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Item 1A. Risk Factors

2023-03-29 compared with 2022-02-28 · 467 added, 391 removed, 600 unchanged (59% of the section changed)

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Also, the risks that we now foresee might affect us to a greater or different degree than currently expected.

There are a number of important factors that could cause our actual results to differ materially from those expressed or implied by any of our forward-looking statements in this

Annual Report.

There are a number of important factors that could cause our actual results to differ materially from those expressed or implied by any of our forward-looking statements in this Annual Report.

These factors include, without limitation, the risk factors listed below, and other factors presented throughout this Annual Report and any other documents filed by us with the SEC and the Canadian securities regulators on SEDAR.

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Risks Related to Our Business

● We have a history of significant losses and have generated de minimis licensing revenue and no revenue from the sale of products since our inception.

● PEDMARK TM is currently our only product candidate.

PEDMARK TM is still in development and there is no assurance that it will receive regulatory approval or that we will successfully develop it into a commercially viable product.

● We may be required to conduct additional clinical trials for PEDMARK TM , which would be costly and time-consuming to complete.

● We may require additional financing to obtain regulatory approval for and commercialize PEDMARK TM , and a failure to obtain this capital when needed on acceptable terms, or at all, could force us to delay, limit, reduce, or terminate our product development, other operations, or commercialization efforts.

● We have a history of significant losses and have generated limited revenue from the sale of products since our inception.

● We may be required to conduct additional clinical trials for PEDMARK ® , which would be costly and time-consuming to complete.

● We may require additional financing to obtain regulatory approval for and commercialize PEDMARK ® , and a failure to obtain this capital when needed on acceptable terms, or at all, could force us to delay, limit, reduce, or terminate further product development, other operations, or commercialization efforts.

● We are currently and may in the future be the target of securities litigation, which may be costly and time-consuming to defend.

● We have only recently transitioned from a development stage biopharmaceutical company to a commercial stage biopharmaceutical company, which may make it difficult for you to evaluate the success of our business to date and to assess our future viability.

● Our business may be adversely affected by the ongoing COVID-19 pandemic.

● Our business involves environmental risks and potential exposure to environmental liabilities.

Risks Related to the Clinical Development and Marketing Approval of Our Product Candidate

● PEDMARK TM has not received marketing approval from the FDA or any comparable foreign authorities.

Risks Related to Marketing Approval of Our Product Candidate

● PEDMARK ® has received marketing approval from the FDA, but not from any comparable foreign authorities.

These approval processes are costly, time-consuming, and inherently unpredictable, and it is possible that our applications for marketing approval will be denied.

● Our NDA for PEDMARK TM received a CRL from the FDA in August 2020 and in November 2021, which in each case identified deficiencies in the third-party manufacturing facility that manufactures PEDMARK TM on our behalf.

Risks Related to Commercialization of Our Product Candidate

● Even if we receive regulatory approvals for PEDMARK TM , it will still be subject to continued regulatory review and could be subject to labeling and other restrictions.

● Sales of PEDMARK TM , assuming it obtains regulatory approval, will depend on reimbursement by payers and these payers are subject to pressures to contain costs.

In addition, coverage and reimbursement for PEDMARK TM may be limited or unavailable in certain market segments.

● PEDMARK TM targets diseases with small patient populations and we may not be effective at identifying patients.

● We may not be able to gain or maintain market acceptance of PEDMARK TM among the medical community, patients, or payers.

● If we fail to comply with applicable healthcare laws and regulations, we may be subject to investigations and civil or criminal penalties and could lose any regulatory approvals that we obtain for PEDMARK TM .

● We have just started to build our commercial team and have limited experience in commercializing pharmaceutical products.

● Our success depends on our ability to successfully commercialize PEDMARK ® .

We are a single product company with only limited commercial experience, which makes it difficult to evaluate our current business, predict our future prospects and forecast our financial performance and growth.

● If we are unable to successfully commercialize PEDMARK ® , our business, results of operations and financial condition may be materially adversely affected.

● Our business is subject to substantial competition.

● Our business may require additional capital.

● The obligations incident to being a public company place significant demands on our management.

● We are highly dependent on our small number of key personnel and advisors.

● The ongoing COVID-19 pandemic and the worldwide attempts to contain it could harm our business and results of operations and financial condition and we could be adversely impacted by it.

● We face a risk of product liability claims and may not be able to obtain adequate insurance.

● Business or economic disruptions or global health concerns could seriously harm our development efforts and increase our costs and expenses.

● Now that we have received regulatory approvals for PEDMARK ® , it will still be subject to continued regulatory review and could be subject to labeling and other restrictions.

● Sales of PEDMARK ® will depend on reimbursement by payers and these payers are subject to pressures to contain costs.

In addition, coverage and reimbursement for PEDMARK ® may be limited or unavailable in certain market segments.

● PEDMARK ® targets diseases with small patient populations and we may not be effective at identifying patients.

● We may not be able to gain or maintain market acceptance of PEDMARK ® among the medical community, patients, or payers.

● Changes in healthcare laws and regulations, as well as changes in healthcare policy, could adversely affect our business.

● PEDMARK TM may be subject to product liability claims.

Risks Related to Third Parties

● We rely on third parties to supply raw materials, to conduct clinical trials, and to manufacture PEDMARK TM .

● We rely on third parties to supply raw materials, to conduct clinical trials, and to manufacture PEDMARK ® .

If these third parties fail to satisfactorily perform for us, or if they fail to comply with applicable legal and regulatory requirements, it could have a material adverse effect on our business.

The above-referenced CRLs resulted from deficiencies identified by the FDA in the third-party manufacturing facility that manufactures PEDMARK TM on our behalf.

Risks Related to Government Regulation

● • The regulatory approval process is lengthy, and we may not be able to obtain all of the regulatory approvals required to manufacture and commercialize PEDMARK ® in all areas in which we are licensed to supply it.

● • We may face significant delays in our clinical studies and trials due to an inability to recruit patients for our clinical studies and trials or to retain patients in the clinical studies and trials we may perform.

● • If our third-party suppliers or contract manufacturers do not maintain appropriate standards of manufacturing in accordance with cGMP and other manufacturing regulations, our development and commercialization activities could suffer significant interruptions or delays.

● • PEDMARK ® is subject to ongoing regulatory review.

If we fail to comply with continuing United States and applicable foreign regulations, we could lose those approvals, and our business would be severely harmed.

● • Enacted and future legislation or judicial action may increase the difficulty and cost for us to commercialize PEDMARK ® or any other drug candidates we may acquire or license and affect the prices we may obtain.

● • If we fail to obtain or subsequently maintain orphan drug exclusivity or regulatory exclusivity for PEDMARK ® and any other orphan drug candidates we may acquire or license, our competitors may sell products to treat the same conditions at greatly reduced prices, and our revenues would be significantly adversely affected.

● • Changes to the Orphan Drug Act or successful legal challenges to the FDA’s interpretation of the Orphan Drug Act may affect our ability to obtain or subsequently maintain orphan drug exclusivity or may affect the scope orphan drug exclusivity for our product.

● • Our operations and relationships with healthcare providers, healthcare organizations, customers and third-party payors are subject to applicable anti-bribery, anti-kickback, fraud and abuse, transparency and other healthcare laws and regulations, which could expose us to, among other things, enforcement actions, criminal

sanctions, civil penalties, contractual damages, reputational harm, administrative burdens and diminished profits and future earnings.

● Risks Related to Our Intellectual Property

● PEDMARK TM is based on intellectual property exclusively licensed to us by OHSU, and the license is terminable in the event of a breach by us under the license agreement.

If we were to lose our license from OHSU, we may be required to terminate any development and commercialization of PEDMARK TM .

● We are dependent on our relationships and license agreements, and we rely upon the patent rights granted to us pursuant to the license agreements.

● Our success will depend significantly on our ability to operate without infringing the patents and other proprietary rights of third parties.

● We may incur substantial costs as a result of litigation or other proceedings relating to patent and other intellectual property rights.

● If we cannot obtain new patents, maintain our existing patents, and protect our trade secrets and other intellectual property, our business and competitive position may be harmed.

● Patent protection for PEDMARK TM may expire before we are able to realize its commercial value.

● Patent protection for PEDMARK ® may expire before we are able to fully realize its commercial value.

● We are currently and may in the future be the target of patent litigation, which may be costly and time-consuming to defend.

● Changes in United States patent law could diminish the value of patents in general, thereby impairing our ability to protect PEDMARK TM .

● Changes in United States patent law could diminish the value of patents in general, thereby impairing our ability to protect PEDMARK ® .

● If we are found to be infringing third-party patents, we may be forced to pay damages and/or obtain a license.

If we cannot obtain a license, we may be prevented from the development, manufacture, or commercialization of PEDMARK TM .

● It is possible that we could lose market exclusivity for PEDMARK TM earlier than expected.

If we cannot obtain a license, we may be prevented from the manufacture and sale of PEDMARK ® .

● It is possible that we could lose market exclusivity for PEDMARK ® earlier than expected.

Risks Related to Our Industry

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We face significant competition from other pharmaceutical, biopharmaceutical, and biotechnology companies, many of which have significantly greater financial, technical, and human resources than we do and may be better equipped to develop, manufacture, and market products.

Risks Related to Owning Our Common Shares

● We may be unable to maintain the listing of our common shares on the Nasdaq Capital Market or the TSX, which would make it more difficult for shareholders to dispose of our common shares.

● The market price of our common shares is highly volatile and could cause the value of your investment to significantly decline.

● Our existing principal shareholders hold a substantial number of our common shares and may be able to exercise influence in matters requiring approval of our shareholders.

● There are a large number of our common shares underlying outstanding options, and reserved for issuance under our stock option plan, that may be sold in the market, which could depress the market price of our shares and result in substantial dilution to our shareholders.

● We may need to raise additional funds in the future to continue our operations.

Any equity offering could result in significant dilution to our shareholders and decrease the value of our common shares.

Any debt offering will increase our financial risk.

● We have not paid any dividends and do not anticipate declaring any dividends in the foreseeable future.

● We may be a passive foreign investment company, which could result in adverse United States federal income tax consequences to U.S.

There are also general risk factors relating to us that you should consider that relate to our business and to our common stock.

Risks Related to Our Business

We have a history of significant losses and have had no revenues to date through the sale of our products.

We have a history of significant losses and have had limited revenues to date through the sale of our product.

If we do not generate significant revenues, we will not achieve profitability.

To date, we have been engaged primarily in research and development activities.

We have had no revenues through the commercial sale of products, and we do not expect to have significant revenues until we are able to either sell our product candidate after obtaining applicable regulatory approvals or we establish collaborations that provide us with up-front payments, licensing fees, milestone payments, royalties or other revenue.

We have incurred significant operating losses every year since our inception in September 1996.

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At December 31, 2022, we had an accumulated deficit of approximately $203.2 million.

We anticipate incurring substantial additional losses due to the need to spend substantial amounts on activities required for regulatory approval of PEDMARK TM , commercial launch preparation of PEDMARK TM , anticipated research and development activities, and general and administrative expenses, among other factors.

We have not commercially introduced any products.

Our ability to attain profitability will depend upon our ability to fund and develop products that are safe, effective and commercially viable, to obtain regulatory approval for the manufacture and sale of our product candidate and to license or otherwise market our product candidate successfully.

Any revenues generated from such product, assuming it is successfully developed, marketed and sold, may not be realized for a number of years.

We anticipate incurring substantial additional losses due to the need to spend substantial amounts on activities required for commercialization of PEDMARK ® in the U.S.

and regulatory approval of PEDMARK ® outside of the U.S., as well as commercial launch preparation of PEDMARK ® outside of the U.S., anticipated research and development activities, and

general and administrative expenses, among other factors.

We may never achieve or sustain profitability on an ongoing basis.

PEDMARK TM is currently our only product candidate and there is no assurance that we will successfully develop PEDMARK TM into a commercially viable product.

PEDMARK ® is currently our only product and there is no assurance that we will successfully develop PEDMARK ® into a commercially viable product.

Since our formation in September 1996, we have engaged in research and development programs.

We have generated no revenue from product sales, do not have any products currently available for sale, and none are expected to be commercially available for sale until we have completed regulatory approval of PEDMARK TM .

PEDMARK TM is currently our only product candidate.

There can be no assurance that the research we fund and manage will lead PEDMARK TM or any future product candidate to become a commercially viable product.

We have completed two-Phase 3 studies for PEDMARK TM .

We anticipate substantial regulatory review prior to the commercialization of PEDMARK TM .

We may require additional financing to obtain marketing approval of PEDMARK TM and commercialize PEDMARK TM and a failure to obtain this capital when needed on acceptable terms, or at all, could force us to delay, limit, reduce or terminate our product development, other operations or commercialization efforts.

Based on available resources, we believe that our cash and cash equivalents of $21.1 million available as of December 31, 2021 are sufficient to fund our anticipated operating and capital requirements for at least the next 12 months, subject to approval of our NDA.

Moreover, we expect to continue to incur losses for the foreseeable future as we continue our development of and seek marketing approvals for PEDMARK TM .

We have recently begun to generate revenue from product sales in the United States after regulatory approval of PEDMARK ® in late 2022.

PEDMARK ® is currently our only product.

There can be no assurance that the research we fund and manage will lead PEDMARK ® or any future product candidate to become a commercially viable product.

We have completed two-Phase 3 studies for PEDMARK ® .

We anticipate substantial regulatory review prior to the commercialization of PEDMARK ® outside of the United States.

We may require additional financing to obtain marketing approval of PEDMARK ® and commercialize PEDMARK ® abroad and a failure to obtain this capital when needed on acceptable terms, or at all, could force us to delay, limit, reduce or terminate our product development, other operations or commercialization efforts outside of the United States.

Based on available resources, we believe that our cash and cash equivalents of $23.8 million available as of December 31, 2022 are sufficient to fund our anticipated operating and capital requirements for at least the next 12 months.

Moreover, we expect to continue to incur losses for the foreseeable future as we continue our development of and seek marketing approvals for PEDMARK ® outside of the United States.

We may not be able to obtain additional financing in sufficient amounts or on acceptable terms when needed.

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If we cannot raise sufficient capital when necessary, we will likely have to curtail operations and you may lose part or all of your investment.

If we do not maintain current or enter into new collaborations with other companies, we might not successfully develop our product candidate or generate sufficient revenues to expand our business.

We currently rely on scientific and research and development collaboration arrangements with academic institutions and other third-party collaborators, including an exclusive worldwide license from OHSU for PEDMARK TM .

We also rely on collaborators for testing PEDMARK TM , including SIOPEL and the Children’s Oncology Group.

Our success depends on our ability to successfully commercialize PEDMARK ® .

We are a single product company with only limited commercial experience, which makes it difficult to evaluate our current business, predict our future prospects, and forecast our financial performance and growth.

We have invested a significant portion of our efforts and financial resources to date into the development and commercialization of our only product, PEDMARK ® .

Our success depends on our ability to effectively commercialize PEDMARK ® , and we expect that all of our product revenues in the foreseeable future will be from sales of PEDMARK ® .

Continued commercialization of PEDMARK ® is subject to many risks.

Until we launched PEDMARK ® , we had never launched or commercialized a product, and there is no guarantee that we will be able to achieve profitability and cash flow positive based on our sales of PEDMARK ® .

There are numerous examples of unsuccessful product launches and failures to meet high expectations of market growth potential, including by pharmaceutical companies with more resources and experience than we have.

The long term commercial success of PEDMARK ® depends on the extent to which patients and physicians accept and adopt PEDMARK ® For example, if the expected patient population is smaller than we estimate or if physicians are unwilling to prescribe or patients are unwilling to take PEDMARK ® , or if patients discontinue from use of the medication at rates that are higher than we expect, or if payers decide not to reimburse for our product, the commercial potential of PEDMARK ® will be limited.

Thus, significant uncertainty remains regarding the ultimate commercial potential of PEDMARK ® .

Moreover, our ability to effectively generate significant product revenue from PEDMARK ® will depend on our ability to, among other things:

• educate patients and physicians successfully about efficacy expectations, side effects expectations, and how to successfully dose and titrate the medication to optimal patient benefit in order to minimize discontinuation due to perceived lack of efficacy or side effects;

• educate pediatric cancer patients who will have cisplatin administration, and the physicians who treat them, as to the benefits to such patients of treatment using PEDMARK ® (in addition to the treatments they are receiving for their cancer);

• achieve and maintain compliance with regulatory requirements, including those related to our required post-approval studies, promotion and advertising requirements;

• increase awareness for and achieve market acceptance of PEDMARK ® through our sales and marketing activities and other arrangements established for the promotion of PEDMARK ® ;

• train, deploy, support, and retain a qualified field sales and marketing force;

• secure continued formulary approvals for PEDMARK ® with a substantial number of targeted payors;

• ensure that our third-party manufacturers manufacture PEDMARK ® in sufficient quantities, in compliance with requirements of the FDA and at acceptable quality and pricing levels, in order to meet commercial demand;

• ensure that our third-party manufacturers develop, validate and maintain commercially viable manufacturing processes that are compliant with cGMP regulations;

• implement and maintain agreements with wholesalers, distributors and group purchasing organizations on commercially reasonable terms;

• ensure that our entire supply chain efficiently and consistently delivers PEDMARK ® to our customers;

• provide co-pay assistance to help qualified patients with out-of-pocket costs associated with their PEDMARK ® prescription, and/or other programs to ensure patient access to our product, educate physicians and patients about the benefits, administration and use of PEDMARK ® , and obtain acceptance of PEDMARK ® as safe and effective by patients and the medical community;

• receive adequate levels of coverage and reimbursement for PEDMARK ® from commercial health plans and governmental health programs;

• generate positive experience with our FennecHears program in helping patients obtain access to PEDMARK ® at an acceptable patient out-of-pocket cost;

• maintain quality relationships with patient advocacy groups;

• influence the nature of publicity related to our product relative to the publicity related to our competitors’ products;

• obtain regulatory approvals for additional indications for the use of PEDMARK ® in treating other patient populations.

