our ADVANCED-1 trial.

In the initial dose

escalation phase of the trial, patients receive six weekly intravesical doses of TARA-002.

The primary objective of the trial is to evaluate

the safety, tolerability and preliminary signs of anti-tumor activity of TARA-002, with the goal of establishing a recommended dose for

a future Phase 2 clinical trial.

The trial is ongoing and we expect data from the Phase 1a portion of the trial in the second quarter

Preclinical Development

We continue to conduct pre-clinical

studies on TARA-002 to better characterize the mechanism of action to help us understand how TARA-002 may perform in potential combinations

with other agents used to treat NMIBC.

In addition, we use pre-clinical data to help us define other cancer targets for TARA-002 both

within the urothelial cancer space and other types of cancer affecting different parts of the body.

Regulatory Interactions

In October 2021, we announced

that the Office of Tissues and Advanced Therapies Division, or the OTAT Division, of the FDA’s Center for Biologics Evaluation

and Research, or CBER, cleared our Investigational New Drug, or IND, application for TARA-002 in NMIBC, allowing us to commence our ADVANCED-1

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

with the goal of establishing a recommended dose for a future Phase 2 clinical trial.

are currently conducting our ADVANCED-1EXP and ADVANCED-2 clinical trials.

ADVANCED-1EXP,

an open-label expansion trial, is evaluating intravesical TARA-002 at the 40KE dose in up to 12 CIS patients, including BCG-naïve,

BCG-unresponsive, and BCG-inadequately treated patients.

Dosing is progressing in the trial, and we anticipate having preliminary data

from the trial in the first half of 2024.

is a Phase 2 open-label trial evaluating intravesical TARA-002 in at

least 102 patients with high-grade CIS.

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

or BCG-experienced, 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).

The Company expects to share preliminary results from

a pre-planned risk-benefit analysis of the ongoing Phase 2 open-label ADVANCED-2 trial in the second half of 2024.

The analysis is expected

to include approximately 10 patients who are six-month evaluable.

continue to conduct pre-clinical studies on TARA-002 to better characterize the mechanism of action to help us understand how TARA-002

may perform in potential combinations with other agents used to treat NMIBC.

In addition, we use pre-clinical data to help us define

other cancer targets for TARA-002 both within the urothelial cancer space and other types of cancer affecting different parts of the

October 2021, we announced that the Office of Tissues and Advanced Therapies Division, or the OTAT Division, of the FDA’s Center

for Biologics Evaluation and Research, or CBER, cleared our Investigational New Drug application for TARA-002 in NMIBC.

had ongoing dialogue with the FDA to align on trial design of ADVANCED-1 and ADVANCED-2, as well as the potential combination trial we

may pursue with TARA-002 in NMIBC.

Manufacturing

We manufacture TARA-002

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 as OK-432.

We have contracted a contract development and manufacturing organization, or CDMO, to manufacture TARA-002.

TARA-002 for the Treatment of Lymphatic

Malformations

Disease Overview

We have worked with the FDA to align on a regulatory pathway and development

plan for TARA-002 for the treatment of LMs.

The International Society for the Study of Vascular Anomalies classifies LMs as either macrocystic,

microcystic, or mixed-cystic.

Macrocystic and microcystic LMs are differentiated by the size of the fluid-containing portion of the malformation.

Macrocystic LMs are characteristically large, fluid-filled cysts with a thin endothelial lining.

Macrocystic LMs are composed of cysts

greater than 2 cubic centimeters in size and present as a soft, fluid-filled swelling beneath normal or slightly discolored skin.

LMs are usually located in the antero-lateral cervical region of the neck;

however, it is possible for this type of LM to originate in

other areas of the body.

In contrast, microcystic LMs have very limited internal space with a thick irregular endothelial lining.

LMs are comprised of cysts less than 2 cubic centimeters in size and are often composed of micro-lymphatic channels that integrate and

infiltrate normal soft tissue.

Microcystic LMs can involve both superficial and deep aspects including muscle and bone.

Microcystic LMs

can thicken or swell causing enlargement of surrounding soft tissue and bones and can be found on any area of the skin or mucous membrane.

Mixed-cystic LMs are comprised of varying degrees of both 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.

There are no approved pharmacotherapies

for LMs, except in Japan and Taiwan where OK-432 is approved.

In these countries, OK-432 has been the standard of care for LMs for over

Treatment of LMs varies

depending on the symptoms and complications that present themselves.

The standard of care outside Japan and Taiwan for the treatment

of LMs is either a partial or complete surgical excision of the cysts.

While surgery is the standard approach to the treatment of LMs

in the head and neck, the region is a difficult area to operate on because of the large number of important anatomical structures in

We manufacture TARA-002 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 as OK-432.

We have contracted a cGMP-compliant

contract development and manufacturing organization, or CDMO, to manufacture TARA-002.

The International

Society for the Study of Vascular Anomalies classifies LMs as either macrocystic, microcystic, or mixed-cystic.

Macrocystic and microcystic

LMs are differentiated by the size of the fluid-containing portion of the malformation.

Macrocystic LMs are characteristically large,

fluid-filled cysts with a thin endothelial lining.

Macrocystic LMs are composed of cysts greater than 2 cubic centimeters in size and

present as a soft, fluid-filled swelling beneath normal or slightly discolored skin.

Macrocystic LMs are usually located in the antero-lateral

cervical region of the neck;

however, it is possible for this type of LM to originate in other areas of the body.

In contrast, microcystic

LMs have very limited internal space with a thick irregular endothelial lining.

Microcystic LMs are comprised of cysts less than 2 cubic

centimeters in size and are often composed of micro-lymphatic channels that integrate and infiltrate normal soft tissue.

LMs can involve both superficial and deep aspects including muscle and bone.

Microcystic LMs can thicken or swell causing enlargement

of surrounding soft tissue and bones and can be found on any area of the skin or mucous membrane.

Mixed-cystic LMs are comprised of varying

degrees of both macrocystic and microcystic LMs.

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.

are no approved pharmacotherapies for LMs, except in Japan and Taiwan where OK-432 is approved.

In these countries, OK-432 has been the

standard of care for LMs for over 25 years.

of LMs varies depending on the symptoms and complications that present themselves.

The standard of care outside Japan and Taiwan for

the treatment of LMs is either a partial or complete surgical excision of the cysts.

While surgery is the standard approach to the treatment

of LMs in the head and neck, the region is a difficult area to operate on because of the large number of important anatomical structures

Major venous and arterial trunks travel through the neck, as do important nerves.

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structures of the head and neck.

Clinical Development

Historical Data on OK- 432, predecessor therapy

When OK-432 is administered

locally for LMs, it is hypothesized that innate immune cells within the cyst are activated and produce a strong immune cascade.

and monocytes infiltrate the cyst and various cytokines, including interleukins IL-6, IL-8, IL-12, interferon, or IFN, -gamma, tumor

necrosis factor, or TNF-alpha, and vascular endothelial growth factor (VEGF) are secreted by immune cells within the cyst in response

to the presence of OK-432.

In concert, these immune activities induce a strong local inflammatory reaction in the cyst wall, resulting

in fluid drainage, shrinkage and fibrotic adhesion of the cyst.

Data on OK- 432, predecessor therapy to TARA-002

When TARA-002 is administered, it is hypothesized that innate and adaptive

immune cells within the cyst or tumor are activated and produce a strong immune cascade.

Neutrophils, monocytes, and lymphocytes infiltrate

the abnormal cells and various cytokines, including interleukins IL-2, IL-6, IL-10, IL-12, interferon, or IFN,-gamma, and tumor necrosis

factor, or TNF,-alpha are secreted by immune cells to induce a strong inflammatory reaction and destroy the abnormal cells.

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

adhesion of the cyst.

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

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There were three treatment groups:

treatment (ITG), delayed treatment (DTG), and open label treatment group.

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

The immediate treatment group received treatment with OK-432

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to treatment based on radiographically confirmed shrinkage in lesions.

Results presented in this

report 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:

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

64 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.

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.

presented in this report 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.

that included subjects enrolled between January 1998 and November 2004.

310 subjects were enrolled with intent to treat:

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

64 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.

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.

data prior to dosing with OK-432.

After dosing, the clinical success rate was 66%, which

was not statistically different from the ITG.

patients with radiographically confirmed

macrocystic lesions had the greatest likelihood of clinical success and in those patients with mixed lesions, clinical success was also

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

patients with radiographically confirmed macrocystic lesions had the greatest likelihood of clinical success and in those patients

with mixed lesions, clinical success was also present.

Success was defined as complete or substantial response.

data prior to dosing with OK-432.

After dosing, the clinical success rate was 66%, which

was not statistically different from the ITG.

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

were analyzed by lesion type across all treatment groups.

TARA-002 Clinical Development

We have an open IND for

LMs with the Vaccines Division.

Later in 2023 we expect to initiate a Phase 2 single arm, open-label clinical trial to evaluate the safety

and efficacy of TARA-002 in pediatric patients with macrocystic and mixed-cystic LMs.

The trial design includes a safety lead-in phase

followed by an expansion phase.

We are conducting trial preparation activities and have identified multiple trial sites.

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

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 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 being airway obstruction and facial paralysis due to massive swelling post-injection

that required tracheostomy and hospitalization.

Clinical Development

We have an open investigational new drug application, or IND, for LMs

with the Vaccines and Related Products Division of the FDA, or 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 pediatric patients with macrocystic

and mixed-cystic LMs.

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

Safety Profile on OK-432, predecessor therapy to TARA-002

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 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 being airway obstruction and facial paralysis due to massive swelling

post-injection that required tracheostomy and hospitalization.

Both of these events were reported as resolved.

The safety findings from

the sponsor-conducted retrospective analysis are consistent with the original analysis reported in Smith et al.

2009, and with safety

data in published studies in approximately 865 patients with LMs after treatment with OK-432.

Historical Preclinical Development on

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 of a 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.

TARA-002 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 a 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.

safety findings from the sponsor-conducted retrospective analysis are consistent with the original analysis reported in Smith et al.

2009, and with safety data in published studies in approximately 865 patients with LMs after treatment with OK-432.

Preclinical Development on OK-432, predecessor therapy to TARA-002

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 of a NDA with the Japan Pharmaceuticals and Medical Devices Agency.

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

Regulatory Interactions

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

Under the FDA’s Rare Pediatric Disease Priority Review Voucher program, a sponsor who receives an approval of a 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.

The robust dataset for OK-432 in LMs has informed our development of

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of Iowa to our open IND with the Vaccines Division.

We received feedback from the Vaccines Division on the protocol for our proposed Phase

2 clinical trial evaluating TARA-002 in LMs.

