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Affimed Reports Promising Phase 1 Efficacy and Safety Data for AFM28 in Relapsed/Refractory Acute Myeloid Leukemia (R/R AML)

On December 09, 2024 Affimed N.V. (Nasdaq: AFMD) ("Affimed", or the "Company"), a clinical-stage immuno-oncology company committed to giving patients back their innate ability to fight cancer, reported the oral presentation of data on AFM28 at the 66th ASH (Free ASH Whitepaper) Annual Meeting and Exposition (Press release, Affimed, DEC 9, 2024, View Source [SID1234648928]). The data, derived from the first-in-human Phase 1 study of AFM28, showed promising results in R/R AML, with signs of clinical efficacy and a well-managed safety profile at doses up to 300 mg weekly.

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The study included 29 heavily pretreated R/R AML patients across six AFM28 dose levels. The median number of prior treatment lines was two and 86% of patients had an adverse risk profile according to the 2022 guidelines from the European LeukemiaNet (ELN2022). AFM28 was administered intravenously once a week across six dose levels, ranging from 25 mg to 300 mg. AFM28 was well tolerated, and the most common treatment-emergent adverse events were IRRs, observed in 45% of patients. All IRRs were mild to moderate (Grade 1 or 2). One patient demonstrated grade 1 cytokine release syndrome (CRS). No neurotoxicity or signs for immune-effector related side effects were seen.

One of six patients treated at 250 mg showed a CR and stayed on treatment for 6.5 months. At the 300 mg dose level, 1 CR and 3 CRi were seen in 10 evaluable patients for a CRcR of 40%. Four of 10 patients are still on treatment with the option to deepen responses.

"Achieving a 40% composite complete remission rate with AFM28 in R/R AML is a significant milestone, especially in this difficult-to-treat patient population. Importantly, we see activity independent of mutational status, including patients with negative prognostic molecular profiles. Safety has been manageable which provides the basis for further development of AFM28 either as single agent or in combination regimens," said Dr. Andreas Harstrick, MD, Chief Medical Officer at Affimed.

The AFM28 Phase 1 study is on-going.

About AFM28

AFM28, a tetravalent, bispecific CD123- and CD16A-binding ICE, is designed to bring our immunotherapeutic approach to patients with acute myeloid leukemia (AML). It engages NK cells to initiate leukemic cell killing via antibody-dependent cellular cytotoxicity, even at low CD123 expression levels. AFM28 is currently in clinical development as monotherapy in patients with R/R AML (NCT05817058).

Fate Therapeutics Presents New Phase 1 Clinical Data of FT819 Off-the-shelf, CAR T-cell Product Candidate for Systemic Lupus Erythematosus

On December 9, 2024 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to bringing a first-in-class pipeline of induced pluripotent stem cell (iPSC)-derived cellular immunotherapies to patients with cancer and autoimmune disorders, reported new clinical and translational data from the Company’s FT819 Phase 1 Autoimmunity study for moderate-to-severe systemic lupus erythematosus (SLE) at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting being held in San Diego, CA (Press release, Fate Therapeutics, DEC 9, 2024, View Source [SID1234648927]). The first three study patients, each of whom presented with active lupus nephritis (LN) despite having been treated with multiple standard-of-care therapies, received fludarabine-free conditioning followed by a single dose of FT819 at 360 million cells. There were no dose-limiting toxicities (DLTs), no events of any grade of cytokine release syndrome (CRS), immune effector-cell associated neurotoxicity syndrome (ICANS), or graft-versus-host disease (GvHD), and rapid, deep, and sustained elimination of CD19+ B cells in the periphery was observed during the first month of treatment. FT819 is the Company’s off-the-shelf, CD19-targeted, 1XX CAR T-cell product candidate comprised of CD8αβ+ T cells with a memory phenotype and high CXCR4 expression to promote tissue trafficking.

"We continue to be very pleased with early clinical observations of fludarabine-free conditioning and FT819 off-the-shelf, CAR T-cell therapy in patients with moderate-to-severe SLE. The remarkable experience of the first patient treated in April is ongoing, as the patient remains on-study in drug-free clinical remission. In addition, the initial clinical and translational data from the two additional patients treated at the first dose level continue to support the potential for disease transformation," said Bob Valamehr, President of Research and Development of Fate Therapeutics. "We are now initiating dose expansion at this first dose level to accelerate development, and are also escalating dose based on the favorable safety profile observed. In addition, I am pleased to announce that the first patient has now been treated with FT819 as an add-on to maintenance therapy without conditioning chemotherapy. We believe our therapeutic approach is highly-differentiated and has the potential to transform disease outcomes without requiring patient apheresis, discontinuation of maintenance therapy, intense conditioning chemotherapy, and extended hospitalization."

