An Open-Label, Multicenter, Phase 2 Study With Safety Lead-In of Intratumoral Vusolimogene Oderparepvec (VO) in Combination With Pembrolizumab in Patients With Angiosarcoma

This is a multicenter, open-label study of Intratumoral Vusolimogene Oderparepvec (VO) to investigate safety and estimate when used in combination with pembrolizumab for treating participants with angiosarcoma. This is the first study evaluating this novel combination in participants with advanced angiosarcoma who have progressed after prior immunotherapy.

Start Date31 Oct 2025

Sponsor / Collaborator

The University of California, San Francisco

[+1]

NCT06264180

/ RecruitingPhase 3

Randomized, Ph3 Clinical Study Comparing Vusolimogene Oderparepvec in Combination With Nivolumab Vs Treatment of Physician's Choice in Patients With Advanced Melanoma That Progressed on Anti-PD-1 and Anti-CTLA-4 Containing Treatment [IGNYTE-3]

This is a randomized, controlled, multicenter, open-label Phase 3 clinical study comparing VO in combination with nivolumab versus Physician's Choice treatment for patients with unresectable Stage IIIb-IV cutaneous melanoma whose disease progressed on an anti PD-1 and an anti-CTLA-4 containing regimen (administered either as a combination regimen or in sequence) or who are not candidates for treatment with an anti-CTLA-4 therapy.

Start Date11 Jul 2024

Sponsor / Collaborator

Replimune, Inc.

NCT06067061

/ TerminatedPhase 1/2IIT

"neoBREASTIM": A Phase 2 Study of Atezolizumab Plus RP1 Oncolytic Immunotherapy in the NeoAdjuvant Setting of Triple-Negative Breast Cancer (TNBC)

Neoadjuvant treatment is an important part of the treatment strategy for locally advanced TNBC having established a positive and significant correlation of pathologic Complete Response (pCR) with long-term clinical benefit such as Event-Free Survival (EFS) and Overall Survival (OS) as shown via large meta-analysis. Much effort has been made to identify novel agents and new drug combinations that can improve pCR rates in this specific clinical setting, which is the leading rationale to evaluate RP1 oncolytic immunotherapy in combination with Atezolizumab.

Start Date05 Apr 2024

Sponsor / Collaborator

Institut Curie

[+2]

100 Clinical Results associated with Vusolimogene oderparepvec

100 Translational Medicine associated with Vusolimogene oderparepvec

100 Patents (Medical) associated with Vusolimogene oderparepvec

Literatures (Medical) associated with Vusolimogene oderparepvec

02 Nov 2025·Future Medicinal Chemistry

“Spiro-pyrrolizidine-benzyloxy hybrid as synergistic partner to doxorubicin cardio-safe breast cancer chemotherapy”

Article

Author: Sivakumar, K. ; Manikandan, H. ; Rajapandiyan, Uthirapathi ; Raj Kumar, M.

PURPOSE OF OBJECTIVE:

This study aims to develop novel spiro-pyrrolizidine-benzyloxy hybrids (RP₁, RP₂, and RP₃) to reduce the dosage and mitigate the side effects of doxorubicin (DOX) while harnessing potential synergistic effects for enhanced anticancer efficacy.

METHODS:

Spiro-pyrrolizidine-benzyloxy hybrids (RP₁, RP₂, and RP₃) were synthesized using isatin, L-proline, and sub-chalcone. The anticancer potential of these compounds was evaluated against MDA-MB-231 breast cancer cells. Based on superior efficacy, RP₁ was selected and compounded with doxorubicin in different ratios. The anticancer efficacy of these compounded formulations was assessed through cell viability assays and IC50 values.

RESULTS:

Among the synthesized hybrids, RP₁ exhibited the highest anticancer efficacy against MDA-MB-231 cells. When RP1 was combined with doxorubicin, the combination showed reduced cell viability, with the most effective ratio being 23.50 µM (20:80) (RP₁: dox), followed by 11.22 µM (50:50) and 8.82 µM (80:20). The compounded formulation resulted in a lower IC50 value compared to doxorubicin alone, indicating enhanced efficacy.

CONCLUSIONS:

Compounding RP₁ with doxorubicin effectively enhances anticancer activity while potentially reducing the side effects associated with doxorubicin's quinone-hydroquinone moiety. The optimized formulation (80:20) presents a promising approach for improving breast cancer treatment outcomes.

09 Oct 2025·ChemPlusChem

Development of Polynitrogen and Halogen‐Containing Bishomocubane‐Based High Energy Density Materials: Synthetic, Theoretical, and Thermogravimetric Studies

Article

Author: Banda, Prashanth Goud ; Lal, Sohan ; Namboothiri, Irishi N. N. ; Javed, Dilshad ; Kumbhakarna, Neeraj ; Tejashree, Gangavara L. ; Chowdhury, Arindrajit

Novel nitro, tetrazole, and halo‐substituted 1,3‐bishomocubanes have been successfully synthesized and characterized by various spectroscopic and analytical techniques, including single‐crystal X‐ray analysis. According to Density Functional Theory (DFT) calculations, performed at B3LYP/6‐311++G(d, p) level of theory, the densities and heats of formation of the newly synthesized compounds are in the range of 1.52–2.26 g cm−3 and −70.8–111.4 kcal mol−1, respectively. These compounds are predicted to exhibit enhanced propulsive properties in terms of density‐specific impulse (ρIsp), compared to that of conventional liquid propellant RP1 and solid propellant binder hydroxy‐terminated polybutadiene (HTPB), which makes them potential candidates for volume‐limited propulsion systems. However, two derivatives have exceptional calculated figures of merit for volume‐limited propulsion systems, a dibromoester (ρIsp 415.8 s), and a dibromonitroalcohol (ρIsp 421.3 s). Though its detonation properties indicate low explosive potential, the dibromonitroalcohol possesses the highest detonation pressure (20.1 GPa) and velocity (6.3 Km s−1), which are closer to the detonation performance of trinitrotoluene (TNT). Stability parameters, including Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO) energy gaps, thermogravimetric analysis, and differential thermal analysis, confirm the robust kinetic and thermal stability of our compounds.

