Core Points - Holzer & Holzer, LLC is investigating Replimune Group, Inc. for potential compliance issues with federal securities laws following the receipt of a Complete Response Letter from the FDA regarding its Biologics License Application for RP1 [1] - The FDA's Complete Response Letter indicated that the IGNYTE trial was not considered adequate to provide substantial evidence of effectiveness for the treatment of advanced melanoma [1] - Following the announcement of the CRL, Replimune's stock price experienced a decline [1] Company Information - Replimune Group, Inc. is focused on developing treatments for advanced melanoma, specifically through the use of RP1 in combination with nivolumab [1] - The company is publicly traded on NASDAQ under the ticker REPL [1] Legal Context - Holzer & Holzer, LLC is a law firm specializing in securities litigation, representing shareholders and investors in class action and derivative litigation [3] - The firm has a history of recovering significant amounts for shareholders affected by corporate misconduct [3]

WOBURN, Mass., July 22, 2025 (GLOBE NEWSWIRE) -- Replimune Group, Inc. (NASDAQ: REPL), a clinical stage biotechnology company pioneering the development of novel oncolytic immunotherapies, today announced that the U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) regarding the Biologics License Application (BLA) for RP1 (vusolimogene oderparepvec) in combination with nivolumab for the treatment of advanced melanoma. The CRL indicates that the FDA is unable to approve the ap ...

RP1: IGNITING A SYSTEMIC IMMUNE RESPONSE TO CANCER - IGNYTE trial showed an objective response rate (ORR) of 32.1% by investigator assessment and 33.6% by independent central review in anti-PD1 failed melanoma patients [24, 37] - In the IGNYTE trial, 14.7% of patients achieved a complete response (CR) [24] - In the IGNYTE trial, 17.9% of patients achieved a partial response (PR) [24] - In the IGNYTE trial, 70.4% of responding patients experienced responses in non-injected lesions, demonstrating systemic benefit [28] - Responses in the IGNYTE trial are durable, with 84.2% lasting >6 months, 74.9% lasting >12 months, and 65.2% lasting >18 months [31] - The median duration of response (DOR) in the IGNYTE trial is 36.6 months [31] - In the ARTACUS clinical trial, RP1 monotherapy showed an ORR of 34.8% and a CRR of 21.7% in solid organ transplant (SOT) patients with non-melanoma skin cancers (NMSC) [51] - In locally advanced CSCC, the complete response rate more than doubled for RP1+cemiplimab vs cemiplimab alone (48.1% vs 22.6%) [71] RP2: FOCUSED ON RARE CANCERS - In uveal melanoma, RP2 monotherapy and in combination with nivolumab showed an ORR of 29.4% [90] Financial Status - The company has a strong financial position with cash of $420.7 million as of March 31, 2024, providing a cash runway into the second half of 2026 [114]

Replimune Group (REPL) 2025 Investor Day June 24, 2025 10:00 AM ET ...

RP1 Clinical Trial Results & Opportunities - In anti-PD1 failed melanoma patients, RP1 plus Nivolumab achieved an Objective Response Rate (ORR) of 32.9% and a median Duration of Response (mDoR) of 33.7 months[78] - In responders, responses in non-injected lesions occurred with similar frequency and depth as injected lesions, indicating systemic benefit[78] - Patients with deep/visceral (+/- superficial) injections had numerically higher response rates vs those who received superficial injections only[78] - In solid organ transplant patients with locally advanced CSCC, RP1 monotherapy achieved an ORR of 34.6% and a Disease Control Rate (DCR) of 65.4%[220] - In a study of resectable cutaneous Squamous Cell Carcinoma (cSCC), RP1 monotherapy resulted in a 100% overall response rate, with 83% achieving pathological complete response[214] RPx Platform Expansion & Pipeline - The company is planning RPx expansion into additional skin cancers, liver and thoracic primary/metastatic cancers[174] - A confirmatory Phase 3 trial (IGNYTE-3) is underway in melanoma, randomizing patients to RP1 + Nivolumab vs Treatment of Physician's Choice[179] - A registrational REVEAL study is ongoing for RP2 in metastatic Uveal Melanoma, comparing RP2 + Nivolumab to Ipilimumab + Nivolumab[243] - RP2 is being evaluated in liver primary/metastases, including a cohort with RP2 + Bevacizumab + Atezolizumab in 2L PD-(L)1 failed Hepatocellular Carcinoma (HCC)[246] Commercialization & Market Opportunity - The company estimates ~10,000 addressable patients across lines of therapy for RP1 in the US melanoma market[111] - The company estimates RPx has the potential to reach up to ~125,000 patients in the US across various cancer types[251] - The company has hired and trained a commercial organization of ~60 customer-facing team members[108]

