BioSenic, a clinical-stage Belgian-headquartered company specializing in serious autoimmune and inflammatory diseases and cell therapy, will be sharing data on its late-clinical asset JTA-004 for the treatment of knee osteoarthritis at the Osteoarthritis Research Society International (OARSI) World Congress 2024.
The event takes place in Vienna, Austria, from April 18 to 21.
The post hoc analysis of a phase 3 study found that a single injection of JTA-004 was safe and efficacious for patients with a newly characterized severe inflammatory subtype of knee osteoarthritis (OA).
This week on the podcast, we talk about this potential new treatment for knee osteoarthritis, and the company’s pipeline, with BioSenic chief scientific officer and chief operating officer, Dr Carole Nicco.
BioSenic is a biotech company specializing in the clinical development of autoimmune disease therapies. The first platform leverages the immunomodulatory properties of arsenic trioxide (ATO) for a new arsenal of formulations, including oral delivery (OATO), for anti-inflammatory and anti-autoimmune indications such as chronic graft-versus-host disease (cGvHD), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). In parallel, BioSenic develops innovative products through a second platform that includes cell therapies and strong IP protection for tissue repair technologies.
What is knee osteoarthritis?
Osteoarthritis affects between 500 and 600 million people worldwide.
The main symptoms are joint pain and stiffness, and problems moving the joint or joints. Some people also have symptoms including swelling, tenderness or a ‘grating’ or cracking when moving the affected joints.
The severity of OA symptoms vary greatly between people, and also between joints.
Almost any joint can be affected by OA, but the condition most often affects the knees, hips and small joints of the hands.
What is JTA-004?
JTA-004 is an intra-articular viscosupplement treatment for knee OA, composed of hyaluronic acid, plasmatic proteins, and clonidine. The post-hoc analysis addresses different subpopulations of OA patients in the data of a phase 3 trial (KOA-2) completed in 2019. The trial was intended to demonstrate that treatment with JTA-004 leads to a reduction in knee pain intensity compared to saline solution or Synvisc-One, three months after injection, in subjects suffering from symptomatic knee OA.
“Hyaluronic acid is like a cushion. It’s a soft product that can help to avoid the friction in the knee. Also, hyaluronic acid can act on some cells, immune cells, that have CD44 receptors on their membrane. Hyaluronic acid could act on immune cells to help avoid inflammation in the knee,” Nicco said.
“And I think that clonidine is a really interesting element of the product because it is well known for its anesthetic effect because it acts on alpha-2 adrenoceptors on cells and that’s well known. Clonidine also acts as an anti-inflammatory compound. The third mechanism of clonidine is that it can act directly on some precise receptors that will act on voltage sodium channels and avoid pain.
“ATO is a really interesting, powerful drug that could be really revolutionary.”
“We also have plasmatic proteins and these proteins mainly act mechanically to make a soft viscous supplement to avoid the mechanical stress on the knee.”
The initial results in a broad pool including patients with several subtypes were inconclusive. However, BioSenic reevaluated the previous data following the publication of a study that identified biomarkers to stratify OA phenotypes, including a disease subtype characterized by systemic inflammation and the most severe symptoms. The conclusion of the post hoc analysis is that JTA-004 is safe and effective for successfully treating symptoms in this inflammatory-driven subgroup.
“The treatment we have with JTA is more specific with patients with immune form of osteoarthritis,” Nicco explained.
Another clinical trial for this potential treatment for knee osteoarthritis will be needed, she added.
About the ALLOB platform
ALLOB is an allogeneic cell therapy platform made of differentiated, bone marrow-sourced mesenchymal stromal cells (MSCs), which can be stored at the point-of-use in hospitals. The platform represents a unique and proprietary approach to organ repair, and specifically to bone regeneration, by turning undifferentiated MSCs from healthy donors into bone-forming cells at the site of injury.
BioSenic is studying the results of a phase 2 trial to optimize the efficacy of ALLOB by determining the best timing for therapeutic intervention and seeking partners to continue the development of the promising underlying therapy strategies.
“This cell therapy was designed to be used as bone repair therapy. The aim is to repair the bone with injecting these cells where production of bone-producing cells could proliferate to repair the bone,” Nicco explained.
“Cell therapy can be difficult to manage because you have to have the production and the injection really rapidly because you cannot preserve the cells, usually. With ALLOB, what is interesting is that it’s cryopreserved. You can have it in stock and preserved for nearly 40 months.”
Nicco said there were problems surrounding the clinical trial, because it started it 2019, when the Covid-19 pandemic hit. That meant people were staying home, and there weren’t as many tibial fractures to conduct the study.
“Another problem is that you have to find the best way to inject your product and it was decided to inject directly after the fracture. We found out post hoc that maybe it would have been better to inject the cells later, as in the previous other clinical trial using ALLOB.”
Nicco said JTA and ALLOB are currently ready, and the company is looking to find partners to complete trials and begin rolling out to patients as soon as possible.
What is arsenic trioxide?
The ATO platform has immunomodulatory properties with fundamental effects on the activated cells of the immune system. One direct application is to treat chronic GvHD, one of the most common and clinically significant complications affecting long-term survival of allogeneic hematopoietic stem cell transplantation (allo-HSCT), a curative treatment for patients with serious blood diseases, including cancers.
BioSenic’s intravenous ATO formulation, Arscimed, has orphan drug designation status by FDA and EMA, and it has shown good safety and significant clinical efficacy for skin, mucosae, and the gastrointestinal tract in an early phase 2a study. The company is planning a phase 3 study with its OATO formulation. OATO will also target moderate-to-severe forms of SLE. BioSenic is also developing a new IP-protected OATO formulation for the treatment of SSc, a serious chronic disease that affects skin, lungs or vascularization, and has no current effective treatment. Preclinical studies on pertinent animal models support the launch of a phase 2 clinical trial.
“Arsenic trioxide is a really interesting, powerful drug that could be really revolutionary,” Nicco said.
“I think that this compound could be incredibly useful for patients with really difficult diseases, autoimmune diseases, and we should be able to bring it to patients for osteoarthritis, for systemic sclerosis, for chronic graft versus host disease.
“With arsenic trioxide, what is interesting is that it acts on different pathways. It acts only on the cells when they are over activated. So it means that when you treat with arsenic trioxide, if there is no need to act in the cells on some pathways, arsenic won’t have any action and will be eliminated. But if there is a pathway where arsenic trioxide can act, or if it can be fixed on a protein or somewhere in the cell, it will act.”
The company is working on an oral delivery of ATO.
To learn more about new treatments for knee osteoarthritis:
Here are some links to more articles on knee osteoarthritis treatment and BioSenic: