On July 17, 2025 Daiichi Sankyo reported that ENHERTU (fam-trastuzumab deruxtecan-nxki) in combination with pertuzumab has been granted Breakthrough Therapy Designation (BTD) in the U.S. for the first-line treatment of adult patients with unresectable or metastatic HER2 positive breast cancer (Press release, Daiichi Sankyo, JUL 17, 2025, View Source [SID1234654428]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

ENHERTU is a specifically engineered HER2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN).

The U.S. Food and Drug Administration (FDA) BTD is designed to accelerate the development and regulatory review of potential new medicines that are intended to treat a serious condition and address a significant unmet medical need. The medicine needs to have shown encouraging preliminary clinical results that demonstrate substantial improvement on a clinically significant endpoint over available medicines.

The FDA granted this BTD based on data from the DESTINY-Breast09 phase 3 trial presented during a special late-breaking oral session at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) (#ASCO25) Annual Meeting.

"This Breakthrough Therapy Designation provides further recognition of the potential benefit of ENHERTU in combination with pertuzumab in the first-line setting of HER2 positive metastatic breast cancer," said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. "If approved, ENHERTU will continue to redefine the treatment of metastatic breast cancer as these latest results from DESTINY-Breast09 demonstrate a median progression-free survival of more than three years when using ENHERTU plus pertuzumab in this disease setting, which is an improvement over the current standard of care that has been in place for more than a decade."

ENHERTU has received nine BTDs, including five BTDs for metastatic breast cancer. In addition to the new BTD, the four previous BTDs for breast cancer were for second-line HER2 positive metastatic breast cancer, later-line HER2 positive metastatic breast cancer, later-line HER2 low metastatic breast cancer and HER2 low or HER2 ultralow metastatic breast cancer. ENHERTU also received four additional BTDs for HER2 positive (IHC 3+) metastatic solid tumors, HER2 positive metastatic colorectal cancer, HER2 (ERBB2) mutant metastatic non-small cell lung cancer (NSCLC) and HER2 positive metastatic gastric cancer.

The latest BTD for ENHERTU represents the thirteenth BTD across the oncology portfolio of Daiichi Sankyo.

About DESTINY-Breast09

DESTINY-Breast09 is a global, multicenter, randomized, open-label, phase 3 trial evaluating the efficacy and safety of ENHERTU (5.4 mg/kg) either alone or in combination with pertuzumab versus standard of care THP (a taxane [docetaxel or paclitaxel], trastuzumab and pertuzumab) as a first-line treatment in patients with HER2 positive metastatic breast cancer.

Patients were randomized 1:1:1 to receive either ENHERTU monotherapy with a pertuzumab matching placebo; ENHERTU in combination with pertuzumab; or THP. Randomization was stratified by prior treatment (de novo metastatic disease versus progression from early-stage disease), hormone receptor (HR) status and PIK3CA mutation status.

The primary endpoint of DESTINY-Breast09 is progression-free survival (PFS) as assessed by blinded independent central review in both the ENHERTU monotherapy and ENHERTU combination arms. Secondary endpoints include investigator-assessed PFS, overall survival, objective response rate, duration of response, pharmacokinetics and safety. The investigational arm assessing ENHERTU monotherapy versus THP remains blinded to patients and investigators and will continue to the final PFS analysis.

DESTINY-Breast09 enrolled 1,157 patients across multiple sites in Africa, Asia, Europe, North America and South America. For more information about the trial, visit ClinicalTrials.gov

About HER2 Positive Metastatic Breast Cancer

Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide.1 More than two million breast cancer cases were diagnosed in 2022, with more than 665,000 deaths globally.1 While survival rates are high for those diagnosed with early breast cancer, only about 30% of patients diagnosed with or progress to metastatic disease are expected to live five years following diagnosis.

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors including breast cancer.3 HER2 protein overexpression may occur as a result of HER2 gene amplification.4 Approximately one in five cases of breast cancer are considered HER2 positive.

HER2 positive metastatic breast cancer is an aggressive disease driven by overexpression or amplification of HER2 that affects 15% to 20% of patients with metastatic breast cancer.6 While HER2 targeted therapies have improved outcomes, prognosis remains poor with most patients experiencing disease progression within two years of first-line treatment with THP, which has been the standard of care for more than a decade.4,7,8,9 Further, approximately one in three patients do not receive any treatment following first-line therapy due to disease progression or death.

