Imiquimod

\"UGN-301’s overall clinical profile did not meet UroGen’s internal benchmarks for advancement to phase 2,\" UroGen explained Thursday.\n UroGen is handing an anti-CTLA-4 antibody back to Agenus after concluding phase 1 data for the bladder cancer drug didn’t reach the benchmark for further development.New Jersey-based UroGen forked over $10 million in upfront cash for the license to the candidate, called zalifrelimab or UGN-301, back in 2019. At the time, the idea was to develop and ultimately commercialize zalifrelimab in combination with UroGen’s TLR7/8 agonist UGN-201 for the treatment of urinary tract cancers.The program was also an opportunity to test out RTGel, UroGen’s sustained-release, hydrogel-based tech designed to improve the therapeutic profiles of existing drugs.But, having now wrapped up a phase 1 dose-escalation study of zalifrelimab, it appears UroGen has lost confidence in the asset.“While the study confirmed proof of concept for RTGel as a viable platform for local delivery of complex immunotherapies, UGN-301’s overall clinical profile did not meet UroGen’s internal benchmarks for advancement to phase 2,” the company explained in its third-quarter earnings release this morning. As a result, UroGen has notified Agenus that it is terminating their license agreement. It means Agenus will miss out on the $115 million in clinical development and regulatory milestones and $85 million in commercial milestone paydays that could have come its way if zalifrelimab had achieved success.Anti-CTLA-4 checkpoint inhibitors have proven their worth in oncology in the form of Bristol Myers Squibb’s blockbuster Yervoy and AstraZeneca’s Imjudo.The decision by UroGen marks the latest rejection for Agenus after Bristol Myers Squibb axed a TIGIT bispecific antibody pact last year and then Incyte broke off an immuno-oncology deal in February. The Massachusetts-based biotech ended last year reorganizing after failing to gain traction with the FDA on its PD-1 candidate balstilimab.

Pritelivir demonstrated clinically meaningful and highly statistically significant superiority (p=0.0047) in lesion healing up to 28 days of treatment, compared with standard-of-care (SoC) treatments in refractory Herpes Simplex Virus (HSV) infected immunocompromised patients Pritelivir was well tolerated and had a favorable safety profile over the treatment duration Full results will be presented at an upcoming medical conference and will form the basis for regulatory filings with the FDA and globally October 16, 2025 - Aicuris Anti-infective Cures AG today announced that the registrational Phase 3 trial (PRIOH-1, NCT03073967) with its lead candidate pritelivir, a first-in-class helicase primase inhibitor for HSV, has met its primary endpoint of superiority (p=0.0047) in lesion healing in patients receiving treatment up to 28 days. Statistical superiority in lesion healing further increased in patients receiving up to 42 days of treatment (p<0.0001). The aim of the trial was to evaluate the efficacy and safety of pritelivir compared to SoC (investigator’s choice of foscarnet, cidofovir, compounded topical cidofovir or imiquimod) in treating immunocompromised patients with refractory HSV infection, with or without resistance (R±R). Pritelivir is a small-molecule antiviral targeting the helicase-primase complex of HSV. The candidate’s novel mechanism of action does not rely on activation by viral enzymes, allowing it to overcome HSV infections that are R±R to treatments, such as acyclovir, valacyclovir, famciclovir and foscarnet. Immunocompromised patients are particularly prone to more severe, prolonged and refractory HSV infections that are difficult to treat and do not respond to SoC. These infection outbreaks can cause painful lesions, drastically reducing quality of life, increasing the risk of hospitalization, and disseminated infection. Several SoC treatments require intravenous infusions and are poorly tolerated with common side effects including kidney toxicity and electrolyte imbalances with risk of seizures requiring in-patient hospital management. With the demonstrated superior efficacy compared with SoC, favorable safety profile and good tolerability, pritelivir, as an oral therapy, has the potential to address the unmet needs of immunocompromised patients. “After working in the infectious disease space for over 20 years, I am excited to have the opportunity to state - we have achieved our goal of demonstrating pritelivir’s statistically superior treatment benefit in a registrational study. We plan to rapidly advance our New Drug Application submission to the FDA, and we look forward to