On February 12, 2025 Biogen Inc. (NASDAQ: BIIB) reported fourth quarter and full year 2024 financial results (Press release, Biogen, FEB 12, 2025, View Source [SID1234650209]). Commenting on the results, President and Chief Executive Officer Christopher A. Viehbacher said:

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"We believe 2024 was an important year on our journey to deliver long-term sustainable growth. We delivered continued revenue growth from our ongoing product launches including LEQEMBI, where we believe there remains a significant long-term opportunity. We also achieved key development milestones across our late-stage pipeline, where we continue to prioritize high-conviction assets with the potential to drive growth well into the next decade. Our financial discipline has enabled a restructuring of our operating expenses with a reallocation of resources toward potential future growth drivers. We believe that continued execution against these key strategic elements, as well as a disciplined approach to business development, will allow us to generate long-term value for our shareholders by bringing innovative medicines to patients."

Financial Highlights
Q4 ’24 Q4 ’23 △
r (CC*)
FY ’24 FY ’23 △
r (CC*)
Total Revenue (in millions) $2,455 $2,386 3% 2% $9,676 $9,836 (2)% (2)%
GAAP diluted EPS $1.83 $1.71 7% N/A $11.18 $7.97 40% N/A
Non-GAAP diluted EPS $3.44 $2.95 17% N/A $16.47 $14.72 12% N/A

Note: Percent changes represented as favorable/(unfavorable) versus the prior year period.
N/A = not applicable.
* Percentage changes in revenue growth at constant currency (CC) are presented excluding the impact of changes in foreign currency exchange rates and hedging gains or losses. Foreign currency revenue values are converted into U.S. dollars using the exchange rates from the end of the previous calendar year.

A reconciliation of GAAP to Non-GAAP financial measures can be found in Table 4 at the end of this news release.
Revenue Summary
(In millions, except percentages) Q4 ’24 Q4 ’23 △
r (CC#)
FY ’24 FY ’23 △ △ (CC#)
Multiple Sclerosis (MS) product revenue(1)
$1,070 $1,168 (8)% (9)% $4,350 $4,662 (7)% (7)%
Rare disease revenue(2)
$535 $472 13% 15% $1,988 $1,803 10% 11%
Biosimilars revenue $202 $188 7% 4% $793 $770 3% 2%
Other product revenue(3)
$26 $4 NMF NMF $83 $12 NMF NMF
Total product revenue $1,833 $1,832 —% —% $7,214 $7,247 —% —%
Revenue from anti-CD20 therapeutic programs $465 $436 7% 7% $1,750 $1,690 4% 4%
Alzheimer’s collaboration revenue(4)
$27 $2 NMF NMF $60 $— NMF NMF
Contract manufacturing, royalty and other revenue $130 $117 12% 9% $653 $899 (27)% (28)%
Total revenue $2,455 $2,386 3% 2% $9,676 $9,836 (2)% (2)%

Note: Percent changes represented as favorable/(unfavorable) versus the prior year period. Numbers may not foot or recalculate due to rounding.
NMF = no meaningful figure.
(1) MS includes TECFIDERA, VUMERITY, AVONEX, PLEGRIDY, TYSABRI and FAMPYRA.
(2) Rare disease includes SPINRAZA, SKYCLARYS and QALSODY.
(3) Other includes ZURZUVAE, ADUHELM and FUMADERM.
(4) Includes Biogen’s 50% share of net revenue and cost of sales, including royalties, from the LEQEMBI Collaboration.
•Fourth quarter and full year 2024 ZURZUVAE revenue was approximately $23 million and approximately $72 million, respectively.
Expense Summary
(In millions, except percentages) Q4 ’24 Q4 ’23 △ FY ’24 FY ’23 △
GAAP cost of sales*
$583 $618 6% $2,310 $2,533 9%
% of Total Revenue 24% 26% 24% 26%
Non-GAAP cost of sales*
$540 $587 8% $2,137 $2,502 15%
% of Total Revenue 22% 25% 22% 25%
GAAP R&D expense $532 $571 7% $2,042 $2,462 17%
Non-GAAP R&D expense $528 $568 7% $1,930 $2,262 15%
GAAP SG&A expense $680 $609 (12)% $2,404 $2,550 6%
Non-GAAP SG&A expense $673 $588 (14)% $2,340 $2,277 (3)%

Note: Percent changes represented as favorable/(unfavorable) versus the prior year period
*Excluding amortization and impairment of acquired intangible assets

2

•The decrease in fourth quarter 2024 GAAP and Non-GAAP cost of sales as a percentage of total revenue was driven primarily by lower idle capacity charges.

