On November 6, 2025 Johnson & Johnson (NYSE:JNJ) reported the U.S. Food and Drug Administration (FDA) approved DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) as a single agent treatment for adult patients with high-risk smoldering multiple myeloma (HR-SMM).1 DARZALEX FASPRO is the first and only approved treatment for HR-SMM, enabling earlier intervention before the disease progresses to active multiple myeloma.

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FDA approval is based on findings from the AQUILA study (NCT03301220), which evaluated the efficacy and safety of DARZALEX FASPRO compared to active monitoring (or "Watch and Wait") in the largest Phase 3 trial in patients with HR-SMM. The AQUILA study demonstrated a significant improvement in the primary endpoint of progression-free survival (PFS), with DARZALEX FASPRO reducing the risk of disease progression to active multiple myeloma or death by 51 percent compared to active monitoring, according to the International Myeloma Working Group (IMWG) diagnostic criteria for multiple myeloma. Today’s milestone follows the May 2025 vote by the U.S. FDA Oncologic Drugs Advisory Committee (ODAC) in favor of the benefit-risk profile of DARZALEX FASPRO as a single agent treatment for patients with HR-SMM.

Smoldering multiple myeloma (SMM) is an asymptomatic malignancy that is genomically the same as active multiple myeloma and where these abnormal cells can be detected in the bone marrow.2,3,4 In 2025, it is estimated that more than 36,000 people will be diagnosed with multiple myeloma in the U.S., and approximately 15 percent of those are classified as smoldering.5,6 An estimated 50 percent of patients diagnosed with HR-SMM are likely to progress to active disease within two years of diagnosis.6 Currently, the standard of care for HR-SMM is active monitoring to track signs of biochemical progression and/or end-organ damage. Recent evidence suggests that people at high-risk of progressing to active multiple myeloma could benefit from earlier therapeutic intervention.6

"Until now, patients diagnosed with smoldering multiple myeloma only have the option to watch and wait for any active signs of progression to active disease," said Peter Voorhees, M.D., Atrium Health/Levine Cancer Institute, Charlotte, N.C.* "Results from AQUILA demonstrated DARZALEX FASPRO significantly delayed disease progression, underscoring the role of early disease intervention for patients with high-risk smoldering multiple myeloma."

The Phase 3 AQUILA study showed after a median follow-up of 65.2 months, 63.1 percent of patients who received DARZALEX FASPRO had not progressed to active myeloma at 5 years (60 months) versus 40.7 percent in the active monitoring group (hazard ratio [HR], 0.49; 95 percent confidence interval [CI], 0.36-0.67; P<0.001). Today, most physicians use the Mayo 2018 criteria (20/2/20) to assess risk status in patients with smoldering myeloma. In a post hoc analysis of AQUILA, 41 percent of patients met the Mayo 2018 HR-SMM classification. Among these patients, median PFS was not reached in the DARZALEX FASPRO arm and was 22.1 months in the active monitoring arm (HR, 0.36; 95 percent CI, 0.23-0.58).1

Beyond the primary endpoint of PFS, patients in AQUILA who received DARZALEX FASPRO saw a higher response rate of 63.4 percent compared to 2.0 percent with active monitoring (P<0.001). The median time to patients receiving first-line multiple myeloma treatment was delayed for patients receiving DARZALEX FASPRO compared to active monitoring, with median time to first treatment NR vs 50.2 months for the active monitoring group (HR, 0.46; 95 percent CI, 0.33-0.62).1

"DARZALEX FASPRO is a foundational therapy in multiple myeloma and illustrates our commitment to improve outcomes for patients at every stage of their disease," said Jordan Schecter, M.D., Vice President, Research & Development, Multiple Myeloma, Oncology, Johnson & Johnson Innovative Medicine. "Data from the AQUILA study reinforce the significant impact DARZALEX FASPRO continues to have for patients. With today’s approval, patients with HR-SMM will now be able to receive this treatment before they progress to active multiple myeloma, giving us the opportunity to shift the treatment paradigm and bring hope to people who are impacted by this disease."

Adverse reactions observed in the pivotal AQUILA study were generally consistent with previous DARZALEX FASPRO studies. The most common adverse reactions (≥20%) in patients with HR-SMM who received DARZALEX FASPRO monotherapy are upper respiratory tract infection, musculoskeletal pain, fatigue, diarrhea, rash, sleep disorder, sensory neuropathy, and injection site reactions.1

Results from AQUILA were first presented at the 2024 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and simultaneously published in The New England Journal of Medicine. A subgroup analysis from the AQUILA study, evaluating the efficacy and safety of DARZALEX FASPRO monotherapy in patients with HR-SMM using IMWG 2020 and IMWG 2020 plus cytogenetic risk models, will be presented at the 2025 ASH (Free ASH Whitepaper) Annual Meeting in Orlando from December 6-9.

About the AQUILA Study

AQUILA (NCT03301220) is a randomized, multicenter Phase 3 study comparing treatment with DARZALEX FASPRO to active monitoring in patients with SMM. Patients received single agent DARZALEX FASPRO as a fixed-duration treatment for up to 36 months. The primary endpoint is progression-free survival (PFS), defined as progression to active multiple myeloma (MM) as assessed by an independent review committee, according to IMWG diagnostic criteria for MM (SLiM-CRAB), or death. Major secondary endpoints included overall response rate, PFS on first-line MM treatment (PFS2), and overall survival. Forty-one percent of patients had 2 or more of the following criteria for high-risk smoldering multiple myeloma: serum monoclonal protein level >2 g/dL, involved-to-uninvolved serum-free light chain ratio >20, and bone marrow plasma cells >20%. DARZALEX FASPRO is only indicated for patients with high-risk smoldering multiple myeloma and is not indicated for other risk categories.

About Multiple Myeloma

Multiple myeloma is a blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.7 In multiple myeloma, these malignant plasma cells proliferate and replace normal cells in the bone marrow.8 Multiple myeloma is the second most common blood cancer worldwide and remains an incurable disease.9 In 2025, it is estimated that more than 36,000 people will be diagnosed with multiple myeloma in the U.S. and more than 12,000 will die from the disease.5 People with multiple myeloma have a 5-year survival rate of 59.8 percent.10 While some people diagnosed with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels, kidney problems or infections.2,10

About Smoldering Multiple Myeloma

Smoldering multiple myeloma (SMM) is an asymptomatic precursor disease state of multiple myeloma where abnormal cells can be detected in the bone marrow.11 People living with SMM do not show signs or symptoms typically associated with active myeloma, such as bone pain, bone fractures, kidney problems, or anemia. However, as abnormal plasma cells are present, organ damage may begin and progress asymptomatically.4,6 Approximately fifteen percent of all cases are classified as SMM, and half of those diagnosed with high-risk SMM are estimated to progress to active multiple myeloma within two years.6

About DARZALEX FASPRO and DARZALEX

DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) received U.S. FDA approval in May 2020 and is approved for ten indications in multiple myeloma, four of which are for frontline treatment in newly diagnosed patients who are transplant eligible or ineligible.1 It is the only subcutaneous CD38-directed antibody approved to treat patients with multiple myeloma. DARZALEX FASPRO is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE drug delivery technology.