Any disruption in our ability to generate product revenue from the sale of PEDMARK ® will have a material and adverse impact on our results of operations.

If we are unable to continue to successfully commercialize PEDMARK ® , our business, results of operations and financial condition may be materially adversely affected.

Our strategy is to successfully commercialize PEDMARK ® in the United States and abroad.

There are risks involved both with maintaining our own sales and marketing capabilities, and with entering into arrangements with third parties to perform these services.

For example, any efforts to maintain a direct sales and marketing organization are subject to numerous risks, including:

● the expense and time required to recruit, retain, and motivate members of the sales force;

● our inability to recruit, retain or motivate adequate numbers of effective marketing personnel and partner marketing agencies;

● the inability to provide adequate training to sales and marketing personnel;

● the expense and time required to monitor regulatory compliance;

● the inability of sales personnel to obtain access to physicians or convince adequate numbers of physicians to prescribe any product;

● unforeseen costs and expenses associated with creating an independent sales and marketing organization.

Similarly, as we enter into arrangements with third parties to perform sales, marketing and distribution services, our product revenue or the profitability associated with any product revenue may be lower than if we were to market and sell any product that we develop ourselves.

In addition, we may not be successful in entering into arrangements with third parties to sell and market our products or may be unable to do so on terms that are favorable to us.

We may have little control over such third parties, and any of them may fail to devote the necessary resources and attention to sell and market our product effectively.

Moreover, we may be negatively impacted by other factors outside of our control relating to such third parties, including, but not limited to, their inability to comply with regulatory requirements.

If we do not establish sales, marketing and distribution capabilities successfully, either on our own or in collaboration with third parties, we will not be successful in commercializing our product.

Finally, because we are using a very small group of exclusive specialty pharmacies to distribute our product, if the organizations that we work with to deliver our drug do not perform in a lawful manner or have issues unrelated to our business, our business could be adversely affected.

Our business is subject to substantial competition.

The biotechnology and pharmaceutical industries are highly competitive.

Many of our competitors have substantially greater financial and other resources, larger research and development staffs and more experience developing products, obtaining FDA and other regulatory approvals of products and manufacturing and marketing products than we have.

We compete against pharmaceutical companies that are developing or currently marketing therapies that will compete with us.

In addition, we compete against biotechnology companies, universities, government agencies, and other research institutions in the development of drug products.

Our business could be negatively impacted if our competitors’ present or future offerings are more effective, safer or less expensive than ours, or more readily accepted by regulators, healthcare providers or third-party payors.

Further, we may also compete with respect to manufacturing efficiency and marketing capabilities.

For all of these reasons, we may not be able to compete successfully.

If we do not maintain current or enter into new collaborations with other companies, we might not successfully develop our product or generate sufficient revenues to expand our business.

We also rely on collaborators for testing PEDMARK ® , including SIOPEL and the Children’s Oncology Group.

The agreements with OHSU are terminable by either party in the event of an uncured breach by the other party.

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Since we conduct a significant portion of our research and development through collaborations, our success may depend significantly on the performance of such collaborators, as well as any future collaborators.

Collaborators might not commit sufficient resources to the research and development or commercialization of our product candidate.

Economic or technological advantages of products being developed by others, among other factors, could lead our collaborators to pursue other product candidates or technologies in preference to those being developed in collaboration with us.

The commercial potential of, development stage of and projected resources required to develop our drug candidate will affect our ability to maintain current collaborations or establish new collaborators.

Collaborators might not commit

sufficient resources to the research and development or commercialization of our product candidate.

Economic or technological advantages of products being developed by others, among other factors, could lead our collaborators to pursue other products or technologies in preference to those being developed in collaboration with us.

There is a risk of dispute with respect to ownership of technology developed under any collaboration.

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Any of these negative impacts on our current or future collaborations could have a material adverse effect on our business and results of operations.

Our product candidate is still in development.

Due to the long, expensive and unpredictable drug development process, we might not ever successfully develop and commercialize our product candidate.

In order to achieve profitable operations, we, alone or in collaboration with others, must successfully fund, develop, manufacture, introduce and market our product candidate.

The time necessary to achieve market success for any individual product is long and uncertain.

Our product candidate and research programs are in clinical development and require significant, time-consuming and costly research, testing and regulatory clearances.

In developing our product candidate, we are subject to risks of failure that are inherent in the development of therapeutic products based on innovative technologies.

The results of preclinical and initial clinical trials are not necessarily predictive of future results.

Our product candidate might not be economical to manufacture or market or might not achieve market acceptance.

In addition, third parties might hold proprietary rights that preclude us from marketing our product candidate or others might market equivalent or superior products.

We may need to conduct additional human clinical trials to assess our product candidate.

If these trials are delayed or are unsuccessful, our development costs will significantly increase, and our business prospects may suffer.

Before obtaining regulatory approvals for the commercial sale of our product candidate, we must demonstrate, through preclinical studies with animals and clinical trials with humans, that our product candidate is safe and effective for use in each target indication.

To date, we have performed only limited clinical trials.

Much of our testing has been conducted on animals or on human cells in the laboratory, and the benefits of treatment seen in animals or on human cells in a laboratory setting may not ultimately be obtained in human clinical trials.

As a result, we may need to perform significant additional research and development activities and conduct extensive preclinical and clinical testing prior to any application for commercial use.

We may suffer significant setbacks in additional clinical trials, and the trials may demonstrate our product candidate to be unsafe or ineffective.

We may also encounter problems in our clinical trials that will cause us to delay, suspend or terminate those clinical trials, which would increase our development costs and harm our financial results and commercial prospects.

Identifying and qualifying patients to participate in clinical trials of our potential products is critically important to our success.

The timing of our clinical trials depends on, among other things, the speed at which we can recruit patients to participate in testing our product candidate.

We have experienced delays in some of our clinical trials and we may experience significant delays in the future.

If patients are unwilling to participate in our trials because of competing clinical trials for similar patient populations, perceived risk or any other reason, the timeline for recruiting patients, conducting trials and obtaining regulatory approval of potential products will be delayed.

Other factors that may result in significant delays include obtaining regulatory or ethics review board approvals for proposed trials, reaching agreement on acceptable terms with prospective clinical trial sites, and obtaining sufficient quantities of drugs for use in the clinical trials.

Such delays could result in the termination of the clinical trials altogether.

Regulatory approval of our product candidate is time-consuming, expensive and uncertain, and could result in unexpectedly high expenses and delay our ability to sell our product.

Regulatory approval of our product is time-consuming, expensive and uncertain, and could result in unexpectedly high expenses and delay our ability to sell our product outside of the United States.

Development, manufacture and marketing of our product is subject to extensive regulation by governmental authorities in the United States and other countries.

This regulation could require us to incur significant unexpected expenses or delay or limit our ability to sell our product candidate.

This regulation could require us to incur significant unexpected expenses or delay or limit our ability to sell our product abroad.

Our clinical studies might be delayed or halted, or additional studies might be required, for various reasons, including:

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● we decide to modify the drug during testing.

If regulatory approval of our product is granted, it will be limited to those indications for which the product has been shown to be safe and effective, as demonstrated to the satisfaction of the FDA and foreign regulators through clinical studies.

Furthermore, approval might entail ongoing requirements for post-marketing studies.

Even if regulatory approval is obtained, labeling and promotional activities are subject to continual scrutiny by the FDA and state and foreign regulatory agencies and, in some circumstances, the Federal Trade Commission.

If regulatory approval of our product is granted outside of the United States, it will be limited to those indications for which the product has been shown to be safe and effective, as demonstrated to the satisfaction of the FDA and foreign regulators through clinical studies.

Furthermore, approval abroad might entail ongoing requirements for post-marketing studies.

Even if regulatory approval is obtained outside for the United States, labeling and promotional activities are subject to continual scrutiny by the FDA and state and foreign regulatory agencies and, in some circumstances, the Federal Trade Commission.

FDA enforcement policy prohibits the marketing of approved products for unapproved, or off-label, uses.

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Further, manufacturing facilities, which we outsource to third parties, must be approved by the FDA before they can be used to manufacture our product, and they are subject to additional FDA inspection.

The CRL that we received from the FDA in August, 2020 and in November, 2021 as a result of deficiencies in the third-party

manufacturing facility that manufactures PEDMARK TM on our behalf is a specific example of the risks associated with our third-party manufacturers.

The CRL that we received from the FDA in August, 2020 and in November, 2021 as a result of deficiencies in the third-party manufacturing facility that manufactures PEDMARK ® on our behalf is a specific example of the risks associated with our third-party manufacturers.

If we fail to comply with any of the FDA’s continuing regulations, or any other regulations under which we may be required to comply outside of the United States, we could be subject to reputational harm and sanctions, including:

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In addition, identification of side effects after a drug is on the market or the occurrence of manufacturing problems could cause subsequent withdrawal of approval, reformulation of the drug, additional testing or changes in labeling of the product.

We may be unable to effectively deploy the proceeds from our recent financings for the development of PEDMARK TM .

On May 5, 2020, we announced the completion of an underwritten public offering of 4.8 million of our common shares at a public offering price of $6.25 per share.

In addition, we issued an additional 0.66 million common shares in connection with the partial exercise of the underwriters’ over-allotment option.

The approximate total gross proceeds from the offering were $34.1 million ($32.2 million net of commissions, fees and issue costs).

Any inability on our part to manage effectively the deployment of this capital could limit our ability to successfully develop PEDMARK TM .

If our licenses to proprietary technology owned by others are terminated or expire, we may suffer increased development costs and delays, and we may not be able to successfully develop our product candidate.

The development of our drug candidate and the manufacture and sale of any products that we develop will involve the use of processes, products and information, some of the rights to which are owned by others.

PEDMARK TM is licensed under agreements with OHSU.

If our licenses to proprietary technology owned by others are terminated or expire, we may suffer increased development costs and delays, and we may not be able to successfully commercialize our product.

The development of our drug and the manufacture and sale of any products that we develop will involve the use of processes, products and information, some of the rights to which are owned by others.

PEDMARK ® is licensed under agreements with OHSU.

Although we have obtained licenses or rights with regard to the use of certain processes, products and information, the licenses or rights could be terminated or expire during critical periods and we may not be able to obtain, on favorable terms or at all, licenses or other rights that may be required.

Some of these licenses provide for limited periods of exclusivity that may be extended only with the consent of the licensor, which may not be granted.

If we are unable to adequately protect or maintain our patents and licenses related to our product candidate, or if we infringe upon the intellectual property rights of others, we may not be able to successfully develop and commercialize our product candidate.

The value of our technology will depend in part upon our ability, and those of our collaborators, to obtain patent protection or licenses to patents, maintain trade secret protection and operate without infringing on the rights of third parties.

If we are unable to adequately protect or maintain our patents and licenses related to our product, or if we infringe upon the intellectual property rights of others, we may not be able to successfully maintain commercial status of our product.

The value of our product will depend in part upon our ability, and those of our collaborators, to obtain patent protection or licenses to patents, maintain trade secret protection and operate without infringing on the rights of third parties.

Although we have successfully pursued patent applications in the past, it is possible that:

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Further, any of our patents, once issued, may be declared by a court to be invalid or unenforceable.

PEDMARK TM is currently protected by methods of use patent that we exclusively licensed from OHSU that expires in the United States in 2038 and a patent owned by us that expires in 2039.

PEDMARK ® is currently protected by methods of use patent that we exclusively licensed from OHSU that expires in the United States in 2038 and two patents owned by us that expires in 2039.

Further, patents are currently pending in the United States and other territories.

In addition, periods of marketing exclusivity for PEDMARK TM may also be possible in the United States under orphan drug status and in Europe under PUMA.

In addition, periods of marketing exclusivity for PEDMARK ® may also be possible in the United States under orphan drug status and in Europe under PUMA.

We may be required to obtain licenses under patents or other proprietary rights of third parties, but the extent to which we may wish or need to do so is unknown.

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Litigation may also be necessary to enforce or defend patents issued or licensed to us or our collaborators or to determine the scope and validity of a third party’s proprietary rights.

By example we have outstanding lititagation against CIPLA.

We could incur substantial costs if litigation is required to defend ourselves in patent suits brought by third parties, if we participate in patent suits brought against or initiated by our collaborators, or if we initiate such suits.

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In addition, others may independently develop or obtain similar technology and may be able to market competing products and obtain regulatory approval through a showing of equivalency to our product that has obtained regulatory approvals, without being required to undertake the same lengthy and expensive clinical studies that we would have already completed.

The vulnerability to off-label use or sale of our product candidate that are covered only by “method of use” patents may cause downward pricing pressure on the product candidate if they are ever commercialized and may make it more difficult for us to enter into collaboration or partnering arrangements for the development of this product candidate.

PEDMARK TM is currently covered by “method of use” patent and “composition of matter” patent.

The vulnerability to off-label use or sale of our product that are covered only by “method of use” patents may cause downward pricing pressure on the product and may make it more difficult for us to enter into collaboration or partnering arrangements for the marketing of this product in the United States and abroad.

PEDMARK ® is currently covered by “method of use” patent and “composition of matter” patent.

“Method of use” patents cover the use of certain compounds to treat specific conditions and “composition of matter” patents cover the chemical composition of the compound.

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Off-label use and sales could limit our sales and exert pricing pressure on any product we develop covered only by method of use patents.

Also, it may be more difficult to find a collaborator to license or support the development of our product candidate that is only covered by method of use patents.

If our third-party manufacturers breach or terminate their agreements with us, or if we are unable to secure arrangements with third party manufacturers on acceptable terms as needed in the future, we may suffer significant delays and additional costs.

We have no experience manufacturing products and do not currently have the resources to manufacture any products that we may develop.

We currently have agreements with contract manufacturers for clinical supplies of PEDMARK TM , including drug substance providers and drug product suppliers, but they might not perform as agreed in the future or may terminate our agreements with them before the end of the required term.

Also, it may be more difficult to find a collaborator to license or support the marketing of our product that is only covered by method of use patents.

We have little experience manufacturing products and do not currently have the resources to manufacture any products that we may develop.

We currently have agreements with contract manufacturers for clinical supplies of PEDMARK ® , including drug substance providers and drug product suppliers, but they might not perform as agreed in the future or may terminate our agreements with them before the end of the required term.

Significant additional time and expense would be required to effect a transition to a new contract manufacturer.

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We may not be able to independently develop manufacturing capabilities or obtain favorable terms for the manufacture of our product.

While we intend to contract for the commercial manufacture of our product candidate, we may not be able to identify and qualify contractors or obtain favorable contracting terms.

While we intend to contract for the commercial manufacture of our product, we may not be able to identify and qualify contractors or obtain favorable contracting terms.

We or our contract manufacturers may also fail to meet required manufacturing standards, which could result in delays or failures in product delivery, increased costs, injury or death to patients, product recalls or withdrawals and other problems that could significantly hurt our business.

The CRL that we received from the FDA in August 2020 and November 2021as a result of deficiencies in the third-party manufacturing facility that manufactures PEDMARK TM on our behalf is a specific example of the risks associated with our third-party manufacturers.

The CRLs that we received from the FDA in August 2020 and November 2021 as a result of deficiencies in the third-party manufacturing facility that manufactures PEDMARK ® on our behalf is a specific example of the risks associated with our third-party manufacturers.

We intend to maintain a second source for back-up commercial manufacturing, wherever feasible.

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Such lead times would vary based on the situation but might be twelve months or longer.

We may lack the resources necessary to effectively market our product candidate, and we may need to rely on third parties over whom we have little or no control and who may not perform as expected.

We may not have the necessary resources to market our product candidate.

If we develop any products with commercial potential, we will either have to develop a marketing capability, including a sales force, which is difficult and expensive to implement successfully, or attempt to enter into a collaboration, merger, joint venture, license or other arrangement with third parties to provide a substantial portion of the financial and other resources needed to market such products.

We may not be able to do so on acceptable terms, if at all.

If we rely extensively on third parties to market our products, the commercial success of such products may be largely outside of our control.

We conduct our business internationally and are subject to laws and regulations of several countries which may affect our ability to access regulatory agencies and may affect the enforceability and value of our licenses.

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Our cash invested in money market funds might be subject to loss.

Even though we believe we take a conservative approach to investing our funds, the nature of financial markets exposes us to investment risk, including the risks that the value and liquidity of our money market investments (the amounts of which substantially exceed the $250,000 amount insured by the FDIC) could deteriorate significantly and the issuers of

the investments we hold could be subject to credit rating downgrades.

While we have not experienced any loss or write down of our money market investments in the past, we cannot guarantee that such losses will not occur in future periods.

Should the clinical development process be successfully completed, our ability to derive revenues from the sale of therapeutics will depend upon our first obtaining FDA as well as foreign regulatory approvals, all of which are subject to a number of unique risks and uncertainties.

Even if we are able to demonstrate the safety and efficacy of our product candidate in clinical trials, if we fail to gain timely approval to commercialize PEDMARK TM from the FDA and other foreign regulatory authorities, we will be unable to generate the revenues we will need to build our business.

The FDA or comparable regulatory authorities in other countries may delay, limit or deny approval of PEDMARK TM for various reasons.

With the clinical development process successfully completed in the United States, our ability to derive further revenues from the sale of PEDMARK ® will depend upon our obtaining foreign regulatory approvals, which are subject to a number of unique risks and uncertainties.

Even if we are able to demonstrate the safety and efficacy of our product in clinical trials abroad, if we fail to gain timely approval to commercialize PEDMARK ® from foreign regulatory authorities, we will be unable to generate the revenues we will need to build our business.

Regulatory authorities in other countries may delay, limit or deny approval of PEDMARK ® for various reasons.

For example, such authorities may disagree with the design, scope or implementation of our clinical trials;

or with our interpretation of data from our preclinical studies or clinical trials;

or may otherwise take the position that PEDMARK TM fails to meet the requirements and standards for regulatory approval.