•The decrease in full year 2024 GAAP and Non-GAAP cost of sales as a percentage of total revenue was driven primarily by product mix, particularly the year-over-year increase in revenue from new product launches, a decrease in contract manufacturing revenue, and lower idle capacity charges.

•The decrease in fourth quarter and full year 2024 GAAP and Non-GAAP R&D expense was driven primarily by savings from the Company’s R&D prioritization and Fit for Growth initiatives.

•The increase in fourth quarter 2024 GAAP and Non-GAAP SG&A was driven primarily by sales and marketing spend to support product launches, partially offset by savings from the Company’s Fit for Growth initiative.

•Full year 2024 GAAP and Non-GAAP SG&A includes higher operational spending on sales and marketing activities in support of LEQEMBI and SKYCLARYS, which was partially offset by cost-reduction measures realized in connection with the Company’s Fit for Growth program.
Other Financial Highlights

•Fourth quarter 2024 GAAP and Non-GAAP collaboration profit sharing was a net expense of approximately $57 million. This includes approximately $51 million related to Biogen’s collaboration with Samsung Bioepis, and approximately $6 million related to Biogen’s collaboration with Sage Therapeutics related to the commercialization of ZURZUVAE in the U.S.

•Full year 2024 GAAP and Non-GAAP collaboration profit sharing was a net expense of approximately $254 million. This includes approximately $227 million related to Biogen’s collaboration with Samsung Bioepis, and approximately $27 million related to Biogen’s collaboration with Sage Therapeutics related to the commercialization of ZURZUVAE in the U.S.

•Fourth quarter 2024 GAAP other expense was approximately $150 million and includes approximately $78 million of net losses on strategic equity investments and approximately $42 million of net interest expense. Fourth quarter 2024 Non-GAAP other expense was approximately $72 million, primarily driven by net interest expense.

•Full year 2024 GAAP other expense was approximately $344 million and includes approximately $183 million of net interest expense and approximately $100 million of net losses on strategic equity investments. Full year 2024 Non-GAAP other expense was approximately $243 million, primarily driven by net interest expense.

•Fourth quarter 2024 GAAP and Non-GAAP effective tax rates were 8.5% and 12.2%, respectively. Fourth quarter 2023 GAAP and Non-GAAP effective tax rates were 14.7% and 17.0%, respectively.

•Full year 2024 GAAP and Non-GAAP effective tax rates were 14.4% and 14.6%, respectively. Full year 2023 GAAP and Non-GAAP effective tax rates were 10.4% and 15.2%, respectively.
Financial Position

•Fourth quarter 2024 net cash flow from operations was approximately $761 million. Capital expenditures were approximately $39 million, and free cash flow, defined as net cash flow from operations less capital expenditures, was approximately $722 million.

•Full year 2024 net cash flow from operations was approximately $2.9 billion. Capital expenditures were approximately $154 million, and free cash flow, defined as net cash flow from operations less capital expenditures, was approximately $2.7 billion.

3

•As of December 31, 2024, Biogen had cash and cash equivalents totaling approximately $2.4 billion with approximately $6.3 billion in total debt, resulting in net debt of approximately $3.9 billion.

•For the fourth quarter of 2024 the Company’s weighted average diluted shares were 146 million. For full year 2024 the Company’s weighted average diluted shares were 146 million.

Full Year 2025 Financial Guidance

For the full year 2025, Biogen expects a Non-GAAP diluted EPS guidance range as follows:
Full Year 2025 Guidance
Non-GAAP diluted EPS
$15.25 to $16.25

This Non-GAAP diluted EPS guidance range, which is based upon FX rates on February 7th, 2025, includes a headwind of approximately $0.35 from foreign exchange when compared to average exchange rates in 2024.

Total revenue is expected to decline by a mid-single digit percentage for 2025 compared to 2024 as further declines in multiple sclerosis product revenue are expected to be partially offset by increases in revenue from product launches.

