What changed in this filing

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Item 1. Business

2022-03-03 compared with 2021-02-12 · 896 added, 854 removed, 121 unchanged (94% of the section changed)

We are a clinical pharmaceutical company

organized as a Nevada corporation in July 2017 to focus on the development of anti-cancer drug candidates for the treatment of

brain and central nervous system tumors, based on intellectual property that we license under license agreements with Houston Pharmaceuticals,

(“HPI”) and The University of Texas M.D.

Anderson Cancer Center (“UTMDACC”) and own pursuant to a

collaboration and asset purchase agreement with Reata Pharmaceuticals, Inc.

(“Reata”).

We are a clinical pharmaceutical company organized

as a Nevada corporation in July 2017 to focus on the development of anti-cancer drug candidates for the treatment of brain and central

nervous system tumors, based on intellectual property that we license under license agreements with Houston Pharmaceuticals, Inc.

and The University of Texas M.D.

Anderson Cancer Center (“UTMDACC”) and own pursuant to a collaboration and asset purchase

agreement with Reata Pharmaceuticals, Inc.

We believe our lead drug candidate, Berubicin,

if approved by the FDA, may be a significant discovery in the treatment of glioblastoma.

Glioblastoma are tumors that arise from

astrocytes, which are star-shaped cells making up the supportive tissue of the brain.

These tumors are usually highly malignant

(cancerous) because the cells reproduce quickly, and they are supported by a large network of blood vessels.

Berubicin is an anthracycline,

which is a class of drugs that are among the most powerful chemotherapy drugs known.

Based on limited clinical data, we believe

Berubicin is the first anthracycline that appears to have crossed the blood brain barrier and target brain cancer cells.

our current focus is solely on the development of Berubicin, we are also in the process of attempting to secure intellectual property

rights in additional compounds that may be developed into drugs to treat cancers.

Berubicin was discovered at MD Anderson

Waldemar Priebe, the founder of the Company.

may be a significant development in the treatment of Glioblastoma and other CNS malignancies, and if approved by the U.S.

Food and Drug

Administration (“FDA”), could give Glioblastoma patients an important new therapeutic alternative to the current standard

Glioblastomas are tumors that arise from astrocytes, which are star-shaped cells making up the supportive tissue of the brain.

These tumors are usually highly malignant (cancerous) because the cells reproduce quickly, and they are supported by a large network of

blood vessels.

Berubicin is an anthracycline, which is a class of drugs that are among the most powerful and extensively used chemotherapy

Based on limited clinical data, we believe Berubicin is the first anthracycline that appears to cross the blood brain barrier

in significant concentrations targeting brain cancer cells.

While our focus is currently on the development of Berubicin, we are also

in the process of attempting to secure intellectual property rights to additional compounds that we plan to develop into drugs to treat

CNS and other cancers.

Berubicin was discovered at UTMDACC by Dr.

Priebe, the founder of the Company.

Through a series of transactions, Berubicin was initially licensed to Reata.

Reata conducted a Phase I clinical trial on Berubicin but subsequently allowed their IND with the FDA to lapse for strategic reasons.

Reata initiated several

Phase I clinical trials with Berubicin for CNS malignancies, one of which was for malignant gliomas, but subsequently allowed their IND

with the FDA to lapse for strategic reasons.

This required us to obtain a new IND for Berubicin before beginning further clinical trials.

On December 17, 2020, we announced

that our IND application with the FDA for Berubicin for the treatment of Glioblastoma Multiforme was in effect.

We intend to initiate

our trial during the first quarter of 2021 to investigate the efficacy of Berubicin in adults with Glioblastoma Multiforme who

have failed first-line therapy.

Recent correspondence between us and the FDA resulted in modifications to our previously disclosed

trial design, including designating overall survival (OS) as the primary endpoint of the study.

OS is a rigorous endpoint that

the FDA has recognized as a basis for approval of oncology drugs when a statistically significant improvement can be shown relative

On December 17, 2020, we announced that our IND application with the FDA for Berubicin for the treatment of Glioblastoma Multiforme was

We initiated this trial for patient enrollment during the second quarter of 2021 with the first patient dosed during the third

quarter of 2021 to investigate the efficacy of Berubicin in adults with Glioblastoma Multiforme who have failed first-line therapy.

first patient on the trial was treated during the third quarter of 2021.

Correspondence between the Company and the FDA resulted in modifications

to our initial trial design, including designating overall survival (OS) as the primary endpoint of the study.

OS is a rigorous endpoint

that the FDA has recognized as a basis for approval of oncology drugs when a statistically significant improvement can be shown relative

to a randomized control arm.

The planned Phase 2 trial will evaluate

the efficacy of Berubicin in patients with Glioblastoma Multiforme who have failed primary treatment for their disease, and results

will be compared to the current standard of care, with 2 to 1 randomization of the 243 patients to Berubicin or Lomustine.

receiving Berubicin will be administered a 2-hour IV infusion of 7.5 mg/m2 berubicin hydrochloride daily for three consecutive

days followed by 18 days off (21-day cycle).

Lomustine is administered orally.

The trial will include an interim analysis that

will evaluate the comparative effectiveness of these treatments.

The trial's adaptive design is intended to allow this interim

analysis of the data to demonstrate meaningful differences in efficacy between treatments and then to allow an adjustment to the

size of the patient population in the trial for maximum efficiency in terms of time in development.

The current trial being conducted will evaluate

the efficacy of Berubicin in patients with Glioblastoma Multiforme who have failed primary treatment for their disease, and results will

be compared to the efficacy of Lomustine, a current standard of care in this setting, with a 2 to 1 randomization of the estimated 243

patients to Berubicin or Lomustine.

Patients receiving Berubicin will be administered a 2-hour IV infusion of 7.5 mg/m2 berubicin hydrochloride

daily for three consecutive days followed by 18 days off (a 21-day cycle).

Lomustine is administered orally once every six weeks.

trial will include an interim analysis that will evaluate the comparative effectiveness of these treatments, which is an adaptive design

intended to demonstrate that there are no differences in efficacy between treatments (futility analysis).

Even if Berubicin is approved,

there is no assurance that patients will choose an infusion treatment, as compared to the current standard of care, which requires

oral administration.

We do not have manufacturing facilities

and all manufacturing activities are contracted out to third parties.

there is no assurance that patients will choose an infusion treatment, as compared to the current standard of care, which requires oral

administration.

We do not have manufacturing facilities and all

manufacturing activities are contracted out to third parties.

Additionally, we do not have a sales organization.

On November 21, 2017, we entered into a

Collaboration and Asset Purchase Agreement with Reata (the “Reata Agreement”).

Pursuant to the Reata Agreement we purchased

all of Reata’s intellectual property and development data regarding Berubicin, including all trade secrets, knowhow, confidential

information and other intellectual property rights, which we refer to as the Reata Data.

On December 28, 2017, we obtained the rights

to a worldwide, exclusive royalty-bearing, license to the chemical compound commonly known as Berubicin from HPI in an agreement

we refer to as the HPI License.

On November 21, 2017, we entered into a Collaboration

and Asset Purchase Agreement with Reata (the “Reata Agreement”).

Pursuant to the Reata Agreement we purchased all of Reata’s

intellectual property and development data regarding Berubicin, including all trade secrets, knowhow, confidential information and other

intellectual property rights.

On December 28, 2017, we obtained the rights to

a worldwide, exclusive royalty-bearing, license to the chemical compound commonly known as Berubicin from HPI in an agreement we refer

to as the HPI License.

HPI is affiliated with Dr.

Priebe, who controls a majority of our shares.

Under the HPI License

we obtained the exclusive right to develop certain chemical compounds for use in the treatment of cancer anywhere in the world.

In the HPI License we agreed to pay HPI:

Under the HPI License we obtained the

exclusive right to develop certain chemical compounds for use in the treatment of cancer anywhere in the world.

In the HPI License we

agreed to pay HPI:

(i) development fees of $750,000 over a three-year period beginning November 2019;

a 2% royalty on net sales;

(ii) a 2% royalty on net sales;

(iii) a $50,000 per year license fee;

(iv) milestone payments of $100,000 upon the commencement of a

Phase II trial and $1.0 million upon the approval of an New Drug Application (“NDA”) for Berubicin;

and (v) 200,000

shares of our common stock.

The patents we licensed from HPI expired in March 2020.

On June 10, 2020, the FDA granted Orphan

Drug Designation (“ODD”) for Berubicin for the treatment of malignant gliomas.

ODD from the FDA is available for drugs

targeting diseases with less than 200,000 cases per year.

ODD may enable market exclusivity of 7 years from the date of approval

of a NDA in the United States.

During that period the FDA generally could not approve another product containing the same drug

for the same designated indication.

Orphan drug exclusivity will not bar approval of another product under certain circumstances,

including if a subsequent product with the same active ingredient for the same indication is shown to be clinically superior to

the approved product on the basis of greater efficacy or safety, or providing a major contribution to patient care, or if the company

with orphan drug exclusivity is not able to meet market demand.

The ODD now constitutes our primary intellectual property protections

although the Company is exploring if there are other patents that could be filed related to Berubicin to extend additional protections.

With the Reata Agreement and the HPI License,

we believe we have obtained all rights and intellectual property necessary to develop Berubicin.

As stated earlier, it is our plan

to obtain additional intellectual property covering other compounds which, subject to the receipt of additional financing, may

be developed into drugs for brain and other cancers.

On January 10, 2020, we entered into a Patent

and Technology License Agreement (the “1244 Agreement”) with The Board of Regents of The University of Texas System,

an agency of the State of Texas, on behalf of the UTMDACC.

Pursuant to the 1244 Agreement, we obtained a royalty-bearing, worldwide,

exclusive license to certain intellectual property rights, including patent rights, related to our WP1244 drug technology.

(iv) milestone payments of $100,000 upon the commencement of a Phase II trial and $1.0 million upon

the approval of an New Drug Application (“NDA”) for Berubicin;

and (v) 200,000 shares of our common stock.

The patents we

licensed from HPI expired in March 2020.

On June 10, 2020, the FDA granted Orphan Drug Designation

(“ODD”) for Berubicin for the treatment of malignant gliomas.

ODD from the FDA is available for drugs targeting diseases with

less than 200,000 cases per year.

ODD may enable market exclusivity of 7 years from the date of approval of a NDA in the United States.

During that period the FDA generally could not approve another product containing the same drug for the same designated indication.

drug exclusivity will not bar approval of another product under certain circumstances, including if a subsequent product with the same

active ingredient for the same indication is shown to be clinically superior to the approved product on the basis of greater efficacy

or safety, or providing a major contribution to patient care, or if the company with orphan drug exclusivity is not able to meet market

The ODD now constitutes our primary intellectual property protections although the Company is exploring if there are other patents

that could be filed related to Berubicin to extend additional protections.

With the Reata Agreement and the HPI License, we

believe we have obtained all rights and intellectual property necessary to develop Berubicin.

As stated earlier, it is our plan to obtain

additional intellectual property covering other compounds which, subject to the receipt of additional financing, may be developed into

drugs for brain and other cancers.

On January 10, 2020, we entered into a Patent and

Technology License Agreement (the “1244 Agreement”) with The Board of Regents of The University of Texas System, an agency

of the State of Texas, on behalf of the UTMDACC.

Pursuant to the 1244 Agreement, we obtained a royalty-bearing, worldwide, exclusive license

to certain intellectual property rights, including patent rights, related to our portfolio of WP1244 drug technology.

In consideration,

we must make payments to UTMDACC including an up-front license fee, annual maintenance fee, milestone payments and royalty payments

(including minimum annual royalties) for sales of licensed products developed under the 1244 Agreement.

The term of the 1244 Agreement

expires on the last to occur of:

we must make payments to UTMDACC including an up-front license fee, annual maintenance fee, milestone payments and royalty payments (including

minimum annual royalties) for sales of licensed products developed under the 1244 Agreement.

The term of the 1244 Agreement expires on

the last to occur of:

(a) the expiration of all patents subject to the 1244 Agreement, or (b) fifteen years after execution;

provided that UTMDACC has the right to terminate the 1244 Agreement in the event that we fail to meet certain commercial diligence

that UTMDACC has the right to terminate the 1244 Agreement in the event that we fail to meet certain commercial diligence milestones.

On May 7, 2020, pursuant to the WP1244 portfolio

license agreement described above, the Company entered into a Sponsored Research Agreement with UTMDACC to perform research relating

to novel anticancer agents targeting CNS malignancies.

license agreement described above, the Company entered into a Sponsored Research Agreement with UTMDACC to perform research relating to

novel anticancer agents targeting CNS malignancies.

The Company agreed to fund approximately $1,134,000 over a two-year period.

The Company paid and recorded $334,000 in 2020 related to this agreement in research and development expenses

in the Company’s Statements of Operations.

The remaining $720,000 will be paid in 2021, of which $400,000 was accrued at

December 31, 2020.

paid and recorded $334,000 in 2020 related to this agreement in research and development expenses in the Company’s Statements of

The remaining $800,000 was paid in 2021.

The principal investigator for this agreement is Dr.

The work conducted under

this Sponsored Research Agreement has produced a new mesylate salt of WP1244 termed WP1874.

We believe the enhanced solubility of this

salt may increase its ability to be formulated for use in an IV infusion, while maintaining similar potency and toxicity characteristics.

As such, WP1874 will be the primary focus in our development efforts of the WP1244 portfolio.

Market for Cancer Drugs and Berubicin

Cancer is the second leading cause of death

in the United States behind heart disease.

Cancer is the second leading cause of death in

the United States behind heart disease.

In 2019, there were an estimated 16.9 million cancer survivors in the United States.

In 2018, the American Cancer Society estimated that nearly 1.7 million new cases would be diagnosed and over 600,000 Americans

would die from cancer.

the American Cancer Society estimated that nearly 1.9 million new cases would be diagnosed and over 600,000 Americans would die from cancer.

Digestive, reproductive, breast and respiratory

cancers comprise 65% of expected cancer diagnoses in 2018, while cancers like leukemia and brain tumors are considered “rare

diseases.”

The worldwide cancer drug business has been

estimated to represent nearly $100 billion in annual sales.

Our lead drug candidate, Berubicin, is in a class of drugs referred

to as anthracyclines, which are chemotherapy drugs designed to destroy the DNA of targeted cancer cells.

