On March 4, 2024 The European Medicines Agency (EMA) reported that it has validated two marketing authorisation applications (MAAs) for AstraZeneca and Daiichi Sankyo’s datopotamab deruxtecan (Dato-DXd) in two types of cancer (Press release, AstraZeneca, MAR 4, 2024, View Source [SID1234640715]). One MAA is for the treatment of adult patients with locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) who require systemic therapy following prior treatment. The other MAA is for the treatment of adult patients with unresectable or metastatic hormone receptor (HR)-positive, HER2-negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have progressed on and are not suitable for endocrine therapy and received at least one additional systemic therapy.

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The validations confirm the completion of the applications and commence the scientific review process by the EMA’s Committee for Medicinal Products for Human Use. The applications are based on data from the pivotal TROPION-Lung01 and TROPION-Breast01 Phase III trials presented during two Presidential Symposia at the 2023 European Society for Medical Oncology Congress.

Datopotamab deruxtecan is a specifically engineered TROP2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed by AstraZeneca and Daiichi Sankyo.

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "Our ambition is for datopotamab deruxtecan to improve upon and replace conventional chemotherapy in the treatment of multiple cancer types. Today’s dual validation of our applications in lung and breast cancers brings this potential medicine a meaningful step closer to redefining treatment expectations for patients with two of the most common cancers in Europe."

Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo, said: "The EMA validation is an important first step toward bringing this TROP2-directed antibody drug conjugate to eligible patients in Europe with nonsquamous lung cancer and HR-positive, HER2-negative breast cancer. This news builds on our recent regulatory progress in the US, where our lung cancer application has been accepted and our breast cancer application is underway, underscoring our commitment to changing the standard of care by developing new medicines to help as many patients worldwide as possible."

Additional regulatory submissions for datopotamab deruxtecan in lung cancer and breast cancer are underway in the US and globally.

Notes

Advanced non-small cell lung cancer
Nearly 500,000 lung cancer cases were diagnosed in Europe in 2022.1 NSCLC is the most common type of lung cancer, accounting for about 80% of cases.1 Approximately 70% and 30% of NSCLC tumours are of nonsquamous or squamous histology, respectively.2 While immunotherapy and targeted therapies have improved outcomes in the first-line setting, most patients eventually experience disease progression and receive chemotherapy.3,4,5 For decades, chemotherapy has been the last treatment available for patients with advanced NSCLC, despite limited effectiveness and known side effects.3,4,5

HR-positive breast cancer
More than 500,000 breast cancer cases were diagnosed in Europe in 2022.6 HR-positive, HER2-negative breast cancer is the most common subtype, accounting for more than 65% of diagnosed cases.7 Breast cancer is considered HR-positive, HER2-negative when tumours test positive for oestrogen and/or progesterone hormone receptors and negative for HER2 (measured as HER2 score of IHC 0, IHC 1+ or IHC 2+/ISH-).7,8 Standard initial treatment for this subtype of breast cancer is endocrine therapy but most patients with advanced disease will develop resistance, underscoring the need for additional options.9,10

TROP2
TROP2 is a protein broadly expressed in several solid tumours, including the majority of NSCLC and HR-positive, HER2-negative breast cancer cases.11,12 High TROP2 expression is associated with increased tumour progression and poor survival.12,13 There is currently no TROP2-directed ADC approved for the treatment of lung cancer.14,15

TROPION-Lung01
TROPION-Lung01 is a global, randomised, multicentre, open-label Phase III trial evaluating the efficacy and safety of datopotamab deruxtecan versus docetaxel in patients with locally advanced or metastatic NSCLC with and without actionable genomic alterations who require systemic therapy following prior treatment. Patients with actionable genomic alterations were previously treated with platinum-based chemotherapy and an approved targeted therapy. Patients without known actionable genomic alterations were previously treated, either in combination or sequentially, with platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor.

The dual primary endpoints of TROPION-Lung01 are progression-free survival (PFS) as assessed by blinded independent central review (BICR) and overall survival (OS). Key secondary endpoints include investigator-assessed PFS, objective response rate (ORR), duration of response (DoR), time to response, disease control rate (DCR) as assessed by both BICR and investigator, and safety. TROPION-Lung01 enrolled approximately 600 patients in Asia, Europe, North America and South America. For more information visit ClinicalTrials.gov.

TROPION-Breast01
TROPION-Breast01 is a global, randomised, multicentre, open-label Phase III trial evaluating the efficacy and safety of datopotamab deruxtecan versus investigator’s choice of single-agent chemotherapy (eribulin, capecitabine, vinorelbine or gemcitabine) in patients with unresectable or metastatic HR-positive, HER2-negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have progressed on and are not suitable for endocrine therapy per investigator assessment and have received at least one additional systemic therapy for unresectable or metastatic disease.

The dual primary endpoints of TROPION-Breast01 are PFS as assessed by BICR and OS. Key secondary endpoints include ORR, DoR, investigator-assessed PFS, DCR, time to first subsequent therapy and safety. TROPION-Breast01 enrolled more than 700 patients in Africa, Asia, Europe, North America and South America. For more information visit ClinicalTrials.gov.

Datopotamab deruxtecan (Dato-DXd)
Datopotamab deruxtecan (Dato-DXd) is an investigational TROP2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, datopotamab deruxtecan is one of six DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programmes in AstraZeneca’s ADC scientific platform. Datopotamab deruxtecan is comprised of a humanized anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

A comprehensive development programme called TROPION is underway globally with more than 14 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple cancers, including NSCLC, triple-negative breast cancer and HR-positive, HER2-negative breast cancer. Beyond the TROPION programme, datopotamab deruxtecan also is being evaluated in novel combinations in several ongoing trials.

On March 4, 2024 Medigene AG (Medigene, FSE: MDG1, Prime Standard), an immuno-oncology platform company focusing on the discovery and development of T cell immunotherapies for solid tumors, reported that the Company has been issued a patent by the Japan Patent Office protecting its inducible Medigene T cell receptor (iM-TCR), a control mechanism to regulate efficacy and safety of its T cell receptor engineered T cell (TCR-T) therapies (Press release, MediGene, MAR 4, 2024, View Source [SID1234640714]).

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"We are delighted with the receipt of the patent grant for our iM-TCR from the Japan Patent Office as we continue to expand and strengthen our IP portfolio. The ability to control the level of TCR activity with our iM-TCR technology after dosing has the potential to deliver more individualized efficacy and safety for patients. This patent grant is further validation of this innovative iM-TCR technology," said Selwyn Ho, CEO at Medigene. "The iM-TCR is a key example of the breadth of our technologies within our End-to-End Platform, that also includes multiple proprietary armoring and enhancement technologies. Combining our optimal 3S (sensitive, specific and safe) TCRs with technologies such as our iM-TCR technology is part of our ambition to deliver innovative solutions that can optimize safety and efficacy of TCR-T therapies."

TCR-T therapies have demonstrated that they can effectively kill tumor cells. However, excessive activation of T cells may lead to premature exhaustion or cell death, as well as unwanted overactivity and potential development of inflammatory responses in the body. The iM-TCR technology modifies the TCR to achieve control of TCR surface expression, allowing for fine-tuning of activity against tumor cells and thereby reducing potential inflammatory responses in the body. This property is of potential benefit to sensitive organs damaged by a sustained inflammatory response of T cells, such as with brain or liver cancer.

On March 1, 2024 Oncopeptides reported that a new article analyzing scientific data on melflufen, marketed in Europe as Pepaxti, was recently published in the peer-reviewed medical journal Clinical Lymphoma, Myeloma & Leukemia (Press release, Oncopeptides, MAR 1, 2024, View Source [SID1234646779]). The results provide further evidence that administration via peripheral venous catheter (PVC) is well tolerated with no local infusion-related reactions or new safety signals and may represent an alternative route of administration.

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The full article can be found here.

Following the recently finalized Type IB variation process, Pepaxti was recently approved for PVC administration within the EU, which was a feature particularly sought after by doctors in Germany, as it is a preferred method by many patients compared to the previously used central venous catheter (CVC) administration.

The phase 2 PORT study is an open-label, randomized, cross-over study which compared pharmacokinetics, safety and tolerability of peripheral or central intravenous administration of melflufen in combination with dexamethasone in patients with relapsed refractory multiple myeloma who had received at least two lines of prior therapy and were refractory to a proteasome inhibitor and an immunomodulatory drug.

"By allowing more choices for route of administration, we allow patients and their doctors more flexibility when using Pepaxti, supporting our ambition to provide as many patients as possible with a safe, efficient drug that maintains a high level of quality of life," says Stefan Norin, Chief Medical Officer at Oncopeptides.

For more information, please see questions and answers for investors, below.

Questions and Answers for investors

What is this?
Oncopeptides, like most other biotech companies conducting medical research, from time to time publish medical data in established scientific journals, such as Clinical Lymphoma, Myeloma & Leukemia, or at medical congresses. These articles and presentations are primarily aimed at healthcare professionals.

The article referenced above is referencing a clinical study showing that CVC and peripheral venous catheter (PVC) administration of melflufen were bioequivalent.

What does this data mean for physicians?
Providing multiple administration options for drugs to treat severe conditions like multiple myeloma can improve patient care by offering more personalized, safer, and convenient treatment pathways, ultimately contributing to better treatment adherence and outcomes.

What does this data mean to Oncopeptides?
The company has received feedback from particularly German doctors asking for the possibility to add PVC as an administration option. This could potentially mean that more patients can be treated with their preferred way of administration, and with time support a higher patient uptake.

