PharmaCyte Biotech, Inc 10-K for FY2024

PharmaCyte Biotech, Inc. (PMCB)

10-K 2024-08-13 For: 2024-04-30

Added on April 12, 2026

About this 10-K

PharmaCyte Biotech, Inc filed this 10-K on August 13, 2024, covering the fiscal year ended April 30, 2024 (FY2024).

Headline figures

Fiscal year ended April 30, 2024, as reported in this filing, compared with the same period a year earlier where the filing states it.

Revenue: $0; compared with $0 a year earlier
Net income: $333.76K; compared with a net loss of $4.32M a year earlier
Diluted EPS: -$1.80; compared with -$0.22 a year earlier

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Nevada	62-1772151
(State or other jurisdiction of incorporation or organization)	(I.R.S. Employer Identification No.)

Large accelerated filer	☐	Accelerated filer	☐
Non-accelerated filer	☒	Smaller reporting company	☒
Emerging growth company	☐

PART 1
ITEM 1.	BUSINESS	1
ITEM 1A.	RISK FACTORS	33
ITEM 1B.	UNRESOLVED STAFF COMMENTS	79
ITEM 1C.	CYBERSECURITY	79
ITEM 2.	PROPERTIES	80
ITEM 3.	LEGAL PROCEEDINGS	80
ITEM 4.	MINE SAFETY DISCLOSURES	80

PART II
ITEM 5.	MARKET FOR REGISTRANT’S COMMON EQUITY, RELATED STOCKHOLDER MATTERS AND ISSUER PURCHASES OF EQUITY SECURITIES.	81
ITEM 6.	[RESERVED]	82
ITEM 7.	MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS	82
ITEM 7A.	QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK	90
ITEM 8.	FINANCIAL STATEMENTS AND SUPPLEMENTARY DATA	90
ITEM 9.	CHANGES IN AND DISAGREEMENTS WITH ACCOUNTANTS ON ACCOUNTING AND FINANCIAL DISCLOSURES	90
ITEM 9A.	CONTROLS AND PROCEDURES	90
ITEM 9B.	OTHER INFORMATION	91
ITEM 9C.	DISCLOSURE REGARDING FOREIGN JURISDICTIONS THAT PREVENT INSPECTIONS	91

PART III
ITEM 10.	DIRECTORS, EXECUTIVE OFFICERS AND CORPORATE GOVERNANCE	92
ITEM 11.	EXECUTIVE COMPENSATION	98
ITEM 12.	SECURITY OWNERSHIP OF CERTAIN BENEFICIAL OWNERS AND MANAGEMENT AND RELATED STOCKHOLDER MATTERS	103
ITEM 13.	CERTAIN RELATIONSHIPS AND RELATED TRANSACTIONS, AND DIRECTOR INDEPENDENCE	105
ITEM 14.	PRINCIPAL ACCOUNTANT FEES AND SERVICES	106
ITEM 15.	EXHIBITS	107
ITEM 16.	FORM 10-K SUMMARY	112

	·	our estimates regarding expenses, future revenues, capital requirements and needs for additional financing;
	·	whether the United States (“U.S.”) Food and Drug Administration (“FDA”) approves our Investigational New Drug Application (“IND”) after we complete the FDA’s requested studies and submit a response to the FDA’s clinical hold, so that we can commence our planned clinical trial involving locally advanced, inoperable, non-metastatic pancreatic cancer (“LAPC”);
	·	the success and timing of our preclinical studies and clinical trials;
	·	the potential that results of preclinical studies and clinical trials may indicate that any of our technologies and product candidates are unsafe or ineffective;
	·	our dependence on third parties in the conduct of our preclinical studies and clinical trials;
	·	the difficulties and expenses associated with obtaining and maintaining regulatory approval of our product candidates;
	·	the material adverse impact that the coronavirus pandemic may have on our business, including our planned clinical trial involving LAPC, which could materially affect our operations as well as the business or operations of third parties with whom we conduct business; and
	·	whether the FDA will approve our product candidates after our clinical trials are completed, assuming the FDA allows our clinical trials to proceed after submission and review of our response to the FDA’s clinical hold.