The most common approved

anthracyclines are daunorubicin and doxorubicin and, prior to the expansion of their generic equivalents, annual revenues generated

from anthracyclines have been estimated in the range of $600 million.

cancers comprise 69% of expected cancer diagnoses in 2022, while cancers like leukemia and brain tumors are considered “rare diseases.”

The worldwide cancer drug business has been estimated

to represent nearly $100 billion in annual sales.

Our lead drug candidate, Berubicin, is in a class of drugs referred to as anthracyclines,

which are chemotherapy drugs designed to destroy the DNA of targeted cancer cells.

The most common approved anthracyclines are daunorubicin

and doxorubicin and, prior to the expansion of their generic equivalents, annual revenues generated from anthracyclines have been estimated

in the range of $600 million.

Many cancers are currently treated with anthracyclines;

primary and metastatic brain cancers have not been among them because heretofore no anthracyclines have been able to penetrate

We believe that based on limited pre-clinical and clinical data, Berubicin appears to show that it can cross the BBB.

However, there is no assurance that Berubicin will be able to demonstrate such traits in more fulsome clinical trials.

Brain cancer in general is considered a

rare disease for which there are few available treatments.

The leading brain tumor drug is temozolomide (“TMZ”), a

drug introduced under the brand name Temodar®.

In 2012, one industry source reported annual revenues of approximately $882

million for Temodar before the expiration of its patent protection, at which point generic versions of the drug began to enter

the market and reduce prices.

Temozolomide may extend progression free survival (“PFS”) but has never been shown to

be curative of any brain cancers.

The Orphan Drug Act and other legislative

initiatives provide incentives, including market exclusivity and accelerated approval pathways, for companies that pursue the development

of treatments for rare diseases and serious diseases for which there are few or no acceptable available treatment alternatives.

Orphan Drug exclusivity prevents for seven years the approval of another product with the same active moiety for the same rare

If a product is a new chemical entity (i.e., generally that the moiety has not previously been approved), it may receive

five years of exclusivity, during which period FDA may not accept for review certain NDAs for another product with the same moiety.

If approval of a product required new clinical data, it may convey three years of exclusivity against approval of certain NDAs

for similar products.

Over the last 10 years, an increasing number of companies have begun using these designations to obtain new

drug approvals for drugs where patent coverage has expired and/or where accelerated approval appears possible.

An IMS Health report

estimated that, in 2013, the sale of drugs with full or partial Orphan Drug exclusivity represented approximately $29 billion in

We consider the receipt of Orphan Drug exclusivity and expedited pathways to approval or further development to be an

important part of our development strategy for our drug candidates.

however, primary and metastatic brain cancers have

not been among them because heretofore no anthracyclines have been able to sufficiently penetrate the BBB.

We believe that based on currently

limited pre-clinical and clinical data, Berubicin appears to show that it can cross the BBB.

However, there is no assurance that Berubicin

will be able to demonstrate such traits in more fulsome clinical trials.

Brain cancer in general is considered a rare disease

for which there are few available treatments.

The leading brain tumor drug is temozolomide (“TMZ”), a drug introduced under

the brand name Temodar®.

In 2012, one industry source reported annual revenues of approximately $882 million for Temodar before the

expiration of its patent protection, at which point generic versions of the drug began to enter the market and reduce prices.

overall survival when used in combination with radiation after preliminary surgery, followed by maintenance therapy as a single agent

The Orphan Drug Act and other legislative initiatives

provide incentives, including market exclusivity and accelerated approval pathways, for companies that pursue the development of treatments

for rare diseases and serious diseases for which there are few or no acceptable available treatment alternatives.

Orphan Drug exclusivity

prevents for seven years the approval of another product with the same active moiety for the same rare disease.

If a product is a new

chemical entity (i.e., generally that the moiety has not previously been approved), it may receive five years of exclusivity, during which

period FDA may not accept for review certain NDAs for another product with the same moiety.

If approval of a product required new clinical

data, it may convey three years of exclusivity against approval of certain NDAs for similar products.

Over the last 10 years, an increasing

number of companies have begun using these designations to obtain new drug approvals for drugs where patent coverage has expired and/or

where accelerated approval appears possible.

An IMS Health report estimated that, in 2013, the sale of drugs with full or partial Orphan

Drug exclusivity represented approximately $29 billion in revenue.

We consider the receipt of Orphan Drug exclusivity and expedited pathways

to approval or further development to be an important part of our development strategy for our drug candidates.

The Berubicin Clinical Therapeutic Opportunity

The Company was created to specialize in

the discovery and development of novel treatments for brain tumors.

Our main focus is currently the development and testing of

Based on limited clinical data, we believe Berubicin is the first anthracycline that appears in animal models and limited

clinical data derived from a Phase 1 human clinical trial to cross the BBB and target cancer cells.

In 2009, Reata, the prior developer

of Berubicin, completed its Phase 1 clinical trial in patients diagnosed with brain cancers, including glioblastoma, the most aggressive

form of brain cancer.

Currently, there are no effective therapies

for glioblastoma.

In the clinical trial completed in February 2009, Berubicin demonstrated one durable complete response (considered

clinically to be a cure) lasting over 11 years in a glioblastoma patient.

This patient remains disease free and clinically stable

as of November 6, 2020.

In the trial, 25 of the 35 patients enrolled

were evaluable for response.

In a prior clinical trial, Berubicin has also shown promising data in a patient population that currently

has a dismal median survival rate of only 14.6 months from glioblastoma diagnosis and few effective therapeutic options.

early results are proven to be reproducible and if we secure regulatory approval to market Berubicin, its apparent ability to

cross the BBB combined with its mechanism of action, more thoroughly discussed below, has the potential to become an effective

treatment for this deadly cancer.

In the United States, 22,850 new glioblastoma

patients are diagnosed, and 15,300 patients die of this deadly disease annually (National Cancer Institute 2015).

Due to the lack

of effective therapies, the five-year survival rate of glioblastoma ranges from 13% for younger aged patients (20 to 44 years)

to 1% for older populations (over 44 years).

The current standard for treatment is surgery, radiation, and chemotherapy with TMZ.

TMZ, the current chemotherapeutic component of the standard of care for glioblastoma, has limited efficacy.

In the TMZ final clinical

trial performed before submitting for FDA approval (573 patients), overall survival was only improved by 2.5 months versus radiation

At least 50% of TMZ treated patients do not respond to TMZ, primarily due to the over-expression of O6-methylguanine methyltransferase

(“MGMT”) and/or lack of a DNA repair pathway in glioblastoma cells.

Given the different mechanism of action of Berubicin,

these patients may show a better outcome and our planned phased 2 clinical trial could be used to support an application for approval

of Berubicin as a frontline therapy.

However, we believe that the most prudent initial investigational objective is a phase 2 stratified

trial that can either serve as a registration trial or provide sufficient data to power a phase 3 registration trial.

Based on data relating to the mechanism

of action of Berubicin, as well as clinical results from the Phase 1 study in brain tumors performed by Reata, the prior developer

of Berubicin, we are conducting a randomized, controlled multicenter study that will evaluate the efficacy of Berubicin versus

Lomustine (CCNU, CeeNU®, or Gleostine®) in patients with recurrent glioblastoma.

Randomization to the two therapies (Berubicin

or Lomustine) will be on a 2:1 basis with 2 patients receiving Berubicin for every patient randomized to Lomustine.

a drug considered effective in patients with glioblastoma that has recurred or progressed following first line therapy.

data available from the Reata Phase 1 clinical trial (RTA 744-C-0401), the FDA has agreed that the dosage for Berubicin will be

at the maximum tolerated dose (“MTD”) determined in that trial.

Thus, patients randomized to the Berubicin arm will

receive a 2-hour IV infusion of 7.5 mg/m2 berubicin hydrochloride daily for three consecutive days followed by 18 days off (21-day

Patients randomized to Lomustine will receive a single oral dose of 130 mg/m2 (rounded to the nearest 5 mg) every 6 weeks,

or per the full prescribing information for Lomustine incorporating institutional standards at each study site.

Efficacy will be measured by the benefit

of Berubicin vs.

Lomustine in terms of overall survival (OS), considered the preferred standard as an endpoint for clinical trials

in Neuro-Oncology.

Secondary endpoints using accepted radiologic methodology (magnetic resonance imaging (“MRI”)),

including both pre- and post-gadolinium T1-weighted scans and T2/fluid attenuated inversion recovery (“FLAIR”) images

will evaluate objective response rates (ORR), which include complete responses (CR) and partial responses (PR) as per RANO (Response

Assessment for Neuro-Oncology), and progression free survival at 6 months (PFS6).

Additional information to be collected include

event free survival (EFS), corticosteroid usage, neurologic status, quality of life, and safety, and for Berubicin, the pharmacokinetics

(PK) at the dose and schedule employed.

The trial will include an interim analysis to estimate the likelihood of achieving statistical

significance for the primary endpoint, OS, after approximately 50% of enrolled patients have reached 6 months on study.

Assuming data from the above described Phase

2 study is positive (and depending on the strength and quality of such data) at its completion we may seek approval to market Berubicin

from relevant regulatory authorities, we may look for a partner with which to conduct a Phase 3 study, or we may attempt to raise

sufficient capital to conduct such a study on our own.

The goal of these potential Phase 3 studies, should they be necessary, is

to develop a body of evidence to support a successful application with the FDA and/or other similar regulatory agencies around

Should we obtain approval from the FDA or other international regulatory agencies to market Berubicin, we will either

partner with third parties to sell and distribute it to physicians and patients, or we will develop our own sales force to do so.

The Company was created to specialize in the discovery

and development of novel treatments for brain tumors.

Our main focus is currently the development and testing of Berubicin.

Based on limited

clinical data, we believe Berubicin is the first anthracycline that appears in animal models and limited clinical data derived from a

Phase 1 human clinical trial to cross the BBB and target cancer cells.

In 2009, Reata, the prior developer of Berubicin, completed its

Phase 1 clinical trial in patients diagnosed with brain cancers, including glioblastoma, the most aggressive form of brain cancer.

Currently, there are no curative therapies for

glioblastoma.

In the clinical trial completed by Reata in February 2009, Berubicin demonstrated one durable complete response lasting

over 13 years in a patient treated on the original Phase 1 clinical trial.

This patient remains disease free and clinically stable as

of November 5, 2021.

The Phase 1 trial was in a patient population that

had a median survival rate of only 14.6 months from glioblastoma diagnosis and few effective therapeutic options.

In this trial, 25 of

the 35 patients enrolled were evaluable for response, and there was 1 complete response, 1 partial response, and 1 minor response, all

indicative of tumor shrinkage.

In addition, 8 other patients had stable disease, for a disease control rate (DCR) of 44%.

If these results

are reproducible and if regulatory approval is secured to market Berubicin, based on its apparent ability to cross the BBB combined with

its mechanism of action, more thoroughly discussed below, we believe this drug has the potential to become an effective treatment for

this deadly cancer.

In the eight major markets for pharmaceuticals

(the US, France, Germany, Italy, Spain, the UK, Japan and China), approximately 55,000 new glioblastoma patients were diagnosed in 2021

with a median survival rate for these patients of only 15 months (GlobalData, 2018).

Due to the lack of effective therapies, the five-year

survival rate of glioblastoma ranges from 13% for younger aged patients (20 to 44 years) to 1% for older populations (over 44 years).

The current standard of care for first-line treatment is surgery, radiation, and chemotherapy with TMZ.

TMZ, the current chemotherapeutic

component of the first-line standard of care for glioblastoma, has limited efficacy.

In the TMZ final clinical trial performed before

submitting for FDA approval (573 patients), overall survival was improved by 2.5 months versus radiation alone, a clearly significant

improvement in survival.

However, at least 50% of TMZ treated patients do not respond to TMZ (or respond very poorly), primarily due to

the O6-methylguanine methyltransferase (“MGMT”) enzyme, which is a DNA repair pathway in glioblastoma cells.

When methylated,

the enzyme has reduced DNA repair activity, and increases the activity of TMZ;

thus unmethylated patients have greater DNA repair activity,

and this confers a poorer prognosis.

Given the different mechanism of action of Berubicin, patients with unmethylated MGMT may show a

better outcome and this will be explored by stratification to the MGMT methylation status of patients on the current trial.

potentially be used to support an application for approval of Berubicin as a frontline therapy, however, we believe that the most prudent

initial investigational objective is the current stratified trial that can either serve as a registration trial or provide sufficient

data to power an additional registration trial.

Based on data relating to the mechanism of action

of Berubicin, as well as clinical results from the Phase 1 study in brain tumors performed by Reata, the prior developer of Berubicin,

we are conducting a randomized, controlled multicenter study that will evaluate the efficacy of Berubicin versus Lomustine (CCNU, CeeNU®,

or Gleostine®) in patients with recurrent glioblastoma.

Randomization to the two therapies (Berubicin or Lomustine) will be on a 2:1

basis with 2 patients receiving Berubicin for every patient randomized to Lomustine.

Lomustine is a drug considered effective in patients

with glioblastoma that has recurred or progressed following first line therapy.

From the data available from the Reata Phase 1 clinical

trial (RTA 744-C-0401), the FDA has agreed that the dosage for Berubicin will be at the maximum tolerated dose (“MTD”) determined

in that trial.

Thus, patients randomized to the Berubicin arm will receive a 2-hour IV infusion of 7.5 mg/m2 berubicin hydrochloride daily

for three consecutive days followed by 18 days off (21-day cycle).

Patients randomized to Lomustine will receive a single oral dose of

130 mg/m2 (rounded to the nearest 5 mg) every 6 weeks, or per the full prescribing information for Lomustine incorporating institutional

standards at each study site.

Efficacy will be measured by the benefit of Berubicin

Lomustine in terms of overall survival (OS), considered the preferred standard as an endpoint for clinical trials in Neuro-Oncology.

Secondary endpoints using accepted radiologic methodology (magnetic resonance imaging (“MRI”)), including both pre- and post-gadolinium

T1-weighted scans and T2/fluid attenuated inversion recovery (“FLAIR”) images will evaluate objective response rates (ORR),

which include complete responses (CR) and partial responses (PR) as per RANO (Response Assessment for Neuro-Oncology), and progression

free survival (PFS).

Additional information to be collected include event free survival (EFS), corticosteroid usage, neurologic status,

quality of life, and safety, and for Berubicin, the pharmacokinetics (PK) at the dose and schedule employed.

