What changed in this filing

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Item 1A. Risk Factors

2024-11-06 compared with 2024-08-13 · 39 added, 34 removed, 1508 unchanged (5% of the section changed)

11 unchanged sentences

In addition to Jelmyto , we are dependent on the success of our lead product candidate, UGN-102, and our other product candidates, including obtaining regulatory approval to market our product candidates in the United States.

The data from our Phase 3 ENVISION trial may be insufficient to support regulatory approval of UGN-102.

The data from our pivotal Phase 3 ENVISION trial and supporting ATLAS and OPTIMA II trials may be insufficient to support regulatory approval of UGN-102.

Clinical drug development involves a lengthy and expensive process with an uncertain outcome, results of earlier studies and trials may not be predictive of future trial results, and our clinical trials may fail to adequately demonstrate the safety and efficacy of our product candidates.

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If our collaboration and licensing arrangements are not successful, we may not be able to capitalize on the market potential of these product candidates.

We currently contract with third-party subcontractors and single-source suppliers for certain raw materials, compounds and components necessary to produce Jelmyto for commercial use, and to produce UGN-102, UGN-103, UGN-104, UGN-201, and UGN-301 for nonclinical studies and clinical trials, and expect to continue to do so to support commercial scale production of UGN-102, UGN-103, UGN-104 and UGN-201, if approved, as well as UGN-301 if approved as a monotherapy or for any approved product that includes UGN-301.

There are significant risks associated with the manufacture of pharmaceutical products and contracting with contract manufacturers, including single-source suppliers.

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We are a biotechnology company with a limited operating history upon which you can evaluate our business and prospects.

We are not profitable and have incurred net losses in each period since we commenced operations in 2004, including net losses of $102.2 million for the year ended December 31, 2023 and a net loss of $33.4 million for the quarter ended June 30, 2024.

As of June 30, 2024, we had an accumulated deficit of $745.0 million.

As of September 30, 2024 we had an accumulated deficit o f $768.7 million.

We expect to continue to incur significant expenses and operating losses for the foreseeable future.

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Since our inception, almost all our resources have been dedicated to the nonclinical and clinical development of our first commercial product, Jelmyto , and our lead product candidate UGN-102.

As of June 30, 2024, we had cash and cash equivalents and marketable securities of $241.3 million.

As of September 30, 2024, we had cash and cash equivalents and marketable securities of $254.2 million.

To fund our operations and develop our product candidates and commercialize Jelmyto , we have relied primarily on equity and debt financings and, following the launch of Jelmyto in June 2020, revenue generated from sales of Jelmyto .

In December 2019, we entered into the ATM Sales Agreement with TD Cowen pursuant to which we may from time to time offer and sell our ordinary shares having an aggregate offering price of up to $100.0 million.

As of June 30, 2024, $27.3 million remain available for sale under the ATM Sales Agreement.

As of September 30, 2024, $27.3 million remain available for sale under the ATM Sales Agreement.

In March 2021, we announced the RTW Transaction with RTW totaling $75 million in funding for our company, which was received in May 2021, to support the launch of Jelmyto and the development of UGN-102.

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On March 13, 2024, we entered into an amended and restated loan agreement with Pharmakon for an additional third and fourth tranche of senior secured loan.

The third tranche of $25.0 million is required to be drawn by September 30, 2024, subject to customary bring down conditions and deliverables.

The fourth tranche of $75.0 million will become available at our option no later than August 29, 2025, subject to (i) having successfully drawn the immediately preceding $25.0 million tranche, (ii) receiving FDA approval of an NDA for UGN-102 no later than June 30, 2025 and (iii) the satisfaction of customary bring down conditions and deliverables.

The third tranche of $25.0 million was funded in September 2024.

The fourth tranche of $75.0 million will become available at our option no later than August 29, 2025, subject to (i) receiving FDA approval of an NDA for UGN-102 no later than June 30, 2025 and (ii) the satisfaction of customary bring down conditions and deliverables.