DARZALEX (daratumumab) received U.S. FDA approval in November 2015 and is approved in eight indications, three of which are in the frontline setting, including newly diagnosed patients who are transplant-eligible and ineligible.12 DARZALEX is the first CD38-directed antibody approved to treat multiple myeloma.12 DARZALEX-based regimens have been used in the treatment of more than 618,000 patients worldwide and more than 68,000 patients in the U.S. alone.

In August 2012, Janssen Biotech, Inc. and Genmab A/S entered a worldwide agreement, which granted Janssen an exclusive license to develop, manufacture and commercialize daratumumab

For more information, visit www.DARZALEX.com.

DARZALEX FASPRO INDICATIONS AND IMPORTANT SAFETY INFORMATION

INDICATIONS

DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) is indicated for the treatment of adult patients with multiple myeloma:

In combination with bortezomib, lenalidomide, and dexamethasone for induction and consolidation in newly diagnosed patients who are eligible for autologous stem cell transplant
In combination with bortezomib, melphalan, and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant
In combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy
In combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant
In combination with pomalidomide and dexamethasone in patients who have received at least one prior line of therapy including lenalidomide and a proteasome inhibitor (PI)
In combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy
In combination with bortezomib and dexamethasone in patients who have received at least one prior therapy
As monotherapy in patients who have received at least three prior lines of therapy including a PI and an immunomodulatory agent or who are double refractory to a PI and an immunomodulatory agent
DARZALEX FASPRO as monotherapy is indicated for the treatment of adult patients with high-risk smoldering multiple myeloma.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

DARZALEX FASPRO is contraindicated in patients with a history of severe hypersensitivity to daratumumab, hyaluronidase, or any of the components of the formulation.

WARNINGS AND PRECAUTIONS

Hypersensitivity and Other Administration Reactions

Both systemic administration-related reactions, including severe or life-threatening reactions, and local injection-site reactions can occur with DARZALEX FASPRO. Fatal reactions have been reported with daratumumab-containing products, including DARZALEX FASPRO.

Systemic Reactions

In a pooled safety population of 1446 patients with multiple myeloma (N=1235) or light chain (AL) amyloidosis (N=193) who received DARZALEX FASPRO as monotherapy or in combination, 7% of patients experienced a systemic administration-related reaction (Grade 2: 3%, Grade 3: 0.8%, Grade 4: 0.1%). In patients with high-risk smoldering multiple myeloma (N=193), systemic administration-related reactions occurred in 17% of patients in AQUILA (Grade 2: 7%, Grade 3: 1%).

In all patients (N=1639), systemic administration-related reactions occurred in 7% of patients with the first injection, 0.5% with the second injection, and cumulatively 1% with subsequent injections. The median time to onset was 3.2 hours (range: 4 minutes to 3.5 days). Of the 283 systemic administration-related reactions that occurred in 135 patients, 240 (85%) occurred on the day of DARZALEX FASPRO administration. Delayed systemic administration-related reactions have occurred in 1% of the patients.

Severe reactions included hypoxia, dyspnea, hypertension, tachycardia, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Other signs and symptoms of systemic administration-related reactions may include respiratory symptoms, such as bronchospasm, nasal congestion, cough, throat irritation, allergic rhinitis, and wheezing, as well as anaphylactic reaction, pyrexia, chest pain, pruritus, chills, vomiting, nausea, hypotension, and blurred vision.

Pre-medicate patients with histamine-1 receptor antagonist, acetaminophen, and corticosteroids. Monitor patients for systemic administration-related reactions, especially following the first and second injections. For anaphylactic reaction or life-threatening (Grade 4) administration-related reactions, immediately and permanently discontinue DARZALEX FASPRO. Consider administering corticosteroids and other medications after the administration of DARZALEX FASPRO depending on dosing regimen and medical history to minimize the risk of delayed (defined as occurring the day after administration) systemic administration-related reactions.

Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with daratumumab-containing products. If ocular symptoms occur, interrupt DARZALEX FASPRO and seek immediate ophthalmologic evaluation prior to restarting DARZALEX FASPRO.

Local Reactions

In this pooled safety population of 1446 patients with multiple myeloma (N=1253) or light chain amyloidosis (N=193), injection-site reactions occurred in 8% of patients, including Grade 2 reactions in 1.1%. The most frequent (>1%) injection-site reaction were injection site erythema and injection site rash. In patients with high-risk smoldering multiple myeloma (N=193), injection-site reactions occurred in 28% of patients, including Grade 2 reactions in 3%. These local reactions occurred a median of 6 minutes (range: 0 minutes to 6.5 days) after starting administration of DARZALEX FASPRO. Monitor for local reactions and consider symptomatic management.

Infections

DARZALEX FASPRO can cause serious, life-threatening, or fatal infections. In patients who received DARZALEX FASPRO in a pooled safety population including patients with smoldering multiple myeloma and light chain (AL) amyloidosis (N=1639), serious infections, including opportunistic infections, occurred in 24% of patients, Grade 3 or 4 infections occurred in 22%, and fatal infections occurred in 2.5%. The most common type of serious infection reported was pneumonia (8.5%).

Monitor patients for signs and symptoms of infection prior to and during treatment with DARZALEX FASPRO and treat appropriately. Administer prophylactic antimicrobials according to guidelines.

Neutropenia

Daratumumab may increase neutropenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX FASPRO until recovery of neutrophils. In lower body weight patients receiving DARZALEX FASPRO, higher rates of Grade 3-4 neutropenia were observed.

Thrombocytopenia

Daratumumab may increase thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Consider withholding DARZALEX FASPRO until recovery of platelets.

Embryo-Fetal Toxicity

Based on the mechanism of action, DARZALEX FASPRO can cause fetal harm when administered to a pregnant woman. DARZALEX FASPRO may cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX FASPRO and for 3 months after the last dose.