The trial will include an

interim analysis to estimate the likelihood of achieving statistical significance for the primary endpoint, OS, compared to the control

arm after approximately 30 to 50% of enrolled patients have reached 6 months on study.

Assuming data from the above described study is

positive (and depending on the strength and quality of such data) at its completion we may seek approval to market Berubicin from relevant

regulatory authorities, we may look for a partner with which to conduct a Phase 3 study, if this is required by authorities based on the

strength of the data submitted, or we may attempt to raise sufficient capital to conduct such a study on our own.

The goal of these potential

Phase 3 studies, should they be necessary, is to develop a body of evidence to support a successful application with the FDA and/or other

similar regulatory agencies around the world.

Should we obtain approval from the FDA or other international regulatory agencies to market

Berubicin, we will either partner with third parties to sell and distribute it to physicians and patients, or we will develop our own

sales force to do so.

Our first product under development is Berubicin,

a development stage anthracycline intended to treat glioblastoma.

Berubicin is an anthracycline, a class of drugs that are among

the most powerful chemotherapy drugs known.

Berubicin intercalates into DNA and interrupts topoisomerase II activity, resulting

in the inhibition of DNA replication and repair, and RNA and protein synthesis.

Based on evidence developed from animal models

and limited clinical data derived from a Phase 1 human clinical trial, Berubicin appears to cross the blood brain barrier and target

cancer cells, specifically glioblastoma, unlike any other known anthracyclines.

Berubicin hydrochloride (HCl) is a novel

synthetic anthracycline with a chemical structure similar to doxorubicin HCl, a cytotoxic anthracycline topoisomerase II inhibitor

isolated from cultures of Streptomyces peucetius var.

Doxorubicin HCl Injection and Doxorubicin HCl for Injection, drugs

related in chemical structure and mechanism of action to Berubicin, are approved by FDA for the treatment of various cancers, including

acute lymphoblastic leukemia, acute myeloblastic leukemia, Hodgkin lymphoma, Non-Hodgkin lymphoma, metastatic breast cancer, metastatic

tumor, metastatic neuroblastoma, metastatic soft tissue sarcoma, metastatic bone sarcomas, metastatic ovarian carcinoma,

metastatic transitional cell bladder carcinoma, metastatic thyroid carcinoma, metastatic gastric carcinoma, and metastatic bronchogenic

carcinoma, as well as part of a multiagent adjuvant chemotherapy for the treatment of women with axillary lymph node involvement

after resection of primary breast cancer.

A liposomal formulation of doxorubicin HCl is also approved for the treatment of ovarian

cancer, AIDS-related Kaposi’s sarcoma, and multiple myeloma.

Doxorubicin HCl is not indicated for

cancers of the brain, where it has limited efficacy due to its poor penetration through the blood-brain barrier.

Further, even

for those cancers that doxorubicin HCl is indicated, development of drug resistance remains a problem.

In an effort to develop

a second generation anthracycline topoisomerase II inhibitor that can circumvent the BBB and the development of drug resistance,

Priebe created a library of high-affinity and sequence-selective deoxyribonucleic acid (“DNA”)-binding agents and

screened against a panel of P-glycoprotein 1 (Pgp) and multidrug resistance-associated protein 1 (MRP1)-overexpressing cells.

led to the identification of berubicin HCl, which preclinical studies appear to show to be less affected by multidrug transporters

than doxorubicin, to be potentially more potent as an inhibitor of cell growth and inducer of apoptosis than doxorubicin, to sequester

preferentially in tumor tissue versus brain tissue, and to improve overall survival in an intracranial orthotopic glioma model.

There is no assurance that Berubicin will be able to demonstrate such traits in future clinical trials.

Glioblastoma has an unfavorable prognosis

mainly due to its high propensity for tumor recurrence, which is inevitable after a median survival time of 32–36 weeks.

A plethora of monotherapy and combination chemotherapy strategies have been evaluated in patients with recurrent glioblastoma.

Although these can result in some minor improvements in progression-free survival, with an estimation of approximately 30% after

six months, no obvious increase in survival has been associated with any particular regimen.

Despite aggressive initial treatment, most

patients develop recurrent diseases which can be treated with reresection, systemic treatment with targeted agents or cytotoxic

chemotherapy, reirradiation, or radiosurgery.

Research into novel therapies is investigating alternative temozolomide regimens,

convection-enhanced delivery, immunotherapy, gene therapy, antiangiogenic agents, poly ADP ribose polymerase inhibitors, or cancer

stem cell signaling pathways.

Overall, the 5-year survival rate is <10%, with a final mortality rate of close to 100%.

the development of novel therapeutic options for patients with recurrent glioblastoma remains a priority.

Given the short-term

efficacy and low survival rate of glioblastoma and other CNS patient groups, we believe there is a significant unmet need, and

financial opportunity.

Less than 40% of glioblastoma patients have

a genetic variation which makes their tumors initially more responsive to TMZ.

However, because nearly all these patients will

quickly become resistant, Berubicin could be prescribed after failure with TMZ.

The remaining 60% of patients initially fail to

respond to TMZ, primarily due to the over-expression of O6-methylguanine methyltransferase (MGMT) and/or lack of a DNA repair pathway

in glioblastoma cells.

If Berubicin shows efficacy in clinical trials, of which there is no assurance, it could become the primary

drug treatment because TMZ is ineffective in this patient population.

Reata licensed in berubicin HCl with the

intent of developing it for commercialization.

Berubicin is an anthracycline, a class of drugs that are among the most

powerful chemotherapy drugs known.

Berubicin intercalates into DNA and interrupts topoisomerase II activity, resulting in the inhibition

of DNA replication and repair, and ultimately RNA and protein synthesis.

Based on evidence developed from animal models and limited clinical

data derived from a Phase 1 human clinical trial, Berubicin appears to cross the blood brain barrier and target cancer cells, specifically

glioblastoma, more effectively and efficiently than any other known anthracyclines.

Berubicin hydrochloride (HCl) is a novel synthetic

anthracycline with a chemical structure similar to doxorubicin HCl, a cytotoxic anthracycline topoisomerase II inhibitor isolated from

cultures of Streptomyces peucetius var.

Doxorubicin HCl Injection and Doxorubicin HCl for Injection, drugs related in chemical

structure and mechanism of action to Berubicin, are approved by the FDA for the treatment of various cancers, including acute lymphoblastic

leukemia, acute myeloblastic leukemia, Hodgkin lymphoma, Non-Hodgkin lymphoma, metastatic breast cancer, metastatic Wilms’ tumor,

metastatic neuroblastoma, metastatic soft tissue sarcoma, metastatic bone sarcomas, metastatic ovarian carcinoma, metastatic transitional

cell bladder carcinoma, metastatic thyroid carcinoma, metastatic gastric carcinoma, and metastatic bronchogenic carcinoma, as well as

part of a multiagent adjuvant chemotherapy for the treatment of women with axillary lymph node involvement after resection of primary

breast cancer.

A liposomal formulation of doxorubicin HCl is also approved for the treatment of ovarian cancer, AIDS-related Kaposi’s

sarcoma, and multiple myeloma.

Doxorubicin HCl is not indicated for cancers of

the brain, where it has limited efficacy due to its poor penetration through the blood-brain barrier.

Further, even for those cancers

that doxorubicin HCl is indicated, development of drug resistance remains a problem.

In an effort to develop a second generation anthracycline

topoisomerase II inhibitor that can circumvent the BBB and the development of drug resistance, Dr.

Priebe created a library of high-affinity

and sequence-selective deoxyribonucleic acid (“DNA”)-binding agents and screened against a panel of P-glycoprotein 1 (Pgp)

and multidrug resistance-associated protein 1 (MRP1)-overexpressing cells.

This led to the identification of berubicin HCl, which preclinical

studies appear to show to be less affected by multidrug transporters than doxorubicin, to be potentially more potent as an inhibitor of

cell growth and inducer of apoptosis than doxorubicin, to sequester preferentially in tumor tissue versus brain tissue, and to improve

overall survival in an intracranial orthotopic glioma model.

There is no assurance that Berubicin will be able to demonstrate such traits

in clinical trials.

Glioblastoma has an unfavorable prognosis mainly

due to its high propensity for tumor recurrence, which is inevitable after a median survival time of 32–36 weeks.

A plethora of

monotherapy and combination chemotherapy strategies have been evaluated in patients with recurrent glioblastoma.

Although these can result

in some minor improvements in progression-free survival, with an estimation of approximately 30% after six months, no obvious increase

in survival has been associated with any particular regimen since the Stupp regimen of TMZ and radiation (2005).

Despite aggressive initial treatment, most patients

develop recurrent diseases which can be treated with reresection, systemic treatment with targeted agents or cytotoxic chemotherapy, reirradiation,

or radiosurgery.

Research into novel therapies is investigating alternative temozolomide regimens, convection-enhanced delivery, immunotherapy,

gene therapy, antiangiogenic agents, poly ADP ribose polymerase inhibitors, or cancer stem cell signaling pathways.

Overall, the 5-year

survival rate is <10%, with a final mortality rate of close to 100%.

Therefore, the development of novel therapeutic options for patients

with recurrent glioblastoma remains a priority.

Given the short-term efficacy and low survival rate of glioblastoma and other central

nervous system patient groups, we believe there is a significant unmet need, and financial opportunity.

Less than 40% of glioblastoma patients have a genetic

variation which makes their tumors initially more responsive to TMZ.

However, because nearly all these patients will quickly become resistant,

Berubicin could be prescribed after failure with TMZ.

The remaining 60% of patients initially fail to respond to TMZ, primarily due to

the over-expression of O6-methylguanine methyltransferase (MGMT) conferring a lack of a DNA repair pathway in glioblastoma cells.

shows efficacy in clinical trials, of which there is no assurance, it could become the primary drug treatment because TMZ is ineffective

in this patient population.

Reata licensed in berubicin HCl with the intent

of developing it for commercialization.

On December 28, 2004, Reata filed an initial IND (IND 68,279;

an injection formulation of berubicin HCl (RTA 744 Injection) for the treatment of anaplastic astrocytoma, anaplastic oligodendroglioma,

anaplastic mixed oligo-astrocytoma, glioblastoma, and gliosarcoma.

Three clinical trials were initiated under IND 68,279, two phase

1 trials and one phase 2 trial.

000) for an injection

formulation of berubicin HCl (RTA 744 Injection) for the treatment of anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic

mixed oligo-astrocytoma, glioblastoma, and gliosarcoma.

Three clinical trials were initiated under IND 68,279, two phase 1 trials and

one phase 2 trial.

The initial phase 1 trial (Study RTA 744-C-0401) was completed and the maximum tolerated dose determined.

A 44% disease control response rate was observed.

A 44% disease

control response rate was observed.

The disease control rate was based on patients with stable disease plus responses.

In the trial, out of 25 patients, one patient achieved a complete response and 10 patients achieved a stable response.

disease control response rate is based on these 11 patients (out of 25 patients).

Regardless, in 2008, Reata decided to curtail

development of RTA 744 Injection for strategic reasons.

Further enrollment in the two ongoing berubicin clinical trials was halted.

Reata submitted a request to inactive the IND on March 17, 2011 (Serial No.

054) and requested that the IND be withdrawn on June

10, 2016 (Serial No.

IND 68,279 was not withdrawn due to safety or efficacy concerns, but rather due to the above noted

corporate reprioritization.

In the trial, out

of 25 patients, one patient achieved a complete response, 1 patient had a partial response, 1 patient had a minor response, and 8 patients

achieved a stable response.

The 44% disease control response rate is based on these 11 patients (out of 25 patients).

Regardless, in 2008,

Reata decided to curtail development of RTA 744 Injection for strategic reasons.

Further enrollment in the two other ongoing berubicin

clinical trials was halted.

Reata submitted a request to inactivate the IND on March 17, 2011 (Serial No.

054) and requested that the

IND be withdrawn on June 10, 2016 (Serial No.

IND 68,279 was not withdrawn due to safety or efficacy concerns, but rather due to

the above noted corporate reprioritization.

CNS was formed in 2017, with Dr.

as the Scientific Founder.

Reata sold CNS all rights to the berubicin investigational drug data, including the data submitted under

IND 68,279, and CNS has assumed sole authority, discretion and responsibility with respect to the development of the drug.

result of the Reata Agreement, we are the direct beneficiaries of the 4 years of active clinical development work performed by

Reata, including the execution of multiple Phase 1 human clinical trials.

Furthermore, should our human trials demonstrate a significant

improvement in glioblastoma patient outcomes, the FDA may grant us an accelerated review schedule under its Breakthrough Therapy

On May 24, 2019, our sublicensee, WPD, signed

the Granting Agreement with the Polish National Center for Research and Development for co-funding of research and development

work in the amount of 22,033,066 PLN (approximately US $5,798,875) for a new drug development as a part of the project “New

approach to glioblastoma treatment addressing the critical unmet medical need”, undertaken pursuant to the WPD Sublicense.

The grant will be co-funded by the European Union, under the Smart Growth Operational Program 2014-2020, Sectoral Programme InnoNeuroPharm,

Priority Axis I:

Support R&D carried out by enterprises, Measure 1.2 Sectorial programs R&D.

The main goal of the WPD Project

is to implement the first in the world multicenter pediatric phase I clinical trial to determine maximum tolerated dose (MTD) and

phase IB and II clinical trials in adults, in order to attempt to determine safety and efficacy of Berubicin.

The WPD Project will

also include preclinical tests to determine the prospective use of Berubicin with temozolomide and with other compounds being developed

by WPD as candidates for anticancer drugs.

The WPD Project includes the implementation

of the following stages of R&D:

Advice Procedure implementation;

Regulatory documentation for “First in Children”

and phase Ib and II clinical trial

in adults preparation;

Manufacturing according to GMP;

In vitro studies on anticancer activity of Berubicin in combination with TMZ and other WPD molecules;

in children”

and Phase Ib in adults clinical trials conducting;

II in adults clinical trial conducting.

Priebe as the

Scientific Founder.

Reata sold CNS all rights to the berubicin investigational drug data, including the data submitted under IND 68,279,

and CNS has assumed sole authority, discretion, and responsibility with respect to the development of the drug.