In the second half of 2023 we expect to initiate this Phase 2 single arm, open-label clinical

trial to evaluate the safety and efficacy of TARA-002 in pediatric patients with macrocystic and mixed-cystic LMs.

The trial design includes

a safety lead-in phase followed by an expansion phase.

We are conducting trial preparation activities and have identified multiple trial

We incorporated feedback from the Vaccines Division on the protocol for our ongoing

Phase 2 clinical trial evaluating TARA-002 in LMs.

Manufacturing

TARA-002 is manufactured

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

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

type 3) Su strain as OK-432.

We have contracted a CDMO to manufacture TARA-002.

IV Choline Chloride for the treatment of Intestinal

Failure Associated Liver Disease

IV Choline Chloride is an

IV substrate replacement therapy initially in development for patients receiving PN who have IFALD.

Choline is a known important

substrate for phospholipids that are critical for healthy liver function.

Because patients receiving PN cannot sufficiently absorb adequate

levels of choline and no available PN components contain sufficient amounts of choline to correct this deficit, they often experience

a prolonged progression to hepatic failure and death, with the only known intervention being a dual small bowel / liver transplant.

approved, IV Choline Chloride would be the first approved therapy for IFALD.

It has been granted ODD by the FDA for the treatment of

IFALD and the prevention of choline deficiency in PN patients.

We are currently undertaking a multinational prevalence study to enhance

understanding of the PN patient population.

We expect to complete the prospective part of the study in mid-2023.

We have entered into a license

agreement with Dr.

Alan Buchman for exclusive rights to the IND, ODD and other regulatory assets related to IV Choline Chloride, as well

as exclusive rights to the data from previously conducted Phase 1 and Phase 2 clinical trials led by Dr.

The results of a randomized,

controlled, Phase 2 clinical trial demonstrated that treatment with IV Choline Chloride resulted in normalization of plasma-free choline

concentrations, improvement of hepatic steatosis, and statistically significant improvement in cholestasis in patients dependent on PN.

We had an end of Phase 2

meeting with the FDA in November 2018 and received the FDA’s feedback on the design of studies necessary to complete the registration

package for IV Choline Chloride for the treatment of IFALD, including a Phase 1 pharmacokinetic study and a Phase 3 trial.

to use the results of our multinational prevalence study of the PN patient population to inform our strategy for IV Choline Chloride.

We manufacture TARA-002 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 as OK-432.

We have contracted a cGMP-compliant

CDMO, to manufacture TARA-002.

Choline Chloride for PN Patients

Choline Chloride is an IV substrate therapy in development for patients receiving PN.

Choline is a known important substrate for phospholipids, a source

of methyl groups needed for many steps in metabolism and plays important roles in modulating gene expression, cell membrane signaling,

lipid transport and metabolism, liver health, brain development and neurotransmission, muscle function and bone health.

The only way to

reliably replenish choline is through exogenous consumption.

Patients receiving PN cannot sufficiently absorb adequate levels of choline

and available PN components do not contain sufficient amounts of choline to correct this deficit.

The use of choline for PN patients is

included in key professional medical society recommendations, including the American Society for Parenteral and Enteral Nutrition, or

IV Choline Chloride has been granted Orphan Drug Designation, or ODD, by the FDA for the prevention of choline deficiency in PN

have entered into a license agreement with Dr.

Alan Buchman for exclusive rights to the IND, ODD and other regulatory assets related

to IV Choline Chloride, as well as exclusive rights to the data from previously conducted Phase 1 and Phase 2 clinical trials led by

results of Dr.

Buchman’s randomized, controlled, Phase 2 clinical trial demonstrated that treatment with IV Choline Chloride resulted

in normalization of plasma-free choline concentrations, improvement of hepatic steatosis, and statistically significant improvement in

cholestasis in patients dependent on PN.

Disease Overview

IFALD is a rare hepatic/metabolic

IFALD, which occurs in patients dependent upon PN, is characterized by choline deficiency, hepatic steatosis, cholestasis, and

rapid progression of liver disease through to hepatic failure and death, in the absence of intestine-liver transplant.

IFALD carries

a relatively poor prognosis, with a 15-34% death rate within one to four years.

When IFALD presents in children, mortality is even higher,

with studies reporting death rates of 23-40% within 18 months.

A patient is considered to have IFALD if she/he:

dependent on PN for more than six months (e.g., has chronic intestinal failure);

evidence of steatosis, determined by imaging techniques or histologic assessments;

evidence of cholestasis (e.g., elevated alkaline phosphatase, or ALP, elevated bilirubin and/or histology);

have evidence of ongoing, progressive liver injury on the basis of multiple abnormal liver function tests, in conjunction with findings

of fibrosis, cirrhosis, and/or end-stage liver disease.

Many patients receiving

PN are entirely dependent on PN for their nutritional needs.

PN delivers nearly all the macro and micro-nutrients necessary for survival

in their patients, with the notable exception of choline.

Consequently, patients dependent on PN support have been shown to be choline

Patients dependent upon PN are unable to synthesize sufficient levels of choline and malabsorption limits the bioavailability

of choline chloride from the PN diet.

The American Society for Parenteral and Enteral Nutrition and the Academy of Nutrition and Dietetics’

Dietitians in Nutrition Support both recommend that choline be developed and routinely included in PN products;

however, there are currently

no FDA-approved choline chloride PN products.

Dependence on PN and resulting

choline deficiency often leads to IFALD, which is the most common adverse outcome in chronic PN adult patients that is associated with

Low free choline plasma concentrations are associated with alanine aminotransferase, or ALT, aspartate aminotransferase, or AST,

and ALP elevations as well as steatosis (fatty liver) and cholestasis (when bile from the liver stops or slows), all indicators of ongoing

liver damage.

Clinical Development

In a Phase 2 randomized,

double-blind, controlled 24-week clinical trial, patients (n=15) receiving nightly PN for > 85% of their nutritional needs (for at

least 12 weeks prior to entry) were randomized to receive via IV infusion (10-12 hours) their usual PN with placebo (n = 8), or PN to

which 2g IV Choline Chloride was added (n = 7).

In the IV Choline Chloride

group, mean choline levels were within or greater than the estimated normal range (i.e., 6.7 to 26.9 nmol/mL) throughout the 24-week

trial and quickly returned to baseline levels when treatment was discontinued.

Upon conversion of the quantification

of computed tomography, or CT, values to magnetic resonance imaging proton density fat fraction, or MRI-PDFF, significant differences

in the least square, or LS, mean change from baseline in estimated MRI-PDFF were observed in the IV Choline Chloride group in comparison

to placebo group at Week 4 through Week 24, demonstrating a clinically meaningful and statistically significant reduction in steatosis.

When LS mean percent changes from baseline in MRI-PDFF were compared between treatment groups, significant differences in LS mean changes

(range, 31.7% to 53.6%) were observed from Weeks 4 to 24 with p-values of 0.0009 to 0.0297 favoring the IV Choline Chloride group.

Liver CT Images:

Before and After Treatment with IV Choline

Alkaline Phosphatase:

At baseline, LS mean ALP

concentration was 239.3 ± 118.93 in the IV Choline Chloride group and 148.1 ± 100.2 in the placebo group.

The mixed model

for repeated measures, or MMRM, analyses demonstrated statistically significant decreases in ALP concentrations at Week 12 (p = 0.008),

Week 16 (p = 0.005), Week 20 (p = 0.007), and Week 24 (p = 0.005) for the IV Choline Chloride group, demonstrating a reduction in cholestasis.

A trend towards significance was observed at Week 4 (p = 0.076) and Week 6 (p = 0.056).

At Week 34, 10 weeks after discontinuation of

IV Choline Chloride treatment, LS mean change from baseline in ALP concentrations still demonstrated statistically significant decreases

(p = 0.002), demonstrating a significant improvement in cholestasis with treatment with IV Choline Chloride (Figure 4).

In the subgroup of subjects

with ALP concentration > 1.5x upper limit of normal (ULN) at baseline, (n=7), mean values at baseline were comparable between the

IV Choline Chloride and placebo groups (294.20 ± 87.947 versus 277.00 ± 128.693, respectively).

In the sub-group analysis,

improvement in ALP was consistent and substantial, with 20-30% improvement over 12-24 weeks of treatment.

Statistical significance was

observed at 12, 16, and 20 weeks.

In the description of the trials above and

elsewhere in this Annual Report on Form 10-K, “n” represents the number of patients in a particular group and “p”

or “p-values” represent the probability that random chance caused the result (e.g., a p-value of 0.001

means that there is a 0.1% probability that the difference between the placebo group and the treatment group is purely due to random

A p-value of less than or equal to 0.05 is a commonly used criterion for statistical significance, and may

be supportive of a finding of efficacy by regulatory authorities.

Improvement in Cholestasis 1 :

Therapeutics re-analysis of patient CRF’s, data on file.

method used for imputation.

placebo subject was excluded from all analyses due to likely IV contrast-induced imaging

abnormalities, confirmed by independent radiologist in subsequent re-analysis.

Preclinical Development

Preclinical Studies Conducted by us

for IV Choline Chloride

PN is a medication used to manage and treat malnourishment and is

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

Currently, 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.

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);

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 restore circulating choline to physiologic

concentrations in patients who are dependent on PN.

Buchman’s Phase 2 randomized, double-blind, controlled 24-week clinical trial, patients (n=15) receiving nightly PN for >

85% of their nutritional needs (for at least 12 weeks prior to entry) were randomized to receive via IV infusion (10-12 hours) their

usual PN with placebo (n = 8), or PN to which 2g IV Choline Chloride was added (n = 7).

the IV Choline Chloride group, mean choline levels were within or greater than the estimated normal range (i.e., 6.7 to 26.9 nmol/mL)

throughout the 24-week trial and quickly returned to baseline levels when treatment was discontinued.

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

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

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

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

Assessment of Choline as an Inhibitor of Human BSEP Mediated Transport

Assessment of Choline as a Substrate of Human BSEP Mediated Transport

Nonclinical 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

Regulatory Interactions

We have received feedback

from the FDA on a number of key aspects of the overall clinical program necessary for registration, including a Phase 1 pharmacokinetic

study and a Phase 3 clinical trial.

We completed a retrospective, observational study of patients dependent on PN for 6 or more months.

The objective of the study was to understand the incidence of cholestasis, a hallmark pathology of IFALD in this patient population by

measuring serum alkaline phosphatase (ALP) levels greater than 1.5 times the upper limit of normal ULN as a key marker of cholestasis.

Results of the study showed:

31% of all patients, irrespective of baseline levels, presented with ALP levels greater than 1.5 times the

ULN at any given time during 6 to 36 months.

