AFM28 / Affimed - LARVOL DELTA

The bispecific innate cell engager AFM28 eliminates CD123+ leukemic stem and progenitor cells in AML and MDS. (PubMed, Nat Commun) - "In addition, AFM28 is well tolerated and demonstrates pharmacodynamic activity in cynomolgus monkeys. Altogether, our results indicate that AFM28 has the potential to reduce relapse-inducing residual disease and promote long-term remissions for patients with AML and MDS with a favorable safety profile."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • CD123 • FCGR3A • IL3RA

AFM28-101: First-in-Human Dose Escalation Study of AFM28 in Patients With Relapsed/Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=30 | Terminated | Sponsor: Affimed GmbH | Trial completion date: Mar 2026 ➔ Jun 2025 | Recruiting ➔ Terminated | Trial primary completion date: Mar 2025 ➔ Nov 2024; As decided by sponsor

Trial completion date • Trial primary completion date • Trial termination • Acute Myelogenous Leukemia • B Cell Lymphoma • Hematological Malignancies • Leukemia • Oncology • IL3RA

Bispecific antibodies in immunotherapy for acute leukemia: latest updates from the 66th annual meeting of the American society of hematology, 2024. (PubMed, Front Oncol) - "Blinatumomab plus standard chemotherapy or in combination with other treatments, such as Mini-Hyper-CVD and Inotuzumab Ozogamicin, improved disease-free survival (DFS) in B-ALL. In AML and related conditions, novel BsAbs like AFM28 (CD123xCD16A) and Vibecotamab (CD123xCD3) showed promising efficacy in heavily pretreated R/R AML and in MDS/CMML following the failure of treatment with hypomethylating agents (HMA). The meeting underscored the transformative potential of BsAbs, especially in ALL-focused trials, with ongoing research aiming to evaluate their safety and efficacy in broader patient populations and combination regimens. This summary highlights the latest progress in BsAb-based immunotherapy presented at the ASH 2024 meeting, held from December 7-10 in San Diego, California."

IO biomarker • Journal • Review • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • IL3RA

SAFETY AND EFFICACY OF AFM28, A CD123-TARGETING INNATE CELL ENGAGER IN PATIENTS WITH RELAPSED/REFRACTORY CD123-POSITIVE ACUTE MYELOID LEUKAEMIA: INTERIM RESULTS FROM A PHASE 1 STUDY (EBMT 2025) - P1 | "Patients received a median of 2 prior lines (range: 1–3) of therapy; prior treatments included haematopoietic stem cell transplantation (n=6 [21%]), venetoclax combinations (n=20 [69%], and intensive chemotherapy (n=16 [55%])...All CRS and IRR events rapidly resolved with symptomatic treatment, and without tocilizumab... AFM28 monotherapy demonstrated early signs of clinical efficacy and a well-managed safety profile up to a weekly dose of 300 mg in patients with R/R AML. These results suggest further development of AFM28 in combination with standard of care therapies or allogenic off-the-shelf NK cells in patients with AML"

Clinical • P1 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Pneumonia • CD123 • FCGR3A • IL3RA

SAFETY AND EFFICACY OF AFM28, A CD123-TARGETING INNATE CELL ENGAGER IN PATIENTS WITH RELAPSED/REFRACTORY CD123-POSITIVE ACUTE MYELOID LEUKAEMIA: INTERIM RESULTS FROM A PHASE 1 STUDY (EBMT 2025) - P1 | "Patients received a median of 2 prior lines (range: 1–3) of therapy; prior treatments included haematopoietic stem cell transplantation (n=6 [21%]), venetoclax combinations (n=20 [69%], and intensive chemotherapy (n=16 [55%])...All CRS and IRR events rapidly resolved with symptomatic treatment, and without tocilizumab... AFM28 monotherapy demonstrated early signs of clinical efficacy and a well-managed safety profile up to a weekly dose of 300 mg in patients with R/R AML. These results suggest further development of AFM28 in combination with standard of care therapies or allogenic off-the-shelf NK cells in patients with AML"

