7 unchanged sentences
Additional discussion of the risks summarized in this risk factor summary, and other risks that we face, can be found below under the heading “Item 1A.
−Removed: Risk Factors” and should be carefully considered, together with other information in this Quarterly Report on Form 10-Q and our other filings with the SEC, before making an investment decision regarding our common stock.
+Added: Risk Factors” and
+Added: should be carefully considered, together with other information in this Quarterly Report on Form 10-Q and our other filings with the SEC, before making an investment decision regarding our common stock.
● We have no approved products and no historical commercial revenue, which makes it difficult to assess our future prospects and financial results.
1 unchanged sentence
● Clinical development is a lengthy and expensive process with an uncertain outcome, and failure can occur at any stage of clinical development.
−Removed: ● Our product candidates may cause undesirable side effects or have other properties adversely impacting safety that delay or prevent their regulatory approval, restrict their approved labeling, or otherwise limit their commercial opportunity, including being required by an independent data monitoring committee or
−Removed: regulatory authorities to, delay or halt or clinical trials, or if such side effects or adverse events are sufficiently severe or prevalent, order us to suspend or cease altogether further development of our product candidates.
+Added: ● Our product candidates may cause undesirable side effects or have other properties adversely impacting safety that delay or prevent their regulatory approval, restrict their approved labeling, or otherwise limit their commercial opportunity, including being required by an independent data monitoring committee or regulatory authorities to, delay or halt or clinical trials, or if such side effects or adverse events are sufficiently severe or prevalent, order us to suspend or cease altogether further development of our product candidates.
● We have incurred significant losses since our inception and anticipate that we will continue to incur significant losses for the foreseeable future.
10 unchanged sentences
● We face significant competition from other biotechnology and pharmaceutical companies.
−Removed: ● We face risks to our business arising from the COVID-19 pandemic, including risks to our ongoing and planned clinical trials and pre-clinical and discovery research.
+Added: ● We may face risks to our business arising from outbreaks of disease, epidemics and pandemics, such as the COVID-19 pandemic, including risks to our ongoing and planned clinical trials and pre-clinical and discovery research.
● Unstable market and economic conditions, including elevated and sustained inflation, may have serious adverse consequences on our business, financial condition and stock price.
23 unchanged sentences
The research, testing, manufacturing, labeling, approval, sale, marketing and distribution of our product candidates will be subject to extensive regulation by the U.S.
−Removed: Food and Drug Administration (“FDA”) and other regulatory authorities in the United States and other countries.
+Added: Food and Drug Administration (the “FDA”) and other regulatory authorities in the United States and other countries.
In addition, even if approved, our pricing and reimbursement will be subject to further review and discussions with payors.
1 unchanged sentence
We will need to successfully conduct and complete large, extensive clinical trials in the target patient populations to support a potential application for regulatory approval by the FDA or corresponding regulatory authorities.
−Removed: Those trials, such as our ongoing VERIFY Phase 3 trial evaluating rusfertide for the treatment of
−Removed: PV or subsequent late-stage product candidates, may not demonstrate the safety and efficacy of our product candidates to support a marketing approval in the United States or other jurisdictions.
+Added: Those trials, such as our ongoing VERIFY Phase 3 trial evaluating rusfertide for the treatment of PV or subsequent late-stage product candidates, may not demonstrate the safety and efficacy of our product candidates to support a marketing approval in the United States or other jurisdictions.
Our product candidates require additional clinical development, regulatory approval and secure sources of commercial manufacturing supply prior to commercialization.
18 unchanged sentences
We may experience delays in ongoing clinical trials, and we do not know whether planned clinical trials will begin on time, need to be redesigned, enroll patients on time or be completed on schedule, if at all.
−Removed: For example, we initially experienced slower than expected patient enrollment in VERIFY, a global Phase 3 clinical trial of rusfertide in PV.
+Added: For example, we
+Added: initially experienced slower than expected patient enrollment in VERIFY, a global Phase 3 clinical trial of rusfertide in PV.
