On February 12, 2025 Pfizer Inc. (NYSE: PFE) reported that the U.S. Food and Drug Administration (FDA) has approved the supplemental Biologics License Application (sBLA) for ADCETRIS (brentuximab vedotin) in combination with lenalidomide and a rituximab product for the treatment of adult patients with relapsed or refractory large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), DLBCL arising from indolent lymphoma, or high-grade B-cell lymphoma (HGBL), after two or more lines of systemic therapy who are not eligible for autologous hematopoietic stem cell transplantation (auto-HSCT) or chimeric antigen receptor (CAR) T-cell therapy (Press release, Seagen, FEB 12, 2025, View Source [SID1234650213]).

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"Each year, more than 3,500 patients in the U.S. with this aggressive form of non-Hodgkin lymphoma experience treatment failure or relapse after two prior lines of therapy," said Roger Dansey, M.D., Chief Oncology Officer, Pfizer. "Today’s approval further reinforces the important role of ADCETRIS as an existing standard of care with overall survival improvement shown for certain types of lymphomas, and now allows physicians to have an option beyond chemotherapy or CAR-Ts for patients with relapsed/refractory large B-cell lymphoma."

The approval is based on efficacy and safety data from the Phase 3 ECHELON-3 study, which demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) in patients with relapsed/refractory DLBCL who received ADCETRIS in combination with lenalidomide and rituximab. The study included patients who were heavily pre-treated, some of whom had received prior CAR-T therapy, and survival benefit was observed irrespective of CD30 expression.

"Patients with large B-cell lymphoma can face a challenging journey, with too many patients enduring multiple rounds of chemotherapy and even CAR-T therapy with limited success," said principal investigator Dr. Craig Portell, Associate Professor, University of Virginia. "For patients who have previously faced setbacks with other therapies, ADCETRIS provides a new therapeutic option with outpatient administration and proven safety and efficacy."

LBCL is a type of non-Hodgkin lymphoma (NHL), that affects immune cells called B lymphocytes, a type of white blood cell crucial to the body’s immune system. DLBCL is the most common, aggressive and difficult-to-treat form of the disease. More than 25,000 cases of DLBCL are diagnosed each year in the United States, accounting for more than 25% of all lymphoma cases. Up to 40% of patients relapse or have refractory disease after frontline treatment, and more than 3,500 patients a year fail two prior lines of therapy and require third-line therapy. Despite recent treatment advances including bispecifics and CAR-T therapy, there remains a high unmet need for patients who are not eligible for these treatments or whose disease returns following treatment with these therapies.

The ECHELON-3 study showed that the ADCETRIS combination reduced patients’ risk of death by 37% compared to placebo in combination with lenalidomide and rituximab (HR 0.63 [95% CI: 0.445-0.891] p=0.0085). The OS benefit was consistent across levels of CD30 expression. Positive outcomes were also observed in key secondary endpoints, including overall response rate (ORR)​ and progression-free survival (PFS).

The safety profile of ADCETRIS in ECHELON-3 was consistent with its known safety profile as presented in the U.S. prescribing information. The most frequently reported treatment-emergent adverse events (TEAEs) Grade 3 or higher for the ADCETRIS versus placebo arms were: neutropenia (43% vs 28%), thrombocytopenia (25% vs 19%) and anemia (22% vs 21%). Peripheral sensory neuropathy was infrequent and low grade for each arm with Grade 3 events of 4% vs 0%.

Detailed data from ECHELON-3 were published in JCO Oncology Practice on January 7, 2025 and presented at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

About ECHELON-3

ECHELON-3 is an ongoing, randomized, double-blind, multicenter Phase 3 study evaluating ADCETRIS plus lenalidomide and rituximab versus lenalidomide and rituximab plus placebo in adult patients with relapsed/refractory or transformed DLBCL, regardless of CD30 expression, who have received two or more prior lines of therapy and are ineligible for stem cell transplant (HSCT) or CAR-T therapy. The study also includes patients with hard-to-treat subtypes with poorer outcomes including double hit/triple hit lymphoma and patients with transformed disease. Patients may be ineligible to receive either HSCT or CAR-T therapy due to co-morbidities or financial, geographic, insurance, manufacturing issues. In this global study, 230 patients were randomized across North America, Europe and Asia-Pacific. The primary endpoint is OS in the intent to treat population, with key secondary endpoints of PFS and ORR as assessed by investigator. Other secondary endpoints include complete response rate, duration of response, safety and tolerability.