In addition, approximately 28% of all patients had persistent ALP elevations greater than

1.5 times the ULN at 36 months.

At baseline, approximately 23% of patients presented with ALP levels greater than 1.5 times the ULN with

approximately 76% presenting with greater than 1.5 times the ULN at any given time during 6 to 36 months and approximately 59% with persistent

ALP elevations greater than 1.5 times the ULN at 36 months.

While medical management demonstrated some improvement in ALP levels, it

was not sufficient for managing ALP levels over the long term in patients on PN.

Results support further exploration in patient population

to determine rates of choline deficiency and steatosis.

We have initiated a prospective observational study to further characterize the

prevalence of choline deficiency, as well as cholestasis and steatosis.

We plan to use information from this prospective study to determine

the appropriate next steps for the development program.

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

We continue to engage with the FDA and plan to use both regulatory

feedback and results from the prevalence study to inform next steps for the IV Choline Chloride development program.

Manufacturing

Through our CDMO, we have

manufactured sufficient amounts of cGMP drug substance and drug product to initiate the planned clinical trials.

Scale up for commercial

demand, if and when applicable, will commence when appropriate.

Our end-to-end manufacturing of IV Choline Chloride is conducted in the

United States by a cGMP-compliant CDMO.

However, due to current macroeconomic factors, such as rising inflation and supply chain shortages,

scaling up may be more difficult than originally anticipated.

Collaborations and License Agreements

Chugai Agreement

On June 17, 2019, we entered

into an agreement, or the Chugai Agreement, with Chugai Pharmaceutical, a company organized and existing under the laws of Japan.

Pharmaceutical has developed and commercialized a therapeutic product, OK-432 (or Existing Product), in Japan and Taiwan, or the Chugai

Territory and owns and controls certain materials and documents related to the Existing Product (or the Chugai Materials).

the Chugai Agreement, Chugai Pharmaceutical has provided us with certain materials and documents relating to the Existing Product and

has provided certain technical services to us for our development and commercialization in territories other than the Chugai Territory,

or the Protara Territory of a new therapeutic product, or the New Product or TARA-002 comparable to the Existing Product beginning on

the effective date of the Chugai Agreement and ending on June 30, 2020, or any other date to be agreed to by the parties, or the Chugai

Service Period.

Under the Chugai Agreement, Chugai Pharmaceutical will exclusively provide the Existing Product and Chugai Materials

to us and will not provide the Existing Product or Chugai Materials to any third parties during the Chugai Service Period, other than

for medical, compassionate use and/or non-commercial research purposes.

Additionally, beginning on the effective date of the Chugai Agreement

and ending on the fifth anniversary of such date or upon the termination of the Chugai Agreement, whichever comes earlier, Chugai Pharmaceutical

will not provide Chugai Materials or technical support to any third-party for the purpose of development and commercialization in the

Protara Territory of a therapeutic product comparable to the Existing Product.

We are responsible, at our sole cost and expense, for

the development and commercialization of the New Product in the Protara Territory.

We have contracted a CDMO,

to manufacture IV Choline Chloride.

Our end-to-end manufacturing of IV Choline Chloride is conducted in the United States by a cGMP-compliant

Collaborations

and License Agreements

On June 17, 2019, we entered into an agreement, or the Chugai Agreement,

with Chugai Pharmaceutical, a company organized and existing under the laws of Japan.

Chugai Pharmaceutical has developed and commercialized

a therapeutic product, OK-432, or Existing Product, in Japan and Taiwan, or the Chugai Territory, and owns and controls certain materials

and documents related to the Existing Product, or the Chugai Materials.

Pursuant to the Chugai Agreement, Chugai Pharmaceutical has provided

us with certain materials and documents relating to the Existing Product and has provided certain technical services to us for our development

and commercialization.

This pertains to territories other than the Chugai Territory, or the Protara Territory, of a new therapeutic product,

or the New Product or TARA-002, comparable to the Existing Product.

Under the Chugai Agreement, Chugai Pharmaceutical will exclusively

provide the Existing Product and Chugai Materials to us and will not provide the Existing Product or Chugai Materials to any third parties

during the Chugai Service Period, other than for medical, compassionate use and/or non-commercial research purposes.

Additionally, beginning

on the effective date of the Chugai Agreement and ending on the fifth anniversary of such date or upon the termination of the Chugai Agreement,

whichever comes earlier, Chugai Pharmaceutical will not provide Chugai Materials or technical support to any third-party for the purpose

of development and commercialization in the Protara Territory of a therapeutic product comparable to the Existing Product.

We are responsible,

at our sole cost and expense, for the development and 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 Amendment, with an effective date as of June 30, 2020.

The Chugai Amendment extends the date through

which Chugai will exclusively provide the Existing Product and materials to us from June 30, 2020 to June 30, 2021, extends 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 a designated

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 a designated

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

As consideration for Chugai Pharmaceutical’s performance under

the Chugai Agreement, we agreed to pay Chugai Pharmaceutical a payment in the low, single-digit millions, which will be made in two installments

with an initial payment made in July 2020, and the remaining majority of the total amount will be payable upon FDA approval of the New

We granted Chugai Pharmaceutical

a right of first refusal on terms to be negotiated between the parties for a license related to the New Product-relevant information,

data and documentation and inventions to develop and commercialize the New Product in the Chugai Territory.

We will be responsible for

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.

In addition, either party

may terminate the Chugai Agreement, in whole or in part, in the event that the other party materially breaches the Chugai Agreement and

fails to cure the breach within 30 days of written notice.

Either party may terminate the Chugai Agreement in its entirety immediately

upon notice to the other party if such other party:

(i) is dissolved or liquidated or takes any corporate action for such purpose;

becomes insolvent or is generally unable to pay, or fails to pay, its debts as they become due;

(iii) files or has filed against it a

petition for voluntary or involuntary bankruptcy or otherwise becomes subject to any proceeding under any domestic or foreign bankruptcy

or insolvency laws;

consideration for Chugai Pharmaceutical’s performance under the Chugai Agreement, we agreed to pay Chugai Pharmaceutical a payment

in the low, single-digit millions, which will be made in two installments with an initial payment made in July 2020, and the remaining

majority of the total amount will be payable upon FDA approval of the New Product.

We granted Chugai Pharmaceutical a right of first refusal on terms

to be negotiated between the parties for a license related to the New Product-relevant information, data and documentation and inventions

to develop and commercialize the New Product in the Chugai Territory.

We will be responsible for manufacturing and supplying, or causing

our CDMO to manufacture and supply, the New Product to Chugai Pharmaceutical.

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.

addition, either party may terminate the Chugai Agreement, in whole or in part, in the event that the other party materially breaches

the Chugai Agreement and fails to cure the breach within 30 days of written notice.

Either party may terminate the Chugai Agreement in

its entirety immediately upon notice to the other party if such other party:

(i) is dissolved or liquidated or takes any corporate action

for such purpose;

(ii) becomes insolvent or is generally unable to pay, or fails to pay, its debts as they become due;

(iii) files or

has filed against it a petition for voluntary or involuntary bankruptcy or otherwise becomes subject to any proceeding under any domestic

or foreign bankruptcy or insolvency laws;

(iv) makes or seeks to make a general assignment for the benefit of creditors;

or (v) applies for or has a receiver,

trustee, custodian or similar agent appointed by order of any court to take charge of or sell any material portion of its property or

In the event that we undergo

a change of control, Chugai Pharmaceutical may terminate the Chugai Agreement upon 90 days’ written notice to us, absent a written

pledge by the new controlling party of its agreement to fulfill and undertake all obligations of ours and to be bound by the Chugai Agreement.

Sponsored Research and License Agreement

On November 28, 2018, we

entered into a sponsored research and license agreement, or the Research Agreement, with The University of Iowa, or the University, pursuant

to which the University will provide access to certain program data related to Chugai Pharmaceutical’s OK-432 and will assist us

in conducting certain clinical studies.

As consideration for the University’s performance under the Research Agreement, we will

pay the University $30,000 per year in funding for the project, taking into consideration the time spent by University employees required

for the Project.

The parties also agree to discuss in good faith potential additional funding required for completion of the project

pursuant to the Research Agreement as applicable and necessary.

In addition, within 45 days of approval of the TARA-002 BLA by the FDA,

we will pay a one-time approval milestone to the University, the amount of which depends on the usefulness of the program data in TARA-002’s

BLA filing, and the milestone amount will range from $0 to $1 million.

We will also be responsible for certain tiered royalties on annual

net sales of products for the indication, which royalty rates are in the low single digit percentages.

These royalty rates are also subject

to a reduction in the event that regulatory authorities determine that the program data is not sufficient for regulatory approval on

its own and additional pediatric efficacy and safety clinical studies are required.

In the event that the annual net sales surpass certain

dollar amount thresholds, we will need to make certain additional milestone payments following the close of the calendar quarter in which

each milestone is reached, 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.

Choline License Agreement

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.

During the term of the Choline Agreement, Dr.

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

Certain milestone and royalty

payments may also be payable to Dr.

or (v) applies

for or has a receiver, trustee, custodian or similar agent appointed by order of any court to take charge of or sell any material portion

of its property or business.

the event that we undergo a change of control, Chugai Pharmaceutical may terminate the Chugai Agreement upon 90 days’ written notice

to us, absent a written pledge by the new controlling party of its agreement to fulfill and undertake all obligations of ours and to

be bound by the Chugai Agreement.

Research and License Agreement

November 28, 2018, we entered into a sponsored research and license agreement, or the Research Agreement, with The University of Iowa,

or the University, pursuant to which the University will provide access to certain program data related to Chugai Pharmaceutical’s

OK-432 and will assist us in conducting certain clinical studies.

As consideration for the University’s performance under the Research

Agreement, we will pay the University $30,000 per year in funding for the project, taking into consideration the time spent by University

employees required for the Project.

The parties also agree to discuss in good faith potential additional funding required for completion

of the project pursuant to the Research Agreement as applicable and necessary.

In addition, within 45 days of approval of the TARA-002

BLA by the FDA, we will pay a one-time approval milestone to the University, the amount of which depends on the usefulness of the program

data in TARA-002’s BLA filing, and the milestone amount will range from $0 to $1 million.

We will also be responsible for certain

tiered royalties on annual net sales of products for the indication, which royalty rates are in the low single digit percentages.

royalty rates are also subject to a reduction in the event that regulatory authorities determine that the program data is not sufficient

for regulatory approval on its own and additional pediatric efficacy and safety clinical studies are required.