	·	Provide additional sequencing data and genetic stability studies;

	·	Conduct a stability study on our final formulated product candidate as well as the cells from our Master Cell Bank (“MCB”);

	·	Evaluate the compatibility of the delivery devices (the prefilled syringe and the microcatheter used to implant the CypCaps™) with our product candidate for pancreatic cancer;

	·	Provide additional detailed description of the manufacturing process of our product candidate for pancreatic cancer;

	·	Provide additional product release specifications for our encapsulated cells;

	·	Demonstrate comparability between the 1st and 2nd generation of our product candidate for pancreatic cancer and ensure adequate and consistent product performance and safety between the two generations;

	·	Conduct a biocompatibility assessment using the capsules material;

	·	Address specified insufficiencies in the Chemistry, Manufacturing and Controls information in the cross-referenced Drug Master File;

	·	Conduct an additional nonclinical study in animals to assess the safety, activity, and distribution of the product candidate for pancreatic cancer; and

	·	Revise the Investigators Brochure to include any additional preclinical studies conducted in response to the clinical hold and remove any statements not supported by the data we generated.

	·	Provide a Certificate of Analysis for pc3/2B1 plasmid that includes tests for assessing purity, safety, and potency;

	·	Perform qualification studies for the drug substance filling step to ensure that the product candidate for pancreatic cancer remains sterile and stable during the filling process;

	·	Submit an updated batch analysis for the product candidate for the specific lot that will be used for manufacturing all future product candidates;

	·	Provide additional details for the methodology for the Resorufin (CYP2B1) potency and the PrestoBlue cell metabolic assays;

	·	Provide a few examples of common microcatheters that fit the specifications in our Angiography Procedure Manual;

	·	Clarify the language in our Pharmacy Manual regarding proper use of the syringe fill with the product candidate for pancreatic cancer; and

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

	·	Stability Studies on Our Clinical Trial Product Candidate for Pancreatic Cancer. We have successfully completed the required product stability studies. The timepoints were 3, 6, 9, 12, 18 and 24 months of our product candidate for pancreatic cancer being stored frozen at -80C. These studies included container closure integrity testing for certain timepoints.

	·	Additional Studies Requested by the FDA. We have successfully completed various additional studies requested by the FDA, including a stability study on the cells from our MCB used to make our CypCaps™.

	·	Determination of the Exact Sequence of the Cytochrome P450 2B1 Gene. We have completed the determination of the exact sequence of the cytochrome P450 2B1 gene inserted at the site previously identified on chromosome 9 using state-of-the-art nanopore sequencing. This is a cutting edge, unique and scalable technology that permits real-time analysis of long DNA fragments. The result of this analysis of the sequence data confirmed that the genes are intact.

	·	Confirmation of the Exact Sequence of the Cytochrome P450 2B1 Gene Insert. An additional, more detailed analysis of the integration site of the cytochrome P450 2B1 gene from the augmented HEK293 cell clone that is used in our CypCaps™ was found to be intact. In this new study, we were able to confirm the previously determined structure of the integrated transgene sequence using more data points. These studies also set the stage for a next step analysis to determine the genetic stability of the cytochrome P450 2B1 gene at the DNA level after multiple rounds of cell growth. This new study has been completed in which our original Research Cell Bank (“RCB”) cells were compared with cells from the MCB. The analysis confirmed that the cytochrome P450 2B1 and the surrounding sequence has remained stable with no changes detected at the DNA level.

	·	Biocompatibility Studies. We have been involved with 10 biocompatibility studies requested by the FDA, eight of which have been completed successfully. To enable the biocompatibility studies to be performed, we had Austrianova Singapore Pte. Ltd. (“Austrianova”) manufacture an additional 400 syringes of empty capsules.

	·	Systemic Toxicity Testing. We evaluated the potential toxicity of the capsule component of our product candidate for pancreatic cancer‌ and determined there is no evidence of toxicity in any of the parameters examined. The study also confirmed previous data that shows our capsule material is bioinert.

