On March 17, 2025 Anocca AB, a leading T-cell immunotherapy company, reported the authorisation of its Clinical Trial Application (CTA) from the regulatory authorities in four European countries under the European Union’s (EU) harmonised framework, for VIDAR-1, with Germany acting as the reference state (Press release, Anocca, MAR 17, 2025, View Source [SID1234655345]). VIDAR-1 is a Phase I/II multi-product umbrella trial in patients with mutated KRAS-positive advanced pancreatic cancer. VIDAR-1 will test multiple products starting with the company’s lead product ANOC-001 that targets mutant KRAS G12V. ANOC-001 is a novel discovery from Anocca’s platform and will be manufactured in the company’s in-house cGMP facility.

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The CTA approval is the first regulatory authorisation in Europe to study a non-viral gene-edited TCR-T therapy in clinical practice, paving the way for the execution of Anocca’s scalable clinical product manufacturing strategy.

Phase I of the multi-centre trial will start in leading university hospitals in four northern European countries: Sweden, Denmark, Germany and The Netherlands. Anocca aims to initiate the study in Q2, 2025.

Reagan Jarvis, co-founder and Chief Executive Officer, commented, "This approval is a significant step in Anocca’s development as we transition to a clinical-stage company. Our highly skilled team is focused on discovering, optimising and manufacturing innovative next generation treatments that harness T-cell immunity and ANOC-001 represents the first of many products that will advance to the clinic in the coming years."

Zahid Bashir, Chief Medical Officer at Anocca, elaborated, "We are excited with the approval of VIDAR-1, as it represents a significant step towards addressing the unmet medical needs in patients with pancreatic cancer."

About the VIDAR-1 clinical programme

VIDAR-1 is designed as a multi-product umbrella trial targeting oncogenic driver mutations in KRAS within pancreatic ductal adenocarcinoma (PDAC). It will investigate up to 20 patients per product in a set of phase I/II studies. Phase I is planned for eight sites in four countries with additional countries and sites in phase II. The company plans to initiate first-in-human clinical studies in Q2, 2025. Patients will be eligible to enrol if they have an HLA, and KRAS mutation, matching an available product.

More information about the clinical trial can be found at the EU’s clinical trials website.

About KRAS and PDAC

Mutant KRAS is implicated in pancreatic, lung and colorectal cancers. G12V and G12D mutations in KRAS affect around 90% of pancreatic cancer patients. The five-year survival rate of patients with PDAC is less than 10% (1). Despite recent advances there are no definitive treatments for advanced patients at present (2).

References

1. Rawla et al (2019). Epidemiology of Pancreatic Cancer: Global Trends, Etiology and Risk Factors. World J Oncol. 10(1):10–27. doi: 10.14740/wjon1166

2. Hu & O’Reilly (2023). Therapeutic developments in pancreatic cancer. Nat Rev Gastroenterol Hepatol 21, 7–24. doi: 10.1038/s41575-023-00840-w

On March 17, 2025 Zentalis Pharmaceuticals, Inc. (Nasdaq: ZNTL), a clinical-stage biopharmaceutical company developing a potentially first-in-class and best-in-class WEE1 inhibitor for patients with ovarian cancer and other tumor types, reported updated clinical data from Part 1b of the ongoing DENALI clinical trial of azenosertib in patients with PROC in an oral presentation at the Society of Gynecologic Oncology (SGO) 2025 Annual Meeting on Women’s Cancer (Press release, Zentalis Pharmaceuticals, MAR 17, 2025, View Source [SID1234651193]).

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DENALI Part 1b is a Phase 2 single-arm study that evaluated azenosertib monotherapy at the 400mg QD 5:2 dose (once daily, five days on, two days off, or the "intermittent schedule") in patients with PROC (n=102).

As of the January 13, 2025 data cutoff, patients with Cyclin E1+ PROC tumors who were response-evaluable (patients who had at least one scan after receiving azenosertib) demonstrated an ORR of 34.9% (15/43; 95% CI: 21.0 – 50.9). In the intent-to-treat patients with Cyclin E1+ PROC (patients who received at least one dose of azenosertib), the ORR was 31.3% (15/48; 95% CI: 18.7 – 46.3), and an mDOR of 6.3 months (95% CI: 2.7 – not estimable). The mDOR is subject to change since there were patients with ongoing responses as of the cutoff date.