The combination of DARZALEX FASPRO with lenalidomide, thalidomide, or pomalidomide is contraindicated in pregnant women because lenalidomide, thalidomide, and pomalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, thalidomide, or pomalidomide prescribing information on use during pregnancy.

Interference With Serological Testing

Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab administration. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient’s serum. The determination of a patient’s ABO and Rh blood type are not impacted.

Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX FASPRO. Type and screen patients prior to starting DARZALEX FASPRO.

Interference With Determination of Complete Response

Daratumumab is a human immunoglobulin G (IgG) kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some DARZALEX FASPRO-treated patients with IgG kappa myeloma protein.

ADVERSE REACTIONS

In multiple myeloma, the most common adverse reaction (≥20%) with DARZALEX FASPRO monotherapy is upper respiratory tract infection. The most common adverse reactions with combination therapy (≥20% for any combination) include fatigue, nausea, diarrhea, dyspnea, insomnia, headache, rash, pyrexia, cough, muscle spasms, back pain, vomiting, hypertension, musculoskeletal pain, upper respiratory tract infection, peripheral neuropathy, peripheral sensory neuropathy, constipation, pneumonia, edema, peripheral edema, and anemia.

The most common adverse reactions (≥20%) in patients with high-risk smoldering multiple myeloma who received DARZALEX FASPRO monotherapy are upper respiratory tract infection, musculoskeletal pain, fatigue, diarrhea, rash, sleep disorder, sensory neuropathy, and injection site reactions.

The most common hematology laboratory abnormalities (≥40%) with DARZALEX FASPRO are decreased leukocytes, decreased lymphocytes, decreased neutrophils, decreased platelets, and decreased hemoglobin.

Please click here to read the full Prescribing Information for DARZALEX FASPRO.

DARZALEX INDICATIONS AND IMPORTANT SAFETY INFORMATION

INDICATIONS

DARZALEX (daratumumab) is indicated for the treatment of adult patients with multiple myeloma:

In combination with bortezomib, melphalan, and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant
In combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy
In combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant
In combination with pomalidomide and dexamethasone in patients who have received at least one prior line of therapy including lenalidomide and a proteasome inhibitor
In combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy
In combination with bortezomib and dexamethasone in patients who have received at least one prior therapy
As monotherapy in patients who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent
CONTRAINDICATIONS

DARZALEX is contraindicated in patients with a history of severe hypersensitivity (eg, anaphylactic reactions) to daratumumab or any of the components of the formulation.

WARNINGS AND PRECAUTIONS

Infusion-Related Reactions

DARZALEX can cause severe and/or serious infusion-related reactions including anaphylactic reactions. These reactions can be life threatening, and fatal outcomes have been reported. In clinical trials (monotherapy and combination: N=2066), infusion-related reactions occurred in 37% of patients with the Week 1 (16 mg/kg) infusion, 2% with the Week 2 infusion, and cumulatively 6% with subsequent infusions. Less than 1% of patients had a Grade 3/4 infusion-related reaction at Week 2 or subsequent infusions. The median time to onset was 1.5 hours (range: 0 to 73 hours). Nearly all reactions occurred during infusion or within 4 hours of completing DARZALEX. Severe reactions have occurred, including bronchospasm, hypoxia, dyspnea, hypertension, tachycardia, headache, laryngeal edema, pulmonary edema, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Signs and symptoms may include respiratory symptoms, such as nasal congestion, cough, throat irritation, as well as chills, vomiting, and nausea. Less common signs and symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, hypotension and blurred vision.

When DARZALEX dosing was interrupted in the setting of ASCT (CASSIOPEIA) for a median of 3.75 months (range: 2.4 to 6.9 months), upon re-initiation of DARZALEX, the incidence of infusion-related reactions was 11% for the first infusion following ASCT. Infusion-related reactions occurring at re-initiation of DARZALEX following ASCT were consistent in terms of symptoms and severity (Grade 3 or 4: <1%) with those reported in previous studies at Week 2 or subsequent infusions. In EQUULEUS, patients receiving combination treatment (n=97) were administered the first 16 mg/kg dose at Week 1 split over two days, ie, 8 mg/kg on Day 1 and Day 2, respectively. The incidence of any grade infusion-related reactions was 42%, with 36% of patients experiencing infusion-related reactions on Day 1 of Week 1, 4% on Day 2 of Week 1, and 8% with subsequent infusions.

Pre-medicate patients with antihistamines, antipyretics, and corticosteroids. Frequently monitor patients during the entire infusion. Interrupt DARZALEX infusion for reactions of any severity and institute medical management as needed. Permanently discontinue DARZALEX therapy if an anaphylactic reaction or life-threatening (Grade 4) reaction occurs and institute appropriate emergency care. For patients with Grade 1, 2, or 3 reactions, reduce the infusion rate when re-starting the infusion.

To reduce the risk of delayed infusion-related reactions, administer oral corticosteroids to all patients following DARZALEX infusions. Patients with a history of chronic obstructive pulmonary disease may require additional post-infusion medications to manage respiratory complications. Consider prescribing short- and long-acting bronchodilators and inhaled corticosteroids for patients with chronic obstructive pulmonary disease.

Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with DARZALEX infusion. If ocular symptoms occur, interrupt DARZALEX infusion and seek immediate ophthalmologic evaluation prior to restarting DARZALEX.

Interference With Serological Testing

Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab infusion. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient’s serum. The determination of a patient’s ABO and Rh blood type is not impacted. Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX. Type and screen patients prior to starting DARZALEX.

Neutropenia and Thrombocytopenia

DARZALEX may increase neutropenia and thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX until recovery of neutrophils or for recovery of platelets.

Interference With Determination of Complete Response

Daratumumab is a human immunoglobulin G (IgG) kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some patients with IgG kappa myeloma protein.

Embryo-Fetal Toxicity

Based on the mechanism of action, DARZALEX can cause fetal harm when administered to a pregnant woman. DARZALEX may cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX and for 3 months after the last dose.

The combination of DARZALEX with lenalidomide, pomalidomide, or thalidomide is contraindicated in pregnant women because lenalidomide, pomalidomide, and thalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, pomalidomide, or thalidomide prescribing information on use during pregnancy.

ADVERSE REACTIONS

The most frequently reported adverse reactions (incidence ≥20%) were: upper respiratory infection, neutropenia, infusion related reactions, thrombocytopenia, diarrhea, constipation, anemia, peripheral sensory neuropathy, fatigue, peripheral edema, nausea, cough, pyrexia, dyspnea, and asthenia. The most common hematologic laboratory abnormalities (≥40%) with DARZALEX are: neutropenia, lymphopenia, thrombocytopenia, leukopenia, and anemia.