FT819 Phase 1 Autoimmunity Study

The ongoing multi-center, Phase 1 clinical trial for patients with moderate-to-severe SLE is designed to evaluate the safety, pharmacokinetics, and anti-B cell activity of FT819 (NCT06308978). The first three patients, all of whom presented with active LN despite having been treated with multiple standard-of-care therapies, received fludarabine-free conditioning consisting of either cyclophosphamide alone or bendamustine alone, followed by a single dose of FT819 at 360 million cells. In all three patients, FT819 was detected in the peripheral blood and rapid, deep, and sustained elimination of CD19+ B cells in the periphery was observed during the first month of treatment. All three patients remain on-study, and there have been no DLTs and no events of any grade of CRS, ICANS, or GvHD. Based on these clinical observations, the Company is initiating dose expansion in up to 10 patients at this first dose level, and is also escalating dose to 720 million cells.

The Company’s FT819 Phase 1 Autoimmunity study also includes a second treatment arm to assess the safety, pharmacokinetics, and anti-B cell activity of a single dose of FT819 as an add-on to maintenance therapy without conditioning chemotherapy in patients with SLE. The first patient has now been treated in this second arm, which is being conducted in parallel with the study’s conditioning arm.

FT819 Patient 1 Case Study

The first patient treated in the Phase 1 Autoimmunity study presented with active LN and severe disease, which was marked by renal BILAG A (British Isles Lupus Assessment Group) disease activity score based on biopsy, SLEDAI-2K (Systemic Lupus Erythematosus Disease Activity Index) score of 20, FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) score of 33 (range 0-52, where a score of 52 indicates no fatigue) and PGA (Physician Global Assessment) score of 2.5 (where a score of 3 indicates most severe activity). Following administration of fludarabine-free conditioning and treatment with a single dose of FT819 at 360 million cells, the patient was discharged from the hospital without notable adverse events (AEs) after a protocol-required three-day stay. Rapid elimination of CD19+ B cells in the periphery was observed following treatment, and B-cell recovery by Month 3 was predominantly comprised of naïve, non-class switched B cells with near-complete elimination of switched memory B cells and deep depletion of plasmablasts, indicative of an immune reset. The patient reported that her debilitating fatigue had entirely resolved without further treatment, and treatment with methylprednisolone was discontinued at Month 3. The patient achieved DORIS (definition of remission in SLE) clinical remission, including with resolution of arthritis and active urinary sediment and with a substantial reduction in proteinuria, as of Month 6 follow-up. The patient continues on-study, in DORIS clinical remission, and remains free of all immunosuppressive therapy.

iPSC-derived CAR T-cell Product Platform

The Company also highlighted the scientific progress of its proprietary iPSC-derived CAR T-cell product platform at the ASH (Free ASH Whitepaper) Annual Meeting. In an oral presentation entitled "Off-the-shelf Product Candidate Incorporates Novel Sword & Shield Technology Designed to Promote Functional Persistence without Conditioning Chemotherapy", the Company compared its novel Sword & Shield technology, which utilizes a 4-1BB-targeted CAR (ADR) alongside the complete knock-out of CD58 (CD58KO) to both target and evade host alloreactive immune cells, to other host immune evasion strategies. In preclinical studies of allogeneic models, the Company showed that its Sword and Shield Technology specifically engaged with alloreactive T cells and supported functional persistence while avoiding the killing of general host T cells and activated anti-tumor T cells. This unique observation was not seen with other approaches that are either too broad and undesirably eliminate most of the host immune system or have limited coverage and cannot adequately protect the allogeneic cell product. In a second presentation entitled "Development of Induced Pluripotent Stem Cell-Derived T Cells Exhibiting Phenotypic and Functional Attributes of Primary CAR T Cells", the Company conducted a series of high-resolution analyses to show stimulated iPSC-derived T cells elicit primary T-cell like activation, proliferation, transcriptional and functional program engagement, and iPSC-derived CAR T cells uniquely emulate antigen-mediated response similar to primary-derived autologous CAR T cells.

About Fate Therapeutics’ iPSC Product Platform

Human induced pluripotent stem cells (iPSCs) possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company’s proprietary iPSC product platform combines multiplexed-engineering of human iPSCs with single-cell selection to create clonal master iPSC lines. Analogous to master cell lines used to mass produce biopharmaceutical drug products such as monoclonal antibodies, the Company utilizes its clonal master iPSC lines as a starting cell source to manufacture engineered cell products which are well-defined and uniform in composition, can be stored in inventory for off-the-shelf availability, can be combined and administered with other therapies, and can potentially reach a broad patient population. As a result, the Company’s platform is uniquely designed to overcome numerous limitations associated with the manufacture of cell therapies using patient- or donor-sourced cells. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 500 issued patents and 500 pending patent applications.