The presentation also demonstrates Cyclin E1 protein overexpression, regardless of CCNE1 gene amplification, as a sensitive and specific predictive biomarker that can be used to identify patients who could potentially derive benefit from azenosertib. Zentalis estimates that about half of PROC patients overexpress Cyclin E1 based on its proprietary immunohistochemistry cutoff.

As of the January 13, 2025 data cutoff, the safety and tolerability profile was consistent with the safety and tolerability profile from the Company’s January 29, 2025 investor event, which included data based off a cutoff date of December 2, 2024, with no new safety findings. Gastrointestinal toxicities and fatigue were found to be the most common treatment-related adverse events.

"The presentation of the updated DENALI Part 1b data at the SGO Annual Meeting supports our continued development of azenosertib," said Ingmar Bruns, M.D., Chief Medical Officer of Zentalis. "The clear anti-tumor activity and durable response observed highlights the potential of azenosertib to become an important treatment option for patients with Cyclin E1+ PROC. We are proud to have shared these data with many of the world’s leading gynecologic oncologists at SGO as part of our continued commitment to patients living with PROC."

"Platinum-resistant ovarian cancer is one of the most challenging types of ovarian cancer to treat. Tumors overexpressing Cyclin E1 protein exhibit poorer outcomes after standard of care chemotherapy regimens," said Fiona Simpkins, M.D., Director of Clinical & Translational Gynecologic Oncology Research at the University of Pennsylvania, and lead principal investigator in the DENALI study. "Developing new therapies for this subset of ovarian cancer patients is urgently needed. DENALI Part 1b results are exciting as they show that the WEE1 inhibitor, azenosertib, is active in a Cyclin E1 biomarker selective population potentially addressing a clinical unmet need."

The Company is on track to initiate enrollment of DENALI Part 2 in the first half of 2025 and expects to disclose topline data from DENALI Part 2 by year end 2026. DENALI Part 2, if successful, has the potential to support an accelerated approval, subject to FDA review. Zentalis plans to treat the same patient population in a Phase 3 randomized confirmatory study, subject to FDA review, which the Company plans to enroll concurrently with DENALI Part 2b.

Tomorrow, the Company will also present preclinical data of azenosertib during a poster presentation at the SGO Annual Meeting. The poster data highlights synergistic effects and significantly improved tumor growth inhibition in in vitro and in vivo preclinical models using a combination of azenosertib and microtubule inhibitor-based ADCs. Together with the previous data that azenosertib synergized with TOPO1 inhibitor based ADCs, these results indicate that azenosertib could be used as a generalizable combination partner with ADCs for improving responses in patients with advanced solid tumors.

The oral presentation and poster can be accessed through the "Publications" section of the Zentalis website.

About Azenosertib

Azenosertib is a novel, selective, and orally bioavailable inhibitor of WEE1 currently being evaluated as a monotherapy and combination clinical studies in ovarian cancer and additional tumor types. WEE1 acts as a master regulator of the G1-S and G2-M cell cycle checkpoints, through negative regulation of both CDK1 and CDK2, to prevent replication of cells with damaged DNA. By inhibiting WEE1, azenosertib enables cell cycle progression, despite high levels of DNA damage, thereby resulting in the accumulation of DNA damage and leading to mitotic catastrophe and cancer cell death.

On March 17, 2025 AstraZeneca reported that Imfinzi (durvalumab) has been approved in the European Union (EU) as monotherapy for the treatment of adults with limited-stage small cell lung cancer (LS-SCLC) whose disease has not progressed following platinum-based chemoradiation therapy (CRT) (Press release, AstraZeneca, MAR 17, 2025, View Source [SID1234651194]).

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The approval by the European Commission follows the positive opinion of the Committee for Medicinal Products for Human Use and is based on results from the ADRIATIC Phase III trial, which were published in The New England Journal of Medicine.