Please click here to read the full Prescribing Information for DARZALEX.

(Press release, Johnson & Johnson, NOV 6, 2025, View Source [SID1234659612])

On November 5, 2025 Novo Nordisk reported sales increased by 12% in Danish kroner and by 15% at CER in the first nine months of 2025; R&D pipeline progress continues

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•Operating profit increased by 5% in Danish kroner and 10% at constant exchange rates (CER) to DKK 95.9 billion, impacted by one-off restructuring costs of around DKK 9 billion related to the company-wide transformation with the aim of streamlining Novo Nordisk’s operations to reinvest for growth. Had Novo Nordisk not incurred such restructuring costs amounting to around DKK 9 billion, operating profit would have increased by 15% in Danish kroner and 21% at CER.
•Sales in US Operations increased by 12% in Danish kroner (15% at CER). Sales in the US were positively impacted by gross-to-net sales adjustments. Sales in International Operations increased by 13% in Danish kroner (16% at CER).

•Sales within Diabetes and Obesity care increased by 12% in Danish kroner to DKK 215.7 billion (15% at CER), mainly driven by Obesity care growth of 37% in Danish kroner to DKK 59.9 billion (41% at CER) and GLP-1 diabetes sales growing 7% in Danish kroner (10% at CER). Rare disease sales increased by 10% in Danish kroner (13% at CER).

•Within R&D, Novo Nordisk announced that the US FDA had approved an indication for Wegovy for the treatment of MASH. Further, Novo Nordisk agreed to acquire Akero Therapeutics, Inc. and its phase 3 FGF21 analogue in MASH and Omeros’ clinical-stage MASP-3 inhibitor zaltenibart within Rare blood disorders. Also within Rare disease, Novo Nordisk submitted Mim8 for regulatory approval in the EU and in the US. Finally, cagrilintide phase 3 development was initiated, with the potential to be the first amylin monotherapy treatment on the market for weight management.

•For the full-year 2025 outlook, sales growth is now expected to be 8-11% at CER with operating profit growth now expected to be 4-7% also at CER, including a negative full-year impact of around DKK 8 billion from the company-wide transformation. Sales and operating profit growth reported in Danish kroner is now expected to be 4 and 6 percentage points lower than at CER, respectively. The narrowing of the guidance ranges reflects lowered growth expectations for Novo Nordisk’s GLP-1 treatments within diabetes and obesity.

•In October, Novo Nordisk announced that the Board of Directors decided to convene an extraordinary general meeting, to be held on 14 November 2025 to elect new members of the Board of Directors of Novo Nordisk.
PROFIT AND LOSS 9M 2025 9M 2024 Growth
as reported Growth
at CER*
DKK million
Net sales 229,920 204,720 12 % 15 %
Operating profit 95,922 91,602 5 % 10 %
Net profit
75,543 72,758 4 % N/A
Diluted earnings per share (in DKK) 16.99 16.29 4 % N/A
* CER: Constant exchange rates (average 2024).

"Our company-wide transformation has already driven operational efficiencies, and we have a renewed focus that can deliver a range of potential treatment options that will serve millions more patients, mainly in obesity. While we delivered robust sales growth in the first nine months of 2025, the lower growth expectations for our GLP-1 treatments have led to a narrowing of our guidance. We agreed to acquire Akero Therapeutics Inc., adding a potential first-and-best-in-class asset within F4 in MASH, and initiated our phase 3 programme with cagrilintide for weight management. We aim to accelerate on all fronts to be able to compete better in dynamic and increasingly competitive markets," said Mike Doustdar, president and CEO.

On 5 November 2025 at 13.00 CET, corresponding to 07.00 am EST, an earnings call will be held. Investors will be able to listen in via a link on novonordisk.com, which can be found under ‘Investors’ (the contents of the company’s website do not form a part of this Form 6-K).
Novo Nordisk A/S
Investor Relations
Novo Alle 1
2880 Bagsværd
Denmark Telephone:
+45 4444 8888
www.novonordisk.com CVR Number:
24 25 67 90
Company announcement No 31 / 2025

Financial report for the period 1 January 2025 to 30 September 2025
Page 2 of 38

STRATEGIC ASPIRATIONS
STRATEGIC ASPIRATIONS 2025
The strategic aspirations are objectives that Novo Nordisk intends to work towards and are not a projection of Novo Nordisk’s financial outlook or expected growth. Novo Nordisk intends to describe how its activities develop in relation to each of the four dimensions on an ongoing basis.

Performance highlights for the first nine months of 2025 (blue indicates third-quarter development).

PERFORMANCE HIGHLIGHTS
Financials
Deliver solid sales and operating profit growth:
–Sales growth of 15% (CER)
–Operating profit growth of 10% (CER), impacted by one-off restructuring costs related to a company-wide transformation as well as impact related to the acquisition of the three former Catalent manufacturing sites
–Had Novo Nordisk not incurred such restructuring costs amounting to around DKK 9 billion, operating profit would have increased by 21% (CER)
Drive operational efficiencies:
–Operational leverage reflecting sales growth

Enable attractive capital allocation to shareholders:
–Free cash flow of DKK 63.9 billion
–DKK 53.2 billion returned to shareholders

e
Innovation and therapeutic focus
Further raise innovation bar for Diabetes treatment:
–Ozempic received positive opinion by CHMP for the treatment of peripheral arterial disease in the EU
–Rybelsus CV indication, based on SOUL, approved in the US and received positive CHMP opinion in the EU
–Resubmission of Awiqli in the US for treatment of type 2 diabetes
to
Develop superior treatment solutions for Obesity:
–Oral semaglutide 25 mg for weight management submitted in the US and in the EU
–In-license agreements of a triple agonist and two oral molecules
–Novo Nordisk to advance subcutaneous and oral amycretin for weight management into phase 3 clinical development
–Semaglutide 7.2 mg submitted in the EU
–Wegovy approved in the US for MASH indication
–Phase 3 programme with cagrilintide initiated
–Initiation of phase 1b/2 programme with triple agonist
Strengthen and progress Rare disease pipeline:
–Sogroya non-replacement indications submitted in the US, Japan
–Alhemo (concizumab) approved in the US for the treatment of haemophilia A and B without inhibitors
–Mim8 submitted for regulatory approval in the EU and in the US
–Agreed to acquire clinical-stage MASP-3 inhibitor zaltenibart

