Periodic Reporting for period 1 - Sense21 (HB-086 and HB-097 for Treatment of Chronic Sensory Neuronal Disorders - Neuropathic Pain and Hearing Loss)
Período documentado: 2022-06-01 hasta 2023-05-31
Pain and hearing loss are chronic disorders that affect >100M patients in the EU alone and represent a large healthcare burden due to limited, non-optimal treatment options. With the aging population and longer survival after cancer therapies (chemotherapy-induced chronic pain), these problems are on the rise.
Patients suffering from chronic neuropathic pain are treated with drugs that were originally developed as antiepileptics, antidepressants, and opioids. While these drugs offer some pain relief to some, they leave a large part of patients still in need for safe, efficacious, and well-tolerated treatments. These drugs act on targets located in the central nervous system, giving rise to adverse effects as dizziness, fatigue, and cognitive problems. Opioid use may lead to development of tolerance, addiction, and abuse. A large part of people offered the available drugs will discontinue chemotherapy treatment, either due to lack of effect, or an unacceptable burden of side effects.
Patients with hearing loss are left with no other options than hearing devices, which only offer enhancement of the sense of hearing; but cannot offer any reparative actions on the underlying neural circuitry.
Hoba Therapeutics holds rights to, and is developing, two molecules, representing a novel family of neuronal growth factors with unique effects on sensory nerve cells and systems. Their features, which include restorative and regenerative effects on lesioned nerve cells, make them strong candidates as novel medical treatments for pain disorders and hearing loss, our target indications. Solid preclinical data generated and validated across several sites suggest superior effects on pain symptoms along with a potential for a prevention effect and signs of restorative effects on nervous tissue.
The actions of HB-086 and HB-097 on sensory nerve cells represent a novel therapeutic approach and a paradigm shift for medical treatment and prevention of chronic pain disorders and hearing loss. Both conditions are associated with dysfunction of groups of nerve cells located near the spinal cord in the case of pain and in the inner ear, in the case of hearing loss. Sensory neurons are essential for perception of external stimuli e.g. sound, touch, injury, smell. HB-086 and HB-097 target cellular systems that are necessary for the function of sensory nerve cells and support cells. Evidence indicates a mode of action which includes normalization of impaired neuronal-glial crosstalk, protection and regeneration of nerve cells and fibers. Our experimental data confirm that HB-086 completely abolishes pain in a number of different models and HB-097 preserves the sense of hearing in relevant models. Treatment effects are long-lasting and indicate a potential for infrequent dosing and prevention of further disease progression.
The overall objective of this EIC accelerator project is to progress the HB-086 and HB-097 to clinical development and obtain clinical proof of principle in humans. The transition from preclinical development to testing first in healthy volunteers and then patients require the generation of a substantial regulatory data package. The objective includes 8 work packages that will provide the supportive data.
www.hobatherapeutics.com
Patients suffering from chronic neuropathic pain are treated with drugs that were originally developed as antiepileptics, antidepressants, and opioids. While these drugs offer some pain relief to some, they leave a large part of patients still in need for safe, efficacious, and well-tolerated treatments. These drugs act on targets located in the central nervous system, giving rise to adverse effects as dizziness, fatigue, and cognitive problems. Opioid use may lead to development of tolerance, addiction, and abuse. A large part of people offered the available drugs will discontinue chemotherapy treatment, either due to lack of effect, or an unacceptable burden of side effects.
Patients with hearing loss are left with no other options than hearing devices, which only offer enhancement of the sense of hearing; but cannot offer any reparative actions on the underlying neural circuitry.
Hoba Therapeutics holds rights to, and is developing, two molecules, representing a novel family of neuronal growth factors with unique effects on sensory nerve cells and systems. Their features, which include restorative and regenerative effects on lesioned nerve cells, make them strong candidates as novel medical treatments for pain disorders and hearing loss, our target indications. Solid preclinical data generated and validated across several sites suggest superior effects on pain symptoms along with a potential for a prevention effect and signs of restorative effects on nervous tissue.
The actions of HB-086 and HB-097 on sensory nerve cells represent a novel therapeutic approach and a paradigm shift for medical treatment and prevention of chronic pain disorders and hearing loss. Both conditions are associated with dysfunction of groups of nerve cells located near the spinal cord in the case of pain and in the inner ear, in the case of hearing loss. Sensory neurons are essential for perception of external stimuli e.g. sound, touch, injury, smell. HB-086 and HB-097 target cellular systems that are necessary for the function of sensory nerve cells and support cells. Evidence indicates a mode of action which includes normalization of impaired neuronal-glial crosstalk, protection and regeneration of nerve cells and fibers. Our experimental data confirm that HB-086 completely abolishes pain in a number of different models and HB-097 preserves the sense of hearing in relevant models. Treatment effects are long-lasting and indicate a potential for infrequent dosing and prevention of further disease progression.
