GTB-3550 TRIKE / GT Biopharma - LARVOL DELTA

[VIRTUAL] GTB-3550 tri-specific killer engager safely activates and delivers IL-15 to NK cells, but not T-cells, in immune suppressed patients with advanced myeloid malignancies, a novel paradigm exportable to solid tumors expressing Her2 or B7H3 (ESMO 2021) - P1/2 | "GTB-3550 TriKE given as a monotherapy safely induced a sustained functional expansion of endogenous NK cells with anti-tumor activity in advanced AML and MDS patients treated with at least 25 mcg/kg/day. Second generation solid tumor TriKE therapeutics against HER2 and B7H3 will be tested clinically next year."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • Solid Tumor • CD276 • CD33 • CD4 • CD8 • HER-2 • IL15

GTB-3550 Tri-specific Killer Engager TriKE™ drives NK cells Expansion and Cytotoxicity in Acute Myeloid Leukemia (AML) and Myelodysplastic Syndromes (MDS) Patients (SITC 2021) - P1/2 | "Immune monitoring suggests that a schedule to maximize function in vivo with repeat courses will further enhance activity. Trial Registration NCT03214666"

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • CD19 • CD33 • CD57 • IL15 • IL2 • LAMP1 • NCAM1 • NKG2D

B7H3-targeted tri-specific killer engagers deliver IL-15 to NK cells but not T-cells, and specifically target solid tumors as a pan-tumor antigen strategy mediated through NK cells (ESMO 2022) - "As proof of concept, a clinical trial of GTB-3550 (a CD33-targeted Tri-specific Killer Engager [TriKE] in AML) induced endogenous NK cell expansion and activation in refractory AML patients. Here we developed GTB-5550 (a B7H3 TriKE) as a novel dual camelid (cam) TriKE containing WT IL-15 and comprised of two cam engagers: targeting CD16 on NK cells and B7H3 on multiple solid tumors...Conclusions B7H3 TriKE delivers an NK cell specific IL-15 signal to expand NK cells and is highly specific against a broad array of cancers. Clinical manufacturing is underway with an IND planned to open clinical trials in 2023 in a number of solid tumors and multiple myeloma."

Pan tumor • Acute Myelogenous Leukemia • Brain Cancer • Glioblastoma • Hematological Malignancies • Multiple Myeloma • Oncology • Ovarian Cancer • Solid Tumor • CD276 • CD33 • IL15 • LAMP1

GTB-5550 (cam16-IL15-camB7H3) trispecific killer engager (TriKE®) drives natural killer cell activation and antibody dependent cellular cytotoxicity against head and neck squamous cell carcinomas (AACR 2022) - "NK cell degranulation and IFN-gamma production of GTB-3550-treated samples were higher compared to that of control samples treated with B7H3 single domain or IL-15 alone. Ongoing experiments will evaluate functionality of GTB-5550 on FA patient samples as well as in spheroid assays. Taken together, this data shows that a GTB-5550 is able to drive NK cell activity against B7H3-expressing HNSCC cells, which presents potential for a B7H3-targeted TriKE to be used to be implemented clinically to treat HNSCC or FA-HNSCC patients."

IO biomarker • Genito-urinary Cancer • Head and Neck Cancer • Oncology • Prostate Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD276 • CD28 • FANCA • IFNG • IL15

GTB-3550 Tri-Specific Killer Engager (TriKE®) for High Risk Hematological Malignancies (clinicaltrials.gov) - P1/2 | N=12 | Terminated | Sponsor: GT Biopharma, Inc. | N=60 ➔ 12 | Trial completion date: Aug 2025 ➔ Sep 2021 | Active, not recruiting ➔ Terminated | Trial primary completion date: Feb 2024 ➔ Aug 2021; Development of GTB-3550 halted due to development of the second generation camelid nanobody TriKE drug product, GTB-3650.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Acute Myelogenous Leukemia • Aggressive Systemic Mastocytosis • Hematological Disorders • Hematological Malignancies • Leukemia • Mast Cell Leukemia • Myelodysplastic Syndrome • Oncology • CD33 • NCAM1

Novel B7-H3 targeting dual nanobody NK cell engagers display robust activity against a broad spectrum of solid and hematologic malignancies. (ESMO-IO 2021) - "These were used to evaluate how the BiKE and GTB-3550 induce NK cell degranulation (CD107a) and interferon gamma production...Results PB NK cells were robustly activated, compared to controls, when treated with GTB-5550 or BiKE and cultured with enzalutamide resistant PCa, osteosarcoma (U2OS, SaOS2), rhabdomyosarcoma (RH30), ovarian carcinoma (MA148, OVCAR8), AML (MV4;11, THP-1) and multiple myeloma (MM1S) cell lines...Legal entity responsible for the study The authors. Funding GT Biopharma, Inc."