There are numerous FDA personnel assigned to review different aspects of a NDA, and uncertainties can be presented by their ability to exercise judgment and discretion during the review process.

During the course of review, the FDA may request or require additional preclinical, clinical, chemistry, manufacturing, and control (“CMC”), or other data and information, and the development and provision of these data and information may be time consuming and expensive.

or may otherwise take the position that PEDMARK ® fails to meet the requirements and standards for regulatory approval.

During the course of review, foreign regulatory bodies may request or require additional preclinical, clinical, chemistry, manufacturing, and control (“CMC”), or other data and information, and the development and provision of these data and information may be time consuming and expensive.

Regulatory approvals may not be granted on a timely basis, if at all, and even if and when they are granted, they may not cover all the indications for which we seek approval.

On February 10, 2020, we submitted an NDA to the FDA for PEDMARK TM for the prevention of ototoxicity associated with cisplatin chemotherapy in pediatric patients ≥1 month to 18 years of age with localized, non-metastatic, solid tumors.

On April 10, 2020, we received notification from the FDA that the NDA was accepted for filing and the original application was granted Priority Review with a PDUFA target action date of August 10, 2020.

On August 10, 2020, we received a CRL from the FDA.

According to the CRL, after recent completion of a pre-approval inspection of the manufacturing facility of our drug product manufacturer, the FDA identified deficiencies that are required to be resolved prior to the approval of PEDMARK™.

In May 2021, we announced the resubmission of our NDA for PEDMARK TM and in June 2021 we further announced that the FDA accepted for filing the resubmission of our NDA and set a PDUFA target action date of November 27, 2021.

On November 29, 2021, we received a CRL from the FDA.

Similar to the previous CRL, after recent completion of a pre-approval inspection of the manufacturing facility of our drug product manufacturer, the FDA identified deficiencies that are required to be resolved prior to the approval of PEDMARK™.

We anticipate resubmitting an NDA in the first quarter of 2022.

If the FDA determines based on the inspection by FDA officials and do not recommend approval relative to the drug product manufacturing facility, or if information deemed necessary by the FDA cannot be provided as part of our NDA submission or during the review period as deemed appropriate on a timely basis, such events could further delay the progress of our NDA and could require additional actions that we cannot complete during the review period, which may adversely impact our business.

If our NDA for PEDMARK TM is ultimately not approved by the FDA, we would not be able to commercialize PEDMARK TM , which would have a material adverse effect on our business.

Further, while we may develop a product candidate with the intention of addressing a large, unmet medical need, the FDA may only approve the use of the drug for indications affecting a relatively small number of patients, thus greatly reducing the market size and our potential revenues.

Further, while we may develop a product with the intention of addressing a large, unmet medical need, the foreign regulatory bodies may only approve the use of the drug for indications affecting a relatively small number of patients, thus greatly reducing the market size and our potential revenues.

The approvals may also contain significant limitations in the form of warnings, precautions or contraindications with respect to conditions of use, which could further narrow the size of the market.

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This risk is especially relevant for us because pharmaceutical companies like us have experienced significant stock price volatility in recent years.

Specifically, we were named in putative securities class action complaints as a result of the decline in our stock price following the August 10, 2020 announcement that we had received a CRL from the FDA regarding our NDA for PEDMARK™ and as result of the decline in our stock price following the November 29, 2021 announcement that we expected to receive

another CRL from the FDA regarding our NDA for PEDMARK™.

Specifically, we were named in putative securities class action complaints as a result of the decline in our stock price following the August 10, 2020 announcement that we had received a CRL from the FDA regarding our NDA for PEDMARK ® and as result of the decline in our stock price following the November 29, 2021 announcement that we expected to receive another CRL from the FDA regarding our NDA for PEDMARK ® .

Regardless of the outcome of this or future litigation, we could incur substantial legal costs and our management’s attention could be diverted from the operation of our business, causing our business to suffer.

Our insurance coverage may be insufficient to cover all legal fees, judgments or settlements.

If the outcome of any such litigation is unfavorable, it could result in us paying significant damages or settlement payments, which could have a material adverse effect on our financial condition.

If the outcome of any

such litigation is unfavorable, it could result in us paying significant damages or settlement payments, which could have a material adverse effect on our financial condition.

We have only recently transitioned from a development stage biopharmaceutical company to a commercial stage biopharmaceutical company, which may make it difficult for you to evaluate the success of our business to date and to assess our future viability.

Other than the FDA approval for PEDMARK ® received in the United States in September 2022, we have no other product candidates in the development stage.

We have only recently demonstrated our ability, or our ability to arrange for a third party, to manufacture a commercial scale medicine and conduct the sales and marketing activities necessary to commercialize a product.

Consequently, any predictions you make about our future success or viability may not be as accurate as they could be if we had more experience commercializing PEDMARK ® .

In addition, as a relatively new commercial stage business, we may encounter unforeseen expenses, difficulties, complications, delays and other known and unknown factors.

To be profitable, we will need to continue to successfully transition from a company with a research and development focus to a company capable of supporting commercial activities.

Ultimately, we may not be successful in such a transition.

There are limitations on the liability of our directors, and we may have to indemnify our officers and directors in certain instances.

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The COVID-19 pandemic is affecting the operations of government entities, such as the FDA, as well as contract research organizations, third-party manufacturers, and other third-parties upon whom we rely.

As a result of “shelter-in-place” orders, quarantines or similar orders or restrictions to control the spread of COVID-19, many companies, including our own, have implemented work-from-home policies for their employees.

The effects of these stay at home orders and work-from-home policies may negatively impact productivity, resulting in delays in our product launch.

The extent of the impact on our operations depends in part on the time these restrictions remain in place, and whether restrictions are reinstated as a result of a rising surge in COVID-19 cases.

These and similar disruptions in our operations could negatively impact our business, operating results and financial condition.

Possible effects may include, but are not limited to, disruption to our product launch, which includes the ability of sales reps to communicate with oncologists, absenteeism in our labor workforce, unavailability of products and supplies used in operations, and a decline in value of our assets, including inventories, property and equipment, and marketable securities.

These and similar disruptions in our operations could negatively impact our business,

operating results and financial condition.

Possible effects may include, but are not limited to, disruption to our product launch outside the United States, which includes the ability of sales reps to communicate with oncologists, absenteeism in our labor workforce, unavailability of products and supplies used in operations, and a decline in value of our assets, including inventories, property and equipment, and marketable securities.

The spread of COVID-19 has also led to disruption and volatility in the global capital markets, which increases the cost of, and adversely impacts access to capital and increases economic uncertainty.

To the extent the COVID-19 pandemic adversely affects our business, financial results and value of our common shares, it may also affect our ability to access

capital and obtain financing, which could in the future negatively affect our liquidity and ability to continue as a going concern.

To the extent the COVID-19 pandemic adversely affects our business, financial results and value of our common shares, it may also affect our ability to access capital and obtain financing, which could in the future negatively affect our liquidity and ability to continue as a going concern.

The global pandemic of COVID-19 continues to evolve rapidly, and the ultimate impact of the COVID-19 pandemic or a similar health epidemic is highly uncertain and subject to change.

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These limitations could negatively affect our business operations and continuity, and could negatively impact our development timelines and ability to timely perform basic business functions, including, without limitation, making SEC filings and preparing financial reports.

If our operations or those of third parties with whom we conduct business are impaired or curtailed as a result of these events, the development and commercialization of our products and product candidate could be impaired or halted, which could have a material adverse impact on our business.

Risks Related to the Clinical Development and Marketing Approval of Our Product Candidate

The marketing approval processes of the FDA and comparable foreign authorities are lengthy, time-consuming and inherently unpredictable, and if we are ultimately unable to obtain marketing approval for our product candidate, our business will be substantially harmed.

Our current product candidate has not gained marketing approval for sale in the United States or any other country, and we cannot guarantee that we will ever have any marketable products.

Our business is substantially dependent on our ability to complete the development of, obtain marketing approval for, and successfully commercialize our product candidate in a timely manner.

We cannot commercialize our product candidate in the United States without first obtaining approval from the FDA to market our product candidate.

Similarly, we cannot commercialize our product candidate outside of the United States without obtaining regulatory approval from comparable foreign regulatory authorities.

Our product candidate could fail to receive marketing approval for many reasons, including the following:

● the FDA or comparable foreign regulatory authorities may disagree with the design or implementation of our clinical trials;

● the FDA or comparable foreign regulatory authorities may find the human subject protections for our clinical trials inadequate and place a clinical hold on an IND at the time of its submission precluding commencement of any trials or a clinical hold on one or more clinical trials at any time during the conduct of our clinical trials;

● the FDA could determine that we cannot rely on Section 505(b)(2) of the FFDCA for our product candidate;

● we may be unable to demonstrate to the satisfaction of the FDA or comparable foreign regulatory authorities that a product candidate is safe and effective for its proposed indication;

● the results of clinical trials may not meet the level of statistical significance required by the FDA or comparable foreign regulatory authorities for approval;

● we may be unable to demonstrate that a product candidate’s clinical and other benefits outweigh its safety risks;

● the FDA or comparable foreign regulatory authorities may disagree with our interpretation of data from preclinical studies or clinical trials;

● the FDA could determine that our application relies, or must rely, upon a listed drug or drugs that we a failed to identify or that approval of our 505(b)(2) application for our product candidate is blocked by patent or non-patent exclusivity of the listed drug or drugs;

● the data collected from clinical trials of our product candidate may not be sufficient to obtain marketing approval in the United States or elsewhere;

● the FDA or comparable foreign regulatory authorities may find inadequate the manufacturing processes or facilities of third-party manufacturers with which we contract for clinical and commercial supplies (for example, see the discussion elsewhere concerning the CRL we received from the FDA in August, 2020);

● the approval policies or regulations of the FDA or comparable foreign regulatory authorities may significantly change in a manner that would delay marketing approval.

Before obtaining marketing approval for the commercial sale of any drug product for a target indication, we must demonstrate in preclinical studies and well-controlled clinical trials and, with respect to approval in the United States, to the satisfaction of the FDA, that the product is safe and effective for its intended use and that the manufacturing facilities, processes, and controls are adequate to preserve the drug’s identity, strength, quality and purity.

In the United States, it is necessary to submit and obtain approval of an NDA from the FDA.

If our operations or those of third parties with whom we conduct business are impaired or curtailed as a result of these events, the development and commercialization of our product and product candidate could be impaired or halted, which could have a material adverse impact on our business.

Because the target patient population for PEDMARK ® is small, we must achieve significant market share and obtain relatively high per-patient prices for our product to achieve meaningful gross margins.

PEDMARK ® targets a small patient population.

A key component of the successful commercialization of a drug product for these indications includes identification of patients and a targeted prescriber base for the drug product.

Due to small patient populations, we believe that we would need to have significant market penetration to achieve meaningful revenues and identifying patients and targeting the prescriber base are key to achieving significant market penetration.

Typically, drugs for conditions with small prevalence have higher prices in order to generate a return on investment, and as a result, the per-patient prices at which we sell PEDMARK ® are relatively high in order for us to generate an appropriate return for the investment in these product development programs and achieve meaningful gross margins, and high per patient prices could drive physicians to seek out compounding pharmacies to provide compounded sodium thiosulfate to fill their prescriptions rather than PEDMARK ® , thereby lowering the PEDMARK ® market share or penetration in the market.

There can be no assurance that we will be successful in achieving a sufficient degree of market penetration and/or obtaining or maintaining high per-patient prices for PEDMARK ® for a small patient populations.

Further, even if we obtain significant market share for PEDMARK ® because the potential target populations are very small, we may not be able to obtain profitability despite obtaining such significant market share.

We face a risk of product liability claims and may not be able to obtain adequate insurance.

Our business exposes us to potential liability risks that may arise from the clinical testing, manufacture, and/or sale of our drug products.

Patients have received substantial damage awards in some jurisdictions against pharmaceutical companies based on claims for injuries allegedly caused by the use of drug products used in clinical trials or after FDA approval.Liability claims may be expensive to defend and may result in large judgments against us.

We currently carry liability insurance that we believe to be adequate.

Our insurance may not reimburse us for certain claims or the coverage

may not be sufficient to cover claims made against us.

We cannot predict all of the possible harms or side effects that may result from the use of our current drug candidates, or any potential future products we may acquire and use in clinical trials or after FDA approval and, therefore, the amount of insurance coverage we currently hold may not be adequate to cover all liabilities we might incur.

If we are sued for any injury allegedly caused by our product, our liability could exceed our ability to pay the liability.

Whether or not we are ultimately successful in any adverse litigation, such litigation could consume substantial amounts of our financial and managerial resources, all of which could have a material adverse effect on our business, financial condition, results of operations, prospects and stock price.

Business or economic disruptions or global health concerns could seriously harm our development efforts and increase our costs and expenses.

Broad-based business or economic disruptions could adversely affect our ongoing or planned research and development activities.

Global health concerns, such as the COVID-19 pandemic, could also result in social, economic, and labor instability in the countries in which we or the third parties with whom we engage operate.

We cannot presently predict the scope and severity of any potential business shutdowns or disruptions, but if we or any of the third parties with whom we engage, including the suppliers, clinical trial sites, regulators and other third parties with whom we conduct business, were to experience shutdowns or other business disruptions, our ability to conduct our business in the manner and on the timelines presently planned could be materially and negatively impacted.

It is also possible that global health concerns such as the COVID-19 pandemic could disproportionately impact the hospitals and clinical sites in which we conduct any of our clinical trials, which could have a material adverse effect on our business and our results of operation and financial condition.

Risks Related to the Clinical Development and Marketing Approval of Our Product outside the United States

The marketing approval processes of foreign authorities are lengthy, time-consuming and inherently unpredictable, and if we are ultimately unable to obtain marketing approval for our product abroad, our business will be substantially harmed.

Our current product has gained marketing approval for sale in the United States but no other country, and we cannot guarantee that we will ever have regulatory approval outside the United States.

Our business is substantially dependent on our ability to complete the development of, obtain marketing approval for, and successfully commercialize our product candidate in abroad a timely manner.

We cannot commercialize our product candidate outside of the United States without obtaining regulatory approval from comparable foreign regulatory authorities.

Our product could fail to receive marketing approval for many reasons, including the following:

● FDA comparable foreign regulatory authorities may disagree with the design or implementation of our clinical trials;

● FDA comparable foreign regulatory authorities may find the human subject protections for our clinical trials inadequate and place a clinical hold on an IND at the time of its submission precluding commencement of any trials or a clinical hold on one or more clinical trials at any time during the conduct of our clinical trials;

● we may be unable to demonstrate to the satisfaction of the FDA comparable foreign regulatory authorities that a product candidate is safe and effective for its proposed indication;

● the results of clinical trials may not meet the level of statistical significance required by the FDA comparable foreign regulatory authorities for approval;

● we may be unable to demonstrate that a product’s clinical and other benefits outweigh its safety risks;

● FDA comparable foreign regulatory authorities may disagree with our interpretation of data from preclinical studies or clinical trials;

● the data collected from clinical trials of our product may not be sufficient to obtain marketing approval outside of the United States;

● FDA comparable foreign regulatory authorities may find inadequate the manufacturing processes or facilities of third-party manufacturers with which we contract for clinical and commercial supplies (for example, see the discussion elsewhere concerning the CRLs we received from the FDA in August, 2020 and November 2021);

● the approval policies or regulations of the FDA comparable foreign regulatory authorities may significantly change in a manner that would delay marketing approval.

Before obtaining marketing approval for the commercial sale of any drug product for a target indication, we must demonstrate in preclinical studies and well-controlled clinical trials and, with respect to approval outside the United States, to the satisfaction of the foreign regulatory authorities, that the product is safe and effective for its intended use and that the manufacturing facilities, processes, and controls are adequate to preserve the drug’s identity, strength, quality and purity.

In September 2022, we obtained approval of our NDA from the FDA.

An NDA must include extensive preclinical and clinical data and supporting information to establish the product’s safety and efficacy for each desired indication.

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The FDA and the Competent Authorities of the Member States of the European Economic Area, or EEA, and comparable foreign regulatory authorities, may also inspect our clinical trial sites and audit clinical study data to ensure that our studies are properly conducted in accordance with the IND regulations, human subject protection regulations, cGCP.

Obtaining approval of an NDA is a lengthy, expensive and uncertain process, and approval may not be obtained.

Upon submission of an NDA, the FDA must make an initial determination that the application is sufficiently complete to accept the submission for filing.

We cannot be certain that any submissions will be accepted for filing and reviewed by the FDA, or ultimately be approved.

If the application is not accepted for review, the FDA may require that we conduct additional clinical studies or preclinical testing, or take other actions before it will reconsider our application.

If the FDA requires additional studies or data, we would incur increased costs and delays in the marketing approval process, which may require us to expend more resources than we have available.

In addition, the FDA might not consider any additional information to be complete or sufficient to support the filing or approval of the NDA.

Regulatory authorities outside of the United States, such as in Europe and Japan and in emerging markets, also have requirements for approval of drugs for commercial sale with which we must comply prior to marketing in those areas.

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The process to develop, obtain marketing approval for, and commercialize product candidates is long, complex and costly, both inside and outside of the United States, and approval is never guaranteed.

The time required to obtain approval by the FDA and comparable foreign authorities is unpredictable but typically takes many years following the

commencement of clinical trials and depends upon numerous factors, including the substantial discretion of the regulatory authorities.

The time required to obtain approval by the FDA and comparable foreign authorities is unpredictable but typically takes many years following the commencement of clinical trials and depends upon numerous factors, including the substantial discretion of the regulatory authorities.

In addition, approval policies, regulations, or the type and amount of clinical data necessary to gain approval may change during the course of a product candidate’s clinical development and may vary among jurisdictions.

