On December 22, 2025 AstraZeneca and Daiichi Sankyo reported that Enhertu (trastuzumab deruxtecan) has been granted Breakthrough Therapy Designation (BTD) in the US for adult patients with HER2-positive early breast cancer with residual invasive disease in the breast and/or axillary lymph nodes after neoadjuvant treatment and high risk of disease recurrence.

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The Food and Drug Administration (FDA) BTD accelerates the development and regulatory review of potential new medicines intended to treat a serious condition and address a significant unmet medical need.

The FDA granted this BTD based on results from the DESTINY-Breast05 Phase III trial presented in a Presidential Symposium at the 2025 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress and subsequently published in The New England Journal of Medicine.

Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: "For patients with residual disease after neoadjuvant treatment, the post-neoadjuvant setting represents a critical opportunity to reduce the risk of recurrence and prevent progression to metastatic disease. This Breakthrough Therapy Designation highlights the impressive clinical benefit of Enhertu over the current standard of care and underscores its potential to become an important treatment option in the post-neoadjuvant setting."

Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: "This tenth Breakthrough Therapy Designation reinforces how Enhertu continues to deliver transformational results that advance the treatment of breast cancer. We look forward to working with the FDA with the goal of bringing Enhertu to the post-neoadjuvant setting of HER2-positive early breast cancer, as DESTINY-Breast05 clearly demonstrated that Enhertu may help halt invasive disease recurrence over the current standard of care, resulting in potentially more patients achieving a cure."

DESTINY-Breast05 is the second positive trial of Enhertu in early breast cancer in 2025. The first trial, DESTINY-Breast11, evaluating patients with high-risk HER2-positive disease in the neoadjuvant setting, is currently under review by the FDA.

Enhertu is a specifically engineered HER2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.

Notes

Post-neoadjuvant Treatment for HER2-Positive Early 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

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours including breast cancer.2 HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and poor prognosis in breast cancer.2 Approximately one in five cases of breast cancer are considered HER2 positive.3

For patients with HER2-positive early breast cancer, achieving pathologic complete response (pCR) with neoadjuvant treatment is the earliest indicator of improved long-term survival.4 However, approximately half of patients who receive neoadjuvant treatment do not experience pCR, putting them at increased risk of disease recurrence.5-9

Despite receiving additional treatment with T-DM1 for residual disease in the post-neoadjuvant setting, approximately 20% of patients still experience invasive disease or death, with no reduction in the risk of central nervous system recurrence.10-11 Once patients are diagnosed with metastatic disease, the five-year survival rate drops from nearly 90% to approximately 30%.12

Post-neoadjuvant therapy represents a key opportunity to minimise the risk of recurrence and prevent progression to metastatic disease for patients with residual disease. New treatment options are needed in the early breast cancer setting to help reduce the likelihood of disease progression and improve long-term outcomes for more patients.13,14

DESTINY-Breast05
DESTINY-Breast05 is a global, multicentre, randomised, open-label, Phase III trial evaluating the efficacy and safety of Enhertu (5.4 mg/kg) versus trastuzumab emtansine (T-DM1) in patients with HER2-positive early breast cancer with residual invasive disease in breast or axillary lymph nodes following neoadjuvant therapy and a high risk of recurrence. High risk of recurrence was defined as presentation with inoperable cancer (prior to neoadjuvant therapy) or pathologically positive axillary lymph nodes following neoadjuvant therapy.

The primary endpoint of DESTINY-Breast05 is investigator-assessed invasive disease-free survival (IDFS). IDFS is defined as the time from randomisation until first invasive local, axillary or distant recurrence or death from any cause. The key secondary endpoint is investigator-assessed disease-free survival. Other secondary endpoints include overall survival, distant recurrence-free interval, brain metastases-free interval and safety.

DESTINY-Breast05 enrolled 1,635 patients in Asia, Europe, North America, Oceania and South America. For more information about the trial, visit ClinicalTrials.gov.