22 Aug 2024·CHEMISTRY-A EUROPEAN JOURNAL

Synthesis, Characterization and Energetic Properties of Hydroxymethyl‐Bishomocubanone Derivatives

Article

Author: Pallikonda, Gangaram ; Mallick, Lovely ; Ahirwar, Parmanand ; Lal, Sohan ; Namboothiri, Irishi N. N. ; Cheekatla, Subba Rao ; Kumbhakarna, Neeraj ; Rao Cheekatla, Subba ; Suresh, Alati ; Chowdhury, Arindrajit ; Desai, Poonam ; Ayyagari, Narasimham

Abstract:

The present work reports synthesis, characterization and theoretical insights on novel hydroxymethyl‐bishomocubanone derivatives. Twelve new bishomocubanes (BHCs) were synthesized and fully characterized by various spectroscopic techniques and single crystal X‐ray analysis. The densities of the title compounds were in the range of 1.30–1.59 g/cm3. Density‐functional theory (DFT) based calculations at B3LYP/6‐311++G(d,p) level of theory were performed on ten selected BHC based cage compounds. Propulsive and ballistic properties of newly synthesized hydroxymethyl‐bishomocubanone derivatives in solid and liquid propulsion systems were calculated, and the results suggested that these compounds are superior to conventional fuel RP1 and binder HTPB. The detonation parameters revealed that these compounds are not explosive in nature and safe to use as solid propellants. Furthermore, kinetic and thermal stabilities of the title compounds were determined by HOMO‐LUMO energy gap, ESP maps, impact sensitivity (h50) and bond dissociation energies (BDEs) followed by thermogravimetric analysis (TGA) and differential thermal analysis (DTA). Three compounds, a dinitroazide (Isp,vac=310.98 s), a dinitrate (Isp,vac=309.51 s), and a dinitronitrate (Isp,vac=309.20s) were found to be excellent candidates for volume limited applications.