	·	Micro-Compression and Swelling Testing. This testing is underway. We are developing and optimizing two reproducible methods for testing and confirming the physical stability and integrity of our CypCaps™ under extreme pressure. These studies required the acquisition of new equipment by Austrianova as well as validation and integration into Austrianova’s Quality Control laboratory.

	·	Break Force and Glide Testing. We are in the process of developing a protocol to measure whether the syringe, attached to the catheter when used to expel the capsules, will still have a break and glide force that is within the specifications we have established. We are setting the specifications based on the syringe/plunger manufacturer’s measured break and glide forces, or alternatively, accepted ranges for glide forces routinely used in the clinic.

	·	Capsules Compatibility with the Syringe and Other Components of the Microcatheter Delivery System. We are in the process of showing that CypCaps™ are not in any way adversely affected by the catheters used by interventional radiologists to deliver them into a patient. Compatibility data is being generated to demonstrate that the quality of the CypCaps™ is maintained after passage through the planned microcatheter systems.

	·	CypCaps Capsules and Cell Viability after Exposure to Contrast Medium. We have commenced testing to show that exposure of CypCaps™ to the contrast medium interventional radiologists ‌used to implant the CypCaps™ in a patient has no adverse effect on CypCaps™. Contrast medium is used to visualize the blood vessels during implantation.

	·	Master Drug File Information. Austrianova is providing additional detailed confidential information on the manufacturing process, including information on the improvements and advancements made to our product candidate for pancreatic cancer since the last clinical trials were conducted with respect to reproducibility and safety. However, Austrianova has not changed the overall physical characteristics of CypCaps™ between the 1st and 2nd generations.

	·	Submission of Data to FDA. We are in the process of providing these data to the FDA. The clinical hold did not reflect any deficiencies of the clinical trial proposed. We seek to resolve these non-clinical issues to enable FDA review of a new clinical protocol that reflects the standard of care for LAPC.

	·	Cancerous diseases may be treated by placing encapsulated drug-converting cells that convert a chemotherapy prodrug near the cancerous tumor;

	·	Confinement and maintenance of therapeutic cells that activate a chemotherapy prodrug may be placed at the site of implantation in a blood vessel near the cancerous tumor results in “targeted chemotherapy”;

	·	Increased efficacy of a chemotherapy prodrug may allow for lower doses of the prodrug to be given to a patient, significantly reducing or even eliminating side effects from the chemotherapy;

	·	Multi-layered trade secret protection and marketing exclusivity for our technology exists and is being expanded;

	·	Cell-in-a-Box^® capsules can prevent immune system attack of functional cells inside them without the need for immunosuppressive drug therapy; and

	·	Promising data with the Cell-in-a-Box^® technology and the cells used with our technology from animal and initial human clinical trials.

	·	A $60,000 payment due under the SG Austria APA;

	·	A payment of Stamp Duty estimated to be $10,000-17,000 to the Singapore Government;

	·	$500,000 to be used to pay off the existing debt of Bio Blue Bird; and

	·	$1,000,000 to SG Austria.

	·	Two percent royalty on all gross sales received by us or our affiliates;

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

	·	Milestone payments of $100,000 within 30 days after enrollment of the first human patient in the first clinical trial for each product; $300,000 within 30 days after enrollment of the first human patient in the first Phase 3 clinical trial for each product; and $800,000 within 60 days after having a NDA or a BLA approved by the FDA or a MAA approved by the EMA in Europe, or its equivalent based on the country in which it is accepted for each product; and

	·	Milestone payments of $50,000 due 30 days after enrollment of the first veterinary patient in the first trial for each product and $300,000 due 60 days after having a BLA, a NDA or a MAA or its equivalent approved based on the country in which it is accepted for each veterinary product.