In the event that the

annual net sales surpass certain dollar amount thresholds, we will need to make certain additional milestone payments following the close

of the calendar quarter in which each milestone is reached, with the payments ranging from $62,500 to $125,000.

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

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

License Agreement

September 27, 2017, we entered into a choline license agreement, or the Choline Agreement, with Alan L.

Buchman, M.D., pursuant to which

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,

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

milestone and royalty payments may also be payable to Dr.

Pursuant to the Choline Agreement, we paid Dr.

Buchman $50,000 in October 2019 because we

had not received at least $5 million in working capital from any source or in any manner as of October 15, 2019.

Buchman $50,000 in

October 2019 because we had not received at least $5 million in working capital from any source or in any manner as of October 15, 2019.

We then paid Dr.

a $550,000 milestone in January 2020 following our receipt of at least $5 million in working capital.

Regardless of whether development or commercialization is undertaken

by us under the Choline Agreement, commencing in November 2022 and during the term of the Choline Agreement, we will pay Dr.

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

Buchman sales

royalties based on aggregate net sales of IV Choline Chloride in each calendar quarter, with the 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 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.

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, 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 milestone 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.

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

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.

Buchman a $550,000 milestone in January 2020 following our receipt of at least $5 million in working capital.

of whether development or commercialization is undertaken by us under the Choline Agreement, commencing in November 2022 and during the

term of the Choline Agreement, we will pay Dr.

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

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

will also pay Dr.

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

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

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 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.

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.

License Agreement

On December 22, 2017, we

entered into a license agreement, or the License Agreement, with The Feinstein Institute for Medical Research, a not-for-profit corporation

organized and existing under the laws of New York, or the Institute.

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;

petition in bankruptcy or insolvency;

(d) a receiver or administrator takes possession of our assets or (e) any similar procedure is

commenced against us in the United States.

On December 22, 2017, we entered into a license agreement, or the License

Agreement, with The Feinstein Institute for Medical Research, a not-for-profit corporation organized and existing under the laws of New

York, or the Institute.

The Institute owns, by assignment, a U.S.

patent related to the

treatment of fatty liver disease in humans.

Pursuant to the License Agreement, the Institute granted us an exclusive, worldwide license,

with the 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 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

patent related to the treatment of fatty liver disease in humans.

to the License Agreement, the Institute granted us an exclusive, worldwide license, with the 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.

As consideration for the

license grant, we agreed to pay the Institute tiered royalties of between 1.0% and 1.5% of all net sales.

In addition, we agreed to pay

the Institute a low double digit percentage of net proceeds resulting from agreements entered into within two years from the effective

date of the License Agreement and a mid-single digit percentage of net proceeds resulting from agreements entered into thereafter.

also agreed to make certain license maintenance payments of $15,000 beginning on the second anniversary of the effective date of the

License Agreement and continuing upon every anniversary thereafter until the first commercial sale of a licensed product.

the first anniversary of the effective date of the License Agreement after the first commercial sale of a licensed product and every

anniversary of the effective date of the License Agreement thereafter, we will pay the Institute $30,000 as a license maintenance fee.

Such license maintenance fees are non-refundable but are creditable against future royalty payments due to the Institute during the 12-month

period following each such anniversary.

We agreed to make certain

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 the Private Placements.

Unless terminated earlier,

the License Agreement will expire upon the expiration of the last to expire patent under the License Agreement.

We may terminate the

License Agreement by giving the Institute 60 days’ prior notice.

Either party may terminate the License Agreement in the event

of a default or breach by the other party that has not been cured within 60 days of such notice.

If we (i) make an assignment for the

benefit of creditors or if proceedings for a voluntary bankruptcy are instituted on our behalf;

(ii) are declared bankrupt or insolvent

or (iii) are convicted of a felony relating to the manufacture, use or sale of the licensed products or a felony relating to moral turpitude,

the Institute may terminate the License Agreement.

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.

and internationally

for our product candidates, novel biological discoveries, epitopes, new therapeutic approaches and potential indications, and other inventions

that are important to our business.

Throughout the development of our product candidates, we will seek to identify additional means of

obtaining patent protection that would potentially enhance commercial success.

We also rely upon trade secrets, know-how, continuing

technological innovation and in-licensing opportunities to develop and maintain our proprietary position.

The patent positions of

biotechnology companies like us are generally uncertain and involve complex legal, scientific and factual questions.

We recognize that

the ability to obtain patent protection and the degree of such protection depends on a number of factors, including the extent of the

prior art, the novelty and non-obviousness of the invention, and the ability to satisfy the enablement requirement of the patent laws.

In addition, the coverage claimed in a patent application can be significantly reduced before the patent is issued, and its scope can

be reinterpreted after issuance.

Consequently, we may not obtain or maintain adequate patent protection for any of our product candidates.

consideration for the license grant, we agreed to pay the Institute tiered royalties of between 1.0% and 1.5% of all net sales.

we agreed to pay the Institute a low double digit percentage of net proceeds resulting from agreements entered into within two years

from the effective date of the License Agreement and a mid-single digit percentage of net proceeds resulting from agreements entered

into thereafter.

We also agreed to make certain license maintenance payments of $15,000 beginning on the second anniversary of the effective

date of the License Agreement and continuing upon every anniversary thereafter until the first commercial sale of a licensed product.

Beginning on the first anniversary of the effective date of the License Agreement after the first commercial sale of a licensed product

and every anniversary of the effective date of the License Agreement thereafter, we will pay the Institute $30,000 as a license maintenance

Such license maintenance fees are non-refundable but are creditable against future royalty payments due to the Institute during

the 12-month period following each such anniversary.

agreed to make certain 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.

terminated earlier, the License Agreement will expire upon the expiration of the last to expire patent under the License Agreement.

may terminate the License Agreement by giving the Institute 60 days’ prior notice.

Either party may terminate the License Agreement

in the event of a default or breach by the other party that has not been cured within 60 days of such notice.

If we (i) make an assignment

for the benefit of creditors or if proceedings for a voluntary bankruptcy are instituted on our behalf;

(ii) are declared bankrupt or

insolvent or (iii) are convicted of a felony relating to the manufacture, use or sale of the licensed products or a felony relating to

moral turpitude, the Institute may terminate the License Agreement.

intellectual property is critical to our business and we strive to protect it, including by obtaining and maintaining patent protection

and internationally for our product candidates, novel biological discoveries, epitopes, new therapeutic approaches and potential

indications, and other inventions that are important to our business.

Throughout the development of our product candidates, we will seek

to identify additional means of obtaining patent protection that would potentially enhance commercial success.

We also rely upon trade

secrets, know-how, continuing technological innovation and in-licensing opportunities to develop and maintain our proprietary position.

patent positions of biotechnology companies like us are generally uncertain and involve complex legal, scientific and factual questions.

We recognize that the ability to obtain patent protection and the degree of such protection depends on a number of factors, including

the extent of the prior art, the novelty and non-obviousness of the invention, and the ability to satisfy the enablement requirement

of the patent laws.

In addition, the coverage claimed in a patent application can be significantly reduced before the patent is issued,

and its scope can be reinterpreted after issuance.

Consequently, we may not obtain or maintain adequate patent protection for any of

our product candidates.

Any patents 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 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 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.

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

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 until 2035.

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, NASH, alcoholic steatohepatitis, or ASH, NASH-associated

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

In addition, in April 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 would 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 for the treatment of IFALD.

The term of individual patents

depends upon the legal term of the patents in the countries in which they are obtained.

In most countries in which we may file, the patent

term is 20 years from the earliest date of filing a non-provisional patent application related to the patent.

patent also may

be accorded a patent term adjustment under certain circumstances to compensate for delays in obtaining the patent from the USPTO.

some instances, such a patent term adjustment may result in a U.S.

patent term extending beyond 20 years from the earliest date of filing

a 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.

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.

We also rely on trade secrets

relating to product candidates and seek to protect and maintain the confidentiality of proprietary information to protect aspects of

our business that are not amenable to, or that we do not consider appropriate for, patent protection.

Although we take steps to protect

our proprietary information and trade secrets, including through contractual means with our employees and consultants, third parties

may independently develop substantially equivalent proprietary information and techniques or otherwise gain access to our trade secrets,

including through breaches of such agreements with our employees and consultants.

Thus, we may not be able to meaningfully protect our

trade secrets.

It is our policy to require our employees, consultants, outside scientific partners, sponsored researchers and other advisors

to execute confidentiality agreements upon the commencement of employment or consulting relationships with us.

These agreements provide

that all confidential information concerning our business or financial affairs developed or made known to the individual during the course

of the individual’s relationship with us is to be kept confidential and not disclosed to third parties except in specific circumstances.

Our agreements with employees also provide that all inventions conceived by the employee in the course of employment with us or from

the employee’s use of our confidential information are our exclusive property.

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

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 United States 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.

For a more comprehensive discussion of the risks related to our intellectual property, please see

“ Risk Factors—Risks Related to Our Intellectual Property.

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

TARA-002 is produced through a proprietary manufacturing

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.

Choline Chloride:

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 until 2035.

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, NASH, alcoholic steatohepatitis,

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

in April 2022, the USPTO issued to us Patent No.

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

We would 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.

term of individual patents depends upon the legal term of the patents in the countries in which they are obtained.

In most countries

in which we may file, the patent term is 20 years from the earliest date of filing a non-provisional patent application related to the

patent also may be accorded a patent term adjustment under certain circumstances to compensate for delays in obtaining

the patent from the USPTO.

In some instances, such a patent term adjustment may result in a U.S.

patent term extending beyond 20 years

from the earliest date of filing a 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.

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.

also rely on trade secrets relating to product candidates and seek to protect and maintain the confidentiality of proprietary information

to protect aspects of our business that are not amenable to, or that we do not consider appropriate for, patent protection.

we take steps to protect our proprietary information and trade secrets, including through contractual means with our employees and consultants,

third parties may independently develop substantially equivalent proprietary information and techniques or otherwise gain access to our

trade secrets, including through breaches of such agreements with our employees and consultants.

Thus, we may not be able to meaningfully

protect our trade secrets.

It is our policy to require our employees, consultants, outside scientific partners, sponsored researchers

and other advisors to execute confidentiality agreements upon the commencement of employment or consulting relationships with us.

agreements provide that all confidential information concerning our business or financial affairs developed or made known to the individual

during the course of the individual’s relationship with us is to be kept confidential and not disclosed to third parties except

in specific circumstances.

Our agreements with employees also provide that all inventions conceived by the employee in the course of

employment with us or from the employee’s use of our confidential information are our exclusive property.

Manufacturing

We rely on CDMOs to produce

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

The manufacture

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

all areas of record keeping, production processes and controls, personnel and quality control.