For 2025 as compared to 2024, Biogen expects operating margin percentage to remain relatively flat. The Fit for Growth program is expected to generate approximately $1 billion of gross savings and $800 million net of reinvestment by the end of 2025. Since the program was initiated in 2023, approximately $400 million of net savings have been achieved, and Biogen expects to realize the balance by the end of 2025. Biogen expects combined Non-GAAP R&D expense and Non-GAAP SG&A expense to total approximately $3.9 billion in 2025.

This financial guidance does not include any impact from potential acquisitions or business development transactions or pending and future litigation or any impact of potential tax or healthcare reform, as all are hard to predict.

This guidance also assumes that foreign exchange rates as of February 7, 2025, will remain in effect for the remainder of the year, net of hedging activities. Other modeling considerations will be provided on the conference call and webcast.

Biogen may incur charges, realize gains or losses, or experience other events or circumstances in 2025 that could cause any of these assumptions to change and/or actual results to vary from this financial guidance.

Biogen does not provide guidance for GAAP reported financial measures (other than revenue) or a reconciliation of forward-looking Non-GAAP financial measures to the most directly comparable GAAP reported financial measures because the Company is unable to predict with reasonable certainty the financial impact of items such as the transaction, integration, and certain other costs related to acquisitions or large business development transactions; unusual gains and losses; potential future asset impairments; gains and losses from equity security investments; and the ultimate outcome of pending or future significant litigation without unreasonable effort. These items are uncertain, depend on various factors, and could have a material impact on GAAP reported results for the guidance period. For the same reasons, the Company is unable to address the significance of the unavailable information, which could be material to future results.

Key Recent Events

•As part of ongoing pipeline prioritization efforts, Biogen has decided to discontinue further development of BIIB113 in early Alzheimer’s disease, BIIB094 in early Parkinson’s disease, BIIB101 in multiple system atrophy, and BIIB143 (cemdomespib) in diabetic peripheral neuropathic pain.

4

•In February 2025, Royalty Pharma plc announced that it had entered into an agreement with Biogen to provide research and development funding of up to $250 million for litifilimab. Following potential regulatory approval, Royalty Pharma plc will be eligible for regulatory milestones and royalties of a mid-single digits percentage of the applicable net sales.

Conference Call and Webcast

The Company’s earnings conference call for the fourth quarter will be broadcast via the internet at 8:30 a.m. ET on February 12, 2025 and will be accessible through the Investors section of Biogen’s website, www.biogen.com. Supplemental information in the form of a slide presentation is also accessible at the same location on the internet and will be subsequently available on the website for at least 90 days.

On February 12, 2025 Artera, the developer of multimodal artificial intelligence (MMAI)-based prognostic and predictive cancer tests, and Tempus, a technology company leading the adoption of AI to advance precision medicine and patient care, reported that they will collaborate to expand access to the ArteraAI Prostate Test (Press release, Tempus, FEB 12, 2025, View Source [SID1234650227]). Through the collaboration, Tempus and Artera will work together in an exclusive manner to commercialize Artera’s prostate cancer risk stratification test. Tempus is currently connected to more than 50% of all oncologists practicing in the United States.

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"We are looking forward to collaborating with Artera to expand access to Artera’s current prostate cancer test," said Ezra Cohen, MD, Chief Medical Officer at Tempus. "Management of localized prostate cancer has always been a balance between doing too much and not enough. Now, by combining our efforts, we can empower clinicians and patients with critical insights to allow an informed decision at this crucial point in their treatment journey, ensuring that each patient receives the care that is right for them."

The ArteraAI Prostate Test is an AI-enabled test that provides predictive and prognostic results for patients with localized prostate cancer. The first of its kind, the test provides actionable insights to empower shared decision-making between the patient and clinician to help personalize treatment plans. Test results can be received in 1-2 days after receiving the patient’s specimen. The test is the first AI risk stratification tool for patients with localized prostate cancer recommended by the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prostate Cancer, and the only test included for its predictive performance regarding the use of short-term androgen deprivation therapy (ADT). The company will roll out new tests for additional indications in the future.

"Collaborating with Tempus is a powerful validation of the hard work and dedication our team at Artera has put into advancing precision medicine," said Andre Esteva, CEO and co-founder of Artera. "With Tempus’ unmatched expertise, depth, and broad reach, this collaboration strengthens our shared mission to revolutionize patient care and drive breakthroughs in the field of oncology."