	·	completion of preclinical studies and formulation studies in compliance with the FDA’s Good Laboratory Practices (“GLP”), protocols and regulations;

	·	submission to the FDA of an IND to support human clinical testing in the U.S.;

	·	approval by an IRB at each clinical site before a trial may be initiated at that site;

	·	performance of adequate and well-controlled clinical trials in accordance with Good Clinical Practices (“GCP”) and other clinical-trial related regulations to evaluate the safety and efficacy of the investigational product candidate for each target indication;

	·	submission to the FDA of a New Drug Application (“NDA”) for a drug or Biologics License Application (“BLA”) for a biologic for marketing approval, including payment of application user fees

	·	satisfactory completion of an FDA inspection of the manufacturing facility or facilities at which the investigational product candidate is produced to assess compliance with cGMP to assure that the facilities, methods and controls are adequate to preserve the product candidate’s identity, strength, quality and purity;

	·	potential FDA audit of the clinical trial sites to assure compliance with GCP and the integrity of the clinical data submitted in support of the NDA or BLA;

	·	satisfactory completion of an FDA Advisory Committee review, if applicable; and

	·	FDA review and approval of the NDA or BLA.

	·	a product comprised of two or more regulated constituent parts that are physically, chemically, or otherwise combined or mixed and produced as a single entity;

	·	two or more separate products packaged together in a single package or as a unit and comprised of drug and device products;

	·	a drug, biologic, or device packaged separately that according to its investigational plan or proposed labeling is intended for use only with an approved individually specified drug, biologic, or device where both are required to achieve the intended use, indication, or effect and where upon approval of the proposed product the labeling of the approved product would need to be changed, e.g., to reflect a change in intended use, dosage form, strength, route of administration, or significant change in dose; or

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

	·	restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market or product recalls;

	·	fines, warning letters or other enforcement-related letters or clinical holds on post-approval clinical trials;

	·	refusal of the FDA to approve pending NDAs/BLAs or supplements to approved NDAs/BLAs, or suspension or revocation of product approvals;

	·	product seizure or detention, or refusal to permit the import or export of products;

	·	injunctions or the imposition of civil or criminal penalties;

	·	consent decrees, corporate integrity agreements, debarment or exclusion from federal healthcare programs; and/or

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

	·	Decentralized procedure. Using the decentralized procedure, an applicant may apply for simultaneous authorization in more than one EU country of medicinal products that have not yet been authorized in any EU country and that do not fall within the mandatory scope of the centralized procedure.

	·	Mutual recognition procedure. In the mutual recognition procedure, a medicine is first authorized in one EU Member State, in accordance with the national procedures of that country. Following this, further marketing authorizations can be sought from other EU countries in a procedure whereby the countries concerned agree to recognize the validity of the original, national marketing authorization.

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

	·	the applicant consents to a second orphan medicinal product application; or

	·	the applicant cannot supply enough orphan medicinal product.

	FY 2024		FY 2023
U.S.:	$	1,557,115	$	5,129,308
All foreign countries, in total:	$	0	$	0

	·	foreign currency exchange rate fluctuations;
	·	greater difficulty in overseeing foreign operations;
	·	logistical and communications challenges;
	·	potential adverse changes in laws and regulatory practices, including export license requirements, trade barriers, tariffs and tax laws;
	·	burdens and costs of compliance with a variety of foreign laws;
	·	political and economic instability;
	·	increases in duties and taxation;
	·	foreign tax laws and potential increased costs associated with overlapping tax structures;
	·	greater difficulty in protecting intellectual property;
	·	the risk of third-party disputes over ownership of intellectual property and infringement of third-party intellectual property by our product candidates;
	·	risks resulting from our extensive supply chain exposure to Asia; and
	·	general social, economic and political conditions in these foreign markets.

	·	We are a biotechnology company with limited resources, a limited operating history and no products approved for clinical trials or commercial sale, which may make it difficult to evaluate our current business and predict our future success and viability.

	·	As a result of the clinical hold that has been placed on our IND by the FDA, it has taken and may continue to take considerable time and expense to respond to the FDA, and no assurance can be given that the FDA will remove the clinical hold in which case our business and prospects will likely suffer material adverse consequences.

	·	We contract with Austrianova for the manufacture of our product candidates for preclinical studies and clinical trials, if allowed to proceed, and expect to continue to do so for commercialization. This reliance on Austrianova increases the risk that we will not have sufficient quantities of our product candidates or such quantities at an acceptable cost, which could delay, prevent or impair our development or commercialization efforts.