Clinical • P1 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Pneumonia • CD123 • FCGR3A • IL3RA

AFM28 Shows Preliminary Activity in CD123+ Relapsed/Refractory AML (OncLive) - P1 | N=30 | NCT05817058 | Sponsor: Affimed GmbH | "AFM28 led to disease control in most patients with CD123-positive, relapsed/refractory acute myeloid leukemia (AML) across 5 dose levels and demonstrated a manageable safety profile that manifested most often in infusion-related reactions (IRRs), according to preliminary data from the phase 1 dose-escalation AFM28-101 trial...Regarding efficacy, 1 complete response (CR) occurred at dose level 5; this lasted for 6 cycles. Four of 10 evaluable patients at dose level 6 achieved a CR or CR with incomplete hematologic recovery as the best response to date, reflecting a composite CR rate of 40%."

P1 data • Acute Myelogenous Leukemia

Engaging Innate Immunity By AFM28, an Innate Cell Engager (ICE®) Targeting CD123-Positive Leukemic Cells in Patients with Relapsed/Refractory Acute Myeloid Leukemia: Safety and Efficacy Results of a First-in-Human Phase 1 Study (ASH 2024) - P1 | "Patients received a median of 2 prior lines (1-3) of antileukemic therapy with 5 patients (21%) with previous hematopoietic stem cell transplantation, 16 patients (67%) previously treated with venetoclax combinations, and 10 patients (42%) treated with intensive chemotherapy...All CRS and IRR events were fast resolving under standard of care treatment without the use of tocilizumab...Conclusions AFM28 monotherapy demonstrated early signs of clinical efficacy and a well-managed safety profile up to a weekly dose of 300mg in patients with R/R AML. These results support further development of AFM28 in combination with e.g., allogenic off-the-shelf NK cells in AML."

Clinical • P1 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Pneumonia • CD123 • FCGR3A • IL3RA

The Bispecific Innate Cell Engager AFM28 Can Leverage AML Patient's NK Cells in Addition to Allogeneic NK Cells, Enabling Elimination of CD123+ Leukemic Stem and Progenitor Cells in AML and MDS (ASH 2024) - "Our results demonstrate that AFM28 monotherapy has the potential to mediate anti-leukemic activity by leveraging the endogenous innate immunity in some AML patients. The anti-leukemic activity of AFM28 may be further increased in combination with allogeneic NK cell immunotherapy to improve responses in patients with low numbers and/or hypofunctional NK cells."

Clinical • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • CD123 • CD34 • CD38 • FCGR3A • IL3RA • KIT

Affimed Reports Promising Phase 1 Efficacy and Safety Data for AFM28 in Relapsed/Refractory Acute Myeloid Leukemia (R/R AML) (GlobeNewswire) - P1 | N=30 | NCT05817058 | Sponsor: Affimed GmbH | "Affimed N.V...today announced the oral presentation of data on AFM28 at the 66th ASH Annual Meeting and Exposition. 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....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."

P1 data • Acute Myelogenous Leukemia

Affimed Reports Third Quarter 2024 Financial Results & Business Update (GlobeNewswire) - "Upcoming Milestones: i) LuminICE-203: Efficacy update of four cohorts to be presented at ASH 2024. ii) AFM24-102: ORR and safety data from the EGFRwt cohort to be presented at a Company conference call on December 17, 2024. iii) AFM28-101: Updated data from the dose escalation to be presented at ASH 2024."

P1 data • P1/2 data • P2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Hodgkin Lymphoma • Oncology • Peripheral T-cell Lymphoma • Solid Tumor

Affimed Announces Acceptance of Three Abstracts at the 2024 ASH Annual Meeting Including an Oral Presentation Underscoring Advancing Clinical Pipeline in Leukemia and Lymphoma (GlobeNewswire) - "An oral presentation will feature clinical results including promising efficacy and safety data from the AFM28 phase 1 dose escalation study in relapsed/refractory acute myeloid leukemia (AML). A poster with preclinical data will highlight the in vitro efficacy of AFM28 in combination with both patient-derived autologous NK cells and healthy volunteer-derived allogeneic NK cells against leukemic blasts....Updated clinical results from all 4 cohorts of the run-in phase from the LuminICE-203 study evaluating acimtamig (AFM13) in combination with AlloNK (AB-101) for relapsed/ refractory Hodgkin Lymphoma will be shared in a poster session."

