On March 19, 2024 Circio Holding ASA (OSE: CRNA) reported that following approval of the investigational new drug (IND) application by the Chinese National Medical Products Administration (NMPA) on 1 March 2024, IOVaxis Therapeutics of Nantong, China, has on 15 March 2024 exercised its option to license mutant RAS cancer vaccines TG01 and TG02 (Press release, Circio, MAR 19, 2024, View Source [SID1234641258]). The license grants IOVaxis exclusive rights to develop and commercialize the TG vaccines in Greater China and Singapore.

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Under the license agreement between the parties, Circio is entitled to receive a milestone payment of USD 3m following the exercise of the license option. The total deal includes up to USD 10m in clinical development milestones, as well as royalties and commercial milestones on future sales.

Due to an ongoing process by IOVaxis to secure capital to cover both the milestone payments and the planned phase 1/2 TG01 clinical program and a re-evaluation around the TG01 intellectual property and data protection rights in China, IOVaxis has requested a six-month payment extension of the option fee and a discussion around certain commercial terms. The parties have agreed that IOVaxis will pay USD 300.000 of the option fee to Circio immediately, and that the remaining balance will be due on 15 September 2024. If the payments are not made by the agreed dates, the exclusive license will expire on 15 September 2024.

Dr. John Wang, CEO of IOVaxis Therapeutics, said: "Our substantially expanded IND-package has now been approved by the NMPA, and we are very eager to bring TG01 into the clinic as rapidly as possible to provide a much-needed targeted therapeutic option to patients in China with RAS-mutated pancreatic cancer. The IND-approval was also a critical milestone for our ongoing investor dialogues to secure the required capital for the planned TG01 development program in China and Singapore, and we are very grateful for the flexibility shown by the Circio team to grant an extension to allow further discussions between the parties and with our investors to take place".

Dr. Erik Digman Wiklund, CEO of Circio Holding ASA, added: "The partnership with IOVaxis is an important component of our aim to bring TG01 development forward through strategic collaborations in multiple settings and geographies. Dr. Wang and his team have shown strong commitment to get the IND approved, which required a substantial investment of time and resources by IOVaxis to develop a broad additional pre-clinical data package. We are very pleased to have such a dedicated partner and expect that the IND approval will make their fundraising successful. We look forward to taking our partnership to the next stage and initiate clinical development in China, which will be the first time TG01 is tested in an Asian patient population".

On March 18, 2024 Carina Biotech Limited (Carina), a clinical stage cell therapy immuno-oncology company, reported three poster presentations from studies of its LGR5-targeting CAR-T program in colorectal cancer and ovarian cancer at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024 that will take place in San Diego, California, on April 5-10 (Press release, Carina Biotech, MAR 18, 2024, View Source;utm_medium=rss&utm_campaign=press-release-carina-to-present-three-poster-presentations-at-aacr-annual-meeting-2024 [SID1234641257]).

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"We are looking forward to sharing data related to our LRG-5 targeted CAR-T program in three poster presentations at the upcoming AACR (Free AACR Whitepaper) annual meeting. One of the posters will highlight the GMP manufacturing and testing findings for our lead LGR5-targeted CAR-T cell therapy candidate CNA3103, that is currently being evaluated in a Phase 1/2 clinical trial for the treatment of adult patients with metastatic colorectal cancer," stated Deborah Rathjen, PhD, Carina’s Chief Executive Officer.

"Our research team will also be presenting preclinical data that demonstrate the potential to develop our LGR5-targeting CAR-T cells as a novel immunotherapy for ovarian cancer and that expand the preclinical body of evidence across a diverse range of cancer families, including ovarian, brain, liver, and stomach, where LGR5-targeting CAR-T cells may be harnessed."

Poster Presentation Details
Title: Preclinical in vivo characterization underpinning LGR5-targeting CAR-T cells as a cancer immunotherapy

Lead Author: Jade Foeng, PhD, Chemokine Biology Laboratory, Department of Molecular and Biomedical Science, The University of Adelaide, South Australia
Session Category: Immunology
Session Title: Adoptive Cell Therapies: CAR-T Cells
Session Date and Time: Sunday, April 7, 2024 1:30 pm PT – 5:00 pm PT
Location: Poster Section 2
Poster Board Number: 24
Published Abstract Number: 56

Title: CAR-T cells targeting LGR5: An effective treatment for chemotherapy resistant ovarian cancer

Lead Author: Wanqi (Jady) Wang, Robinson Research Institute, The University of Adelaide, South Australia
Session Category: Clinical Research
Session Title: Adoptive Cell Therapy 2
Session Date and Time: Tuesday, April 9, 2024 1:30 pm PT – 5:00 pm PT
Location: Poster Section 40
Poster Board Number: 11
Published Abstract Number: 6320

Title: From bench to bedside: GMP manufacturing and testing of LGR5-targeting CAR-T against colorectal cancer