	·	Disruptions in the global economy and supply chains may have a material adverse effect on our business, financial condition and results of operations and the financial condition of the third parties on which we rely, including Austrianova.

	·	The recent and ongoing COVID-19 pandemic has affected and could continue to affect our operations, as well as the business or operations of third parties with whom we conduct business. Our business could be adversely affected by the effects of other future health pandemics in regions where we or third parties on which we rely have significant business operations.

	·	If we are unable to successfully raise sufficient capital, our future clinical trials and product development could be limited, and our long-term viability may be threatened.

	·	Due to the significant resources required for the development of our programs, and depending on our ability to access capital, we must prioritize development of certain product candidates. We may expend our limited resources on programs that do not yield a successful product candidate and fail to capitalize on product candidates or indications that may be more profitable or for which there is a greater likelihood of success.

	·	We currently have no commercial revenue and may never become profitable.

	·	If we are unable to obtain, or if there are delays in obtaining, required approval from the applicable regulatory agencies, we will not be able to commercialize our product candidates and our ability to generate revenue will be materially impaired.

	·	If allowed to proceed with our clinical development program, we intend to conduct clinical trials for certain of our product candidates at sites outside of the U.S., and the U.S. regulatory agencies may not accept data from trials conducted in such locations.

	·	Promising results in previous clinical trials of our encapsulated live cell and ifosfamide combination for advanced pancreatic cancer may not be replicated in future clinical trials which could result in development delays or a failure to obtain marketing approval.

	·	We may not be able to protect our intellectual property rights throughout the world.

	·	We rely and expect to continue to rely heavily on third parties to conduct our preclinical studies, plan to rely on third parties to conduct our and clinical trials, assuming they are allowed to proceed, and those third parties may not perform satisfactorily, including failing to meet deadlines for the completion of such studies and trials.

	·	Disruptions in the global economy and supply chains may have a material adverse effect on our business, financial condition and results of operations and the financial condition of the third parties on which we rely, including Austrianova.

	·	You may experience future dilution as a result of future equity offerings.

	·	If we fail to comply with the continuing listing standards on Nasdaq, our securities could be delisted which could limit investors’ ability to make transactions in our securities and subject us to additional trading restrictions.

	·	We may experience volatility in our stock price, which may adversely affect the trading price of our common stock.

	·	A large number of shares may be issued and subsequently sold upon the exercise of existing options and warrants and the conversion of preferred shares.

	·	We are a “smaller reporting company” under the Commission’s disclosure rules and have elected to comply with the reduced disclosure requirements applicable to smaller reporting companies.

	·	As a non-accelerated filer, we are not required to comply with the auditor attestation requirements of the Sarbanes-Oxley Act.

	·	Reliance on the third party for regulatory compliance and quality assurance;

	·	The possible breach of the manufacturing agreement by the third party;

	·	The possible misappropriation of our proprietary information, including our trade secrets and know-how; and

	·	The possible termination or nonrenewal of the agreement by the third party at a time that is costly or inconvenient for us.

	·	our ability to complete the studies requested by the FDA with respect to our IND filing;

	·	whether the FDA lifts the clinical hold on our IND filing for LAPC;

	·	the progress and results of our development efforts for our product candidates;

	·	the costs, timing and outcome of regulatory review of our product candidates;

	·	the costs and timing of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending any intellectual property-related claims;

	·	the effect of competing technological and market developments;

	·	market acceptance of our product candidates;

	·	the rate of progress in establishing coverage and reimbursement arrangements with domestic and international commercial third-party payors and government payors;

	·	the extent to which we acquire or in-license other products and technologies; and

	·	legal, accounting, insurance and other professional and business-related costs.