Clinical trials can be delayed for a variety of reasons, including if a clinical trial is modified, suspended or terminated by us.
4 unchanged sentences
The clinical hold was triggered by a non-clinical finding in a 26-week rasH2 transgenic mouse model indicating benign and malignant subcutaneous skin tumors.
−Removed: Also, in April 2022, the FDA indicated that it intended to rescind Breakthrough Therapy Designation for rusfertide in PV.
−Removed: For additional information, see the risk factor entitled “O ur product candidates may cause undesirable side effects or have other properties adversely impacting safety that delay or prevent their regulatory approval, restrict their approved labeling, or otherwise limit their commercial opportunity” below.
+Added: Also, in April 2022, the FDA indicated that it intended to rescind Breakthrough Therapy Designation for rusfertide in PV, and we voluntarily withdrew our request.
+Added: For additional information, see the risk factor entitled “Our product candidates may cause undesirable side effects or have other properties adversely impacting safety that delay or prevent their regulatory approval, restrict their approved labeling, or otherwise limit their commercial opportunity” below.
In addition, there are a significant number of global clinical trials in hematologic disorders that are currently ongoing, especially in Phases 2 and 3, making it highly competitive and challenging to recruit subjects.
16 unchanged sentences
Our product candidates may cause undesirable side effects or have other properties adversely impacting safety that delay or prevent their regulatory approval, restrict their approved labeling, or otherwise limit their commercial opportunity.
−Removed: If undesirable side effects or adverse events are caused by our product candidates or by other companies’ similar approved drugs or product candidates, then we may elect to, or be required by an independent data monitoring committee or regulatory authorities to, delay or halt our clinical trials.
+Added: If undesirable side effects or adverse events are caused by our product candidates or by other companies’ similar approved drugs or product candidates, then we may elect to, or be required by an independent data monitoring
+Added: committee or regulatory authorities to, delay or halt our clinical trials.
If such side effects or adverse events are sufficiently severe or prevalent, the FDA or comparable foreign regulatory authorities could order us to suspend or cease altogether further development of our product candidates.
4 unchanged sentences
In particular, we provided the requested individual patient clinical safety reports, updated the investigator brochure and patient informed consent forms, performed a comprehensive review of the most recent safety database, and included new safety and stopping rules in the study protocols.
−Removed: The clinical hold was initially triggered by a non-clinical finding in a 26-week rasH2 transgenic mouse model indicating benign and
−Removed: malignant subcutaneous skin tumors.
+Added: The clinical hold was initially triggered by a non-clinical finding in a 26-week rasH2 transgenic mouse model indicating benign and malignant subcutaneous skin tumors.
The rasH2 signal also prompted a re-examination of the four cases of cancer observed across all rusfertide clinical trials involving over 160 patients, and a comprehensive review of the safety database, including cases of suspected unexpected serious adverse reactions.
10 unchanged sentences
We have incurred significant operating losses every year since inception and expect to continue to incur operating losses for the foreseeable future.
−Removed: As of March 31, 2023, we had an accumulated deficit of $570.5 million.
+Added: As of June 30, 2023, we had an accumulated deficit of $608.9 million.
We expect to continue to incur significant research, development and other expenses related to our ongoing operations and product development.
2 unchanged sentences
If any of our product candidates fail in clinical trials or do not gain regulatory approval or fail to achieve market acceptance, we may never become profitable.
−Removed: Revenue we generate from our collaboration with Janssen, and any future collaboration arrangements may not be sufficient to sustain our operations.
+Added: Revenue we generate from our collaboration with Janssen, and any future collaboration
+Added: arrangements may not be sufficient to sustain our operations.
Failure to become and remain profitable may adversely affect the market price of our common stock and our ability to raise capital and continue operations.
5 unchanged sentences
Absent the funding support obtained under the Restated Agreement, our further development of the collaboration product candidates would require significant additional capital from us, or the establishment of alternative collaborations with third parties, which may not be possible.
−Removed: As of March 31, 2023, we had cash, cash equivalents and marketable securities of $230.8 million.