About ENHERTU

ENHERTU (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the U.S. only) is a HER2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, ENHERTU is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca’s ADC scientific platform. ENHERTU consists of a HER2 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

ENHERTU (5.4 mg/kg) is approved in more than 85 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2 positive (immunohistochemistry [IHC] 3+ or in-situ hybridization (ISH)+) breast cancer who have received a prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial.

ENHERTU (5.4 mg/kg) is approved in more than 85 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2 low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.

ENHERTU (5.4 mg/kg) is approved in more than 40 countries for the treatment of adult patients with unresectable or metastatic hormone receptor (HR) positive, HER2 low (IHC 1+ or IHC 2+/ISH-) or HER2 ultralow (IHC 0 with membrane staining) breast cancer, as determined by a locally or regionally approved test, that have progressed on one or more endocrine therapies in the metastatic setting based on the results from the DESTINY-Breast06 trial.

ENHERTU (5.4 mg/kg) is approved in more than 60 countries worldwide for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations, as detected by a locally or regionally approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 and/or DESTINY-Lung05 trials. Continued approval in China and the U.S. for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

ENHERTU (6.4 mg/kg) is approved in more than 70 countries worldwide for the treatment of adult patients with locally advanced or metastatic HER2 positive (IHC 3+ or IHC 2+/ISH+) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01, DESTINY-Gastric02 and/or DESTINY-Gastric06 trials. Continued approval in China for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

ENHERTU (5.4 mg/kg) is approved in more than 10 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2 positive (IHC 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options based on efficacy results from the DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02 trials. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

About the ENHERTU Clinical Development Program

A comprehensive global clinical development program is underway evaluating the efficacy and safety of ENHERTU as a monotherapy or in combination or sequentially with other anti-cancer therapies across multiple HER2 targetable cancers.

On July 17, 2025 Oncotelic Therapeutics, Inc. (OTCQB: OTLC) ("Oncotelic" or the "Company"), a clinical stage biopharmaceutical company developing RNA targeted and small molecule therapeutics for cancer and rare diseases, reported the publication of new translational research evaluating TGFB2 expression and promoter methylation as potential prognostic markers in pancreatic ductal adenocarcinoma (PDAC) (Press release, Oncotelic, JUL 17, 2025, View Source [SID1234654427]). The article, "TGFB2 Expression and Methylation Predict Overall Survival in Pancreatic Ductal Adenocarcinoma Patients," appears in the International Journal of Molecular Sciences (IJMS). The work involved investigators affiliated with Sapu Biosciences, LLC ("Sapu"), a wholly owned subsidiary of GMP Biotechnology Limited ("GMP Bio"), of which Oncotelic holds a 45% ownership interest.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Access the publication: DOI 10.3390/ijms26136357 (open access via IJMS).

Study Highlights

Clinical data from the OT 101 P001 PDAC study suggest that targeting TGFB2 merits additional evaluation in younger patients; in a treated subset characterized by low IL 6, median OS was 12.7 months.
Investigator Commentary

"These findings give clinicians a practical way to stratify patients and design more precise, age focused trials, an urgently needed step toward improving outcomes in this notoriously lethal disease. OT-101, TGFB2 targeted approach deserves testing in randomized clinical trials," said Professor Wasif Saif, MD, co author of the study and Director of Eisenberg Center for Translational Therapeutics and Co-director of gastro-enterology Oncology Program at Karmanos Cancer Institute. He further added. "Our analysis shows that high TGFB2 expression was significantly associated with reduced overall survival ("OS") in patients under 65 (TGFB2 high median vs. low median OS: 17.9 vs. 66.9 months) but not in older cohorts. Moreover, elevated TGFB2 methylation showed improved survival in younger patients (high methylation vs. low methylation median OS: 66.9 vs. 17.9 months). In addition, our clinical data from a Pancreatic Ductal Adenocarcinoma trial using OT-101, an antisense oligonucleotide targeting TGFB2, further supported these findings that young patients treated with OT-101 showed improved OS compared to untreated controls. TGFB2 is not just another biomarker; its expression clearly delineates a younger subset of pancreatic cancer patients who experience far poorer survival, and a patient population we are challenged more commonly over the last few years."

Additional Company Perspective

"Younger adults now represent the fastest-growing slice of PDAC incidence ( 4 % per year in the 15-34 bracket). Once diagnosed, their absolute outcomes remain grim-five-year survival for all PDAC is only ~12 %. We see OT-101 playing an important therapeutic role in combating early onset PDAC," said Wen Han Chang, PhD, the lead bioinformatic scientist and Sr. Manager of Nanomedicine.

"Our PDAOAI knowledge platform helped our team efficiently assemble and interrogate the multi omic and clinical datasets underlying this manuscript-an example of how we aim to accelerate therapeutic insight generation," added Scott Myers, Product Manager.

