A Phase 1/2, First-in-Human, Single and Multiple Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of HMB-001 in Participants With Glanzmann Thrombasthenia

The goal of this clinical trial is to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of HMB-001 in Participants with Glanzmann Thrombasthenia.
The main questions it aims to answer are:
* Parts A, B, and C: To determine the safety and tolerability of HMB-001
* Part A: To establish the dose level(s) and dosing interval(s) of HMB-001 to be investigated in Parts B and C
* Parts B and C: To estimate the ability of HMB-001 to prevent the number and severity of bleeds
Part A will assess differing singular doses of HMB-001 in small groups of participants. The dose administered to a newly enrolled participant (or groups of participants) may only increase if analysis of data from previous dosing shows it is safe to do so. The planned duration of participation in Part A is approximately 6 months, which consists of a Screening Period, an optional Run-in Observation Period, and a follow-up period of 8 weeks.
Part B is similar to Part A as it involves testing different dose levels of HMB-001 in small groups of participants. However, in Part B, HMB-001 is given multiple times over a 3-month period, either weekly, every 2 weeks, or every 4 weeks. Part B consists of a Screening Period, a Run-in Observation Period, a 3-month Treatment Period, and a Safety Follow-up following the last dose of HMB-001.
Part C is open to participants from Part B and consists of approximately a 9-month Treatment Period and a Safety Follow-up following the last dose of HMB-001.

Start Date13 Dec 2022

Sponsor / Collaborator

Hemab Therapeutics ApS

ISRCTN66310879 / RecruitingPhase 1/2

A Phase I/II, first-in-human, single and multiple ascending dose study to investigate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of HMB-001 in participants With Glanzmann thrombasthenia

Start Date02 Nov 2022

Sponsor / Collaborator

Richmond Pharmacology Ltd.

100 Clinical Results associated with HMB-001

100 Translational Medicine associated with HMB-001

100 Patents (Medical) associated with HMB-001

Literatures (Medical) associated with HMB-001

01 Oct 2010·British poultry scienceQ3 · AGRICULTURAL & FORESTRY SCIENCE

Influence ofin ovoinjection of disaccharides, glutamine andβ-hydroxy-β-methylbutyrate on the development of small intestine in duck embryos and neonates

Q3 · AGRICULTURAL & FORESTRY SCIENCE

Article

Author: X.L. Xiong ; H.F Wan ; J. Xu ; R. Wang ; W. Chen ; J. Peng

1. The objective of the present study was to examine the effect of in ovo injection of disaccharides (DS), disaccharides and glutamine (DS + Gln) or disaccharides and β-hydroxy-β-methylbutyrate (DS + HMB) at d 23 of incubation on the development of the small intestine. 2. In DS + Gln-injected ducks, the greatest relative small intestine mass and muscularis layer thickness among 4 treatments was observed from d 25 of incubation to 7 d of age. 3. Jejunal sucrase activity in DS-injected ducks was significantly greater than in controls at hatch and on d 7. 4. In DS + HMB-treated ducks, a tendency toward slightly higher jejunal DNA concentration was observed throughout the experiment. 5. Greater body weight was found in DS + Gln and DS + HMB treated ducks in the first two weeks. However, there was no significant difference in the market weight (35 d) of ducks among the 4 treatments. 6. The results of present study suggest that administering disaccharides and Gln, or disaccharides and HMB, to the duck embryos exerted a beneficial effect on the early development of small intestine and on growth performance.

Nature cardiovascular research

A bispecific antibody approach for the potential prophylactic treatment of inherited bleeding disorders

Article

Author: Rea, Catherine J ; Olsen, Eva H N ; Urbanus, Rolf T ; Faber, Johan H. ; Gandhi, Prafull S ; Olsen, Ole H. ; Løvgreen, Monika N ; Urbanus, Rolf T. ; Zivkovic, Minka ; de Bus, Ian-Arris ; Bloem, Karien ; Schluckebier, Gerd ; Gandhi, Prafull S. ; Olsen, Ole H ; Faber, Johan H ; Sørensen, Benny ; Rea, Catherine J. ; Schutgens, Roger E. ; Bonde, Amalie C. ; Johansson, Eva ; Bonde, Amalie C ; Løvgreen, Monika N. ; Bjørn, Søren E. ; Schutgens, Roger E ; Østergaard, Henrik ; Olsen, Eva H. N. ; Elm, Torben ; Bjørn, Søren E ; Alskär, Oskar