The overall objective of this EIC accelerator project is to progress the HB-086 and HB-097 to clinical development and obtain clinical proof of principle in humans. The transition from preclinical development to testing first in healthy volunteers and then patients require the generation of a substantial regulatory data package. The objective includes 8 work packages that will provide the supportive data.
www.hobatherapeutics.com
Development and scale-up of the HB-086 production process are critical path activities. An important deliverable was met in May 2023 with the successful completion of manufacturing in the first pilot batch. The yield was 20% higher than calculated and the preliminary specifications were met. The full panel of established analytics is being performed to confirm the results. Concurrently, technology transfer and the establishment of a master cell bank were finalized at the selected external contract manufacturing organization (CDMO).
The availability of HB-086 drug substance has allowed the engagement of a subcontractor for non-GLP and GLP toxicology studies. The planning and writing of toxicology study protocols for the experiments are complete, and ethical approvals obtained. Further work has identified a suitable formulation for preclinical testing, and the development of a clinical trial formulation is initiated.
Understanding of the HB-086 pharmacology has been generated through biodistribution and rodent PK/PD studies. Results have confirmed the anticipated dissociation between the short plasma half-life (4-5hrs) and long duration of efficacy, as expected based on the biological and neurotrophic nature of the drug. For measurements of the HB-086 concentration in plasma, an analytic method has been developed and is undergoing validation for toxicology studies and clinical trials.
Results from cell- and animal experiments have strengthened the understanding of the mechanism of action and confirmed effects of HB-086. Single dose studies have confirmed a dose response relationship, and an early onset of effect. Additionally, comparable anti-nociceptive effects of mouse meteorin and HB-086 were confirmed.
Finally, the preparations for submission of a clinical trial application are ongoing and meetings with regulatory authorities are planned for 2H of 2023.
The availability of HB-086 drug substance has allowed the engagement of a subcontractor for non-GLP and GLP toxicology studies. The planning and writing of toxicology study protocols for the experiments are complete, and ethical approvals obtained. Further work has identified a suitable formulation for preclinical testing, and the development of a clinical trial formulation is initiated.
Understanding of the HB-086 pharmacology has been generated through biodistribution and rodent PK/PD studies. Results have confirmed the anticipated dissociation between the short plasma half-life (4-5hrs) and long duration of efficacy, as expected based on the biological and neurotrophic nature of the drug. For measurements of the HB-086 concentration in plasma, an analytic method has been developed and is undergoing validation for toxicology studies and clinical trials.
Results from cell- and animal experiments have strengthened the understanding of the mechanism of action and confirmed effects of HB-086. Single dose studies have confirmed a dose response relationship, and an early onset of effect. Additionally, comparable anti-nociceptive effects of mouse meteorin and HB-086 were confirmed.
Finally, the preparations for submission of a clinical trial application are ongoing and meetings with regulatory authorities are planned for 2H of 2023.
The generated data support advancement towards the overall project objective – submission of a clinical trial application to the EMA.
Confirmation and scale-up of the HB-086 production process, along with a successful technology transfer to the CDMO, are important deliverables, which de-risk the manufacturing part of drug development. The conducted 10x scale-up strongly indicates that the process is adequate for further increases in batch sizes.
Production of preclinical drug substance allows initiation of the planned toxicology and formulation programs.
Results from pharmacology studies further strengthen the profiling of the drug candidate and confirm the selection of HB-086 as the lead molecule. The data will strengthen the IP position, as two patents have been filed, and at least the manufacturing process and the pending formulation warrants novel IP.
The progress has impacted the company’s position in moving from being a research focused to becoming a drug developing company. A change was reflected in the hiring of 2½ new FTEs in the last year.
Based on the progress, a series A financing round is nearing completion, and upon close, will finance activities up to and including a phase 1 study for HB-086.
Confirmation and scale-up of the HB-086 production process, along with a successful technology transfer to the CDMO, are important deliverables, which de-risk the manufacturing part of drug development. The conducted 10x scale-up strongly indicates that the process is adequate for further increases in batch sizes.
Production of preclinical drug substance allows initiation of the planned toxicology and formulation programs.
Results from pharmacology studies further strengthen the profiling of the drug candidate and confirm the selection of HB-086 as the lead molecule. The data will strengthen the IP position, as two patents have been filed, and at least the manufacturing process and the pending formulation warrants novel IP.
The progress has impacted the company’s position in moving from being a research focused to becoming a drug developing company. A change was reflected in the hiring of 2½ new FTEs in the last year.
Based on the progress, a series A financing round is nearing completion, and upon close, will finance activities up to and including a phase 1 study for HB-086.