Replimune Group (REPL) 2025 Conference Summary Company Overview - **Company**: Replimune Group (REPL) - **Event**: Jefferies 2025 Healthcare Global Conference - **Date**: June 5, 2025 Key Updates and Core Points 1. **Regulatory Progress**: The company is on track for a PDUFA date on July 22, having completed late cycle meetings and manufacturing inspections, with label negotiations forthcoming [11][61][63] 2. **ASCO Data Highlights**: At the ASCO meeting, Replimune presented data showing RP1's systemic activity in visceral lesions, with increased response rates in deep lesions compared to superficial ones, supporting the hypothesis of enhanced patient outcomes [12][14][19] 3. **Safety Profile**: The safety profile of RP1 was emphasized, with no increased bleeding rates from liver injections and manageable pneumothorax from lung injections, which is crucial for physician confidence [13][14] 4. **Commercialization Strategy**: The company is focusing on logistics and biosafety for RP1, indicating that standard cleaning procedures are sufficient for handling the product, which is not classified as an airborne virus [15][16] 5. **Physician Engagement**: Key opinion leaders (KOLs) are shifting their focus to incorporating RP1 into their practices, with a significant portion of patients having deeper lesions that require image guidance for treatment [19][20] 6. **Market Targeting**: Replimune plans to target approximately 350 accounts in the U.S. that treat over half of melanoma patients, with an initial focus on 150 high-volume accounts for rapid adoption [24][46] 7. **Payer Engagement**: The reimbursement model is favorable, with existing procedural codes supporting the use of RP1, and payers recognizing the unmet need in the disease setting [32][33] 8. **Commercial Infrastructure**: The company has established a commercial team of about 60 people, including sales representatives and interventional radiology coordinators, to support the launch and ensure effective communication with healthcare providers [71][72] 9. **Future Expansion Plans**: Replimune is exploring additional indications for RP1, including non-melanoma skin cancers and earlier disease settings, with ongoing trials in uveal melanoma [80][82] Additional Important Insights 1. **Clinical Trial Insights**: The IGNITE study showed a consistent efficacy response across various patient subgroups, reinforcing the potential for a broad label upon approval [66][68] 2. **Interventional Radiology Role**: Interventional radiologists are expected to play a critical role in the treatment process, with a growing interest in active treatment options like RP1 [53][55] 3. **Operational Efficiency**: The company has managed to keep operational expenses (OpEx) in check, with favorable cost of goods sold (COGS) due to in-house manufacturing capabilities [76][78] 4. **Patient-Centric Approach**: The treatment plan allows flexibility in lesion selection and injection sequence, emphasizing a practical approach to patient care [21][29] This summary encapsulates the key points discussed during the Replimune Group conference, highlighting the company's strategic direction, regulatory progress, and market engagement efforts.

Core Insights - Replimune Group, Inc. presented data on RP1 plus nivolumab at the 2025 ASCO Annual Meeting, highlighting robust responses in both injected and non-injected lesions, with deep injections showing higher response rates compared to superficial injections [1][2][4] Group 1: Clinical Trial Findings - The IGNYTE clinical trial involved 140 anti-PD-1 failed melanoma patients, showing an objective response rate (ORR) of 32.9% and a complete response rate of 15.0% [4] - Landmark overall survival (OS) rates at 1, 2, and 3 years were reported as 75.3%, 63.3%, and 54.8% respectively, with median OS not yet reached [4] - Deep injections resulted in higher ORR: 29.8% for superficial injections, 42.9% for deep/visceral plus superficial injections, and 40.9% for deep/visceral injections only [4] Group 2: Safety and Tolerability - RP1 injections into the liver and lung were generally well tolerated, with few organ-specific adverse events [4] - No bleeding events were reported after liver injections, and lung injections had low rates of pneumothorax, typically of low grade and manageable [4] - Standard disinfection procedures were confirmed sufficient for RP1 clean-up, with no transmission of RP1 reported to date [10] Group 3: Product Information - RP1 is Replimune's lead product candidate, engineered from a proprietary strain of herpes simplex virus, designed to maximize tumor killing potency and activate a systemic anti-tumor immune response [6][8] - The RPx platform aims to induce a strong and durable systemic response while being synergistic with various cancer treatment modalities [8]