Even if our product candidate were to successfully obtain approval from regulatory authorities, any such approval might significantly limit the approved indications for use, including more limited patient populations, require that precautions, warnings or contraindications be included on the product labeling, including black box warnings, require expensive and time-consuming post-approval clinical studies, risk evaluation and mitigation strategies or surveillance as conditions of approval, or, through the product label, the approval may limit the claims that we may make, which may impede the successful commercialization of our product candidate.

Even if our product were to successfully obtain approval from regulatory authorities outside the United States, any such approval might significantly limit the approved indications for use, including more limited patient populations, require that precautions, warnings or contraindications be included on the product labeling, including black box warnings, require expensive and time-consuming post-approval clinical studies, risk evaluation and mitigation strategies or surveillance as conditions of approval, or, through the product label, the approval may limit the claims that we may make, which may impede the successful commercialization of our product candidate.

Following any approval for commercial sale of our product candidate, certain changes to the product, such as changes in manufacturing processes and additional labeling claims, as well as new safety information, may require new studies and will be subject to additional FDA notification, or review and approval.

Also, marketing approval for any of our product candidate may be withdrawn.

If we are unable to obtain marketing approval for our product candidate in one or more jurisdictions, or any approval contains significant limitations, our ability to market to our full target market will be reduced and our ability to realize the full market potential of our product candidate will be impaired.

Furthermore, we may not be able to obtain sufficient funding or generate sufficient revenue and cash flows to continue or complete the development of any of our current or future product candidates.

Our risk of delay in product approvals is increased if the United States government is fully or partially shut down due to lack of continuity in funding.

Our business operations, and particularly the timing of the outcome of review of our NDA filing for marketing approval of PEDMARK TM , are directly and indirectly affected by the operations of the United States government, including but not limited to the FDA.

Any interruption in the continuity of funding of all or a part of government activities could have a significant negative effect on our business, including the timing of that review decision.

The United States government shuts down from time to time, most recently from December 22, 2018 to January 25, 2019.

We cannot predict the likelihood, duration, impact, or timing of any future shutdown.

There can be no assurance that if such shutdown(s) were to occur in the future, adequate funds would be available to the FDA and other U.S.

government agencies to allow them to continue their activities uninterrupted.

Even when funding is restored following one or more shutdowns, we cannot predict the ongoing impact of such shutdowns on our business, or the degree to which funding would be restored to the FDA or other agencies having an impact on our business.

If we are unable to submit an application for approval under Section 505(b)(2) of the FFDCA or if we are required to generate additional data related to safety and efficacy in order to obtain approval under Section 505(b)(2), we may be unable to meet our anticipated development and commercialization timelines.

Our current strategy for seeking marketing authorization in the United States for our product candidate relies primarily on Section 505(b)(2) of the FFDCA, which permits use of a marketing application, referred to as a 505(b)(2) application, where at least some of the information required for approval comes from studies not conducted by or for the applicant and for which the applicant has not obtained a right of reference or use.

The FDA interprets this to mean that an applicant may rely for approval on such data as that found in published literature or the FDA’s finding of safety or effectiveness, or both, of a previously approved drug product owned by a third party.

There is no assurance that the FDA would find the published literature or third-party data relied upon by us in a 505(b)(2) application sufficient or adequate to support approval, and the FDA may require us to generate additional data to support the safety and efficacy of our product candidate.

Consequently, we may need to conduct substantial new research and development activities beyond those we currently plan to conduct.

Such additional new research and development activities would be costly and time-consuming and there is no assurance that such data generated from such additional activities would be sufficient to obtain approval.

If the data to be relied upon in a 505(b)(2) application are related to drug products previously approved by the FDA and covered by patents that are listed in the FDA’s Orange Book, we would be required to submit with our 505(b)(2) application an appropriate patent certification or statement.

The type of patent certification that would enable us to obtain approval of our application before a listed patent expires, known as a Paragraph IV Certification, would require us to certify that we do not infringe the listed patent or that such patent is invalid or unenforceable.

We would be required to provide timely notice to the patent owner and the holder of the approved NDA.

If a patent infringement action is initiated against us within 45 days from receipt of our Paragraph IV Certification, the approval of our NDA

would be subject to a stay of up to 30 months or more while we defend against such a suit.

Approval of our product candidate under Section 505(b)(2) may, therefore, be delayed until patent exclusivity expires or until we successfully challenge those patents.

Alternatively, we may elect to generate sufficient clinical data so that we would no longer need to rely on third-party data, which would be costly and time-consuming and there would be no assurance that such data generated from such additional activities would be sufficient to obtain approval.

We may not be able to obtain shortened review of our applications, and the FDA may not agree that our product candidate qualifies for marketing approval.

If we are required to generate additional data to support approval, we may be unable to meet anticipated or reasonable development and commercialization timelines, may be unable to generate the additional data at a reasonable cost, or at all, and may be unable to obtain marketing approval of our product candidate.

If the FDA changes its interpretation of Section 505(b)(2) allowing reliance on data in published literature or a previously approved drug application owned by a third party, or there is a change in the law affecting Section 505(b)(2), this could delay or even prevent the FDA from approving any Section 505(b)(2) application that we submit.

Even if we receive marketing approval for our product candidate, such approved products will be subject to ongoing obligations and continued regulatory review, which may result in significant additional expense.

Additionally, our product candidate, if approved, could be subject to labeling and other restrictions, and we may be subject to penalties and legal sanctions if we fail to comply with regulatory requirements or experience unanticipated problems with our approved products.

If the FDA approves our product candidate, the manufacturing processes, labeling, packaging, distribution, adverse event reporting, storage, advertising, promotion and recordkeeping for the product will be subject to extensive and ongoing regulatory requirements.

Also, marketing approval for any of our product may be withdrawn.

If we are unable to obtain marketing approval for our product in one or more jurisdictions, or any approval contains significant limitations, our ability to market to our full target market will be reduced and our ability to realize the full market potential of our product will be impaired.

Furthermore, we may not be able to obtain sufficient funding or generate sufficient revenue and cash flows to continue or complete the development of any future product candidates.

Now that we have achieved marketing approval for our product in the United States, it will be subject to ongoing obligations and continued regulatory review, which may result in significant additional expense.

Our product could be subject to labeling and other restrictions, and we may be subject to penalties and legal sanctions if we fail to comply with regulatory requirements or experience unanticipated problems with our approved product.

Now that the FDA has approved our product, the manufacturing processes, labeling, packaging, distribution, adverse event reporting, storage, advertising, promotion and recordkeeping for the product will be subject to extensive and ongoing regulatory requirements.

These requirements include submissions of safety and other post-marketing information and reports, registration, as well as continued compliance with cGMP regulations and cGCP for any clinical trials that we conduct post-approval.

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● injunctions or the imposition of civil or criminal penalties.

The FDA’s policies may change, and additional government regulations may be enacted that could prevent, limit or delay marketing approval, manufacturing or commercialization of our product candidate.

The FDA’s and foreign regulatory agencies policies may change, and additional government regulations may be enacted that could prevent, limit or delay marketing approval, manufacturing or commercialization of our product.

We cannot predict the likelihood, nature or extent of government regulation that may arise from future legislation or administrative action, either in the United States or abroad.

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Agencies like the FDA and national competition regulators in European countries regulate the promotion and uses of drugs not consistent with approved product labeling requirements.

If we are found to have improperly promoted our current product candidate for uses beyond those that are approved, we may become subject to significant liability.

Regulatory authorities like the FDA and national competition laws in Europe strictly regulate the promotional claims that may be made about prescription products, such as PEDMARK TM , if approved.

If we are found to have improperly promoted PEDMARK ® for uses beyond those that are approved, we may become subject to significant liability.

Regulatory authorities like the FDA and national competition laws in Europe strictly regulate the promotional claims that may be made about prescription products, such as PEDMARK ® .

In particular, a product may not be promoted for uses that are not approved by the FDA or comparable foreign regulatory authorities as reflected in the product’s approved labeling, known as “off-label” use, nor may it be promoted prior to obtaining marketing approval.

If we receive marketing approval for our product candidate for our proposed indications, physicians may nevertheless use our products for their patients in a manner that is inconsistent with the approved label if the physicians personally believe in their professional medical judgment it could be used in such manner.

If we receive marketing approval for our product candidate for our proposed indications, physicians may nevertheless use our product for their patients in a manner that is inconsistent with the approved label if the physicians personally believe in their professional medical judgment it could be used in such manner.

Although physicians may prescribe legally available drugs for off-label uses, manufacturers may not market or promote such off-label uses.

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For example, the FDA requires substantial evidence, which generally consists of two adequate and well-controlled head-to-head clinical trials, for a company to make a claim that its product is superior to another product in terms of safety or effectiveness.

Generally, unless we perform clinical trials meeting that standard comparing our product candidate to competitive products and these claims are approved in our product labeling, we will not be able promote our current product candidate as superior to other products.

Generally, unless we perform clinical trials meeting that standard comparing our product

candidate to competitive products and these claims are approved in our product labeling, we will not be able promote our product as superior to other products.

If we are found to have made such claims, we may become subject to significant liability.

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Our current and future relationships with healthcare professionals, investigators, consultants, collaborators, actual customers, potential customers and third-party payors in the United States and elsewhere may be subject, directly or indirectly, to applicable anti-kickback, fraud and abuse, false claims, physician payment transparency, health information privacy and security and other healthcare laws and regulations, which could expose us to sanctions.

Healthcare providers, physicians and third-party payors in the United States and elsewhere will play a primary role in the recommendation and prescription of our drug candidates if it obtains marketing approval.

Our current and future arrangements with healthcare professionals, investigators, consultants, collaborators, actual customers, potential customers and third-party payors may expose us to broadly applicable fraud and abuse and other healthcare laws, including, without limitation, the federal Anti-Kickback Statute and the federal False Claims Act, that may constrain the business or financial arrangements and relationships through which we sell, market and distribute any drug candidates for which we obtain marketing approval.

Healthcare providers, physicians and third-party payors in the United States and elsewhere will play a primary role in the recommendation and prescription of our drug post-marketing approval.

In addition, we may be subject to physician payment transparency laws and patient privacy and security regulation by the federal government and by the U.S.

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If our operations are found to be in violation of any of these laws or any other governmental regulations that may apply to us, we may be subject to significant civil, criminal and administrative penalties, including, without limitation, damages, fines, imprisonment, exclusion from participation in government healthcare programs, such as Medicare and Medicaid, and the curtailment or restructuring of our operations, which could significantly harm our business.

entities may be subject to criminal, civil or administrative sanctions, including exclusion from participation in government healthcare programs, which could also affect our business.

If any of the physicians or other healthcare providers or entities with whom we expect to do business, including our current and future collaborators, if any, are found not to be in compliance with applicable laws, those persons or entities may be subject to criminal, civil or administrative sanctions, including exclusion from participation in government healthcare programs, which could also affect our business.

The impact of recent healthcare reform legislation and other changes in the healthcare industry and healthcare spending on us is currently unknown and may adversely affect our business model.

In the United States and some foreign jurisdictions, legislative and regulatory changes and proposed changes regarding the healthcare system could prevent or delay marketing approval of our drug candidates, restrict or regulate post-approval activities and affect our ability to profitably sell any drug candidates for which we obtain marketing approval.

In the United States and some foreign jurisdictions, legislative and regulatory changes and proposed changes regarding the healthcare system could prevent or delay marketing approval of PEDMARK ® , restrict or regulate post-approval activities and affect our ability to profitably sell PEDMARK ® .

Our revenue prospects could be affected by changes in healthcare spending and policy in the United States and abroad.

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Among other things, healthcare reform may contain provisions that may reduce the profitability of drug products, including, for example, revising the methodology by which rebates owed by manufacturers for covered outpatient drugs under the Medicaid Drug Rebate Program are calculated, extending the Medicaid Drug Rebate Program to utilization of prescriptions of individuals enrolled in Medicaid managed care plans, imposing mandatory discounts for certain Medicare Part D beneficiaries, and subjecting drug manufacturers to payment of an annual fee.

We expect that healthcare reform measures that may be adopted in the future, may result in more rigorous coverage criteria and in additional downward pressure on the price that we receive for our product if it is approved for marketing.

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

The implementation of cost containment measures or other healthcare reforms may prevent us from being able to generate revenue or commercialize our drugs.

implementation of cost containment measures or other healthcare reforms may prevent us from being able to generate revenue or commercialize our drugs.

It is likely that federal and state legislatures within the United States and foreign governments will continue to consider changes to existing healthcare legislation.

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The continuing efforts of the government, insurance companies, managed care organizations and other payors of healthcare services to contain or reduce costs of healthcare may adversely affect:

● the demand for our product candidate;

● our ability to set a price that we believe is fair for our product candidate;

● our ability to obtain coverage and reimbursement approval for our product candidate;

● the demand for our product;

● our ability to set a price that we believe is fair for our product;

● our ability to obtain coverage and reimbursement approval for our product;

● our ability to generate revenues and achieve or maintain profitability;

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If we fail to comply with environmental, health and safety laws and regulations, we could become subject to fines or penalties or incur costs that could have a material adverse effect on our business, financial condition or results of operations.

Our research and development activities and our third-party manufacturers’ and suppliers’ activities involve the controlled storage, use, and disposal of hazardous materials, including the components of our product candidate and other hazardous compounds.

We and our manufacturers and suppliers are subject to laws and regulations governing the use, manufacture, storage, handling, and disposal of these hazardous materials.

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We cannot eliminate the risk of contamination, which could cause an interruption of our commercialization efforts, research and development efforts and business operations, environmental damage resulting in costly clean-up and liabilities under applicable laws and regulations governing the use, storage, handling, and disposal of these materials and specified waste products.

Although we believe that the safety procedures utilized by us and our third-party

manufacturers for handling and disposing of these materials generally comply with the standards prescribed by these laws and regulations, we cannot guarantee that this is the case or eliminate the risk of accidental contamination or injury from these materials.

Although we believe that the safety procedures utilized by us and our third-party manufacturers for handling and disposing of these materials generally comply with the standards prescribed by these laws and regulations, we cannot guarantee that this is the case or eliminate the risk of accidental contamination or injury from these materials.

In such an event, we may be held liable for any resulting damages and such liability could exceed our resources and state or federal or other applicable authorities may curtail our use of specified materials and/or interrupt our business operations.

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We do not currently carry biological or hazardous waste insurance coverage.

Risks Related to Commercialization of Our Product Candidate

Even if we obtain the required regulatory approvals in the United States and other territories, the commercial success of our product candidate will depend on market awareness and acceptance of our product candidates.

Even if we obtain marketing approval for PEDMARK TM , it may not gain market acceptance among physicians, key opinion leaders, healthcare payors, patients and the medical community.

Market acceptance of PEDMARK TM depends on a number of factors, including:

Our employees, sales agents and consultants may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements.

We are exposed to the risk of fraud or other misconduct by our employees, sales agents or consultants.

Misconduct could include failures to comply with FDA regulations, provide accurate information to the FDA, comply with manufacturing standards, comply with federal and state healthcare fraud and abuse laws and regulations, report financial information or data accurately or disclose unauthorized activities to us.

In particular, sales, marketing and business arrangements in the healthcare industry are subject to extensive laws and regulations intended to prevent fraud, kickbacks, self-dealing, and other abusive practices.

These laws and regulations may restrict or prohibit a wide range of pricing, discounting, marketing and promotion, sales commission, customer incentive programs, and other business arrangements.

Misconduct could also involve the improper use of information obtained in the course of clinical trials, which could result in regulatory sanctions and serious harm to our reputation.

It is not always possible to identify and deter such misconduct, and the precautions we take to detect and prevent this activity may not be effective in controlling unknown or unmanaged risks or losses or in protecting us from governmental investigations or other actions or lawsuits stemming from a failure to be in compliance with such laws or regulations.

If any such actions are instituted against us, and we are not successful in defending ourselves or asserting our rights, those actions could have a significant impact on our business, including the imposition of significant fines or other sanctions.

Risks Related to Commercialization of Our Product

After regulatory approvals in the United States and other territories, the commercial success of our product will depend on market awareness and acceptance of our product.

After obtaining marketing approval for PEDMARK ® , it may not gain market acceptance among physicians, key opinion leaders, healthcare payors, patients and the medical community.

Market acceptance of PEDMARK ® depends on a number of factors, including:

● the timing of market introduction;

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● the clinical indications for which it is approved, and the label approved by regulatory authorities for use with the product, including any precautions, warnings or contraindications that may be required on the label;

● acceptance by physicians, key opinion leaders and patients of PEDMARK TM as a safe and effective treatment;

● acceptance by physicians, key opinion leaders and patients of PEDMARK ® as a safe and effective treatment;

● the cost, safety and efficacy of treatment in relation to alternative treatments;

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Market acceptance is critical to our ability to generate revenue.

PEDMARK TM , if approved and commercialized, may be accepted in only limited capacities or not at all.

If PEDMARKTM is not accepted by the market to the extent that we expect, we may not be able to generate revenue and our business would suffer.

If the market opportunities for our product candidate are smaller than we believe they are, then our revenues may be adversely affected, and our business may suffer.

The market opportunities that our product candidate is being developed to address are rare.

Our projections of both the number of people who are administered Cisplatin, as well as the subset of people who have the potential to benefit from treatment with our product candidate, and our assumptions relating to pricing are based on estimates.

PEDMARK ® , may be accepted in only limited capacities or not at all.

If PEDMARK ® is not accepted by the market to the extent that we expect, we may not be able to generate revenue and our business would suffer.

If the market opportunities for our product are smaller than we believe they are, then our revenues may be adversely affected, and our business may suffer.

The market opportunities that our product is being developed to address are rare.

Our projections of both the number of people who are administered cisplatin, as well as the subset of people who have the potential to benefit from treatment with our product, and our assumptions relating to pricing are based on estimates.

Given the small number of patients that we are targeting, our eligible patient population and pricing estimates may differ significantly from the actual market addressable by our product candidate.

Coverage and reimbursement may be limited or unavailable in certain market segments for our product candidate, which could make it difficult for us to sell our products profitably.