+Added: As of June 30, 2023, we had cash, cash equivalents and marketable securities of $313.4 million.
Based upon our current operating plan and expected expenditures, we believe that our existing cash, cash equivalents, and marketable securities will be sufficient to fund our operations for at least the next 12 months.
−Removed: However, we expect that
−Removed: we will need to have access to substantial additional funds in the future in order to complete clinical development or commercialize our product candidates to a point where our operations generate net cash inflows.
+Added: However, we expect that we will need to have access to substantial additional funds in the future in order to complete clinical development or commercialize our product candidates to a point where our operations generate net cash inflows.
Raising additional capital may cause dilution to our existing stockholders, restrict our operations or require us to relinquish rights to our product candidates or technologies.
8 unchanged sentences
Risks Related to our Reliance on Third Parties
−Removed: If Janssen does not elect to continue the development of JNJ-2113 (formerly known as PN-235), our business and business prospects would be adversely affected.
+Added: If Janssen does not elect to continue the development of JNJ-2113 (formerly PN-235), our business and business prospects would be adversely affected.
JNJ-2113, the product candidate in development pursuant to our Janssen collaboration, may prove to have undesirable or unintended side effects or other characteristics adversely affecting its safety, efficacy or cost effectiveness that could prevent or limit its approval for marketing and successful commercial use, or that could delay or prevent the commencement and/or completion of clinical trials.
3 unchanged sentences
For example, during the fourth quarter of 2021, following a pre-specified interim analysis criteria, a portfolio decision was made by Janssen to stop further development of both PTG-200 and PN-232 in favor of JNJ-2113.
−Removed: If the Restated Agreement with Janssen is terminated early, or if Janssen’s development activities are terminated early or suspended for an extended period of time, or are otherwise unsuccessful, our business and business prospects would be materially and adversely affected.
+Added: If the Restated Agreement with Janssen is
+Added: terminated early, or if Janssen’s development activities are terminated early or suspended for an extended period of time, or are otherwise unsuccessful, our business and business prospects would be materially and adversely affected.
We may have disagreements with Janssen during the term of the Janssen License and Collaboration Agreement, and if they are not settled amicably or in the favor of Protagonist, the result may harm our business.
13 unchanged sentences
We and our CROs are required to comply with GCPs, which are regulations and guidelines promulgated by the FDA, the European Medicines Agency (“EMA”) and comparable foreign regulatory authorities for all of our product candidates in clinical development.
−Removed: If we or any of our CROs fail to comply with applicable GCPs, the clinical data generated in our clinical trials may be deemed unreliable and the FDA, EMA or comparable foreign regulatory authorities may not accept the data or require us to perform additional clinical trials before considering our filing for regulatory approval or approving our marketing application.
+Added: If we or any of our CROs fail to comply with applicable GCPs, the clinical data generated in our clinical trials may be deemed unreliable and the FDA, the EMA or comparable foreign regulatory authorities may not accept the data or require us to perform additional clinical trials before considering our filing for regulatory approval or approving our marketing application.
In addition, significant portions of the clinical studies for our product candidates are expected to be conducted outside of the United States, which will make it more difficult for us to monitor CROs and perform visits of our clinical trial sites (particularly during the ongoing pandemic) and will force us to rely heavily on CROs to ensure the proper and timely conduct of our clinical trials and compliance with applicable regulations, including GCPs.
1 unchanged sentence
If CROs do not successfully carry out their contractual duties or obligations or meet expected deadlines, if they need to be replaced or if the quality or accuracy of the clinical data they obtain is compromised due to the failure to adhere to our clinical protocols, regulatory requirements or for other reasons, our clinical trials may be extended, delayed or terminated and we may not be able to obtain regulatory approval for or successfully commercialize our product candidates.
−Removed: As a result, our results of operations and the commercial prospects for our product candidates would be harmed, our costs could increase substantially and our ability to generate revenue could be delayed significantly.