Acute Myelogenous Leukemia • Genito-urinary Cancer • Hematological Malignancies • Multiple Myeloma • Oncology • Osteosarcoma • Ovarian Cancer • Prostate Cancer • Rhabdomyosarcoma • Sarcoma • Solid Tumor • AR • CREB5 • IFNG • IL15 • LAMP1

[VIRTUAL] GTB-3550 TriKE™ for the Treatment of High-Risk Myelodysplastic Syndromes (MDS) and Refractory/Relapsed Acute Myeloid Leukemia (AML) Safely Drives Natural Killer (NK) Cell Proliferation At Initial Dose Cohorts (ASH 2020) - P1/2 | "The previous MTD of continuous infusion rhIL-15 was 2 mcg/kg/day (Conlon et al, Clin. This novel GTB-3550 TriKE administered by continuous infusion led to NK cell proliferation in all patients at initial dose levels and no clinically significant targeted toxicity. Though no objective responses were seen at the initially low dose cohorts tested, these early data suggest proof of principle that the drug has immune activity in humans. Subsequent patients given higher dose levels will determine if NK cell proliferation translates into clinical efficacy."

Acute Myelogenous Leukemia • Cardiovascular • Hematological Malignancies • Hepatology • Leukemia • Myelodysplastic Syndrome • Oncology • CD33 • CD8 • FLT3 • IL15 • NCAM1

GTB-3550 Tri-Specific Killer Engager (TriKE®) for High Risk Hematological Malignancies (clinicaltrials.gov) - P1/2; N=60; Active, not recruiting; Sponsor: GT Biopharma, Inc.; Recruiting ➔ Active, not recruiting

Enrollment closed • Acute Myelogenous Leukemia • Aggressive Systemic Mastocytosis • Hematological Disorders • Hematological Malignancies • Leukemia • Mast Cell Leukemia • Myelodysplastic Syndrome • Oncology • CD33 • MRI • NCAM1

GT BioPharma’s Next Generation Camelid TriKE Nanobody Platform Highlighted at ESMO Congress 2021 (PRNewswire) - P1, N=60; NCT03214666; Sponsor: GT Biopharma, Inc; “The presentation at ESM0 highlighted the activity of camelid TriKEs in preclinical B7H3 positive and HER2+ solid tumor cancer models. GT Biopharma plans to advance these TriKEs into the clinic in 2022….In addition to the ESMO presentation…Phase 1 safety and feasibility clinical trial with GTB-3550….The three most recent patients (numbers 10-12) have all tolerated the treatment well.….Three most recent patients was consistent with the data previously reported on the first nine patients, and demonstrated activation, proliferation, and persistence of CD16 positive NK cells. Patient 11 had a bi-phenotypic leukemia which co-expressed both CD19 (a lymphoid marker) and CD33 (the myeloid marker which is targeted by GTB-3550); this patient showed a 50% reduction in CD33-positive leukemic cells (blasts), evidence of anti-leukemic activity of GTB-3550. Patients 10 and 12 did not experience blast cell reduction.”

New trial • P1 data • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Solid Tumor

GT Biopharma Announces Updated Positive Safety Data From Phase 1 GTB-3550 Monotherapy TriKE Trial an Investigational Immunotherapy for Refractory Cancers to be Presented at ESMO Congress 2021 (PRNewswire) - “GT Biopharma, Inc….announced that Jeffrey Miller, MD, University of Minnesota Medical School, Professor of Medicine, Division of Hematology, Oncology and Transportation will present a mini-oral presentation at the European Society for Medical Oncology (ESMO) Congress 2021 to be held virtually September 16-21. The mini-oral presentation will present updated positive Phase 1 safety data, progress, and preclinical data going beyond hematologic malignancies to solid tumors of a Phase 1 GTB-3550 TriKE trial.”

P1 data • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Solid Tumor

GT Biopharma Advances GTB-3650, a Second-Generation Tri-Specific Killer Engager -TriKE, Into IND-Enabling Studies (PRNewswire) - "GT Biopharma...announces the advancement of GTB-3650 into IND-enabling studies, with which it plans to supplant the ongoing Phase 1 program with GTB-3550."

