Contineum Therapeutics, Inc.

Current report

The risk factors below that we have marked with an asterisk (*) reflect substantive changes from, or additions to, the risks described under Part I, Item 1A “Risk Factors” included in our Annual Report on Form 10-K for the year ended December 31, 2025, filed on March 5, 2026. These changes reflect our clinical and regulatory updates and other matters occurring after the date we filed our Annual Report on Form 10-K for the year ended December 31, 2025.

Current report

Risks Related to Development, Clinical Testing, and Regulatory Approval

Current report

We are heavily dependent on the success of PIPE-791, our lead drug candidate, which is in the early stages of clinical development. If PIPE-791, PIPE-307 or our other drug candidates do not progress through clinical development, eventually receive regulatory approval or, even if approved, are not successfully commercialized, our business will be materially adversely harmed.*

Current report

We currently have no products that are approved for commercial sale and may never be able to develop a marketable product. To date, we have invested a significant portion of our efforts and financial resources on the development of PIPE-791 and PIPE-307. We wholly-own, and are pursuing the clinical development of, PIPE-791 for the treatment of idiopathic pulmonary fibrosis (“IPF”). In the first quarter of 2026, we initiated patient dosing in PROPEL-IPF, our global Phase 2 clinical trial of PIPE-791 for the treatment of IPF. As of October 10, 2026, we have received regulatory authorization to conduct the trial in 25 countries, including in the European Union, the United Kingdom, Japan, Australia, Canada, South Korea and Taiwan, and have opened more than 100 clinical sites. In the fourth quarter of 2025, we completed enrollment in an exploratory PIPE-791 Phase 1b clinical trial for the treatment of chronic pain associated with two separate indications, chronic osteoarthritis pain (“COAP”) and chronic lower back pain (“CLBP”). In April 2026, we reported topline data from this trial, which met its primary objective of assessing safety and tolerability. Although patients treated with PIPE-791 in this Phase 1b clinical trial generally demonstrated improvements from baseline in pain that were numerically greater than those in the placebo arm, the trial was exploratory in nature and was not designed or powered to demonstrate statistically significant efficacy. We believe these data support further evaluation of PIPE-791 for the potential treatment of chronic pain, but we are prioritizing the allocation of our capital and clinical development resources to PROPEL-IPF, and we have not determined whether, when, or on what terms we will further develop PIPE-791 for chronic pain, if at all. In February 2023, we entered into a license agreement (the “J&J License Agreement”) with an affiliate of Johnson & Johnson (“J&J”) pursuant to which we granted J&J an exclusive, worldwide license to develop, manufacture and commercialize PIPE-307 in all indications in exchange for an upfront payment and the right to receive future milestone payments and royalties. In December 2024, J&J initiated a Phase 2 MOONLIGHT-1 trial of PIPE-307 to evaluate the efficacy, safety, and tolerability of PIPE-307 as a monotherapy in adult participants with major depressive disorder (“MDD”). J&J completed enrollment of 105 adult participants in the MOONLIGHT-1 trial in June 2026. In September 2026, we announced that J&J reported to us that the MOONLIGHT-1 trial did not achieve its primary efficacy endpoint, which evaluated improvement from baseline in the Montgomery-Åsberg Depression Rating Scale (“MADRS”) total score at Day 5 compared with placebo. PIPE-307 was well-tolerated in the trial, with no new safety signals observed. J&J informed us that it is evaluating the MOONLIGHT-1 data, including data related to prespecified exploratory endpoints, to inform next steps for PIPE-307. J&J may de…

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Current report

The research, testing, manufacturing, labeling, approval, sale, packaging, marketing, and distribution of drug products are subject to extensive regulation by the FDA and comparable regulatory authorities in other countries. We are not permitted to market or sell PIPE-791, and J&J will not be permitted to market or sell PIPE-307, in the United States until we or J&J, as applicable, receive approval of an NDA from the FDA for such drug candidate. Further, we are not permitted to market or sell PIPE-791, and J&J will not be permitted to market or sell PIPE-307, in any foreign countries until we or J&J, as applicable, receive the requisite approvals from such countries. Neither we nor J&J have submitted an NDA to the FDA or comparable applications to other regulatory authorities for PIPE-791 or PIPE-307, respectively, in any indication. Neither party will be in a position to do so for several years, if ever. If we are unable to obtain the necessary regulatory approvals for PIPE-791 in any country, we will not be able to commercialize such drug candidate in that country. Similarly, if J&J is unable to obtain the necessary regulatory approvals for PIPE-307 in any country, it will not be able to commercialize such drug candidate in that country. In both cases, our financial position will be materially adversely affected, and we may not be able to generate sufficient revenue to continue our business.