We may require additional capital to complete clinical trials, obtain regulatory approval for and commercialize our product candidates, and otherwise fund our operations.

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In March of 2024, we amended and restated the loan agreement, pursuant to which the Lenders agreed to make additional term loans to the Borrower in an aggregate principal amount of up to $100.0 million to be funded in two tranches.

We are required to draw the third tranche of $25.0 million by September 30, 2024.

There is no assurance that the additional term loans will be funded as expected or at all.

The third tranche of $25.0 million was funded in September 2024.

There is no assurance that the additional term loans will become available.

The obligations of the Borrower under the loan agreement with Pharmakon are guaranteed on a full and unconditional basis by UroGen Pharma Ltd.

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If we fail to establish and maintain an effective sales and marketing infrastructure, we will be unable to successfully commercialize our product candidates, which in turn would have an adverse effect on our business, financial condition and results of operations.

If we are unable to effectively train and equip our sales force, our ability to successfully commercialize Jelmyto will be harmed.*

If we are unable to effectively train and equip our sales force, our ability to successfully commercialize Jelmyto and any future product candidates will be harmed.*

Our sales force has only promoted Jelmyto since its launch in June 2020.

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Lack of coverage due to turnover of personnel, and/or inability to identify and integrate additional personnel would have a negative impact on our ability to engage with physicians and other stakeholders.

If we are unable to effectively train, deploy and retain our sales force and equip them with effective materials, including medical and sales literature to help them inform and educate customers about the benefits and risks of Jelmyto and its proper administration, our efforts to successfully commercialize Jelmyto could be put in jeopardy, which would negatively impact our ability to generate product revenues.

If we are unable to effectively train, deploy and retain our sales force and equip them with effective materials, including medical and sales literature to help them inform and educate customers about the benefits and risks of Jelmyto, any future product candidates, and their proper administration, our efforts to successfully commercialize Jelmyto and any future product candidates could be put in jeopardy, which would negatively impact our ability to generate product revenues.

There can be no assurance that our sales force will continue to have in-person access to physicians as a result of pandemics, epidemics or public health emergencies, or that digital materials and virtual engagement will be effective at growing and sustaining prescription levels of Jelmyto .

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We are aware of several pharmaceutical companies that are developing drugs in the general fields of urology and uro-oncology, such as AADi, LLC, Biocancell Ltd., Bristol Myers Squibb, CG Oncology Inc., enGene Holdings, Ferring Pharmaceuticals, FKD Therapies Oy, GSK, ImmunityBio, Janssen, Merck Sharp & Dohme Corp, Pfizer, Prokarium, Protara Therapeutics, Roche, Samyang Biopharma, Steba Biotech Ltd., SURGE Therapeutics, Viralytics Limited and Vyriad.

We are aware that Ferring Pharmaceuticals began production of Adstiladrin, approved by the FDA for the treatment of high-risk BCG-unresponsive NMIBC, in the second half of 2023.

We are aware that Ferring Pharmaceuticals is marketing Adstiladrin, approved by the FDA for the treatment of high-risk BCG-unresponsive NMIBC, and that in 2024 the FDA approved ImmunityBio's product ANKTIVA for the treatment of BCG-unresponsive NMIBC with CIS, with or without papillary tumors.

We are also aware there are companies among this list conducting clinical trials in various phases in the same indications in which we are developing products.

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The FDA can delay, limit or deny approval of our product candidates for many reasons.

While we initiated the submission of a rolling NDA to the FDA for UGN-102 as a treatment for low-grade intermediate risk NMIBC in January 2024, there is no guarantee that the FDA will accept the NDA for filing once the rolling submission is complete or eventually approve UGN-102 for the indication and patient population that we request or approve the labeling that we believe is necessary or desirable for the successful commercialization of UGN-102, as the FDA has the authority to refuse to file or approve NDAs for a variety of reasons.