Coverage and reimbursement may be limited or unavailable in certain market segments for our product, which could make it difficult for us to sell our product profitably.

There is significant uncertainty related to third-party coverage and reimbursement of newly approved pharmaceuticals.

Market acceptance and sales of our product candidate, should it receive marketing approval, will depend significantly on the availability of coverage and adequate reimbursement from third-party payors and may be affected by existing and future healthcare reform measures.

Market acceptance and sales of our product will depend significantly on the availability of coverage and adequate reimbursement from third-party payors and may be affected by existing and future healthcare reform measures.

Patients who are prescribed treatments for their conditions and providers performing the prescribed services generally rely on third-party payors to reimburse all or part of the associated healthcare costs.

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Increasingly, third-party payors are requiring that drug companies provide them with predetermined discounts from list prices and are challenging the prices charged for drugs and products.

Coverage and reimbursement may not be available for any product that we commercialize and, even if coverage is provided, the level of reimbursement may not be satisfactory.

Inadequate reimbursement levels may adversely affect the demand for, or the price of, our drug candidate if it obtains marketing approval.

Coverage and reimbursement may not be available for PEDMARK ® and, even if coverage is provided, the level of reimbursement may not be satisfactory.

Inadequate reimbursement levels may adversely affect the demand for, or the price of, PEDMARK ® .

Reimbursement by a third-party payor may depend upon a number of factors, including the third-party payor’s determination that use of a product is, among other things:

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One third-party payor’s decision to cover a particular drug product does not ensure that other payors will also provide coverage for the drug product, or even if coverage is available, establish an adequate reimbursement rate.

We cannot be sure that coverage or adequate reimbursement will be available for our product candidate.

We cannot be sure that coverage or adequate reimbursement will be available for our product.

Also, we cannot be sure that reimbursement amounts will not reduce the demand for, or the price of, our product.

If reimbursement is not available or is available only to limited levels, we may not be able to commercialize certain of our products.

If reimbursement is not available or is available only to limited levels, we may not be able to commercialize our product.

In the United States, third-party payors are increasingly attempting to contain healthcare costs by limiting both coverage and the level of reimbursement of new drugs.

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Even if favorable coverage and reimbursement status is attained for our product, less favorable coverage policies and reimbursement rates may be implemented in the future.

We face substantial competition, which may result in others discovering, developing or commercializing products before, or more successfully, than we do.

We face substantial competition, which may result in others discovering, developing or commercializing products more successfully, than we do.

The life sciences industry is highly competitive, and we face significant competition from many pharmaceutical, biopharmaceutical and biotechnology companies that are generally developing and marketing therapeutic products.

Such competition may include large pharmaceutical and biotechnology companies, specialty pharmaceutical and generic companies and medical technology companies.

Our future success depends on our ability to demonstrate and maintain a competitive advantage with respect to the design, development and commercialization of our product candidate for the treatment of orphan and ultra-orphan diseases for which there is a small patient population in both the United States and in all other potential markets.

Our future success depends on our ability to demonstrate and maintain a competitive advantage with respect to the design, development and commercialization of our product for the treatment of orphan and ultra-orphan diseases for which there is a small patient population in both the United States and in all other potential markets.

A drug designated an orphan drug may receive up to seven years of exclusive marketing in the United States for that indication.

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These companies also have significantly greater research and marketing capabilities than we do and may also have products that have been approved or are in late stages of development, and have collaborative arrangements in our target markets with leading companies and research institutions.

Established companies may also invest heavily to accelerate discovery and development of compounds that could make our product candidate obsolete.

Established companies may also invest heavily to accelerate discovery and development of compounds that could make our product obsolete.

As a result of all of these factors, maintaining orphan drug designation for our product candidate is essential to our viability since our competitors may, among other things:

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We believe that our ability to successfully compete will depend on our ability to maintain orphan drug designation as well as:

● our ability to design and successfully execute appropriate clinical trials;

● our ability to recruit and enroll patients for our clinical trials;

● the results of our clinical trials and the efficacy and safety of our product candidate;

● the speed at which we develop our product candidate;

● achieving and maintaining compliance with regulatory requirements applicable to our business;

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● adequate levels of reimbursement under private and governmental health insurance plans, including Medicare and Medicaid;

● our ability to protect intellectual property rights related to our product candidate;

● our ability to commercialize and market our product candidate if it obtains marketing approval;

● our ability to manufacture and sell commercial quantities of any approved our product candidate;

● acceptance of our product candidate by physicians, other healthcare providers and patients;

● our ability to protect intellectual property rights related to our product;

● our ability to commercialize and market our product;

● our ability to manufacture and sell commercial quantities of our product;

● acceptance of our product by physicians, other healthcare providers and patients;

● the cost of treatment in relation to alternative therapies.

If our competitors are able to obtain orphan drug exclusivity for their products that are for the same indication as our product candidate, we may not be able to have our product approved by the applicable regulatory authority for a significant period of time or benefit from that exclusivity.

We have orphan drug designation in the United States for PEDMARK TM for the prevention of platinum induced ototoxicity in pediatric patients.

Generally, if a product with an orphan drug designation subsequently receives the first marketing approval for the indication for which it has such designation, that product is entitled to a period of marketing exclusivity, which precludes the applicable regulatory authority from approving another marketing application for the same drug for the same indication for that time period.

The applicable period is seven years in the United States with the potential for an additional six months under pediatric orphan drug status.

Maintaining orphan drug designation for PEDMARK TM may be important to its success.

Even with orphan drug designation, we may not be able to maintain it.

For example, if a competitive product that treats the same disease as our product candidate is shown to be clinically superior to our product candidate, any orphan drug designation we have obtained will not block the approval of such competitive product and we may effectively lose what had previously been orphan drug designation.

Orphan drug designation for PEDMARK TM also will not bar the FDA from approving another STS drug product for another indication.

In the United States, reforms to the Orphan Drug Act, if enacted, could also materially affect our ability to maintain orphan drug designation for PEDMARK TM for cisplatin induced ototoxicity in pediatric cancer.

Price controls may be imposed in foreign markets, which may adversely affect our future profitability.

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Reference pricing used by various European Union member states and parallel distribution, or arbitrage between low-priced and high-priced member states, can further reduce prices.

In some countries, we may be required to conduct a clinical trial or other studies that compare the cost-effectiveness of our product candidate to other available therapies in order to obtain or maintain reimbursement or pricing approval.

In some countries, we may be required to conduct a clinical trial or other studies that compare the cost-effectiveness of our product to other available therapies in order to obtain or maintain reimbursement or pricing approval.

Publication of discounts by third-party payors or authorities may lead to further pressure on the prices or reimbursement levels within the country of publication and other countries.

If reimbursement of our products is unavailable or limited in scope or amount, or if pricing is set at unsatisfactory levels, our business could be adversely affected.

Rapid technological change could make our products obsolete.

If reimbursement of our product is unavailable or limited in scope or amount, or if pricing is set at unsatisfactory levels, our business could be adversely affected.

Rapid technological change could make our product obsolete.

Pharmaceutical technologies have undergone rapid and significant change, and we expect that they will continue to do so.

As a result, there is significant risk that our product candidate may be rendered obsolete or uneconomical by new discoveries before we recover any expenses incurred in connection with their development.

If our product candidate is rendered obsolete by advancements in pharmaceutical technologies, our prospects will suffer.

As a result, there is significant risk that our product may be rendered obsolete or uneconomical by new discoveries before we recover any expenses incurred in connection with their development.

If our product is rendered obsolete by advancements in pharmaceutical technologies, our prospects will suffer.

We face a risk of product liability claims and may not be able to obtain adequate insurance.

Our business exposes us to potential liability risks that may arise from the clinical testing, manufacture, and/or sale of our pharmaceutical products.

Our business exposes us to potential liability risks that may arise from the clinical testing, manufacture, and/or sale of our pharmaceutical product.

Patients have received substantial damage awards in some jurisdictions against pharmaceutical companies based on claims for injuries allegedly caused by the use of pharmaceutical products used in clinical trials or after FDA approval.

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However, our insurance may not reimburse us for certain claims or the coverage may not be sufficient to cover claims made against us.

We cannot predict all of the possible harms or side effects that may result from the use of our drug candidate and, therefore, the amount of insurance coverage we currently hold may not be adequate to cover all liabilities we might incur.

If we are sued for any injury allegedly caused by our products, our liability could exceed our ability to pay the liability.

We cannot predict all of the possible harms or side effects that may result from the use of our drug and, therefore, the amount of insurance coverage we currently hold

may not be adequate to cover all liabilities we might incur.

If we are sued for any injury allegedly caused by our product, our liability could exceed our ability to pay the liability.

Risks Related to Government Regulation

PEDMARK ® is subject to ongoing regulatory review.

If we fail to comply with continuing United States and applicable foreign regulations, we could lose those approvals, and our business would be severely harmed.

We are and will continue to be subject to continuing regulatory review for our product, including the review of our required nonclinical and clinical post-marketing studies, and other clinical results which are reported after our drug becomes commercially available.

As greater numbers of patients use a drug following its approval, side effects and other problems may be observed after approval that were not seen or anticipated during preapproval clinical studies and trials.

In addition, both we and the manufacturing facilities we use to make our product will also be subject to periodic review and inspection by the FDA.

The subsequent discovery of previously unknown problems with us, the manufacturing facilities or our product may result in restrictions on us, the manufacturing facilities or our product, including withdrawal of our product from the market.

If we fail to comply with applicable continuing regulatory requirements, we may be subject to fines, suspension, or withdrawal of regulatory approval, product recalls and seizures, operating restrictions, and criminal prosecutions.

Our product promotion and advertising are also subject to regulatory requirements and continuing regulatory review.

In particular, the marketing claims we will be permitted to make in labeling or advertising regarding our product will be limited by the terms and conditions of the FDA-approved labeling and available scientific data.

We must submit copies of our advertisements and promotional labeling to the FDA at the time of initial publication or dissemination.

If the FDA believes these materials or statements promote our product for unapproved indications, or with unsubstantiated claims, or if we fail to provide appropriate safety related information, the FDA could allege that our promotional activities misbrand our product.

Specifically, the FDA could issue an untitled letter or warning letter, which may demand, among other things, that we cease such promotional activities and issue corrective advertisements and labeling to all recipients of the misbranded materials.

The FDA also could take enforcement action including seizure of allegedly misbranded product, injunction, or criminal prosecution against us and our officers or employees.

If we repeatedly or deliberately fail to submit such advertisements and labeling to the agency, the FDA could withdraw our approvals.

Moreover, the Department of Justice can bring civil or criminal actions against companies and executives that promote drugs or biologics for unapproved uses, based on the Federal Food, Drug, and Cosmetic Act, the False Claims Act, and other federal laws governing the marketing and reimbursement for such products under federally supported healthcare programs such as Medicare and Medicaid.

Monetary penalties in such cases have often been substantial, and civil penalties can include costly mandatory compliance programs and potential exclusion of a company’s products from federal healthcare programs.

Enacted and future legislation or judicial action may increase the difficulty and cost for us to commercialize PEDMARK ®

In the United States, there have been a number of court cases, legislative and regulatory changes, and other potential changes relating to the healthcare system that restrict or regulate post-approval activities, which may affect our ability to profitably sell PEDMARK ® or any other drug candidates for which we obtain marketing approval.

The Medicare Prescription Drug Improvement and Modernization Act of 2003, or MMA, changed the way Medicare covers and pays for drug products.

The legislation expanded Medicare coverage for outpatient drug purchases by those covered by Medicare under a new Part D and introduced a reimbursement methodology based on average sales prices for Medicare Part B physician-administered drugs.

In addition, this legislation authorized Medicare Part D prescription drug plans to use formularies whereby they can limit the number of drugs that will be covered in any therapeutic class.

As a result of this legislation and the expansion of federal coverage of drug products, there is additional pressure to contain and reduce costs.

While the MMA applies only to drug benefits for Medicare beneficiaries, private payors often follow Medicare coverage policy and payment limitations in setting their own reimbursement rates, and any reduction in reimbursement that results from the MMA may result in a similar reduction in payments from private payors.

These cost reduction initiatives and other provisions of the MMA could decrease the coverage and reimbursement that we receive for our product and could seriously harm our business.

Manufacturers’ contributions to this area, including donut hole coverage (as described below) or potential excise taxes, are increasing and are subject to additional changes in the future.

In 2010, former President Obama signed into law the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act of 2010 (together, the “Health Care Reform Law”), a sweeping law intended to broaden access to health insurance, reduce or constrain the growth of healthcare spending, enhance remedies against fraud and abuse, add new transparency requirements for healthcare and health insurance industries, impose new taxes and fees on the health industry, and impose additional health policy reforms.

The Health Care Reform Law, among other things, revised the definition of Average Manufacturer Price used by the Medicaid Drug Rebate Program for reporting purposes, imposed a significant annual fee on companies that manufacture or import branded prescription drug products and established an annual non-deductible fee on entities that sell branded prescription drugs or biologics to specified government programs in the United States.

The Health Care Reform Law also expanded the 340B drug discount program (excluding orphan drugs), including the creation of new penalties for non-compliance and included a discount (now 70%, on brand name drugs for Medicare Part D participants in the coverage gap, or “donut hole.” The Health Care Reform Law increased the Medicaid rebates for line extensions or reformulated drugs, which could substantially increase our Medicaid rebate rate (in effect limiting reimbursement for these patients).

Beginning in January 2017, former President Trump signed two Executive Orders and other directives designed to delay the implementation of certain provisions of the Health Care Reform Law or otherwise circumvent some of the requirements for health insurance mandated by the Health Care Reform Law.

These actions include directing applicable federal agencies to waive, defer, grant exemptions from, or delay the implementation of any provision of the Health Care Reform Law that would impose a fiscal or regulatory burden on states, individuals, healthcare providers, health insurers, or manufacturers of pharmaceuticals or medical devices.

On October 13, 2017, an Executive Order was signed terminating the cost sharing subsidies that reimburse insurers under the Health Care Reform Law.

Several state Attorneys Generals filed suit to stop the administration from terminating the subsidies, but their request for a restraining order was denied by a federal judge in California on October 25, 2017.

Further, on June 14, 2018 the United States Court of Appeals for the Federal Circuit ruled that the federal government was not required to pay more than $12.0 billion in Health Care Reform Law risk corridor payments to third-party payors.

The effects of this gap in reimbursement on third-party payors, the viability of the Health Care Reform Law marketplace, providers, and our business, are not yet known.

On December 18, 2019, the United States Court of Appeals for the Fifth Circuit ruled that the Health Care Reform Law’s individual mandate is unconstitutional but sent the matter back down to a district court to determine whether that provision can be removed from the rest of the Health Care Reform Law.

On March 2, 2020, the U.S.

Supreme Court agreed to review the Fifth Circuit’s ruling, and oral argument was heard on November 10, 2020.

On June 17, 2021, the U.S.

Supreme Court dismissed the challenge to the Health Care Reform Law in a 7-2 decision.

Additionally, in response to controversies regarding pricing of drug products, there has been a recent push to propose legislation, both on state and federal levels, that would require greater disclosure as to the reasoning behind drug prices and, in some cases, could give state or federal-level commissions the right to impose cost controls on certain drugs.

These and other new provisions are likely to continue the pressure on pharmaceutical pricing, may require us to modify our business practices with healthcare practitioners, and may also increase our regulatory burdens and operating costs.

In that regard, President Biden and members of Congress in both parties have expressed concerns about high drug prices.

However, whether and to what extent any such positions will result in changes of the law, and how any such changes could impact our business, cannot be determined at this time.

Legislative and regulatory proposals also have been made to expand post-approval requirements, restrict sales and promotional activities for drug products, and with respect to orphan drug designation and exclusivity.

In addition, increased scrutiny by the United States Congress of the FDA’s approval process may subject us to more stringent product labeling and post-marketing testing and other requirements.

Delays in feedback from the FDA may affect our ability to quickly update or adjust our label in the interest of patient adherence and tolerability.

We cannot predict whether other legislative changes will be adopted or how such changes would affect the pharmaceutical industry generally and specifically the commercialization of PEDMARK ® .

If we fail to obtain or subsequently maintain orphan drug exclusivity or regulatory exclusivity for PEDMARK ® , our competitors may sell products to treat the same conditions at greatly reduced prices, and our revenues would be significantly adversely affected.

In the United States, orphan drug designation entitles a party to financial incentives such as opportunities for grant funding towards clinical trial costs, tax advantages, and user-fee waivers.

The company that first obtains FDA approval for a designated orphan drug for a given rare disease receives marketing exclusivity for use of that drug for the stated disease or condition for a period of seven years, with an additional six months of exclusivity if the product also qualifies for pediatric exclusivity.

Orphan drug exclusive marketing rights may be lost if the FDA later determines that the request for designation was materially defective, a subsequent product is deemed clinically superior, or if the manufacturer is unable to deliver sufficient quantity of the drug.

Because the extent and scope of patent protection for some of our drug products may be particularly limited, orphan drug designation – and ultimately, orphan drug exclusivity – is especially important for our product.

For eligible drugs, we plan to rely on the orphan exclusivity period to maintain a competitive position.

However, if we do not obtain orphan drug exclusivity for our drug candidates or we cannot maintain orphan exclusivity for our drug candidates, our competitors may then sell the same drug to treat the same condition and our revenues will be reduced.

Also, without strong patent protection, competitors may sell a generic version upon the expiration of orphan exclusivity if our patent position is not upheld.

Even after an orphan drug is approved, the FDA can subsequently approve a drug for the same condition if the FDA concludes that the later drug is safer, more effective or makes a major contribution to patient care.

The FDA can discontinue orphan drug exclusivity after it has been granted if the orphan drug cannot be manufactured in sufficient quantities to meet demand.

Finally, there can be no assurance that the exclusivity provisions currently in the law may not be changed in the future and the impact of any such changes (if made) on us.