SCLC is a highly aggressive form of lung cancer, with an estimated 8,000 people treated for LS-SCLC across the five major European countries each year.1-2 LS-SCLC typically recurs and progresses rapidly, despite initial response to standard-of-care chemotherapy and radiotherapy.3-4 The prognosis for LS-SCLC is particularly poor, as only 15-30% of patients survive for five years after diagnosis.5

Suresh Senan, PhD, radiation oncologist at the Amsterdam University Medical Centers, The Netherlands, and principal investigator in the trial, said: "This approval marks a turning point for patients with limited-stage small cell lung cancer in Europe, bringing them an immunotherapy option for the first time. An unprecedented 57% of patients treated with durvalumab were still alive at three years in the ADRIATIC trial. This significant advance establishes a new benchmark in a setting where the standard of care has remained unchanged for decades."

Dave Fredrickson, Executive Vice President, Oncology Haematology Business Unit, AstraZeneca, said: "Imfinzi has the potential to transform how limited-stage small cell lung cancer is treated as the first immunotherapy approved in Europe in this setting. As the only immunotherapy approved for both early and late-stage disease, Imfinzi is poised to become the foundation for transforming outcomes for people with small cell lung cancer."

In the trial, results showed Imfinzi reduced the risk of death by 27% versus placebo (based on an overall survival [OS] hazard ratio [HR] of 0.73; 95% confidence interval [CI] 0.57-0.93; p=0.0104). Estimated median OS was 55.9 months for Imfinzi versus 33.4 months for placebo. An estimated 57% of patients treated with Imfinzi were alive at three years compared to 48% for placebo.

Imfinzi also reduced the risk of disease progression or death by 24% (based on a progression-free survival [PFS] HR of 0.76; 95% CI 0.61-0.95; p=0.0161) versus placebo. Median PFS was 16.6 months for Imfinzi versus 9.2 months for placebo. An estimated 46% of patients treated with Imfinzi had not experienced disease progression at two years compared to 34% for placebo.

The safety profile for Imfinzi was generally manageable and consistent with the known profile of this medicine. No new safety signals were observed.

Imfinzi is approved in the US and several other countries in this setting based on the ADRIATIC results. Regulatory applications are currently under review in Japan and several other countries for this indication. Imfinzi is also approved in combination with chemotherapy for the treatment of extensive-stage SCLC based on the CASPIAN Phase III trial.

Notes

Small cell lung cancer
Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths.6-7 Lung cancer is broadly split into non-small cell lung cancer (NSCLC) and SCLC, with about 15% of cases classified as SCLC.8

LS-SCLC (Stage I-III) accounts for approximately 30% of SCLC diagnoses and is classified when the disease is generally only in one lung or one side of the chest.9 The prognosis for patients with LS-SCLC remains poor despite curative-intent treatment with standard-of-care concurrent CRT (cCRT).10

ADRIATIC
The ADRIATIC trial is a randomised, double-blind, placebo-controlled, multi-centre global Phase III trial evaluating Imfinzi monotherapy and Imfinzi plus Imjudo (tremelimumab) versus placebo in the treatment of 730 patients with LS-SCLC who had not progressed following cCRT. In the experimental arms, patients were randomised to receive a 1500mg fixed dose of Imfinzi with or without Imjudo 75mg every four weeks for up to four doses/cycles each, followed by Imfinzi every four weeks for up to 24 months.

The dual primary endpoints were PFS and OS for Imfinzi monotherapy versus placebo. Key secondary endpoints included OS and PFS for Imfinzi plus Imjudo versus placebo, safety and quality of life measures. The trial included 164 centres in 19 countries across North and South America, Europe and Asia.

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 addition to its indications in SCLC, Imfinzi is also 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 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 and chemotherapy for the treatment of metastatic NSCLC.

Imfinzi is also approved in combination with chemotherapy (gemcitabine plus cisplatin) 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 EU.

In March 2025, perioperative Imfinzi added to standard-of-care chemotherapy met the primary endpoint of event-free survival in the MATTERHORN Phase III trial in resectable gastric and gastroesophageal junction cancers.

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 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 EU and Japan.

Since the first approval in May 2017, more than 374,000 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 SCLC, NSCLC, bladder cancer, breast cancer, several gastrointestinal and gynaecologic cancers, and other solid tumours.