+Added: As a result, our results of
+Added: operations and the commercial prospects for our product candidates would be harmed, our costs could increase substantially and our ability to generate revenue could be delayed significantly.
We face a variety of manufacturing risks and rely on third parties to manufacture our drug substance and clinical drug product and we intend to rely on third parties to produce commercial supplies of any approved product candidate.
2 unchanged sentences
As we proceed with the development and potential commercialization of our product candidates, we will need to increase the scale at which the drug is manufactured which will require the development of new manufacturing processes to potentially reduce the cost of goods.
−Removed: We will rely on our internal process research and development efforts and those of contract manufacturers to develop the good manufacturing processes (“GMPs”) required for cost-effective,
−Removed: large-scale production.
+Added: We will rely on our internal process research and development efforts and those of contract manufacturers to develop the good manufacturing processes (“GMPs”) required for cost-effective, large-scale production.
If we and our contract manufacturers are not successful in converting to commercial-scale manufacturing, then our product costs may not be competitive and the development and/or commercialization of our product candidates would be materially and adversely affected.
Moreover, our contract manufacturers are the sole source of supply for our clinical product candidates.
−Removed: If we were to experience an unexpected loss of supply for any reason, whether as a result of manufacturing, supply or storage issues, natural disasters, the COVID-19 pandemic or otherwise, we could experience delays, disruptions, suspensions or termination of our clinical trial and planned development program, or be required to restart or repeat, any ongoing clinical trials.
+Added: If we were to experience an unexpected loss of supply for any reason, whether as a result of manufacturing, supply or storage issues, natural disasters, outbreaks of disease, epidemics and pandemics, such as the COVID-19 pandemic, or otherwise, we could experience delays, disruptions, suspensions or termination of our clinical trial and planned development program, or be required to restart or repeat, any ongoing clinical trials.
We also rely on our contract manufacturers to purchase from third-party suppliers the materials necessary to produce our product candidates for our clinical trials.
35 unchanged sentences
With respect to our product candidates, we may choose to partner with third parties that have direct sales forces and established distribution systems, either to augment our own sales force and distribution systems or in lieu of our own sales force and distribution systems, and in the case of the Restated Agreement with Janssen, we may elect to exercise our Co-Detailing Option (allows us to elect to provide up to 30% of the selling effort in the United States for any IL-23R antagonist compounds approved for commercial sale), which would require us to establish a U.S.
−Removed: If we are not
−Removed: successful in commercializing our product candidates, either on our own or through collaborations with one or more third parties, our future revenue will be materially and adversely impacted.
+Added: If we are not successful in commercializing our product candidates, either on our own or through collaborations with one or more third parties, our future revenue will be materially and adversely impacted.
Recently enacted and future legislation may increase the difficulty and cost for us to obtain marketing approval of and commercialize our product candidates and affect the prices we may obtain.
39 unchanged sentences
Our efforts, or those of any strategic licensing or collaboration partner, to educate the medical community and third-party payors on the benefits of our product candidates may require significant resources, may be under-resourced compared to large well-funded pharmaceutical entities and may never be successful.
−Removed: If ay product candidates we may develop in the future are approved but fail to achieve an adequate level of acceptance by physicians,
−Removed: patients, third-party payors and others in the medical community, we will not be able to generate sufficient revenue to become or remain profitable.
+Added: If ay product candidates we may develop in the future are approved but fail to achieve an adequate level of acceptance by physicians, patients, third-party payors and others in the medical community, we will not be able to generate sufficient revenue to become or remain profitable.
Risks Related to our Business and Industry
15 unchanged sentences
While patients may not like therapies that involve frequent blood draws, these therapies are inexpensive and may present pricing challenges for us if our drug candidates are successfully developed and approved.
−Removed: The COVID-19 pandemic has and could continue to adversely impact our business, including our ongoing and planned clinical trials and pre-clinical and discovery research.
−Removed: The extent to which the COVID-19 pandemic will continue to impact our business is uncertain and cannot be predicted.