P1 data • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Hodgkin Lymphoma • Leukemia • Oncology

First-in-Human Dose Escalation Study of AFM28 in Patients With Relapsed/Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Affimed GmbH | Active, not recruiting ➔ Recruiting

Enrollment open • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • IL3RA

Affimed Reports Second Quarter 2024 Financial Results & Business Update (GlobeNewswire) - "Upcoming Milestones: LuminICE-203: Efficacy update of cohorts 1-4 expected to be presented at a future scientific conference in Q4 2024...AFM28-101: Data from the study is expected to be presented at a scientific conference in Q4 2024."

P1 data • P2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Hodgkin Lymphoma • Leukemia • Lymphoma • Oncology

First-in-Human Dose Escalation Study of AFM28 in Patients With Relapsed/Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=24 | Active, not recruiting | Sponsor: Affimed GmbH | Recruiting ➔ Active, not recruiting | N=50 ➔ 24

Enrollment change • Enrollment closed • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • IL3RA

THE BISPECIFIC INNATE CELL ENGAGER AFM28 INDUCES POTENT ANTI-TUMOR ACTIVITY AGAINST AML IN A XENOGRAFT MOUSE MODEL AND IN A BONE MARROW NICHE IN VITRO MODEL (EHA 2024) - "AFM28 demonstrated significant anti-leukemic activity in both in vivo and ex vivo settings. The therapeuticeffects of AFM28 were recapitulated in the fully human bone marrow niche model, in which key immunesuppressive cellular components (i. e."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • ADGRG1 • CD123 • CD34 • FCGR3A • IL3RA

Affimed Reports First Quarter 2024 Financial Results & Business Update (GlobeNewswire) - P1 | N=50 | NCT05817058 | Sponsor: Affimed GmbH | "AFM28 (CD123 / CD16A): Completed enrollment of the sixth and final cohort in the multi-center Phase 1 open-label, dose-escalation study (AFM28-101), of AFM28 monotherapy in CD123-positive r/r acute myeloid leukemia (AML). Of 6 patients treated at dose level 6 at 300mg, 1 patient showed a CR, 1 patient a CRi and 3 patients achieved SD, a CR/CRi rate of 33%. Of 6 patients treated at dose level 5 at 250 mg, 1 patient showed a CR, ongoing after 5 months; 5 patients achieved a SD as best response. No dose-limiting toxicities were reported in dose levels 5 and 6. Data from the study is expected to be presented at a future scientific conference."

Enrollment closed • P1 data • Acute Myelogenous Leukemia

Affimed Announces Acceptance of an Abstract on Preclinical Data of its Innate Cell Engager AFM28 at the European Hematology Association 2024 Congress (GlobeNewswire) - "Affimed N.V...announced the publication of an abstract for the annual congress of the European Hematology Association (EHA), taking place in Madrid, Spain, June 13 – 16, 2024. The abstract presents preclinical data of Affimed’s CD16A/CD123-targeting ICE, AFM28, in an acute myeloid leukemia (AML) mouse xenograft model and shows that increasing doses of AFM28 lead to a dose-dependent tumor growth control, resulting in an increased median life span of the treated mice compared to controls....In a newly engineered ex vivo Human Organotypic Marrow Environment (HOME) model, the combination of AFM28 and allogeneic NK cells can lead to an effective reduction of CD123-expressing AML patient-derived leukemic blasts and stem cells. Importantly, the HOME model exhibits key immune suppressive cellular components, i.e. mesenchymal niche cells, enhancing the translational relevance of AFM28 preclinical activity."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Affimed Reports 2023 Financial Results and Operational Progress (GlobeNewswire) - P1 | N=50 | NCT05817058 | Sponsor: Affimed GmbH | "Completed enrollment of the fifth cohort, recruiting patients in the sixth and final cohort in the multi-center Phase 1 open-label, dose-escalation study (AFM28-101), of AFM28 monotherapy in CD123-positive r/r AML. No dose-limiting toxicities were reported. Further clinical development of AFM28 is planned in combination with an allogeneic off-the-shelf NK cell product....Further progress updates from AFM28-101 dose escalation expected in Q2 2024."