About OT 101 (trabedersen)

OT 101 is an investigational phosphorothioate antisense oligonucleotide designed to down regulate transforming growth factor beta 2 (TGFB2), a cytokine implicated in tumor immune evasion, fibrosis, and resistance mechanisms across multiple solid tumors. OT 101 has received Rare Pediatric Disease Designation for diffuse intrinsic pontine glioma (DIPG) via the Company’s 45% joint venture, GMP Bio. Additional development work is ongoing across multiple tumor settings.

On July 17, 2025 Vas Narasimhan, CEO of Novartis, reporting on Q2 2025 results, said (Press release, Novartis, JUL 17, 2025, View Source [SID1234654425]):

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Novartis delivered another strong quarter, with double-digit sales and core operating income growth. We continue to drive strong performance on our ongoing launches for Kisqali, Pluvicto, and Scemblix, demonstrating the replacement power in our portfolio. We also delivered important pipeline milestones including a third positive Phase III readout for Pluvicto in hormone-sensitive prostate cancer and global filings for OAV101 IT in SMA. Our robust balance sheet and confidence in our mid and long-term growth enable us to initiate an up-to USD 10 billion share buyback as part of our commitment to balanced capital allocation."

Key figures

Q2 2025
Q2 2024
% change
H1 2025
H1 2024
% change

USD m
USD m
USD
cc

USD m
USD m
USD
cc
Net sales
14 054
12 512
12
11

27 287
24 341
12
13
Operating income
4 864
4 014
21
25

9 527
7 387
29
33
Net income
4 024
3 246
24
26

7 633
5 934
29
31
EPS (USD)
2.07
1.60
29
32

3.91
2.91
34
37
Free cash flow
6 333
4 615
37

9 724
6 653
46

Core operating income
5 925
4 953
20
21

11 500
9 490
21
24
Core net income
4 710
4 008
18
19

9 192
7 689
20
22
Core EPS (USD)
2.42
1.97
23
24

4.69
3.77
24
27

1. Constant currencies (cc), core results and free cash flow are non-IFRS measures. An explanation of non-IFRS measures can be found on page 40 of the Condensed Interim Financial Report. Unless otherwise noted, all growth rates in this Release refer to same period in prior year.

Strategy

Our focus

Novartis is a "pure-play" innovative medicines company. We have a clear focus on four core therapeutic areas (cardiovascular-renal-metabolic, immunology, neuroscience and oncology), with multiple significant in-market and pipeline assets in each of these areas, that address high disease burden and have substantial growth potential. In addition to two established technology platforms (chemistry and biotherapeutics), three emerging platforms (gene & cell therapy, radioligand therapy and xRNA) are being prioritized for continued investment into new R&D capabilities and manufacturing scale. Geographically, we are focused on growing in our priority geographies – the US, China, Germany and Japan.

Our priorities

1.
Accelerate growth: Renewed attention to deliver high-value medicines (NMEs) and focus on launch excellence, with a rich pipeline across our core therapeutic areas.
2.
Deliver returns: Continuing to embed operational excellence and deliver improved financials. Novartis remains disciplined and shareholder-focused in our approach to capital allocation, with substantial cash generation and a strong capital structure supporting continued flexibility.
3.
Strengthen foundations: Unleashing the power of our people, scaling data science and technology and continuing to build trust with society.

Financials

Second quarter

Net sales were USD 14.1 billion (+12%, +11% cc), with volume contributing 12 percentage points to growth. Generic competition had a negative impact of 2 percentage points, pricing had a positive impact of 1 percentage point, and currency had a positive impact of 1 percentage point.

Operating income was USD 4.9 billion (+21%, +25% cc), mainly driven by higher net sales, partly offset by higher investments behind priority brands and launches and net expense from legal matters.

Net income was USD 4.0 billion (+24%, +26% cc), mainly driven by higher operating income, partly offset by higher net financial expense. EPS was USD 2.07 (+29%, +32% cc), benefiting from the lower weighted average number of shares outstanding.

Core operating income was USD 5.9 billion (+20%, +21% cc), mainly driven by higher net sales, partly offset by higher investments behind priority brands and launches. Core operating income margin was 42.2% of net sales, increasing 2.6 percentage points (3.4 percentage points cc).

Core net income was USD 4.7 billion (+18%, +19% cc), mainly due to higher core operating income, partly offset by higher income taxes and net financial expense. Core EPS was USD 2.42 (+23%, +24% cc), benefiting from the lower weighted average number of shares outstanding.