Current report

Clinical drug development is a lengthy, expensive and risky process with uncertain timelines and uncertain outcomes. The results of earlier preclinical studies and clinical trials, including those conducted by third parties, may not be predictive of future results. If clinical trials for the drug candidates we develop do not meet safety or efficacy endpoints or are prolonged or delayed, these drug candidates may not receive the required regulatory approvals, and therefore could not be commercialized on a timely basis or at all. Further, the results of our preclinical studies, clinical trials, or analyses may not be indicative of results that may be obtained in later trials.*

Current report

Before obtaining marketing approval from regulatory authorities for the sale of the drug candidates we develop, these drug candidates must undergo extensive clinical trials to demonstrate their safety and efficacy in humans. The research and development of drugs is extremely risky. Only a small percentage of drug candidates that enter the clinical development process ever receive marketing approval. Failure or delay can occur at any time during the clinical trial process. To date, we have focused substantially all of our efforts and financial resources on identifying, acquiring, and developing drug candidates, including conducting preclinical studies and early-stage clinical trials. Clinical testing is expensive and can take many years to complete, and we cannot be certain that any clinical trials for the drug candidates we develop will be conducted as planned or completed on schedule, if at all. Our inability to successfully complete preclinical and clinical development for PIPE-791 could result in additional costs to us and negatively impact our ability to generate revenue. Similarly, if J&J elects not to pursue or cannot successfully complete preclinical and clinical development for PIPE-307, we will not be eligible to receive future milestone payments or royalties under the J&J License Agreement. As a result, our future success is primarily dependent on our ability to successfully develop, obtain regulatory approval for, and then successfully commercialize PIPE-791 and J&J’s election and ability to successfully develop, obtain regulatory approval for, and then successfully commercialize PIPE-307. We currently generate no revenues from sales of any products, and we may never be able to develop or commercialize a marketable product. Further, we may never receive additional milestone payments or royalties under the J&J License Agreement.

Current report

Our only active clinical trial is our PROPEL-IPF Phase 2 clinical trial of PIPE-791 for the treatment of IPF. The results from our preclinical studies and the early clinical trials for PIPE-791 may not be predictive of the results of PROPEL-IPF or any later-stage clinical trials conducted for PIPE-791 in IPF or for any other indication. In addition, results of third-party studies, as well as our evaluations of third-party compounds, may not be predictive of results for our other drug candidates. Drug candidates in clinical trials, including PIPE-791 and PIPE-307, may fail to show the desired safety and efficacy traits despite having progressed through preclinical studies and early-stage clinical trials. For example, the Phase 2 MOONLIGHT-1 and VISTA clinical trials of PIPE-307 did not achieve their respective primary efficacy endpoints despite Phase 1 trial data for PIPE-307 supporting these trials. In addition, conclusions based on promising data from analyses of earlier clinical trial results may be shown to be incorrect in subsequent clinical trials that have pre-specified end points or may not be considered adequate by regulatory authorities.

Current report

Even if the current and anticipated clinical trials for PIPE-791 and PIPE-307 are completed as planned, we cannot be certain that their results will support the safety and efficacy requirements sufficient to pursue later clinical trials and eventually obtain regulatory approval, and, as a result, we may never generate commercial revenues from these drug candidates. Moreover, if we or J&J are not able to differentiate PIPE-791 and PIPE-307, respectively, against other approved products for the indications being targeted for PIPE-791 and PIPE-307, or if any of the other circumstances described above occur, our business would be materially harmed and our ability to generate revenue from these drug candidates would be severely impaired.