As a result of the Reata

Agreement, we are the direct beneficiaries of the 4 years of active clinical development work performed by Reata, including the execution

of multiple Phase 1 human clinical trials.

On May 24, 2019, our sublicensee, WPD, signed the

Granting Agreement with the Polish National Center for Research and Development for co-funding of research and development work in the

amount of 22,033,066 PLN (approximately US $5,798,875) for new drug development as a part of the project “New approach to glioblastoma

treatment addressing the critical unmet medical need”, undertaken pursuant to the WPD Sublicense.

The grant will be co-funded by

the European Union, under the Smart Growth Operational Program 2014-2020, Sectoral Programme InnoNeuroPharm, Priority Axis I:

R&D carried out by enterprises, Measure 1.2 Sectorial programs R&D.

This grant funding is dependent upon WPD funding a portion

of the trial estimated at 35-40% of the total cost, and we can provide no assurance that they can or will be able to do so.

The main goal

of the WPD Project is to implement the first in the world multicenter pediatric phase I clinical trial and phase II clinical trials in

adults, in order to continue to explore the safety and efficacy of Berubicin.

The WPD Project will also include preclinical tests to determine

the prospective use of Berubicin with temozolomide and with other compounds being developed by WPD as candidates for anticancer drugs.

Berubicin Clinical Trial

In the first clinical trial for Berubicin,

which was referred to as Study RTA 744-C-0401, 25 of the 35 patients enrolled were evaluable for response.

One patient achieved

a complete response, remained on study through seven cycles of therapy and was withdrawn for adverse events unrelated to Berubicin.

The patient was disease free as of November 6, 2020.

In the first clinical trial for Berubicin, which

was referred to as Study RTA 744-C-0401, 25 of the 35 patients enrolled were evaluable for response.

One patient achieved a complete response,

remained on study through seven cycles of therapy and was withdrawn for adverse events unrelated to Berubicin.

The patient was disease

free as of November 5, 2021.

Study RTA 744-C-0401 was a Phase 1 dose-finding,

1 unchanged sentence

anaplastic oligodendroglioma, anaplastic mixed oligo-astrocytoma, glioblastoma multiforme or gliosarcoma.

The study was an open-label, accelerated

dose-escalation study to determine the maximum tolerated dose starting with patients who were not taking concurrent enzyme-inducing

anti-epileptic drugs (EIAEDs) that could interfere with Berubicin drug metabolism.

Intra-patient dose-escalation was allowed after

a patient had received a minimum of 4 cycles.

Berubicin injection was administered either daily for three consecutive days repeated

every three weeks (Group A), or once-weekly for four-consecutive weeks repeated every five weeks (Group C).

Enrollment for a planned

dose escalation in Group B (patients on EIAEDs) was not initiated after it was determined that the standard of care had changed

and an insufficient number of patients being treated with these anti-epileptic drugs would make it difficult to accrue the requisite

number of patients.

The MTD for the remaining groups was determined in a stepwise fashion such that once the MTD for Group A (three

days in a row every 3 weeks) was determined, Group C was initiated at the MTD from Group A, given on a weekly basis for 4 of every

5 weeks to evaluate the tolerability and MTD of Berubicin on this alternative schedule.

The study was an open-label, accelerated dose-escalation

study to determine the maximum tolerated dose starting with patients who were not taking concurrent enzyme-inducing anti-epileptic drugs

(EIAEDs) that could interfere with Berubicin drug metabolism.

Intra-patient dose-escalation was allowed after a patient had received a

minimum of 4 cycles.

Berubicin injection was administered either daily for three consecutive days repeated every three weeks (Group A),

or once-weekly for four-consecutive weeks repeated every five weeks (Group C).

Enrollment for a planned dose escalation in Group B (patients

on EIAEDs) was not initiated after it was determined that the standard of care had changed and an insufficient number of patients being

treated with these anti-epileptic drugs would make it difficult to accrue the requisite number of patients.

The MTD for the remaining

groups was determined in a stepwise fashion such that once the MTD for Group A (three days in a row every 3 weeks) was determined, Group

C was initiated at the MTD from Group A, given on a weekly basis for 4 of every 5 weeks to evaluate the tolerability and MTD of Berubicin

on this alternative schedule.

Study Results

The first patient was enrolled into the

study in November 2005 and as of February 2009, the study was closed to accrual with no active patients remaining on study.

was administered to a total of 54 patients (35 male and 19 female) with ages ranging from 25 to 70 years.

Thirty-seven of the patients

(69%) entered the study with a diagnosis of glioblastoma multiforme, seven of which were secondary to transformation from anaplastic

The time from the initial brain tumor diagnosis to enrollment on the study ranged from four months to 301 months (this

last timing for a patient diagnosed with childhood anaplastic astrocytoma).

The first patient was enrolled into the study in

November 2005 and as of February 2009, the study was closed to accrual with no active patients remaining on study.

Berubicin was administered

to a total of 54 patients (35 male and 19 female) with ages ranging from 25 to 70 years.

Thirty-seven of the patients (69%) entered the

study with a diagnosis of glioblastoma multiforme, seven of which were secondary to transformation from anaplastic astrocytoma.

from the initial brain tumor diagnosis to enrollment on the study ranged from four months to 301 months (this last timing for a patient

diagnosed with childhood anaplastic astrocytoma).

Twenty-five of the 35 patients

enrolled in Group A were evaluable for response (under the Macdonald criteria described below).

One patient receiving Berubicin

at 2.4 mg/m2/day achieved a complete response.

The patient remained on study through 7 cycles of therapy before being withdrawn

for elevated liver function tests unrelated to study drug, and in follow-up remains disease free and clinically stable as of November

One additional patient receiving Berubicin

at 7.5 mg/m2/day achieved an unconfirmed partial response as their best recorded response, unconfirmed since the scan showing the

partial response required a second scan corroborating the response.

Although the patient had an 80% reduction in tumor volume after

two cycles of therapy, at the end of four cycles of therapy when an additional scan was obtained, despite the fact that the initial

lesion remained reduced, the patient developed a new lesion and was assessed as having disease progression, thus the PR could not

be confirmed.

Ten additional patients in Group A had stable disease of 2-to-8 cycles in duration, with a median progression free

survival of four cycles (12 weeks).

One patient receiving Berubicin at 2.4

mg/m2/day achieved a complete response.

The patient remained on study through 7 cycles of therapy before being withdrawn for elevated

liver function tests unrelated to study drug, and in follow-up remains disease free and clinically stable as of November 5, 2021.

One additional patient receiving Berubicin at 7.5

mg/m2/day achieved an unconfirmed partial response as their best recorded response, unconfirmed since the scan showing the partial response

required a second scan corroborating the response.

Although the patient had an 80% reduction in tumor volume after two cycles of therapy,

at the end of four cycles of therapy when an additional scan was obtained, despite the fact that the initial lesion remained reduced,

the patient developed a new lesion and was assessed as having disease progression, thus the PR could not be confirmed.

Ten additional

patients in Group A had stable disease of 2-to-8 cycles in duration, with a median progression free survival of four cycles (12 weeks).

In Group C, seven patients were evaluable for response and all had progressive disease.

patients were discontinued from the study prior to the end of cycle 2 due to clinical deterioration and/or disease progression.

Twelve patients were discontinued from the study

prior to the end of cycle 2 due to clinical deterioration and/or disease progression.

Macdonald criteria :

The Macdonald

criteria, similarly to other systems, divides response into four types of response based on imaging (MRI) and clinical features:

The Macdonald criteria,

similarly to other systems, divides response into four types of response based on imaging (MRI) and clinical features:

Imaging Features

18 unchanged sentences

§ Clinical deterioration

Measurements of lesions are obtained from

axial post contrast T1 images.

The maximal diameter is obtained, and then the second diameter is obtained at right angles to the

The product of these measurements is then used as the size of the lesion for the purpose of comparison.

Measurements of lesions are obtained from axial

post contrast T1 images.

The maximal diameter is obtained, and then the second diameter is obtained at right angles to the first.

product of these measurements is then used as the size of the lesion for the purpose of comparison.

Summary of Adverse Events :

events documented during Study RTA 744-C-0401 for all CTC grades of severity and regardless of relationship to study medication

are identified below.

The adverse events

documented during Study RTA 744-C-0401 for all CTC grades of severity and regardless of relationship to study medication are identified

Serious Adverse Event

17 unchanged sentences

Depressed level of consciousness

The larger number of events related to the

central nervous system is consistent with the impact of the underlying malignant disease in the brain of these patients.

Myelosupression,

i.e., a decrease in the number of bone-marrow derived cells, is expected and consistent with the known toxicities of anthracyclines,

which can be managed by the use of effective supportive care.

Based on data relating to the mechanism

of action of Berubicin, as well as clinical results from the Phase 1 study in brain tumors performed by Reata, the prior developer

of Berubicin, we are conducting a randomized, controlled multicenter study that will evaluate the efficacy of Berubicin versus

Lomustine (CCNU, CeeNU®, or Gleostine®) in patients with recurrent glioblastoma.

Randomization to the two therapies (Berubicin

or Lomustine) will be on a 2:1 basis with 2 patients receiving Berubicin for every patient randomized to Lomustine.

a drug considered effective in patients with glioblastoma that has recurred or progressed following first line therapy.

data available from the Reata Phase 1 clinical trial (RTA 744-C-0401), the FDA has agreed that the dosage for Berubicin will be

at the maximum tolerated dose (“MTD”) determined in that trial.

Thus, patients randomized to the Berubicin arm will

receive a 2-hour IV infusion of 7.5 mg/m2 berubicin hydrochloride daily for three consecutive days followed by 18 days off (21-day

Patients randomized to Lomustine will receive a single oral dose of 130 mg/m2 (rounded to the nearest 5 mg) every 6 weeks,

or per the full prescribing information for Lomustine incorporating institutional standards at each study site.

Efficacy will be measured by the benefit

of Berubicin vs.

Lomustine in terms of overall survival (OS), considered the preferred standard as an endpoint for clinical trials

in Neuro-Oncology.

Secondary endpoints using accepted radiologic methodology (magnetic resonance imaging [“MRI”]),

including both pre- and post-gadolinium T1-weighted scans and T2/fluid attenuated inversion recovery (“FLAIR”) images

will evaluate objective response rates (ORR), which include complete responses (CR) and partial responses (PR) as per RANO (Response

Assessment for Neuro-Oncology), and progression free survival at 6 months (PFS6).

Additional information to be collected include

event free survival (EFS), corticosteroid usage, neurologic status, quality of life, and safety, and for Berubicin, the pharmacokinetics

(PK) at the dose and schedule employed.

The trial will include an interim analysis to estimate the likelihood of achieving statistical

significance for the primary endpoint, OS, after approximately 50% of enrolled patients have reached 6 months on study.

Assuming data from the above described Phase

2 study is positive (and depending on the strength and quality of such data) at its completion we may seek an expedited pathway

to approval to market Berubicin from relevant regulatory authorities, we may look for a partner with which to conduct a Phase 3

study, or we may attempt to raise sufficient capital to conduct such a study on our own.

The goal of these potential Phase 3 studies,

should they be necessary, is to develop a body of evidence to support a successful application with the FDA and/or other similar

regulatory agencies around the world.

Should we obtain approval from the FDA or other international regulatory agencies to market

Berubicin, we will either partner with third parties to sell and distribute it to physicians and patients, or we will develop our

own sales force to do so.

We operate in a highly competitive segment

of the pharmaceutical market, which market is highly competitive as a whole.

We face competition from numerous sources including

commercial pharmaceutical and biotechnology enterprises, academic institutions, government agencies, and private and public research

institutions.

Many of our competitors may have significantly greater financial, product development, manufacturing and marketing

Additionally, many universities and private and public research institutes are active in cancer research, and some may

be in direct competition with us.

We may also compete with these organizations to recruit scientists and clinical development personnel.

Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements

with large and established companies.

The unmet medical need for more effective

cancer therapies is such that oncology drugs are one of the leading class of drugs in development.

These include a wide array of

products against cancer targeting many of the same indications as our drug candidates.

While the introduction of newer targeted

agents may result in extended overall survival, induction therapy regimens are likely to remain a cornerstone of cancer treatment

in the foreseeable future.

The larger number of events related to the central

nervous system is consistent with the impact of the underlying malignant disease in the brain of these patients.

Myelosupression, i.e.,

a decrease in the number of bone-marrow derived cells, is expected and consistent with the known toxicities of anthracyclines, which can

be managed by the use of effective supportive care.

Based on data relating to the mechanism of action

of Berubicin, as well as clinical results from the Phase 1 study in brain tumors performed by Reata, the prior developer of Berubicin,

we are conducting a randomized, controlled multicenter study that will evaluate the efficacy of Berubicin versus Lomustine (CCNU, CeeNU®,

or Gleostine®) in patients with recurrent glioblastoma.

Randomization to the two therapies (Berubicin or Lomustine) will be on a 2:1

basis with 2 patients receiving Berubicin for every patient randomized to Lomustine.

Lomustine is a drug considered effective in patients

with glioblastoma that has recurred or progressed following first line therapy.

From the data available from the Reata Phase 1 clinical

trial (RTA 744-C-0401), the FDA has agreed that the dosage for Berubicin will be at the maximum tolerated dose (“MTD”) determined

in that trial.

Thus, patients randomized to the Berubicin arm will receive a 2-hour IV infusion of 7.5 mg/m2 berubicin hydrochloride daily

for three consecutive days followed by 18 days off (21-day cycle).

Patients randomized to Lomustine will receive a single oral dose of

130 mg/m2 (rounded to the nearest 5 mg) every 6 weeks, or per the full prescribing information for Lomustine incorporating institutional

standards at each study site.

Efficacy will be measured by the benefit of Berubicin

Lomustine in terms of overall survival (OS), considered by the FDA as the only endpoint acceptable for clinical trials in Neuro-Oncology

which form the basis for a request for approval of a New Drug Application.

Secondary endpoints using accepted radiologic methodology (magnetic

resonance imaging “MRI”), including both pre- and post-gadolinium T1-weighted scans and T2/fluid attenuated inversion recovery

(“FLAIR”) images will evaluate objective response rates (ORR), which include complete responses (CR) and partial responses

(PR) as per RANO (Response Assessment for Neuro-Oncology), and progression free survival at 6 months (PFS6).