News (Medical) associated with Vusolimogene oderparepvec

08 Dec 2025

·www.biospace.com

Rare Disease Leaders Call for Regulatory Consistency After Chaotic Year

iStock, cagkansayin As the FDA unveils a parade of initiatives aimed at accelerating drug development for rare diseases, experts appeal for a consistent approval process that will support and further catalyze momentum. Rare diseases should be enjoying a moment at Marty Makary’s FDA. The FDA commissioner, along with Center for Biologics Evaluation and Research director Vinay Prasad, has made numerous statements throughout the year apparently supportive of easing market access for new rare disease treatments and recently unveiled a plausible mechanism pathway for ultrarare conditions. But action on this front has been vague and some say arbitrary—as some drugs are given the benefit of the doubt while others are turned away. This year, the FDA has greenlit treatments for Barth syndrome and glioma , while investigational drugs for advanced melanoma and for pyruvate dehydrogenase complex deficiency , an ultra-rare mitochondrial disease, were rejected. UniQure’s Huntington’s disease gene therapy, once seemingly market-bound, is now in limbo. “I see the breakdown as we don’t have a consistent policy for relentlessly progressive diseases,” Steven Grossman, policy and regulatory consultant and author of the FDA Matters blog, said during a recent BioSpace webinar . “We need to have a consistent policy when to say, ‘Yes, unproven, but you can have it,’ and ‘No, unproven makes enough of a difference here.’” Huntington’s disease FDA Minutes Confirm Challenging Path Ahead for UniQure’s Huntington’s Gene Therapy Investor optimism has waned as final minutes from uniQure’s pre-BLA meeting with the FDA convey that data from the company’s Phase I/II studies of AMT-130 are “unlikely” to provide the primary evidence to support a biologics license application. December 4, 2025 · 2 min read · Heather McKenzie Mark Veich, CEO of Advancium Health Network, a Deerfield Management and the Deerfield Foundation initiative advancing pediatric medical devices and drug therapies, agreed that a consistent approval process is required. “I think, like anything, when there’s uncertainty, people tend to shy away from working in that space, investing in that space,” Veich told BioSpace in an interview last month. “If there could be some standardization in this kind of rare disease space, I think everybody wins.” That could be easier said than done, however, John Stanford, founder & executive director of Incubate, told BioSpace . “It’s hard to balance, it’s hard to standardize” when rare disease captures such a “broad set of maladies.” One Size Fits All? While the nature of rare diseases means there’s unlikely to be one prescription for everybody, Veich said, the FDA could provide consistent guidelines in terms of clinical trial requirements. He suggested, for example, that if there was a standard number of patients required, possibly based on the prevalence of a disease, “that would be helpful.” Other standards Veich would like to see implemented are those around the use of real-world data, natural history studies and artificial intelligence and machine learning in clinical trials. A debate over the value and applicability of natural history studies was at the heart of both uniQure’s regulatory issues with AMT-130 and the rejection of Biohaven’s spinocerebellar ataxia therapy troriluzole. FDA FDA Reversals Send UniQure, Biohaven, Capricor, More Into a ‘Tailspin’ Since July, several biotechs have been forced to pivot as previous agreements with the FDA around evidence required for approval were reversed, a phenomenon that, according to experts, could portend a more restrictive regulator. November 24, 2025 · 7 min read · Heather McKenzie Using real-world evidence in rare disease trials as opposed to a placebo would accelerate patient recruitment because patients and parents currently fear being assigned to receive a placebo, Veich said. This ethical quandary was also a subject of a debate during a panel hosted by BioSpace at BIO2025 in June. Many people will argue that there is “equipoise” in conducting randomized trials for investigational rare disease drugs because the drug has not yet been proven to work, Ultragenyx CEO Emil Kakkis said. “The problem is, in reality, most things that go into Phase III have had a Phase II study and have some evidence that maybe the drug might work. Otherwise, they wouldn’t invest in Phase III to begin with.” For Stanford, there is also a broader ethical question that applies to the rare disease drug development space. He posed the question of whether a rare skin condition should “fall to the back of the line over a rare pediatric cancer.” “I don’t think there’s consensus,” Stanford said. “I think a lot of it comes down to personal beliefs about what helps the most people, and almost a utilitarianism view that I think is very different depending on who you talk to in the ecosystem.” The FDA has laid out where it stands on this issue—sort of. Implemented in 1992 in response to the HIV/AIDS crisis, the agency’s Accelerated Approval program is intended to “facilitate and expedite development and review of new drugs to address an unmet medical need in the treatment of a serious or life-threatening condition.” While “life-threatening” is self-explanatory, the FDA isn’t as clear on how it defines “serious.” And even in the life-threatening category, some experts say prioritization is given to certain diseases over others. “The system that’s being run now is kind of based on exceptionalism, and the rules are completely arbitrary,” Grossman said at the BioSpace event. “Why does DMD get a little extra consideration, but maybe not ALS?” Recent regulatory history in these two therapeutic areas gives weight to such a question. The FDA approved Sarepta’s exon-skipping Duchenne muscular dystrophy treatment Vyondys 53 in December 2019—four months after it rejected the drug due to safety concerns. In July of this year, the FDA again appeared to bow to DMD patient advocates and political pressure over safety risks when it lifted the voluntary hold on Sarepta’s Elevidys less than a week after the company conceded to the agency’s request to stop shipments of the gene therapy after the deaths of two teenage patients. Conversely, BrainStorm Cell Therapeutics’ ALS candidate NurOwn remains stalled in a Phase IIIb trial after an advisory committee voted 17-1 in August 2023 against its approval, citing lack of efficacy. NurOwn missed the primary endpoint in its initial Phase III trial—a fate also experienced by several other drugs approved by the FDA between 2018 and 2021. On the other hand, in September 2022, Amylyx’s ALS drug Relyvrio was granted a rare second adcomm after losing the first vote 4-6 in March of the same year. Relyvrio prevailed in September on new analyses and was ultimately approved later that month. The momentum spurred by the approval of this third-ever ALS treatment came crashing down in March 2024, however, when Relyvrio failed its confirmatory study and the company’s co-CEOs Josh Cohen and Justin Klee elected to pull it from the U.S. and Canadian markets, honoring a promise made to regulators. Vyondys 53, as well as another exon-skipper from Sarepta called Amondys 45, could face a similar fate after both drugs failed to significantly improve motor function in a confirmatory trial last month. However, Sarepta has said it intends to move ahead with plans to traditional approval of the treatments based on “encouraging trends” in the ESSENCE study. But when it comes to the perception of prioritization, Veich said it’s just that: perception. Diseases like ALS, DMD and spinal muscular atrophy are featured in the news more often than an orphan disease, which affects less than 200,000 people, he said. This creates a kind of catch-22 situation: because they’re written about more, they’re easier to understand. “But I don’t know that the FDA is giving them any favoritism,” he said. “The FDA first and foremost, in my view, is just making sure that patients are safe.” Winners and Losers Whether one therapeutic area is prioritized over another at the FDA is an open debate. But Stanford said one particular agency initiative, the Commissioner’s National Priority Voucher program , is providing some companies with a unique advantage. Launched in June, the CNPV intends to shorten the drug review timeline from 10–12 months to 1–2 months for certain drugs. Vouchers are granted to companies and products that are “aligned with U.S. national priorities,” such as those delivering more innovative cures or addressing a health crisis or an unmet public health need. “We seem to be in a winners and losers moment,” Stanford said. “If you’re a winner, if you get one of the Commissioner’s sort of subjective review vouchers, great—then you love this idea that you’re going to get your stuff out of the FDA within a month.” But, “If we’re trying to build a business plan on whether or not we will be in the FDA Commissioner’s good graces, that is not something that a venture model is great at betting on.” Richard Pazdur , who filed retirement papers last week after less than a month as director of the Center for Drug Evaluation and Research, has raised concerns about the legality of such programs, arguing that they could put patients at risk. FDA Pazdur Questions Safety, Legality of FDA’s Expedited Drug Approval Programs Richard Pazdur, the new director of the Center for Drug Evaluation and Research, raised concerns amid the rollout of several FDA initiatives seeking to shorten the drug review process. November 25, 2025 · 2 min read · Tristan Manalac As for the business side, Stanford pointed to the FDA’s rejection of Replimune’s oncolytic immunotherapy RP1 for advanced melanoma as an example of what can happen when this certainty is lacking. “It definitely sent shudders through some of the ecosystem of, ‘Wow, things can go sideways pretty quickly beyond just the science.’” Replimune’s stock plummeted 75% following the complete response letter and has been on a rollercoaster ride ever since—a nauseating experience to which executives at uniQure and Capricor Therapeutics can likely relate. “I think the folks who designed some of the accelerated approval pathways would like to hope that medicines that can do the most good for the most dire cases get through faster, all things being equal,” Stanford said. “That falls apart really fast when you actually get into CDER and CBER [where] there are finite resources at the agency to undertake reviews, and expediting a promising asset likely means deprioritizing others.” Another important consideration, Stanford noted, is maintaining—or restoring—trust in the FDA. “What we also don’t want to do is move medicines that don’t work along too quickly and weaken confidence in the whole system,” he said. “I do think we’re going through a moment—whether it’s because of MAHA medicine skepticism, or some drugs that did make it through whose efficacy has been questioned by payers—where people are questioning the FDA more than they normally do, and that’s got to be something we’re really mindful of.”

