What did “no efficacy or safety issues” cover in these FDA letter announcements?

FDA Complete Response Letter, July 13, 2020 · page 15

In summary, we remain concerned that your proposed cantharidin combination product is not safe for use by HCPs. We are concerned that the risk of accidental exposure will outweigh the benefit of the treatment with this combination product. Inherent design issues exist with this product that may contribute to serious harm if accidental exposure occurs during use. Thus, additional mitigation strategies are needed and could include the need for device design changes to optimize applicator use along with other revisions to the product user interface taking into consideration our previously identified concerns and the data collected from your HF validation study. After you implement additional risk mitigation strategies/modifications, we recommend you conduct an additional HF validation study to ensure that these modifications address the observed use errors and use difficulties and do not introduce any new risks.

Verrica Pharmaceuticals Form 8-K, filed July 14, 2020

Verrica believes that the positive results from its two double-blind Phase 3 trials (CAMP-1 and CAMP-2), which evaluated VP-102 compared to placebo in patients two years of age and older diagnosed with molluscum, have demonstrated favorable safety, efficacy and tolerability. Specific results from the CAMP-1 and CAMP-2 studies showed that 46 and 54 percent, respectively, of subjects treated with VP-102 achieved complete clearance of all baseline and new molluscum lesions at the end of the trials (Day 84), versus 18 and 13 percent, respectively, of subjects in the vehicle groups (p<0.0001). There were no serious adverse events reported in VP-102-treated subjects, and most adverse events reported in subjects receiving VP-102 were local skin reactions and mild to moderate in severity.

Verrica Pharmaceuticals Form 8-K, filed July 14, 2020

Complete Response Letter Requests Additional Chemistry, Manufacturing, and Controls (CMC) and Human Factors Information – – No Clinical Safety or Efficacy Issues Identified

Verrica Pharmaceuticals Form 8-K, filed July 14, 2020

According to the CRL, the FDA is seeking additional information regarding certain aspects of the CMC (Chemistry, Manufacturing, and Controls) process for the drug/device combination, as well as Human Factors validation. Importantly, the FDA did not identify any clinical deficiencies.

FDA Complete Response Letter, February 26, 2021 · page 8

During a review of records requested under Federal Food, Drug, and Cosmetic Act section 704(a)(4), provided by Rovi Pharma Industrial Services S.A. (FEI 3016688535) manufacturing facility, the FDA noted objectionable conditions. These objectionable conditions will be conveyed to the representative of the facility within 10 business days of issuance of this Complete Response letter. Satisfactory resolution of these objectionable conditions is required (e.g., preapproval inspection and/or adequate facility responses addressing these conditions) before this application may be approved.

FDA Complete Response Letter, February 26, 2021 · page 9

You have not demonstrated that the currently proposed in-process control for the ( mL± mL) in the drug product manufacturing process is appropriate. As previously communicated to you, conduct and provide results of an extraction study to demonstrate that the labeled volume of the drug product solution (5 mL) can be consistently withdrawn from vials, including vials that are . Revise the based on the results of the extraction study conducted.

CorMedix Form 8-K, filed March 1, 2021

FDA noted concerns at the third-party manufacturing facility after a review of records requested by FDA and provided by the manufacturing facility. FDA did not specify the issues and CorMedix intends to work with the manufacturing facility to develop a plan for resolution when FDA informs the facility of the specific concerns.

CorMedix Form 8-K, filed March 1, 2021

FDA did not request additional clinical data, and did not identify any deficiencies related to the data submitted on the efficacy or safety of DefenCath from LOCK-IT-100. In draft labeling discussed with FDA, the Agency added that the initial approval will be for the limited population of patients with kidney failure receiving chronic hemodialysis through a central venous catheter.

FDA Complete Response Letter, September 16, 2021 · page 9

ADDITIONAL COMMENTS Labeling and Human Factor comments and recommendations will be conveyed in a separate correspondence.

Verrica Pharmaceuticals Form 8-K, filed September 20, 2021

announced that it received a complete response letter from the U.S. Food and Drug Administration (the “ FDA ”) identifying deficiencies at a facility of a contract manufacturing organization for its New Drug Application (the “ NDA ”) for VP-102 for the treatment of molluscum contagiosum. The identified deficiencies do not specifically relate to the manufacturing of VP-102, but instead raise general quality issues at the facility. The FDA did not identify any clinical, safety or product specific chemistry, manufacturing, and controls deficiencies related to the NDA.

Verrica Pharmaceuticals Form 8-K, filed November 12, 2021

On September 20, 2021, Verrica announced that the U.S. Food and Drug Administration (“FDA”) issued a Complete Response Letter (“CRL”) regarding its New Drug Application (“NDA”) for VP-102 (cantharidin 0.7% Topical Solution) for the treatment of molluscum contagiosum (“molluscum”). According to the CRL, the FDA identified deficiencies at a facility of a contract manufacturing organization (“CMO”), which were not specifically related to the manufacturing of VP-102 but instead raised general quality issues at the facility. The FDA did not identify any clinical, safety or product specific Chemistry, Manufacturing, and Controls (“CMC”) deficiencies related to VP-102. Following the CRL, on September 22, 2021 Verrica received a General Advice Letter from the FDA with recommendations to improve YCANTH’s user interface.

FDA Complete Response Letter, August 4, 2022 · page 4

Please refer to correspondence dated July 20, 2022, which addresses the proposed proprietary name, Defencath. This proposed name is unacceptable due to confusion with another product that is also under review. Therefore, the ultimate acceptability of your proposed proprietary name, Defencath, is dependent upon which application is approved first.

CorMedix Form 8-K, filed August 9, 2022

A second Complete Response Letter (CRL) was received from the FDA stating that the DefenCath NDA cannot be approved until deficiencies recently conveyed to the contract manufacturing organization (CMO) and the supplier of the active pharmaceutical ingredient (API) heparin during inspections are resolved to the satisfaction of FDA. There were no other deficiencies related to DefenCath cited in the CRL, and the Company expects that resolution of the site-specific compliance deficiencies will clear a pathway for FDA to approve the DefenCath NDA.

FDA Complete Response Letter, July 21, 2025 · page 1

After our complete review, we have concluded that we cannot grant final approval because of the deficiencies outlined below.

FDA Complete Response Letter, July 21, 2025 · page 1

However, the numerically higher response rate cannot be adequately interpreted due to heterogeneity of the RPL-001-16 trial patient population, including the type of prior therapy received, such as single agent anti-PD-1 or combination checkpoint inhibitor, duration and setting of prior anti-PD-1 therapy, and extent of disease at baseline, and due to the heterogeneity of the patient population reported in the literature.

Replimune Form 8-K, filed July 22, 2025

The CRL indicates that the FDA is unable to approve the application in its present form. The FDA has indicated that the IGNYTE trial is not considered to be an adequate and well-controlled clinical investigation that provides substantial evidence of effectiveness. Furthermore, the FDA said the trial cannot be adequately interpreted due to the heterogeneity of the patient population. The CRL also states that there are items related to the confirmatory trial study design which need to be addressed, including contribution of components. Importantly, no safety issues were raised.