Enhertu
Enhertu 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 programme 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 (5.4mg/kg) in combination with pertuzumab is approved in the US as a 1st-line treatment for adult patients with unresectable or metastatic HER2-positive (IHC 3+ or ISH+) breast cancer, as determined by an FDA-approved test based on the results from the DESTINY-Breast09 trial.

Enhertu (5.4mg/kg) is approved in more than 90 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+ or 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 (5.4mg/kg) is approved in more than 85 countries/regions 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 (5.4mg/kg) is approved in more than 55 countries/regions worldwide 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 (5.4mg/kg) is approved in more than 60 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumours 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 US for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Enhertu (6.4mg/kg) is approved in more than 70 countries/regions 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 (5.4mg/kg) is approved in more than 10 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumours 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.

Enhertu development programme
A comprehensive global clinical development programme is underway evaluating the efficacy and safety of Enhertu as a monotherapy, in combination or sequentially with other cancer medicines across multiple HER2-targetable cancers.

(Press release, AstraZeneca, DEC 22, 2025, View Source [SID1234661586])

On December 22, 2025 Astrazeneca reported The LATIFY Phase III trial of ceralasertib in combination with Imfinzi (durvalumab) did not meet the primary endpoint of overall survival (OS) versus standard-of-care docetaxel in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). The trial evaluated patients without actionable genomic alterations (AGAs) whose disease progressed on or after prior immunotherapy and platinum-based chemotherapy.

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Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: "Our goal in the LATIFY trial was to reinvigorate the immune response of patients with lung cancer whose tumours stopped responding to available therapies by combining ATR inhibition with immunotherapy. While we are disappointed by this result, we remain committed to pioneering new medicines to address the urgent need to improve outcomes for patients with lung cancer through our industry-leading portfolio."

The combination of ceralasertib and Imfinzi was generally well tolerated, and the safety profile was consistent with the known profiles of each individual medicine, with no new safety concerns identified. These data will be presented at a forthcoming medical meeting.

Notes

NSCLC
Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths.1 Lung cancer is broadly split into small cell lung cancer (SCLC) or NSCLC, the latter accounting for about 80-85% of cases.2-3 Patients are most commonly diagnosed with metastatic disease, when the tumour has spread outside the lung.4 Approximately 12% of people with metastatic NSCLC will still be alive five years after diagnosis.5

LATIFY
LATIFY is a randomised, open-label, multi-centre, global Phase III trial of ceralasertib plus Imfinzi in patients with locally advanced or metastatic NSCLC without AGAs, and whose disease has progressed on or after prior anti-PD-(L)1 therapy and platinum-based chemotherapy. Patients were randomised 1:1 to receive ceralasertib 240mg twice daily oral tablets for seven days in combination with a 1,500mg fixed dose of Imfinzi on day eight every four weeks or docetaxel every three weeks until disease progression, unacceptable toxicity, withdrawal of consent or a discontinuation criterion was met.

The trial enrolled 594 patients across more than 20 countries. The primary endpoint is OS and secondary endpoints include progression-free survival, objective response rate, duration of response, time to response, disease control rate and patient reported outcomes.

Ceralasertib
Ceralasertib is an oral, potent and selective inhibitor of the ATR kinase, which is crucial for DNA damage responses and cell survival. Ceralasertib acts on the tumour microenvironment, moving it from a suppressed immune state into an activated state when combined with immunotherapy.

Imfinzi
Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.

In lung cancer, Imfinzi is the global standard of care based on OS in the curative-intent setting of unresectable, Stage III NSCLC in patients whose disease has not progressed after chemoradiotherapy (CRT). Additionally, Imfinzi is approved as a perioperative treatment in combination with neoadjuvant chemotherapy in resectable NSCLC, and in combination with a short course of Imjudo (tremelimumab) and chemotherapy for the treatment of metastatic NSCLC. Imfinzi is also approved for limited-stage SCLC in patients whose disease has not progressed following concurrent platinum-based CRT; and in combination with chemotherapy for the treatment of extensive-stage SCLC.