Phase 3Drug ApprovalPhase 2

24 Nov 2025

·www.biospace.com

FDA Reversals Send UniQure, Biohaven, Capricor, More Into a ‘Tailspin’

iStock, DesignRage Since July, several biotechs have been forced to pivot as previous agreements with the FDA around evidence required for approval were reversed, a phenomenon that, according to experts, could portend a more restrictive regulator. Last month, uniQure stunned investors and patients alike with the announcement that the FDA had changed its tune on the evidence required for a biologics license application submission for its Huntington’s disease gene therapy. By all accounts, the treatment was on track for market approval based on groundbreaking pivotal three-year data that showed a 75% slowing of the intractable disease. Now, uniQure’s biologics license application, originally planned for early 2026, is up in the air. UniQure is not alone. This year, several other biotechs, including Capricor Therapeutics and Biohaven , have been similarly forced to reassess their timelines after having their best laid—and FDA-authorized—plans reversed. On a recent BioSpace webinar , BMO Capital Markets analyst Evan Seigerman spoke of the “uncertainty” biopharma companies are currently facing with regard to the FDA. He spoke specifically about Replimune, which in July was hit with a surprise rejection for RP1, its candidate for advanced melanoma. “Today, they had one set of guidance from FDA with regard to clinical trial design, or how they could have a unique trial design . . . and then all of a sudden, there’s a 180,” Seigerman said of the company’s experience, “and it throws everything into a tailspin.” The whiplash at the top of the FDA’s ranks could be playing a role in this instability. Since the beginning of 2025, the Center for Drug Evaluation and Research (CDER) has changed hands four times, while its biologics counterpart CBER has seen three different directors—though one, George Tidmarsh, was only in charge for 10 days during current head Vinay Prasad’s short-lived summer absence. Graig Suvannavejh, managing director of Equity Research at Mizuho Securities, put this regulatory variability down to philosophical differences between the current regime and the FDA under past leaders like former CBER Director Peter Marks, “who has said to industry, ‘We’re flexible. We understand that there are areas of high medical need—patients need solutions, they need hope—and we’re open for business.” About today’s FDA, Suvannavejh told BioSpace he believes the agency still wants to be flexible but may “dial up the criteria a bit more where you need to show a more compelling risk/reward profile.” Here, BioSpace looks at four companies in a newfound state of flux after unexpected pushback from the FDA on products that looked destined for the market. uniQure On Sept. 24, uniQure was riding high. The Massachusetts- and Amsterdam–based biotech was gearing up to launch the first-ever genetic treatment for Huntington’s disease after three-year data from a pivotal Phase I/II trial of gene therapy AMT-130 showed 75% slowing of the devastating neurodegenerative disease. Plans were underway to biologics license application (BLA) in the first quarter of 2026, and uniQure’s shares soared 248%. Researchers and patients were ecstatic . Five weeks later, it all came screeching to a halt. Following a pre-BLA meeting, uniQure revealed that the FDA “no longer agrees” that the Phase I/II data for the treatment will be “adequate to provide the primary evidence in support of a BLA submission.” This, despite the company having aligned with the agency on the protocols and statistical analyses used—specifically, comparing AMT-130 to a natural history external control, according to uniQure’s announcement . The company in its announcement called this a “key shift” from multiple type B meetings held with the FDA over the past year. “Consequently, the timing of the BLA submission for AMT-130 is now unclear.” Since uniQure’s latest announcement, more than 10,000 Huntington’s patients, families and supporters have signed two petitions calling for the FDA to reconsider. “For families who have long awaited new treatment options, the FDA’s actions feel like a serious setback and have raised urgent concerns about transparency, consistency, and trust in the regulatory process,” Christina DeGryse, a Huntington’s disease advocate who shared the petitions with BioSpace , wrote in an email. UniQure expects final minutes from the pre-BLA meeting within 30 days of the Nov. 3 announcement. BioSpace reached out for further comment and was informed that the press release contained the only “information” and “perspective” the company would share prior to that time. Huntington’s disease UniQure’s Huntington’s Breakthrough Brings Hope to Patients but Experts Urge Caution Pivotal results from uniQure’s gene therapy for Huntington’s disease have brought new light to patients who have known only disappointment in recent years—but one expert worries that communication of the results is creating “false expectations.” October 27, 2025 · 6 min read · Heather McKenzie Biohaven Biohaven also went to the FDA with an application based on a unique trial design for troriluzole, its candidate for spinocerebellar ataxia (SCA). Like Huntington’s, SCA is a genetic, inherited, life-threatening degenerative disease with no approved treatments. While the NDA was accepted on Feb. 11, the treatment was ultimately rejected earlier this month. In its CRL , the FDA pointed to issues with Biohaven’s Study 206-RWE “that can be inherent to real-world evidence and external control studies, including potential bias, design flaws, lack of pre-specification