IND • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

GT Biopharma Provides Second Quarter 2021 Business Update (PRNewswire) - “Reported Positive, Interim Data Results from First-in-Human GTB-3550 TriKE® Phase I Clinical Trial for the Treatment of Refractory/Relapsed Acute Myeloid Leukemia (AML) and High-Risk Myelodysplastic Syndromes (MDS): The Phase I safety study is expected to complete later this fall and the Company has scheduled an interim data publication for September 16-21, 2021 at the European Society for Medical Oncology Conference to be held in Paris, France.”

P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

GT Biopharma Announces Sponsored Research Agreement With Dr. Jeffrey S. Miller Of The University Of Minnesota (PRNewswire) - “GT Biopharma…announced it has entered into a sponsored research agreement (SRA) with Jeffrey S. Miller, M.D., Deputy Director of the University of Minnesota's Masonic Cancer Center and Consulting Chief Scientific Officer of GT Biopharma. The SRA is focused on supporting GT Biopharma's continued clinical develop of TriKE™ therapeutic product candidates, and to gain an increased understanding of changes in the patient's native NK cell population as a result of TriKE™ therapy. The SRA is a fixed sum contract worth Two Million Seventy-Four Thousand Six Hundred Eighty-Six dollars ($2,074,686) payable over the next two years in equal quarterly payments. GT Biopharma has early termination rights without financial penalty, and will receive an exclusive worldwide license to any patentable inventions which arise under the SRA...GTB-3550 was well tolerated by all patients with no cytokine release syndrome observed."

Licensing / partnership • Oncology

GT Biopharma Announces Interim GTB-3550 Trike Monotherapy Clinical Trial Results At 2021 Raymond James Human Health Innovation Conference (PRNewswire) - P1, N=60; NCT03214666; Sponsor: GT Biopharma, Inc; “Highlights to date from patients treated with GTB-3550 TriKE™ monotherapy in the dose escalation Phase 1 clinical trial for the treatment of high-risk MDS and refractory/relapsed AML: 57% of patients experienced significant reduction in AML/MDS cancer cell burden when treated with doses of GTB-3550 ranging from 25mcg/kg/day to 150mcg/kg/day. Up to 63.7% reduction in bone marrow blast levels observed in some patients. GTB-3550 was well tolerated by all patients with no cytokine release syndrome observed….The Phase 1 safety part of the study is expected to conclude in late August 2021 with data publication currently scheduled for end of September 2021.”

P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

DR. JEFFREY S. MILLER TO PRESENT ON PROGRESS OF GTB-3550 TRIKE PHASE I TRIAL ACCOMPANYING GT BIOPHARMA'S COMPANY PRESENTATION AT RAYMOND JAMES HUMAN HEALTH INNOVATION CONFERENCE (GT Biopharma Press Release) - “GT Biopharma, Inc…announced that Dr. Jeffrey S. Miller will be giving an update on the progress of the GTB-3550 TriKE™ Phase I trial accompanying the Company's corporate update presentation at the upcoming Raymond James Human Health Innovation Conference on Tuesday, June 22, 2021 at 11:20 AM ET.”

P1 data • Oncology

GT BIOPHARMA ANNOUNCES GTB-3550 TRIKE(TM) REDUCES BONE MARROW BLAST LEVELS, IMPROVES NK CELL FUNCTION AND PROLIFERATION, AND NO TOXICITIES OBSERVED IN AML AND MDS PATIENTS (GT Biopharma Press Release) - P1/2, N=60; NCT03214666; Sponsor: GT Biopharma, Inc.; "GT Biopharma, Inc...pleased to announce the presentation of interim results for...GTB-3550 for the treatment of high-risk myelodysplastic syndromes (MDS) and refractory/relapsed acute myeloid leukemia (AML)...presented the interim results during an Oral Session at the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition on December 5, 2020...Patient #7...achieved a bone marrow blast level reduction from 12% to 4.6% and stable hematologic parameters including normal platelet counts throughout therapy...Patients treated with GTB-3550 TriKE displayed no signs of clinical immune activation such as cytokine release syndrome (CRS) or serious adverse events (SAEs) or fevers, tachycardia or constitutional symptoms at any dose (5-50mcg/kg/day) evaluated to date."