The CDMOs that we partner

with have the capability to produce clinical supply required for clinical trials, as well as support commercial scale-up activities for

both products.

We manufacture TARA-002

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,

rely on CDMOs to produce our drug candidates in accordance with cGMP as well as regulations for use in clinical trials and for commercial

The manufacture of pharmaceuticals is subject to extensive cGMP regulations, which impose various procedural and documentation

requirements and govern all areas of record keeping, production processes and controls, personnel and quality control.

CDMOs that we partner with have the capability to produce clinical supply required for clinical trials, as well as support commercial

scale-up activities for both products.

manufacture TARA-002 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 as OK-432.

We have contracted a CDMO to manufacture TARA-002.

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.

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.

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

Sales and Marketing

We plan to become a fully-integrated

commercial biopharmaceutical company 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 both of our current product candidates in the United States first and then in other geographies.

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

of new drugs is very competitive, and we could potentially face worldwide competition from other pharmaceutical companies, biotechnology

companies and ultimately generic or biosimilar products.

Our potential competitors may develop or market therapies that are available

sooner, more clinically effective, safer or less expensive than any therapeutic products we develop.

Numerous companies are engaged in

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.

and Marketing

plan to become a fully-integrated commercial biopharmaceutical company pursuing our mission of supporting and improving the lives of

patients suffering from cancer and rare diseases.

approved by the FDA, we plan to commercialize both of our current product candidates in the United States first and then in other geographies.

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.

process for commercialization of new drugs is very competitive, and we could potentially face worldwide competition from other pharmaceutical

companies, biotechnology companies and ultimately generic or biosimilar products.

Our potential competitors may develop or market therapies

that are available sooner, more clinically effective, safer or less expensive than any therapeutic products we develop.

Numerous companies

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

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.

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 of LMs.

There are no approved pharmacotherapies

currently available for the treatment of LMs and the current treatment options include a high-risk surgical procedure and off-label use

of sclerosants, including doxycycline, bleomycin, ethanol and sodium tetradecyl sulfate.

There are a number of drug development companies

and academic researchers exploring oral and topical formulations of various agents for the treatment of LMs including macrolides, phosphodiesterase

inhibitors, and calcineurin/mTOR inhibitors.

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

are no approved pharmacotherapies currently available for the treatment of LMs and the current treatment options include a high-risk

surgical procedure and off-label use of sclerosants, including doxycycline, bleomycin, ethanol and sodium tetradecyl sulfate.

a number of drug development companies and academic researchers exploring oral and topical formulations of various agents for the treatment

of LMs including macrolides, phosphodiesterase inhibitors, and calcineurin/mTOR inhibitors.

These are in early development.

TARA-002, if approved for

the treatment of NMIBC, would be subject to competition from existing treatment methods of surgery, chemotherapy and immunomodulatory

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.

Additional product candidates in development include Japanese BCG Laboratory’s BCG Tokyo, Pfizer

Inc.’s Sasanlimab in combination with BCG, ImmunityBio, Inc.’s VesAnktiva in combination with BCG, CG Oncology Inc.’s

CG0070, Sesen Bio, Inc.’s Vicineum, enGene Inc.’s, EG-70, Seagen Inc.’s PADCEV, Janssen’s TAR200 combined with

gemcitabine plus or minus Cetrelimab, Urogen Pharma Ltd.’s Jelmyto,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

Pharmaceuticals, Inc., AstraZeneca PLC, Bristol-Myers Squibb Company, Roche Group, Asieris Pharmaceuticals, BeiGene, Ltd, NanOlogy, LLC,

Linton Pharm Co., Ltd., Lindis Biotech GmbH, Theralase Technologies Inc., Taizhou Hanzhong biomedical co.

Ltd., Shionogi & Co., Ltd.,

Rapamycin Holdings, Inc., Vaxiion Therapeutics Inc., Incyte Corporation, LiPac Oncology, Inc., Anika Therapeutics Inc., Surge Pharmaceuticals

TARA-002, if approved for the treatment of NMIBC, would be subject

to competition from existing treatment methods of surgery, chemotherapy and immunomodulatory therapy.

For example, the current standard

of care for NMIBC includes intravesical BCG TICE (manufactured by Merck & Co., Inc.).

Other products approved for the treatment of

NMIBC include Merck & Co., Inc.’s Keytruda, Endo International plc’s Valstar, and Ferring B.V.’s Adstiladrin.

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, ImmunityBio, Inc.’s VesAnktiva in combination with BCG, CG Oncology Inc.’s CG0070, enGene Inc.’s,

EG-70, Seagen 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 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.

Ltd., Shionogi & Co.

Ltd., Rapamycin Holdings, Inc., Vaxiion Therapeutics Inc., Incyte Corporation,

LiPac Oncology, Inc., Anika Therapeutics Inc., Surge Pharmaceuticals Pvt.

Ltd., and Istari Oncology, Inc.

There are no treatments

currently available for IFALD.

With respect to IV Choline Chloride for the treatment of IFALD, IV Choline Chloride is the only sterile

injectable form of choline chloride that can be combined with parenteral nutrition.

Further, if approved, IV Choline Chloride will be

protected by Orphan Drug Designation exclusivity for seven years.

Government Regulation and Product Approval

The FDA and other regulatory

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,

record keeping, approval, advertising, promotion, marketing, post-approval monitoring, and post-approval reporting of drugs and biologics

such as those we are developing.

We, along with third-party contractors, will be required to navigate the various preclinical, clinical

and commercial approval requirements of the governing regulatory agencies of the countries in which we wish to conduct studies or seek

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 process required by the FDA before biopharmaceutical product

candidates may be marketed in the United States generally involves the following:

are no treatments currently available for patients on PN who are choline-deficient.

IV Choline Chloride is the only sterile injectable

form of choline chloride that can be combined with parenteral nutrition.

Further, the U.S.

Patent and Trademark Office, or USPTO, issued

to us Patent No.

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

Regulation and Product Approval

FDA and other regulatory 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, record keeping, approval, advertising, promotion, marketing, post-approval monitoring, and post-approval reporting

of drugs and biologics such as those we are developing.

We, along with third-party contractors, will be required to navigate the various

preclinical, clinical and commercial approval requirements of the governing regulatory agencies of the countries in which we wish to

conduct studies or seek approval or licensure of our product candidates.

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 process required by the FDA before biopharmaceutical

product candidates may be marketed in the United States generally involves the following:

of preclinical laboratory tests and animal studies performed in accordance with the FDA’s current Good Laboratory Practices,

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use in the United States.

Preclinical and Clinical Development

Prior to beginning the first

clinical trial with a product candidate, we must submit an IND to the FDA.

An IND is a request for authorization from the FDA to administer

an investigational new drug product to humans.

The central focus of an IND submission is on the general investigational plan and the

protocol(s) for clinical trials.

The IND also 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;

available human data or literature to support the use of the investigational product.

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 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

GCPs, which include the requirement that all research subjects provide their informed consent for their participation in any clinical

Clinical trials are conducted under protocols detailing, among other things, the objectives of the 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 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 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 trial may move forward at designated check points based on access to certain data from the trial and may halt the clinical

trial if it determines that there is an unacceptable safety risk for subjects or other grounds, such as no demonstration of efficacy.

and Clinical Development

to beginning the first clinical trial with a product candidate, we must submit an IND to the FDA.

An IND is a request for authorization

from the FDA to administer an investigational new drug product to humans.

The central focus of an IND submission is on the general investigational

plan and the protocol(s) for clinical trials.

The IND also includes results of animal and in vitro studies assessing the toxicology,

pharmacokinetics, pharmacology, and pharmacodynamic characteristics of the product candidate;

chemistry, manufacturing, and controls

and any available human data or literature to support the use of the investigational product.

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 can begin.

Submission of an IND therefore may or may not result in FDA authorization to begin a clinical trial.

trials involve the administration of the investigational product to human subjects under the supervision of qualified investigators in

accordance with GCPs, which include the requirement that all research subjects provide their informed consent for their participation

in any clinical trial.

Clinical trials are conducted under protocols detailing, among other things, the objectives of the 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 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 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 trial may move forward at designated check points based on access to certain data from the trial and

may halt the clinical trial if it determines that there is an unacceptable safety risk for subjects or other grounds, such as no demonstration

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 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.

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 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.

2—The investigational product is administered to a limited patient population with a specified disease or condition to evaluate

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provide an adequate basis for product approval.

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

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 so-called Phase 4 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.

Application Submission, Review and Approval

Assuming successful completion

of all required testing in accordance with all applicable regulatory requirements, the results of product development, nonclinical 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 pertinent 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.

Once an NDA or BLA has been

submitted, the FDA’s goal is to review standard applications within ten months after it accepts the application for filing, or,

if the application qualifies for priority review, six months after the FDA accepts the application for filing.

In both standard and priority

reviews, the review process is often significantly 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 to provide clinical insight on application review questions.

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 GCP.

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 may 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.

A Complete Response letter will describe all of the deficiencies that the FDA has identified in the NDA or

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 regulatory approval of

a product is granted, such approval will be granted for particular indications and may entail 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

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 Phase 4 post-market

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.

Orphan Drug Designation

Under the Orphan Drug Act,

the FDA may grant orphan 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 designation must be requested

before submitting an NDA or BLA.

After the FDA grants orphan designation, the generic identity of the therapeutic agent and its potential

orphan use are disclosed publicly by the FDA.

The orphan drug designation does not convey any advantage in, or shorten the duration of,

the regulatory review or approval process.

If a product that has orphan

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.

Orphan 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 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.

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 for a rare pediatric disease may be eligible for a voucher

that can be used to obtain a priority review for a subsequent human drug or biologic application after the date of approval of the rare

pediatric disease drug product, referred to as a priority review voucher, or PRV.

A rare pediatric disease designation does not guarantee

that a sponsor will receive a PRV upon approval of its NDA or BLA.

If a PRV is received, it may be sold or transferred an unlimited number

Congress has extended the PRV program until September 30, 2024, with the potential for PRVs to be granted until September

Post-Approval Requirements

Any products manufactured

or distributed pursuant to FDA approvals are subject to pervasive and continuing regulation by the FDA, including, among other things,

requirements relating to quality control and quality assurance, record-keeping, reporting of adverse experiences, periodic reporting,

product sampling and distribution, and advertising and promotion of the product.

After approval, most changes to the approved product,

such as adding new indications or other labeling claims, are subject to prior FDA review and approval.

There also are continuing user

fee requirements, under which FDA assesses an annual program fee for each product identified in an approved NDA or BLA.