Additional information to

be collected include event free survival (EFS), corticosteroid usage, neurologic status, quality of life, and safety, and for Berubicin,

the pharmacokinetics (PK) at the dose and schedule employed.

The trial will include an interim analysis that will evaluate the comparative

effectiveness of these treatments, which is an adaptive design intended to demonstrate that there are no significant differences in efficacy

between treatments (futility analysis).

The overall survival endpoint is designed to show a statistical difference between the two therapies.

Assuming data from the above-described study is

positive (and depending on the strength and quality of such data) at its completion we may seek an expedited pathway to approval to market

Berubicin from relevant regulatory authorities, we may look for a partner with which to conduct a Phase 3 study, or we may attempt to

raise sufficient capital to conduct such a study on our own.

The goal of these potential Phase 3 studies, should they be necessary, is

to develop a body of evidence to support a successful application with the FDA and/or other similar regulatory agencies around the world.

Should we obtain approval from the FDA or other international regulatory agencies to market Berubicin, we will either partner with third

parties to sell and distribute it to physicians and patients, or we will develop our own sales force to do so.

We operate in a highly competitive segment of the

pharmaceutical market, which market is highly competitive as a whole.

We face competition from numerous sources including commercial pharmaceutical

and biotechnology enterprises, academic institutions, government agencies, and private and public research institutions.

Many of our competitors

may have significantly greater financial, product development, manufacturing and marketing resources.

Additionally, many universities

and private and public research institutes are active in cancer research, and some may be in direct competition with us.

We may also compete

with these organizations to recruit scientists and clinical development personnel.

Smaller or early-stage companies may also prove to

be significant competitors, particularly through collaborative arrangements with large and established companies.

The unmet medical need for more effective cancer

therapies is such that oncology drugs are one of the leading class of drugs in development.

These include a wide array of products against

cancer targeting many of the same indications as our drug candidates.

While the introduction of newer targeted agents may result in extended

overall survival, induction therapy regimens are likely to remain a cornerstone of cancer treatment in the foreseeable future.

The current standard for the initial treatment

of glioblastoma is surgery, followed by radiation in combination with TMZ, followed by maintenance TMZ.

While the percentage of

patients who survive two years from the diagnosis of glioblastoma has more than tripled from 8% to 25% in the last five years,

largely because of the use of TMZ, the overall survival remains dismal.

Treatment with Lomustine is considered

to be the standard of care for recurrent glioblastoma even though it is not formally approved by the FDA for this purpose, a fact which

highlights the lack of available options for treatment.

While the percentage of patients who survive two years from the diagnosis of glioblastoma

has increased because of the use of TMZ, overall survival for GBM patients remains dismal.

There are currently at least 77 different experimental

therapies under clinical development in the United States for recurrent GBM based on the clinicaltrials.gov website.

are operating in a highly competitive clinical trial environment, moving towards the pharmaceutical market, which is also extremely

competitive for patients with GBM.

We also face competition from numerous sources including commercial pharmaceutical and biotechnology

enterprises, academic institutions, government agencies, and private and public research institutions.

Many of our competitors

may have significantly greater cancer research capabilities, as well as financial, product development, manufacturing and marketing

Additionally, many universities and private and public research institutes are active in cancer research, and some

may be in direct competition with us.

In addition, we also compete with these organizations to recruit scientists and clinical

development personnel.

Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative

arrangements with large and established companies.

Thus, we are operating

in a highly competitive clinical trial environment, moving towards the pharmaceutical market, which is also extremely competitive for

patients with GBM.

We also face competition from numerous sources including commercial pharmaceutical and biotechnology enterprises, academic

institutions, government agencies, and private and public research institutions.

Many of our competitors may have significantly greater

cancer research capabilities, as well as financial, product development, manufacturing, and marketing resources.

Additionally, many universities

and private and public research institutes are active in cancer research, and some may be in direct competition with us.

we also compete with these organizations to recruit scientists and clinical development personnel.

Smaller or early-stage companies may

also prove to be significant competitors, particularly through collaborative arrangements with large and established companies.

Intellectual Property

Under the HPI License we obtained the exclusive

right to develop certain patented chemical compounds for use in the treatment of cancer anywhere in the world.

We have licensed

the right to certain intellectual property covering products comprised of anthracycline antibiotic compound, methods for manufacture

and use for the treatment of cancer.

The licensed intellectual property originally included certain material patents in the United

States and their foreign counterparts throughout the world.

patents have expired, and as such, we may be subject to increased

On June 10, 2020, the FDA granted Orphan

Drug Designation (“ODD”) for Berubicin for the treatment of malignant gliomas.

ODD from the FDA is available for drugs

targeting diseases with less than 200,000 cases per year.

ODD may enable market exclusivity of 7 years from the date of approval

of a NDA in the United States.

During that period the FDA generally could not approve another product containing the same drug

for the same designated indication.

Orphan drug exclusivity will not bar approval of another product under certain circumstances,

including if a subsequent product with the same active ingredient for the same indication is shown to be clinically superior to

the approved product on the basis of greater efficacy or safety, or providing a major contribution to patient care, or if the company

with orphan drug exclusivity is not able to meet market demand.

The ODD now constitutes our primary intellectual property protections

although the Company is exploring if there are other patents that could be filed related to Berubicin to extend additional protections.

We plan to file additional patent applications

that potentially might allow for further increase of the exclusive market protection for use of Berubicin.

However, we can provide

no assurance that we will be able to file or receive additional patent protection.

The failure to receive such additional patent

protection will reduce the barrier to entry for competition for Berubicin, which may adversely affect our operations.

right to develop certain chemical compounds for use in the treatment of cancer anywhere in the world.

We have licensed the right to certain

intellectual property covering products comprised of anthracycline antibiotic compound, methods for manufacture and use for the treatment

The licensed intellectual property originally included certain material patents in the United States and their foreign counterparts

throughout the world.

patents have expired, and as such, we may be subject to increased competition.

On June 10, 2020, the FDA granted Orphan Drug Designation

(“ODD”) for Berubicin for the treatment of malignant gliomas.

ODD from the FDA is available for drugs targeting diseases with

less than 200,000 cases per year.

ODD may enable market exclusivity of 7 years from the date of approval of a NDA in the United States.

During that period the FDA generally could not approve another product containing the same drug for the same designated indication.

drug exclusivity will not bar approval of another product under certain circumstances, including if a subsequent product with the same

active ingredient for the same indication is shown to be clinically superior to the approved product on the basis of greater efficacy

or safety, or providing a major contribution to patient care, or if the company with orphan drug exclusivity is not able to meet market

The ODD now constitutes our primary intellectual property protections although the Company is exploring if there are other patents

that could be filed related to Berubicin to extend additional protections.

2021, the Company received Fast Track Designation from the FDA for Berubicin.

Fast Track Designation is designed to facilitate the

development and expedite the review of drugs to treat serious conditions and fill an unmet medical need.

We are exploring the possibility to file additional

patent applications that potentially might allow for further increase of the exclusive market protection for use of Berubicin.

we can provide no assurance that we will be able to file or receive additional patent protection.

The failure to receive such additional

patent protection will reduce the barrier to entry for competition for Berubicin, which may adversely affect our operations.

Governmental Regulation

Government authorities in the United States,

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

testing, manufacture, quality control, approval, labeling, packaging, storage, record-keeping, promotion, advertising, distribution,

post-approval monitoring and reporting, marketing and export and import of products such as those we are developing.

The pharmaceutical

drug product candidates that we develop must be approved by the FDA before they may be marketed and distributed.

In the United States, the FDA regulates

pharmaceutical products under the Federal Food, Drug, and Cosmetic Act, and implementing regulations.

Pharmaceutical products are

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

The process of obtaining regulatory approvals and the

subsequent compliance with appropriate federal, state, local and foreign statutes and regulations require the expenditure of substantial

time and financial resources.

Failure to comply with the applicable U.S.

requirements at any time during the product development

process, approval process or after approval, may subject an applicant to administrative or judicial sanctions.

FDA and related

enforcement activity could include refusal to approve pending applications, withdrawal of an approval, a clinical hold, warning

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

of government contracts, restitution, disgorgement or civil or criminal penalties.

Any agency or judicial enforcement action could

have a material adverse effect on us.

The process required by the FDA before a pharmaceutical product may be marketed in the United

States generally involves the following:

Government authorities in the United States, at

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

manufacture, quality control, approval, labeling, packaging, storage, record-keeping, promotion, advertising, distribution, post-approval

monitoring and reporting, marketing and export and import of products such as those we are developing.

The pharmaceutical drug product

candidates that we develop must be approved by the FDA before they may be marketed and distributed.

In the United States, the FDA regulates pharmaceutical

products under the Federal Food, Drug, and Cosmetic Act, and implementing regulations.

Pharmaceutical products are also subject to other

federal, state and local statutes and regulations.

The process of obtaining regulatory approvals and the subsequent compliance with appropriate

federal, state, local and foreign statutes and regulations require the expenditure of substantial time and financial resources.

to comply with the applicable U.S.

requirements at any time during the product development process, approval process or after approval,

may subject an applicant to administrative or judicial sanctions.

FDA and related enforcement activity could include refusal to approve

pending applications, withdrawal of an approval, a clinical hold, warning letters, product recalls, product seizures, total or partial

suspension of production or distribution injunctions, fines, refusals of government contracts, restitution, disgorgement or civil or criminal

Any agency or judicial enforcement action could have a material adverse effect on us.

The process required by the FDA before

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

Completion of preclinical laboratory tests, animal studies and formulation studies according to Good Laboratory Practices or other applicable regulations;

Submission to the FDA of an Investigational New Drug application, or IND, which must become effective before human clinical studies may begin;

Performance of adequate and well-controlled human clinical studies according to the FDA’s current good clinical practices (“GCP”), to establish the safety and efficacy of the proposed pharmaceutical product for its intended use;

Submission to the FDA of an NDA for a new pharmaceutical product;

Satisfactory completion of an FDA inspection of the manufacturing facility or facilities where the pharmaceutical product is produced, to assess compliance with current good manufacturing practices (“cGMP”), to assure that the facilities, methods and controls are adequate to preserve the pharmaceutical product’s identity, strength, quality and purity;

Potential FDA audit of the preclinical and clinical study sites that generated the data in support of the NDA;

FDA review and approval of the NDA.

The lengthy process of seeking required

approvals and the continuing need for compliance with applicable statutes and regulations require the expenditure of substantial

resources and approvals, and continued compliance is inherently uncertain.

Before testing any compounds with potential

therapeutic value in humans, the pharmaceutical product candidate enters the preclinical testing stage.

Preclinical tests include

laboratory evaluations of product chemistry, toxicity and formulation, as well as animal studies to assess the potential safety

and activity of the pharmaceutical product candidate.

These early proof-of-principle studies are done using sound scientific procedures

and thorough documentation.

The conduct of the single and repeat dose toxicology and toxicokinetic studies in animals must comply

with federal regulations and requirements including good laboratory practices.

The sponsor must submit the results of the preclinical

tests, together with manufacturing information, analytical data, any available clinical data or literature and a proposed clinical

protocol, to the FDA as part of the IND.

The IND automatically becomes effective 30 days after receipt by the FDA, unless the FDA

has concerns and notifies the sponsor.

In such a case, the IND sponsor and the FDA must resolve any outstanding concerns before

the clinical study can begin.

If resolution cannot be reached within the 30-day review period, either the FDA places the IND on

clinical hold or the sponsor withdraws the application.

The FDA may also impose clinical holds on a pharmaceutical product candidate

at any time before or during clinical studies for various reasons.

Accordingly, we cannot be sure that submission of an IND will

result in the FDA allowing clinical studies to begin, or that, once begun, issues will not arise that suspend or terminate such

clinical study.

Clinical studies involve the administration

of the pharmaceutical product candidate to healthy volunteers or patients under the supervision of qualified investigators, generally

physicians not employed by or under the clinical study sponsor’s control.

Clinical studies are conducted under protocols

detailing, among other things, the objectives of the clinical study, dosing procedures, subject selection and exclusion criteria,

how the results will be analyzed and presented and the parameters to be used to monitor subject safety.

Each protocol must be submitted

to the FDA as part of the IND.

The lengthy process of seeking required approvals

and the continuing need for compliance with applicable statutes and regulations require the expenditure of substantial resources and approvals,

and continued compliance is inherently uncertain.

Before testing any compounds with potential therapeutic

value in humans, the pharmaceutical product candidate enters the preclinical testing stage.

Preclinical tests include laboratory evaluations

of product chemistry, toxicity and formulation, as well as animal studies to assess the potential safety and activity of the pharmaceutical

product candidate.

These early proof-of-principle studies are done using sound scientific procedures and thorough documentation.

of the single and repeat dose toxicology and toxicokinetic studies in animals must comply with federal regulations and requirements including

good laboratory practices.

The sponsor must submit the results of the preclinical tests, together with manufacturing information, analytical

data, any available clinical data or literature and a proposed clinical protocol, to the FDA as part of the IND.

The IND automatically

becomes effective 30 days after receipt by the FDA, unless the FDA has concerns and notifies the sponsor.

In such a case, the IND sponsor

and the FDA must resolve any outstanding concerns before the clinical study can begin.

If resolution cannot be reached within the 30-day

review period, either the FDA places the IND on clinical hold or the sponsor withdraws the application.

The FDA may also impose clinical

holds on a pharmaceutical product candidate at any time before or during clinical studies for various reasons.

Accordingly, we cannot

be sure that submission of an IND will result in the FDA allowing clinical studies to begin, or that, once begun, issues will not arise

that suspend or terminate such clinical study.

Clinical studies involve the administration of

the pharmaceutical product candidate to healthy volunteers or patients under the supervision of qualified investigators, generally physicians

not employed by or under the clinical study sponsor’s control.

Clinical studies are conducted under protocols detailing, among other

things, the objectives of the clinical study, dosing procedures, subject selection and exclusion criteria, how the results will be analyzed

and presented and the parameters to be used to monitor subject safety.

Each protocol must be submitted to the FDA as part of the IND.

Clinical studies must be conducted in accordance with GCP.

Further, each clinical study must be

reviewed and approved by an independent institutional review board (“IRB”) at, or servicing, each institution at which

the clinical study will be conducted.

An IRB is charged with protecting the welfare and rights of study participants and considers

such items as whether the risks to individuals participating in the clinical studies are minimized and are reasonable in relation

to anticipated benefits.