Abstract:

Inherited bleeding disorders such as Glanzmann thrombasthenia (GT) lack prophylactic treatment options. As a result, serious bleeding episodes are treated acutely with blood product transfusions or frequent, repeated intravenous administration of recombinant activated coagulation factor VII (rFVIIa). Here we describe HMB-001, a bispecific antibody designed to bind and accumulate endogenous FVIIa and deliver it to sites of vascular injury by targeting it to the TREM (triggering receptor expressed on myeloid cells)-like transcript-1 (TLT-1) receptor that is selectively expressed on activated platelets. In healthy nonhuman primates, HMB-001 prolonged the half-life of endogenous FVIIa, resulting in its accumulation. Mouse bleeding studies confirmed antibody-mediated potentiation of FVIIa hemostatic activity by TLT-1 targeting. In ex vivo models of GT, HMB-001 localized FVIIa on activated platelets and potentiated fibrin-dependent platelet aggregation. Taken together, these results indicate that HMB-001 has the potential to offer subcutaneous prophylactic treatment to prevent bleeds in people with GT and other inherited bleeding disorders, with a low-frequency dosing regimen.

News (Medical) associated with HMB-001

09 Feb 2024

·www.prnewswire.com

Hemab Therapeutics Presents Positive Phase 1 Results for HMB-001 in Glanzmann Thrombasthenia at 2024 EAHAD Annual Congress

HMB-001 was well tolerated with no drug-related adverse or thromboembolic events; dose-dependent improvements in blood-clotting activity support the potential of HMB-001 as a first-in-class prophylactic treatment for Glanzmann Thrombasthenia and other blood clotting disorders Preclinical HMB-001 findings were published in the February 2024 issue of Nature Cardiovascular Research COPENHAGEN, Denmark and CAMBRIDGE, Mass., Feb. 9, 2024 /PRNewswire/ -- Hemab Therapeutics, a clinical-stage biotechnology company developing novel prophylactic therapeutics for serious, underserved bleeding and thrombotic disorders, today presented initial results from Phase 1 of its ongoing evaluation of HMB-001. A novel bispecific antibody, HMB-001 is in development as a prophylactic treatment for the bleeding disorder Glanzmann Thrombasthenia (Glanzmann). The data were presented as one of 10 abstracts selected for the SLAM oral presentation session at the 17th Annual Congress of the European Association for Haemophilia and Allied Disorders (EAHAD) held this week in Frankfurt, Germany. "The first clinical data for HMB-001 in Glanzmann suggest that the demonstrated mechanism is suitable as a new prophylactic treatment for people with neglected blood clotting disorders who face severe, potentially life-threatening bleeds every day," said Joe Vogel, Senior Director and Program Lead for HMB-001 at Hemab. "With Phase 2 already underway, we are committed to advancing clinical evaluation of HMB-001 toward bringing life-changing preventative treatments to improve patients' quality of life." The Phase 1/2 first-in-human open-label study in patients with Glanzmann is evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of HMB-001. As part of the UK-based Phase 1 single-ascending dose, seven patients received subcutaneous HMB-001 at 0.2 mg/kg, (n=1), 0.5 mg/kg (n=3) or 1.25 mg/kg (n=3). Over a 56-day observation period, HMB-001 was well tolerated; the most common adverse events (AEs) were mild or moderate in severity. No AEs or serious adverse events were deemed related to HMB-001. There were no dose-limiting toxicities and no thromboembolic events reported. Treatment with HMB-001 resulted in a dose-dependent pharmacodynamic effect of endogenous Factor VIIa accumulation that was associated with decreases in prothrombin time and improvement in exploratory