About Large B-cell Lymphoma

LBCL accounts for about 1/3 of cases of NHL, a type of cancer that starts in the lymphocytes and affects immune cells called B lymphocytes. LBCL occurs most often in older people, with a median age of 67 at diagnosis. About 60-70% of people have advanced-stage disease when diagnosed, and up to 40% have disease that relapses or becomes refractory to initial therapy, and more than 3,500 patients a year fail two prior lines of therapy and require third-line therapy.

DLBCL is the most common and aggressive type of LBCL and is difficult to treat. More than 25,000 cases of DLBCL are diagnosed each year in the United States, accounting for more than 25% of all lymphoma cases. DLBCL can develop spontaneously or as a result of diseases such as chronic lymphocytic lymphoma/small lymphocytic lymphoma, follicular lymphoma, or marginal zone lymphoma.

About ADCETRIS

More than 55,000 patients have been treated with ADCETRIS in the U.S. since its first U.S. approval in 2011, and more than 140,000 patients have been treated with ADCETRIS globally.

ADCETRIS is an antibody-drug conjugate (ADC) comprised of a CD30-directed monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Pfizer’s proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-positive tumor cells.

ADCETRIS is approved in eight indications in the U.S.:

Adult patients with relapsed or refractory large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL) NOS, DLBCL arising from indolent lymphoma, or high-grade B-cell lymphoma (HGBL), after two or more lines of systemic therapy who are not eligible for auto-HSCT or chimeric antigen receptor (CAR) T-cell therapy, in combination with lenalidomide and a rituximab product (2025)
Adult patients with previously untreated Stage III/IV classical Hodgkin lymphoma (cHL) in combination with doxorubicin, vinblastine, and dacarbazine (2018)
Pediatric patients 2 years and older with previously untreated high risk cHL in combination with doxorubicin, vincristine, etoposide, prednisone and cyclophosphamide (2022)
Adult patients with cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation (2015)
Adult patients with cHL after failure of auto-HSCT or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates (2011)
Adult patients with previously untreated systemic anaplastic large cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCL), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified, in combination with cyclophosphamide, doxorubicin, and prednisone (2018)
Adult patients with sALCL after failure of at least one prior multi-agent chemotherapy regimen. (2011)
Adult patients with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) after prior systemic therapy (2017)
Pfizer and Takeda jointly develop ADCETRIS. Under the terms of the collaboration agreement, Pfizer has U.S. and Canadian commercialization rights, and Takeda has rights to commercialize ADCETRIS in the rest of the world. Pfizer and Takeda are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely responsible for development costs.

ADCETRIS (brentuximab vedotin) for injection U.S. Important Safety Information

BOXED WARNING

PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML): JC virus infection resulting in PML, and death can occur in ADCETRIS-treated patients.

CONTRAINDICATION

Contraindicated with concomitant bleomycin due to pulmonary toxicity (e.g., interstitial infiltration and/or inflammation).

WARNINGS AND PRECAUTIONS

Peripheral neuropathy (PN): ADCETRIS causes PN that is predominantly sensory. Cases of motor PN have also been reported. ADCETRIS-induced PN is cumulative. Monitor for symptoms such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain, or weakness. Patients experiencing new or worsening PN may require a delay, change in dose, or discontinuation of ADCETRIS.

Anaphylaxis and infusion reactions: Infusion-related reactions (IRR), including anaphylaxis, have occurred with ADCETRIS. Monitor patients during infusion. If an IRR occurs, interrupt the infusion and institute appropriate medical management. If anaphylaxis occurs, immediately and permanently discontinue the infusion and administer appropriate medical therapy. Premedicate patients with a prior IRR before subsequent infusions. Premedication may include acetaminophen, an antihistamine, and a corticosteroid.

Hematologic toxicities: Fatal and serious cases of febrile neutropenia have been reported with ADCETRIS. Prolonged (≥1 week) severe neutropenia and Grade 3 or 4 thrombocytopenia or anemia can occur with ADCETRIS.

Administer G-CSF primary prophylaxis beginning with Cycle 1 for adult patients who receive ADCETRIS in combination with chemotherapy for previously untreated Stage III/IV cHL or previously untreated PTCL or relapsed or refractory LBCL and pediatric patients who receive ADCETRIS in combination with chemotherapy for previously untreated high risk cHL.

Monitor complete blood counts prior to each ADCETRIS dose. Monitor more frequently for patients with Grade 3 or 4 neutropenia. Monitor patients for fever. If Grade 3 or 4 neutropenia develops, consider dose delays, reductions, discontinuation, or G-CSF prophylaxis with subsequent doses.