The IRB also approves the informed consent form that must be provided to each clinical study subject or

his or her legal representative and must monitor the clinical study until completed.

Further, each clinical study must be reviewed and approved by an independent

institutional review board (“IRB”) at, or servicing, each institution at which the clinical study will be conducted.

is charged with protecting the welfare and rights of study participants and considers such items as whether the risks to individuals participating

in the clinical studies are minimized and are reasonable in relation to anticipated benefits.

The IRB also approves the informed consent

form that must be provided to each clinical study subject or his or her legal representative and must monitor the clinical study until

Human clinical studies are typically conducted

8 unchanged sentences

In some instances, an NDA approval may be obtained based on Phase 2 clinical data with the understanding that the approved drug can be sold subject to a confirmatory trial to be conducted post-approval.

Post-approval studies, or Phase 4 clinical

studies, may be conducted after initial marketing approval.

These studies are often used to gain additional experience from the

treatment of patients in the intended therapeutic indication.

The FDA also may require Phase 4 studies, Risk Evaluation and Mitigation

Strategies (“REMS”) and post-marketing surveillance, among other things, to monitor the effects of an approved product

or place conditions on an approval that could restrict the distribution or use of the product.

Progress reports detailing the results of

the clinical studies must be submitted at least annually to the FDA and written IND safety reports must be submitted to the FDA

and the investigators for serious and unexpected adverse events or any finding from tests in laboratory animals that suggests a

significant risk for human subjects.

Phase 1, Phase 2 and Phase 3 clinical studies may not be completed successfully within any

specified period, if at all.

The FDA or the sponsor or its data safety monitoring board may suspend a clinical study at any time

on various grounds, including a finding that the research subjects or patients are being exposed to an unacceptable health risk.

Similarly, an IRB can suspend or terminate approval of a clinical study at its institution if the clinical study is not being conducted

in accordance with the IRB’s requirements or if the pharmaceutical product has been associated with unexpected serious harm

Concurrent with clinical studies, companies

may complete additional animal studies and must also develop additional information about the chemistry and physical characteristics

of the pharmaceutical product as well as 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 pharmaceutical

product candidate and, among other things, must develop methods for testing the identity, strength, quality and purity of the final

pharmaceutical product.

Additionally, appropriate packaging must be selected and tested and stability studies must be conducted

to demonstrate that the pharmaceutical product candidate does not undergo unacceptable deterioration over its shelf life.

Post-approval studies, or Phase 4 clinical studies,

may be conducted after initial marketing approval.

These studies are often used to gain additional experience from the treatment of patients

in the intended therapeutic indication.

The FDA also may require Phase 4 studies, Risk Evaluation and Mitigation Strategies (“REMS”)

and post-marketing surveillance, among other things, to monitor the effects of an approved product or place conditions on an approval

that could restrict the distribution or use of the product.

Progress reports detailing the results of the clinical

studies must be submitted at least annually to the FDA and written IND safety reports must be submitted to the FDA and the investigators

for serious and unexpected adverse events or any finding from tests in laboratory animals that suggests a significant risk for human subjects.

Phase 1, Phase 2 and Phase 3 clinical studies may not be completed successfully within any specified period, if at all.

The FDA or the

sponsor or its data safety monitoring board may suspend a clinical study at any time on various grounds, including a finding that the

research subjects or patients are being exposed to an unacceptable health risk.

Similarly, an IRB can suspend or terminate approval of

a clinical study at its institution if the clinical study is not being conducted in accordance with the IRB’s requirements or if

the pharmaceutical product has been associated with unexpected serious harm to patients.

Concurrent with clinical studies, companies may

complete additional animal studies and must also develop additional information about the chemistry and physical characteristics of the

pharmaceutical product as well as 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 pharmaceutical product candidate and, among

other things, must develop methods for testing the identity, strength, quality and purity of the final pharmaceutical product.

Additionally,

appropriate packaging must be selected and tested and stability studies must be conducted to demonstrate that the pharmaceutical product

candidate does not undergo unacceptable deterioration over its shelf life.

The results of product development, preclinical

studies and clinical studies, along with descriptions of the manufacturing process, analytical tests conducted on the chemistry

of the pharmaceutical product, proposed labeling and other relevant information are submitted to the FDA as part of an NDA requesting

approval to market the product.

studies and clinical studies, along with descriptions of the manufacturing process, analytical tests conducted on the chemistry of the

pharmaceutical product, proposed labeling and other relevant information are submitted to the FDA as part of an NDA requesting approval

to market the product.

The submission of an NDA is subject to the payment of substantial user fees.

A waiver of such fees

may be obtained under certain limited circumstances.

The FDA reviews all NDAs submitted before

it accepts them for filing and may request additional information rather than accepting an NDA for filing.

Once the submission

is accepted for filing, the FDA begins an in-depth review of the NDA.

Under the goals and policies agreed to by the FDA under the

Prescription Drug User Fee Act (“PDUFA”), the FDA has 10 months after the 60-day filing date in which to complete its

initial review of a standard review NDA and respond to the applicant, and six months after the 60-day filing date for a priority

The FDA does not always meet its PDUFA goal dates for standard and priority NDAs.

After the NDA submission is accepted for

filing, the FDA reviews the NDA application to determine, among other things, whether the proposed product is safe and effective

for its intended use, and whether the product is being manufactured in accordance with cGMP to assure and preserve the product’s

identity, strength, quality and purity.

The FDA may refer applications for novel pharmaceutical products or pharmaceutical products

which present difficult questions of safety or efficacy to an advisory committee, typically a panel that includes clinicians and

other experts, for review, evaluation and a recommendation as to whether the application should be approved and under what conditions.

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

During the pharmaceutical product approval process, the FDA also will determine whether a REMS is necessary to assure

the safe use of the pharmaceutical product.

If the FDA concludes that a REMS is needed, the sponsor of the NDA must submit a proposed

A waiver of such fees may be obtained

under certain limited circumstances.

The FDA reviews all NDAs submitted before it accepts

them for filing and may request additional information rather than accepting an NDA for filing.

Once the submission is accepted for filing,

the FDA begins an in-depth review of the NDA.

Under the goals and policies agreed to by the FDA under the Prescription Drug User Fee Act

(“PDUFA”), the FDA has 10 months after the 60-day filing date in which to complete its initial review of a standard review

NDA and respond to the applicant, and six months after the 60-day filing date for a priority review NDA.

The FDA does not always meet

its PDUFA goal dates for standard and priority NDAs.

After the NDA submission is accepted for filing,

the FDA reviews the NDA application to determine, among other things, whether the proposed product is safe and effective for its intended

use, and whether the product is being manufactured in accordance with cGMP to assure and preserve the product’s identity, strength,

quality and purity.

The FDA may refer applications for novel pharmaceutical products or pharmaceutical products which present difficult

questions of safety or efficacy to an advisory committee, typically a panel that includes clinicians and other experts, for review, evaluation

and a recommendation as to whether the application should be approved and under what conditions.

The FDA is not bound by the recommendations

of an advisory committee, but it considers such recommendations carefully when making decisions.

During the pharmaceutical product approval

process, the FDA also will determine whether a REMS is necessary to assure the safe use of the pharmaceutical product.

If the FDA concludes

that a REMS is needed, the sponsor of the NDA must submit a proposed REMS;

the FDA will not approve the NDA without a REMS, if required.

Before approving an NDA, the FDA will inspect

the facilities at which the product is manufactured.

The FDA will not approve the product 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, the FDA will typically inspect one or more clinical sites as well

as the site where the pharmaceutical product is manufactured to assure compliance with GCP and cGMP.

If the FDA determines 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.

In addition, the FDA will require the review and approval of product

The NDA review and approval process

is lengthy and difficult and the FDA may refuse to approve an NDA if the applicable regulatory criteria are not satisfied or may

require additional clinical data or other data and information.

Even if such data and information is submitted, the FDA may ultimately

decide that the NDA does not satisfy the criteria for approval.

Data obtained from clinical studies are not always conclusive and

the FDA may interpret data differently than we interpret the same data.

The FDA will issue a complete response letter if the agency

decides not to approve the NDA.

The complete response letter usually describes all of the specific deficiencies in the NDA identified

The deficiencies identified may be minor, for example, requiring labeling changes, or major, for example, requiring

additional clinical studies.

Additionally, the complete response letter may include recommended actions that the applicant might

take to place the application in a condition for approval.

If a complete response letter is issued, the applicant may either resubmit

the NDA, addressing all of the deficiencies identified in the letter, or withdraw the application.

If a product receives regulatory approval,

the approval may be significantly limited to specific diseases and dosages or the indications for use may otherwise be limited,

which could restrict the commercial value of the product.

Further, the FDA may require that certain contraindications, warnings

or precautions be included in the product labeling.

In addition, the FDA may require Phase 4 testing which involves clinical studies

designed to further assess pharmaceutical product safety and effectiveness and may require testing and surveillance programs to

monitor the safety of approved products that have been commercialized.

Before approving an NDA, the FDA will inspect the

facilities at which the product is manufactured.

The FDA will not approve the product 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, the FDA will typically inspect one or more clinical sites as well as the site where the pharmaceutical

product is manufactured to assure compliance with GCP and cGMP.

If the FDA determines 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.

In addition, the FDA will require the review and approval of product labeling.

The NDA review and approval process is lengthy

and difficult, and the FDA may refuse to approve an NDA if the applicable regulatory criteria are not satisfied or may require additional

clinical data or other data and information.

Even if such data and information is submitted, the FDA may ultimately decide that the NDA

does not satisfy the criteria for approval.

Data obtained from clinical studies are not always conclusive and the FDA may interpret data

differently than we interpret the same data.

The FDA will issue a complete response letter if the agency decides not to approve the NDA.

The complete response letter usually describes all of the specific deficiencies in the NDA identified by the FDA.

The deficiencies identified

may be minor, for example, requiring labeling changes, or major, for example, requiring additional clinical studies.

Additionally, the

complete response letter may include recommended actions that the applicant might take to place the application in a condition for approval.

If a complete response letter is issued, the applicant may either resubmit the NDA, addressing all of the deficiencies identified in the

letter, or withdraw the application.

If a product receives regulatory approval, the

approval may be significantly limited to specific diseases and dosages or the indications for use may otherwise be limited, which could

restrict the commercial value of the product.

Further, the FDA may require that certain contraindications, warnings, or precautions be

included in the product labeling.

In addition, the FDA may require Phase 4 testing which involves clinical studies designed to further

assess pharmaceutical product safety and effectiveness and may require testing and surveillance programs to monitor the safety of approved

products that have been commercialized.

Expedited Development and Review Programs

The FDA has a Fast Track program that is

intended to expedite or facilitate the process for reviewing new pharmaceutical products that meet certain criteria.

Specifically,

new pharmaceutical products are eligible for Fast Track designation if they are intended to treat a serious condition and demonstrate

the potential to address unmet medical needs for the condition.

Fast Track designation applies to the combination of the product

and the specific indication for which it is being studied.

Unique to a Fast Track product, the FDA may consider for review sections

of the NDA on a rolling basis before the complete application is submitted, if the sponsor provides a schedule for the submission

of the sections of the NDA, if the FDA determines that the schedule is acceptable and if the sponsor pays any required user fees

upon submission of the first section of the NDA.

Any product submitted to the FDA for market,

including a Fast Track program, may also be eligible for other FDA programs intended to expedite development and review, such as

priority review and accelerated approval.

Any product is eligible for priority review if it is intended to treat a serious condition

and it offers a significant improvement in the treatment, diagnosis or prevention of a disease compared to marketed products.

FDA will attempt to direct additional resources to the evaluation of an application for a new pharmaceutical product designated

for priority review in an effort to facilitate the review.

Additionally, accelerated approval may be available for a product intended

to treat a serious condition that provides meaningful therapeutic benefit over existing treatments, which means the product may

be approved on the basis of adequate and well-controlled clinical studies establishing that the product has an effect on a surrogate

endpoint that is reasonably likely to predict a clinical benefit, or on the basis of an effect on an intermediate clinical endpoint.

As a condition of accelerated approval, the FDA may require the sponsor to perform adequate and well-controlled post-marketing

clinical studies.

In addition, the FDA currently requires pre-approval of promotional materials for products receiving accelerated

approval, which could impact the timing of the commercial launch of the product.

Fast Track designation, priority review and accelerated

approval do not change the standards for approval but may expedite the development or approval process.

2021, the Company received Fast Track Designation from the FDA for Berubicin.

The FDA’s Fast Track program is intended

to expedite or facilitate the process for reviewing new pharmaceutical products that meet certain criteria.

Specifically, new pharmaceutical

products are eligible for Fast Track designation if they are intended to treat a serious condition and demonstrate the potential to address

unmet medical needs for the condition.

Fast Track designation applies to the combination of the product and the specific indication for

which it is being studied.

Unique to a Fast Track product, the FDA may consider for review sections of the NDA on a rolling basis before

the complete application is submitted, if the sponsor provides a schedule for the submission of the sections of the NDA, if the FDA determines

that the schedule is acceptable and if the sponsor pays any required user fees upon submission of the first section of the NDA.

Any product submitted to the FDA for market, including

a Fast Track program, may also be eligible for other FDA programs intended to expedite development and review, such as priority review

and accelerated approval.

Any product is eligible for priority review if it is intended to treat a serious condition and it offers a significant

improvement in the treatment, diagnosis or prevention of a disease compared to marketed products.

The FDA will attempt to direct additional

resources to the evaluation of an application for a new pharmaceutical product designated for priority review in an effort to facilitate

Additionally, accelerated approval may be available for a product intended to treat a serious condition that provides meaningful

therapeutic benefit over existing treatments, which means the product may be approved on the basis of adequate and well-controlled clinical

studies establishing that the product has an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit, or

on the basis of an effect on an intermediate clinical endpoint.

We believe that our potentially pivotal CNS-201 study of Berubicin for

the treatment of recurrent GBM is such a study.

As a condition of accelerated approval, the FDA may require the sponsor to perform adequate

and well-controlled post-marketing clinical studies.

In addition, the FDA currently requires pre-approval of promotional materials for

products receiving accelerated approval, which could impact the timing of the commercial launch of the product.

Fast Track designation,

priority review and accelerated approval do not change the standards for approval but may expedite the development or approval process.