On February 12, 2025 Orca Bio, a late-stage biotechnology company committed to transforming the lives of patients through high-precision cell therapy, reported positive data on its investigational allogeneic T-cell immunotherapies will be presented across four sessions at the 2025 Tandem Meetings of ASTCT and CIBMTR, February 12-15, 2025, in Honolulu, HI (Press release, Orca Bio, FEB 12, 2025, View Source;utm_medium=rss&utm_campaign=orca-bio-presents-positive-phase-1-and-1b-data-on-orca-t-and-orca-q-at-the-2025-tandem-meetings-of-astct-and-cibmtr [SID1234650210]).

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"We are pleased to present positive findings across four presentations at the 2025 Tandem Meetings, underscoring our commitment to engaging global experts in a collective effort to advance the field for patients and the physicians who treat them," said Scott McClellan, MD, chief medical officer at Orca Bio. "These data add to our growing body of clinical evidence which reinforces the potential of our high-precision approach to offer new and potentially transformative treatment options for patients."

Highlights include:

New research that sheds light on early T-cell activation following treatment with Orca Bio’s lead investigational allogeneic T-cell immunotherapy, Orca-T, compared with unmanipulated peripheral blood stem cell grafts, in addition to the identification of a novel T-cell subset which may be predictive of long-term immune activation after Orca-T administration.
Three-year follow-up data from the Phase 1b trial of Orca-T demonstrating improved overall survival in AML, ALL and high-risk MDS patients compared to a conventional allogeneic stem cell transplant (alloHSCT) with post-transplant cyclophosphamide (PTCy)-based GvHD prophylaxis. Results previously presented at the 2024 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.
Encouraging results from a single-center open-label Phase 1 study of an expanded group of older patients treated with Orca Bio Orca-T and a reduced-intensity conditioning (RIC) regimen. Cohorts of fewer patients were previously presented at the 2023 ASH (Free ASH Whitepaper) Annual Meeting and the 50th Annual Meeting of the EBMT.
Results from the Phase 1 trial of Orca Bio’s second investigational allogeneic T-cell immunotherapy, Orca-Q, demonstrating promising outcomes without the use of pharmacological GvHD prophylaxis in patients with fully matched donors. Data previously presented at the 2024 ASH (Free ASH Whitepaper) Annual Meeting.
The abstracts are available at www.tandemmeetings.com. Details of the presentations follow:

Oral Session: Session L – Autoimmune Disease and Immune Reconstitution

Title: FOXP3 and Helios Expressing CD4+ T Conventional Cells Correlate with T Cell Activation after Orca-T Allogeneic T Cell Immunotherapy

Date and Time: February 15, 2025 at 10:30 AM HST

Location: Ballroom C (HCC)

Poster Session: Acute and Chronic Leukemia (AML, MDS, MPD ALL, CML) – Clinical

Title: Observational Comparison of Overall Survival between Phase 1b Orca-T and Registry-Based Post-Transplant Cyclophosphamide Patients

Date and Time: February 13, 2025 at 6:45 PM HST

Location: Exhibit Hall 3 (HCC)

Poster Session: Graft-versus-Host and Graft-versus-Tumor – Clinical: Prevention, Treatment and Biomarkers

Title: Phase 1 Trial Results for Patients with Advanced Hematologic Malignancies Treated with Allogeneic T Cell Immunotherapy and Reduced Intensity Conditioning

Date and Time: February 13, 2025 at 6:45 PM HST

Location: Exhibit Hall 3 (HCC)

Poster Session: Acute and Chronic Leukemia (AML, MDS, MPD ALL, CML) – Clinical

Title: Preliminary Safety and Efficacy of Myeloablative Orca-Q with No GvHD Prophylaxis for Treatment of Advanced Hematologic Malignancies

Date and Time: February 13, 2025 at 6:45 PM HST

Location: Exhibit Hall 3 (HCC)

About Orca-T
Orca-T is an investigational allogeneic T-cell immunotherapy being evaluated in clinical trials for the treatment of multiple hematologic malignancies. Orca-T is comprised of highly purified regulatory T-cells, CD34+ stem cells and conventional T-cells derived from peripheral blood from either related or unrelated matched donors. Orca-T is currently being evaluated in Precision-T, a pivotal Phase 3 clinical trial, which has completed enrollment at leading transplant centers across the U.S. Orca-T has received Regenerative Medicine Advanced Therapy (RMAT) designation from the U.S. Food and Drug Administration.