The orphan drug exclusivity contained in the Orphan Drug Act has been the subject of recent scrutiny from the press, from some members of Congress and from some in the medical community.

There can be no assurance that the exclusivity granted in the Orphan Drug Act to orphan drugs approved by the FDA will not be modified in the future, and as to how any such change might affect our product, if approved.

Changes to the Orphan Drug Act or successful legal challenges to the FDA’s interpretation of the Orphan Drug Act may affect our ability to obtain or subsequently maintain orphan drug exclusivity or affect the scope of orphan drug exclusivity for our product.

There can be no assurance whether the exclusivity provisions in the Orphan Drug Act may be changed in the future and the impact of such changes, if made on us.

The orphan drug exclusivity contained in the Orphan Drug Act has been the subject of recent scrutiny from the press, from some members of Congress and from some in the medical community.

Furthermore, the FDA’s interpretations of the Orphan Drug Act have been successfully challenged in court and future court decisions could continue that trend.

Our operations and relationships with healthcare providers, healthcare organizations, customers and third-party payors are subject to applicable anti-bribery, anti-kickback, fraud and abuse, transparency and other healthcare laws and regulations, which could expose us to, among other things, enforcement actions, criminal sanctions, civil penalties, contractual damages, reputational harm, administrative burdens and diminished profits and future earnings.

Our current and future arrangements with healthcare providers, healthcare organizations, third-party payors, customers, and patients expose us to broadly applicable anti-bribery, fraud and abuse and other healthcare laws and regulations that may constrain the business or financial arrangements and relationships through which we research, market, sell and distribute our drug.

In addition, we may be subject to patient data privacy and security regulation by the U.S.

federal government and the states and the foreign governments in which we conduct our business.

Restrictions under applicable federal and state anti-bribery and healthcare laws and regulations include the following:

• the Federal health care program Anti-Kickback Statute, which prohibits individuals and entities from, among other things, knowingly and willfully soliciting, offering, receiving or providing remuneration, directly or indirectly, in cash or in kind, to induce or reward, or in return for, either the referral of an individual for, or the purchase, order or recommendation of, any good or service, for which payment may be made under a federal and state healthcare program such as Medicare and Medicaid.

A person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation;

• the federal criminal and civil false claims and civil monetary penalties laws, including the federal False Claims Act, which can be imposed through civil whistleblower or qui tam actions against individuals or entities, prohibits, among other things, knowingly presenting, or causing to be presented, to the federal government, claims for payment that are false or fraudulent, knowingly making, using or causing to be made or used, a false record or statement material to a false or fraudulent claim, or from knowingly making a false statement to avoid, decrease or conceal an obligation to pay money to the federal government.

In addition, certain marketing practices, including off-label promotion, may also violate false claims laws.

Moreover, the government may assert that a claim including items and services resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the federal False Claims Act;

• HIPAA, which imposes criminal and civil liability, prohibits, among other things, knowingly and willfully executing, or attempting to execute a scheme to defraud any healthcare benefit program, or knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false statement in connection with the delivery of or payment for healthcare benefits, items or services;

similar to the federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation;

• HIPAA, as amended by HITECH, which impose obligations on certain healthcare providers, health plans, and healthcare clearinghouses, known as covered entities, as well as their business associates that perform certain services involving the storage, use or disclosure of individually identifiable health information, including mandatory contractual terms, with respect to safeguarding the privacy, security, and transmission of individually identifiable health information, and require notification to affected individuals and regulatory authorities of certain breaches of security of individually identifiable health information;

• the federal legislation commonly referred to as the Physician Payments Sunshine Act, enacted as part of the ACA, and its implementing regulations, which requires certain manufacturers of covered drugs, devices, biologics and medical supplies that are reimbursable under Medicare, Medicaid, or the Children’s Health Insurance Program, with certain exceptions, to report annually to CMS information related to certain payments and other transfers of value to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), physician assistants, certain types of advanced care practice nurses and teaching hospitals, as well as ownership and investment interests held by the physicians described above and their immediate family members, with the information made publicly available on a searchable website;

Foreign Corrupt Practices Act of 1977, as amended, which prohibits, among other things, U.S.

companies and their employees and agents from authorizing, promising, offering, or providing, directly or indirectly, corrupt or improper payments or anything else of value to foreign government officials, employees of public international organizations and foreign government owned or affiliated entities, candidates for foreign political office, and foreign political parties or officials thereof;

• analogous state and foreign laws and regulations, such as state anti-kickback and false claims laws, that may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third-party payors, including private insurers;

• certain state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government in addition to requiring drug and therapeutic biologics manufacturers to report information related to payments to physicians and other healthcare providers or marketing expenditures and pricing information, state and local laws that require the registration of pharmaceutical sales representatives, and state laws governing the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts.

If we or our collaborators, manufacturers or service providers fail to comply with applicable federal, state or foreign laws or regulations, we could be subject to enforcement actions, which could affect our ability to develop, market and sell our product successfully and could harm our reputation and lead to reduced acceptance of our product by the market.

These enforcement actions include, not only civil and criminal penalties, but also exclusion from participation in government-funded healthcare programs, and exclusion from eligibility for the award of government contracts for our product.

Efforts to ensure that our current and future business arrangements with third parties comply with applicable healthcare laws and regulations could involve substantial costs.

It is possible that governmental authorities will conclude that our business practices do not comply with current or future statutes, regulations, agency guidance or case law involving applicable fraud and abuse or other healthcare laws and regulations.

If our operations are found to be in violation of any such requirements, we may be subject to significant penalties, including civil, criminal and administrative penalties, damages, fines, disgorgement, imprisonment, the curtailment or restructuring of our operations, loss of eligibility to obtain approvals from the FDA, exclusion from participation in government contracting, healthcare reimbursement or other government programs, including Medicare and Medicaid, integrity oversight and reporting obligations, or reputational harm, any of which could adversely affect our financial results.

Although effective compliance programs can mitigate the risk of investigation and prosecution for violations of these laws, these risks cannot be entirely eliminated.

Any action against us for an alleged or suspected violation could cause us to incur significant legal expenses and could divert our management’s attention from the operation of our business, even if our defense is successful.

In addition, achieving and sustaining compliance with applicable laws and regulations may be costly to us in terms of money, time and resources.

Risks Related to Third Parties

We rely on third-party suppliers and other third parties for production of our product candidate and our dependence on these third parties may impair the advancement of our research and development programs and the development of our product candidate.

We do not currently own or operate manufacturing facilities for clinical or commercial production of our product candidate.

We lack the resources and the capability to manufacture our product candidate on a clinical or commercial scale.

Instead, we rely on, and expect to continue to rely on, third parties for the supply of raw materials and manufacture of drug supplies necessary to conduct our preclinical studies and clinical trials.

Our reliance on third parties may expose us to more risk than if we were to manufacture our current product candidate or other products ourselves.

We rely on third-party suppliers and other third parties for production of our product and our dependence on these third parties may impair the advancement of our research and development programs and the development of our product.

We do not currently own or operate manufacturing facilities for clinical or commercial production of our product.

We lack the resources and the capability to manufacture our product on a clinical or commercial scale.

Instead, we rely on, and expect to continue to rely on, third parties for the supply of raw materials and manufacture of drug supplies necessary to

conduct our preclinical studies and clinical trials.

Our reliance on third parties may expose us to more risk than if we were to manufacture our current product or other products ourselves.

Delays in production by third parties could delay our clinical trials or have an adverse impact on any commercial activities.

In addition, the fact that we are dependent on third parties for the manufacture of and formulation of our product candidate means that we are subject to the risk that the products may have manufacturing defects that we have limited ability to prevent or control.

Although we oversee these activities to ensure compliance with our quality standards, budgets and timelines, we have had and will continue to have less control over the manufacturing of our product candidate than potentially would be the case if we were to manufacture our product candidate.

Further, the third parties we deal with could have staffing difficulties, might undergo changes in priorities or may become financially distressed, which would adversely affect the manufacturing and production of our product candidate.

In addition, the fact that we are dependent on third parties for the manufacture of and formulation of our product means that we are subject to the risk that the products may have manufacturing defects that we have limited ability to prevent or control.

Although we oversee these activities to ensure compliance with our quality standards, budgets and timelines, we have had and will continue to have less control over the manufacturing of our product than potentially would be the case if we were to manufacture our product.

In addition, a third party could be acquired by, or enter into an exclusive arrangement with, one of our competitors, which would adversely affect our ability to access the formulations we require.

The facilities used by our current contract manufacturers and any future manufacturers to manufacture our product candidate must be inspected by the FDA during the review of our NDA.

We do not control the manufacturing process of, and are completely dependent on, our contract manufacturers for compliance with the regulatory requirements, known as cGMP, for manufacture of both active drug substances and finished drug products.

If our contract manufacturers cannot successfully manufacture material that conforms to our specifications and the strict regulatory requirements of the FDA or others, the FDA may refuse to approve our NDA.

The CRLs that we received from the FDA in August 2020 and November 2021, as a result of deficiencies in the third-party manufacturing facility that manufactures PEDMARK TM on our behalf is a specific example of the risks associated with our third-party manufacturers.

If the FDA or a comparable foreign regulatory authority does not approve our NDA because of concerns about the manufacture of our product candidate or if significant manufacturing issues arise in the future, we may need to find alternative manufacturing facilities, which would significantly impact our ability to develop our product candidate, to obtain marketing approval of our NDA or to continue to market our product candidate, if approved.

Although we are ultimately responsible for

ensuring compliance with these regulatory requirements, we do not have day-to-day control over a contract manufacturing organization (“CMO”) or other third-party manufacturer’s compliance with applicable laws and regulations, including cGMP and other laws and regulations, such as those related to environmental health and safety matters.

Any failure to achieve and maintain compliance with these laws, regulations and standards could subject us to the risk that we may have to suspend the manufacturing of our product candidate or that obtained approvals could be revoked, which would adversely affect our business and reputation.

In addition, third-party contractors, such as our CMOs, may elect not to continue to work with us due to factors beyond our control.

Although we have contracts in place, they may also refuse to work with us because of their own financial difficulties, business priorities or other reasons, at a time that is costly or otherwise inconvenient for us.

If we were unable to find adequate replacement or another acceptable solution in time, our clinical trials could be delayed or our commercial activities could be harmed.

On August 10, 2020, we received a CRL.

According to the CRL, after recent completion of a pre-approval inspection of the manufacturing facility of our drug product manufacturer, the FDA identified deficiencies resulting in a Form 483, which is a list of conditions or practices that are required to be resolved prior to the approval of PEDMARK™.

Similarly, on November 29, 2021, we received another CRL due to a pre-approval inspection of the manufacturing facility of our drug product manufacturer in which the FDA again identified deficiencies resulting in a Form 483, which is a list of conditions or practices that are required to be resolved prior to the approval of PEDMARK™.

We anticipate resubmitting an NDA in the first quarter of 2022.

If our NDA for PEDMARK TM is ultimately not approved by the FDA, we would not be able to commercialize PEDMARK TM , which would have a material adverse effect on our business.

Problems with the quality of the work of third parties may lead us to seek to terminate our working relationships and use alternative service providers.

However, making this change may be costly and may delay clinical trials.

In addition, it may be very challenging, and in some cases impossible, to find replacement service providers that can develop and manufacture our drug candidates in an acceptable manner and at an acceptable cost and on a timely basis.

In addition, it may be very challenging, and in some cases impossible, to find replacement service providers that can develop and manufacture our drug in an acceptable manner and at an acceptable cost and on a timely basis.

The sale of products containing any defects or any delays in the supply of necessary services could adversely affect our business, financial condition, results of operations, and prospects.

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Supply sources could be interrupted from time to time and, if interrupted, supplies may not be resumed (whether in part or in whole) within a reasonable timeframe and at an acceptable cost or at all.

We plan to rely on third parties to conduct clinical trials for our product candidate.

If these third parties do not successfully carry out their contractual duties or meet expected deadlines, it may cause delays in commencing and completing clinical trials of our product candidate or we may be unable to obtain marketing approval for or commercialize our product candidate.

Clinical trials must meet applicable FDA and foreign regulatory requirements.

We do not have the ability to independently conduct clinical trials for our product candidate.

We expect to rely on third parties, such as CROs, medical institutions, clinical investigators and contract laboratories, to conduct all of our clinical trials of our product candidate;

We plan to rely on third parties to conduct clinical trials for our product.

If these third parties do not successfully carry out their contractual duties or meet expected deadlines, we may be unable to obtain marketing approval for or commercialize our product outside of the United States.

Clinical trials must meet applicable foreign regulatory requirements.

We do not have the ability to independently conduct clinical trials for our product abroad.

We expect to rely on third parties, such as CROs, medical institutions, clinical investigators and contract laboratories, to conduct all of our clinical trials of our product;

however, we remain responsible for ensuring that each of our clinical trials is conducted in accordance with our investigational plan and protocol.

Moreover, the FDA and other foreign regulatory authorities require us to comply with IND and human subject protection regulations and cGCP standards, for conducting, monitoring, recording, and reporting the results of clinical trials to ensure that the data and results are scientifically credible and accurate and that the trial subjects are adequately informed of the potential risks of participating in clinical trials.

Moreover, the other foreign regulatory authorities require us to comply with IND and human subject protection regulations and cGCP standards, for conducting, monitoring, recording, and reporting the results of clinical trials to ensure that the data and results are scientifically credible and accurate and that the trial subjects are adequately informed of the potential risks of participating in clinical trials.

Our reliance on third parties does not relieve us of these responsibilities and requirements.

Regulatory authorities enforce these cGCP through periodic inspections of trial sponsors, principal investigators and trial sites.

If we or any of our third-party contractors fail to comply with applicable cGCP, the clinical data generated in our clinical trials may be deemed unreliable and the FDA or comparable foreign regulatory authorities may require us to perform additional clinical trials before approving our marketing applications.

There is no assurance that upon inspection by a given regulatory authority, such regulatory

authority will determine that any of our clinical trials comply with cGCP.

Our failure to comply with these regulations may require us to repeat clinical trials, which would delay the marketing approval process.

If we or any of our third-party contractors fail to comply with applicable cGCP, the clinical data generated in our clinical trials may be deemed unreliable and the foreign regulatory authorities may require us to perform additional clinical trials before approving our marketing applications.

There is no assurance that upon inspection by a given regulatory authority, such regulatory authority will determine that any of our clinical trials comply with cGCP.

Our failure to comply with these regulations may require us to repeat clinical trials, which would delay the marketing approval process abroad.

There are significant requirements imposed on us and on clinical investigators who conduct clinical trials that we sponsor.

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We cannot ensure that the CROs or clinical investigators in our trials will not make mistakes or otherwise compromise the integrity or validity of data, any of which would have a significant negative effect on our ability to obtain marketing approval, our business, and our financial condition.

We or the third parties we rely on may encounter problems in clinical trials that may cause us or the FDA or foreign regulatory agencies to delay, suspend or terminate our clinical trials at any phase.

These problems could include the possibility that we may not be able to manufacture sufficient quantities of materials for use in our clinical trials, conduct clinical trials at our preferred sites, enroll a sufficient number of patients for our clinical trials at one or more sites, or begin or successfully complete clinical trials in a timely fashion, if at all.

Furthermore, we, the FDA or foreign regulatory agencies may suspend clinical trials of our product candidate at any time if we or they believe the subjects participating in the trials are being exposed to unacceptable health risks, whether as a result of adverse events occurring in our trials or otherwise, or if we or they find deficiencies in the clinical trial process or conduct of the investigation.

The FDA and foreign regulatory agencies could also require additional clinical trials before or after granting of marketing approval for any products, which would result in increased costs and significant delays in the development and commercialization of such products and could result in the withdrawal of such products from the market after obtaining marketing approval.

Our failure to adequately demonstrate the safety and efficacy of a product candidate in clinical development could delay or prevent obtaining marketing approval of the product candidate and, after obtaining marketing approval, data from post-approval studies could result in the product being withdrawn from the market, either of which would likely have a material adverse effect on our business.

We or the third parties we rely on may encounter problems in clinical trials that may cause us or the foreign regulatory agencies to delay, suspend or terminate our clinical trials at any phase.

complete clinical trials in a timely fashion, if at all.

Furthermore, we or foreign regulatory agencies may suspend clinical trials of our product at any time if we or they believe the subjects participating in the trials are being exposed to unacceptable health risks, whether as a result of adverse events occurring in our trials or otherwise, or if we or they find deficiencies in the clinical trial process or conduct of the investigation.

The foreign regulatory agencies could also require additional clinical trials before or after granting of marketing approval for our product, which would result in increased costs and significant delays in the development and commercialization of our product and could result in the withdrawal of our product from the market after obtaining marketing approval.

Our failure to adequately demonstrate the safety and efficacy of our product in clinical development could delay or prevent obtaining marketing approval of the product and, after obtaining marketing approval, data from post-approval studies could result in our product being withdrawn from the market, either of which would likely have a material adverse effect on our business.

Risks Related to Our Intellectual Property

We are dependent on our relationships and license agreements, and we rely upon the patent rights granted to us pursuant to the license agreements.

Our commercial success will depend in large part on our ability to use patents and regulatory exclusivity to exclude others from competing with our products.

Our commercial success will depend in large part on our ability to use patents and regulatory exclusivity to exclude others from competing with our product.

The patent position of emerging pharmaceutical companies like us can be highly uncertain and involve complex legal and technical issues.

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While we are not currently aware of any third-party patents which we may infringe, there can be no assurance that we do not or will not infringe on patents held by third parties or that third parties will not claim that we have infringed on their patents.

In the event that our technologies infringe or violate the patent or other proprietary rights of third parties, we may be prevented from pursuing product development, manufacturing or commercialization of our products that utilize such technologies.

There may be patents held by others of which we are unaware that contain claims that our products or

operations infringe.

There may be patents held by others of which we are unaware that contain claims that our product or operations infringe.