In addition to its indications in lung cancers, Imfinzi is also approved in combination with chemotherapy in locally advanced or metastatic biliary tract cancer and in combination with Imjudo in unresectable hepatocellular carcinoma (HCC). Imfinzi is also approved as a monotherapy in unresectable HCC in Japan and the European Union (EU), and in resectable, early-stage and locally advanced gastric and gastroesophageal junction cancers in the US.

Perioperative Imfinzi in combination with neoadjuvant chemotherapy is approved for muscle-invasive bladder cancer. In May 2025, Imfinzi added to Bacillus Calmette-Guérin induction and maintenance therapy met the primary endpoint of disease-free survival for patients with high-risk non-muscle-invasive bladder cancer in the POTOMAC Phase III trial.

Imfinzi in combination with chemotherapy followed by Imfinzi monotherapy is approved as a 1st-line treatment for primary advanced or recurrent endometrial cancer (mismatch repair deficient disease only in the US and EU). Imfinzi in combination with chemotherapy followed by Lynparza (olaparib) and Imfinzi is approved for patients with mismatch repair proficient advanced or recurrent endometrial cancer in the EU and Japan.

Since the first approval in May 2017, more than 414,000 patients have been treated with Imfinzi. As part of a broad development programme, Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with NSCLC, bladder cancer, breast cancer, ovarian cancer and several gastrointestinal cancers.

(Press release, AstraZeneca, DEC 22, 2025, View Source [SID1234661585])

On December 22, 2025 Vividion Therapeutics, Inc. (Vividion), a clinical-stage biopharmaceutical company, and a wholly owned and independently operated subsidiary of Bayer AG, reported the publication of a manuscript describing the discovery and preclinical characterization of small molecules that activate KEAP1 via a novel covalent allosteric molecular glue mechanism to drive degradation of NRF2.

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The article, "A covalent allosteric molecular glue suppresses NRF2-dependent cancer growth" (Roy et al., Cancer Discov.), establishes NRF2 degradation via KEAP1 activation as a promising therapeutic approach for NRF2-activated cancers, including non-small cell lung cancer, esophageal squamous cell carcinoma, and head and neck squamous cell carcinoma.

"NRF2 has long stood as a symbol of undruggable cancer biology. Our team has opened a new chapter in targeting this critical cancer pathway through the discovery of KEAP1 activators," said Aleksandra Rizo, M.D., Ph.D., President and Chief Executive Officer of Vividion. "This research reflects the power of our platform to reveal unexpected allosteric mechanisms that could directly contribute to improved therapeutic efficacy, and ultimately better patient outcomes, for people with hard-to-treat cancers."

NRF2 is a transcription factor that promotes tumor growth, immune suppression, and resistance to cancer therapies. However, despite its clear role in disease progression, NRF2 has resisted direct pharmacologic inhibition due to its lack of canonical small-molecule binding pockets. Using Vividion’s covalent-first chemoproteomics platform, researchers discovered electrophilic small molecules that covalently bind to a specific cysteine residue on KEAP1 (C151) and induce an allosteric conformational change that enhances KEAP1’s interaction with the CUL3 E3 ligase complex. This stabilization of the KEAP1-CUL3 complex restores KEAP1’s ability to drive NRF2 degradation.

In preclinical models, these KEAP1 activators led to robust suppression of NRF2 signaling and showed meaningful antitumor activity across several tumor types with NRF2 pathway activation. Importantly, pharmacologic NRF2 degradation also enhanced the effects of multiple chemotherapies and radiotherapy, supporting the therapeutic potential of KEAP1 activation in overcoming treatment resistance in NRF2-driven cancers. Collectively, these findings provide a strong mechanistic and translational rationale for the clinical evaluation of KEAP1 activators.