Establish presence in Cardiovascular & Emerging Therapy Areas:
–Semaglutide 2.4 mg in MASH submitted for regulatory approval in Japan and in the EU
–Phase 2 trials with CDR123L in patients with chronic heart failure and preserved or reduced ejection fraction initiated
–Agreed to acquire Akero and its phase 3 FGF21 analogue in MASH
–Phase 3 trial with coramitug initiated in people living with ATTR cardiomyopathy.
Commercial execution
Strengthen diabetes leadership to more than one-third:
–Diabetes value market share declined by 2.3 percentage points to 31.6% (MAT)
More than DKK 25 billion* in Obesity care sales by 2025:
–Obesity care sales increased by 41% (CER) to DKK 59.9 billion

Secure a sustained growth outlook for Rare Disease:
–Rare disease sales increased by 13% (CER) to DKK 14.3 billion
e-t
Purpose and sustainability (ESG)
Progress towards zero environmental impact:
–Overall CO2e emissions (scope 1, 2 and full scope 3) increased by 21% compared to the first nine months of 2024

Adding value to society:
–Medical treatment provided to 42.4 million people living with diabetes and 3.2 million people living with obesity

* on a full-year basis.

Strategic aspirations Performance highlights Commercial execution Financials Cash flow and capital allocation Outlook Innovation and therapeutic focus Purpose and sustainability Corporate Governance Legal Financial Information
Company announcement No 31 / 2025

Financial report for the period 1 January 2025 to 30 September 2025
Page 3 of 38

PERFORMANCE HIGHLIGHTS
FINANCIAL HIGHLIGHTS FOR THE FIRST NINE MONTHS OF 2025
PROFIT AND LOSS 9M 2025 9M 2024 % change
9M 2025 to
9M 2024 % change
9M 2025 to
9M 2024 at CER¹
(Amounts are in DKK million, except for earnings per share)
Net sales
229,920 204,720 12 % 15 %
Gross profit 186,280 173,222 8 % 12 %
Gross margin 81.0% 84.6%
Sales and distribution costs (48,421) (43,400) 12 % 15 %
Percentage of sales 21.1% 21.2%
Research and development costs (37,391) (34,260) 9 % 10 %
Percentage of sales 16.3% 16.7%
Administrative costs (4,420) (3,696) 20 % 22 %
Percentage of sales 1.9% 1.8%
Other operating income and expenses (126) (264) N/A N/A
Operating profit (EBIT)
95,922 91,602 5 % 10 %
Operating margin 41.7% 44.7%
Financial items (net) 433 32 N/A N/A
Profit before income taxes 96,355 91,634 5 % N/A
Income taxes (20,812) (18,876) 10 % N/A
Effective tax rate 21.6% 20.6%
Net profit 75,543 72,758 4 % N/A
Net profit margin 32.9% 35.5%
OTHER KEY NUMBERS
Depreciation, amortisation and impairment losses 16,420 13,909 18 % N/A
Capital expenditure (PP&E) 41,711 31,063 34 % N/A
Net cash generated from operating activities 111,483 108,667 3 % N/A
Free cash flow1
63,887 71,760 (11 %) N/A
EBITDA1
112,342 105,511 6 % 11 %
Adjusted net profit1
87,748 80,042 10 % N/A
Total assets 512,288 397,441 29 % N/A
Equity 169,896 120,522 41 % N/A
Equity ratio 33.2% 30.3%
Diluted earnings per share / ADR (in DKK) 16.99 16.29 4 % N/A
Full-time equivalent employees end of period 78,554 71,880 9 % N/A
1) See appendix 7: Non-IFRS financial measures (additional information).

These unaudited consolidated financial statements for the first nine months of 2025 have been prepared in accordance
with IAS 34 ‘Interim Financial Reporting’ and additional Danish disclosure requirements for listed companies.
The accounting policies adopted in the preparation are consistent with those applied in the Annual Report 2024 of Novo
Nordisk.

Strategic aspirations Performance highlights Commercial execution Financials Cash flow and capital allocation Outlook Innovation and therapeutic focus Purpose and sustainability Corporate Governance Legal Financial Information
Company announcement No 31 / 2025

Financial report for the period 1 January 2025 to 30 September 2025
Page 4 of 38

COMMERCIAL EXECUTION
SALES DEVELOPMENT ACROSS THERAPEUTIC AREAS
Sales grew by 12% measured in Danish kroner and by 15% at CER in the first nine months of 2025, driven by Obesity care sales growth of 41% (CER), driven by Wegovy and Diabetes care sales growth of 8% (CER), driven by Ozempic. Rare disease sales increased by 13% (CER).

Sales split per therapy Sales 9M 2025
DKK million Sales 9M 2024
DKK million Growth
as reported Growth
at CER Share of growth
at CER
Diabetes and Obesity care segment
Injectable GLP-1 97,885 90,568 8 % 11 % 32 %
– Ozempic
95,264 86,489 10 % 13 % 36 %
– Victoza
2,621 4,079 (36 %) (34 %) (4 %)
Rybelsus
16,790 16,384 2 % 5 % 2 %
Total GLP-1 114,675 106,952 7 % 10 % 34 %
Long-acting insulin1
14,055 13,937 1 % 3 % 1 %
Premix insulin2
7,806 7,922 (1 %) 0 % 0 %
Fast-acting insulin3
13,703 12,505 10 % 12 % 5 %
Human insulin 4,172 5,122 (19 %) (15 %) (2 %)
Total insulin 39,736 39,486 1 % 3 % 4 %
Other Diabetes care4
1,348 1,608 (16 %) (14 %) (1 %)
Total Diabetes care 155,759 148,046 5 % 8 % 37 %
Wegovy
57,242 38,340 49 % 54 % 66 %
Saxenda
2,660 5,400 (51 %) (49 %) (8 %)
Total Obesity care 59,902 43,740 37 % 41 % 58 %
Diabetes and Obesity care total 215,661 191,786 12 % 15 % 95 %
Rare disease segment
Rare blood disorders5
8,936 8,740 2 % 5 % 1 %
Rare endocrine disorders6
4,125 3,070 34 % 37 % 4 %
Other Rare disease7
1,198 1,124 7 % 9 % 0 %
Rare disease total 14,259 12,934 10 % 13 % 5 %
Total sales 229,920 204,720 12 % 15 % 100 %
1) Comprises Tresiba, Xultophy, Levemir and Awiqli.
2) Comprises Ryzodeg and NovoMix.
3) Comprises Fiasp and NovoRapid.
4) Primarily NovoNorm, needles and GlucaGen HypoKit.
5) Comprises NovoSeven, NovoEight, Esperoct, Refixia, NovoThirteen and Alhemo.
6) Primarily Norditropin and Sogroya.
7) Primarily Vagifem and Activelle.