	·	successfully complete development activities, including the remaining preclinical studies and planned clinical trials for our product candidates;

	·	complete and submit NDAs or BLAs to the FDA and MAAs to the EMA, and obtain regulatory approval for indications for which there is a commercial market;

	·	complete and submit applications to, and obtain regulatory approval from, other foreign regulatory authorities;

	·	manufacture any approved products in commercial quantities and on commercially reasonable terms;

	·	develop a commercial organization, or find suitable partners, to market, sell and distribute approved products in the markets in which we have retained commercialization rights;

	·	achieve acceptance among patients, clinicians and advocacy groups for any products we develop;

	·	obtain coverage and adequate reimbursement from third parties, including government payors; and

	·	set a commercially viable price for any products for which we may receive approval.

	·	Foreign regulatory requirements that could restrict or limit our ability to conduct our clinical trials;

	·	Administrative burdens of conducting clinical trials under multiple foreign regulatory schemes;

	·	Foreign exchange fluctuations; and

	·	Diminished protection of intellectual property in some countries.

	·	delay or failure in reaching agreement with the FDA or a comparable foreign regulatory authority on a trial design that we are able to execute;

	·	delay or failure in obtaining authorization to commence a trial, including approval from the appropriate IRB to conduct testing of a candidate on human subjects, or inability to comply with conditions imposed by a regulatory authority regarding the scope or design of a clinical trial;

	·	delay in reaching, or failure to reach, agreement on acceptable terms with prospective contract research organizations (“CROs”) and clinical trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and trial sites;

	·	inability, delay or failure in identifying and maintaining a sufficient number of trial sites, many of which may already be engaged in other clinical programs;

	·	delay or failure in recruiting and enrolling suitable volunteers or patients to participate in a trial;

	·	delay or failure in developing and validating companion diagnostics, if they are deemed necessary, on a timely basis;

	·	failure of trial participants to complete a trial or return for post-treatment follow-up;

	·	inability to monitor trial participants adequately during or after treatment;

	·	clinical sites and investigators deviating from trial protocols, failing to conduct the trial in accordance with regulatory requirements or dropping out of a trial;

	·	failure to initiate or delay of or inability to complete a clinical trial as a result of a clinical hold imposed by the FDA or comparable foreign regulatory authority due to observed safety findings or other reasons;

	·	negative or inconclusive results in our clinical trials, and our decision to or regulators’ requirement that we conduct additional non-clinical studies, clinical trials or that we abandon one or more of our product development programs; or

	·	inability to manufacture sufficient quantities of a drug candidate of acceptable quality for use in clinical trials.

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

	·	we may be unable to demonstrate to the satisfaction of the FDA or comparable foreign regulatory agencies that a drug 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 agencies for approval;

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

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

	·	the data collected from clinical trials of our drug candidates may not be sufficient to support the submission of a NDA, BLA, or other submission or to obtain regulatory approval in the U.S. or elsewhere;

	·	upon review of our clinical trial sites and data, the FDA or comparable foreign regulatory agency may find our record keeping or the record keeping of our clinical trial sites to be inadequate;

	·	the manufacturing processes or facilities of third-party manufacturers with which we contract for clinical and commercial supplies may fail to meet the requirements of the FDA or comparable foreign regulatory agencies;

	·	the FDA or comparable foreign regulatory agencies may fail to approve the companion diagnostics we contemplate developing internally or with partners; and

	·	the change of the medical standard of care or the approval policies or regulations of the FDA or comparable foreign regulatory agencies may significantly change in a manner that renders our clinical data insufficient for approval.

	·	The size and nature of the patient population;

	·	The severity of the disease under investigation;

	·	The proximity of patients to clinical sites;

	·	The eligibility criteria for the trial;

	·	Our ability to recruit clinical trial investigators with the appropriate competencies and experience;

	·	The design of the clinical trial;

	·	Efforts to facilitate timely enrollment;

	·	The patient referral practices of physicians;

	·	Competing clinical trials for the same patient population; and

	·	Clinicians’ and patients’ perceptions as to the potential advantages and risks of the drug being studied in relation to other available therapies, including any new drugs that may be approved for the indications we are investigating.