In addition, given the complexities and uncertainties of patent laws, there may be patents of which we are aware that we may ultimately be held to infringe, particularly if the claims of the patent are determined to be broader than we believe them to be.

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The outcome of intellectual property litigation is subject to substantial uncertainties and may, for example, turn on the interpretation of claim language by the court, which may not be to our advantage, or on the testimony of experts as to technical facts upon which experts may reasonably disagree.

As discussed above under the heading “Business – Overview – Product Candidate,” on October 29, 2021, Hope Medical Enterprises, Inc.

As discussed above under the heading Legal Proceedings “Business – Overview – Product,” on October 29, 2021, Hope Medical Enterprises, Inc.

(“Hope”) filed two petitions for inter partes review (“IPR”) with the Patent Trial and Appeal Board (“PTAB”) of the USPTO.

In its petitions, Hope seeks to invalidate our U.S.

10,596,190 (“US ‘190”), which is exclusively in-licensed from Oregon Health & Science University (“OHSU”) and relates to a method of using our PEDMARK™ product, and our U.S.

10,596,190 (“US ‘190”), which is exclusively in-licensed from Oregon Health & Science University (“OHSU”) and relates to a method of using PEDMARK ® , and our U.S.

10,792,363 (“US ’363”), which relates to an anhydrous form of STS, which is the active pharmaceutical ingredient in our PEDMARK ® product.

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On January 11, 2022, our licensor OHSU filed a Request for Supplemental Examination of US ‘190 requesting the consideration by the USPTO of certain prior art references, including references cited by Hope in its Petition for IPR that are relevant to the granted claim of the patent.

On January 28, 2022, the USPTO found that the cited references constitute a substantial new question of patentability and ordered an ex parte reexamination of the single US ‘190 claim

of pursuant to 35 U.S.C.

On January 28, 2022, the USPTO found that the cited references constitute a substantial new question of patentability and ordered an ex parte reexamination of the single US ‘190 claim of pursuant to 35 U.S.C.

We are unable to predict the outcome of the ex parte reexamination.

If the USPTO does not uphold the ‘190 claim as granted or in amended form, our ability to protect our PEDMARK TM product beyond the market exclusivity granted from Orphan Drug Designation and PUMA may be adversely affected.

If the USPTO does not uphold the ‘190 claim as granted or in amended form, our ability to protect our PEDMARK ® product beyond the market exclusivity granted from Orphan Drug Designation and PUMA may be adversely affected.

Under our license agreements, we have the right to bring legal action against any alleged infringers of the patents we license.

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Moreover, regardless of the outcome, intellectual property litigation against or by us could significantly disrupt our development and commercialization efforts, divert our management’s attention and quickly consume our financial resources.

In addition, if third parties file patent applications or issue patents claiming technology that is also claimed by us in pending applications, we may be required to participate in interference proceedings with the USPTO or in other proceedings outside the United States, including oppositions, to determine priority of invention or patentability.

the United States, including oppositions, to determine priority of invention or patentability.

Even if we are successful in these proceedings, we may incur substantial costs, and the time and attention of our management and scientific personnel will be diverted from product development or other more productive matters.

Our proprietary rights may not adequately protect our technologies and product candidate.

Our commercial success will depend in part on our ability to obtain patents and protect our existing patent position as well as our ability to maintain adequate protection of other intellectual property for our technologies, product candidate, and any future products in the United States and other countries.

Our proprietary rights may not adequately protect our technologies and product.

Our commercial success will depend in part on our ability to obtain patents and protect our existing patent position as well as our ability to maintain adequate protection of other intellectual property for our technologies, product, and any future products in the United States and other countries.

If we do not adequately protect our intellectual property, competitors may be able to use our technologies and erode or negate any competitive advantage we may have, which could harm our business and ability to achieve profitability.

The laws of some foreign countries do not protect our proprietary rights to the same extent or in the same manner as United States laws, and we may encounter significant problems in protecting and defending our proprietary rights in these countries.

We will be able to protect our proprietary rights from unauthorized use by third parties only to the extent that our proprietary technologies and product candidate are covered by valid and enforceable patents or are effectively maintained as trade secrets.

We apply for patents covering both our technologies and product candidate, as we deem appropriate.

However, we may fail to apply for patents on important technologies or product candidate in a timely fashion, or at all.

We will be able to protect our proprietary rights from unauthorized use by third parties only to the extent that our proprietary technologies and product are covered by valid and enforceable patents or are effectively maintained as trade secrets.

We apply for patents covering both our technologies and product, as we deem appropriate.

However, we may fail to apply for patents on important technologies or product in a timely fashion, or at all.

Our existing patents and any future patents we obtain may not be sufficiently broad to prevent others from practicing our technologies or from developing competing products and technologies.

We cannot be certain that our patent applications will be approved or that any patents issued will adequately protect our intellectual property.

While we are responsible for and have control over the filing and prosecuting of patent applications and maintaining patents which cover making, using or selling PEDMARK TM , we may lose any such rights if we decide to allow any licensed patent to lapse.

If we fail to appropriately prosecute and maintain patent protection for any of our product candidate, our ability to develop and commercialize those product candidate may be adversely affected and we may not be able to prevent competitors from making, using and selling competing products.

While we are responsible for and have control over the filing and prosecuting of patent applications and maintaining patents which cover making, using or selling PEDMARK ® , we may lose any such rights if we decide to allow any licensed patent to lapse.

If we fail to appropriately prosecute and maintain patent protection for PEDMARK ® , our ability to develop and commercialize PEDMARK ® may be adversely affected and we may not be able to prevent competitors from making, using and selling competing products.

Moreover, the patent positions of pharmaceutical companies are highly uncertain and involve complex legal and factual questions for which important legal principles are evolving and remain unresolved.

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● we or our licensors were the first to file patent applications for these inventions;

● any of the patents that cover our product candidate will be eligible to be listed in the FDA’s compendium of “Approved Drug Products with Therapeutic Equivalence Evaluation,” sometimes referred to as the FDA’s Orange Book;

● any of the patents that cover our product will be eligible to be listed in the FDA’s compendium of “Approved Drug Products with Therapeutic Equivalence Evaluation,” sometimes referred to as the FDA’s Orange Book;

● others will independently develop similar or alternative technologies or duplicate any of our technologies;

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The actual protection afforded by a patent varies based on products or processes, from country to country and depends upon many factors, including the type of patent, the scope of its coverage, the availability of regulatory related extensions, the availability of legal remedies in a particular country, the validity and enforceability of the patents and our financial ability to enforce our patents and other intellectual property.

Our ability to maintain and solidify our proprietary position for our products will depend on our success in obtaining effective claims and enforcing those claims once granted.

Our ability to maintain and solidify our proprietary position for our product will depend on our success in obtaining effective claims and enforcing those claims once granted.

Our issued patents and those that may issue in the future, or those licensed to us, may be challenged, narrowed, invalidated or circumvented, and the rights granted under any issued patents may not provide us with proprietary protection or competitive advantages against competitors with similar products.

Due to the extensive amount of time required for the development, testing and regulatory review of a potential product, it is possible that, before any of our product candidate can be commercialized, any related patent may expire or remain in force for only a short period following commercialization, thereby reducing any advantage of the patent.

We may also rely on trade secrets to protect some of our technology, especially where we do not believe patent protection is appropriate or obtainable.

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We may not be able to protect our intellectual property rights throughout the world.

Filing, prosecuting and defending patents on our product candidate in all countries throughout the world would be prohibitively expensive, and our intellectual property rights in some countries outside the United States can be less extensive than those in the United States.

Filing, prosecuting and defending patents on our product in all countries throughout the world would be prohibitively expensive, and our intellectual property rights in some countries outside the United States can be less extensive than those in the United States.

In addition, the laws of some foreign countries do not protect intellectual property rights to the same extent as federal and state laws in the United States.

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Competitors may use our technologies in jurisdictions where we have not obtained patent protection to develop their own products and further, may export otherwise infringing products to territories where we have patent protection, but enforcement rights are not as strong as those in the United States.

These products may compete with our product candidate in jurisdictions where we do not have any issued patents and our patent claims or other intellectual rights may not be effective or sufficient to prevent them from so competing.

These products may compete with our product in jurisdictions where we do not have any issued patents and our patent claims or other intellectual rights may not be effective or sufficient to prevent them from so competing.

Many companies have encountered significant problems in protecting and defending intellectual property rights in foreign jurisdictions.

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Accordingly, our efforts to enforce our intellectual property rights around the world may be inadequate to obtain a significant commercial advantage from the intellectual property that we develop or license.

The patent protection for our product candidate may expire before we are able to maximize their commercial value, which may subject us to increased competition and reduce or eliminate our opportunity to generate product revenue.

The patents for our product candidate have varying expiration dates and, if these patents expire, we may be subject to increased competition and we may not be able to recover our development costs or market any of our approved products profitably.

Third parties may seek approval to market their own products similar to or otherwise competitive with our product.

In these circumstances, we may need to defend or assert our patents, including by filing lawsuits alleging patent infringement.

For example, we have received a Paragraph IV certification notice letter from CIPLA, Inc., or CIPLA, indicating that it has submitted to FDA an abbreviated new drug application, or ANDA, seeking approval to manufacture and sell a generic version PEDMARK ® (sodium thiosulfate solution) prior to the expiration of certain Orange Book-listed patents protecting PEDMARK ® .

In an ANDA, the applicant must certify for each listed patent that (1) the required patent information has not been filed;

(2) the listed patent has expired;

(3) the listed patent has not expired, but will expire on a particular date and approval is sought after patent expiration;

or (4) the listed patent is invalid, unenforceable or will not be infringed by the new product.

A certification that the new product will not infringe the already approved product’s listed patent or that such patent is invalid is known as a Paragraph IV certification.

The CIPLA ANDA contains Paragraph IV certifications with respect to two of our patents covering PEDMAR, U.S.

Patent ‘190, expiration date May 2038;

and ‘728, expiration date May 2039.

We filed a patent infringement lawsuit against CIPLA, and vigorously defend and enforce our intellectual property rights protecting PEDMARK, but we can offer no assurance that our efforts we will be successful in which case our business may be materially and adversely affected.

The patent protection for our product may expire before we are able to maximize their commercial value, which may subject us to increased competition and reduce or eliminate our opportunity to generate product revenue.

The patents for our product have varying expiration dates and, if these patents expire, we may be subject to increased competition and we may not be able to recover our development costs or market any of our approved products profitably.

In some of the larger potential market territories, such as the United States and Europe, patent term extension or restoration may be available to compensate for time taken during aspects of the product’s development and regulatory review.

For example, depending on the timing, duration and specifics of FDA marketing approval of our product candidate, if any, one of the United States patents covering each of such approved product(s) or the use thereof may be eligible for up to five years of patent term restoration under the Hatch-Waxman Act.

For example, depending on the timing, duration and specifics of FDA marketing approval of our product, if any, one of the United States patents covering each of such approved product(s) or the use thereof may be eligible for up to five years of patent term restoration under the Hatch-Waxman Act.

The Hatch-Waxman Act allows a maximum of one patent to be extended per FDA-approved product.

Patent term extension also may be available in certain foreign countries upon regulatory approval of our product candidate.

Patent term extension also may be available in certain foreign countries upon regulatory approval of our product.

Nevertheless, we may not be granted patent term extension either in the United States or in any foreign country because of, for example, failing to apply within applicable deadlines, failing to apply prior to expiration of relevant patents or otherwise failing to satisfy applicable requirements.

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While an inadvertent lapse may sometimes be cured by payment of a late fee or by other means in accordance with the applicable rules, there are many situations in which noncompliance can result in abandonment or lapse of the patent or patent application, resulting in partial or complete loss of patent rights in the relevant jurisdiction.

If we fail to maintain the patents and patent applications directed to our product candidate, our competitors might be able to enter the market earlier than should otherwise have been the case, which would have a material adverse effect on our business.

If we fail to maintain the patents and patent applications directed to our product, our competitors might be able to enter the market earlier than should otherwise have been the case, which would have a material adverse effect on our business.

We may become involved in lawsuits to protect our patents or other intellectual property rights, which could be expensive, time-consuming and ultimately unsuccessful.

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To counter infringement or unauthorized use, we may be required to file infringement claims, directly or through our licensors, which can be expensive and time consuming.

In addition, in an infringement proceeding, a court may decide that a patent of ours or of our licensors is not

valid or is unenforceable, or may refuse to stop the other party from using the technology at issue on the grounds that our patents do not cover the technology in question.

In addition, in an infringement proceeding, a court may decide that a patent of ours or of our licensors is not valid or is unenforceable, or may refuse to stop the other party from using the technology at issue on the grounds that our patents do not cover the technology in question.

An adverse result in any litigation or defense proceedings could put one or more of our patents or the patents we license at risk of being invalidated or interpreted narrowly and could put our or our licensors’ patent applications at risk of not issuing.

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We may not be able to prevent, alone or with our licensors, misappropriation of our proprietary rights, particularly in countries where the laws may not protect those rights as fully as in the United States.

In addition, potential infringers of our intellectual property rights may have substantially more resources than we do to defend their position, which could adversely affect the outcome of any such dispute.

In addition, potential infringers of our intellectual property rights may have

substantially more resources than we do to defend their position, which could adversely affect the outcome of any such dispute.

Furthermore, because of the substantial amount of discovery required in connection with intellectual property litigation, there is a risk that some of our confidential and proprietary information could be compromised by disclosure during this type of litigation.

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If securities analysts or investors perceive these results to be negative, it could have a substantial adverse effect on the price of our common stock.

Third-party claims of intellectual property infringement or misappropriation may adversely affect our business and could prevent us from developing or commercializing our product candidate.

Third-party claims of intellectual property infringement or misappropriation may adversely affect our business and could impede our ability to profitably commercialize our product.

Our commercial success depends in part on us not infringing the patents and proprietary rights of third parties.

There is a substantial amount of litigation, both within and outside the United States, involving patent and other intellectual property rights in the biotechnology and pharmaceutical industries, including patent infringement lawsuits, interferences, oppositions, ex-parte review and inter partes reexamination and post-grant review proceedings before the USPTO and corresponding foreign patent offices.

Numerous United States and foreign issued patents and pending patent applications owned by third parties exist in the fields in which we are developing and may develop our product candidate.

As the biotechnology and pharmaceutical industries expand and more patents are issued, the risk increases that our product candidate may be subject to claims of infringement of the patent rights of third parties.

Numerous United States and foreign issued patents and pending patent applications owned by third parties exist in the fields in which we are developing and may develop our product.

As the biotechnology and pharmaceutical industries expand and more patents are issued, the risk increases that our product may be subject to claims of infringement of the patent rights of third parties.

If a third party claims that we infringe on their products or technology, we could face a number of issues, including:

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Except for the preceding exceptions, patent applications in the United States and elsewhere are generally published only after a waiting period of approximately 18 months after the earliest filing.

Therefore, patent applications covering our product candidate could have been filed by others without the

knowledge of us or our licensors.

Additionally, pending patent applications which have been published can, subject to certain limitations, be later amended in a manner that could cover our product candidate or the use or manufacture of our product candidate.

Therefore, patent applications covering our product could have been filed by others without the knowledge of us or our licensors.

Additionally, pending patent applications which have been published can, subject to certain limitations, be later amended in a manner that could cover our product or the use or manufacture of our product.

We may also face a claim of misappropriation if a third party believes that we inappropriately obtained and used trade secrets of such third party.

If we are found to have misappropriated a third party’s trade secrets, we may be prevented from further using such trade secrets, limiting our ability to develop our product candidate, and we may be required to pay damages.

If any third-party patents were held by a court of competent jurisdiction to cover aspects of our materials, formulations, methods of manufacture or methods for treatment, the holders of any such patents would be able to block our ability to develop and commercialize the applicable product candidate until such patent expired or unless we obtain a license.

If we are found to have misappropriated a third party’s trade secrets, we may be prevented from further using such trade secrets, and we may be required to pay damages.

If any third-party patents were held by a court of competent jurisdiction to cover aspects of our materials, formulations, methods of manufacture or methods for treatment, the holders of any such patents would be able to block our ability to develop and commercialize our product until such patent expired or unless we obtain a license.

These licenses may not be available on acceptable terms, if at all.

Even if we were able to obtain a license, the rights may be nonexclusive, which could result in our competitors gaining access to the same intellectual property.

Ultimately, we could be prevented from commercializing a product, or be forced to cease some aspect of our business operations, if, as a result of actual or threatened patent infringement claims, we are unable to enter into licenses on acceptable terms.

Parties making claims against us may obtain injunctive or other equitable relief, which could effectively block our ability to further develop and commercialize our product candidate.

Ultimately, we could be prevented from commercializing our product, or be forced to cease some aspect of our business operations, if, as a result of actual or threatened patent infringement claims, we are unable to enter into licenses on acceptable terms.

Parties making claims against us may obtain injunctive or other equitable relief, which could effectively block our ability to further develop and commercialize our product.

Defending against claims of patent infringement or misappropriation of trade secrets could be costly and time-consuming, regardless of the outcome.

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In the event of a successful claim of infringement against us, we may have to pay substantial damages, including treble damages and attorneys’ fees for willful infringement, pay royalties, redesign our infringing products or obtain one or more licenses from third parties, which may be impossible or require substantial time and monetary expenditure.

In addition, the uncertainties associated with litigation could have a material adverse effect on our ability to raise the funds necessary to continue our clinical trials, continue our research programs, license necessary technology from third parties, or enter into development collaborations that would help us bring our product candidate to market.

Changes in United States patent law could diminish the value of patents in general, thereby impairing our ability to protect our product candidate.

Changes in United States patent law could diminish the value of patents in general, thereby impairing our ability to protect our product.

As is the case with other pharmaceutical companies, our success is heavily dependent on intellectual property, particularly on obtaining and enforcing patents and patent rights.

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An important change introduced by the AIA is that, as of March 16, 2013, the United States transitioned to a “first-inventor-to-file” system for deciding which party should be granted a patent when two or more patent applications are filed by different parties claiming the same invention.