and unmeasured confounding factors,” according to the company’s November press release announcing the rejection. This was a concern the regulator had apparently communicated in March 2024, when it told the company that “a large and robust treatment effect would be needed” to outweigh the biases associated with a real-world, externally controlled study. Biohaven argued in the same press release that data showing troriluzole slowed patients’ decline by 50% to 70% versus untreated external comparators and delayed disease progression by 1.5 years to 2.2 years met this bar. In a Nov. 5 note to investors, William Blair analysts wrote: “The question will now be if the FDA is becoming more restrictive despite sponsors aligning on prior feedback.” Following the rejection, Biohaven’s stock dropped more than 40%. In turn, the company slashed annual R&D spending by 60% and hit up Wall Street, seeking $150 million . The company has requested a Type A meeting with the FDA to discuss the CRL, according to William Blair. Replimune Cancer-focused Replimune has been riding an FDA-themed rollercoaster. In July, the company was hit with a surprise rejection for its advanced melanoma drug, RP1—again, despite apparent alignment with the FDA on trial design. “The issues highlighted in the CRL were not raised by the agency during the mid- and late-cycle reviews,” CEO Sushil Patel said in a prepared statement along with the company’s press release announcing the rejection of the BLA. “Additionally, we had also aligned on the design of the confirmatory study.” For Replimune, this apparent regulatory reversal has “been quite a flashpoint,” said Seigerman, who covers the company. He and his colleagues at BMO Capital Markets initially suspected that the “final hour shake up” could be the doing of Prasad, who they wrote in a July 22 note, “has previously been critical of the approvability of uncontrolled data.” But it was later revealed by multiple media outlets that Oncology Center of Excellence director—and now CDER head— Richard Pazdur had intervened in the decision. CBER mishandled the RP1 review from the beginning, an anonymous FDA official told STAT News , prompting Pazdur and his team to get involved. Pazdur’s team had raised questions about RP1’s efficacy, according to STAT . In September, following a Type A meeting with the FDA, Replimune issued an ominous press release in which it said that a path forward for RP1 under the accelerated approval pathway “has not been determined.” The revelation caused a nearly 40% crash in the biotech’s stock price. But just when it seemed all hope was lost, the company announced that the FDA had accepted a resubmission for the drug in advanced melanoma. Replimune’s shares soared by around 93% to $8.69 apiece. Duchenne muscular dystrophy With Prasad Back at FDA, Capricor To Fight DMD Cardiomyopathy Rejection Capricor Therapeutics met with the FDA last week for a type A meeting, during which CEO Linda Marbán aimed to explain to the regulator that it got it wrong. Capricor plans to resubmit the application based on deramiocel’s existing dataset. August 20, 2025 · 7 min read · Heather McKenzie Capricor Therapeutics San Diego–based Capricor may have been the first canary for this trend. On July 11, the biotech received a CRL for its cell therapy deramiocel, in development for cardiomyopathy associated with Duchenne muscular dystrophy. In what has since become a familiar refrain, CEO Linda Marbán said during the company’s second-quarter earnings call in August that the rejection “was unexpected given the trajectory of positive interactions” with the FDA. “We believe we consistently met the agency’s expectations throughout the review process,” Marbán said during the same call. Craig McDonald, director of the MDA Neuromuscular Disease Clinics at UC Davis and lead investigator on Capricor’s HOPE-2 and HOPE-3 trials, struck a similar note in an interview with BioSpace in July. “The previous leadership in the FDA really found the data quite compelling and encouraged the BLA submission,” he said . During Capricor’s pre-BLA meeting in August 2024, the biotech requested to switch the primary efficacy endpoint of its Phase III HOPE-3 trial to left ventricular ejection fraction (LVEF), Marbán told investors on the Q2 call. The goal had previously been a change from baseline in upper limb function. The FDA instead encouraged Capricor to submit its application based on currently available data from the Phase II HOPE-2 trial and HOPE-2 open-label extension (OLE) trials matched to an external natural history comparator. A topline readout from HOPE-3 is expected “in the coming weeks,” a company spokesperson told BioSpace by email. Capricor plans to resubmit the BLA for deramiocel “pending the results” of this readout . . . “leveraging the data in support of its application for approval,” according to its third quarter update . .responsive-container { display: flex; flex-wrap: wrap; border: 1px solid #ededed; font-family: Helvetica, Arial, Sans-Serif; padding: 20px 20px 10px 20px; } .column-left { flex: 1; max-width: 45%; padding: 20px 20px 10px 20px; } .column-right { flex: 2; padding: 20px 20px 10px 20px; } @media (max-width: 768px) { .column-left, .column-right { max-width: 100%; flex: 100%; padding: 10px 0; } } Subscribe to ClinicaSpace! Clinical trial results, research news, the latest in cancer, cell and gene therapy hbspt.forms.create({ region: "na1", portalId: "4413123", formId: "674f4dc0-7371-4190-86cc-e1afd00b08ea", onFormSubmitted: function($form, data) { window.dataLayer = window.dataLayer || []; window.dataLayer.push({ 'event': 'GTMevent', 'event_name': 'newsletter_sign_up' }); } });