	·	Restrictions on such products, approved manufacturers or manufacturing processes;

	·	Restrictions on the labeling or marketing of a product;

	·	Restrictions on product distribution or use;

	·	Requirements to conduct post-marketing studies or clinical trials;

	·	Notices of noncompliance, such as warning or untitled letters from the FDA, or inspectional observations;

	·	Withdrawal of the products from the market;

	·	Refusal to approve pending applications or supplements to approved applications that we submit;

	·	Recall of products;

	·	Fines, restitution or disgorgement of profits or revenues;

	·	Suspension or withdrawal of marketing approvals;

	·	Clinical hold or suspension of any of our ongoing clinical trials;

	·	Refusal to permit the import or export of products;

	·	Product seizure; or

	·	Injunctions, consent decrees, or the imposition of civil or criminal penalties

	·	The efficacy and safety of the product;

	·	The potential advantages of the product compared to alternative treatments;

	·	The prevalence and severity of any side effects;

	·	The clinical indications for which the product is approved;

	·	Whether the product is designated under physician treatment guidelines as a first-line therapy or as a second- or third-line therapy;

	·	Limitations or warnings, including distribution or use restrictions, contained in the product’s approved labeling;

	·	Our ability to offer the product for sale at competitive prices;

	·	Our ability to establish and maintain pricing sufficient to realize a meaningful return on our investment;

	·	The product’s convenience and ease of administration compared to alternative treatments;

	·	The willingness of the target patient population to try, and of physicians to prescribe, the product;

	·	The strength of sales, marketing and distribution support;

	·	The approval of other new products for the same indications;

	·	Changes in the standard of care for the targeted indications for the product;

	·	The timing of market introduction of our approved products as well as competitive products and other therapies;

	·	Availability and amount of reimbursement from government payors, managed care plans and other third-party payors;

	·	Adverse publicity about the product or favorable publicity about competitive products; and

	·	Potential product liability claims.

	·	A regulatory agency may withdraw its approval of the product candidate or seize the product candidate;

	·	We may be required to recall the product candidate or change the way the product is administered;

	·	Additional restrictions may be imposed on the marketing of, or the manufacturing processes for, the product candidate;

	·	We may be subject to fines, injunctions or the imposition of civil or criminal penalties;

	·	A regulatory agency may require the addition of labeling statements, such as a “black box” warning or a contraindication;

	·	We may be required to create a Medication Guide outlining the risks of the previously unidentified side effects for distribution of our product candidate to patients;

	·	We could be sued and held liable for harm caused to patients;

	·	The product candidate may become less competitive; and

	·	Our reputation may suffer.

	·	Collaborators may have significant discretion in determining the efforts and resources that they will apply to these collaborations;

	·	Collaborators may not perform their obligations as expected;

	·	Changes in the collaborators’ strategic focus or available funding, or external factors, such as an acquisition, may divert resources or create competing priorities;

	·	Collaborators may delay discovery and preclinical development, provide insufficient funding for product development of targets selected by us, stop or abandon preclinical or clinical development of a product candidate or must repeat or conduct new preclinical and clinical development of a product candidate;

	·	Collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with our products or product candidates if the collaborators believe that competitive products are more likely to be successfully developed than ours;

	·	Product candidates may be viewed by our collaborators as competitive with their own product candidates or products, which may cause collaborators to cease to devote resources to the development of our product candidates;

	·	Disagreements with collaborators, including disagreements over proprietary rights, contract interpretation or the preferred course of development might cause delays or termination of the preclinical or clinical development or commercialization of product candidates. This might lead to additional responsibilities for us with respect to product candidates, or might result in litigation or arbitration, any of which would be time-consuming and expensive;

	·	Collaborators may not properly maintain or defend our intellectual property rights or intellectual property rights licensed to us or may use our proprietary information in such a way as to invite litigation that could jeopardize or invalidate our intellectual property or proprietary information or expose us to potential litigation;

	·	Collaborators may infringe the intellectual property rights of third parties, which may expose us to litigation and potential liability; and

	·	Collaborations may be terminated at the convenience of the collaborator and, if terminated, we could be required to raise additional capital to pursue further development or commercialization of our product candidates.