Strategic aspirations Performance highlights Commercial execution Financials Cash flow and capital allocation Outlook Innovation and therapeutic focus Purpose and sustainability Corporate Governance Legal Financial Information
Company announcement No 31 / 2025

Financial report for the period 1 January 2025 to 30 September 2025
Page 5 of 38

DIABETES AND OBESITY CARE
Diabetes care, sales and market share development
Sales in Diabetes care increased by 5% measured in Danish kroner and by 8% at CER to DKK 155,759 million, mainly driven by growth of GLP-1-based products. Novo Nordisk has a strategic aspiration of strengthening the Diabetes care leadership, aiming at reaching a global value market share of more than one-third in 2025. Novo Nordisk’s global diabetes value market share decreased by 2.3% percentage points over the last 12 months to 31.6%. In IO countries, tirzepatide is categorised under GLP-1 diabetes only in IQVIA data, despite having indications for Diabetes and Obesity in most launched countries. Novo Nordisk is the market leader and has a total GLP-1 volume market share, across Diabetes and Obesity care, of 59.0% globally. Within the US Operations and IO Operations, Novo Nordisk has a total GLP-1 volume market share of 47.3% and 68.4%, respectively.

In the following sections, unless otherwise noted, market data are based on moving annual total (MAT) from August 2024 and August 2025 provided by the independent data provider IQVIA. EUCAN covers Europe and Canada, Emerging Markets covers mainly Latin America, the Middle East and Africa. APAC covers Japan, Korea, Oceania, and Southeast Asia. Region China covers Mainland China, Hong Kong and Taiwan.
Diabetes care, development per geographical area Novo Nordisk’s share of the total diabetes market (value, MAT) Diabetes care, sales development
August August Sales 9M 2025
DKK million Growth
at CER
2025 2024
Global 31.6 % 33.8 % 155,759 8 %
US Operations 32.7 % 34.8 % 84,595 11 %
International Operations 28.2 % 30.7 % 71,164 4 %
– EUCAN * 32.3 % 35.3 % 32,376 8 %
– Emerging Markets ** 25.2 % 29.0 % 15,982 0 %
– APAC *** 17.3 % 18.7 % 9,496 6 %
– Region China **** 32.4 % 33.1 % 13,310 0 %

Source: IQVIA, August 2025 data. *Data for EUCAN available for 26 European markets and Canada representing approximately 100% of Novo Nordisk’s Diabetes care in the area. **Data for Emerging Markets available for 13 markets representing approximately 78% of Novo Nordisk’s Diabetes care in the area. ***Data for APAC available for five markets representing approximately 78% of Novo Nordisk’s Diabetes care in the area ****Data for mainland China, excluding Hong Kong and Taiwan. In IO countries, tirzepatide is categorised under GLP-1 diabetes only, despite having indications for diabetes and obesity in most launched countries.

GLP-1-based therapies for type 2 diabetes
Sales of GLP-1-based products for type 2 diabetes (Rybelsus, Ozempic and Victoza) increased by 7% measured in Danish kroner and by 10% at CER to DKK 114,675 million. The estimated global GLP-1 share of total diabetes prescriptions increased to 7.4% compared with 6.5% 12 months ago. It is possible for a patient to have a prescription for more than one diabetes treatment. Novo Nordisk has a value market share of 49.3%.
GLP-1 diabetes, development per geographical area Novo Nordisk’s share of the diabetes GLP-1 market (value, MAT) GLP-1 diabetes, sales development
August August Sales 9M 2025
DKK million Growth
at CER
2025 2024
Global 49.3 % 55.7 % 114,675 10 %
US Operations 48.1 % 53.3 % 73,252 10 %
International Operations 56.3 % 71.6 % 41,423 10 %
– EUCAN * 58.4 % 72.9 % 22,523 15 %
– Emerging Markets ** 47.7 % 64.2 % 8,333 6 %
– APAC *** 46.4 % 72.8 % 5,243 12 %
– Region China **** 82.2 % 79.9 % 5,324 (4 %)

Source: IQVIA, August 2025 data. Data for EUCAN available for 26 European markets and Canada representing approximately 100% of Novo Nordisk’s Diabetes care in the area. **Data for Emerging Markets available for 13 markets representing approximately 78% of Novo Nordisk’s Diabetes care in the area. ***Data for APAC available for five markets representing approximately 78% of Novo Nordisk’s Diabetes care in the area ****Data for mainland China, excluding Hong Kong and Taiwan. Note: the estimated GLP-1 share of prescriptions is based on volume packs from IQVIA. Volume packs are converted into full-year patients/prescriptions based on WHO assumptions for average daily doses, or if not available, Novo Nordisk assumptions. In IO countries, tirzepatide is categorised under GLP-1 diabetes only, despite having indications for diabetes and obesity in most launched countries.

Strategic aspirations Performance highlights Commercial execution Financials Cash flow and capital allocation Outlook Innovation and therapeutic focus Purpose and sustainability Corporate Governance Legal Financial Information
Company announcement No 31 / 2025

Financial report for the period 1 January 2025 to 30 September 2025
Page 6 of 38

Ozempic sales increased by 10% measured in Danish kroner and by 13% at CER to DKK 95,264 million. Sales growth was driven by both US Operations and International Operations. US sales were positively impacted by gross-to-net sales adjustments.

Rybelsus sales increased by 2% measured in Danish kroner and by 5% at CER to DKK 16,790 million. Sales growth was driven by International Operations, mainly within EUCAN, APAC and China, offset by decreasing sales in US Operations.

Victoza sales decreased by 36% measured in Danish kroner and by 34% at CER to DKK 2,621 million. The decline was driven by the GLP-1 diabetes market moving towards once-weekly treatments in both US Operations and International Operations.

US Operations
Sales of GLP-1 Diabetes care products in US Operations increased by 7% measured in Danish kroner and by 10% at CER. The sales increase was driven by Ozempic, partially countered by Victoza and Rybelsus. Ozempic sales in the US were positively impacted by gross-to-net sales adjustments followed by increasing volume growth, partially countered by lower realised prices. Novo Nordisk has a 48.1% value market share. The estimated GLP-1 share of total diabetes prescriptions has increased to 19.6% compared with 17.2% 12 months ago.