Free cash flow amounted to USD 6.3 billion (+37% USD), compared with USD 4.6 billion in the prior-year quarter, driven by higher net cash flows from operating activities.

First half

Net sales were USD 27.3 billion (+12%, +13% cc), with volume contributing 14 percentage points to growth. Generic competition had a negative impact of 2 percentage points, pricing had a positive impact of 1 percentage point, benefiting from revenue deduction adjustments mainly in the US, and currency had a negative impact of 1 percentage point.

Operating income was USD 9.5 billion (+29%, +33% cc), mainly driven by higher net sales and contingent consideration adjustments, partly offset by higher investments behind priority brands and launches.

Net income was USD 7.6 billion (+29%, +31% cc), mainly driven by higher operating income, partly offset by higher income taxes and net financial expense. EPS was USD 3.91 (+34%, +37% cc), benefiting from the lower weighted average number of shares outstanding.

Core operating income was USD 11.5 billion (+21%, +24% cc), mainly driven by higher net sales, partly offset by higher investments behind priority brands and launches. Core operating income margin was 42.1% of net sales, increasing 3.1 percentage points (3.7 percentage points cc).

Core net income was USD 9.2 billion (+20%, +22% cc), mainly due to higher core operating income, partly offset by higher income taxes and net financial expense. Core EPS was USD 4.69 (+24%, +27% cc), benefiting from the lower weighted average number of shares outstanding.

Free cash flow amounted to USD 9.7 billion (+46% USD), compared with USD 6.7 billion in the prior-year period, driven by higher net cash flows from operating activities.

Q2 priority brands

Underpinning our financial results in the quarter is a continued focus on key growth drivers (ranked in order of contribution to Q2 growth) including:

Kisqali
(USD 1 177 million, +64% cc) sales grew strongly across all regions, including +100% growth in the US with strong momentum from the recently launched early breast cancer indication as well as continued share gains in metastatic breast cancer
Entresto
(USD 2 357 million, +22% cc) sustained robust, demand-led growth globally
Kesimpta
(USD 1 077 million, +33% cc) sales grew across all regions driven by increased demand and strong access
Scemblix
(USD 298 million, +79% cc) sales grew across all regions, demonstrating the continued high unmet need in CML and continued strong momentum from the recently launched early-line indication in the US
Leqvio
(USD 298 million, +61% cc) continued steady growth, with a focus on increasing account and patient adoption, and continuing medical education
Pluvicto
(USD 454 million, +30% cc) showed encouraging demand uptake in the US following the pre-taxane metastatic castration-resistant prostate cancer (mCRPC) approval, as well as continued access expansion ex-US in the post-taxane mCRPC setting
Cosentyx
(USD 1 629 million, +6% cc) sales grew mainly in the US and Europe, driven by recent launches as well as volume growth in core indications
Fabhalta
(USD 120 million) sales grew driven by continued launch execution across all markets in PNH as well as recent launches in IgAN and C3G in the US
Lutathera
(USD 207 million, +17% cc) sales grew mainly in the US, Europe and Japan due to increased demand and earlier-line adoption, particularly in the US and Japan
Zolgensma
(USD 297 million, -17% cc) sales declined reflecting a lower incidence of SMA compared to prior year, while demand remained robust

Net sales of the top 20 brands in the second quarter and first half

Q2 2025
% change
H1 2025
% change

USD m
USD
cc
USD m
USD
cc
Entresto
2 357
24
22
4 618
22
22
Cosentyx
1 629
7
6
3 163
11
11
Kisqali
1 177
64
64
2 133
59
60
Kesimpta
1 077
35
33
1 976
38
38
Tafinlar + Mekinist
573
10
7
1 125
13
13
Promacta/Revolade
502
-8
-9
1 048
-2
-1
Jakavi
524
11
8
1 016
7
8
Xolair
443
4
2
899
9
10
Ilaris
477
30
27
896
24
24
Pluvicto
454
32
30
825
26
26
Tasigna
327
-27
-27
704
-16
-15
Zolgensma
297
-15
-17
624
-3
-3
Sandostatin Group
303
-3
-3
620
-7
-6
Leqvio
298
64
61
555
67
66
Scemblix
298
82
79
536
79
78
Lutathera
207
18
17
400
16
16
Exforge Group
191
7
7
370
0
3
Lucentis
173
-37
-39
362
-39
-38
Diovan Group
154
-4
-4
304
1
3
Galvus Group
123
-18
-17
247
-17
-14
Top 20 brands total
11 584
16
14
22 421
16
17

R&D update – key developments from the second quarter

New approvals
Vanrafia
(atrasentan)
FDA granted accelerated approval for Vanrafia for the reduction of proteinuria in adults with primary IgA nephropathy (IgAN) at risk of rapid disease progression. Vanrafia can be seamlessly added to supportive care in IgAN and used as a foundational therapy.
Coartem
(artemether and lumefantrine)
In July, Swissmedic approved Coartem Baby, the first clinically proven malaria treatment specifically designed for newborns and infants between 2-5 kg. This milestone paves the way for registration in eight African countries through the Marketing Authorization for Global Health Products (MAGHP) procedure.