Biopharmaceutical

manufacturers and their subcontractors are required to register their establishments with the FDA and certain state agencies, and are

subject to periodic unannounced inspections by the FDA and certain state agencies for compliance with cGMP, which impose certain procedural

and documentation requirements upon sponsors and their third-party manufacturers.

Changes to the manufacturing process are strictly regulated,

and, depending on the significance of the change, may require prior FDA approval before being implemented.

FDA regulations also require

investigation and correction of any deviations from cGMP and impose reporting requirements upon sponsor and third-party manufacturers.

Accordingly, manufacturers must continue to expend time, money and effort in the area of production and quality control to maintain compliance

with cGMP and other aspects of regulatory compliance.

The FDA may withdraw approval

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;

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.

Submission, Review and Approval

successful completion of all required testing in accordance with all applicable regulatory requirements, the results of product development,

nonclinical 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 pertinent 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.

an NDA or BLA has been submitted, the FDA’s goal is to review standard applications within ten months after it accepts the application

for filing, or, if the application qualifies for priority review, six months after the FDA accepts the application for filing.

standard and priority reviews, the review process is often significantly 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 to provide clinical insight on application review questions.

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 GCP.

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.

FDA may 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.

A Complete 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.

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.

regulatory approval of a product is granted, such approval will be granted for particular indications and may entail 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 Phase

4 post-market 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.

Drug Designation

the Orphan Drug Act, the FDA may grant orphan 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 designation

must be requested before submitting an NDA or BLA.

After the FDA grants orphan designation, the generic identity of the therapeutic agent

and its potential orphan use are disclosed publicly by the FDA.

The orphan drug designation does not convey any advantage in, or shorten

the duration of, the regulatory review or approval process.

a product that has orphan 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.

Orphan 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.

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 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.

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 for a rare

pediatric disease may be eligible for a voucher that can be used to obtain a priority review for a subsequent human drug or biologic

application after the date of approval of the rare pediatric disease drug product, referred to as a priority review voucher, or PRV.

A rare pediatric disease designation does not guarantee that a sponsor will receive a PRV upon approval of its NDA or BLA.

received, it may be sold or transferred an unlimited number of times.

Congress has extended the PRV program until September 30,

2024, with the potential for PRVs to be granted until September 30, 2026.

Post-Approval

products manufactured or distributed pursuant to FDA approvals are subject to pervasive and continuing regulation by the FDA, including,

among other things, requirements relating to quality control and quality assurance, record-keeping, reporting of adverse experiences,

periodic reporting, product sampling and distribution, and advertising and promotion of the product.

After approval, most changes to

the approved product, such as adding new indications or other labeling claims, are subject to prior FDA review and approval.

are continuing user fee requirements, under which FDA assesses an annual program fee for each product identified in an approved NDA or

Biopharmaceutical manufacturers and their subcontractors are required to register their establishments with the FDA and certain

state agencies, and are subject to periodic unannounced inspections by the FDA and certain state agencies for compliance with cGMP, which

impose certain procedural and documentation requirements upon sponsors and their third-party manufacturers.

Changes to the manufacturing

process are strictly regulated, and, depending on the significance of the change, may require prior FDA approval before being implemented.

FDA regulations also require investigation and correction of any deviations from cGMP and impose reporting requirements upon sponsor

and third-party manufacturers.

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

quality control to maintain compliance with cGMP and other aspects of regulatory compliance.

FDA may withdraw approval 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;

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:

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consent decrees or the imposition of civil or criminal penalties.

The FDA closely regulates

the marketing, labeling, advertising and promotion of biopharmaceuticals.

A company can make only those claims relating to safety and

efficacy, purity and potency of a biopharmaceutical that are approved by the FDA and in accordance with the provisions of the approved

FDA closely regulates the marketing, labeling, advertising and promotion of biopharmaceuticals.

A company can make only those claims

relating to safety and efficacy, purity and potency of a biopharmaceutical that are approved by the FDA and in accordance with the provisions

of the approved label.

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

Failure to comply

with these requirements can result in, among other things, adverse publicity, warning letters, corrective advertising and potential civil

and criminal penalties.

Physicians may prescribe legally available products for uses that are not described in the product’s labeling

and that differ from those approved by the FDA.

Failure to comply with these requirements can result in, among other things, adverse publicity, warning letters, corrective advertising

and potential civil and criminal penalties.

Physicians may prescribe legally available products for uses that are not described in the

product’s labeling and that differ from those approved by the FDA.

Such off-label uses are common across medical specialties.

Physicians may believe that

such off-label uses are the best treatment for many patients in varied circumstances.

The FDA does not regulate the behavior of physicians

in their choice of treatments.

The FDA does, however, restrict manufacturer’s communications on the subject of off-label use of

their products.

Biosimilars and Reference Product Exclusivity

The Patient Protection and

Affordable Care Act, as amended by the Health Care and Education Reconciliation Act, or ACA, signed into law in 2010, includes a subtitle

called the Biologics Price Competition and Innovation Act of 2009, or BPCIA, which created an abbreviated approval pathway for biological

products that are biosimilar to or interchangeable with an FDA-approved reference biological product.

To date, a number of biosimilars

have been licensed under the BPCIA, and numerous biosimilars have been approved in Europe.

The FDA has issued several guidance documents

outlining its approach to the review and approval of biosimilars.

Biosimilarity, which

requires that there be no clinically meaningful differences between the biological product and the reference product in terms of

may believe that such off-label uses are the best treatment for many patients in varied circumstances.

The FDA does not regulate the

behavior of physicians in their choice of treatments.

The FDA does, however, restrict manufacturer’s communications on the subject

of off-label use of their products.

and Reference Product Exclusivity

Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act, or ACA, signed into law in

2010, includes a subtitle called the Biologics Price Competition and Innovation Act of 2009, or BPCIA, which created an abbreviated approval

pathway for biological products that are biosimilar to or interchangeable with an FDA-approved reference biological product.

a number of biosimilars have been licensed under the BPCIA, and numerous biosimilars have been approved in Europe.

The FDA has issued

several guidance documents outlining its approach to the review and approval of biosimilars.

Biosimilarity,

which requires that there be no clinically meaningful differences between the biological product and the reference product in terms of

safety, purity, and potency, can be shown through analytical studies, animal studies, and a clinical trial or trials.

Interchangeability requires that a product is biosimilar to the reference product and the product must demonstrate 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

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.

During this 12-year period of exclusivity, another company may still market a competing version

of the reference product if the FDA approves a full BLA for the competing product containing that applicant’s own preclinical data

and data from adequate and well-controlled clinical trials to demonstrate the safety, purity and potency of its product.

The BPCIA also

created certain exclusivity periods for biosimilars approved as interchangeable products.

At this juncture, it is unclear whether products

deemed “interchangeable” by the FDA will, in fact, be readily substituted by pharmacies, which are governed by state pharmacy

The BPCIA is complex and

continues to be interpreted and implemented by the FDA.

In addition, recent government proposals have sought to reduce the 12-year reference

product exclusivity period.

Other aspects of the BPCIA, some of which may impact the BPCIA exclusivity provisions, have also been the

subject of recent litigation.

As a result, the ultimate impact, implementation, and impact of the BPCIA is subject to significant uncertainty.

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),

Interchangeability

requires that a product is biosimilar to the reference product and the product must demonstrate 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.

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 by the FDA.

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.

During this 12-year period of exclusivity, another company may

still market a competing version of the reference product if the FDA approves a full BLA for the competing product containing that applicant’s

own preclinical data and data from adequate and well-controlled clinical trials to demonstrate the safety, purity and potency of its

The BPCIA also created certain exclusivity periods for biosimilars approved as interchangeable products.

At this juncture, it

is unclear whether products deemed “interchangeable” by the FDA will, in fact, be readily substituted by pharmacies, which

are governed by state pharmacy law.

BPCIA is complex and continues to be interpreted and implemented by the FDA.

In addition, recent government proposals have sought to

reduce the 12-year reference product exclusivity period.

Other aspects of the BPCIA, some of which may impact the BPCIA exclusivity provisions,

have also been the subject of recent litigation.

As a result, the ultimate impact, implementation, and impact of the BPCIA is subject

to significant uncertainty.

Healthcare Laws and Compliance Requirements

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.

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), the U.S.

Department of Justice, or DOJ and individual U.S.

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.

The federal Anti-Kickback

Statute prohibits, among other things, any person or entity, from knowingly and willfully offering, paying, soliciting or receiving any

remuneration, directly or indirectly, overtly or covertly, in cash or in kind, to induce or in return for purchasing, leasing, ordering

or arranging for the purchase, lease or order of any item or service reimbursable, in whole or in part, under Medicare, Medicaid or other

federal healthcare programs.

Attorney offices within the DOJ, and state and local

For example, 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.

federal Anti-Kickback Statute prohibits, among other things, any person or entity, from knowingly and willfully offering, paying, soliciting

or receiving any remuneration, directly or indirectly, overtly or covertly, in cash or in kind, to induce or in return for purchasing,

leasing, ordering or arranging for the purchase, lease or order of any item or service reimbursable, in whole or in part, under Medicare,

Medicaid or other federal healthcare programs.

The term remuneration has been interpreted broadly to include anything of value.

The Anti-Kickback Statute

has been interpreted to apply to arrangements between therapeutic product manufacturers on one hand and prescribers, purchasers, and

formulary managers on the other.

The Anti-Kickback

Statute has been interpreted to apply to arrangements between therapeutic product manufacturers on one hand and prescribers, purchasers,

and formulary managers on the other.

There are a number of statutory exceptions and regulatory safe harbors protecting some common activities

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for protection under a statutory exception or regulatory safe harbor.

Additionally, the intent

standard under the Anti-Kickback Statute was amended by the Patient Protection and Affordable Care Act, as amended by the Health Care

and Education Reconciliation Act of 2010, or the Affordable Care Act, 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 Affordable

Care Act 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).

The federal false claims,

including the FCA, and civil monetary penalty laws, which imposes significant penalties and can be enforced by private citizens through

civil qui tam actions, prohibit any person or entity from, among other things, knowingly presenting, or causing to be presented, a false

or fraudulent claim for payment to, or approval by, the federal government, including federal healthcare programs, such as Medicare and

Medicaid, knowingly making, using, or causing to be made or used a false record or statement material to a false or fraudulent claim

to the federal government, or knowingly making a false statement to improperly avoid, decrease or conceal an obligation to pay money

to the federal government.