The success of our product candidates is subject to significant risks, including risks associated with successfully completing current and future clinical trials, such as:

While the FDA accepted our NDA for UGN-102 in October 2024, there is no guarantee that the FDA will eventually approve UGN-102 for the indication and patient population that we request or approve the labeling that we believe is necessary or desirable for the successful commercialization of UGN-102, as the FDA has the authority to refuse to approve NDAs for a variety of reasons.

Additionally, the FDA or other comparable foreign regulatory authorities may also require a panel of experts, referred to as an advisory committee, to deliberate on the adequacy of the safety and efficacy data to support approval of UGN-102.

We currently anticipate that the FDA will require an advisory committee for UGN-102.

The opinion of the advisory committee, although not binding, may have a significant impact on our ability to obtain approval for UGN-102 based on the completed clinical trials, as the FDA or comparable foreign regulatory authorities often adheres to the advisory committee’s recommendations.

However, even if the advisory committee provides a positive recommendation, there is no guarantee that the FDA will follow the advisory committee’s recommendations and there are numerous examples of the FDA departing from the recommendations of its advisory committee.

Accordingly, the regulatory approval pathway for our product candidates may be uncertain, complex, expensive and lengthy, and approval may not be obtained.

The success of our product candidates is subject to significant risks and uncertainties, including risks associated with successfully completing current and future clinical trials, such as:

the FDA’s acceptance of our parameters for regulatory approval relating to UGN-102 and our other product candidates, including our proposed indications, primary and secondary endpoint assessments and measurements, safety evaluations and regulatory pathways, and proposed labeling and packaging;

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our ability to demonstrate meaningful clinical or other benefits which outweigh any safety or other perceived risks, through the completion of our clinical trials for our product candidates;

the FDA’s need to schedule an advisory committee meeting, and to conduct such meeting, in a timely manner to evaluate and decide on the approval of our potential future NDA for UGN-102;

if applicable, the recommendation of the FDA’s advisory committee to approve our applications to market UGN-102 and our other product candidates in the United States, without limiting the approved labeling, specifications, distribution or use of the products, or imposing other restrictions;

the FDA’s decision to schedule an advisory committee meeting, and to conduct such meeting, in a timely manner to evaluate and make a recommendation regarding our NDA for UGN-102;

if an advisory committee meeting is scheduled, the outcome of remains uncertain and it is possible that the advisory committee will have an adverse or split recommendation with respect to our applications to market UGN-102 and our other product candidates in the United States;

if applicable, even if FDA’s advisory committee recommends approval of our applications to market UGN-102 and our other product candidates in the United States, without limiting the approved labeling, specifications, distribution or use of the products, or imposing other restrictions, the FDA is not bound by the advisory committee’s recommendation and there are a number of instances where the FDA has voted against the recommendations of advisory committees;

the FDA’s determination of safety and efficacy of our product candidates;

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Even if we receive approval of any of the product candidates in our pipeline or future product candidates, there is no assurance that we will be able to successfully commercialize any of them.

The data from our Phase 3 ENVISION trial may be insufficient to support regulatory approval of UGN-102.*

The data from our pivotal Phase 3 ENVISION trial and supporting ATLAS and OPTIMA II trials may be insufficient to support regulatory approval of UGN-102.*

On July 27, 2023, we announced that UGN-102 met its primary endpoints in the Phase 3 ATLAS and ENVISION trials.

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Any performance failure on the part of such third parties could delay the clinical development of our product candidates or delay or prevent us from obtaining regulatory approval or commercializing our current or future product candidates, depriving us of potential product revenue and resulting in additional losses.