On March 17, 2025 AstraZeneca and Alteogen Inc. reported to have entered into an exclusive license agreement for ALT-B4, a novel hyaluronidase utilising Hybrozyme platform technology (Press release, AstraZeneca, MAR 17, 2025, View Source [SID1234651195]). Under the terms of the agreement, AstraZeneca will acquire worldwide rights to use ALT-B4 to develop and commercialise subcutaneous formulations of several oncology assets. Alteogen will be responsible for clinical and commercial supply of ALT-B4 to AstraZeneca.

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Subcutaneous formulations have the potential to offer many advantages including time savings for patients, clinical staff, and health systems due to shorter administration times.

Cristian Massacesi, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca, said: "We are dedicated to advancing new medicines for people with cancer and that includes new methods of delivery which are more convenient for patients, physicians and healthcare systems. We look forward to collaborating with Alteogen on several assets in our portfolio with the goal of bringing new subcutaneous options to patients that can transform the way cancer care is delivered."

Dr Soon Jae Park, Chief Executive Officer of Alteogen, said: "We are excited to expand our Hybrozyme Technology by collaborating with AstraZeneca in their development of novel subcutaneous cancer medicines to meet the needs of patients."

Financial considerations
AstraZeneca will make an upfront payment to Alteogen and additional payments upon achievement of specific development, regulatory and sales-related milestones. Additionally, Alteogen will receive royalties on the sales of the commercialised products.

The transaction does not impact AstraZeneca’s financial guidance for 2025.

Notes

ALT-B4
ALT-B4 is Alteogen’s proprietary human recombinant hyaluronidase enzyme developed utilizing Hybrozyme technology. ALT-B4 can enable the large volume subcutaneous administration of drugs that are typically administered as an IV infusion. ALT-B4 does this by temporarily hydrolyzing hyaluronan in the extracellular matrix.

On March 17, 2025 EsoBiotec SA, a biotechnology company pioneering in vivo cell therapies that has demonstrated promising early clinical activity, reported it has entered into a definitive agreement to be acquired by AstraZeneca (Press release, EsoBiotec, MAR 17, 2025, View Source [SID1234651164]). The EsoBiotec Engineered NanoBody Lentiviral (ENaBL) platform empowers the immune system to attack cancers and could offer many more patients access to transformative cell therapy treatments delivered in just minutes rather than the current process which takes weeks.

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ENaBL uses highly targeted lentiviruses to deliver genetic instructions to specific immune cells, such as T cells, which programme them to recognise and destroy tumour cells for cancer treatment or autoreactive cells for potential use in immune-mediated diseases. This approach enables cell therapies to be administered through a simple IV injection and without the need for immune cell depletion.

Traditional cell therapies require cells to be removed from a patient, genetically modified outside the body, and then readministered to the patient as a medicine after immune cell depletion, typically taking weeks. By engineering immune cells directly within the patient’s body, the EsoBiotec in vivo approach has the potential to address many of the barriers associated with traditional cell therapies, reducing complexities and manufacturing timelines, thereby increasing access for patients.

Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: "We are excited about the acquisition of EsoBiotec and the opportunity to rapidly advance their promising in vivo platform. We believe it has the potential to transform cell therapy and will enable us to scale these innovative treatments so that many more patients around the world can access them. EsoBiotec will accelerate and expand the impact of our recent investments and marks a major step forward in realising our ambition to harness the full potential of cell therapy."

Jean-Pierre Latere, PhD, CEO, EsoBiotec, said: "We look forward to working with AstraZeneca, a global leader in drug development, to advance our shared goal of bringing transformative cost-effective cell therapies to more patients globally. By combining our expertise and resources, we can accelerate the development of our in vivo platform which has a novel delivery technology we believe will have broad therapeutic applicability."

EsoBiotec will become a wholly owned subsidiary of AstraZeneca, with operations in Belgium.

Financial considerations
AstraZeneca will acquire all outstanding equity of EsoBiotec for a total consideration of up to $1,000m, on a cash and debt free basis. This will include an initial payment of $425m on deal closing, and up to $575m in contingent consideration based on development and regulatory milestones.

The transaction is expected to close in the second quarter of 2025, subject to customary closing conditions and regulatory clearances.

Centerview Partners UK LLP is acting as exclusive financial advisor to EsoBiotec.

Cooley LLP is acting as legal advisor to EsoBiotec. Covington & Burling LLP is acting as legal advisor to AstraZeneca.