Current report

Clinical trial failure may result from a multitude of factors including flaws in trial design, dose selection, placebo effect, patient enrollment criteria, relatively smaller sample size in earlier clinical trials, and failure to demonstrate favorable safety or efficacy traits. As such, failure in clinical trials can occur at any stage of testing. A number of companies in the biopharmaceutical industry have suffered setbacks in the advancement of clinical trials due to lack of efficacy or adverse safety profiles, notwithstanding promising results in earlier trials, and we cannot be certain that we will not face similar setbacks. Based upon negative or inconclusive results, we may decide, or regulators may require us, to conduct additional clinical trials or preclinical studies or halt further clinical investigation. In addition, data obtained from clinical trials are susceptible to varying interpretations, and regulators may not interpret the data from these trials as favorably as we do, which may further delay, limit or prevent marketing approval. Furthermore, as more drug candidates within a particular class of drugs proceed through clinical development to regulatory review and approval, the amount and type of clinical data that may be required by regulatory authorities may increase or change. The outcome of preclinical testing and early clinical trials may not be predictive of the success of later clinical trials, and preliminary or interim results of a clinical trial do not necessarily predict final results. For example, PIPE-791 and/or PIPE-307 may fail to show the desired safety and efficacy in clinical development despite positive results in preclinical studies, or having successfully advanced through early-stage clinical trials. The failure of any drug candidate to demonstrate safety and efficacy in any clinical trial or for any indication could negatively impact the perception of the use of this drug candidate to treat other indications and the perception of any other drug candidate we develop (and therefore hinder the ability to successfully move forward with the development of the drug candidate in other indications or the development of our other drug candidates) or cause regulatory authorities to require additional testing before approving any of the drug candidates we develop.

Current report

We may experience delays in initiating and successfully completing the clinical trials that we intend to conduct, including our current and planned clinical trials for PIPE-791. Any delays in initiating and successfully completing our clinical trials could increase our costs, slow the development and approval process and harm the commercial prospects of our drug candidates. Similarly, if J&J elects to further develop PIPE-307, it may experience delays in initiating and completing any future clinical trials it conducts, which would delay our receipt of potential milestone payments or royalties under the J&J License Agreement. Any of these occurrences could materially harm our business, financial condition and results of operations.*

Current report

We may experience delays in initiating and completing any clinical trials that we intend to conduct, including PROPEL-IPF and our planned future clinical trials for PIPE-791, and we do not know whether our clinical trials will begin on time, need to be redesigned, enroll sufficient numbers of patients on time, or be completed on schedule, or at all. J&J will face similar concerns if it elects to conduct future clinical trials for PIPE-307. A clinical trial can be delayed for a variety of reasons, including delays related to:

Current report

•the FDA or comparable foreign regulatory authorities disagreeing as to the design or implementation of the clinical trial;

Current report

•obtaining regulatory approval to commence the clinical trial;

Current report

•obtaining IRB approval at each site within the United States or IEC or other approval at sites outside the United States;

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•recruiting suitable patients to participate in the clinical trial in a timely manner and in sufficient numbers;

Current report

•having patients complete the clinical trial or return for post-treatment follow-up;

Current report

•imposition of a clinical hold by regulatory authorities, including as a result of unforeseen safety issues or side effects or failure of clinical trial sites or investigators to adhere to regulatory requirements or follow trial protocols;

Current report

•clinical sites or investigators deviating from the clinical trial protocol or dropping out of the clinical trial, potentially necessitating the addition of new sites or investigators;

Current report

•third-party contractors failing to comply with regulatory requirements or meet their contractual obligations in a timely manner, or at all, or deviating from the clinical trial protocol;

Current report

•addressing patient safety concerns that arise during the clinical trial, including a decision by the initiating party, regulatory authorities, or IRBs, IECs or other relevant entities to suspend or terminate the clinical trial;

Current report

•adding a sufficient number of clinical trial sites;

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•increased or unforeseeable costs in conducting a clinical trial;

Current report

•timely manufacturing sufficient quantities of a drug candidate, and accessing sufficient quantities of other materials (e.g. placebo, equipment) for use in the clinical trial; and

Current report

•potential disruptions caused by public health emergencies (“PHEs”) such as COVID-19, including difficulties in initiating clinical sites, enrolling and retaining participants, diversion of healthcare resources away from clinical trials, travel or quarantine policies that may be implemented, and other factors.