−Removed: The pandemic’s impact on our business will depend on a variety of factors, including the timing, extent, effectiveness and durability of vaccine programs or other treatments, new or continuing travel and other restrictions and public health measures, such as social distancing, business closures or disruptions, and the development and spread of COVID-19 variants.
−Removed: As the COVID19 pandemic evolves, we could experience additional disruptions or increased expenses that may adversely impact our business, including:
−Removed: ● delays or difficulties in enrolling patients in our ongoing clinical trials and our future clinical trials;
+Added: Outbreaks of disease, epidemics and pandemics, such as the COVID-19 pandemic, have and could continue to adversely impact our business, including our ongoing and planned clinical trials and pre-clinical and discovery research.
+Added: We have experienced delays in our existing and planned clinical trials due to worldwide impacts related to the COVID-19 pandemic, and our future results of operations and liquidity could be adversely impacted by direct and indirect impacts of epidemics and pandemics.
+Added: We have and could in the future experience additional disruptions or increased expenses that may adversely impact our business, including delays or difficulties in enrolling patients in our ongoing clinical trials and our future clinical trials;
delays or difficulties in clinical site initiation, including difficulties in recruiting clinical site investigators and clinical site staff, or maintaining ongoing operations at such sites;
−Removed: ● delays in manufacturing, receiving the supplies, materials and services needed to conduct clinical trials and pre-clinical research.
−Removed: While the extent of the impact of the COVID-19 pandemic on our business and financial results is uncertain, a continued and prolonged public health crisis such as the COVID-19 pandemic could have a material negative impact on our business, financial condition, and operating results.
+Added: and delays in manufacturing, receiving the supplies, materials and services needed to conduct clinical trials and pre-clinical research.
+Added: A continued and prolonged public health crisis such as the COVID-19 pandemic could have a material negative impact on our business, financial condition, and operating results.
Unstable market and economic conditions, including elevated and sustained inflation, may have serious adverse consequences on our business, financial condition and stock price.
14 unchanged sentences
The failure of financial institutions could adversely affect our ability to pay our operational expenses or make other payments.
−Removed: Our cash held in non-interest-bearing and interest-bearing accounts exceeds the Federal Deposit Insurance Corporation (FDIC) insurance limits.
+Added: Our cash held in non-interest-bearing and interest-bearing accounts exceeds the Federal Deposit Insurance Corporation (the “FDIC”) insurance limits.
If such banking institutions were to fail, we could lose all or a portion of those amounts held in excess of such insurance limitations.
−Removed: For example, the FDIC took control of Silicon Valley Bank on March 10, 2023.
+Added: For example, the FDIC took control of Silicon Valley Bank
+Added: on March 10, 2023.
The Federal Reserve subsequently announced that account holders would be made whole.
20 unchanged sentences
The scope and enforcement of each of these laws is uncertain and subject to rapid change in the current environment of healthcare reform.
−Removed: Federal and state enforcement bodies have continued to increase their scrutiny of interactions between healthcare companies and healthcare providers, which has led to a number of significant investigations, prosecutions, convictions and settlements in the healthcare industry.
+Added: Federal and state enforcement bodies have continued to increase their scrutiny of
+Added: interactions between healthcare companies and healthcare providers, which has led to a number of significant investigations, prosecutions, convictions and settlements in the healthcare industry.
Additionally, as a result of these investigations, healthcare providers and entities may have to agree to additional onerous compliance and reporting requirements as part of a consent decree or corporate integrity agreement.
15 unchanged sentences
We expect to expand the size of our organization in the future, and we may experience difficulties in managing this growth.
−Removed: As of March 31, 2023, we had 103 full-time equivalent employees, including 80 full-time equivalent employees engaged in research and development.
+Added: As of June 30, 2023, we had 106 full-time equivalent employees, including 81 full-time equivalent employees engaged in research and development.
As our development and commercialization plans and strategies develop, we expect to need additional managerial, operational, scientific, sales, marketing, research, development, regulatory, manufacturing, financial and other resources.
4 unchanged sentences
Our business is increasingly dependent on critical, complex and interdependent information technology systems, including Internet-based systems, to support business processes as well as internal and external communications.