thrombin generation analyses. The pharmacokinetic profile and half-life of HMB-001 support dosing every two weeks or a less-frequent dosing regimen. "People living with bleeding disorders like Glanzmann face devastating bleed events and considerable psychosocial impacts—from severe pain and social stigmatization to depression and isolation—but have no approved preventative treatments to turn to," said Suthesh Sivapalaratnam, MD, PhD, Queen Mary University of London, Barts Health NHS Trust. "These Phase 1 data support further investigation into the promise of HMB-001 for patients and providers across the globe who are awaiting innovation to improve the standard of care." Hemab has begun dosing and is actively enrolling in Phase 2, the multiple-ascending dose of the study, which will be expanded to sites across Europe and the U.S. For more information, visit clinicaltrials.gov (NCT06211634). In addition, Hemab announced that preclinical research findings of HMB-001 are now available online as part of the February 2024 issue of Nature Cardiovascular Research. The study results demonstrate the ability of HMB-001 to accumulate and potentiate the activity of endogenous Factor VIIa selectively on activated platelets, providing a sustained and localized procoagulant activity that may support prophylactic treatment of Glanzmann or other bleeding disorders. Read the paper here. About Glanzmann Thrombasthenia Glanzmann Thrombasthenia (Glanzmann) is a rare and severe bleeding disorder associated with debilitating and sometimes life-threatening bleeding episodes. Initial findings from the international Glanzmann's 360 (GT360) natural history study—Hemab's research initiative in partnership with UK specialist research consultancy Haemnet—found that 87% of the 104 respondents reported experiencing at least one bleed in the previous week, with 37% of those bleeds requiring medical treatment. These bleeding episodes significantly impact the mental health and quality of life of people living with Glanzmann. Low mood, emotional problems, and social isolation were reported by participants (66%, 50%, and 44% respectively), and 80% reported that they missed school or work due to bruising or bleeding. To date, there are no effective prophylactic treatment options for Glanzmann. About HMB-001 HMB-001 is bispecific antibody that binds and stabilizes endogenous Factor VIIa with one antibody arm and binds to TLT-1 on activated platelets with the other arm. This allows for accumulation of endogenous Factor VIIa in the body, recruitment of Factor VIIa directly to the surface of the activated platelets where it is known to facilitate clotting, and avoidance of clotting activity in the absence of tissue damage. HMB-001 is designed to be a first-in-class prophylactic treatment for Glanzmann Thrombasthenia with the potential to treat other debilitating rare bleeding disorders. The U.S. Food and Drug Administration granted Fast Track Designation to HMB-001 for the treatment of Glanzmann. About Hemab Therapeutics Hemab is a clinical-stage biotech company developing novel prophylactic therapeutics for serious, underserved bleeding and thrombotic disorders. Based in Cambridge, MA and Copenhagen, Denmark, Hemab is progressing a pipeline of monoclonal and bispecific antibody-based therapeutics to transform the treatment paradigm for patients with high unmet need. The company's strategic guidance, Hemab 1-2-5™, targets the development of 5 assets by 2025 to deliver long-awaited innovation for patients with high unmet need blood-clotting disorders like Glanzmann Thrombasthenia, Factor VII Deficiency, Von Willebrand Disease, and others. Learn more at hemab.com. Follow us on LinkedIn and X (formerly known as Twitter). SOURCE Hemab Therapeutics