Regulatory updates
OAV101 IT (onasemnogene abeparvovec)
Regulatory submissions for OAV101 IT in patients with spinal muscular atrophy (SMA) were completed in the US and EU.

Results from ongoing trials and other highlights
Pluvicto
(lutetium Lu177 vipivotide tetraxetan)
At a prespecified interim analysis, the Phase III PSMAddition trial in PSMA+ metastatic hormone-sensitive prostate cancer (mHSPC) met its primary endpoint with a statistically significant and clinically meaningful benefit in radiographic progression-free survival (rPFS) in patients treated with Pluvicto plus standard of care (SoC) versus SoC alone. The study also showed a positive trend in overall survival in favor of the Pluvicto arm. Data will be presented at an upcoming medical meeting and, based on FDA feedback, submitted for regulatory review in H2 2025.
Cosentyx
(secukinumab)
In the Phase III GCAptAIN study, Cosentyx did not demonstrate a statistically significant improvement in sustained remission compared to placebo in adults with newly diagnosed or relapsing giant cell arteritis (GCA). Safety in GCA was consistent with the known safety profile of Cosentyx.
Kisqali
(ribociclib)
A new subgroup analysis of the Phase III NATALEE trial in HR+/HER2- early breast cancer (eBC) showed that patients receiving Kisqali plus endocrine therapy continued to see consistent reductions in risk of recurrence across all efficacy measures, regardless of age and menopausal status, at median follow-up of 44.2 months. Data presented at ASCO (Free ASCO Whitepaper).
Fabhalta
(iptacopan)
In the Phase IIIb APPULSE-PNH study, adult PNH patients with hemoglobin (Hb) levels ≥10g/dL who switched to Fabhalta from anti-C5 therapies experienced clinically meaningful improvements in Hb levels. The vast majority (92.7%) achieved Hb ≥12g/dL, reaching normal or near-normal levels. No patients treated with Fabhalta required transfusions, experienced breakthrough hemolysis or had any major adverse vascular events during the treatment period. Data presented at EHA (Free EHA Whitepaper).
Scemblix (asciminib)
In the Phase IIIb ASC4START trial evaluating the tolerability and efficacy of Scemblix versus nilotinib in adult patients with newly diagnosed Ph+ CML-CP, patients treated with Scemblix had a 55% lower risk of discontinuation due to AEs vs nilotinib, and 12.7% more patients treated with Scemblix achieved major molecular responses by week 12 vs those treated with nilotinib. Data presented at ASCO (Free ASCO Whitepaper) and EHA (Free EHA Whitepaper).
Votoplam
The Phase II PIVOT-HD study of votoplam in patients with Stage 2 and Stage 3 Huntington’s disease met its primary endpoint of reduction in blood Huntingtin (HTT) protein levels at Week 12 (p<0.0001), with durable, dose-dependent lowering observed through Month 12. Across all dose levels and disease stages, votoplam showed a favorable safety and tolerability profile, with no treatment-related serious adverse events or neurofilament light chain protein (NfL) spikes. Together with our partner, PTC Therapeutics, we are evaluating the results and plan to engage with the HD community and regulatory authorities to inform next steps.
Remibrutinib
A Phase II study with remibrutinib in food allergy met its primary endpoint with a statistically significant and clinically meaningful benefit. These data support remibrutinib’s potential as a first-in-class oral BTK inhibitor that reduces the risk of severe allergic reactions, including anaphylaxis. Phase III study planning is underway.
Ianalumab
Novartis will not advance investigation of ianalumab in hidradenitis suppurativa following a Phase II proof-of-concept study which did not meet our target criteria despite demonstrating efficacy vs placebo. No new safety signals were observed and all other studies for ianalumab in B-cell driven diseases continue as planned.
Rapcabtagene autoleucel (YTB323)
A Phase I/II study of rapcabtagene autoleucel, a rapidly manufactured CD19 CAR-T therapy using the T-Charge platform, demonstrated the expansion of CAR-T cells, deep B cell depletion, early and sustained improvement in overall disease activity, and a favorable benefit/risk profile in 21 patients with severe refractory SLE up to 12 months after treatment. Data presented at EULAR.