Core Viewpoint - Replimune Group, Inc. is set to present at the 2025 Jefferies Global Healthcare Conference, highlighting its focus on developing innovative oncolytic immunotherapies for cancer treatment [1][2]. Company Overview - Replimune Group, Inc. was founded in 2015 and is headquartered in Woburn, MA, with a mission to transform cancer treatment through novel oncolytic immunotherapies [3]. - The company's proprietary RPx platform utilizes a potent HSV-1 backbone aimed at maximizing immunogenic cell death and inducing a systemic anti-tumor immune response [3]. - The RPx platform is designed for dual local and systemic activity, enabling direct virus-mediated tumor killing, which releases tumor-derived antigens and modifies the tumor microenvironment to foster a robust systemic immune response [3]. - Replimune's product candidates are expected to work synergistically with both established and experimental cancer treatment modalities, allowing for versatile development either alone or in combination with other treatment options [3].

Financial Performance and Projections - The company has not generated any revenue from product sales and may never be profitable[168] - The company has incurred net losses since inception and anticipates continuing substantial losses in the foreseeable future, with no products approved for commercial sale to date[243] - For the years ended March 31, 2025 and 2024, the company reported net losses of $247.3 million and $215.8 million, respectively, with an accumulated deficit of $948.6 million as of March 31, 2025[244] - The company anticipates continuing to incur significant losses in the foreseeable future, particularly as it continues research and development for RP1 and other product candidates[244] - Future capital requirements will depend on various factors, including the costs of research and development, obtaining marketing approvals, and commercialization activities[250] - The company may need to expand its internal manufacturing, marketing, and sales capabilities as operations grow, which could impose significant responsibilities on management[228] - Future reimbursement for approved product candidates may be less than projected, impacting net revenue and profitability[238] - The potential market for the company's product candidates is difficult to estimate, and actual markets may be smaller than projected due to reliance on various assumptions[239] Product Development and Regulatory Risks - The FDA has accepted and granted priority review for the company's lead product candidate, RP1[170] - The company faces risks related to product development, including the potential for negative or inconclusive results from clinical trials[171] - The company’s ability to commercialize product candidates is contingent on successful clinical trials demonstrating safety and efficacy[171] - The regulatory approval process is lengthy and unpredictable, potentially impacting the ability to generate revenue[190] - The company may experience delays in testing or approvals, impacting development costs and timelines[176] - The company’s product candidates are in various stages of development and are not approved for commercial sale[168] - The company may require additional financing to achieve its goals due to a history of losses and the likelihood of incurring substantial future losses[168] - The company faces intense competition from other biopharmaceutical and biotechnology companies, which may hinder its ability to commercialize products successfully[219] Collaboration and Supply Chain Challenges - The company has entered into agreements with BMS and Regeneron for the supply of anti-PD-1 therapies for ongoing clinical trials[178] - The company relies on third-party suppliers like BMS and Regeneron for anti-PD-1 therapies, and any failure in these relationships could delay the development and commercialization of its product candidates[270] - Collaboration agreements with partners may not be successful, potentially affecting the company's ability to develop and commercialize its product candidates[271] - The company relies on third-party manufacturers for raw materials and product candidates, which may lead to delays in clinical development and commercialization if performance failures occur[285] - The company has only one in-house manufacturing site, and lacks long-term commitments from suppliers, which could result in supply limitations and potential revenue losses[286] Legal and Compliance Risks - The company faces risks related to intellectual property, including potential infringement claims from third parties and the need to maintain and protect its intellectual property rights[253] - The company may incur substantial costs and face delays if it needs to replace third-party service providers due to performance issues[282] - The company is subject to various healthcare laws, and violations could result in significant penalties and adversely affect financial results[304] - The company is exposed to risks of employee misconduct, which could lead to significant fines or sanctions affecting its financial condition[310] - The company faces potential liabilities under environmental, health, and safety laws, which could result in substantial costs and impact business success[311] Market and Economic Conditions - The stock price of the company has been volatile, influenced by factors such as clinical trial results, regulatory developments, and competition in the biopharmaceutical sector[341] - Unfavorable market conditions could adversely affect the company's ability to raise capital and strain suppliers, impacting overall business performance[359] - Global financial markets are experiencing extreme disruption, leading to volatility in securities prices and potential adverse economic conditions affecting the company's liquidity[360] - Unfavorable global economic conditions and geopolitical events, including military conflicts and trade disputes, could adversely impact the company's operations and objectives[364] Internal Control and Governance - The company has identified material weaknesses in its internal control over financial reporting, which could lead to misstatements in financial statements[330] - The company is implementing comprehensive control protocols to address identified weaknesses in internal controls over financial reporting[334] - Ineffective internal control could increase the risk of financial reporting fraud and misappropriation of assets, potentially leading to regulatory investigations and civil or criminal sanctions[336] - The company did not maintain effective IT general controls relevant to financial statement preparation, increasing the risk of misstatements[332] Environmental and Regulatory Compliance - Compliance with FDA regulations is critical; failure to meet these standards could result in delays in product approvals and commercialization[291] - Legislative and regulatory changes in healthcare could increase compliance costs and adversely affect the ability to market products and achieve profitability[307] - Compliance with the Drug Supply Chain Security Act (DSCSA) may increase operational expenses and impose significant administrative burdens[309] - The company is subject to stringent data privacy and security obligations, with potential penalties for non-compliance that could adversely affect financial condition[313]