Lead Author: Veronika Bandara, PhD, Molecular Immunology Laboratory, Robinson Research Institute, The University of Adelaide, South Australia
Session Category: Clinical Research
Session Title: Adoptive Cell Therapy 2
Session Date and Time: Tuesday, April 9, 2024 1:30 pm PT – 5:00 pm PT
Location: Poster Section 40
Poster Board Number: 22
Published Abstract Number: 6311

On March 19, 2024 AstraZeneca reported that it has entered into a definitive agreement to acquire Fusion Pharmaceuticals Inc., a clinical-stage biopharmaceutical company developing next-generation radioconjugates (RCs) (Press release, AstraZeneca, MAR 19, 2024, View Source [SID1234641248]). The acquisition marks a major step forward in AstraZeneca delivering on its ambition to transform cancer treatment and outcomes for patients by replacing traditional regimens like chemotherapy and radiotherapy with more targeted treatments.

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RCs have emerged as a promising modality in cancer treatment over recent years. These medicines deliver a radioactive isotope directly to cancer cells through precise targeting using molecules such as antibodies, peptides or small molecules. This approach has many potential advantages compared to traditional radiotherapy including minimising damage to healthy cells and enabling access to tumours not reachable through external beam radiation.

This acquisition complements AstraZeneca’s leading oncology portfolio with the addition of the Fusion pipeline of RCs, including their most advanced programme, FPI-2265, a potential new treatment for patients with metastatic castration-resistant prostate cancer (mCRPC). FPI-2265 targets prostate-specific membrane antigen (PSMA), a protein that is highly expressed in mCRPC, and is currently in a Phase II trial.

The acquisition brings new expertise and pioneering R&D, manufacturing and supply chain capabilities in actinium-based RCs to AstraZeneca. It also strengthens the Company’s presence in and commitment to Canada.

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "Between thirty and fifty per cent of patients with cancer today receive radiotherapy at some point during treatment, and the acquisition of Fusion furthers our ambition to transform this aspect of care with next-generation radioconjugates. Together with Fusion, we have an opportunity to accelerate the development of FPI-2265 as a potential new treatment for prostate cancer, and to harness their innovative actinium-based platform to develop radioconjugates as foundational regimens."

John Valliant, Chief Executive Officer, Fusion, said: "This acquisition combines Fusion’s expertise and capabilities in radioconjugates, including our industry-leading radiopharmaceutical R&D, pipeline, manufacturing and actinium-225 supply chain, with AstraZeneca’s leadership in small molecules and biologics engineering to develop novel radioconjugates. Expanding on our existing collaboration with AstraZeneca where we have advanced FPI-2068, an EGFR-cMET targeted radioconjugate into Phase I clinical trials, gives us a unique opportunity to accelerate the development of next-generation radioconjugates with the aim of transforming patient outcomes."

Fusion will become a wholly owned subsidiary of AstraZeneca, with operations continuing in Canada and the US.

Financial considerations
Under the terms of the definitive agreement, AstraZeneca, through a subsidiary, will acquire all of Fusion’s outstanding shares pursuant to a plan of arrangement for a price of $21.00 per share in cash at closing plus a non-transferable contingent value right of $3.00 per share in cash payable upon the achievement of a specified regulatory milestone. The upfront cash portion of the consideration represents a transaction value of approximately $2bn, a 97% premium to Fusion’s closing market price of $10.64 on 18th March 2024 and an 85% premium to the 30-day volume-weighted average price (VWAP) of $11.37 before this announcement. Combined, the upfront and maximum potential contingent value payments represent, if achieved, a transaction value of approximately $2.4bn, a 126% premium to Fusion’s closing market price on 18th March 2024 and a 111% premium to the 30-day VWAP. As part of the transaction, AstraZeneca will acquire the cash, cash equivalents and short term investments on Fusion’s balance sheet, which totalled $234m as of 31st December 2023.

The transaction is expected to close in the second quarter of 2024, subject to customary closing conditions, including the approval of Fusion shareholders and regulatory clearances.

Notes

Radioconjugates in oncology
RCs combine the precise targeting of antibodies, small molecules or peptides with potent medical radioisotopes to deliver radiation directly to cancer cells. By seeking out cancer cells, RCs provide a more precise mechanism of cancer cell killing compared with traditional radiation therapy, with the goal of improving efficacy while minimising toxicity on healthy cells. RCs are administered via systemic delivery, which enables their use in tumour types not accessible to external beam radiation and the targeting of cancer cells that have spread from the main tumour to other sites in the body.

About FPI-2265
FPI-2265 is an actinium-225 based PSMA-targeting RC for mCRPC, currently in a Phase II trial.

Actinium-225 emits alpha particles and holds the promise of being a next-generation radioisotope in cancer treatment. By delivering a greater radiation dose over a shorter distance, alpha particles such as actinium-225 have the potential for more potent cancer cell killing, and targeted delivery, thereby minimising damage to surrounding healthy tissue.