Additionally,

the intent standard under the Anti-Kickback Statute was amended by the Patient Protection and Affordable Care Act, as amended by the

Health Care and Education Reconciliation Act of 2010, or the Affordable Care Act, 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.

the Affordable Care Act 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).

federal false claims, including the FCA, and civil monetary penalty laws, which imposes significant penalties and can be enforced by

private citizens through civil qui tam actions, prohibit any person or entity from, among other things, knowingly presenting, or causing

to be presented, a false or fraudulent claim for payment to, or approval by, the federal government, including federal healthcare programs,

such as Medicare and Medicaid, knowingly making, using, or causing to be made or used a false record or statement material to a false

or fraudulent claim to the federal government, or knowingly making a false statement to improperly avoid, decrease or conceal an obligation

to pay money to the federal government.

A claim includes “any request or demand” for money or property presented to the U.S.

For instance, historically, pharmaceutical and other healthcare companies have been prosecuted under these laws for allegedly providing

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

Other companies have been

prosecuted for causing false claims to be submitted because of the companies’ marketing of the product for unapproved, off-label,

and thus generally non-reimbursable, uses.

HIPAA created additional

federal criminal statutes that prohibit, among other things, knowingly and willfully executing, or attempting to execute, a scheme to

defraud or to obtain, by means of false or fraudulent pretenses, representations or promises, any money or property owned by, or under

the control or custody of, any healthcare benefit program, including private third-party payors, willfully obstructing a criminal investigation

of a healthcare offense, and knowingly and willfully falsifying, concealing or covering up by trick, scheme or device, a material fact

or making any materially false, fictitious or fraudulent statement in connection with the delivery of or payment for healthcare benefits,

items or services.

Like the Anti-Kickback Statute, the Affordable Care Act 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.

For instance, historically, pharmaceutical and other healthcare companies have been prosecuted under these laws for allegedly

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

Other companies

have been prosecuted for causing false claims to be submitted because of the companies’ marketing of the product for unapproved,

off-label, and thus generally non-reimbursable, uses.

created additional federal criminal statutes that prohibit, among other things, knowingly and willfully executing, or attempting to execute,

a scheme to defraud or to obtain, by means of false or fraudulent pretenses, representations or promises, any money or property owned

by, or under the control or custody of, any healthcare benefit program, including private third-party payors, willfully obstructing a

criminal investigation of a healthcare offense, and knowingly and willfully falsifying, concealing or covering up by trick, scheme or

device, a material fact or making any materially false, fictitious or fraudulent statement in connection with the delivery of or payment

for healthcare benefits, items or services.

Like the Anti-Kickback Statute, the Affordable Care Act 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.

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.

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.

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.

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

law, certain products not

usually self-administered (including injectable drugs) may be eligible for coverage under Medicare through Medicare Part B.

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

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

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

addition, many pharmaceutical manufacturers must calculate and report certain price reporting metrics to the government, such as average

sales price, or ASP, 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.

is 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.

Additionally, the federal

Physician Payments Sunshine Act, or the Sunshine Act, within the Affordable Care Act, and its implementing regulations, require that

certain manufacturers of drugs, devices, biological and medical supplies for which payment is available under Medicare, Medicaid or the

Children’s Health 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),

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.

It is 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.

Additionally,

the federal Physician Payments Sunshine Act, or the Sunshine Act, within the Affordable Care Act, and its implementing regulations, require

that certain manufacturers of drugs, devices, biological and medical supplies for which payment is available under Medicare, Medicaid

or the Children’s Health 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 professionals (such as physicians assistants and nurse practitioners) and teaching hospitals, or to entities or individuals

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are often not pre-empted, and may have a more prohibitive effect than the Sunshine Act, thus further complicating compliance efforts.

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

All of our 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.

Coverage, Pricing and Reimbursement

Significant uncertainty

exists 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:

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.

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.

Pricing and Reimbursement

uncertainty exists 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.

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:

covered benefit under its health plan;

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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.

Third-party payors are increasingly

challenging the price, examining the medical necessity, and reviewing the cost-effectiveness of medical products, therapies and services,

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.

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 will be.

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 we

obtain regulatory approval.

payors are increasingly challenging the price, examining the medical necessity, and reviewing the cost-effectiveness of medical products,

therapies and services, 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.

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 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.

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.

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.

Different pricing and reimbursement

schemes exist in other countries.

In the European Union, governments influence the price of biopharmaceutical products through their

pricing and reimbursement rules and control of national health care systems that fund a large part of the cost of those products to consumers.

Some jurisdictions operate positive and negative list systems under which products may only be marketed once a reimbursement price has

To obtain reimbursement or pricing approval, some of these countries may require the completion of clinical trials that

compare the cost effectiveness of a particular product candidate to currently available therapies.

Other member states allow companies

to fix their own prices for medicines but monitor and control company profits.

The downward pressure on health care costs has become

pricing and reimbursement schemes exist in other countries.

In the European Union, governments influence the price of biopharmaceutical

products through their pricing and reimbursement rules and control of national health care systems that fund a large part of the cost

of those products to consumers.

Some jurisdictions operate positive and negative list systems under which products may only be marketed

once a reimbursement price has been agreed.

To obtain reimbursement or pricing approval, some of these countries may require the completion

of clinical trials that compare the cost effectiveness of a particular product candidate to currently available therapies.

states allow companies to fix their own prices for medicines but monitor and control company profits.

The downward pressure on health

care costs has become intense.

As a result, increasingly high barriers are being erected to the entry of new products.

In addition, in some countries, cross-border

imports 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.

In addition, in

some countries, cross-border imports from low-priced markets exert a commercial pressure on pricing within a country.

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, the Affordable

Care Act has substantially changed healthcare financing and delivery by both governmental and private insurers.

Among the Affordable

Care Act provisions of importance to the pharmaceutical and biotechnology industries, in addition to those otherwise described above,

are the following:

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.

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.

example, the Affordable Care Act has substantially changed healthcare financing and delivery by both governmental and private insurers.

Among the Affordable Care Act provisions of importance to the pharmaceutical and biotechnology industries, in addition to those otherwise

described above, are the following:

annual, nondeductible fee on any entity that manufactures or imports certain specified branded prescription drugs and biologic agents

3 unchanged sentences

at 100% of the Average Manufacturer Price, or the AMP;

new Medicare Part D coverage gap discount program, in which manufacturers must now agree to offer 70% point-of-sale discounts off

negotiated prices of applicable brand drugs to eligible beneficiaries during their coverage gap period, as a condition for the manufacturers’

outpatient drugs to be covered under Medicare Part D;

a Medicare Part D coverage gap discount program, in which manufacturers must agree to offer 70% point-of-sale discounts off negotiated prices of applicable brand drugs to eligible beneficiaries during their coverage gap period, as a condition for the manufacturers’ outpatient drugs to be covered under Medicare Part D;

extension of manufacturers’ Medicaid rebate liability to covered drugs dispensed to individuals who are enrolled in Medicaid

23 unchanged sentences

tax on high-cost employer-sponsored health coverage and medical device tax and also eliminated the health insurer tax.

On June 17, 2021,

In June 2021, the

Supreme Court dismissed a challenge on procedural grounds that argued the Affordable Care Act is unconstitutional in its entirety

2 unchanged sentences

Further, prior to the U.S.

Supreme Court ruling, on January 28, 2021, President Biden issued an executive order to initiate a special

Supreme Court ruling, in January 2021, President Biden issued an executive order to initiate a special

enrollment period for purposes of obtaining health insurance coverage through the Affordable Care Act marketplace.

1 unchanged sentence

also instructed certain governmental agencies to review and reconsider their existing policies and rules that limit access to healthcare,

including among others, reexamining Medicaid demonstration projects and waiver programs that include work requirements, and policies

that create unnecessary barriers to obtaining access to health insurance coverage through Medicaid or the Affordable Care Act.

possible that the Affordable Care Act will be subject to judicial or Congressional challenges in the future.

including among others, reexamining Medicaid demonstration projects and waiver programs that include work requirements, and policies that

create unnecessary barriers to obtaining access to health insurance coverage through Medicaid or the Affordable Care Act.

It is possible

that the Affordable Care Act will be subject to judicial or Congressional challenges in the future.

It is unclear how such challenges

and the healthcare reform measures of the Biden administration will impact the Affordable Care Act and our business.

We anticipate that the Affordable

Care Act, if substantially maintained in its current form, will continue to result in additional downward pressure on coverage and the

price that we receive for any approved product, and could seriously harm our business.

Any reduction in reimbursement from Medicare and

other government programs may result in a similar reduction in payments from private payors.

The implementation of cost containment measures

or other healthcare reforms may prevent us from being able to generate revenue, attain profitability, or commercialize our products.

Such reforms could have an adverse effect on anticipated revenue from product candidates that we may successfully develop and for which

we may obtain regulatory approval and may affect our overall financial condition and ability to develop product candidates.

anticipate that the Affordable Care Act, if substantially maintained in its current form, will continue to result in additional downward

pressure on coverage and the price that we receive for any approved product, and could seriously harm our business.

Any reduction in

reimbursement from Medicare and other government programs may result in a similar reduction in payments from private payors.

The implementation

of cost containment measures or other healthcare reforms may prevent us from being able to generate revenue, attain profitability, or

commercialize our products.

Such reforms could have an adverse effect on anticipated revenue from product candidates that we may successfully

develop and for which we may obtain regulatory approval and may affect our overall financial condition and ability to develop product

Further legislation or regulation

14 unchanged sentences

varied from 1% in 2022 to up to 3% in the final fiscal year of this sequester.

Additionally, on March 11, 2021, President Biden signed

the American Rescue Plan Act of 2021 into law, which eliminates the statutory Medicaid drug rebate cap, currently set at 100% of a drug’s

average manufacturer price, for single source and innovator multiple source drugs, beginning January 1, 2024.

In January 2013, the American

Taxpayer Relief Act of 2012 was signed into law, which, among other things, further reduced Medicare payments to several types of providers,

including hospitals, imaging centers and cancer treatment centers, and increased the statute of limitations period for the government

to recover overpayments to providers from three to five years.

Additionally, there has

been increasing legislative and enforcement interest in the United States with respect to specialty drug pricing practices.

Specifically,

there have been several recent U.S.

Congressional inquiries and proposed federal legislation designed to, among other things, bring more

transparency to drug pricing, reduce the cost of prescription drugs under Medicare, review the relationship between pricing and manufacturer

patient programs, and reform government program reimbursement methodologies for drugs.

For example, the Trump administration used several

means to propose or implement drug pricing reform, including through federal budget proposals, executive orders and policy initiatives.

For example, on July 24, 2020 and September 13, 2020, the Trump administration announced several executive orders related to prescription

drug pricing that attempt to implement several of the administration’s proposals.