Zigakibart
Updated results from the Phase I/II study for zigakibart in IgAN showed a robust and clinically meaningful reduction in proteinuria of 60.4% from baseline and eGFR stabilization over 100 weeks of treatment. To date, this is the longest duration of treatment reported for an anti-APRIL agent, demonstrating long-term safety and efficacy. Data presented at ERA. The Phase III BEYOND trial is ongoing with anticipated readout in 2026.
Selected transactions
Novartis has completed the acquisition of Regulus Therapeutics, a clinical-stage biopharmaceutical company focused on developing microRNA therapeutics. Regulus’ lead asset, farabursen, is a potential first-in-class oligonucleotide targeting miR-17 for the treatment of autosomal dominant polycystic kidney disease (ADPKD) that recently completed Phase Ib. The acquisition is aligned with the therapeutic area focus of Novartis and leverages its strength and expertise in renal disease.

In July, Novartis entered into an agreement with Sironax, granting Novartis an exclusive option to acquire its Brain Delivery Module (BDM) platform, a differentiated blood-brain-barrier crossing technology designed to enhance the brain delivery of therapeutics of various modalities.

Capital structure and net debt

Retaining a good balance between investment in the business, a strong capital structure, and attractive shareholder returns remains a priority.

During the first half of 2025, Novartis repurchased a total of 48.8 million shares for USD 5.3 billion on the SIX Swiss Exchange second trading line under the USD 15 billion share buyback (announced in July 2023 and completed on July 1, 2025, with a total of 140.9 million shares repurchased over this period). In addition, 1.6 million shares (equity value of USD 0.2 billion) were repurchased from employees. In the same period, 11.2 million shares (equity value of USD 0.6 billion) were delivered to employees related to equity-based compensation plans. Novartis aims to offset the dilutive impact from equity-based compensation plans of employees over the remainder of the year. Consequently, the total number of shares outstanding decreased by 39.2 million versus December 31, 2024. These treasury share transactions resulted in an equity decrease of USD 4.9 billion and a net cash outflow of USD 5.4 billion.

Net debt increased to USD 23.8 billion at June 30, 2025, compared to USD 16.1 billion at December 31, 2024. The increase was mainly due to the free cash flow of USD 9.7 billion being more than offset by the USD 7.8 billion annual dividend payment, cash outflows for treasury share transactions of USD 5.4 billion and net cash outflow for M&A, intangible assets transactions and other acquisitions of USD 3.1 billion.

As of Q2 2025, the long-term credit rating for the company is Aa3 with Moody’s Ratings and AA- with S&P Global Ratings.

2025 outlook

Barring unforeseen events; growth vs. prior year in cc
Net sales
Expected to grow high single-digit
Core operating income
Expected to grow low-teens

Key assumption:
•
We continue to assume Entresto US generic entry in mid-2025 for forecasting purposes, though timing of generic entry is subject to ongoing IP and regulatory litigation

Foreign exchange impact

If mid-July exchange rates prevail for the remainder of 2025, the foreign exchange impact for the year would be positive 1 percentage point on net sales and negative 1 percentage point on core operating income. The estimated impact of exchange rates on our results is provided monthly on our website.

Key figures1

Q2 2025
Q2 2024
% change
H1 2025
H1 2024
% change

USD m
USD m
USD
cc

USD m
USD m
USD
cc
Net sales
14 054
12 512
12
11

27 287
24 341
12
13
Operating income
4 864
4 014
21
25

9 527
7 387
29
33
As a % of sales
34.6
32.1

34.9
30.3

Net income
4 024
3 246
24
26

7 633
5 934
29
31
EPS (USD)
2.07
1.60
29
32

3.91
2.91
34
37
Net cash flows from operating activities
6 664
4 875
37

10 309
7 140
44

Non-IFRS measures

Free cash flow
6 333
4 615
37

9 724
6 653
46

Core operating income
5 925
4 953
20
21

11 500
9 490
21
24
As a % of sales
42.2
39.6

42.1
39.0

Core net income
4 710
4 008
18
19

9 192
7 689
20
22
Core EPS (USD)
2.42
1.97
23
24

4.69
3.77
24
27

1. Constant currencies (cc), core results and free cash flow are non-IFRS measures. An explanation of non-IFRS measures can be found on page 40 of the Condensed Interim Financial Report. Unless otherwise noted, all growth rates in this Release refer to same period in prior year.