−Removed: The size and complexity of our internal computer systems and those of our CROs, contract manufacturers, collaboration partner, and other third parties on which we rely may make them potentially vulnerable to
−Removed: breakdown, telecommunications and electrical failures, malicious intrusion such as ransomware and computer viruses that may result in the impairment of key business processes.
+Added: The size and complexity of our internal computer systems and those of our CROs, contract manufacturers, collaboration partner, and other third parties on which we rely may make them potentially vulnerable to breakdown, telecommunications and electrical failures, malicious intrusion such as ransomware and computer viruses that may result in the impairment of key business processes.
Our systems are potentially vulnerable to data security breaches, by employees or others, that may expose sensitive data to unauthorized persons.
17 unchanged sentences
We may be sued if any product we develop allegedly causes injury or is found to be otherwise unsuitable during product testing, manufacturing, marketing or sale.
−Removed: Any such product liability claims may include allegations of defects in manufacturing, defects in design, a failure to warn of dangers inherent in the product, negligence, strict liability and a breach of warranties.
+Added: Any such product liability claims may include allegations of defects in manufacturing, defects in design, a failure to warn of dangers inherent in the product, negligence, strict
+Added: liability and a breach of warranties.
If we cannot successfully defend ourselves against product liability claims, we may incur substantial liabilities or be required to stop development or, if approved, limit commercialization of our product candidates.
1 unchanged sentence
We currently carry clinical trial liability insurance for our clinical trials.
−Removed: Although we maintain such
−Removed: insurance, any claim that may be brought against us could result in a court judgment or settlement in an amount that is not covered, in whole or in part, by our insurance or that is in excess of the limits of our insurance coverage.
+Added: Although we maintain such insurance, any claim that may be brought against us could result in a court judgment or settlement in an amount that is not covered, in whole or in part, by our insurance or that is in excess of the limits of our insurance coverage.
Our insurance policies also have various exclusions, and we may be subject to a product liability claim for which we have no coverage.
20 unchanged sentences
Additional foreign price controls or other changes in pricing regulation could restrict the amount that we are able to charge for our product candidates.
−Removed: Accordingly, in markets outside the United States, the reimbursement for our products may be reduced compared with the United States and may be insufficient to generate commercially reasonable revenues and profits.
+Added: Accordingly, in markets
+Added: outside the United States, the reimbursement for our products may be reduced compared with the United States and may be insufficient to generate commercially reasonable revenues and profits.
Risks Related to our Intellectual Property
25 unchanged sentences
We also rely on trade secret protection and confidentiality agreements to protect proprietary scientific, business and technical information and know-how that is not or may not be patentable or that we elect not to patent.
−Removed: For example, we primarily rely on trade secrets and confidentiality agreements to protect our peptide therapeutics technology platform.
−Removed: Any disclosure to or misappropriation by third parties of our confidential proprietary information could enable competitors to quickly duplicate or surpass our technological achievements, thus eroding our competitive
−Removed: position in our market.
+Added: For example, we primarily rely on trade secrets and confidentiality agreements to protect our peptide therapeutics
+Added: technology platform.
+Added: Any disclosure to or misappropriation by third parties of our confidential proprietary information could enable competitors to quickly duplicate or surpass our technological achievements, thus eroding our competitive position in our market.
If we are unable to protect the confidentiality of our trade secrets and proprietary know-how or if competitors independently develop viable competing products, our business and competitive position may be harmed.
81 unchanged sentences
Our stock price has fluctuated in the past and is likely to be volatile in the future.
−Removed: From January 1, 2023 through March 31, 2023, the reported sale price of our common stock has fluctuated between $10.62 and $25.69 per share.
+Added: From January 1, 2023 through June 30, 2023, the reported sale price of our common stock has fluctuated between $10.62 and $30.10 per share.
The stock market in general and the market for biotechnology companies in particular have experienced extreme volatility that has often been unrelated to the operating performance of particular companies.
43 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.