Phase 3Phase 2Gene Therapy

06 Nov 2025

·www.globenewswire.com

Replimune Reports Fiscal Second Quarter 2026 Financial Results and Provides Corporate Update

WOBURN, Mass., Nov. 06, 2025 (GLOBE NEWSWIRE) -- Replimune Group, Inc. (Nasdaq: REPL), a clinical stage biotechnology company pioneering the development of novel oncolytic immunotherapies, today announced financial results for the fiscal second quarter ended September 30, 2025 and provided a business update. The Company announced on October 20, 2025, that the U.S. Food and Drug Administration (FDA) has accepted the Biologics License Application (BLA) resubmission of RP1 for the treatment of advanced melanoma with a Prescription Drug User Fee Act (PDUFA) target action date set for April 10, 2026. The resubmission is considered by the FDA to be a complete response to the complete response letter received on July 21, 2025. In the Type A meeting minutes, the FDA indicated that the IGNYTE-3 trial could potentially support approval. “After a collaborative dialogue and productive engagement with the FDA we are encouraged by the acceptance of our BLA resubmission for RP1 in combination with nivolumab,” said Sushil Patel, Ph.D., CEO of Replimune. "We are currently partnering with the agency on the ongoing review to bring this important therapy to patients.” Program Highlights & Milestones RP1 (vusolimogene oderparepvec) The global Phase 3 trial, IGNYTE-3 assessing RP1 in combination with nivolumab is ongoing. The trial is expected to enroll approximately 400 patients globally and is evaluating RP1 in combination with nivolumab versus a control arm of physician’s choice in patients with advanced melanoma who have progressed on anti-PD-1 and anti-CTLA-4 therapies or are ineligible for anti-CTLA-4 treatment. The primary endpoint of this trial is overall survival, and key secondary endpoints are progression free survival and overall response rate.Acral melanoma data for RP1 plus nivolumab was recently presented at the ESMO Congress 2025. The analysis of acral melanoma data from the IGNYTE anti-PD-1 failed melanoma cohort showed treatment with RP1 combined with nivolumab resulted in an objective response rate (ORR) of 44% (8/18) with a median duration of response of 11.9 months. The safety profile was favorable with generally transient grade 1 and 2 treatment related adverse events.Additionally, a poster from ESMO featuring data from the IGNYTE clinical trial showed that RP1 plus nivolumab provided responses across multiple advanced non-melanoma skin cancer (NMSC) tumor types, including anti–PD-1 naïve and failed disease, as well as both in locally advanced and metastatic disease. The ORR was 100.0%, 33.3%, 66.7%, and 56.3% in patients with anti–PD-1 naïve MCC, BCC, angiosarcoma, and CSCC, respectively. The ORR was 26.3%, 30.0%, 37.5%, and 15.2% in patients with anti–PD-1 failed MCC, BCC, angiosarcoma, and CSCC, respectively. The IGNYTE clinical trial cohort in NMSC is ongoing.Data from the ongoing ARTACUS Phase 2 trial evaluating the potential of RP1 as monotherapy in cutaneous squamous cell carcinoma patients following organ transplant were recently presented during an oral session at the Society for Melanoma Research 22nd International Congress. A publication for ARTACUS is planned for 2026. RP2 The registration-directed Phase 2/3 REVEAL trial of RP2 in metastatic uveal melanoma is currently enrolling. The clinical trial is expected to enroll approximately 280 patients with metastatic uveal melanoma who are immune checkpoint inhibitor-naïve and evaluate RP2 in combination with nivolumab versus ipilimumab in combination with nivolumab. The primary endpoints of the trial are overall survival and progression free survival, and key secondary endpoints are overall response rate and disease control rate.The Phase 2 clinical trial of RP2 combined with atezolizumab and bevacizumab in anti-PD-1/PD-L1 progressed hepatocellular carcinoma is currently enrolling. The protocol is being amended to include RP2 as monotherapy with data planned by the end of 2026. The trial is being conducted under a collaboration and supply agreement with Roche. The Company also expects to enroll its first patient in the fourth quarter of 2025 in a cohort evaluating RP2 in patients with biliary tract cancer. This cohort will evaluate RP2 combined with durvalumab. Upcoming Events Society for Immunotherapy of Cancer (SITC) 2025 40th Annual Meeting being held November 5th to 9th, 2025: Late-Breaking Oral Presentation: Biomarker and updated clinical data for RP1 plus nivolumab in anti-PD-1 failed melanoma from the IGNYTE trial demonstrate reversal of mechanisms of resistance to immune checkpoint blockade (Abstract 1327, November 7th, 4:45 pm ET)Poster: RP1 plus nivolumab in patients with and without prior BRAF-directed therapy: A subgroup analysis of patients with anti–PD-1 failed BRAF-mutant melanoma from the IGNYTE clinical trial (Poster 611, November 7, 5:35-7:00 pm ET)Poster: Retreatment with RP1 in combination with nivolumab in patients with advanced anti–PD-1 failed melanoma (Poster 600, November 8, 5:10-6:35 pm ET) Financial Highlights Cash Position: As of September 30, 2025, cash, cash equivalents and short-term investments were $323.6 million, as compared to $483.8 million as of fiscal year ended March 31, 2025. The decrease in cash balance was a result of cash burn related to operating activities in advancing the company’s clinical development plans.Based on the current operating plan, the Company believes that existing cash, cash equivalents and short-term investments, as of September 30, 2025 will enable the Company to fund operations late into the fourth quarter of 2026 which includes the potential commercialization of RP1 in skin cancers and for working capital and general corporate purposes and excludes any potential revenue. R&D Expenses: Research and development expenses were $57.9 million for the fiscal second quarter and $43.4 million for the fiscal second quarter ended September 30, 2024. This increase was primarily due to an increase in RP1 direct research costs related to the IGNYTE-3 confirmatory study and other study costs including lab and operating supplies, as well as increased RP2 study costs. In addition, personnel-related costs increased as we continued to prepare for a potential commercial launch of RP1. Research and development expenses included $4.4 million in stock-based compensation expenses for the fiscal