What are medical journals?
Medical journals refer to written documents that present research findings, case studies, reviews, and other scientific information in the field of medicine. They are often published in scientific journals after undergoing a rigorous peer-review process.

Why are they important for a biotech company such as Oncopeptides?
Medical publications help to establish credibility, promote transparency, and provide valuable evidence for the efficacy and safety of treatments or interventions. By sharing research findings and clinical experiences, companies can contribute to the broader medical knowledge base, influencing patient care and industry standards.

What was the type IB process you refer to?
As Oncopeptides communicated on September 28, 2023, the company has decided to not extend its indication for Pepaxti into earlier lines of treatment. Despite the company not having an intention to expand the indication, the European Commission approved the application to do so. To address this, Oncopeptides in December submitted a so called type IB-variation to remove the new indication from the product information, ultimately leading to the same intended outcome. This process has now been finalized, with the added benefit that peripheral administration is a method of administration in the officially approved conditions of use a medicine, a feature sought after by doctors in Germany.

Do these publications affect product development?
The data from research and clinical trials, when published, can provide insights into the development of new drugs or new indications for existing ones. They can also guide the direction of future research projects.

How do healthcare professionals use these publications?
Healthcare professionals rely on medical publications to stay updated on the latest research, innovative techniques, and best practices. This knowledge helps them make informed decisions about patient care and treatment choices.

Can the general public access these publications?
It depends on the publication. While many medical journals require subscriptions, there are open-access journals and resources where research is freely available. The article in question is free to access.

Why is the peer-review process in medical publications crucial?
Peer review ensures that the research presented in the publication is of high quality, scientifically sound, and free from biases. Experts in the field evaluate the research, which helps maintain the credibility and trustworthiness of the findings.

How do medical publications benefit patients?
By driving advancements in medical science, these publications play a role in the development of newer, safer, and more effective treatments. When healthcare companies share their findings, it speeds up the dissemination of crucial information, ultimately leading to better patient outcomes.

On March 1, 2024, C4 Therapeutics, Inc. ("C4T") reported to have entered into a Research Collaboration and License Agreement ("License Agreement") with Merck KGaA, Darmstadt, Germany ("MKDG"), which operates its healthcare business as EMD Serono in the U.S. and Canada, to exclusively discover two targeted protein degraders against critical oncogenic proteins that C4T has progressed within its internal discovery pipeline (Filing, C4 Therapeutics, MAR 1, 2024, View Source [SID1234641009]).

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Pursuant to the terms of the License Agreement, C4T grants MKDG a worldwide, exclusive license under certain of C4T’s intellectual property rights to discover two targeted protein degraders against critical oncogenic proteins. MKDG is responsible for all development, regulatory approval, manufacturing and commercialization costs. Under the terms of the License Agreement, MKDG has agreed to make an upfront cash payment of $16.0 million and will fund C4T’s discovery research efforts. C4T is eligible to receive approximately $740 million in aggregate in discovery, regulatory, and commercial milestone payments across the collaboration, plus tiered royalties on net sales. Royalties payable from MKDG to C4T range from mid-single digit to low-double digit percent, subject to reductions under certain circumstances as described in the License Agreement.

Under the License Agreement, the royalty term for all contemplated royalties shall terminate on a product-by-product and country-by-country basis on the latest of (i) the ten (10) year anniversary of the first commercial sale of such product in such country, and (ii) the expiration of the last-to-expire licensed patent that covers such product in such country.

The License Agreement includes customary representations and warranties, covenants and indemnification obligations for a transaction of this nature. The License Agreement became effective upon signing and will continue until all of MKDG’s applicable payment obligations under the License Agreement have been performed or have expired, or the agreement is earlier terminated. Under the terms of the License Agreement, each of C4T and MKDG has the right to terminate the License Agreement for material breach by, or insolvency of, the other party. MKDG may also terminate the License Agreement in its entirety, or on a product-by-product or country-by-country basis, for convenience upon sixty (60) days’ notice.

The foregoing description of the License Agreement is only a summary and is qualified in its entirety by reference to the License Agreement, a copy of which C4T intends to file as an exhibit to C4T’s Quarterly Report on Form 10-Q for the period ending March 31, 2024.

On March 1, 2024 NeoGenomics, Inc. (NASDAQ: NEO), a leading oncology testing services company, reported the company will participate in the upcoming TD Cowen 44th Annual Health Care Conference in Boston, Massachusetts (Press release, NeoGenomics Laboratories, MAR 1, 2024, View Source [SID1234640712]).

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Members of NeoGenomics’ management team will participate in a fireside chat on Tuesday, March 5th at 9:10 a.m. ET. A live and archived audio webcast of the presentation will be available on the "News, Events, and Webcasts" tab via the Investor Relations section of the Company’s website at ir.neogenomics.com.