Cytokine release syndrome • P1/2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

GT BIOPHARMA ANNOUNCES FDA DATA - GTB-3550 TriKE REDUCES CANCER CELLS BY 61.7% FOR A HIGH-RISK MYELODYSPLASTIC SYNDROMES (HR-MDS) PATIENT (PRNewswire) - P1/2, N=60; NCT03214666; Sponsor: GT Biopharma, Inc; "With TriKE™ GTB-3550 at 50mcg/kg/day (three consecutive 96-hour continuous infusions), the patient achieved a successful bone marrow blast level reduction from 12% before GTB-3550 therapy to 4.6% post GTB-3550 therapy determined by morphological assessment...our clinical data demonstrates that our proprietary CD16 and IL-15 incorporated in TriKE™ safely activates and harnesses the patient's native NK cell's cancer killing ability in a target-directed fashion without the need for highly expensive and intrusive supplemental NK cell therapies."

P1/2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

GT Biopharma Adds University of Wisconsin--Madison Carbone Cancer Center as Second Site in Ongoing Phase 1/2 Clinical Trial of GTB-3550 TriKE, a Novel NK Cell Therapeutic Cancer Treatment (PRNewswire) - "GT Biopharma, In...announced the addition of a new clinical trial site for its ongoing GTB-3550 TriKE™ multicenter Phase I/II trial (ClinicalTrials.gov NCT03214666). The University of Wisconsin – Madison Carbone Cancer Center will serve as the second site for this program, with Kalyan Vara Ganesh Nadiminti M.D., UW Assistant Professor in Hematology, Oncology and Palliative Care, serving as lead investigator...UM's Masonic Cancer Center is the initial site of the GTB-3550 TriKE™ Phase 1/2 trial....GTB-3550 TriKE™ is being evaluated in patients age 18 and older with CD33+ malignancies (primary induction failure or relapsed acute myeloid leukemia [AML] with failure of one reinduction attempt, or high-risk myelodysplastic syndromes [MDS] progressed on two lines of therapy)."

Trial status • Acute Myelogenous Leukemia • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

GT Biopharma Announces Update On The Commencement Of The GTB-3550 TriKE Monotherapy Phase 2 Clinical Trial And Solid Tumor TriKE Product Candidates (PRNewswire) - P2, N=60; NCT03214666; Sponsor: GT Biopharma, Inc; “GT Biopharma, Inc…is pleased to provide an update concerning the commencement of the GTB-3550 TriKE™ monotherapy Phase 2 clinical trial, and certain of its solid tumor targeting TriKE™ product candidates. Highlights to date from patients treated with GTB-3550 TriKE™ in the dose escalation Phase 1 clinical trial for the treatment of high-risk myelodysplastic syndromes (MDS) and refractory/relapsed acute myeloid leukemia (AML): Up to 63.7% Reduction in Bone Marrow Blast Levels seen in some patients. Restoration of Patient's Endogenous NK Cell Function, Proliferation and Immune Surveillance. No Progenitor-derived or Autologous/Allogenic Cell Therapy Required. No Cytokine Release Syndrome Observed.”

Cytokine release syndrome • P2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • Solid Tumor

GT Biopharma Reports Fourth Quarter and Year End 2020 Results and Business Update (PRNewswire) - "'The emerging data from our GTB-3550 TriKE™ program in hematological malignancies, MDS and AML, are encouraging in both safety and efficacy profiles. The ongoing data profile has demonstrated significant differences from all other NK cell therapies and NK engager companies, making TriKE™ a monotherapy, off-the-shelf platform therapeutic'...As of December 31, 2020, cash, cash equivalents and investments were $5.3 million, compared to $0.3 million as of December 31, 2019. The increase in cash, cash equivalents and investments was primarily due to proceeds from the issuance of convertible notes payable of $12.5 million, offset by cash used in operating activities of $7.3 million....The Company anticipates clinical costs to increase significantly in 2021."

Clinical • Commercial • Acute Myelogenous Leukemia • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

GT BIOPHARMA ANNOUNCES GTB-3550 TRIKE MONOTHERAPY RESCUES AND RESTORES NK CELL IMMUNE SURVEILLANCE IN RELAPSED/REFRACTORY AML AND MDS CANCER PATIENTS (GT Biopharma Press Release) - P1/2, N=60; TriKE (NCT03214666); Sponsor: GT Biopharma; “GT Biopharma…announced today additional interim results from its GTB-3550 TriKE™ first-in-human Phase I/II clinical trial for the treatment of high-risk myelodysplastic syndromes (MDS) and refractory/relapsed acute myeloid leukemia (AML)…Up to 63.7% Reduction in Bone Marrow Blast Levels Resulting in Clinical Benefit; Restores Patient's Endogenous NK Cell Function, Proliferation and Immune Surveillance; No Progenitor-derived or Autologous/Allogenic Cell Therapy Required; No Cytokine Release Syndrome Observed; 3 out of the last 5 Patients Treated Respond (25mcg/kg/day to 100mcg/kg/day therapeutic dose range).”