Post-Approval Requirements

Any pharmaceutical products for which the

Company receives FDA approvals are subject to continuing regulation by the FDA, including, among other things, cGMP compliance,

record-keeping requirements, reporting of adverse experiences with the product, providing the FDA with updated safety and efficacy

information, product sampling and distribution requirements, complying with certain electronic records and signature requirements

and complying with FDA promotion and advertising requirements, which include, among others, standards for direct-to-consumer advertising,

prohibitions on promoting pharmaceutical products for uses or in patient populations that are not described in the pharmaceutical

product’s approved labeling (known as “off-label use”), industry-sponsored scientific and educational activities

and promotional activities involving the internet.

Failure to comply with FDA requirements can have negative consequences, including

adverse publicity, enforcement letters from the FDA, actions by the U.S.

Any pharmaceutical products for which the Company

receives FDA approvals are subject to continuing regulation by the FDA, including, among other things, cGMP compliance, record-keeping

requirements, reporting of adverse experiences with the product, providing the FDA with updated safety and efficacy information, product

sampling and distribution requirements, complying with certain electronic records and signature requirements and complying with FDA promotion

and advertising requirements, which include, among others, standards for direct-to-consumer advertising, prohibitions on promoting pharmaceutical

products for uses or in patient populations that are not described in the pharmaceutical product’s approved labeling (known as “off-label

use”), industry-sponsored scientific and educational activities and promotional activities involving the internet.

Failure to comply

with FDA requirements can have negative consequences, including adverse publicity, enforcement letters from the FDA, actions by the U.S.

Department of Justice and/or U.S.

Department of Health

and Human Services’

Office of Inspector General, mandated corrective advertising or communications with doctors, and civil

or criminal penalties.

Although physicians may prescribe legally available pharmaceutical products for off-label uses, manufacturers

may not directly or indirectly market or promote such off-label uses.

We expect to rely on third parties

for the production of clinical and commercial quantities of our products.

Manufacturers of our products are required to comply

with applicable FDA manufacturing requirements contained in the FDA’s cGMP regulations.

cGMP regulations require, among other

things, quality control and quality assurance, as well as the corresponding maintenance of records and documentation.

Pharmaceutical

product manufacturers and other entities involved in the manufacture and distribution of approved pharmaceutical products 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 and other laws.

Accordingly, manufacturers must continue to expend

time, money and effort in the area of production and quality control to maintain cGMP compliance.

Discovery of problems with a

product after approval may result in restrictions on a product, manufacturer or holder of an approved NDA, including withdrawal

of the product from the market.

In addition, changes to the manufacturing process generally require prior FDA approval before being

implemented and other types of changes to the approved product, such as adding new indications and additional labeling claims,

are also subject to further FDA review and approval.

Pharmaceutical Coverage, Pricing and

Reimbursement

Significant uncertainty exists as to the

coverage and reimbursement status of any pharmaceutical product candidates for which we may obtain regulatory approval.

United States and in markets in other countries, sales of any products for which we receive regulatory approval for commercial

sale will depend in part upon the availability of reimbursement from third-party payers.

Third-party payers include government

payers such as Medicare and Medicaid, managed care providers, private health insurers and other organizations.

The process for

determining whether a payer will provide coverage for a pharmaceutical product may be separate from the process for setting the

price or reimbursement rate that the payer will pay for the pharmaceutical product.

Third-party payers may limit coverage to specific

pharmaceutical products on an approved list, or formulary, which might not, and frequently does not, include all of the FDA-approved

pharmaceutical products for a particular indication.

Third-party payers are increasingly challenging the price and examining the

medical necessity and cost-effectiveness of medical products and services, in addition to their safety and efficacy.

A payer’s

decision to provide coverage for a pharmaceutical product does not imply that an adequate reimbursement rate will be approved.

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.

In addition, in the United States there is a growing emphasis on comparative effectiveness

research, both by private payers and by government agencies.

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 the FDA

Department of Health and Human Services’ Office of Inspector General, mandated corrective advertising

or communications with doctors, and civil or criminal penalties.

Although physicians may prescribe legally available pharmaceutical products

for off-label uses, manufacturers may not directly or indirectly market or promote such off-label uses.

We expect to rely on third parties for the production

of clinical and commercial quantities of our products.

Manufacturers of our products are required to comply with applicable FDA manufacturing

requirements contained in the FDA’s cGMP regulations.

cGMP regulations require, among other things, quality control and quality

assurance, as well as the corresponding maintenance of records and documentation.

Pharmaceutical product manufacturers and other entities

involved in the manufacture and distribution of approved pharmaceutical products 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 and other laws.

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

control to maintain cGMP compliance.

Discovery of problems with a product after approval may result in restrictions on a product, manufacturer

or holder of an approved NDA, including withdrawal of the product from the market.

In addition, changes to the manufacturing process generally

require prior FDA approval before being implemented and other types of changes to the approved product, such as adding new indications

and additional labeling claims, are also subject to further FDA review and approval.

Pharmaceutical Coverage, Pricing and Reimbursement

Significant uncertainty exists as to the coverage

and reimbursement status of any pharmaceutical product candidates for which we may obtain regulatory approval.

In the United States and

in markets in other countries, sales of any products for which we receive regulatory approval for commercial sale will depend in part

upon the availability of reimbursement from third-party payers.

Third-party payers include government payers such as Medicare and Medicaid,

managed care providers, private health insurers and other organizations.

The process for determining whether a payer will provide coverage

for a pharmaceutical product may be separate from the process for setting the price or reimbursement rate that the payer will pay for

the pharmaceutical product.

Third-party payers may limit coverage to specific pharmaceutical products on an approved list, or formulary,

which might not, and frequently does not, include all of the FDA-approved pharmaceutical products for a particular indication.

payers are increasingly challenging the price and examining the medical necessity and cost-effectiveness of medical products and services,

in addition to their safety and efficacy.

A payer’s decision to provide coverage for a pharmaceutical product does not imply that

an adequate reimbursement rate will be approved.

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.

In addition, in the United States there is

a growing emphasis on comparative effectiveness research, both by private payers and by government agencies.

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 the FDA approvals.

Our pharmaceutical product candidates may not be considered medically necessary or cost-effective.

To the extent other

drugs or therapies are found to be more effective than our products, payers may elect to cover such therapies in lieu of our products

and/or reimburse our products at a lower rate.

Orphan Drug exclusivity prevents for seven

years the approval of another product with the same active moiety for the same rare disease.

If a product is a new chemical entity

(i.e., generally that the moiety has not previously been approved), it may receive five years of exclusivity, during which period

FDA may not accept for review certain NDAs for another product with the same moiety.

If approval of a product required new clinical

data, it may convey three years of exclusivity against approval of certain NDAs for similar products.

The marketability of any pharmaceutical

product candidates for which we may receive regulatory approval for commercial sale may suffer if the government and third-party

payers fail to provide adequate coverage and reimbursement.

In addition, emphasis on managed care in the United States has increased

and we expect this will continue to increase the pressure on pharmaceutical pricing.

Coverage policies and third-party reimbursement

rates may change at any time.

Even if favorable coverage and reimbursement status is attained for one or more products for which

we may receive regulatory approval, less favorable coverage policies and reimbursement rates may be implemented in the future.

To the extent other drugs or therapies are found to be more effective than our products, payers may elect to cover such therapies in lieu

of our products and/or reimburse our products at a lower rate.

Orphan Drug exclusivity prevents for seven years

the approval of another product with the same active moiety for the same rare disease.

On June 10, 2020, the FDA granted Orphan Drug Designation

for Berubicin for the treatment of malignant gliomas.

If a product is a new chemical entity (i.e., generally that the moiety has not previously

been approved), it may receive five years of exclusivity, during which period FDA may not accept for review certain NDAs for another product

with the same moiety.

If approval of a product required new clinical data, it may convey three years of exclusivity against approval of

certain NDAs for similar products.

The marketability of any pharmaceutical product

candidates for which we may receive regulatory approval for commercial sale may suffer if the government and third-party payers fail to

provide adequate coverage and reimbursement.

In addition, emphasis on managed care in the United States has increased and we expect this

will continue to increase the pressure on pharmaceutical pricing.

Coverage policies and third-party reimbursement rates may change at

Even if favorable coverage and reimbursement status is attained for one or more products for which we may receive regulatory

approval, less favorable coverage policies and reimbursement rates may be implemented in the future.

International Regulation

In addition to regulations in the United

States, we will be subject to a variety of foreign regulations governing clinical trials and commercial sales and distribution

of our future drugs.

Whether or not we obtain FDA approval for a drug, we must obtain approval of a drug by the comparable regulatory

authorities of foreign countries before we can commence clinical trials or marketing of the drug in those countries.

process varies from country to country, and the time may be longer or shorter than that required for FDA approval.

The requirements

governing the conduct of clinical trials, product licensing, pricing and reimbursement vary greatly from country to country.

Under European Union regulatory systems,

marketing authorizations may be submitted either under a centralized or mutual recognition procedure.

The centralized procedure

provides for the grant of a single marketing authorization that is valid for all European Union member states.

The mutual recognition

procedure provides for mutual recognition of national approval decisions.

Under this procedure, the holder of a national marketing

authorization may submit an application to the remaining member states.

Within 90 days of receiving the applications and assessment

report, each member state must decide whether to recognize approval.

In addition to regulations in Europe and

the United States, we will be subject to a variety of foreign regulations governing clinical trials and commercial distribution

of our future drugs.

In addition to regulations in the United States,

we will be subject to a variety of foreign regulations governing clinical trials and commercial sales and distribution of our future drugs.

Whether or not we obtain FDA approval for a drug, we must obtain approval of a drug by the comparable regulatory authorities of foreign

countries before we can commence clinical trials or marketing of the drug in those countries.

The approval process varies from country

to country, and the time may be longer or shorter than that required for FDA approval.

The requirements governing the conduct of clinical

trials, product licensing, pricing and reimbursement vary greatly from country to country.

Under European Union regulatory systems, marketing

authorizations may be submitted either under a centralized or mutual recognition procedure.

The centralized procedure provides for the

grant of a single marketing authorization that is valid for all European Union member states.

The mutual recognition procedure provides

for mutual recognition of national approval decisions.

Under this procedure, the holder of a national marketing authorization may submit

an application to the remaining member states.

Within 90 days of receiving the applications and assessment report, each member state must

decide whether to recognize approval.

In addition to regulations in Europe and the United

States, we will be subject to a variety of foreign regulations governing clinical trials and commercial distribution of our future drugs.

License Agreements

On November 21, 2017, we entered into a

Collaboration and Asset Purchase Agreement with Reata.

Pursuant to the Reata Agreement we purchased all of Reata’s intellectual

property and development data regarding Berubicin, including all trade secrets, knowhow, confidential information and other intellectual

property rights.

In exchange for these rights, we agreed to pay Reata an amount equal to 2.25% of the net sales of Berubicin for

a period of 10 years from our first commercial sale of Berubicin plus $10,000.

Reata also agreed to use commercially reasonable

efforts, at the Company’s expense, to provide development assistance related to the product and/or product intellectual property.

The Reata Agreement will terminate ten years after the date of the first commercial sale of product, provided the agreement may

be earlier terminated due to a material breach of the agreement by either party, or if either party undergoes a bankruptcy event.

On December 28, 2017, we obtained the rights

to a worldwide, exclusive royalty-bearing, license to the chemical compound commonly known as Berubicin from HPI in an agreement

we refer to as the HPI License.

Under the HPI License we obtained the exclusive right to develop certain patented chemical compounds

for use in the treatment of cancer anywhere in the world.

In the HPI License we agreed to pay HPI:

(i) development fees of $750,000

over a three-year period beginning November 2019;

(ii) a 2% royalty on net sales;

(iii) a $50,000 per year license fee;

(iv) milestone

payments of $100,000 upon the commencement of a Phase II trial and $1.0 million upon the approval of a NDA for Berubicin;

200,000 shares of our common stock.

We had the right, although we chose not to exercise such right, exercisable before December

28, 2020, to terminate the HPI License in full upon payment to HPI in the amount of $2,000,000 (the “Buy-Out Fee”).

Upon payment of the Buy-Out Fee, (i) our obligation to pay any additional development payments, license fee and the

milestone payments would have ceased;

(ii) HPI would have transferred ownership of all development data in its possession to us

and (iii) HPI would have transferred to us any regulatory submissions including any IND, NDA or ANDA related to the patent

The payment of the Buy-Out Fee would not have relieved us of our obligation to use commercially reasonable development

efforts to develop a licensed product by the development deadline as provided in the HPI License.

On November 21, 2017, we entered into a Collaboration

and Asset Purchase Agreement with Reata (the “Reata Agreement”).

Pursuant to the Reata Agreement we purchased all of Reata’s

intellectual property and development data regarding Berubicin, including all trade secrets, knowhow, confidential information and other

intellectual property rights.

On December 28, 2017, the Company entered into

a Technology Rights and Development Agreement with Houston Pharmaceuticals, Inc.

HPI is affiliated with Dr.

Priebe, our founder and significant shareholder.

Pursuant to this agreement, the Company obtained a worldwide exclusive license to the

chemical compound commonly known as WP744.

In exchange for these rights, the Company agreed to pay consideration to HPI as follows:

a royalty of 2% of net sales of any product utilizing WP744 for a period of ten years after the first commercial sale of such;

$100,000 upon beginning Phase II clinical trials (paid in 2021);

and (iii) $200,000 upon the approval by the FDA of a New Drug Application

for any product utilizing WP744;

and (iv) a series of quarterly development payments totaling $750,000 beginning immediately after the

Company’s raise of $7,000,000 of investment capital.

In addition, the Company issued 200,000 shares of the Company’s common

stock valued at $0.045 per share to HPI upon execution of the agreement.

During the year ended December 31, 2021 and 2020, the Company

recognized $450,000 and $237,500, respectively related to this agreement.

Unrelated to this agreement, the Company purchases pharmaceutical

products from HPI for the manufacturing of Berubicin API.

HPI is able to offer superior pricing and timelines compared to alternative

The purchases from HPI are related party transactions and reviewed and approved by the Company’s audit committee.

With the Reata Agreement and the HPI License, we

believe we have obtained all rights and intellectual property necessary to develop Berubicin.