On February 12, 2025 Ferring Pharmaceuticals reported three abstracts featuring ADSTILADRIN (nadofaragene firadenovec-vncg) will be presented at the 2025 American Society of Clinical Oncologists Genitourinary Cancers (ASCO GU) Symposium held February 13-15 in San Francisco (Press release, Ferring Pharmaceuticals, FEB 12, 2025, View Source [SID1234650228]). ADSTILADRIN is the first and only intravesical non-replicating gene therapy approved by the U.S. Food and Drug Administration (FDA) for patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors (±Ta/T1).

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Mayo Clinic will present additional updated early results in a poster presentation of an independent, retrospective real-world outcomes study conducted at three of their sites. The study is evaluating complete response rates, high-grade recurrence-free survival, cystectomy-free survival, overall survival, and adverse events among patients treated with ADSTILADRIN for high-risk BCG-unresponsive NMIBC.

"Understanding real-world outcomes in patients with BCG-unresponsive NMIBC is essential for informing how we approach treatment and deliver care," said Mark D. Tyson, M.D., urologic oncologist and associate professor, Mayo Clinic, Scottsdale, Ariz., and principal investigator of this independent study. "These initial encouraging post-marketing results provide valuable insights into the benefits of using ADSTILADRIN in everyday clinical practice, allowing providers to make more informed decisions and deliver the best possible care for patients."

Additional abstracts to be presented include the study protocols for two studies in the ABLE (ADSTILADRIN in BLadder CancEr) clinical trial program – the three-arm ABLE-22 study and the two-arm ABLE-32 study. Clinical sites were recently activated for both studies which are investigating the efficacy and safety of ADSTILADRIN in high-risk and intermediate-risk NMIBC.

"These real-world data extend the body of evidence for efficacy, safety, and low treatment burden of ADSTILADRIN in NMIBC patients who no longer respond to BCG, building on the positive five-year results from our pivotal Phase 3 trial announced last year," said Bipin Dalmia, Global Head of Uro-Oncology & Urology Franchise, Ferring Pharmaceuticals. "As the first and only FDA approved intravesical bladder-sparing monotherapy for BCG-unresponsive NMIBC patients, ADSTILADRIN is fully available throughout the United States, offering a convenient quarterly dosing schedule that may help encourage treatment adherence. The continuation of our clinical trial program further highlights our commitment to advancing the science in our journey to establish ADSTILADRIN as the new standard of care and backbone therapy across the urothelial cancer disease spectrum."

About ADSTILADRIN Presentations at ASCO (Free ASCO Whitepaper) GU
ADSTILADRIN poster titles and presentation times at ASCO (Free ASCO Whitepaper) GU, February 13-15, 2025, are:

Real-world outcomes of nadofaragene firadenovec in BCG-unresponsive non-muscle invasive bladder cancer. Abstract #716 (Poster #D13), Friday, February 14, 11:30 a.m. PST
ABLE-22: Safety and efficacy evaluation of nadofaragene firadenovec alone or in combination with chemotherapy or immunotherapy—a randomized, open-label, phase 2 study. Abstract #TPS891 (Poster #J19), Friday, February 14, 11:30 a.m. PST
ABLE-32: A randomized, controlled, phase 3B clinical trial of nadofaragene firadenovec-vncg versus observation in patients with intermediate-risk non–muscle-invasive bladder cancer. Abstract #TPS888 (Poster #J16), Friday, February 14, 11:30 a.m. PST
About ABLE-22 and ABLE-32
ABLE-22 (NCT06545955) is a three-arm, Phase 2 trial evaluating ADSTILADRIN as a monotherapy and as part of combination with chemotherapy or an immune checkpoint inhibitor in patients with high-risk BCG-unresponsive NMIBC. Investigators in all three arms of the ABLE-22 study will have the option to re-induce appropriate patients who do not achieve a complete response to the initial single dose or combination regimen, an option that was not included in the original Phase 3 study.