Financial Data and Key Metrics Changes - The company ended the fiscal year with cash and cash equivalents totaling $483.8 million, compared to $420.7 million at the end of the previous fiscal year, indicating a year-over-year increase of approximately 15% [21] - Research and development expenses for the fiscal fourth quarter were $54 million, up from $42.6 million in the same quarter of the previous year, reflecting a 27% increase [22] - The net loss for the fiscal fourth quarter was $74.1 million, compared to a net loss of $55.1 million in the same quarter of the previous year, representing a 34% increase in losses [23] Business Line Data and Key Metrics Changes - The company is preparing for the potential approval and launch of RP-one, which is positioned as a first choice for advanced melanoma patients who have previously received an anti PD-one regimen [6][7] - The IGNITE-three confirmatory study is underway, with a primary endpoint of overall survival, and enrollment in the US is on track with over 100 sites planned globally [7] Market Data and Key Metrics Changes - Approximately 13,000 patients progress on or after PD-one treatment annually in the US, with about 80% of these patients eligible for RP-one [11] - The company has identified roughly 350 key accounts that treat half of the melanoma population, indicating a focused approach for the launch [15] Company Strategy and Development Direction - The company aims to establish RPX as a new interventional immuno-oncology treatment paradigm, focusing on deep lesion injections to benefit patients beyond skin cancer [8] - The company has completed the build-out of its customer-facing organization and is well-capitalized to execute its commercialization plans [8][16] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the upcoming PDUFA date and the potential for RP-one to address significant unmet needs in advanced melanoma treatment [6][40] - The company has received breakthrough designation and priority review from the FDA, with no impediments expected for the July 22 PDUFA date [40][41] Other Important Information - The company is planning an Investor Day for June 24, where it will discuss the current melanoma landscape and the RP-one roadmap for commercial success [20] - The company has a comprehensive understanding of the market landscape, prescriber adoption, and referral patterns, which supports the anticipated broad and rapid adoption of RP-one [12][15] Q&A Session Summary Question: What sort of medical education work are you going to be doing at ASCO ahead of the launch of RP-one? - The company will present important posters at ASCO, including data on systemic and visceral activity, and will share response rates for different lesion types [25][26] Question: Can you give us some color around your expectation for the launch trajectory? - The company anticipates broad and rapid adoption across hospitals and communities, with a heavier lift initially within the hospital setting [30][32] Question: Can you discuss the impact you're seeing from the recent regulatory changes? - The company has seen committed engagement from the FDA and completed necessary inspections, feeling well-positioned for the upcoming PDUFA [38][40] Question: Could you just talk to your experience to date with the IGNITE III trial? - The company is focusing on enrolling US sites for the IGNITE III trial and expects to see continued enrollment in other countries post-PDUFA [45][47] Question: Can you talk about manufacturing resiliency and cost of goods profile? - The company has invested in manufacturing early, ensuring sufficient inventory for rapid support at launch and attractive cost of goods [52][53] Question: What are the gating factors that exist between now and the PDUFA date? - The company has completed inspections and discussions on CMC, feeling confident there are no bottlenecks towards the PDUFA date [58][61]