Current report

We commenced our international Phase 2 clinical trial (PROPEL-IPF) examining the safety and efficacy of PIPE-791 in IPF participants in the first quarter of 2026. As of October 21, 2026, we have received regulatory authorization to conduct the trial in 25 countries, including in the European Union, the United Kingdom, Japan, Australia, Canada, South Korea and Taiwan, and have opened more than 100 clinical sites. These regulatory authorizations were granted following review by the regulatory authorities in each of these countries of our available data package, including our preclinical and Phase 1 data on PIPE-791. We intend to continue adding additional countries and sites as we obtain required authorizations. We have engaged in pre-IND discussions with the FDA regarding the PROPEL-IPF trial. During these discussions, the FDA expressed concerns about LPAR1 antagonists and the potential for adverse effects related to blood pressure. The FDA indicated its concerns were informed by data from other programs and recommended we collect additional clinical data to further analyze whether similar risks exist with respect to PIPE-791. To date, we have not identified any clinically-relevant adverse safety signals related to PIPE-791 in our completed clinical trials, including with respect to blood pressure. As our development program advances, we intend to collect much of the safety data the FDA recommended we collect through our ongoing PROPEL-IPF trial and other planned clinical trials and studies. We believe the data generated through these trials and studies, if completed, will provide additional safety data in patients with IPF supportive of enabling future clinical trials that include clinical sites in the United States. There is no guarantee that our efforts to gather this additional safety data will be successful or that any data we gather will be favorable or deemed sufficient by the FDA. The FDA may require us to conduct additional studies or clinical trials or provide additional patient data, which could be costly, time-consuming and difficult to complete. We will continue to engage with the FDA on our proposed data package and approach, but until we have aligned our approach with the FDA, we cannot be sure that any additional data package or approach will result in the FDA allowing us to commence our PROPEL-IPF trial or any other pulmonary fibrosis clinical trial in the United States. Based on enrollment to date at our clinical sites outside the United States, we do not currently expect a delay in the anticipated timing for the completion of PROPEL-IPF if we are not able to include clinical sites in the United States in this clinical trial. However, if we are unable to eventually obtain clearance from the FDA to include clinical sites in the United States in PROPEL-IPF or in future clinical trials, or if obtaining such clearance is delayed, our planned Phase 3 development of PIPE-791 in the United States could be delayed, our development costs …

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Current report

A clinical trial may be suspended or terminated by the initiating party, the IRBs or IECs of the institutions in which such clinical trial is being conducted, the FDA or other regulatory authorities, or recommended for termination by a Data and Safety Monitoring Board (“DSMB”) for such trial. Such authorities may impose a suspension or termination or recommend an alteration due to a number of factors, including failure to conduct the clinical trial in accordance with regulatory requirements, such as GCP requirements, or the clinical trial protocols, inspection of the clinical trial operations or clinical trial site by the FDA or other regulatory authorities resulting in significant inspectional observations or the imposition of a clinical hold, unforeseen safety issues or adverse side effects, failure to demonstrate a benefit from using a drug, changes in governmental regulations or administrative actions, or lack of adequate funding to continue the clinical trial.

Current report

Furthermore, we rely on CROs and clinical trial sites to ensure the proper and timely conduct of our clinical trials and, while we have agreements governing their committed activities, we have limited influence over their actual performance, as described in the section titled “—Risks related to our dependence on third parties.”

Current report

If the commencement or completion of any clinical trials for PIPE-791 or any of our future drug candidates is delayed, or if a clinical trial is terminated prior to completion, the commercial prospects of the applicable drug candidate could be harmed, and our ability to generate revenues or royalties from such drug candidate may be delayed. In addition, any delays in our clinical trials could increase our costs, slow the development and approval process and jeopardize our ability to commence product sales and generate revenues. Any of these occurrences could materially harm our business, financial condition and results of operations. In addition, many of the factors that may cause, or lead to, a delay in the commencement or completion of a clinical trial may also ultimately lead to the denial of regulatory approval of the applicable drug candidate.