Medigene AG Announces KRAS G12V as First Target for TCR-guided T Cell Engagers

On December 9, 2024 Medigene AG (Medigene or the "Company", FSE: MDG1, Prime Standard), an oncology platform company focused on the research and development of T cell receptor (TCR)-guided therapies for the treatment of cancer, reported the selection of Kirsten rat sarcoma viral oncogene homologue (KRAS) G12V, in the context of HLA*A11, as the initial target for the co-development of T cell receptor-guided T cell engagers (TCR-TCEs) with WuXi Biologics (Press release, MediGene, DEC 9, 2024, View Source [SID1234648926]).

The selection of this first target is a key step for the partnership between Medigene and WuXi Biologics, which aims to advance multiple TCR-TCEs over the next three years. The collaboration seeks to harness Medigene’s expertise in the generation and characterization of highly sensitive, specific and safe (3S) TCRs with WuXi Biologics’ unique anti-CD3 monoclonal antibody (mAb), its TCE platform and proprietary bispecific antibody platform WuXiBody.

"Rapid selection of KRAS G12V as the target for this first program, also known as MDG3010 in Medigene’s pipeline, marks the initial step for the development of a TCR-TCE library for the treatment of difficult-to-treat tumors. This fast program progression reflects the highly effective collaboration between the teams," said Selwyn Ho, CEO of Medigene. "We believe that the combination of Medigene’s 3S TCR and WuXi Biologics’ CD3 mAb and bispecific platform offers the potential of a best-in-class therapeutic that precisely targets broad numbers of patients expressing this validated common KRAS mutation, in an off-the-shelf administration."

KRAS mutations are widely recognized as the most common oncogene mutations and play a significant role in indications that affect a large number of patients, such as pancreatic, small bowel, colorectal, and lung cancers.1 In pancreatic cancer, KRAS mutations are among the earliest and most critical genetic alterations, present in over 95% of cases; here, G12D and G12V are the most frequent (~65%).2,3 In 2020, pancreatic cancer was the seventh leading cause of cancer-related deaths globally for both men and women, with nearly as many newly diagnosed patients (496,000) as deaths (466,000) from this single indication.4

The bispecific therapies market offers a significant opportunity in the fight against cancer, addressing the unmet need in both solid and hematologic tumors. Over 5 million cancer patients worldwide face low five-year survival rates, highlighting the urgent demand for innovative treatments. Bispecific TCR-TCEs, which harness the immune system to target cancer cells more precisely, are projected to grow at a compound annual rate of 40.9% from 2023 to 2030. By 2030, the market is expected to surpass USD 80 billion5, reflecting its potential to transform cancer treatment and improve patient outcomes.

Datopotamab deruxtecan granted breakthrough therapy designation in US for patients with previously treated advanced EGFR-mutated non-small cell lung cancer

On December 9, 2024 AstraZeneca reported Datopotamab deruxtecan (Dato-DXd) has been granted Breakthrough Therapy Designation (BTD) in the US for the treatment of adult patients with locally advanced or metastatic epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) with disease progression on or after treatment with an EGFR-tyrosine kinase inhibitor (TKI) and platinum-based chemotherapy (Press release, AstraZeneca, DEC 9, 2024, View Source [SID1234648925]).

The US Food and Drug Administration (FDA) BTD is designed to accelerate the development and regulatory review of potential new medicines that are intended to treat serious conditions and address significant unmet medical needs. 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 TROPION-Lung05 Phase II trial with supporting data from the TROPION-Lung01 Phase III trial. Results from a pooled analysis of patients with previously treated EGFRm NSCLC in these studies were presented this month at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Asia 2024 Congress. This is the first BTD for datopotamab deruxtecan.

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "This Breakthrough Therapy Designation reinforces datopotamab deruxtecan as a promising potential therapy for patients with EGFR-mutated lung cancer who continue to face significant unmet needs following disease progression on or after initial treatments. We are proud to have long supported patients with EGFR-mutated lung cancer and look forward to the possibility of bringing another innovative treatment option to this community."

Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo, said: "The Breakthrough Therapy Designation granted by the FDA underscores the significant unmet need for new treatments for patients with previously treated EGFR-mutated non-small cell lung cancer who have experienced disease progression. Datopotamab deruxtecan has the potential to play an important role in improving outcomes and we look forward to working closely with the FDA to bring this medicine to patients as quickly as possible."

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.