As stated earlier, it is our plan to obtain

additional intellectual property covering other compounds which, subject to the receipt of additional financing, may be developed into

drugs for brain and other cancers.

On August 30, 2018, we entered into a sublicense

agreement with WPD Pharmaceuticals, Inc., or WPD, pursuant to which we granted WPD an exclusive sublicense, even as to us, for

the patent rights we licensed pursuant to the HPI License within the following countries:

Poland, Estonia, Latvia, Lithuania, Belarus,

Ukraine, Moldova, Romania, Bulgaria, Serbia, Macedonia, Albania, Armenia, Azerbaijan, Georgia, Montenegro, Bosnia, Croatia, Slovenia,

Slovakia, Czech Republic, Hungary, Chechnya, Uzbekistan, Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan, Greece, Austria, and

The sublicense agreement provides that WPD must use commercially reasonable development efforts to attempt to develop and

commercialize licensed products in the above mentioned territories, which means the expenditure of at least $2.0 million on the

development, testing, regulatory approval or commercialization of the licensed products during the three year period immediately

following the date of the sublicense agreement.

In the event that WPD fails to use commercially reasonable development efforts

to by the foregoing three-year deadline, we have the right to terminate this sublicense agreement.

In consideration for the rights

granted under the sublicense agreement, to the extent we are required to make any payments to HPI pursuant to the HPI License as

a result of this sublicense agreement, WPD agreed to advance us such payments, and to pay us a royalty equal to 1% of such payments.

agreement with WPD Pharmaceuticals, Inc., or WPD, pursuant to which we granted WPD an exclusive sublicense, even as to us, for the patent

rights we licensed pursuant to the HPI License within the following countries:

Poland, Estonia, Latvia, Lithuania, Belarus, Ukraine, Moldova,

Romania, Bulgaria, Serbia, Macedonia, Albania, Armenia, Azerbaijan, Georgia, Montenegro, Bosnia, Croatia, Slovenia, Slovakia, Czech Republic,

Hungary, Chechnya, Uzbekistan, Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan, Greece, Austria, and Russia.

The sublicense agreement

provides that WPD must use commercially reasonable development efforts to attempt to develop and commercialize licensed products in the

above mentioned territories, which means the expenditure of at least $2.0 million on the development, testing, regulatory approval or

commercialization of the licensed products during the three year period immediately following the date of the sublicense agreement.

of December 31, 2021, WPD has demonstrated that it has exercised commercially reasonable development efforts under this agreement.

consideration for the rights granted under the sublicense agreement, to the extent we are required to make any payments to HPI pursuant

to the HPI License as a result of this sublicense agreement, WPD agreed to advance us such payments, and to pay us a royalty equal to

1% of such payments.

WPD is a Polish corporation that is majority-owned by an entity controlled by Dr.

Priebe, our founder and largest shareholder.

Priebe, our founder and largest

On August 31, 2018, we entered into a sublicense

agreement with Animal Life Sciences, LLC, or ALI, pursuant to which we granted ALI an exclusive sublicense, even as to us, for

the patent rights we licensed pursuant to the HPI License solely for the treatment of cancer in non-human animals through any type

of administration.

In consideration for the rights granted under the sublicense agreement, ALI agreed to issue us membership interests

in ALI equal to 1.52% of the outstanding ALI membership interests.

As additional consideration for the rights granted, to the extent

we are required to make any payments to HPI pursuant to the HPI License as a result of this sublicense agreement, ALI agreed to

advance us such payments, and to pay us a royalty equal to 1% of such payments.

Priebe holds 38% of the membership interests

On January 10, 2020, we entered into a Patent

and Technology License Agreement (the “1244 Agreement”) with The Board of Regents of The University of Texas System,

an agency of the State of Texas, on behalf of The University of Texas M.

Anderson Cancer Center (“UTMDACC”).

to the 1244 Agreement, we obtained a royalty-bearing, worldwide, exclusive license to certain intellectual property rights, including

patent rights, related to our WP1244 drug technology.

In consideration, we must make payments to UTMDACC including an up-front

license fee, annual maintenance fee, milestone payments and royalty payments (including minimum annual royalties) for sales of

licensed products developed under the 1244 Agreement.

The term of the 1244 Agreement expires on the last to occur of:

(a) the expiration

of all patents subject to the 1244 Agreement, or (b) fifteen years after execution;

provided that UTMDACC has the right to terminate

the 1244 Agreement in the event that we fail to meet certain commercial diligence milestones.

On May 7, 2020, pursuant to the WP1244 Portfolio

license agreement described above, the Company entered into a Sponsored Research Agreement with UTMDACC to perform research relating

to novel anticancer agents targeting CNS malignancies.

agreement with Animal Life Sciences, LLC, or ALI, pursuant to which we granted ALI an exclusive sublicense, even as to us, for the patent

rights we licensed pursuant to the HPI License solely for the treatment of cancer in non-human animals through any type of administration.

In consideration for the rights granted under the sublicense agreement, ALI agreed to issue us membership interests in ALI equal to 1.52%

of the outstanding ALI membership interests.

As additional consideration for the rights granted, to the extent we are required to make

any payments to HPI pursuant to the HPI License as a result of this sublicense agreement, ALI agreed to advance us such payments, and

to pay us a royalty equal to 1% of such payments.

Priebe, our founder and significant shareholder, holds 38% of the membership interests

On January 10, 2020, Company entered into a Patent

and Technology License Agreement (the “1244 Agreement”) with The Board of Regents of The University of Texas System, an agency

of the State of Texas, on behalf of UTMDACC.

Pursuant to the 1244 Agreement, the Company obtained a royalty-bearing, worldwide, exclusive

license to certain intellectual property rights, including patent rights, related to the WP1244 drug technology.

In consideration, the

Company must make payments to UTMDACC including an up-front license fee, annual maintenance fee, milestone payments and royalty payments

(including minimum annual royalties) on sales of licensed products developed under the Agreement.

The term of the Agreement expires on

the last to occur of:

(a) the expiration of all patents subject to the Agreement, or (b) fifteen years after execution;

provided that

UTMDACC has the right to terminate this Agreement in the event that the Company fails to meet certain commercial diligence milestones.

The commercial diligence milestones are as follows (i) initiated PC toxicology to support filing of Investigational New Drug Application

(“IND”) or New Drug Application (“NDA”) for the Licensed Product within the eighteen (18) month period following

the Effective Date (ii) file and IND for the Licensed Product within three (3) year period following the Effective Date and (iii) Commencement

of Phase I Study within the five (5) year period following the Effective Date.

During the year ended December 31, 2021, the Company paid

$48,668 to UTMDACC related to this agreement.

On May 7, 2020, pursuant to the 1244 Agreement

described above, the Company entered into a Sponsored Research Agreement with UTMDACC to perform research relating to novel anticancer

agents targeting CNS malignancies.

The Company agreed to fund approximately $1,134,000 over a two-year period.

The Company paid and recorded $334,000 in 2020 related to this agreement in research and development expenses

in the Company’s Statements of Operations.

The remaining $720,000 will be paid in 2021, of which $400,000 was accrued at

December 31, 2020.

During the year ended December

31, 2020, the Company paid $334,000 and accrued $400,000 related to this agreement in research and development expenses in the Company’s

Consolidated Statements of Operations.

During the year ended December 31, 2021, the Company paid $800,000 to UTMDACC related to this agreement.

The principal investigator for this agreement is Dr.

The work conducted under this Sponsored Research Agreement has produced a

new mesylate salt of WP1244 termed WP1874.

We believe the enhanced solubility of this salt may increase its ability to be formulated for

use in an IV infusion, while maintaining similar potency and toxicity characteristics.

As such, WP1874 will be the primary focus in our

development efforts of the WP1244 portfolio.

On March 20, 2020, we entered into a Development

Agreement with WPD Pharmaceuticals (“WPD”) (the “Development Agreement”), a company founded by Dr.

Pursuant to the Development Agreement, WPD agreed to use its commercially reasonable efforts in good faith to develop and commercialize

certain products that WPD had previously sublicensed, solely in the field of pharmaceutical drug products for the treatment of

any viral infection in humans, with a goal of eventual approval of in certain territories consisting of:

Poland, Estonia, Latvia,

Lithuania, Belarus, Ukraine, Romania, Armenia, Azerbaijan, Georgia, Slovakia, Czech Republic, Hungary, Uzbekistan, Kazakhstan,

Greece, Austria, Russia, Netherlands, Turkey, Belgium, Switzerland, Sweden, Portugal, Norway, Denmark, Ireland, Finland, Luxembourg,

Pursuant to the Development Agreement, we agreed to pay WPD the following payments:

(i) an upfront payment of $225,000

to WPD (paid in April 2020);

and (ii) within thirty days of the verified achievement of the Phase II Milestone, (such verification

shall be conducted by an independent third party mutually acceptable to the parties hereto), we will make a payment of $775,000

WPD agreed to pay us a development fee of 50% of the net sales for any products in the above territories;

provided that

Poland shall not be included as a territory after WPD receives marketing approval for a product in one-half of the countries included

in the agreed upon territories or upon the payment by WPD to us of development fees of $1.0 million.

The term of the Development

Agreement will expire on the expiration of the sublicense pursuant to which WPD has originally sublicensed the products, which

will occur upon the expiration of the patents subject to the sublicense agreement, the earliest of which expires in 2024.

As of February 11, 2021, we had three full

time employees.

We also have two part-time employees serving as our chief medical and scientific officers, and accordingly, a high

percentage of the work performed for our development projects is conducted by qualified part-time staff and independent contractors.

Agreement with WPD Pharmaceuticals (“WPD”) (the “Development Agreement”), a company founded by Dr.

to the Development Agreement, WPD agreed to use its commercially reasonable efforts in good faith to develop and commercialize certain

products that WPD had previously sublicensed, solely in the field of pharmaceutical drug products for the treatment of any viral infection

in humans, with a goal of eventual approval of in certain territories consisting of:

Poland, Estonia, Latvia, Lithuania, Belarus, Ukraine,

Romania, Armenia, Azerbaijan, Georgia, Slovakia, Czech Republic, Hungary, Uzbekistan, Kazakhstan, Greece, Austria, Russia, Netherlands,

Turkey, Belgium, Switzerland, Sweden, Portugal, Norway, Denmark, Ireland, Finland, Luxembourg, Iceland.

Pursuant to the Development Agreement,

we agreed to pay WPD the following payments:

(i) an upfront payment of $225,000 to WPD (paid in April 2020);

and (ii) within thirty days

of the verified achievement of the Phase II Milestone, (such verification shall be conducted by an independent third party mutually acceptable

to the parties hereto), we will make a payment of $775,000 to WPD.

WPD agreed to pay us a development fee of 50% of the net sales for

any products in the above territories;

provided that Poland shall not be included as a territory after WPD receives marketing approval

for a product in one-half of the countries included in the agreed upon territories or upon the payment by WPD to us of development fees

of $1.0 million.

The term of the Development Agreement will expire on the expiration of the sublicense pursuant to which WPD has originally

sublicensed the products, which will occur upon the expiration of the patents subject to the sublicense agreement, the earliest of which

expires in 2024.

On February 19, 2021, CNS entered into an Investigational

Medicinal Product Supply Agreement with WPD, a related party.

CNS agreed to sell the Berubicin drug product to WPD at historical cost

of manufacturing without markup so that WPD may conduct the clinical trials contemplated by the sublicense agreement.

WPD agreed to pay

CNS the following payments:

(i) an upfront payment of $131,073 upon execution of the agreement, (ii), a payment of $262,145 upon

final batch release and certification performed by WPD's subcontractor, and (iii) a final payment of $262,145 upon Clinical Trial Application

acceptance by the relevant regulatory authority.

All three milestones have been met as of December 31, 2021.

In addition, as of December

31, 2021, the drug product with a cost of approximately $655,000 has been delivered to WPD and is being held at a third party depot.

As such, the full amount of approximately $655,000 is now due from WPD.

As of December 31, 2021, CNS has invoiced the three amounts plus

pass through cost for a total of $656,938.

However, as of December 31, 2021, WPD has not remitted payment for the invoices and, as such,

we have not recorded a receivable due to the collectability issues.

Subsequent to December 31, 2021, the Company has received payment

for the first amount due of $131,073.

The Company is continuing to work with WPD to resolve this situation.

As of March 3, 2022, we had three full time employees.

We also have two part-time employees serving as our chief medical and scientific officers, and accordingly, a high percentage of the work

performed for our development projects is conducted by qualified part-time staff and independent contractors.

Legal Proceedings

We are not subject to any litigation.

Our corporate and executive offices are

in located in a leased facility in Houston, Texas.

We believe our facilities are sufficient to meet our current needs and that

suitable space will be available as and when needed.

From time to time in the ordinary course of our

business, we may be involved in legal proceedings, the outcomes of which may not be determinable.

The results of litigation are inherently

unpredictable.

Any claims against us, whether meritorious or not, could be time consuming, result in costly litigation, require significant

amounts of management time and result in diversion of significant resources.

We have insurance policies covering any potential losses

where such coverage is cost effective.

We are not at this time involved in any additional

legal proceedings that we believe could have a material effect on our business, financial condition, results of operations or cash flows.

Our corporate and executive offices are located

in a leased facility in Houston, Texas.

We believe our facilities are sufficient to meet our current needs and that suitable space will

be available as and when needed.

We do not own any real property.

2 unchanged sentences

On this Web site, we post the following filings as soon as reasonably practicable after they are electronically filed with or furnished

Securities and Exchange Commission (“SEC”):

our Annual Reports on Form 10-K;

our Quarterly Reports on Form

our Quarterly Reports on Form 10-Q;

our Current Reports on Form 8-K;

our proxy statements related to our annual stockholders’

and any amendments

to those reports or statements.

our proxy statements related to our annual stockholders’ meetings;

and any amendments to those

reports or statements.

All such filings are available on our Web site free of charge.

The charters of our audit, nominating

and governance and compensation committees and our Code of Business Conduct and Ethics Policy are also available on our Web site

and in print to any stockholder who requests them.

The content on our Web site is not incorporated by reference into this Form

10-K unless expressly noted.

The charters of our audit, nominating and governance

and compensation committees and our Code of Business Conduct and Ethics Policy are also available on our Web site and in print to any

stockholder who requests them.

The content on our Web site is not incorporated by reference into this Form 10-K unless expressly noted.

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