Enrollment status • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

First-in-Human Dose Escalation Study of AFM28 in Patients With Relapsed/Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=50 | Recruiting | Sponsor: Affimed GmbH

Trial completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • IL3RA

Affimed Reports Third Quarter 2023 Financial Results and Highlights Operational Progress (GlobeNewswire) - "Based on the results from the AFM24 monotherapy study, a fourth expansion cohort of patients with EGFR-mutant NSCLC has been added to the AFM24-102 study and is enrolling and treating patients. Data from this cohort is expected in the first half of 2024....AFM28 is investigated in a multi-center Phase 1 open-label, dose-escalation study (AFM28-101), in r/r AML. Dose level three was completed with no dose-limiting toxicities; completed enrollment in the fourth dose cohort. Clinical development of AFM28 is planned as both single-agent and in combination with an allogeneic off-the-shelf NK cell product....Data release from the first three expansion cohorts of the Phase 1/2a study AFM24+atezolizumab combination study planned in December 2023....Further progress updates from AFM28-101 dose escalation planned in H1 2024."

P1 data • P1/2 data • Trial status • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Novel bispecific innate cell engager AFM28 efficiently directs allogenic NK cells to CD123+ leukemic blasts and stem cells in Acute Myeloid Leukemia and Myelodysplastic Neoplasms (DGHO 2023) - P1 | "AFM28 induced NK cell activation at low picomolar concentrations and mediated efficacious and significant depletion of CD123+ blasts and LSCs in primary AML and HR-MDS samples. The ability to eradicate LSCs without seriously affecting normal hematopoiesis promises durable responses and the potential for long-term remission. A phase 1 dose-escalation study of AFM28 monotherapy (NCT05817058) has been initiated and the combination with allogenic NK cells is envisioned."

IO biomarker • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • CD123 • CD34 • FCGR3A • IL3RA • KIT

ENGAGING INNATE IMMUNITY: A PHASE 1 DOSE ESCALATION STUDY TO ASSESS SAFETY AND TOLERABILITY OF AFM28 MONOTHERAPY IN PATIENTS WITH RELAPSED/REFRACTORY CD123-POSITIVE ACUTE MYELOID LEUKEMIA (AML) (EHA 2023) - "N/A ADCC, Acute myeloid leukemia, NK cell, Immune therapy"

Clinical • Monotherapy • P1 data • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • CD123 • FCGR3A • FLT3

"How can afm28 beat them?" (@maddstone1)

Affimed Announces Abstracts at the Annual Meeting of the European Hematology Association (GlobeNewswire) - "A post-hoc subgroup analysis from the AFM13 REDIRECT study in patients with relapsed/refractory (r/r) peripheral T cell lymphoma (PTCL) is accepted as a poster presentation; A trial in progress abstract of the phase 1 dose escalation study to assess safety and tolerability of AFM28 monotherapy in patients with r/r CD123-positive acute myeloid leukemia (AML) is accepted for online publication."

P1 data • P2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma

PRE‑CLINICAL MODELS OF ACUTE MYELOID LEUKEMIA DEMONSTRATE AFM28 EFFICIENTLY DIRECTS ALLOGENEIC NK CELLS TO CD123+ LEUKEMIC BLASTS AND STEM CELLS (EBMT 2023) - "AFM28 induced highly potent and selective lysis of CD123+ leukemic cells, including LSCs and progenitor cells, by allogeneic NK cells. The capacity to eradicate LSCs could increase the frequency and durability of responses, induce long-term remission, and prevent disease relapse after conventional treatment or aSCT in patients with AML. A first-in-human clinical investigation of AFM28 is being initiated."

Preclinical • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • CD123 • CD34 • CSF2 • FCGR3A • STAT5