Clinical ResultPhase 1Fast TrackPhase 2

11 Dec 2023

·www.prnewswire.com

Hemab Therapeutics Announces First Patient Dosed in Phase 2 Clinical Study Investigating HMB-001 for the Treatment of Glanzmann Thrombasthenia

HMB-001 is a novel bispecific antibody designed to be the first prophylactic treatment for Glanzmann Thrombasthenia (GT) and other debilitating bleeding disorders Phase 1 was successfully completed in the UK; Hemab plans additional sites in Europe and the U.S. for Phase 2 The U.S. FDA has cleared the Investigational New Drug (IND) application and granted Fast Track Designation to HMB-001 for the treatment of GT COPENHAGEN, Denmark and CAMBRIDGE, Mass., Dec. 11, 2023 /PRNewswire/ -- Hemab Therapeutics, a clinical-stage biotechnology company developing novel prophylactic therapeutics for serious, underserved bleeding and thrombotic disorders, announced today that it has completed Phase 1, the single ascending dose part, and transitioned to Phase 2, the multiple ascending dose part, of its Phase 1/2 clinical study of HMB-001 in Glanzmann Thrombasthenia (GT), a platelet disorder that causes severe, potentially life-threatening bleeding episodes. The company also announced that the U.S. Food and Drug Administration (FDA) has cleared Hemab's investigational new drug application (IND) for HMB-001 in GT, enabling enrollment in the U.S. Phase 1 of the clinical study was completed in the UK, and Phase 2 will include additional sites in Europe as well as the U.S. In addition, the FDA granted Fast Track designation to HMB-001, emphasizing the seriousness and high unmet need for treatments for GT. The Fast Track program enables Hemab to have more frequent interactions with the FDA to facilitate the development of HMB-001. "People living with Glanzmann Thrombasthenia can experience frequent, sometimes severe bleeds that can be life-threatening and compromise their quality of life. Currently, there are no prophylactic treatment options that would reduce or prevent these bleeding episodes," said Benny Sorensen, MD, PhD, CEO of Hemab. "The completion of Phase 1 on time and transitioning to Phase 2 is an important milestone for HMB-001 and Hemab. Furthermore, expanding our clinical study into the U.S., following clearance of the IND, and Fast Track designation are a testament to the importance of advancing prophylactic treatment for people living with Glanzmann Thrombasthenia." The Phase 1/2 clinical study evaluates the safety, tolerability, pharmacodynamics, and pharmacokinetics of HMB-001. Initial efficacy signals based on an assessment of changes in bleeding frequency will also be measured. The study is composed of three parts: Part A, single ascending dose, Part B, multiple ascending dose, and Part C, extended dosing. Hemab plans to report data from the Phase 1, single ascending dose portion, at an international scientific conference in early 2024. The Phase 1/2 study design was detailed in the company's poster presentation (number 1225), "A Phase 1/2, First-in-Human, Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of HMB-001 in Participants with Glanzmann Thrombasthenia," at the 65th American Society of Hematology Annual Meeting and Exposition. About Glanzmann Thrombasthenia Glanzmann Thrombasthenia (GT) is a rare and severe bleeding disorder associated with debilitating and sometimes life-threatening bleeding episodes. Initial findings from the international Glanzmann's 360 (GT360) natural history study, Hemab's research initiative in partnership with UK specialist research consultancy Haemnet, found that 87% of the 104 respondents reported experiencing at least one bleed in the previous week, and 37% of those bleeds required medical treatment. These bleeding episodes have a significant impact on the mental health and quality of life of people living with GT. Low mood, emotional problems, and social isolation were reported by participants (66%, 50%, and 44% respectively) and 80% reported that they missed school or work due to bruising or bleeding. To date, there are no effective prophylactic treatment options for people living with GT. About HMB-001 HMB-001 is bispecific antibody that binds and stabilizes endogenous factor VIIa (FVIIa) with one antibody arm and binds to TLT-1 on activated platelets with the other arm. This allows for accumulation of endogenous FVIIa in the body, recruitment of FVIIa directly to the surface of the activated platelets where it is known to facilitate clotting, and avoidance of clotting activity in the absence of tissue damage. HMB-001 is designed to be a first-in-class prophylactic treatment for Glanzmann Thrombasthenia with the potential to treat other debilitating rare bleeding disorders. About Hemab Therapeutics Hemab is a clinical-stage biotech company developing novel prophylactic therapeutics for serious, underserved bleeding and thrombotic disorders. Based in Cambridge, MA and Copenhagen, Denmark, Hemab is progressing a pipeline of monoclonal and bispecific antibody-based therapeutics to transform the treatment paradigm for patients with high unmet need. The company's strategic guidance, Hemab 1-2-5TM, targets the development of 5 independent assets by 2025 to deliver long-awaited innovation for patients with high unmet need blood-clotting disorders like Glanzmann Thrombasthenia, Factor VII Deficiency, Bernard Soulier Syndrome, Von Willebrand Disease, and other serious disorders. Learn more at hemab.com. SOURCE Hemab Therapeutics

Fast TrackPhase 2INDASH

24 Jun 2023

·www.prnewswire.com

Hemab Therapeutics Presents New Preclinical Research Demonstrating Effects of Its Bispecific Antibody HMB-001 in Factor VII Deficiency