A third party that files a patent application in the USPTO after that date but before a licensor or us could therefore be awarded a patent covering an invention of ours even if said licensor or

we had made the invention before it was made by the third party.

A third party that files a patent application in the USPTO after that date but before a licensor or us could therefore be awarded a patent covering an invention of ours even if said licensor or we had made the invention before it was made by the third party.

This will require us to be cognizant going forward of the time from invention to filing of a patent application.

Furthermore, our ability to obtain and maintain valid and enforceable patent rights depends on whether the differences between the licensor’s or our technology and the prior art allow our technology to be patentable over the prior art.

Since patent applications in the United States and most other countries are confidential for a period of time after filing, we cannot be certain that a licensor or we were the first to either (a) file any patent application related to our product candidate or (b) invent any of the inventions claimed in our patents or patent applications.

Since patent applications in the United States and most other countries are confidential for a period of time after filing, we cannot be certain that a licensor or we were the first to either (a) file any patent application related to our product or (b) invent any of the inventions claimed in our patents or patent applications.

Among some of the other changes introduced by the AIA are changes that limit where a patentee may file a patent infringement suit and providing opportunities for third parties to challenge any issued patent in the USPTO.

This applies to all United States patents, even those issued before March 16, 2013.

Because of a lower evidentiary standard in USPTO proceedings compared to the evidentiary standard in United States federal court necessary to invalidate a patent claim, a third party could potentially provide evidence in a USPTO proceeding sufficient for the USPTO to hold a claim invalid as unpatentable even though the same evidence may be insufficient to invalidate the claim if first presented in a district court action.

Accordingly, a third party may attempt to use the USPTO procedures to invalidate patent rights that would not have been invalidated if first challenged by the third party as a defendant in a district court action.

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The following examples are illustrative:

● Others may be able to make products that are similar to our product candidate but that are not covered by the claims of the patents that we license from others or may license or own in the future;

● Others may be able to make products that are similar to our product but that are not covered by the claims of the patents that we license from others or may license or own in the future;

● Others may independently develop similar or alternative technologies or otherwise circumvent any of our technologies without infringing our intellectual property rights;

● Any of our collaborators might not have been the first to conceive and reduce to practice the inventions covered by the patents or patent applications that we license or will, in the future, own or license;

● Any of our collaborators might not have been the first to conceive and reduce to practice the inventions covered by the patents or patent applications that we own or license or will, in the future, own or license;

● Issued patents that have been licensed to us may not provide us with any competitive advantage, or may be held invalid or unenforceable, as a result of legal challenges by our competitors;

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We may need to license certain intellectual property from third parties, and such licenses may not be available or may not be available on commercially reasonable terms.

A third party may hold intellectual property, including patent rights, that are important or necessary to the development or commercialization of our product candidate.

It may be necessary for us to use the patented or proprietary technology of third parties to commercialize our product candidate, in which case we would be required to obtain a license from these third parties.

A third party may hold intellectual property, including patent rights, that are important or necessary to the development or commercialization of our product.

It may be necessary for us to use the patented or proprietary technology of third parties to commercialize our product, in which case we would be required to obtain a license from these third parties.

Such a license may not be available on commercially reasonable terms or at all, which could materially harm our business.

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We may be subject to claims that we or our employees, consultants or independent contractors have inadvertently or otherwise improperly used or disclosed confidential information of these third parties or our employees’ former employers.

Further, we may be subject to ownership disputes in the future arising, for example, from conflicting obligations of consultants or others who are involved in developing our product candidate.

Further, we may be subject to ownership disputes in the future arising, for example, from conflicting obligations of consultants or others who are involved in developing our product.

We may also be subject to claims that former employees, consultants, independent contractors, collaborators or other third parties have an ownership interest in our patents or other intellectual property.

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Our reliance on third parties requires us to share our trade secrets, which increases the possibility that a competitor will discover them or that our trade secrets will be misappropriated or disclosed.

Because we rely on third parties to assist with research and development and to manufacture our product candidate, we must, at times, share trade secrets with them.

Because we rely on third parties to assist with research and development and to manufacture our product, we must, at times, share trade secrets with them.

We seek to protect our proprietary technology in part by entering into confidentiality agreements and, if applicable, material transfer agreements, consulting agreements or other similar agreements with our advisors, employees, third-party contractors and consultants prior to beginning research or disclosing proprietary information.

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● the inability to find partners, if necessary, for support, including research, development, manufacturing or clinical needs;

● the failure of tests or studies necessary to submit an NDA, such as clinical studies, bioequivalence studies in support of a 505(b)(2) regulatory filing, or stability studies;

● the failure of clinical trials to demonstrate the safety and efficacy of our product candidate to the extent necessary to obtain regulatory approvals;

● the failure of clinical trials to demonstrate the safety and efficacy of our product to the extent necessary to obtain regulatory approvals;

● the failure by us or third-party investigators, CROs, or other third parties involved in the research to adhere to regulatory requirements applicable to the conduct of clinical trials;

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● the inability to obtain regulatory approval of our product candidate following completion of clinical trials, or delays in obtaining such approvals.

There can be no assurance that if our clinical trials are successfully initiated and completed, we will be able to obtain approval by the FDA in the U.S.

or similar regulatory authorities elsewhere in the world in a timely manner, if at all.

For example, as described elsewhere, we received a CRL from the FDA in August, 2020 and November 2021, regarding our NDA for PEDMARK TM , stating that it was unable to approve the application in its current form based on deficiencies identified by the FDA after completion of a pre-approval inspection of the manufacturing facility of our third-party drug product manufacturer.

Even if we are successful in resolving some or all of the matters raised by the FDA in the CRL, there is significant risk that we will be unable to obtain FDA approval for PEDMARK TM on a timely basis or at all.

If we fail to successfully develop and commercialize PEDMARK TM we may be unable to generate sufficient revenues to attain profitability, and our reputation in the industry and in the investment community would likely be damaged, each of which would cause our stock price to decrease.

There can be no assurance that if our clinical trials are successfully initiated and completed, we will be able to obtain approval by regulatory authorities elsewhere in the world in a timely manner, if at all.

For example, as described elsewhere, we received a CRL from the FDA in August, 2020 and November 2021, regarding our NDA for PEDMARK ® , stating that it was unable to approve the application in its current form based on deficiencies identified by the FDA after completion of a pre-approval inspection of the manufacturing facility of our third-party drug product manufacturer.

Although we are successful in resolving the matters raised by the FDA in the CRL, there is no guarantee we will receive regulatory approval elsewhere in the world for PEDMARK ® on a timely basis or at all.

If we fail to successfully develop and commercialize PEDMARK ® outside of the United States, we may be unable to generate sufficient revenues to attain profitability, and our reputation in the industry and in the investment community would likely be damaged, each of which would cause our stock price to decrease.

We use hazardous materials and chemicals in our research and development, and our failure to comply with laws related to hazardous materials could materially harm us.

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We may be required to incur significant costs to comply with environmental laws and regulations, which may change from time to time.

Efforts to reduce product pricing and health care reimbursement and changes to government policies could negatively affect the commercialization of our product candidate.

If our product candidate achieves regulatory approval, we may be materially adversely affected by the continuing efforts of governmental and third-party payers to contain or reduce health care costs.

For example, if we succeed in bringing one or more products to market, such products may not be considered cost-effective and the availability of consumer reimbursement may not exist or be sufficient to allow the sale of such products on a competitive basis.

The constraints on pricing and availability of competitive products may further limit our pricing and reimbursement policies as well as adversely impact market acceptance and commercialization of our product candidate.

Efforts to reduce product pricing and health care reimbursement and changes to government policies could negatively affect the profitability of our product.

Now that our product has achieved regulatory approval in the United States, we may be materially adversely affected by the continuing efforts of governmental and third-party payers to contain or reduce health care costs.

In many markets, the pricing or profitability of healthcare products is subject to government control.

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Some proposals include measures that would limit or eliminate payments from third-party payors to the consumer for certain medical procedures and treatments or allow government control of pharmaceutical pricing.

The adoption of any such proposals or reforms could adversely affect the commercial viability of our product candidate.

The adoption of any such proposals or reforms could adversely affect the commercial viability of our product.

In the United States, there have been and continue to be a number of legislative initiatives to contain healthcare costs.

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Government efforts to reduce Medicaid expenses may lead to increased use of managed care organizations by Medicaid programs.

This may result in managed care organizations influencing prescription decisions for a larger segment of the population and a corresponding constraint on prices and reimbursement for our products.

This may result in managed care organizations influencing prescription decisions for a larger segment of the population and a corresponding constraint on prices and reimbursement for our product.

Since its enactment, there have been judicial and Congressional challenges to numerous aspects of the Affordable Care Act.

There may also be federal and state regulatory changes that impact the Affordable Care Act or healthcare programs, insurance coverage or reimbursement generally.

These efforts have increased uncertainty regarding the availability of healthcare programs, insurance coverage and reimbursement as a general matter as well as for our product candidate, and we cannot predict how these events will impact our business.

These efforts have increased uncertainty regarding the availability of healthcare programs, insurance coverage and reimbursement as a general matter as well as for our product, and we cannot predict how these events will impact our business.

In addition, there has been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products, which have resulted in several recent Congressional inquiries and proposed bills designed to, among other things, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs, reduce the price of drugs under Medicare and reform government program reimbursement methodologies for products.

We expect that additional state and federal healthcare reform measures will be adopted in the future, any of which could limit the amounts that federal and state governments will pay for healthcare products and services, which could result in reduced demand for our product candidate or additional pricing pressures.

Any significant changes in the healthcare system in the United States, Canada or abroad would likely have a substantial impact on the manner in which we conduct business and could have a material adverse effect on our ability to raise capital and the viability of product commercialization.

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Historically, the market price of our common shares has been highly volatile and the market for our common shares has from time-to-time experienced significant price and volume fluctuations, some of which are unrelated to our operating performance.

From January 1, 2018 to February 25, 2022, the closing trading price of our stock fluctuated from a high of $18.45 Canadian dollars (“CAD”) per share to a low of CAD$4.38 per share on the TSX.

From September 13, 2017 (the date our common shares were first listed on the Nasdaq Capital Market) to February 25, 2022, the closing trading price of our stock fluctuated from a high of $14.33 per share to a low of $3.30 on the Nasdaq Capital Market.

From January 1, 2018 to March 27, 2023, the closing trading price of our stock fluctuated from a high of $18.45 Canadian dollars (“CAD”) per share to a low of CAD$4.38 per share on the TSX.

From September 13, 2017 (the date our common shares were first listed on the Nasdaq Capital Market) to March 27, 2023, the closing trading price of our stock fluctuated from a high of $14.33 per share to a low of $3.30 on the Nasdaq Capital Market.

Historically, our common shares have had a low trading volume, and may continue to have a low trading volume in the future.

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The market price of our common shares may be significantly affected by many factors, including without limitation:

● the development of our sole product candidate, PEDMARK TM ;

● the commercialization of our sole product candidate, PEDMARK ® ;

● the need to raise additional capital and the terms of any transaction we are able to enter into;

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Our existing principal shareholders hold a substantial number of our common shares and may be able to exercise influence in matters requiring approval of our shareholders.

At February 25, 2022, our current shareholders separately representing more than 5% ownership of our common shares collectively represented beneficial ownership of approximately 40.28% of our common shares.

At March 29, 2023, our current shareholders separately representing more than 5% ownership of our common shares collectively represented beneficial ownership of approximately 43.51% of our common shares.

In particular, Southpoint Capital Advisors LP (“Southpoint Capital”) owns or exercises control over approximately 4.0 million shares, representing approximately 15.47% of our issued and outstanding common shares;

Essetifin SpA, owns approximately 4.0 million shares, or approximately 15.15% of our issued and outstanding common shares;

and Sonic Fund II, LP, owns approximately 2.4 million shares, or approximately 9.25% of our issued and outstanding common shares.

Southpoint Capital, Essetifin SpA, Sonic Fund II, LP, and our other significant shareholders, and other insiders, acting alone or together, might be able to influence the outcomes of matters that require the approval of our shareholders, including but not limited to certain equity transactions (such as a financing), an acquisition or merger with another company, a sale of substantially all of our assets, the election and removal of directors, or amendments to our incorporating documents.

Sonic Fund II, LP, owns approximately 2.5 million shares, or approximately 9.47% of our issued and outstanding common shares;

and Avaro Capital Advisors, owns approximately 1.7 million shares, or approximately 6.34% of our issued and outstanding common shares.

Southpoint Capital, Essetifin SpA, Sonic Fund II, LP, Avaro Capital Advisors, and our other significant shareholders, and other insiders, acting alone or together, might be able to influence the outcomes of matters that require the approval of our shareholders, including but not limited to certain equity transactions (such as a financing), an acquisition or merger with another company, a sale of substantially all of our assets, the election and removal of directors, or amendments to our incorporating documents.

These shareholders might make decisions that are adverse to your interests.

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It may also impair our ability to obtain additional financing.

At February 25, 2022, we had outstanding warrants to purchase approximately 0.04 million shares of our common shares at an exercise price of $6.80 per common share.

In addition, at February 25, 2022, there were approximately 4.3 million common shares issuable upon the exercise of outstanding stock options with a weighted average exercise price of $5.13 per common share.

may also issue further warrants as part of any future financings in addition to the additional 2.2 million options to acquire our common shares currently remaining and available for future awards under our stock option plan.

At March 29, 2023, we had outstanding warrants to purchase approximately 0.2 million shares of our common shares at an exercise price of $7.71 per common share.

In addition, at March 29, 2023, there were approximately 4.5 million common shares issuable upon the exercise of outstanding stock options with a weighted average exercise price of $5.43 per common share.

We may also issue further warrants as part of any future financings in addition to the additional 2.1 million options to acquire our common shares currently remaining and available for future awards under our stock option plan.

We may need to raise additional funds in the future to continue our operations.

Any equity offering could result in significant dilution to the ownership interests of shareholders and may result in dilution of the value of such interests and any debt offering will increase financial risk.

In order to satisfy our anticipated capital requirements to develop our product, we may need to raise additional funds through either the sale of additional equity, the issuance of securities convertible into equity, the issuance of debt, the establishment of collaborations that provide us with funding, the out-license or sale of certain aspects of our intellectual property portfolio, or from other sources.

In order to satisfy our anticipated capital requirements to commercialize our product, we may need to raise additional funds through either the sale of additional equity, the issuance of securities convertible into equity, the issuance of debt, the establishment of collaborations that provide us with funding, the out-license or sale of certain aspects of our intellectual property portfolio, or from other sources.

The most likely sources of financing that may be available to us in the near term are the sale of common shares and/or securities convertible or exercisable into common shares and the issuance of debt.

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Any transaction involving the issue of common shares, or securities convertible or exercisable into common shares, could result in immediate and substantial dilution to present and prospective holders of our common shares.

Alternatively, we may rely on debt financing and assume debt obligations that require us to make substantial interest and capital payments and to pledge some or all of our assets as collateral to secure such debt obligations.

Alternatively, we may rely on debt financing and assume debt obligations that require us to make

substantial interest and capital payments and to pledge some or all of our assets as collateral to secure such debt obligations.

Failure to meet out debt obligations could result in an acceleration of the debt and enforcement against our assets pledged as collateral, either of which would have an adverse effect on our operations and prospects.

Our management has significant flexibility in using the current available cash.

In addition to general corporate purposes (including working capital, research and development, business development and operational purposes), we currently intend to use our available cash to continue the development of our drug candidate PEDMARK™, to seek regulatory approval for PEDMARK™, and to invest in precommercial activities for PEDMARK™.

In addition to general corporate purposes (including working capital, research and development, business development and operational purposes), we currently intend to use our available cash to commercialize our product in the United States while continuing to seek regulatory approval for, and to invest in precommercial activities for PEDMARK ® outside of the United States.

Depending on future developments and circumstances, we may use some of our available cash for other purposes, which may have the potential to decrease our cash runway.

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As a result, you may not be able to recoup your investment through the payment of dividends on your common shares and the lack of a dividend payable on our common shares might depress the value of your investment.

For the foreseeable future, we plan to use all available funds to finance the development of our product candidate and operate our business.

For the foreseeable future, we plan to use all available funds to finance the commercialization of our product and operate our business.

Our directors will determine if and when dividends should be declared and paid in the future based on our financial position at the relevant time, but since we have no present plans to pay dividends, you should not expect receipt of dividends either for your cash needs or to enhance the value of our common shares held by you.

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If we are a PFIC for any taxable year, we intend to provide to a U.S.

Holder such information as the Internal Revenue Service (“IRS”) may require, including a PFIC annual

information statement, in order to enable the U.S.

Holder such information as the Internal Revenue Service (“IRS”) may require, including a PFIC annual information statement, in order to enable the U.S.

Holder to make and maintain a “qualified electing fund” election.

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However, if we fail to maintain an effective system of disclosure controls or internal controls over financial reporting, we may discover material weaknesses that we would then be required to disclose.

Any material weaknesses identified in our internal controls could have an adverse effect on our business.

Any material weaknesses identified in our internal controls could have an adverse effect on

our business.

We may not be able to accurately or timely report on our financial results, and we might be subject to investigation by regulatory authorities.

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It is also possible that the overall scope of Section 404 may be revised in the future, thereby causing ourselves to review, revise or reevaluate our internal control processes, which may result in the expenditure of additional human and financial resources.

Risks Related to Bridge Bank Debt Facility

We may be unable to maintain the covenants in the Bridge Bank Facility which could have a material adverse effect on the Company’s business

Failure to resubmit the NDA by March 31, 2022 or obtain approval by September 30, 2022 or other events of default allow Bridge Bank to declare the facility immediately due and payable which may have a material adverse effect on the Company’s business.

The Company currently has $5.0 million funded under the Bridge Bank facility.

Unresolved Staff Comments

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 1A. Risk Factors