Cytokine release syndrome • P1/2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

GT BIOPHARMA ANNOUNCES ENROLLMENT OF PATIENT 10 IN GTB-3550 TRIKE PHASE I/II CLINICAL TRIAL (GT Biopharma Press Release) - P1/2, N=60; NCT03214666; Sponsor: GT Biopharma, Inc; “GT Biopharma, Inc…is pleased to announce the enrollment of Patient 10 in its GTB-3550 TriKE™ first-in-human Phase I/II clinical trial for the treatment of high-risk myelodysplastic syndromes (MDS) and refractory/relapsed acute myeloid leukemia (AML). Patient 10 will be dosed at 100mcg/kg/day…Highlights from the first nine patients treated with GTB-3550 TriKE™ include: Up to 63.7% Reduction in Bone Marrow Blast Levels. Restores Patient's Endogenous NK Cell Function, Proliferation and Immune Surveillance. No Progenitor-derived or Autologous/Allogenic Cell Therapy Required. No Cytokine Release Syndrome Observed. 3 out of the Last 5 Patients Treated (25mcg/kg/day to 100mcg/kg/day) Respond.”

Cytokine release syndrome • P1/2 data • Trial status • Acute Myelogenous Leukemia • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

GT Biopharma's TriKE Interim Clinical Trial Results Presented At Innate Killer Summit 2021 (PRNewswire) - P1/2, N=60; NCT03214666; Sponsor: GT Biopharma, Inc; "GT Biopharma, Inc...presented updated interim Phase I/II clinical trial results for the Company's lead therapeutic candidate, GTB-3550 TriKE™, being evaluated for the treatment of high-risk myelodysplastic syndromes (MDS) and refractory/relapsed acute myeloid leukemia (AML) at the Innate Killer Summit 2021, held March 23-25...Up to 63.7% Reduction in Bone Marrow Blast Levels. Restores Patient's Endogenous NK Cell Function, Proliferation and Immune Surveillance. No Progenitor-derived or Autologous/Allogenic Cell Therapy Required. No Cytokine Release Syndrome Observed. 3 out of the Last 5 Patients Treated (25mcg/kg/day to 100mcg/kg/day) Respond."

Cytokine release syndrome • P1/2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

GT Biopharma Announces Updated Interim GTB-3550 Trike Clinical Trial Results (Yahoo Finance) - P1/2; N=60; TriKE (NCT03214666); Sponsor: GT Biopharma, Inc; “GT Biopharma…announce updated interim Phase I/II clinical trial results for the Company's lead therapeutic candidate, GTB-3550, being evaluated for the treatment of high-risk myelodysplastic syndromes (MDS) and refractory/relapsed acute myeloid leukemia (AML)…All patients treated at the lower doses exhibited no signs of toxicity, and did not experience any Grade of Cytokine Release Syndrome (CRS)…Patient 9 treated at the 100mcg/kg/day dose level achieved a 63.7% reduction in bone marrow blast levels from 22% before therapy to 8% after therapy. All patients treated at these higher doses of GTB-3550 did not experience any Grade of Cytokine Release Syndrome (CRS)…No Cytokine Release Syndrome (CRS) Observed…Improved NK Cell Function, Proliferation & Persistence.”

Cytokine release syndrome • P1/2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

GT Biopharma Transfers TriKE Manufacturing To Cytovance Biologics In Preparation For Expanded And Multiple Liquid And Solid Tumor Clinical Trials (PRNewswire) - "GT Biopharma, Inc...announced it has signed an expanded GMP manufacturing agreement with Cytovance Biologics for the manufacture of all TriKEs™...'This move positions the Company for large-scale commercial manufacturing in anticipation of an expanded GTB-3550 TriKE™ Phase 1/2 for Acute Myeloid Leukemia (AML) and Myelodysplastic syndromes...look forward to progressing our solid tumor TriKEs™ (PD-L1, B7H3 and Herc 2), which represent the largest portion of the cancer market, last quarter to early first quarter next year. This expanded manufacturing capability positions us to initiate the process of additional clinical trials expected in early 2022.'"

Licensing / partnership • New trial • Acute Myelogenous Leukemia • Hematological Malignancies • Myelodysplastic Syndrome • Oncology