On July 17, 2025 NKGen Biotech, Inc. (OTC: NKGN) ("NKGen" or the "Company"), a clinical-stage biotechnology company focused on the development and commercialization of innovative autologous and allogeneic natural killer ("NK") cell therapeutics, and HekaBio K.K., headquartered in Chuo-ku, Tokyo ("HekaBio"), reported a strategic partnership to accelerate the regulatory, manufacturing and commercial development of NKGen’s autologous NK cell therapy, troculeucel, in Japan following HekaBio’s recently announced investment in common equity of NKGen (Press release, NKGEN Biotech, JUL 17, 2025, View Source [SID1234654424]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

HekaBio will lead all clinical trials in Japan and oversee all regulatory activities with Japan’s Pharmaceuticals and Medical Devices Agency for pre-market approval of troculeucel in several neurodegenerative disease indications, including Alzheimer’s and Parkinson’s Diseases.

As troculeucel is an autologous, non-genetically modified cell therapy, there is allowance under regenerative medicine regulations in Japan to offer this therapy to patients on an accelerated path, much faster than in other major markets. HekaBio will fully leverage the regulation and its domestic strategic partner network, aiming for first dosing in Japanese patients over the next 12 months. Beyond intractable disease, troculeucel has the potential to also support Japan’s aging population in the longevity/wellness space.

"Japan has always had an advanced progressive health care system where great attention has been placed on the use of novel autologous cell therapies for prevention, longevity, and wellness as well as for the treatment of more chronic illnesses," said Paul Y. Song, MD, Chairman and Chief Executive Officer ("CEO") of NKGen. "I am convinced that HekaBio’s clinical, regulatory, and commercial expertise will guide us to satisfy all regulatory requirements, find the best local manufacturing partner to make our therapy readily available, and ultimately develop the best commercial strategy for Japan. We are very excited to partner with HekaBio."

"Dementia, particularly Alzheimer’s Disease, and other neurodegenerative diseases together present significant health and social challenges in Japan due to the country’s aging population. We are very excited about our partnership with NKGen and look forward to advancing troculeucel for the benefit of patients and society," said Rob Claar, CEO of HekaBio.

On July 17, 2025 GSK plc (LSE/NYSE: GSK) reported that the US Food and Drug Administration (FDA) Oncologic Drugs Advisory Committee (ODAC) voted against the overall benefit/risk profile at the proposed dosage of Blenrep (belantamab mafodotin-blmf) combinations (Press release, GlaxoSmithKline, JUL 17, 2025, View Source [SID1234654423]). The belantamab mafodotin combinations were evaluated in adults with relapsed or refractory multiple myeloma who have received at least one prior line of therapy.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The FDA will consider the recommendation of the committee as it finalises its review on Blenrep in advance of the 23 July 2025 PDUFA date.

GSK remains confident in the benefit/risk profile of Blenrep (belantamab mafodotin-blmf) and will continue to work closely with the FDA as they complete their review for Blenrep in patients with relapsed or refractory multiple myeloma where there is high unmet need for novel treatment options that extend survival.

Blenrep combinations are approved in relapsed or refractory multiple myeloma in the UK1 and Japan2, as well as other markets, including Switzerland (based on the results of DREAMM-8). Applications are currently under review in all major markets globally, including the European Union3, and China4 (based on the results of DREAMM-7, with Breakthrough Therapy Designation for the combination and priority review for the application).

About multiple myeloma
Multiple myeloma is the third most common blood cancer globally and is generally considered treatable but not curable.5,6 There are approximately more than 180,000 new cases of multiple myeloma diagnosed globally each year.7 Multiple myeloma is a significant and enduring health concern in the US, where more than 35,000 cases were diagnosed in 2024.8 Research into new therapies is needed as multiple myeloma commonly becomes refractory to available treatments.9 Many patients with multiple myeloma are treated in a community cancer setting, leaving an urgent need for new, effective therapies with manageable side effects that can be administered outside of an academic centre.10,11

About Blenrep
Blenrep is an ADC comprising a humanised BCMA monoclonal antibody conjugated to the cytotoxic agent auristatin F via a non-cleavable linker. The drug linker technology is licensed from Seagen Inc.; the monoclonal antibody is produced using POTELLIGENT Technology licensed from BioWa Inc., a member of the Kyowa Kirin Group.

Indication
Blenrep combinations were approved in relapsed or refractory multiple myeloma in the UK in April 2025 and in Japan in May 2025. Applications are currently under review in all major markets.