The Phase 3B ABLE-32 (NCT06510374) trial is assessing ADSTILADRIN in patients with intermediate-risk NMIBC (IR NMIBC), for which there are no U.S. FDA-approved treatment options.

About ADSTILADRIN
ADSTILADRIN (nadofaragene firadenovec-vncg) is the first and only FDA-approved intravesical non-replicating gene-therapy for the treatment of adult patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors. It is a non-replicating adenovirus vector-based therapy containing the gene interferon alfa-2b, administered locally as a monotherapy by catheter directly into the bladder once every three months. The vector enters the cells of the bladder wall, releasing the active gene and causing the bladder’s cell walls to secrete high and transient local expression of interferon alfa-2b protein, a naturally occurring protein the body uses to fight cancer. This approach essentially turns the bladder wall cells into interferon microfactories, enhancing the body’s own natural defenses against the cancer.

ADSTILADRIN has been studied in a clinical trial program that includes 157 patients with high-risk, BCG-unresponsive NMIBC who had been treated with adequate BCG previously and did not see benefit from additional BCG treatment (full inclusion criteria published on clinicaltrials.gov: NCT02773849).1

Ferring is leading the future in uro-oncology treatment with ADSTILADRIN at the center, while expanding access with the support of new, state-of-the-art manufacturing facilities. As announced in January 2024, ADSTILADRIN is fully available and accessible in the U.S. ADSTILADRIN has confirmed 99 percent coverage for commercial and government-insured patients. As of April 1, 2024, in accordance with the Centers for Medicare and Medicaid Services (CMS), ADSTILADRIN established an Average Sales Price (ASP). Since the establishment of ASP, all covered claims submitted for reimbursement have received payment within an average of 25 days.2

Ferring is committed to investing in novel therapies, developing life-changing solutions that address unmet medical needs, and aiding the uro-oncology community in helping patients live better lives. More information is available in the U.S. at FerringUroOncology.com and on the dedicated Ferring Uro-Oncology channels on LinkedIn and X.

About Non-Muscle Invasive Bladder Cancer (NMIBC)
NMIBC is a form of bladder cancer that is found in the inner layer cells of the bladder and does not invade into or beyond the muscle wall.3 In the United States, bladder cancer is the sixth most common cancer,4 fourth among men,5 and it is estimated that there will be approximately 84,870 new cases of bladder cancer in the U.S. in 2025.5 Historically, 75% of bladder cancer presents as NMIBC.6 In patients with high-risk NMIBC, intravesical BCG remains the first-line standard-of-care. However, approximately one third of patients with NMIBC will not respond to BCG therapy and 50% of those with an initial response will experience recurrence or progression of their disease.7 Current treatment options for BCG-unresponsive patients are very limited, and National Comprehensive Cancer Network (NCCN) guidelines recommend cystectomy (partial or complete removal of the bladder).8

INDICATION
ADSTILADRIN is a non-replicating adenoviral vector-based gene therapy indicated for the treatment of adult patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS: ADSTILADRIN is contraindicated in patients with prior hypersensitivity reactions to interferon alfa or to any component of the product.

WARNINGS AND PRECAUTIONS:

Risk with delayed cystectomy: Delaying cystectomy in patients with BCG-unresponsive CIS could lead to development of muscle invasive or metastatic bladder cancer, which can be lethal. If patients with CIS do not have a complete response to treatment after 3 months or if CIS recurs, consider cystectomy.
Risk of disseminated adenovirus infection: Persons who are immunocompromised or immunodeficient may be at risk for disseminated infection from ADSTILADRIN due to low levels of replication-competent adenovirus. Avoid ADSTILADRIN exposure to immunocompromised or immunodeficient individuals.
DOSAGE AND ADMINISTRATION: Administer ADSTILADRIN by intravesical instillation only. ADSTILADRIN is not for intravenous use, topical use, or oral administration.

USE IN SPECIFIC POPULATIONS: Advise females of reproductive potential to use effective contraception during ADSTILADRIN treatment and for 6 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during ADSTILADRIN treatment and for 3 months after the last dose.

ADVERSE REACTIONS: The most common (>10%) adverse reactions, including laboratory abnormalities (>15%), were glucose increased, instillation site discharge, triglycerides increased, fatigue, bladder spasm, micturition (urination urgency), creatinine increased, hematuria (blood in urine), phosphate decreased, chills, pyrexia (fever), and dysuria (painful urination).