Sales growth in US Operations was positively impacted by gross-to-net sales adjustments, mainly related to Ozempic. Further, sales growth was driven by a prescription volume growth of the GLP-1 diabetes class of more than 10% in the third quarter of 2025 compared with the third quarter of 2024, countered by a decline in market share. Novo Nordisk’s share of total monthly prescriptions was 45.1%, while the share of new-to-brand prescriptions has decreased to 38.8%.

International Operations
Sales of GLP-1 Diabetes care products in International Operations increased by 7% measured in Danish kroner and by 10% at CER. The estimated GLP-1 share of total diabetes prescriptions has increased to 5.2% compared with 4.4% 12 months ago. Novo Nordisk is the market leader with a value market share of 56.3% compared with 71.6% 12 months ago.

EUCAN
Sales of GLP-1 Diabetes care products in EUCAN increased by 14% measured in Danish kroner and by 15% at CER. The sales growth reflects the uptake of Ozempic and Rybelsus. The estimated GLP-1 share of total diabetes prescriptions has increased to 10.0% compared with 8.4% 12 months ago. Novo Nordisk is the market leader in EUCAN with a value market share of 58.4%.

Emerging Markets
Sales of GLP-1 Diabetes care products in Emerging Markets decreased by 1% measured in Danish kroner and increased by 6% at CER. The estimated GLP-1 share of total diabetes prescriptions has increased to 3.1% compared with 2.5% 12 months ago. Novo Nordisk is the market leader in Emerging Markets with a value market share of 47.7%.

APAC
Sales of GLP-1 Diabetes care products in APAC increased by 10% measured in Danish kroner and by 12% at CER. The sales growth reflects increased sales of Rybelsus and Ozempic, partially offset by lower sales of Victoza. The estimated GLP-1 share of total diabetes prescriptions has increased to 3.1% compared with 2.4% 12 months ago. Novo Nordisk has a value market share of 46.4%.

Region China
Sales of GLP-1 Diabetes care products in Region China decreased by 7% measured in Danish kroner and by 4% at CER. The sales decline is driven by lower sales of Ozempic as well as Victoza. Ozempic is negatively impacted by wholesaler inventory movements. The GLP-1 share of total diabetes prescriptions has decreased to 3.1% compared with 3.4% 12 months ago. Novo Nordisk is the market leader in Region China with a value market share of 82.2%.

(Press release, Novo Nordisk, NOV 5, 2025, View Source [SID1234659469])

On November 5, 2025 BioDlink (1875.HK) reported to have congratulated its partner Lepu Biopharma (2157.HK) on receiving conditional marketing approval from China’s National Medical Products Administration (NMPA) for MEIYOUHENG (Becotatug Vedotin injection). This Class 1 innovative antibody-drug conjugate (ADC) targets the epidermal growth factor receptor (EGFR) for the treatment of recurrent or metastatic nasopharyngeal carcinoma (R/M NPC). Significantly, this is the world’s first approved non-photoimmunological EGFR-targeted ADC and a first-in-class innovation. This project is BioDlink’s first commercial ADC manufacturing initiative globally, validating its robust capabilities in the commercialization of complex biologics.

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This approval builds on BioDlink’s earlier success with Lepu Biopharma’s ADC program that achieved 100% first-pass success across technology transfer, Process Performance Qualification (PPQ), and Pre-Approval Inspection (PAI).

The program, designated as a Breakthrough Therapy Project, required rapid tech transfer and full production line delivery from monoclonal-antibody Drug Substance through ADC Drug Product.

BioDlink’s performance in this project secured BLA approval on October 30, 2025, demonstrating its capacity to meet aggressive regulatory timelines and ensure commercial readiness for global markets.

ADC manufacturing is technologically demanding, requiring exceptional process capabilities and robust quality systems. BioDlink participated in the entire development and production cycle, from technology transfer, process development, and analytical method establishment to clinical sample and GMP-compliant commercial batch manufacturing. This reflects the company’s end-to-end capabilities in supporting complex biologics from R&D to market launch.

Through close coordination with Lepu Biopharma and multiple regulatory authorities, BioDlink established an integrated quality management system. This system ensures seamless coordination across the entire production chain—accelerate the timeline for pivotal clinical batch production and subsequent PPQto meet aggressive regulatory submission goals and aligns with global GMP standards, including those of China, the U.S., and the EU. BioDlink’s manufacturing facilities have obtained GMP certifications from several countries and Foreign Manufacturer Approval from Japan’s PMDA. This collaboration sets a practical model for efficient multi-party industry collaboration and resource integration in the biopharma sector.

BioDlink’s manufacturing facilities have obtained GMP certifications from China, Brazil, Argentina, Indonesia, Egypt, Colombia, Pakistan and Thailand, as well as Foreign Manufacturer Approval from Japan’s PMDA. And also passed EU-QP 5 times in these years. This achievement marks a major step forward for ADC commercialization and demonstrates a practical model for multi-party industry collaboration and efficient resource integration.

Dr. Ziye Sui, Executive Director and CEO of Lepu BioPharma, commented: "We sincerely thank the BioDlink team for their outstanding CDMO services and strong collaboration. This approval also establishes a practical pathway for multi-party collaboration, offering new hope for R/M NPC patients who have failed anti-PD-(L)1 and platinum-based therapies."

Dr. Jian Zhang, Chief Operating Officer, BioDlink, noted: "The approval of this pilot batch highlights the increasing technical and quality coordination demands placed on both the Marketing Authorization Holder (MAH) and the CDMO. Moving forward, we will continue working closely with our partners to accelerate the launch of innovative medicines to benefit patients worldwide."

About Becotatug Vedotin

MEIYOUHENG (Becotatug Vedotin injection) is an ADC comprised of an EGFR-targeted monoclonal antibody conjugated with the potent microtubulin inhibiting payload monomethyl auristatin E via a valine-citrulline linker. It is the world’s first approved EGFR-targeted ADC and a first-in-class innovation, for the treatment of recurrent or metastatic nasopharyngeal carcinoma (R/M NPC).

It binds specifically with high affinity to EGFR on the surface of tumor cells, releases the potent payload upon internalization and lysosomal protease cleavage of the linker and results in tumor cell death. EGFR is highly expressed in colorectal cancer, lung cancer, head and neck cancer and other malignant solid tumors, and is expressed in 89% advanced NPC. Therefore, EGFR is an important target for cancer treatment.