second quarter ended September 30, 2025.S,G&A Expenses: Selling, general and administrative expenses were $26.4 million for the fiscal second quarter ended September 30, 2025, as compared to $15.5 million for the fiscal second quarter ended September 30, 2024. Selling, general and administrative expenses included $4.0 million in stock-based compensation expenses for the fiscal second quarter ended September 30, 2025.Net Loss: Net loss was $83.1 million for the fiscal second quarter ended September 30, 2025 and $53.1 million for the fiscal second quarter ended September 30, 2024. About RP1 RP1 (vusolimogene oderparepvec) is Replimune’s lead product candidate and is based on a proprietary strain of herpes simplex virus engineered and genetically armed with a fusogenic protein (GALV-GP R-) and GM-CSF intended to maximize tumor killing potency, the immunogenicity of tumor cell death, and the activation of a systemic anti-tumor immune response. About RP2 RP2 is based on a proprietary strain of herpes simplex virus engineered and genetically armed with a fusogenic protein (GALV-GP R-) and GM-CSF intended to maximize tumor killing potency, the immunogenicity of tumor cell death and the activation of a systemic anti-tumor immune response. RP2 additionally expresses an anti-CTLA-4 antibody-like molecule, as well as GALV-GP R- and GM-CSF. RP2 is intended to provide targeted and potent delivery of these proteins to the sites of immune response initiation in the tumor and draining lymph nodes, with the goal of focusing systemic-immune-based efficacy on tumors and limiting off-target toxicity. About Replimune Replimune Group, Inc., headquartered in Woburn, MA, was founded in 2015 with the mission to transform cancer treatment by pioneering the development of novel oncolytic immunotherapies. Replimune’s proprietary RPx platform is based on a potent HSV-1 backbone intended to maximize immunogenic cell death and the induction of a systemic anti-tumor immune response. The RPx platform is intended to ignite local activity consisting of direct selective virus-mediated killing of the tumor resulting in the release of tumor derived antigens and altering of the tumor microenvironment to then activate a strong and durable systemic response. The RPx product candidates are expected to be synergistic with most established and experimental cancer treatment modalities, leading to the versatility to be developed alone or combined with a variety of other treatment options. For more information, please visit www.replimune.com. Forward Looking StatementsThis press release contains forward looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, including statements regarding our expectations about our cash runway, the status of the FDA review or interactions following the complete response letter, the design and advancement of our clinical trials, the timing and sufficiency of our clinical trial outcomes to support potential approval of any of our product candidates, the regulatory review process and timing of potential product approval, our goals to develop and commercialize our product candidates, patient enrollments in our existing and planned clinical trials and the timing thereof, and other statements identified by words such as “could,” “expects,” “intends,” “may,” “plans,” “potential,” “should,” “will,” “would,” or similar expressions and the negatives of those terms. Forward-looking statements are not promises or guarantees of future performance, and are subject to a variety of risks and uncertainties, many of which are beyond our control, and which could cause actual results to differ materially from those contemplated in such forward-looking statements. These factors include risks related to our limited operating history, our ability to generate positive clinical trial results for our product candidates, the costs and timing of operating our in-house manufacturing facility, the timing and scope of regulatory approvals, the availability of combination therapies needed to conduct our clinical trials, changes in laws and regulations to which we are subject, competitive pressures, our ability to identify additional product candidates, political and global macro factors including the impact of a global pandemic and related public health issues and the ongoing political and military conflicts, including trade conflicts, and other risks as may be detailed from time to time in our Annual Reports on Form 10-K and Quarterly Reports on Form 10-Q and other reports we file with the Securities and Exchange Commission. Our actual results could differ materially from the results described in or implied by such forward-looking statements. Forward-looking statements speak only as of the date hereof, and, except as required by law, we undertake no obligation to update or revise these forward-looking statements. Investor InquiriesChris BrinzeyICR Healthcare339.970.2843chris.brinzey@icrhealthcare.com Media InquiriesArleen GoldenbergReplimune917.548.1582 media@replimune.com Replimune Group, Inc.Condensed Consolidated Statements of Operations(Amounts in thousands, except share and per share amounts)(Unaudited) Three Months EndedSeptember 30, Six Months EndedSeptember 30, 2025 2024 2025 2024 Operating expenses: Research and development$57,877 $43,448 $115,721 $86,420 General and administrative 26,414 15,468 58,994 29,863 Total operating expenses 84,291 58,916 174,715 116,283 Loss from operations (84,291) (58,916) (174,715) (116,283)Other income (expense): Research and development incentives 377 408 797 846 Investment income 3,696 5,394 8,411 10,106 Interest expense on finance lease liability (518) (531) (1,039) (1,065)Interest expense on debt obligations (1,488) (1,438) (2,963) (2,864)Other (expense) income, net (876) 2,028 (284) 2,433 Total other income (expense), net 1,191 5,861 4,922 9,456 Net loss$(83,100) $(53,055) $(169,793) $(106,827)Net loss per common share, basic and diluted$(0.90) $(0.68) $(1.85) $(1.45)Weighted average common shares outstanding, basic and diluted 91,915,769 78,570,135 91,717,076 73,903,650 Replimune Group, Inc.Condensed Consolidated Balance Sheets(Amounts In thousands, except share and per share amounts)(Unaudited) September 30,2025 March 31,2025 (in thousands)Consolidated Balance Sheet Data: Cash, cash equivalents and short-term investments$323,644 $483,804Working capital 280,849 433,518Total assets 389,450 551,328Total stockholders' equity 263,336 415,843