In the UK, Blenrep is indicated in adults for the treatment of multiple myeloma:

in combination with bortezomib and dexamethasone in patients who have received at least one prior therapy; and
in combination with pomalidomide and dexamethasone in patients who have received at least one prior therapy including lenalidomide.
IMPORTANT SAFETY INFORMATION FOR BLENREP
More information can be found in the Blenrep Summary of Product Characteristics and Patient Information leaflets available on the MHRA Products website.12

About DREAMM-7
DREAMM-7 is a multicentre, open-label, randomised phase III clinical trial evaluating the efficacy and safety of belantamab mafodotin combined with bortezomib plus dexamethasone (BVd) compared to daratumumab combined with bortezomib plus dexamethasone (DVd) in patients with relapsed or refractory multiple myeloma who previously were treated with at least one prior line of multiple myeloma therapy, with documented disease progression during or after their most recent therapy. The trial enrolled 494 participants who were randomised 1:1 to receive either BVd or DVd. Belantamab mafodotin was administered at a dose of 2.5mg/kg intravenously every three weeks in combination for the first eight cycles and then continued as a single agent. The primary endpoint was progression-free survival (PFS) as per an independent review committee, with secondary endpoints including overall survival (OS), duration of response (DOR), and minimal residual disease (MRD) negativity rate as assessed by next-generation sequencing. Other secondary endpoints include overall response rate (ORR), safety, and patient reported and quality of life outcomes.

In DREAMM-7, BVd nearly tripled median PFS versus DVd (36.6 months versus 13.4 months, respectively (hazard ratio [HR]: 0.41 [95% confidence interval (CI): 0.31-0.53], p-value<0.00001). DREAMM-7 also met the key secondary endpoint of OS, showing a statistically significant and clinically meaningful 42% reduction in the risk of death at a median follow-up of 39.4 months favouring BVd (n=243) versus DVd (n=251) (HR 0.58; 95% CI: 0.43-0.79; p=0.00023). The three-year OS rate was 74% in the BVd arm and 60% in the DVd arm.

PFS results were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Plenary Series in February 2024 and published in the New England Journal of Medicine. OS results were presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2024.13,14

About DREAMM-8
DREAMM-8 is a multicentre, open-label, randomised phase III clinical trial evaluating the efficacy and safety of belantamab mafodotin in combination with pomalidomide plus dexamethasone (BPd) compared to bortezomib and pomalidomide plus dexamethasone (PVd) in patients with relapsed or refractory multiple myeloma previously treated with at least one prior line of multiple myeloma therapy, including a lenalidomide-containing regimen, and who have documented disease progression during or after their most recent therapy. The trial included 302 participants who were randomised 1:1 to receive either BPd or PVd. Compared to the patient population studied in the DREAMM-7 trial, patients in DREAMM-8 were more heavily pre-treated in that all had prior exposure to lenalidomide, 78% were refractory to lenalidomide, 25% had prior daratumumab exposure and of those most were daratumumab refractory. Belantamab mafodotin was administered at a dose of 2.5mg/kg intravenously for the first cycle and then 1.9mg/kg intravenously every four weeks. The primary endpoint was PFS as per an independent review committee, with key secondary endpoints including OS and MRD negativity rate as assessed by next-generation sequencing. Other secondary endpoints include ORR, DOR, safety, and patient reported and quality of life outcomes.

At the primary analysis at a median follow-up of 21.8 months, the median PFS was not yet reached (95% CI: 20.6-not yet reached [NR]) with the Blenrep combination compared to 12.7 months in the bortezomib combination (95% CI: 9.1-18.5). A positive OS trend was observed but not statistically significant (HR: 0.77 [95% CI: 0.53-1.14]) at the interim analysis. OS follow-up continues and further analyses are planned.

With additional follow-up, a clinically meaningful benefit continued to be observed, with a near-tripling of the median PFS for the Blenrep combination versus the bortezomib combination (32.6 months versus 12.5 months, respectively (HR: 0.49 [95% CI: 0.35-0.68]). At the end of one year, 71% (95% CI: 63-78) of patients in the BPd combination group compared to 51% (95% CI: 42-60) in the PVd combination group were alive and had not progressed. A benefit for BPd was observed across all pre-specified subgroups including those with poor prognostic features, such as patients who were refractory to lenalidomide and patients with high-risk cytogenetics.

Results were first presented at the 2024 ASCO (Free ASCO Whitepaper) Annual Meeting and published in the New England Journal of Medicine.15 Updated PFS results were presented at European Hematology Association (EHA) (Free EHA Whitepaper) Congress (EHA) (Free EHA Whitepaper) 2025.