You are encouraged to report negative side effects of prescription drugs to FDA. Visit www.FDA.gov/medwatch or call 1-800-332-1088. You may also contact Ferring Pharmaceuticals at 1-888-FERRING.

Please click to see the full Prescribing Information.

On February 12, 2025 Replimune Group, Inc. (Nasdaq: REPL), a clinical stage biotechnology company pioneering the development of novel oncolytic immunotherapies, reported financial results for the fiscal third quarter ended December 31, 2024 and provided a business update (Press release, Replimune, FEB 12, 2025, View Source [SID1234650211]).

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"Over the past couple of months, we have achieved significant regulatory milestones for RP1 in anti-PD-1 failed melanoma," said Sushil Patel, Ph.D., CEO of Replimune. "With Priority Review and a PDUFA date set for July 22, 2025, by the FDA, our efforts are focused on ensuring a successful commercial launch of RP1 upon approval. Our commercial strategy is built on a deep understanding of the patient population and prescriber landscape, coupled with a launch model designed to effectively deliver intratumoral therapy. With over $500 million in cash, we are well-capitalized to execute our plans and are excited to provide further updates as we transition to a commercial-stage company."

Program Highlights & Milestones

RP1

RP1 combined with Opdivo (nivolumab) in anti-PD1 failed melanoma
In January, the FDA accepted the BLA for RP1 in combination with nivolumab for patients with advanced melanoma. The BLA was granted Priority Review by the FDA with a PDUFA action date of July 22, 2025.
The BLA is supported by the primary analysis data of the IGNYTE trial, evaluating RP1 combined with nivolumab in patients with anti-PD-1 failed melanoma.
Enrolling into the confirmatory Phase 3 trial, IGNYTE-3, with over 100 sites planned globally. This trial will assess RP1 in combination with nivolumab 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.
RP2

RP2 in uveal melanoma
Enrolled the first patient in a registration-directed study of RP2 in metastatic uveal melanoma in patients who are immune checkpoint inhibitor-naïve. The study will enroll approximately 280 patients and evaluate RP2 in combination with nivolumab versus ipilimumab in combination with nivolumab. The primary endpoints of the study are overall survival and progression free survival and key secondary endpoints are overall response rate and disease control rate.
RP2 in hepatocellular carcinoma (HCC)
Enrolled the first patient in a Phase 2 clinical trial with RP2 combined with atezolizumab and bevacizumab in anti-PD1/PD-L1 progressed HCC. The trial is an open label trial that will enroll 30 patients and evaluate RP2 combined with the second-line therapy of atezolizumab and bevacizumab. The study is being conducted under a collaboration and supply agreement with Roche.
Financial Highlights

Financing: Completed a public offering of shares of the Company’s common stock and pre-funded warrants, raising approximately $156.0 million net of issuance costs. Proceeds from the financing will be used to fund the continued development of our RPx platform, including expanding our ongoing studies within RP1 and broadening clinical development plans for RP2, as well as for working capital and general corporate purposes.
Cash Position: As of December 31, 2024, cash, cash equivalents and short-term investments were $536.5 million, as compared to $420.7 million as of fiscal year ended March 31, 2024. The increase in cash balance was directly related to the public offering in November, somewhat offset by cash utilized in 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 December 31, 2024 will enable the Company to fund operations into the fourth quarter of 2026 which includes scale up for 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 $48.0 million for the fiscal third quarter ended December 31, 2024, as compared to $42.8 million for the fiscal third quarter ended December 31, 2023. This increase was primarily due to an increase in personnel-related costs, as well as consulting and facility-related costs. Research and development expenses included $4.6 million in stock-based compensation expenses for the fiscal third quarter ended December 31, 2024.
S,G&A Expenses: Selling, general and administrative expenses were $18.0 million for the fiscal third quarter ended December 31, 2024, as compared to $13.7 million for the fiscal third quarter ended December 31, 2023. Selling, general and administrative expenses included $4.1 million in stock-based compensation expenses for the fiscal third quarter ended December 31, 2024.
Net Loss: Net loss was $66.3 million for the fiscal third quarter ended December 31, 2024, as compared to a net loss of $51.1 million for the fiscal third quarter ended December 31, 2023.
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.