The FDA also released a final rule and guidance

implementing a portion of the importation executive order providing pathways for states to build and submit importation plans for drugs

Further, on November 20, 2020, the Department of Health and Human Services, or HHS, finalized a regulation removing safe

harbor protection for price reductions from pharmaceutical manufacturers to plan sponsors under Part D, either directly or through pharmacy

benefit managers, unless the price reduction is required by law.

The implementation of the rule was delayed by the Biden administration

from January 1, 2022 to January 1, 2023 in response to ongoing litigation.

The rule also creates a new safe harbor for price reductions

reflected at the point-of-sale, as well as a new safe harbor for certain fixed fee arrangements between pharmacy benefit managers and

manufacturers, the implementation of which also was delayed until January 1, 2023.

On November 20, 2020, CMS issued an interim final

rule implementing former President Trump’s Most Favored Nation, or MFN, executive order, which would tie Medicare Part B payments

for certain physician-administered drugs to the lowest price paid in other economically advanced countries, and was effective as of January

As a result of litigation challenging the MFN model, on August 10, 2021, CMS published a proposed rule that rescinded the MFN

model interim final rule.

As a result of litigation challenging the MFN model, on December 27, 2021, CMS published a final rule that

rescinded the Most Favored Nation model interim final rule.

In July 2021, the Biden administration released an executive order, “Promoting

Competition in the American Economy,” with multiple provisions aimed at prescription drugs.

In response to Biden’s executive

order, on September 9, 2021, HHS released a Comprehensive Plan for Addressing High Drug Prices that outlines principles for drug pricing

reform and sets out a variety of potential legislative policies that Congress could pursue to advance these principles.

Additionally, in March 2021, President Biden signed the

American Rescue Plan Act of 2021 into law, which eliminated the statutory Medicaid drug rebate cap, which was previously set at 100% of

a drug’s average manufacturer price, for single source and innovator multiple source drugs, effective January 1, 2024.

Additionally, there has been

increasing legislative and enforcement interest in the United States with respect to specialty drug pricing practices.

Specifically, there

have been several recent U.S.

Congressional inquiries and proposed federal legislation designed to, among other things, bring more transparency

to drug pricing, reduce the cost of prescription drugs under Medicare, review the relationship between pricing and manufacturer patient

programs, and reform government program reimbursement methodologies for drugs.

For example, the Trump administration used several means

to propose or implement drug pricing reform, including through federal budget proposals, executive orders and policy initiatives.

example, in July 2020 and September 2020, the Trump administration announced several executive orders related to prescription drug pricing

that attempt to implement several of the administration’s proposals.

The FDA also released a final rule and guidance implementing

a portion of the importation executive order providing pathways for states to build and submit importation plans for drugs from Canada.

Further, in November 2020, the Department of Health and Human Services, or HHS, finalized a regulation removing safe harbor protection

for price reductions from pharmaceutical manufacturers to plan sponsors under Part D, either directly or through pharmacy benefit managers,

unless the price reduction is required by law.

The implementation of the rule was delayed by the Biden administration from January 1,

2022 to January 1, 2023 in response to ongoing litigation.

The rule also created a new safe harbor for price reductions reflected at the

point-of-sale, as well as a new safe harbor for certain fixed fee arrangements between pharmacy benefit managers and manufacturers, the

implementation of which also was delayed until January 1, 2023.

In January 2024, the FDA authorized the state of Florida to import certain

prescription drugs from Canada, and future authorizations may occur.

In July 2021, the Biden administration released an executive order,

“Promoting Competition in the American Economy,” with multiple provisions aimed at prescription drugs.

In response to Biden’s

executive order, in September 2021, HHS released a Comprehensive Plan for Addressing High Drug Prices that outlines principles for drug

pricing reform and sets out a variety of potential legislative policies that Congress could pursue to advance these principles.

No legislation

or administrative actions have been finalized to implement these principles.

In addition, on August 16, 2022, President Biden signed

into law the Inflation Reduction Act of 2022, which, among other things, contains substantial drug pricing reforms that will reduce drug

spending by the federal government.

In addition, on August 16, 2022, President Biden signed into

law the Inflation Reduction Act of 2022, which, among other things, contains substantial drug pricing reforms that will reduce drug spending

by the federal government.

For example, the Inflation Reduction Act of 2022 limits the prices paid by Medicare for various prescription

1 unchanged sentence

beneficiaries.

Although the effect of the Inflation Reduction Act of 2022 on our business and the pharmaceutical industry in general

is not yet known, the Inflation Reduction Act of 2022 could affect the prices we can charge and the reimbursement we can receive for

our product candidates, if approved, thereby reducing our profitability.

We also expect that additional state and federal healthcare

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

Although the effect of the Inflation Reduction Act of 2022 on our business and the pharmaceutical industry in general is

not yet known, the Inflation Reduction Act of 2022 could affect the prices we can charge and the reimbursement we can receive for our

product candidates, if approved, thereby reducing our profitability.

We also expect that additional state and federal healthcare reform

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

products and services, which could result in reduced demand for our product candidates if approved or additional pricing pressures.

The Foreign Corrupt Practices Act

The Foreign Corrupt Practices

Act, or the FCPA, prohibits any U.S.

individual or business from paying, offering, or authorizing payment or offering of anything of

value, directly or indirectly, to any foreign official, political party or candidate for the purpose of influencing any act or decision

of the foreign entity in order to assist the individual or business in obtaining or retaining business.

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.

Additional Regulation

In addition to the foregoing,

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.

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.

Foreign Corrupt Practices Act

Foreign Corrupt Practices Act, or the FCPA, prohibits any U.S.

individual or business from paying, offering, or authorizing payment or

offering of anything of value, directly or indirectly, to any foreign official, political party or candidate for the purpose of influencing

any act or decision of the foreign entity in order to assist the individual or business in obtaining or retaining business.

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.

addition to the foregoing, 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.

other laws govern our use, handling and disposal of various biological, chemical and radioactive substances used in, and wastes generated

by, our 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.

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.

of December 31, 2023, we had 27 employees, 26 of whom were full-time employees and one of whom was a temporary employee.

As of December

we had 25 employees, all of whom were full-time employees.

As of December 31, 2022, 13 of our employees were engaged in research and

development activities and 12 of our employees were engaged in business development, legal, finance, market development, information

systems, facilities, human resources or administrative support.

As of December 31, 2022, all of our employees were located in the United

None of our United States employees are represented by any collective bargaining agreements.

We believe that we maintain good

relations with our employees.

COVID-19 and Related Macroeconomic Conditions

The COVID-19 pandemic and

related macroeconomic conditions, such as supply chain shortages, inflation and economic volatility have, and may continue to have, an

impact on our results of operations.

We will continue to monitor whether such conditions would have a material impact on our operations,

liquidity and capital resources.

Further, rising inflation has, in part, caused a disruption in the capital markets, which may lead to

a recession or market correction that could impact our access to capital, and could in the future negatively affect our liquidity.

recession or market correction, continued supply chain disruptions and/or inflation could materially affect our business and the value

of our common stock.

See “ —Risks Related to Our Financial Condition ” below.

Corporate Information

On January 9, 2020, Protara

Therapeutics, Inc.

(formerly ArTara Therapeutics, Inc., formerly Proteon Therapeutics, Inc., or the Company or Protara), and privately-held

ArTara Subsidiary, Inc., or Private ArTara, completed the merger and reorganization, or the Merger, in accordance with the terms of the

Agreement and Plan of Merger and Reorganization, dated September 23, 2019, or the Merger Agreement, by and among the Company, Private

ArTara and REM 1 Acquisition, Inc., a wholly owned subsidiary of the Company, or Merger Sub, whereby Merger Sub merged with and into

Private ArTara, with Private ArTara surviving as a wholly owned subsidiary of the Company.

The Merger was structured as a reverse merger

and Private ArTara was determined to be the accounting acquirer based on the terms of the Merger and other factors.

We were originally incorporated

in Delaware in March 2006, and at that time, acquired Proteon Therapeutics, LLC, the predecessor of Protara, which was formed in June

Our principal executive

offices are located at 345 Park Avenue South, 3 rd Floor, New York, New York 10010, our telephone number is (646) 844-0337

and our website address is www.protaratx.com.

The contents of our website are not incorporated into this Annual Report on Form 10-K and

our reference to the URL for our website is intended to be an inactive textual reference only.

The information contained on, or that

can be accessed through, our website is not a part of this document.

Unless the context requires

otherwise, references in this Annual Report on Form 10-K to “Protara”, “TARA”, “we”, “us”,

the “Company” and “our” refer to Protara Therapeutics, Inc.

(formerly ArTara Therapeutics, Inc., formerly Proteon

Therapeutics, Inc.) and our subsidiaries.

Available Information

Annual Reports on Form 10-K,

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.

31, 2023, 17 of our employees were engaged in research and development activities and 10 of our employees were engaged in business development,

legal, finance, market development, information systems, facilities, human resources or administrative support.

As of December 31, 2023,

all of our employees were located in the United States.

None of our United States employees are represented by any collective bargaining

We believe that we maintain good relations with our employees.

January 9, 2020, Protara Therapeutics, Inc.

(formerly ArTara Therapeutics, Inc., formerly Proteon Therapeutics, Inc., or the Company

or Protara), and privately-held ArTara Subsidiary, Inc., or Private ArTara, completed the merger and reorganization, or the Merger, in

accordance with the terms of the Agreement and Plan of Merger and Reorganization, dated September 23, 2019, or the Merger Agreement,

by and among the Company, Private ArTara and REM 1 Acquisition, Inc., a wholly owned subsidiary of the Company, or Merger Sub, whereby

Merger Sub merged with and into Private ArTara, with Private ArTara surviving as a wholly owned subsidiary of the Company.

was structured as a reverse merger and Private ArTara was determined to be the accounting acquirer based on the terms of the Merger and

other factors.

were originally incorporated in Delaware in March 2006, and at that time, acquired Proteon Therapeutics, LLC, the predecessor of Protara,

which was formed in June 2001.

principal executive offices are located at 345 Park Avenue South, 3 rd Floor, New York, New York 10010, our telephone number

is (646) 844-0337 and our website address is www.protaratx.com.

The contents of our website are not incorporated into this Annual Report

on Form 10-K and our reference to the URL for our website is intended to be an inactive textual reference only.

The information contained

on, or that can be accessed through, our website is not a part of this document.

the context requires otherwise, references in this Annual Report on Form 10-K to “Protara”, “TARA”, “we”,

“us”, the “Company” and “our” refer to Protara Therapeutics, Inc.

(formerly ArTara Therapeutics,

Inc., formerly Proteon Therapeutics, Inc.) and our subsidiaries.

Reports on Form 10-K, 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.

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