Current report

Principal investigators for our clinical trials may serve as scientific advisors or consultants to us from time to time and receive compensation in connection with such services. Under certain circumstances, we may be required to report some of these relationships to the FDA. The FDA may conclude that a financial relationship between us and a principal investigator has created a conflict of interest or otherwise affected interpretation of a clinical trial. The FDA may therefore question the integrity of the data generated at the applicable clinical trial site, and the utility of the clinical trial itself may be jeopardized. This could result in a delay in approval, or rejection, of our marketing applications by the FDA and may ultimately lead to the denial of marketing approval of a drug candidate.

Current report

The regulatory approval processes of the FDA and comparable foreign regulatory authorities are unpredictable, lengthy, and time-consuming, and if we are ultimately unable to obtain regulatory approval to commercialize PIPE-791 or any other drug candidates that we develop or if J&J elects to not continue to develop PIPE-307 or is unable to obtain regulatory approval to commercialize it, our business will be substantially harmed.*

Current report

The time required to obtain approval by the FDA and comparable foreign regulatory authorities to commercialize a drug is unpredictable but typically takes many years following the commencement of clinical trials and depends upon numerous factors, including the indication being studied, the available data and the substantial discretion of the regulatory authorities. In addition, approval policies, regulations, or the type and amount of clinical data necessary to gain approval for an indication may change during a drug candidate’s clinical development and may vary among jurisdictions. We have not obtained regulatory approval for PIPE-791, and J&J has not obtained regulatory approval for PIPE-307. It is possible that neither of these drug candidates or any future drug candidates we elect to develop will receive the regulatory approvals required for commercialization. We are not permitted to market PIPE-791 or any other drug candidates that we develop in the United States until we receive approval of an NDA from the FDA. Similarly, if J&J elects to continue to develop PIPE-307, it will not be permitted to market PIPE-307 in the United States until it receives approval of an NDA from the FDA.

Current report

Prior to obtaining approval to commercialize a drug candidate in the United States or abroad, the initiating party must demonstrate with substantial evidence from well-controlled clinical trials, and to the satisfaction of the FDA or comparable foreign regulatory authority, that such drug candidate is safe and effective for its intended indication. In addition, data obtained from preclinical trials and clinical trials are susceptible to varying interpretations, and regulatory authorities may not interpret this data as favorably as the initiating party, which may further delay, limit, or prevent development efforts, clinical trials, or marketing approval. For example, even if we believe the preclinical and clinical data for PIPE-791 in an indication is promising, such data may not be sufficient to support approval by the FDA and other comparable regulatory authorities for this indication. Furthermore, as more competing drug candidates within a class of drugs proceed through clinical development to regulatory review and approval, the amount and type of clinical data that may be required by regulatory authorities may increase or change.

Current report

The FDA or any foreign regulatory authority can delay, limit, or deny approval of PIPE-791, PIPE-307 or any other drug candidates that we elect to develop for any indication, or require us or J&J, as applicable, to conduct additional preclinical or clinical testing or abandon a program for many reasons, including:

Current report

•the initiating party may be unable to demonstrate to the satisfaction of the FDA or comparable foreign regulatory authorities that a drug candidate is safe and effective for its proposed indication;

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•serious and unexpected drug-related side effects experienced by participants in a clinical trial or by individuals using drugs similar to the drug candidate being studied in the clinical trial, or other products containing an active ingredient in such drug candidate;

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•negative or ambiguous results from a clinical trial or results that may not meet the level of statistical significance required by the FDA or comparable foreign regulatory authorities for approval;

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•the inability to demonstrate that a drug candidate’s clinical and other benefits outweigh its safety risks;

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•the FDA or comparable foreign regulatory authorities may disagree with the interpretation of data from preclinical studies or clinical trials or determine that any information we submit is not sufficient to support market approval;

Current report

•the data collected from clinical trials may not be acceptable or sufficient to support the submission of an NDA or other submission or to obtain regulatory approval in the United States or elsewhere, and the initiating party may be required to conduct additional clinical trials;