We have not yet completed submission of our NDA for UGN-102 or the other product candidates in our pipeline, and we may be delayed in obtaining or failing to obtain such regulatory approvals and to commercialize our product candidates.*

We have not yet completed submission of our NDA for certain product candidates in our pipeline, and we may be delayed in obtaining or fail to obtain such regulatory approvals and to commercialize our product candidates.*

The process of developing, obtaining regulatory approval for and commercializing our product candidates is long, complex, costly and uncertain, and delays or failure can occur at any stage.

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timely manufacture of sufficient quantities of the product candidate for use in clinical trials.

These risks and uncertainties impact all of our nonclinical programs that we pursue.

These risks and uncertainties impact all our nonclinical programs that we pursue.

If we are unsuccessful in advancing our nonclinical product candidates into clinical trials in a timely fashion, our business may be harmed.

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If one of our collaborators terminates its agreement with us, we may find it more difficult to attract new collaborators and perception of us in the business and financial communities could be harmed.

We currently contract with third-party subcontractors and single-source suppliers for certain raw materials, compounds and components necessary to produce Jelmyto for commercial use, and to produce UGN-102, UGN-103, UGN-104, UGN-201 and UGN-301 for nonclinical studies and clinical trials, and expect to continue to do so to support commercial scale production of UGN-102, UGN-103, UGN-104, and UGN-201, if approved, as well as UGN-301 if approved as a monotherapy or for any approved product that includes UGN-301.

There are significant risks associated with the manufacture of pharmaceutical products and contracting with contract manufacturers, including single-source suppliers.

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We do not have any control over the availability of these compounds and components beyond our existing contractual arrangements.

If we or our suppliers and manufacturers are unable to purchase these raw materials on acceptable terms, at sufficient quality levels, or in adequate quantities, if at all, the development and commercialization of our product candidates or any future product candidates, would be delayed or there would be a shortage in supply, which would impair our ability to meet our development objectives for our product candidates or generate revenues from the sale of Jelmyto or any other approved products.

If we or our suppliers and manufacturers are unable to manufacture our drug components or purchase required raw materials on acceptable terms, at sufficient quality levels, or in adequate quantities, if at all, the development and commercialization of our product candidates or any future product candidates, would be delayed or there would be a shortage in supply, which would impair our ability to meet our development objectives for our product candidates or generate revenues from the sale of Jelmyto or any other approved products.

We expect to continue to rely on these or other subcontractors and suppliers to support our commercial requirements for Jelmyto , as well as UGN-102 or any of our other product candidates if approved for marketing by the FDA or foreign regulatory authorities.

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While we currently have over 12 months of mitomycin API and/or Jelmyto finished product on hand to continue our commercial and clinical operations as planned, we may face such delays or costs in future years.

Although we believe we have sufficient quantities of bulk mitomycin API for planned manufacturing operations for 12 months, a prolonged supply interruption of certain components could adversely affect our ability to conduct commercialization activities and planned clinical trials.

A prolonged supply interruption of certain components could adversely affect our ability to conduct commercialization activities and planned clinical trials.

If any third party in our supply or distribution chain for materials or finished product is adversely impacted by restrictions resulting from pandemics, epidemics or public health emergencies or other disruptions caused by the outbreak of war, terrorist attacks or other acts of hostility, including staffing shortages, production slowdowns and disruptions in delivery systems, our supply chain may be disrupted, limiting our ability to manufacture and distribute Jelmyto for commercial sales and our product candidates for our clinical trials and research and development operations.

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If we fail to manage our growth effectively, our business could be disrupted.*

As of June 30, 2024, we had 203 employees, of whom 40 are based in Israel and 163 are based in the United States.

As of September 30, 2024, we had 217 employees, of whom 40 are based in Israel and 177 are based in the United States.

We will need to continue to expand our development, quality, managerial, operational, finance, marketing, sales and other resources to manage our operations and clinical trials, continue our development activities and commercialize our product candidates, if approved.

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and certain of our research and development facilities and key vendors and suppliers are located in Israel.