HMB-001 recognizes and binds to factor VII (FVII) protein variants associated with moderate/severe FVII deficiency and drives accumulation of endogenous FVII/FVIIa to normal ranges in in-vivo models COPENHAGEN, Denmark and BOSTON, June 24, 2023 /PRNewswire/ -- Hemab Therapeutics, a clinical-stage biotechnology company developing the first prophylactic therapeutics for serious, underserved bleeding and thrombotic disorders, announced results today from preclinical research of HMB-001 in models of factor VII (FVII) deficiency at the International Society on Thrombosis and Haemostasis (ISTH) 2023 Congress in Montreal. "We believe that HMB-001 has the potential to transform treatment in several serious bleeding disorders and have already initiated a Phase 1/2 study in Glanzmann Thrombasthenia," said Benny Sorensen, MD, PhD, CEO and President of Hemab. "The new preclinical data presented today show HMB-001 successfully targeted and accumulated endogenous FVIIa to levels that would be expected to provide clinical benefit in FVII deficiency, supporting the potential for HMB-001 in an additional underserved bleeding disorder." FVII is a protein necessary in the formation of hemostatic plugs to control bleeding. FVII deficiency can cause spontaneous or excessive and prolonged bleeding after injury or surgery; heavy or prolonged menstrual bleeding in women; and in very severe cases, life-threatening bleeding inside the skull or digestive tract. HMB-001, Hemab's lead candidate, is a bispecific antibody that binds to and stabilizes endogenous activated FVII (FVIIa) with one antibody arm and localizes FVIIa to the surface of activated platelets by binding to TLT-1 with the other arm. This allows for accumulation of FVIIa in the body and recruitment of FVIIa directly to the surface of activated platelets at the site of vascular injury where FVIIa is known to facilitate the formation of protective hemostatic plugs to stop bleeding. The preclinical research presented at ISTH, "HMB-001, a Bispecific anti-FVIIa/anti-TLT-1 Antibody Demonstrates Effect in Models of FVII Deficiency," assessed key requirements for HMB-001 to function in FVII deficiency, specifically its ability to bind with FVII protein variants associated with moderate/severe deficiency and the potential of HMB-001 to accumulate FVIIa in an in-vivo non-human primate model of FVII deficiency. A panel of 12 FVII variants from the European Association for Haemophilia and Allied Disorders (EAHAD) database was produced based on high prevalence and association with moderate/severe FVII deficiency phenotype as well as proximity to the HMB-001 binding site. In subsequent binding studies, HMB-001 was shown to bind to all FVII variants at clinically relevant concentrations. The ability of HMB-001 to accumulate endogenous FVIIa in FVII deficiency was assessed using small interfering RNA (siRNA) to knock down FVII/FVIIa to levels between 10 to 30 percent of normal in animal models (n=3). After continuous, stable knock down, HMB-001 (5 mg/kg) was administered. The total accumulation of FVIIa observed with HMB-001 was comparable to the normal range seen in healthy animals. These initial results suggest HMB-001 may have potential application as a treatment for FVII deficiency. About HMB-001 HMB-001 is bispecific antibody that binds and stabilizes endogenous factor VIIa (FVIIa) with one antibody arm and TLT-1 on activated platelets with the other arm. This allows for accumulation of FVIIa in the body, recruitment of FVIIa directly to the surface of the activated platelets where it is known to facilitate clotting, and avoidance of clotting activity in the absence of tissue damage. HMB-001 was designed to be a first-in-class prophylactic treatment for Glanzmann Thrombasthenia (GT) with potential for other debilitating rare bleeding disorders, including factor VII deficiency. About Hemab Therapeutics Hemab is a clinical-stage biotech company developing the first prophylactic therapeutics for serious, underserved bleeding and thrombotic disorders. Based in the US and Denmark, Hemab is progressing a pipeline of monoclonal and bispecific antibody-based therapeutics to transform the treatment paradigm for patients with high unmet need. The company's strategic guidance, Hemab 1-2-5™, targets the development of 5 clinical assets by 2025 to deliver long-awaited innovation for patients with high unmet need blood clotting disorders like Glanzmann Thrombasthenia, factor VII deficiency, Bernard Soulier Syndrome, Von Willebrand Disease and other serious disorders. Learn more at hemab.com. Media Contact: Lia Dangelico [email protected] 540-303-0180 SOURCE Hemab Therapeutics

Clinical Result

100 Deals associated with HMB-001

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Indication	Highest Phase	Country/Location	Organization	Date
Thrombasthenia	Phase 2	US	Hemab Therapeutics ApS	13 Dec 2022
Thrombasthenia	Phase 2	BE	Hemab Therapeutics ApS	13 Dec 2022
Thrombasthenia	Phase 2	IT	Hemab Therapeutics ApS	13 Dec 2022
Bernard-Soulier Syndrome	Phase 1	DK	Hemab Therapeutics ApS	30 Jan 2022
Factor VII Deficiency	Phase 1	DK	Hemab Therapeutics ApS	30 Jan 2022
Hemophilia B	Phase 1	DK	Hemab Therapeutics ApS	30 Jan 2022
Hemorrhage	Preclinical	DK	Hemab Therapeutics ApS	04 Feb 2022

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


HMB-001 (ISTH2022)	Not Applicable	Thrombasthenia	-	HMB-001	lajymiwbjs(bsauftepyd) = lyivtpwqfp zeczrbouhb (gmbnzywolk ) View more	-	09 Jul 2022

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