(Press release, BioDlink, NOV 5, 2025, View Source [SID1234659486])

On November 5, 2025 NuCana plc (NASDAQ: NCNA) ("NuCana" or the "Company") reported that the China National Intellectual Property Administration ("CNIPA") has granted an important patent covering the composition of matter for NUC-7738. This patent (ZL 202010794701.2) is expected to serve as a key component of the patent protection for NUC-7738, which currently consists of over 85 issued patents worldwide. The composition of matter patent covers the chemical structure of NUC-7738, NuCana’s novel anti-cancer agent currently being evaluated in a Phase 1/2 clinical study (NuTide:701) in combination with pembrolizumab for patients with PD-1 inhibitor refractory or resistant melanoma. Securing this patent represents an important milestone for NuCana, strengthening its long-term global intellectual property strategy, while supporting potential opportunities to address unmet needs for innovative cancer therapies in China.

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Hugh S. Griffith, NuCana’s Founder and Chief Executive Officer said: "We welcome the CNIPA’s decision to grant this important new patent, which further strengthens the intellectual property protection of NUC-7738. The encouraging clinical data observed to date, together with the recent translational findings presented at ESMO (Free ESMO Whitepaper) 2025, continue to build confidence in the therapeutic potential of NUC-7738 in combination with PD-1 inhibition. As we aim to expand the NuTide:701 study with additional patients, we look forward to reinforcing the overall data package and progressing toward our goal of bringing meaningful new treatment options to patients with cancer."

(Press release, Nucana, NOV 5, 2025, https://ir.nucana.com/news-releases/news-release-details/nucana-announces-grant-composition-matter-patent-nuc-7738-china [SID1234659470])

On November 5, 2025 HanchorBio Inc. (TPEx: 7827), a global clinical-stage biotechnology company advancing next-generation immunotherapies for oncology and autoimmune diseases, reported that the preclinical data on HCB301, a novel tri-specific immunotherapeutic fusion protein, has been accepted for presentation at the 40th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), taking place November 5-9, 2025, in National Harbor, Maryland. Featured in a poster presentation, the data highlight HCB301’s differentiated design and multi-pronged antitumor mechanism, which engages both innate and adaptive immunity.

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HCB301 is designed to simultaneously:

Block SIRPα-CD47 interaction to enable macrophage-mediated phagocytosis
Block PD-1-PD-L1 signaling to restore exhausted T-cell function
Trap TGFβ to overcome stromal and immune exclusion in tumor microenvironment (TME)
This tripartite approach aims to overcome the limitations of existing checkpoint inhibitors by activating both arms of the immune system, especially in tumors with immunologically ‘cold’ or suppressive tumor microenvironments (TMEs) resistant to current treatments.

In addition to the HCB301 preclinical poster presented on November 5, HanchorBio will also present two late-breaking abstracts on November 7 to showcase clinical data on its SIRPα-Fc fusion protein HCB101. Together, the three posters underscore the breadth and translational strength of HanchorBio’s proprietary Fc-Based Designer Biologics (FBDB) platform across innate and adaptive immune pathways.

Scott Liu, Ph.D., Founder, Chairman, and CEO of HanchorBio, commented: "HCB301 builds directly on the foundation of HCB101, our clinical-stage SIRPα-engineered fusion protein. By integrating PD-1 blockade and TGFβ neutralization into a single molecule, HCB301 represents what we believe to be the first-in-class tri-specific fusion protein that simultaneously targets immune checkpoints, immune suppression, and macrophage dysfunction. This design reflects our commitment to building modular, next-generation immunotherapies with global translation potential. With IND clearance and first-patient dosing now achieved in both the US and China, HCB301 demonstrates the scalability of our FBDB platform and the executional readiness of our team across regions. As we advance HCB301 into the clinical stage, this milestone further positions HanchorBio as a long-term innovation partner for global co-development, particularly in cancers with high resistance to conventional immunotherapies."

Preclinical highlights of HCB301 (SITC Poster #P321)
Title: HCB301, a tri-specific fusion protein targeting SIRPα/CD47, PD-1/PD-L1, and TGFβ, promotes anti-tumor macrophage and T cell activity in preclinical models of solid tumors

Strong immune activation: HCB301 induced robust antibody-dependent cellular phagocytosis (ADCP), activated tumor-associated macrophages, and increased CD8+ T cell infiltration.
Synergistic antitumor efficacy: In CT26, MC38, and B16F10 models, HCB301 demonstrated superior tumor growth inhibition compared with single- or dual-arm comparators.
TGFβ suppression: HCB301 potently neutralized active TGFβ, reversing TME immunosuppression, and restoring T cell function.
Fc-effector tuning: Selective Fc engineering optimized immune activation while minimizing off-target toxicity.
"HCB301 was purpose-built to break through the resistance barriers that limit current PD-1 or CD47 monotherapies," remarked Wenwu Zhai, Ph.D., Chief Scientific Officer of HanchorBio. "Each of its three arms addresses a key axis of tumor immune evasion: CD47 for innate immune clearance, PD-1 for adaptive immune reactivation, and TGFβ for TME remodeling. Our preclinical data show that HCB301 delivers synergistic immune activation and tumor control, strongly supporting its advancement into the clinic."

About HCB301
Based on company analysis, HCB301 is the first clinical-stage tri-specific recombinant Fc-fusion protein that simultaneously targets SIRPα/CD47, PD-1/PD-L1, and TGFβ. It was designed using HanchorBio’s FBDB platform, which enables modular multi-arm immunotherapies with tunable Fc regions and enhanced manufacturability.

HCB301 integrates:

A high-affinity SIRPα domain that binds cancer cells’ CD47 to promote macrophage phagocytosis
A PD-1 extracellular domain that blocks PD-L1 and restores T-cell effector function
A TGFβRII domain that traps active TGFβ to alleviate immunosuppressive signals in the tumor microenvironment
The protein shows a favorable safety profile in repeat-dose toxicology studies in cynomolgus monkeys. Its differential tumor vs. RBC binding profile may reduce the risk of anemia, thrombocytopenia, or other cytopenia while maintaining potent anti-tumor activity.

HCB301 achieved IND clearance and first-patient dosing in both the US and China in 2025. The ongoing Phase 1 study (HCB301-101; NCT06487624) is a multi-regional, multi-center, open-label, dose-finding, first-in-human trial evaluating the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical efficacy of HCB301 in patients with advanced solid tumors or relapsed and refractory classical Hodgkin lymphoma.

(Press release, Hanchor Bio, NOV 5, 2025, View Source [SID1234659487])