Serious infections and opportunistic infections: Infections such as pneumonia, bacteremia, and sepsis or septic shock (including fatal outcomes) have been reported in ADCETRIS-treated patients. Closely monitor patients during treatment for infections.

Tumor lysis syndrome: Patients with rapidly proliferating tumor and high tumor burden may be at increased risk. Monitor closely and take appropriate measures.

Increased toxicity in the presence of severe renal impairment: The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with severe renal impairment. Avoid use in patients with severe renal impairment.

Increased toxicity in the presence of moderate or severe hepatic impairment: The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with moderate or severe hepatic impairment. Avoid use in patients with moderate or severe hepatic impairment.

Hepatotoxicity: Fatal and serious cases have occurred in ADCETRIS-treated patients. Cases were consistent with hepatocellular injury, including elevations of transaminases and/or bilirubin, and occurred after the first ADCETRIS dose or rechallenge. Preexisting liver disease, elevated baseline liver enzymes, and concomitant medications may increase the risk. Monitor liver enzymes and bilirubin. Patients with new, worsening, or recurrent hepatotoxicity may require a delay, change in dose, or discontinuation of ADCETRIS.

PML: Fatal cases of JC virus infection resulting in PML have been reported in ADCETRIS-treated patients. First onset of symptoms occurred at various times from initiation of ADCETRIS, with some cases occurring within 3 months of initial exposure. In addition to ADCETRIS therapy, other possible contributory factors include prior therapies and underlying disease that may cause immunosuppression. Consider PML diagnosis in patients with new-onset signs and symptoms of central nervous system abnormalities. Hold ADCETRIS if PML is suspected and discontinue ADCETRIS if PML is confirmed.

Pulmonary toxicity: Fatal and serious events of noninfectious pulmonary toxicity, including pneumonitis, interstitial lung disease, and acute respiratory distress syndrome, have been reported. Monitor patients for signs and symptoms, including cough and dyspnea. In the event of new or worsening pulmonary symptoms, hold ADCETRIS dosing during evaluation and until symptomatic improvement.

Serious dermatologic reactions: Fatal and serious cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported with ADCETRIS. If SJS or TEN occurs, discontinue ADCETRIS and administer appropriate medical therapy.

Gastrointestinal (GI) complications: Fatal and serious cases of acute pancreatitis have been reported. Other fatal and serious GI complications include perforation, hemorrhage, erosion, ulcer, intestinal obstruction, enterocolitis, neutropenic colitis, and ileus. Lymphoma with pre-existing GI involvement may increase the risk of perforation. In the event of new or worsening GI symptoms, including severe abdominal pain, perform a prompt diagnostic evaluation and treat appropriately.

Hyperglycemia: Serious cases, such as new-onset hyperglycemia, exacerbation of pre-existing diabetes mellitus, and ketoacidosis (including fatal outcomes) have been reported with ADCETRIS. Hyperglycemia occurred more frequently in patients with high body mass index or diabetes. Monitor serum glucose and if hyperglycemia develops, administer anti-hyperglycemic medications as clinically indicated.

Embryo-fetal toxicity: Based on the mechanism of action and animal studies, ADCETRIS can cause fetal harm. Advise females of reproductive potential of this potential risk, and to use effective contraception during ADCETRIS treatment and for 2 months after the last dose of ADCETRIS. Advise male patients with female partners of reproductive potential to use effective contraception during ADCETRIS treatment and for 4 months after the last dose of ADCETRIS.

ADVERSE REACTIONS

The most common adverse reactions (≥20%) in adult patients are peripheral neuropathy, nausea, fatigue, musculoskeletal pain, constipation, diarrhea, vomiting, pyrexia, upper respiratory tract infection, mucositis, abdominal pain, and rash. The most common laboratory abnormalities (≥20%) in adult patients are decreased neutrophils, increased creatinine, decreased hemoglobin, decreased lymphocytes, increased glucose, increased ALT, and increased AST.

The most common Grade ≥3 adverse reactions (≥5%) in combination with AVEPC in pediatric patients were neutropenia, anemia, thrombocytopenia, febrile neutropenia, stomatitis, and infection.

DRUG INTERACTIONS

Concomitant use of strong CYP3A4 inhibitors has the potential to affect the exposure to monomethyl auristatin E (MMAE). Closely monitor adverse reactions.