Phase 2Clinical ResultPhase 3Financial StatementImmunotherapy

100 Deals associated with Vusolimogene oderparepvec

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Indication	Highest Phase	Country/Location	Organization	Date
Melanoma	NDA/BLA	United States	Replimune Group, Inc.	21 Nov 2024
Unresectable Melanoma	Phase 3	United States	Replimune, Inc.	11 Jul 2024
Unresectable Melanoma	Phase 3	France	Replimune, Inc.	11 Jul 2024
Unresectable Melanoma	Phase 3	Germany	Replimune, Inc.	11 Jul 2024
Unresectable Melanoma	Phase 3	Poland	Replimune, Inc.	11 Jul 2024
Unresectable Melanoma	Phase 3	Spain	Replimune, Inc.	11 Jul 2024
Unresectable Melanoma	Phase 3	United Kingdom	Replimune, Inc.	11 Jul 2024
Hemangiosarcoma	Phase 2	United States	Replimune, Inc.	31 Oct 2025
Microsatellite instability-high cancer	Phase 2	United States	Replimune, Inc.	30 Jan 2022
Basal Cell Carcinoma	Phase 2	United States	Replimune, Inc.	15 May 2020

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03767348 (IGNYTE, Pubmed \| J Clin Oncol) Manual	Phase 2	Melanoma	140	Vusolimogene oderparepvec + Nivolumab	iljvantlql(ljrlaamajd) = kzxvkuynce lkjdfvzbro (yrxucyidfv, 25.2% - 41.3) View more	Positive	20 Nov 2025
NCT03767348 (IGNYTE, ESMO2025)	Phase 1/2	Skin Neoplasms	99	RP1 + nivo (MCC)	flouacopuj(qhnqsmrhmx) = wdsjxiwkxl mcrsykrofs (izeoukxtey ) View more	Positive	17 Oct 2025
NCT03767348 (IGNYTE, ESMO2025)	Phase 1/2	Skin Neoplasms	99	RP1 + nivo (LA/Met + CSCC)	flouacopuj(qhnqsmrhmx) = kcurydqixm mcrsykrofs (izeoukxtey ) View more	Positive	17 Oct 2025
NCT03767348 (IGNYTE, ESMO2025)	Phase 2	Acral Lentiginous Malignant Melanoma	18	RP1 + nivolumab (acral melanoma)	kwttzplbwe(cbdtcnvmqq) = the most common TRAEs (any grade) were chills, pyrexia, fatigue, injection-site pain, and nausea jcjzmszvce (eqcvveyxqj ) View more	Positive	17 Oct 2025
NCT03767348 (IGNYTE, ASCO2025)	Phase 2	Skin Neoplasms	-	RP1 + nivolumab	swjxgctgxy(ivjwhorasw) = sdyrxdxkbr vqjdzyqupw (xxcmkvkvqs ) View more	-	30 May 2025
NCT06264180 (IGNYTE-3, ASCO2025)	Phase 3	Melanoma BRAF V600-mutant	-	Vusolimogene oderparepvec + Nivolumab	edpzfdtcfr(yblfnzdvtu) = sncqwewmaj wujnjlvwxa (azomtphugj )	Positive	30 May 2025
NCT03767348 (IGNYTE, HOPA2025)	Phase 1/2	Skin Neoplasms	278	RP1 plus nivolumab	cvpzmhrkfj(bharqcwzvk) = oyyknvrkyy qvfcrvnvrz (wzjlogdvow ) View more	Positive	09 Apr 2025
NCT03767348 (IGNYTE, SITC2024 \| NEWS) Manual	Phase 2	Melanoma Second line	140	Vusolimogene oderparepvec + Nivolumab	ropjbdqwkc(njubcgiwhi) = yokahtusov pugsfzpmzq (bvwfnekweb ) View more	Positive	05 Nov 2024
NCT03767348 (IGNYTE, ESMO2024) Manual	Phase 2	Melanoma Second line	140	RP1+nivolumab	micvrlsxtp(pqnmudvmyd) = fqgmlcafvf vxwdsfmyyw (fnoalahrki ) View more	Positive	15 Sep 2024
NCT03767348 (IGNYTE, ESMO2024) Manual	Phase 2	Melanoma Second line	140	RP1+nivolumab (pts with primary anti–PD-1 resistance)	micvrlsxtp(pqnmudvmyd) = qjeqzwbemq vxwdsfmyyw (fnoalahrki )	Positive	15 Sep 2024
NCT03767348 (IGNYTE, Company_Website) Manual	Phase 1/2	Refractory Melanoma Second line	140	RP1 plus nivolumab	pcsewjpnni(yrcwdrzqyu) = kykxiweove blguywsygo (focpfaprkk )	Positive	06 Jun 2024
NCT03767348 (IGNYTE, ASCO2024) Manual	Phase 1/2	Melanoma	156	RP1 + nivolumab	wthaqyhhfd(opxmwbofom) = raakyrjqpt pszpafltjy (ajywpilyst ) View more	Positive	24 May 2024

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