AstraZeneca and Daiichi Sankyo recently announced the submission of a new Biologics License Application for accelerated approval in the US for datopotamab deruxtecan for the treatment of adult patients with locally advanced or metastatic EGFRm NSCLC who have received prior systemic therapies, including an EGFR-directed therapy.

Notes

Advanced non-small cell lung cancer
Nearly 2.5 million lung cancer cases were diagnosed globally in 2022.1 Lung cancer is broadly split into small or non-small cell lung cancer, the latter accounting for about 80% of cases.2 Approximately 10 to 15% of patients with NSCLC in the US and Europe, and 30 to 40% of patients in Asia have an EGFR mutation.3,4 The majority of EGFR mutations occur in tumours of nonsquamous histology.5

For patients with tumours that have an EGFR mutation, the established 1st-line treatment in the metastatic setting is an EGFR-TKI.6 While EGFR-TKIs have improved outcomes in the 1st-line setting, most patients eventually experience disease progression and receive subsequent therapies, such as chemotherapy.7-10

TROP2 is a protein broadly expressed in the majority of NSCLC tumours.11 There is currently no TROP2-directed ADC approved for the treatment of lung cancer.6,12

TROPION-Lung05
TROPION-Lung05 is a global, multicentre, single-arm, open-label Phase II trial evaluating the efficacy and safety of datopotamab deruxtecan in patients with locally advanced or metastatic NSCLC with actionable genomic alterations who have progressed on at least one TKI (with or without other systemic therapies) and on or after one regimen of platinum-based chemotherapy. Patients receiving up to four prior lines of treatment with tumours with one or more genomic alterations including EGFR, ALK, ROS1, NTRK, BRAF, RET or MET were eligible for the trial.

The primary trial endpoint is objective response rate (ORR) as assessed by blinded independent central review (BICR). Secondary efficacy endpoints include duration of response (DoR), disease control rate (DCR), clinical benefit rate, progression-free survival (PFS), time to response (TTR), overall survival (OS) and safety.

TROPION-Lung05 enrolled 137 patients globally in Asia, Europe and North America. For more information visit ClinicalTrials.gov.

TROPION-Lung01
TROPION-Lung01 is a global, randomized, multicentre, open-label Phase III trial evaluating the efficacy and safety of datopotamab deruxtecan versus docetaxel in adult 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 an approved targeted therapy and platinum-based chemotherapy. Patients without known actionable genomic alterations were previously treated, concurrently or sequentially, with platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor.

The dual primary endpoints of TROPION-Lung01 are PFS as assessed by BICR and OS. Key secondary endpoints include investigator-assessed PFS, ORR, DoR, TTR, and DCR as assessed by both BICR and investigator, and safety.

TROPION-Lung01 enrolled approximately 600 patients in Asia, Europe, North America, Oceania and South America. For more information visit ClinicalTrials.gov.

Primary PFS results and interim OS results from TROPION-Lung01 were presented at the ESMO (Free ESMO Whitepaper) 2023 Congress. Final OS results were presented at IASLC 2024 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer and simultaneously published in the Journal of Clinical Oncology in September 2024.

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 global clinical development programme is underway with more than 20 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple cancers, including NSCLC, triple-negative breast cancer and HR-positive, HER2-low or negative breast cancer. The programme includes seven Phase III trials in lung cancer and five Phase III trials in breast cancer evaluating datopotamab deruxtecan as a monotherapy and in combination with other anticancer treatments in various settings.

Daiichi Sankyo collaboration
AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly develop and commercialise Enhertu (trastuzumab deruxtecan) in March 2019 and datopotamab deruxtecan in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of Enhertu and datopotamab deruxtecan.

Affimed to Host Investor Conference Call Highlighting Clinical Data from AFM24 in Combination with Atezolizumab in Non-Small Cell Lung Cancer

On December 9, 2024 Affimed N.V. (Nasdaq: AFMD) ("Affimed", or the "Company"), a clinical-stage immuno-oncology company committed to giving patients back their innate ability to fight cancer, reported that it will host a conference call on Tuesday, December 17, at 8:30 a.m. EST / 14:30 CET to review clinical data from AFM24-102, the combination trial of its AFM24 innate cell engager ICE with atezolizumab in non-small cell lung cancer (Press release, Affimed, DEC 9, 2024, View Source [SID1234648924]).

The conference call will be available via phone and webcast. The live audio webcast of the call will be available in the "Webcasts" section on the "Investors" page of the Affimed website at View Source To access the call by phone, please use link
https://register.vevent.com/register/BI9c2d6fa7af764cb7b550c5ce464ce5cf, and you will be provided with dial-in details and a pin number.

Note: To avoid delays, we encourage participants to dial into the conference call 15 minutes ahead of the scheduled start time. A replay of the webcast will be accessible at the same link for 30 days following the call.