USE IN SPECIAL POPULATIONS

Lactation: Breastfeeding is not recommended during ADCETRIS treatment.

Please see the full Prescribing Information, including BOXED WARNING, for ADCETRIS here. There may be a delay as the document is updated with the latest information. It will be available as soon as possible. Please check back for the updated full information shortly.

On February 12, 2025 Rezolute, Inc. (Nasdaq: RZLT) ("Rezolute" or the "Company"), a late-stage biopharmaceutical company dedicated to developing transformative therapies for rare diseases with serious unmet needs, reported financial results and provided a business update for the three months ended December 31, 2024 (Press release, Rezolute, FEB 12, 2025, View Source [SID1234650212]).

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"We have made significant regulatory progress with ersodetug and our focus in 2025 remains squarely on advancing both Phase 3 trials for patients with congenital HI and tumor HI," said Nevan Charles Elam, Chief Executive Officer and Founder of Rezolute. "We are encouraged by our momentum and remain dedicated to providing meaningful and innovative treatments for patients with limited options."

Recent Pipeline Progress and Anticipated Milestones

Congenital HI

· The U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation to ersodetug for the treatment of hypoglycemia due to congenital HI.
·
sunRIZE, a Phase 3, multicenter, double-blind, randomized, controlled safety and efficacy registrational study, is ongoing.

○ Enrollment of U.S. participants is anticipated to occur in the second quarter of 2025.
○ Overall study enrollment expected to conclude in the second quarter of 2025, with topline results expected in the fourth quarter of 2025, subject to outcomes from an interim analysis.

· An independent Data Monitoring Committee (DMC) reviewed safety and pharmacokinetics of ersodetug in eight infant participants in the open-label arm of the sunRIZE study.
○ Ersodetug administered between 5-10 mg/kg during a bi-weekly loading phase and a monthly maintenance phase was generally safe and well-tolerated.
○ Observed ersodetug drug levels at peak and trough were comparable to exposures in older pediatric participants in the Phase 2b RIZE study and validate the chosen dose regimen of 5 and 10 mg/kg administered bi-weekly and monthly.
○ Subsequent infant participants may be enrolled into the double-blind, placebo-controlled study.
○ The DMC did not analyze efficacy and the Company remains blinded to the results.

· An interim analysis of the primary study endpoint (change in hypoglycemia events) is planned for this quarter, with results and study update to be announced early in the second quarter.
○ Three possible outcomes from the analysis include: (i) futility and the study should be stopped, (ii) continue the study as is or (iii) continue the study as is but increase the sample size by 33% (18 additional patients) to enhance statistical confidence in the final outcome.

Tumor HI

· During the quarter, FDA granted Orphan Drug Designation to ersodetug for the treatment of hypoglycemia due to tumor HI.
· A Phase 3 registrational study for ersodetug in patients with tumor HI is anticipated to begin in the first half of 2025.
· Topline results are expected in the second half of 2026.

Fiscal Second Quarter Financial Results

Cash, cash equivalents and investments in marketable securities were $105.3 million as of December 31, 2024, compared to $127.1 million as of June 30, 2024.

Research and development expenses were $12.6 million for the second quarter of fiscal 2025, compared with $12.0 million for the same period a year ago, with the increase primarily attributable to increased expenditures in clinical trial activities, manufacturing costs and higher personnel-related expenses, which include employee compensation.

General and administrative expenses were $4.5 million for the second quarter of fiscal 2025, compared with $3.2 million for the same period a year ago, with the increase primarily attributable to professional fees and employee-related expenses as a result of increased headcount.

Net loss was $15.7 million for the second quarter of fiscal 2025 compared with a net loss of $13.9 million for the same period a year ago.

About Ersodetug

Ersodetug is a fully human monoclonal antibody that binds to a unique allosteric site on insulin receptors to counteract the effects of insulin receptor over-activation by insulin and related substances (such as IGF-2), thereby improving hypoglycemia in the setting of hyperinsulinism (HI). Because ersodetug acts downstream from the pancreas, it has the potential to be universally effective at treating hypoglycemia due to any form of HI.

About sunRIZE

The Phase 3 sunRIZE study is a multi-center, randomized, double-blind, placebo-controlled, parallel arm study designed to evaluate the efficacy and safety of ersodetug in patients with congenital HI who are experiencing poorly controlled hypoglycemia. Participants between the ages of 3 months to 45 years old are eligible to participate. The study is enrolling up to 56 participants in more than a dozen countries around the world.

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.

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 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.