If any of these current or future trials or the related facilities or our or our vendors' and suppliers' facilities in Israel were to be damaged, destroyed or otherwise unable to operate, whether due to war, acts of hostility, earthquakes, fire, floods, hurricanes, storms, tornadoes, other natural disasters, employee malfeasance, terrorist acts, pandemic, power outages or otherwise, or if performance of our clinical trials are disrupted for any other reason, such an event could cause significant development and product delays.

If any of these current or future trials or the related facilities or our vendors' and suppliers' facilities in Israel were to be damaged, destroyed or otherwise unable to operate, whether due to war, acts of hostility, earthquakes, fire, floods, hurricanes, storms, tornadoes, other natural disasters, employee malfeasance, terrorist acts, pandemic, power outages or otherwise, or if performance of our clinical trials are disrupted for any other reason, such an event could cause significant development and product delays.

If we experience delays in achieving our development objectives within a timeframe that meets our prospective customers’ expectations, our business, prospects, financial results and reputation could be harmed.

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In addition, the IRA, among other things, (1) directs HHS to negotiate the price of certain single-source drugs and biologics covered under Medicare and (2) imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation.

These provisions will take effect progressively starting in fiscal year 2023.

On August 29, 2023, HHS announced the list of the first ten drugs that will be subject to price negotiations, although the Medicare drug price negotiation program is currently subject to legal challenges.

HHS has and will continue to issue and update guidance as these programs are implemented.

It is currently unclear how the IRA will be implemented but is likely to have a significant impact on the pharmaceutical industry.

These provisions took effect progressively starting in fiscal year 2023.

On August 15, 2024, HHS announced the agreed-upon reimbursement prices of the first ten drugs that were subject to price negotiations, although the Medicare drug price negotiation program is currently subject to legal challenges.

HHS will select up to fifteen additional drugs covered under Part D for price negotiation in 2025.

Further, in response to the Biden administration's October 2022 executive order, on February 14, 2023, HHS released a report outlining three new models for testing by the Center for Medicare and Medicaid Innovation which will be evaluated on their ability to lower the cost of drugs, promote accessibility, and improve quality of care.

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On December 20, 2019, we entered into the ATM Sales Agreement pursuant to which we may from time to time offer and sell our ordinary shares, having an aggregate offering price of up to $100.0 million, to or through TD Cowen, acting as sales agent or principal, in any manner deemed to be an “at-the market offering”.

As of June 30, 2024, $27.3 million remain available for sale under the ATM Sales Agreement.

As of September 30, 2024, $27.3 million remain available for sale under the ATM Sales Agreement.

The shares will be offered and sold pursuant to our shelf registration statement on Form S-3 filed with the SEC on November 15, 2022, which was declared effective on November 29, 2022.

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For example, effective in 2022, the U.S.

Tax Cuts and Jobs Act of 2017 eliminates the option to deduct research and development expenditures in the current period and requires U.S.

Tax Cuts and Jobs Act of 2017 eliminated the option to deduct research and development expenditures in the current period and requires U.S.

taxpayers to capitalize and amortize them over five or fifteen years pursuant to Internal Revenue Code Section 174.

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Further, our operations could be disrupted by the obligations of our employees to perform military service.

As of June 30, 2024, we had 40 employees based in Israel.

As of September 30, 2024, we had 40 employees based in Israel.

Of these employees, some may be military reservists, and may be called upon to perform military reserve duty of up to 36 days per year (and in some cases more) until they reach the age of 40 (and in some cases, up to the age of 45 or older).

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The loss of one or more of our executive officers could delay or prevent the continued successful implementation of our growth strategy, could affect our ability to manage our company effectively and to carry out our business plan, or could otherwise be detrimental to us.

As of June 30, 2024, we had 203 employees.

As of September 30, 2024, we had 217 employees.

Therefore, knowledge of our product candidates and clinical trials is concentrated among a small number of individuals.

63 unchanged sentences

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-Q

Item 1A. Risk Factors