On March 18, 2024 Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA testing, reported a collaboration with the Fédération Francophone de Cancérologie Digestive and CHU Dijon Bourgogne on the CIRCULATE-PRODIGE-70 study, a randomized, multicenter, prospective phase III clinical trial in France investigating molecular residual disease (MRD)-guided adjuvant treatment in stage II colorectal cancer (CRC) patients (Press release, Natera, MAR 18, 2024, View Source [SID1234641247]).

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The study’s main objective is to determine the benefit of adjuvant chemotherapy (ACT) in stage II CRC patients with detectable circulating tumor DNA (ctDNA) post-surgery. Patients who are Signatera MRD-positive will be randomized to receive ACT (FOLFOX 6m) or pursue observation (no chemotherapy). Patients who are Signatera MRD-negative will be treated according to the standard of care (observation). Approximately 1,600 patients will be tested with Signatera, and a successful study result is expected to pave the way for the adoption and reimbursement of Signatera in France. The initial readout is expected in 2025.

CIRCULATE-France is complementary to the CIRCULATE-Japan and CIRCULATE-US trials. While the Japanese and U.S. trials evaluate the benefit of MRD-guided treatment in stage III and high-risk stage II CRC patients, the French trial is focused on stage II CRC.

"With more than 44,000 people in France affected by CRC, there is a significant need for more accurate tools to identify those who will benefit from adjuvant systemic therapy and those who can be treated with surgery alone," said Julien Taieb, MD, PhD, head of the gastroenterology and gastrointestinal oncology department at the Université Paris-Cité and principal investigator of the study. "We believe this randomized study could establish a new standard of MRD-guided care in stage II colorectal cancer, potentially improving treatment decisions for thousands of patients."

Natera has joined the study in progress. A separate methylation-based tumor-naive ctDNA assay, developed in-house by UMR-1138 Centre de Recherche des Cordeliers, was used to screen the first 800 patients for eligibility. The principal investigators elected to add Signatera, Natera’s personalized and tumor-informed MRD test, to enhance MRD detection.

"We are pleased to have been selected to support this pivotal trial, which underscores the value of personalized MRD testing across various clinical settings in colorectal cancer," said Adham Jurdi, MD, senior medical director of oncology at Natera. "We are encouraged by the early momentum of this study and look forward to partnering with the Fédération Francophone de Cancérologie Digestive to improve survival and outcomes for colorectal cancer patients in France."

About Signatera

Signatera is a personalized, tumor-informed, molecular residual disease test for patients previously diagnosed with cancer. Custom-built for each individual, Signatera uses circulating tumor DNA to detect and quantify cancer left in the body, identify recurrence earlier than standard of care tools, and help optimize treatment decisions. The test is available for clinical and research use and is covered by Medicare for patients with colorectal cancer, breast cancer, ovarian cancer and muscle invasive bladder cancer, as well as for immunotherapy monitoring of any solid tumor. Signatera has been clinically validated across multiple cancer types and indications, with published evidence in more than 50 peer-reviewed papers.

On March 18, 2024 Eureka Therapeutics, Inc., a clinical-stage biotechnology company developing novel T-cell therapies to treat cancer, reported the advancement of its ARYA-3 clinical trial to Phase II (NCT04864054) (Press release, Eureka Therapeutics, MAR 18, 2024, View Source [SID1234641246]). This milestone represents one of the first engineered T-cell programs targeting solid tumors to reach Phase II.

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The ARYA-3 trial is evaluating Eureka’s investigational ARTEMIS ECT204 T-cell therapy in adult patients with GPC3-positive advanced hepatocellular carcinoma (HCC), the predominant type of liver cancer. Glypican 3 (GPC3) is a promising target for HCC therapies and is found in more than 70% of HCC cells. The GPC3 protein is also expressed in other solid tumors, including ovarian and lung cancer.

The ARYA-3 trial has successfully completed Phase I and is now enrolling patients in Phase II. During this phase, the treatment’s efficacy and safety are evaluated in a larger patient population, offering crucial insights into its potential therapeutic benefits.

"We are excited by the favorable safety profile and promising early efficacy signals in Phase I of our ARYA-3 study. Moving to Phase II marks a significant milestone in our mission to advance cutting-edge therapies for cancer treatment," said Dr. Cheng Liu, President and CEO of Eureka Therapeutics. "We remain committed to building a pipeline of next-generation T-cell therapy for solid tumors."

ARYA-3 is an Open-Label, Dose Escalation, Multi-Center Phase I/II Clinical Trial of ECT204 T-Cell Therapy. In this study, a patient’s T cells are collected and genetically modified to express Eureka’s proprietary anti-GPC3 ARTEMIS T cell receptors (AbTCR). These modified T cells are then reintroduced into the patient to specifically seek out and destroy GPC3-expressing cancer cells. Eureka has previously demonstrated that its proprietary ARTEMIS T-cell receptor platform has several advantages over conventional chimeric antigen receptors (CARs), including better tumor infiltration, safety, and T cell persistence. The clinical trial is actively enrolling patients at both City of Hope and Kansas University Medical Center.

Patients, caregivers and health care professionals interested in Eureka’s clinical trials and technology can find more information by visiting eurekaconnectme.com.