"By showing that KEAP1 can be pharmacologically activated, Vividion has pioneered a new therapeutic approach to treating NRF2-driven cancers," said Matt Patricelli, Ph.D., Chief Scientific Officer of Vividion. "Mechanistic insights from these studies informed the design of our clinical KEAP1 activator, VVD-037, and its rational combinations with other cancer therapies. We’re excited to continue to explore its potential across the many cancer types driven by NRF2 dysregulation."

VVD-037, Vividion’s lead KEAP1 activator, is currently being evaluated in a Phase I clinical trial (NCT05954312) in patients with solid tumors characterized by NRF2 pathway activation.

(Press release, Vividion Therapeutics, DEC 22, 2025, View Source [SID1234661583])

On December 22, 2025 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported it will webcast its presentation at the 44th Annual J.P. Morgan Healthcare Conference on Monday, January 12, 2026. The presentation is scheduled for 2:15 p.m. Pacific Time (5:15 p.m. Eastern Time) and may be accessed from the "Investors & Media" page of Regeneron’s website at View Source A replay and transcript of the webcast will be archived on the Company’s website for at least 30 days.

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(Press release, Regeneron, DEC 22, 2025, View Source [SID1234661582])

On December 22, 2025 Propanc Biopharma, Inc. (Nasdaq: PPCB) ("Propanc" or the "Company"), a biopharmaceutical company developing novel treatments for chronic diseases such as recurrent and metastatic cancer, reported that the Company and its joint research partners at the Universities of Jaén and Granada published key findings in a peer reviewed journal, Scientific Reports, regarding the impact of proenzymes on pancreatic ductal adenocarcinoma (PDAC) fibroblasts. From the publishers of Nature, Scientific Reports is an online, open access journal, which publishes primary research from all areas of the natural and clinical sciences. The article is entitled, "Impact of pancreatic proenzymes on pancreatic ductal adenocarcinoma associated fibroblasts," and available online. The tumor microenvironment (TME) plays a pivotal role in tumor initiation, progression, and the form of pre-metastatic niches. PDAC is characterized by a dense fibrotic stroma containing a significant enriched population of cancer-associated fibroblasts (CAFs). The interplay between CAFs and tumor cells is crucial in driving tumor advancement and metastasis, underscoring the potential benefits of novel therapeutic strategies targeting stromal cells to improve patient survival. PRP, consisting of two bovine derived pancreatic proenzymes, trypsinogen and chymotrypsinogen, have shown efficacy in cancer treatment. The findings demonstrate PRP exerts multifaceted effects. Results underscore the candidacy of PRP as a potential disruptor of the TME.

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Future clinical investigation is planned to validate the translational potential of PRP as an adjunct therapy for PDAC patients who no longer respond to standard treatment regimen. Despite recent advancements in clinical management, PDAC remains one of the most aggressive and deadliest forms of cancer, projected to become the second leading cause of cancer-related deaths by 2030. PDAC is characterized by its late-stage diagnosis, limited treatment options, and poor prognosis.

"Our findings demonstrate that PRP exerts multifaceted effects specifically over the CAFs population and tumor cells. All together, these results highlight PRP as a promising adjunct therapeutic candidate capable of disrupting key interactions within the PDAC TME," said Dr. Belén Toledo, PhD, joint lead researcher from the University of Jaén.

"After several years of research pioneered with our scientific researchers, we find ourselves publishing compelling scientific evidence that PRP has the potential to dramatically alter the way we perceive poor patients diagnosed with this killer disease," said Mr. James Nathanielsz, Propanc’s Chief Executive Officer. "We plan to undertake our Phase 1b study in advanced cancer patients suffering from solid tumors in Q3, 2026, and further announcements are anticipated. This pivotal study will determine our target dose for Phase 2 studies in which PDAC is one of our target therapeutic indications. We look forward to advancing PRP into the clinic as soon as possible to help PDAC patients with such a poor survival prognosis."

(Press release, Propanc, DEC 22, 2025, View Source [SID1234661581])