presenting a comprehensive analysis of these positive results at a medical conference next year,” adds Larry Edwards, CEO of Aicuris. “This major milestone underscores our commitment to developing innovative therapies focused on improving the lives of immunocompromised patients.” “Refractory HSV infections pose a significant challenge for patients whose immune systems are impaired. We are proud that the Phase 3 trial met its primary endpoint, bringing us closer to providing an innovative treatment for these patients,” said Cynthia Wat, MD, CMO of Aicuris. “With encouraging safety, convenient oral dosing, and the statistically superior efficacy in treating R±R HSV as demonstrated in this pivotal trial, pritelivir could be a paradigm shift for immunocompromised patients globally. I would like to thank all patients and clinical investigators who made these results possible.” The open-label, comparative trial (NCT03073967 / Eudra-CT 2023-510088-37-00) was conducted in centers across 15 countries and enrolled 158 immunocompromised participants. All pritelivir-treated patients received a loading dose of 400 mg of pritelivir on the first day of treatment followed by 100 mg each subsequent day until all lesions were healed. 102 R±R HSV patients were randomized 1:1 and treated with pritelivir or investigator´s choice to demonstrate superior efficacy (percentage of fully healed lesions) and evaluate the safety profile of pritelivir. In addition, HSV patients were treated with pritelivir in two additional non-randomized cohorts: one study-arm included 35 patients who were R±R to acyclovir and foscarnet or intolerant to foscarnet, the second study-arm included 21 acyclovir-sensitive patients. Herpes Simplex Virus (HSV) includes two types, HSV-1 and HSV-2, both of which cause lifelong infections. HSV-1 typically leads to labial herpes, typically resulting in cold sores, while HSV-2 is commonly associated with genital herpes. These viruses can cause recurrent painful lesions and sores and, in severe cases, complications such as encephalitis, meningitis, disseminated disease, keratitis and neonatal herpes. HSV infections are widespread globally, with a significant impact on public health. According to the World Health Organization, an estimated 3.8 billion people under the age of 50, or 64% of the global population, were infected with HSV-1 in 2020. 520 million people aged 15 to 49 were living with genital herpes caused by HSV-2. The disease burden is particularly high in immunocompromised patients, who may experience more severe, more frequent and treatment-refractory HSV manifestations. Pritelivir, a novel helicase-primase inhibitor developed by Aicuris, targets both HSV-1 and HSV-2. These viruses are responsible for genital, oral or disseminated infections with increasing severity that are often difficult to treat with a higher risk of resistance development in immunocompromised people. Unlike traditional antivirals, pritelivir blocks viral DNA synthesis by inhibiting the helicase-primase complex, a mechanism distinct from marketed nucleoside analogues. Because of this distinct mode of action, pritelivir is active against viral strains that are resistant to nucleoside analogs.1 Earlier trials in immunocompetent and immunocompromised individuals showed a favorable safety profile and early signs of clinical efficacy compared to standard-of-care treatments like valacyclovir and foscarnet. Based on the earlier clinical trial results, pritelivir received FDA breakthrough designation. In July, the last patient was enrolled in the Phase 3 pivotal trial, the outcomes of which are expected to serve as a basis for filing for marketing authorization in 2026. Aicuris is meeting the needs of the growing population of immunocompromised people who require precise therapies to effectively treat infection. Our flagship product, PREVYMIS®, marketed by our partner MSD, prevents CMV in a defined group of transplant recipients. Our pivotal Phase 3 candidate, pritelivir, aims to address refractory HSV infections in a broad population of patients with weakened immune systems. For immunocompromised people, an otherwise manageable infection can mean life or death. Aicuris, with its expertise and growing pipeline, is committed to providing therapeutic solutions for them now and in the future. 1 Sallée, L. and Boutolleau, D. (2024), Management of Refractory/Resistant Herpes Simplex Virus Infections in Haematopoietic Stem Cell Transplantation Recipients: A Literature Review. Rev Med Virol, 34: e2574. https://doi.org/10.1002/rmv.2574 The content above comes from the network. if any infringement, please contact us to modify.